98

Presidential
LecturePresidential Lecture ST

Cohort to Genome
Nobuo YAEGASHI
Tohoku University

The prospective cohort study is one of the epi-

pan Earthquake, a cohort of 150 thousand inhabi-

demiological methods with little measurement

tants of the disaster areas was formed in combi-

bias but requires enormous time and effort andnation with their health survey. New findings

cost to conduct research. The Japan Environ-and information as the basis of genome-omics

ment and Childrenʼs Study（Ecochil）is a nation-

medicine have been published one after another.

wide prospective cohort study, which aims pri-

The 70,000 people of the cohort are three genera-

marily to clarify environmental factors and ge-

tions cohort, which include 20,000 pregnant

netic factors that influence neurological develop-

women in Miyagi prefecture and their family. It

ment etc. by recruiting 100,000 pregnant women.

draws worldwide attention as the first three gen-

Their infants will be followed for 13 years after

eration birth cohort.

birth. Parts of the data are now analyzed and re-the prospective cohort studies of the field of ob-leased. In addition, in the Tohoku Medical Mega

stetrics and gynecology and will mention the im-

Bank project that began after the Great East Ja-

pact on future genome research.

The lecture will outline

99

Special Lecture ST

The Dawn of a New Era in Fetal Behavioral Science
SpecialLectureToshiyuki HATA
Kagawa University

1. Our previous activities in OB/GYN ultrasound

2000；15：2438-42；Obstet Gynecol 1998；91：

study

218-23；Ultrasound Obstet Gynecol 1998；12：

In 1992, we reported the use of ophthalmic ar-

235-9, 2002；19：471-4；Arch Gynecol Obstet

tery velocimetry in pregnant women for the first2012；286：1431-5；Ultrasound Med Biol 2012；

time in the world（Lancet 1992；340：182-3）. In

38：396-401）, as well as in the evaluation of thethis work, we demonstrated that the vascular re-normal and abnormal placenta（Placenta 2009；sistance of the ophthalmic artery is significantly

30：391-7, 2010；32：105-15, 2016；45：32-6；Ul-

reduced in women with pregnancy-induced hy-

trasoundpertension（PIH）. Subsequently, we demon-

uog.18837）.

strated that there is a difference in the circula-

2. The dawn of a new era in fetal behavior re-tion of the maternal ophthalmic artery between

searchObstetGynecoldoi ： 10.1002 /mild and severe PIH cases（Am J Obstet Gynecol

The development and abnormalities of the1997；177：174-8）. Furthermore, we reported

brain and central nervous system of a fetus canthat vascular resistance is reduced in pregnan-

be assessed directly by observing the fetal move-cies associated with small-for-gestational-age fe-ment and behavior in womb. A major limitation

tuses（Ultrasound Obstet Gynecol 1998；11：328-of conventional 2D ultrasound is the inability to31）,as well as in pregnant women with diabetes

detect the movement and behavior of a fetus that

（Hum Reprod 2000；15：222-3）.

occur outside of the imaging plane. 4D ultra-

We performed intrauterine sonography with asound has overcome this limitation and opened

20-MHz high-frequency miniature（2.4-mm di-

new doors to advance the field of research（Infameter）ultrasound transducer to observe em-

Child Dev 2010；19：99-118；J Obstet Gynecol

bryos in the early stages of pregnancy（Am J Ob-

Res 2016；45：32-6；J Perinat Med 2017；45：

stet Gynecol 1995；173：1770-4；Hum Reprod729-36）, thus contributing to the dawn of a new

1996；11：2758-61, 1997；12：1873-6, 1997；12：

era in fetal behavior research that includes fetal

2286-91）. We also demonstrated that intrauterine

neurology and fetal psychology .

sonography can be used effectively to observe

3. Fetal behavior in the first half of pregnancy

the development of the embryonic brain and cen-

By observing fetal movements at 10-13 weeks

tral nervous system（Hum Reprod 2000；15：

of gestation, we demonstrated that there is a dif-

1407-12；Ultrasound Obstet Gynecol 2009；34：

ference in fetal behaviors between 10-11 and 12-47-51）.

13 weeks of gestation（Int J Gynecol Obstet

3D/4D ultrasound can be used to monitor fetal

2010；109：190-3）. Furthermore, we monitored

growth and diagnose fetal abnormalities（Humfetal movements for 60 minutes at 14-18 weeks of

Reprodgestation and demonstrated that fetuses were in

1997；12 ： 1800-4,

1998 ； 13 ： 740-3,100SpecialLecturethe active and resting phases for 59.4 and 40.6%

of borderline fetal behavior（5.08%）, of whichof the time, respectively（J Ultrasound Med

13.6%（n=3）had developmental disorders after

2001；20：1271-5）. Movement of the arms wasbirth.

observed the most frequently at 14-16 weeks, and

6. Inter-twin contact and fetal behavior in twinthat of the arms and legs was observed the mostpregnancies

frequently at 17-19 weeks（J Perinat Med 2017；

We used 4D ultrasound to observe twin preg-

45：737-43）.

nancies in the early stages of pregnancy（10-13

4. Fetal behavior in the last half of pregnancy

weeks of gestation）for the first time, and re-

We examined the frequencies of various fetal

ported the characteristics of inter-twin contact

facial expressions（mouthing, yawning, smiling,

and frequencies of reactions towards such inter-

tongue expulsion, scowling, sucking, and blink-action（Int J Gynecol Obstet 2010；108：104-7；Jing）after 20 weeks of gestation, and found that

Matern Fetal Neonatal Med 2012；25：226-30；

mouthing was the most frequent up to 9 months,

Ultrasound Med Biol 2011；37：1948-51）. Fur-and both mouthing and blinking were the mostthermore, we demonstrated that at less than 20

frequent after 9 months（Int J Gynecol Obstet

weeks of gestation, the movement of twin fetuses

2006；94：108-13,

2014；

is significantly restricted compared with that of

126：275-9；J Matern Fetal Neonatal Med doi：singleton fetuses due to the limited space in the10.1080/14767058.2017.1330880）.

uterus and mutual interference（J Perinat Med

5. KANET test

doi：10.1515/jpm-2017-0158）.

2013；121：257-60,

The Kurjak Antenatal Neurodevelopmental

7. Future perspectives in fetal behavior researchtest（KANET）is used in 4D ultrasound to assess

1）Elucidate the mechanisms of fetal brain andfetal neurobehavior. Using the KANET test, wecentral nervous system functions

demonstrated for the first time that for the as-2）Develop novel neurological diagnostic test ap-

sessment of fetal behaviors, particularly facial

plicable during the fetal period

expressions, we must consider differences in3）Discover novel fetal behaviors

race and ethnicity（J Perinat Med 2016；44：217-

4）Elucidate the neurological development and21）.In addition, we demonstrated that there is no

personality formation in twin fetuses

sex difference in the fetal neurobehavioral func-

As listed above, we anticipate that future re-tion or its development, or in the developmental

search in fetal behavior will help uncover theprocesses of the brain and central nervous sys-function and development of the fetal brain andtem（J Perinat Med 2016；44：585-8）.

central nervous system, heralding a new era ofSince June 2013, we have performed the
KANET test in 433 cases, and identified 22 cases

knowledge.

101

The Best of the best：Symposium 1（Oncology） ST
Recent Development of Precision Medicine for Gynecologic Cancers; Bench to Bedside

1）Analysis of Genomic Alterations and Drug Sensitivity of!

Gynecologic Tumor Toward Genomic based Medicine
Symposium

Akira HIRASAWA
Keio University【Objective】

lines

Ovarian cancer（OC）is difficult to detect early

We applied DSRT technology to determine de-and has a poor prognosis. Therefore, appropriate

tailed dose-response curves from 306 drugs in 29

cancer preventive measures are necessary forestablished OC cell lines. The panel included 137

those with high risk of ovarian cancer onset, andapproved as well as emerging, investigational,

personalized treatment strategies should be cho-and pre-clinical oncology drugs, all of which

sen for unaffected patients. About 10-20% of

were tested at five different concentrations, overovarian cancer is inherited due to pathogenic

a 10,000-fold concentration range. The area under

germline variants of the cancer-related genes；

the dose-response curve estimated the drug-

however, this frequency in Japanese patients issensitivity score.

largely unknown. Considering that pathologic【Result】

variants of somatic cells could predict the mo-

1. Prevalence of pathogenic germline variants

lecular mechanisms and therapeutic targets, andand the clinicopathological characteristics

the data from drug sensitivity and resistanceOut of 230 patients, 41 women with OC had

testing（DSRT）of the tumor cells could help topathogenic germline variants in OC-associatedselect the candidate drugs, we aimed to establish

genes. Nineteen（8.3%）and eight cases（3.5%）car-

individualized

ried germ line BRCA1 and BRCA2 pathogenic

therapeuticstrategy

fromgenomic analysis and DSRT data.

variants, respectively, and only one case had【Method】

gross deletion covering more than one exon of

1. Prevalence of germline variants
Samples from 230 individuals, having ovarian,

BRCA1 . Six cases（2.6%）carried pathogenic
germ line variants of MMR genes（MLH1 , MSH2,

fallopian tube, or peritoneal cancer, were recu-

MSH6 , or PMS2 ）.

ruited in this study. Germ-line DNA was en-

2. Profiling of somatic variants

riched, followed by sequencing.
2. Detection of ovarian cancer cell mutation

Profile of the somatic pathogenic variants importantly

include： TP53,

KMT2C,

BRCA1,

Target capture sequencing was performed on

BRCA2, NF1, FAT3, ERBB2 genes in high-grade

DNA taken from the same cancer tissues asserous carcinoma, ARID1A and KMT2C in clear

those analyzed for germline variants, using thecell carcinoma, ARID1A, PTEN, KMT2C, andsame method.

PIK3CA in endometrial carcinoma, and KMT2C,

3. High-throughput DSRT of ovarian cancer cell

TP53, ERBB2, PTEN, and KRAS in mucinous

102

carcinoma.

groups of OC cell lines.

3. DSRT profiling【Conclusion】

Bioinformatic processing of the drug-response

Using the integrated data with genomic analy-

data from OC cell lines indicated that the clus-

sis and DSRT, personalized cancer prevention

ters were according to drug categories, rather

and treatment may be established for gyneco-than the histological origin. Many emerging or

logical cancer.

non-approved drugs were found sensitive in sub-Symposium

103

The Best of the best：Symposium 1（Oncology） ST
Recent Development of Precision Medicine for Gynecologic Cancers; Bench to Bedside!

2）Large scale Exploration of Novel Therapeutic Targets Using ClinicalFeatures of Ovarian Cancer as Biomarkers

Tohoku University【Objectives】【Methods】

Ovarian cancer is the most challenging gyne-

Research（1）Functional genomics HTS using

cologic malignancy despite current comprehen-

RNA interference（RNAi）was performed in thesive treatments. The development of individual-

Quellos HTS core, at the University of Washing-ized medicine specific for each tumor and pa-

ton, USA. Two ovarian cancer cell lines, TOV

tient is gaining recognition as a next-generation

112 D（c-Myc dependent growth）and CaOV 3

ovarian cancer treatment strategy. We con-（c-Myc independent growth）, were used. An

ducted research aimed at developing novel

RNAi library covering 6,550 genes（three inde-

therapeutic methods using the clinical features

pendent siRNAs for each gene）was applied viaof ovarian cancer as biomarkers. We focused on

HTS and 94 genes showed synthetic lethal action

the following two features：（1）c-Myc gene am-with c-Myc overexpression in the primaryplification or overexpression（which is observed

screen. These genes were subjected to network

in 30-60% of ovarian cancers）,（2）acquisition ofanalysis and pathway analysis. Thirty genes

cisplatin resistance. One current example of indi-

were further selected and subjected to secon-

vidualized treatment is the treatment of BRCA-

dary screening with siRNA independent of the li-

deficient ovarian cancers with a PARP（polybrary. Finally, the synthetic lethal mechanism

ADP ribose polymerase）inhibitor. The combinedwith c-Myc alteration was further analyzed onloss of BRCA and PARP activity results in syn-the extracted gene.

thetic lethality. Synthetic lethal action can poten-

Research（2）Functional genomics HTS was per-tially be utilized for novel cancer therapeutics toformed using A2780CP70, a cisplatin resistantdecrease side effects. However, it is difficult toovarian cancer cell line, in the same way as Re-

determine suitable synthetic lethal molecules forsearch（1）. A group of genes that cancels cis-therapeutic targets. Therefore, we focused on

platin resistance by functional inhibition was ex-

High Throughput Screening（HTS）, which al-plored, from the same RNAi library as above,lows many compounds to be screened using ancomparing IC20 concentration of the cisplatin-

automated robot. Considering the characteristics

added and non-added groups. A secondaryof the above（1）（2）biomarkers, we used HTS toscreening with siRNA independent of the library

search for new therapeutic targets with syn-was conducted for the 30 genes selected in thethetic lethal action.

primary screening. The mechanism of overcoming cisplatin resistance of target candidate mole-Symposium

Masafumi TOYOSHIMA

104

cules was analyzed in detail.

reaction pathway, we found that TIE-1 regulates
nucleotide excision repair（NER）. Furthermore,

Symposium【Results】

we found that TIE-1 regulates the expression

Research（1）From the HTS and validation as-

level of the XPC complex, which recognizes

says, Furin, a proprotein convertase, was se-

DNA distortion due to crosslinking. We adminis-

lected as a target molecule which shows syn-tered 7 anticancer drugs with different cell kill-thetic lethal action with c-Myc overexpression.

ing mechanisms to the TIE-1 knockdown ovarian

Expression vectors for c-Myc and Furin werecancer cell line. The IC50s of cisplatin and car-constructed and transfected into OSE2 cells, anboplatin were markedly decreased compared toestablished cell line from normal ovarian surface

other drugs. Nine samples of ovarian cancers

epithelium. We found that cell proliferation wasfrom patients who underwent surgery at our in-significantly increased only when Furin and c-stitute, were collected during a secondary de-

Myc were simultaneously overexpressed. Immu-

bulking surgery and evaluated with anti-TIE-1

nohistochemical staining analysis of ovarian can-IHC. The expression level of TIE-1 protein wascers showed no correlation between the expres-significantly increased in samples from tumors

sion level of Furin and c-Myc and overall patientresistant to paclitaxel and carboplatin（TC）ther-

prognosis. However, in sub-group analysis, highapy（n=6）than those that responded to TC ther-

Furin expression in the c-Myc high expression

apy（n=3）. These results indicate that TIE-1 is in-group was significantly correlated with poor

volved in cisplatin resistance of ovarian cancer

prognosis. We identified Furin as a potential

by enhancing NER through the regulation oftherapeutic target molecule, which shows a syn-

XPC, and that TIE-1 inhibition is effective forthetic lethal effect with c-Myc overexpression in

overcoming drug resistance in DNA cross-ovarian cancer.

linking anti-cancer drugs.

Research（2）Of the leads from HTS and validation assays, we focused on a tyrosine kinase re-【Conclusions】

ceptor, TIE-1, which increased cisplatin sensitiv-

We consistently search for novel therapeutic

ity in the A2780CP70 ovarian cancer cell line.

targets using clinical features of ovarian cancer

Overexpression of TIE-1 significantly reduced

as biomarkers. The targets of cancer therapy arecisplatin sensitivity in three types of ovarian

becoming more specific with the progress of can-cancer cell lines. In addition, TIE-1 expression

cer genomics research. It is creative that welevels were significantly increased in each cis-

adopted unbiased, large-scale screening of novel

platin resistance-acquiring strain compared totherapeutic targets, using two different biomark-their three parent lines. Emission spectroscopic

ers. In this study, we used HTS and secondary

analysis showed that TIE-1 expression does notverification to identify two novel ovarian cancer

change intracellular cisplatin concentrations, in-mechanisms：high co-expression of Furin and c-

dicating that TIE-1 does not alter cisplatin up-

Myc in ovarian cancer with poor prognosis andtake or export. Cisplatin-treated TIE-1 knock-TIE-1 inhibition of cisplatin resistance. Further

down cells showed significantly increased ex-

research will be needed to develop the target

pression of γH2AX, a marker for DNA double

molecules identified in this study for clinicalstrand breaks. By examining the DNA damage

practice.

105

The Best of the best：Symposium 1（Oncology） ST
Recent Development of Precision Medicine for Gynecologic Cancers; Bench to Bedside3）Individualized Therapeutic Approach forConquering Refractory Serous Endometrial Cancer（SEC）

Kyoto University【Introduction】

chemical（IHC）staining were conducted using

Endometrial cancer（EC）is one of the leading

2 cohorts of endometrial cancers, 91 samples ofcauses of gynecologic malignancy, and the inci-

Kyoto University cohort and 462 samples of Brit-dence of EC in Japan has nearly doubled in the

ish Columbia University cohort, under protocols

past decade. Most patients present with low

approved by the Institutional Review Board tograde and early stage disease with favorable

investigate SEC-specific pathways. Tumor infil-

prognosis, but cases of high-grade tumors are ag-

trating CD8+T cells（TILs）and CD33+cells

gressive and frequently diagnosed with tumor（MDSC）were counted and MDSC-TIL ratio was

spread beyond the uterus. Serous endometrial

calculated to assess tumor micro-environmental

cancer（SEC）is a histological subtype which rep-

immunity.

resents highly progressive properties with poor

For in vitro assay, four human SEC cell lines,

prognosis, and its oncogenic profile is known dif-

SPAC-1L, SPEC2, ARK1, and ARK2, were used.

ferent from endometrioid endometrial cancers.

Cellular proliferation, migration, and invasion

Although SEC is known to harbor several ge-

were assessed with or without siRNAs for target

netic alterations, it still remains unclear whichgenes. In vivo tumorigenesis was also assessedmolecular pathway is responsible for its unfavor-

with NOD-SCID mice. Furthermore, proliferation

able features, especially therapy-refractory andassay and apoptosis assay were performed inmetastatic natures. Recent studies exhibited

STAT1 suppressed SPAC-1L cells treated by cis-anti-tumor immunity evasion（ATIE）is also

platin. In addition, cleaved-Casp3 protein expres-known to play crucial roles in refractory cancers,

sion, DNA repair, DNA damage status, andbut ATIE in SEC has not been clarified so far

STAT1 phosphorylation was also assessed in

due to lacking immunocompetent assessment

these manner. For assessing the cellular func-

models. In this study, we aimed to figure out

tional impact of STAT1 pathway activity,

SEC-specific pathways to reveal the mechanism

dominant-negative STAT1 on sites of serine-727

promoting tumor growth and progression, andor tyrosine-701 were introduced in SPAC-1L

we also provide biological evidence that SEC-

cells, respectively.

driver gene is associated with its clinical mali-

A mouse endometrial cancer cell line, ppp268,

cious roles such as chemo-resistance and ATIE.

was established by conditional uterine deletion【Methods】

of Pten and Trp53 using the Cre/loxP approach,

Gene expression microarray and immunohisto-

and murine cMyc was further introduced to de-

Symposium

Tsukasa BABA

106

velop ppp268-cMyc cells for assessing immuno-

of STAT1 significantly increased DNA damage

competent tumorigenicity on C57BL6 mice.

resulting in higher apoptosis activity and promi-【Results】

nent

cleaved-Casp3

proteinexpression.

In

Symposium

Genome-wide analysis revealed STAT1 path-

STAT1 suppressed cells treated with cisplatin,

way was significantly highly activated in SEC,

DNA repair pathways were not affected but only

and its expression was confirmed significantly

cellular uptake of cisplatin was prominently in-higher in SECs tissue by IHC staining in both co-creased. This blockade of cisplatin uptake washorts. Furthermore, high STAT1 status in SEC

induced through STAT1 phosphorylation on

emergedco-serine-727 in nucleus（nSer-pSTAT1）, but a CK2

localization of ICAM-1 ＆ PD-L1 was observed at

inhibitor（CK2I）as a regulator of phosphorylation

tumor frontier with TILs, and TILs were more

reduced nSer-pSTAT1 to enhance DNA damage

frequently observed in the center of tumors

induced by cisplatin, and xenograft tumor was

without recurrence resulting in that overall sur-almost diminished by cisplatin and CK2I.

a

poor

prognosis.

In

SECs,

vival was significantly better in cases with low
MDSC-TIL ratio.

Immunocompetent tumorigenicity got superior by transduction of cMyc, and cMyc tumor

It was confirmed that IFNg induced STAT1

exhibited highly nuclear atypia and glandular

expression not only to promote cellular prolifera-

structure mimicking SEC. In cMyc tumors,tion, adhesion, and invasion, but to induce ex-

MDSCs were more frequently observed, andpression of cMyc, ICAM-1 and PD-L1 in SPAC-1L

MDSC-TIL ratio was also high.

cells. In contrast, suppression of STAT1 by【Discussion】

shRNA or dominant negative plasmid inhibited
xenograft tumor growth on NOD-SCID mice.

Previous studies showed that STAT1 activates anti-proliferative and pro-apoptotic genes

In silico analysis using cBioPortal addressed

as a tumor suppressor；in contrast, STAT1 in

amplification of MYC and up-regulated of MYC

SEC appears to function as a tumor pro-survival

mRNA in 42% SPECs. A hundred and eight ofgene. The highly-progressive features of SEC

the 227 up-regulated genes in the SEC signaturemight be partially due to constitutively highharbored the MYC binding site motif by

STAT1 expression and consequent up-regulation

GATHER analysis, and the predictive MYC ac-of downstream STAT1 target genes under ativity signature score was statistically higher inhighly orchestrated series of tumor microenvi-

SECs than in other subtypes of endometrial can-ronment components, and we propose that con-cers, while that in SPAC-1L cells was diminishedstitutively high STAT1 expression in SEC has awith STAT1 knockdown.

tumor promoting role rather than tumor sup-Among four SEC cell lines, highly STAT1 ex-

pressing role through nSer-pSTAT1.

pressing cells, ARK2 and SPAC-1L, were more

These results indicate that STAT1 pathway

resistant to cisplatin than other 2 cell lines, andincluding Myc activity is associated with SEC

suppressing

sensitized

aggressive features and may confer SEC refrac-

SPAC-1L to cisplatin. Cisplatin treatment inhib-

STAT 1

tory phenotypes by enhancing cisplatin resis-

itedproliferationofexpression

knockdowntance and ATIE. Therefore, targeting STAT1

SPAC-1L significantly, and Cispatin IC50 value

STAT 1

pathway might be a promising intervention for

was remarkably decreased compared to wild

SEC management.

type counterpart. Furthermore, down regulation

107

The Best of the best：Symposium 1（Oncology） ST
Recent Development of Precision Medicine for Gynecologic Cancers; Bench to Bedside4）Individualization of Cancer Stem Cells and Development of
Personalized Medicine in Cervical Cancer

Saitama Cancer Center / The University of Tokyo【Introduction】
Cancerous tissues consist of polyclonal cellswith wide variety of metabolic status and prolif-

among the CSC clones induced from HPV infected iPS cells.
【Method】

eration activities. In general, so-called cancer［1］The expression profiles of the molecules in-stem cell（CSC）hypothesis suggests that CSCs

volved in self-renewal ability of CSCs were in-have an ability to acquire heterogenic cell prop-

vestigated in clinical samples of cervical cancer

erties and lose self-renewal ability in the process

tissues. It is known that BMP（Bone Morphoge-of tumor formation. This heterogeneity can lead

netic Protein）, one of the TGF-β superfamily, isto therapeutic resistance and a novel approach to

involved in the differentiation of stem cells.

target CSCs instead of already differentiatedGremlin 1, a molecule that has an antagonistic ef-

clones is required. In-vitro models to investigate

fect on BMP, was evaluated for its applicability

the biology of CSCs is highly important for theas a prognostic marker and as an individualiza-

development of future cancer treatment. It istion marker for treatment choice. Under ap-

known that human papillomavirus（HPV）on-

proval of the institutional ethical committee,

coprotein E6 inhibits p53-dependent apoptosis.

Gremlin 1 expression was assessed in the cervi-

Therefore, the acquisition of mechanisms to es-

cal cancer tissues of 104 patients（stage I to stage

cape apoptosis may be a critical step to generateII）who underwent surgery at the University of

CSCs in cervical cancer.

Tokyo Hospital from 2005 to 2014. By stimulating【Objective】

CaSKi cells, a cervical cancer cell line withIn this study, our challenge is directed to gain

Gremlin 1, the changes in CSC marker expres-knowledge contributing to future personalized

sion patterns and CSC-like cell properties were

medicine targeting CSCs. We conducted several

evaluated.［2］Using three-dimensional culture

experiments, aiming［1］to clarify the association

technology, CSCs were induced on a non-of CSCs-related molecules with cancer recur-

adherent plate from HPV 16, 18 positive cervicalrence and prognosis in clinical cases,［2］to eluci-

cancer cell lines（SiHa, CaSki, HeLa）. The CSCs

date the mechanism for apoptosis tolerance inderived from those different cell lines wereCSCs,［3］to analyze amino acid metabolic path-given a stress with an anticancer agent and an

way activities to reveal the differences in theapoptosis inducer and evaluated for the inci-

metabolic properties between CSCs and cancer

dence of apoptosis.［3］To identify distinctive

cells, and［4］to examine HPV-type specificities

properties between CSCs and functionally-

Symposium

Katsuyuki ADACHI

108

Symposium

differentiated cancer cells, metabolome analysis

sis, we found the elevation of serine and glu-

covering total amino acid metabolites was car-tamine levels accompanied with TCA circuit ac-ried out.［4］We established a method to induce

tivation in CSCs but not in CC.［4］Induction ofreserve cells（iRCs）from iPS cells. The iPS-

iRCs with comparable characteristics to the re-derived iRCs were transfected with HPV 16 andserve cells present in SCJ from human iPS cells

HPV 18. The acquisition of CSC-like properties

was established. This iRCs expressed SCJ

was evaluated in the transfectants. The HPV-

marker such as CK7, AGR2, CD63, and MMP7.

type specific characteristics of the infected iRC

Furthermore, the iRC with HPV 16, 18 geneclones was analyzed.

transductions demonstrated CSC-like cell prop-【Results】［1］High Gremlin 1 expression in the cervicalerties.
【Summary】

cancer specimens was associated with shorter

Cervical cancers with high expression ofprogression-free survival（P=0.0004）. The stimu-

Gremlin 1 had poor prognosis, supporting the im-lation with Gremlin 1 facilitated dedifferentia-

portance of therapeutic approach targeting CSCs

tion of CaSKi cells into CSCs, with enhanced ex-in those patients. CSCs showed altered aminopression of stem cell markers. This finding pro-acid metabolism compared to CC, with activation

poses that inhibition of Gremlin 1 signaling couldof the enzymes involved in TCA cycle. The dif-

be a new therapeutic strategy to increase the re-ference of acid metabolism might be a future tar-sponse to anti-cancer drugs.［2］CSCs derived

get for CSC treatment. Our in-vitro data suggest

from SiHa were resistant to the apoptosis induc-that IRE pathway inhibitor would be a promisingtion by ER stress inducers, whereas the apopto-

strategy to solve CSCs resistance to Cisplatin

sis was efficiently induced in CC. This resistancewhich rely on ER stress-induced apoptosis as its

to ER stress inducer in CSCs were abrogated by

anticancer efficacy, and demonstrate possibility

the addition of blockers for the ER stress clear-of overcoming Cisplatin tolerance by using IRE

ance pathway. The CSCs derived from SiHa,

pathway inhibitor in combination. Our in-vitro

CaSKi, and HeLa showed distinctive morphology.

technology to generate CSCs from iPS cells of

The ability to form spheres which is paralleled

the patientʼs cervical tissue contribute to the de-with the capacity of dedifferentiation into CSCs

velopment of novel therapy targeting CSCs.

was highest in CaSKi.［3］In metabolome analy-

109

The Best of the best：Symposium 2（Reproduction/Endocrinology, Perinatology and Womenʼs Healthcare） ST
The Latest Knowledge Obtained from the Prospective Study in the Reproduction/
Perinatology and the Prospect of Preemptive Medicine!

1）Efficacy of a Prospective Multifaceted Community based Intervention
to Prevent Preterm BirthKumamoto University

To prevent early preterm birth and reduce theand 32.2%, respectively. The mean gestational

low birth weight infants, we conducted Ku-

age at birth, birth rate of low birth weightmamoto RAINBOW Project, a multifaceted im-（LBW）infants, very LBW infants, and preterm

plementation focused on the reduction of cho-birth of the subjects were 38.9 weeks, 8.10%,

rioamnionitis and periodontal disease, as well as

0.65%, and 4.58%, respectively. The subjects who

instruction regarding lifestyle factors that canwere enrolled in this project primarily gave

reduce the likelihood of premature labor. Follow-

birth in 2013 and 2014. The community-based

ing model studies conducted in two areas, webirth rate of LBW infants in Kumamoto prefec-

have implemented the project in Kumamoto Pre-

ture was 9.19% in these two years, which was

fecture from Aug. 2012 to Jan. 2014 and 20,701

significantly reduced from the mean birth rate

pregnant women were enrolled. The incidence of（10.02%）in the preceding 6 years.

bacterial vaginosis and periodontitis were 12.0%

Symposium

Takashi OHBA

110

The Best of the best：Symposium 2（Reproduction/Endocrinology, Perinatology and Womenʼs Healthcare） ST
The Latest Knowledge Obtained from the Prospective Study in the Reproduction/
Perinatology and the Prospect of Preemptive Medicine2）Prospective Cohort Studies of Maternal and Neonatal Screening
Methods for Developing Preemptive Medicine for Congenital Infection
Symposium

Kenji TANIMURA
Kobe University【Objective】
Recently, it has been demonstrated that earlyintervention with antiviral drugs may improveneurological outcome in infants with symptomatic congenital CMV infection（CCI）.
It is known that maternal acetylspiramycin（AcSPM）therapy can reduce the incidence ofcongenial T.gondii infection（CTI）.
Therefore, detection of mothers and newborns
at high risk for congenital infection（CI）is important.
We conducted four prospective cohort studies
to establish the useful maternal and neonatal
screening methods for CTI or CCI.
【Methods】
These studies were approved by the institutional review boards, and informed consent was
obtained.
A）A prospective study to evaluate the efficacy
of maternal screening for CTI
From 2005 to 2017, pregnant women with positive or equivocal T. gondii IgM underwent serum IgG avidity measurements. They were divided into 3 groups based on avidity index（AI）：acute infection（AI＜30%）, borderline（30% AI 35%）
, and chronic infection（AI＞35%）. Pregnant women with an AI＜30% andthose who desired medication underwent
AcSPM therapy. Amniocentesis followed bymultiplex nested PCR for T .gondii -DNA in theamniotic fluid（AF）was performed when thewomen with an AI 35% desired it. At birth,
PCR for the AF and/or umbilical cord blood（UCB）was performed when informed consent! !

!

was obtained. The presence of CTI was assessedby blood PCR, IgM, and imaging examinations ofinfants.
B. A prospective study to evaluate the efficacy ofmaternal and neonatal screening for CCI1）Neonatal universal urine screening and antiviral therapy for symptomatic CCI
Neonates born at Kobe University Hospitaland affiliated hospitals were prospectively
screened for urinary CMV-DNA by PCR from2009 to 2017, and CMV-positive newborns were
further examined. Newborns diagnosed as symptomatic CCI were treated with valganciclovir（VGCV）for 6 weeks. Clinical neurological outcomes were evaluated at age of 12 months.
2）Predictive factors of CCI in high-risk pregnant
women.
From 2009 to 2016, 300 CMV IgM-positive
pregnant women were enrolled. The maternalclinical and laboratory findings, including serum
CMV IgM and IgG；AI；C7-HRP；PCR for thematernal serum, urine, and uterine cervical secretion；and fetal ultrasound findings, were
evaluated. To determine predictive factors for
CCI, logistic regression analyses were performed.
3）Maternal serological screening for CCI in lowrisk pregnant women.
From 2010 to 2016, 2,193 pregnant women at
low-risk for CCI underwent screening of IgG and
AI. IgG-negative women underwent educational
intervention and remeasurement of IgG at 34-35

111

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【Results】
A. A prospective study to evaluate the efficacy ofmaternal screening for CTI
・Ninety（22%）of the 402 pregnant women withpositive or equivocal IgM had an AI＜30%.
・Seven newborns with CTI were detected.
They had an AI＜30% and positive PCR resultsin the AF or UCB.
・All six live births, including one infant who underwent medication for 1 year, had no sequelae.
None of women with an AI≧30% had CTI.
B. A prospective study to evaluate the efficacy ofmaternal and neonatal screening for CCI1）Neonatal universal urine screening and antiviral therapy for symptomatic CCI.
・In the urine screening of 10,356 newborns, 48（0.46%）tested positive for CMV-DNA.
・Twenty-two were diagnosed as symptomatic
CCI and 18 received antiviral therapy.
・Six infants developed severe sequelae（43%）,
2 developed mild sequelae（14%）, and 6 developed normally（43%）at age of 12 months.
2）Predictive factors of CCI in high-risk pregnant
women.
・Twenty-two（7.3%）of the 300 IgM-positive
women had CCI.
・Multivariable analysis revealed that the presence of ultrasound fetal abnormalities（OR, 32；
95% CI, 8.5-120）and positive PCR results in theuterine cervical secretion（OR, 16；95% CI, 5.054）were independent predictive factors of CCI in
IgM-positive women.
3）Maternal serological screening for CCI in low-risk pregnant women.
・A total of 1,562 women of the 2,193（71%）tested
positive for IgG, and 631（29%）were negative.
・Five（0.8%）of the 631 IgG-negative women had
seroconversion, and 1 of them had asymptomatic
CCI.
・Eighty-eight of the 183 women with an AI
45% had an AI＜35% and/or IgM＞1.2, and 2 had
CCI（1 asymptomatic, 1 symptomatic）.
・Seven（0.5%）of the 1,287 women with an AI＞45% together with IgM 1.2 had newborns
with CCI, including 3 symptomatic and 4 asymptomatic CCI.
・The application of an AI＜35% for CCI screening yielded 22% sensitivity, 95% specificity, 2.5%
PPV, 99.5% NPV, and 95% accuracy and was
similar to that of IgM（93% accuracy）.
・Multivariable logistic regression analyses
demonstrated that threatened premature labor（OR 8.4, 95%CI 1.5-48）was a single risk factor for
CCI in women with non-primary infection.

!

!

【Conclusions】
・Maternal screening using T. gondii IgG, IgM,
AI measurements and PCR test is useful for detecting a high risk pregnancy and useful for diagnosing and treating CTI.
・The present studies for the first time demonstrate that the presence of CMV-DNA in the maternal uterine cervical secretion and ultrasoundfetal abnormalities are predictive factors for CCI
in high-risk pregnant women and that threatened premature labor is a risk factor for CCI in
pregnant women with non-primary CMV infection.
・Maternal serological CMV screening can identify pregnancies with CCI from primary infection, but overlooks a number of those from nonprimary infection.
・The combination of early diagnosis throughscreening newborn urine samples and antiviraltreatment may improve neurological outcome insymptomatic CCI infants.
In conclusion, preemptive strategies using maternal or neonatal universal screening and drug
therapy for mothers or newborns at high-risk
can reduce the occurrence of CI and sequela associated with it.

Symposium

GW. Women with an AI 45% received further
examinations, including IgM. CCI was diagnosedby the detection of CMV-DNA in the newborn
urine. Primary infection was defined as an AI＜
35% and/or positive IgM（＞1.2 index）. Serum
samples from women with an AI＞45% werestored, and the IgM levels were measured later.
The efficacy of AI and IgM for CCI screening
was compared.
In addition, risk factors for CCI in pregnant
women with non-primary infection were determined by logistic regression analyses.

112

The Best of the best：Symposium 2（Reproduction/Endocrinology, Perinatology and Womenʼs Healthcare） ST
The Latest Knowledge Obtained from the Prospective Study in the Reproduction/
Perinatology and the Prospect of Preemptive Medicine

3）Elucidation of Environmental Factors and Pathological Conditions!

!

Affecting Fetal Development Focus on Perinatal Mental HealthSymposium

Hidekazu NISHIGORI
Tohoku University【Objective】
It is well known that the fetal environment affects the development of children, and perinatal
mental health is also important as an environmental factor. The present study focused on areas related to perinatal mental health with theprincipal aim of clarifying risk factors. Moreover,the present study aimed to clarify the pathologyof fetal brain function developmental abnormalities in using the fertile henʼs egg-embryo-chicksystem as an experimental animal model and todevelop an early detection method of fetal brain
function developmental abnormalities applying
fetal electrocardiogram as basic research forclarification of pathology and preemptive medical treatment.
【Method 1】
We used the data of the Japan Environment
and Childrenʼs Study（JECS）, a large-scale prospective birth cohort study in Japan. JECS is a
project of the Ministry of the Environment and isa survey aimed at clarifying the relationship between environmental factors and pediatric diseases from the gestation period. From January
2011, pregnant women were recruited and approximately 100,000 mother and child pairs are
participating；the survey will continue until thechild becomes 13 years old. Tohoku University isparticipating in the survey as the Miyagi Re-

gional Center, which is one of the 15 regional
centers located throughout Japan. Although theinvestigation was temporarily suspended due tothe Great East Japan Earthquake in March 2011,
it was quickly resumed and 9,217 sets are participating in Miyagi. Primary fixed data at birth（approximately 10,000 pairs）and complete fixeddata at birth（approximately 100,000 pairs）could
be analyzed. Psychotropic drug use and risk ofcongenital anomalies in pregnant women wereset as complete fixed data, and the other tasks
were analyzed using primary fixed data. Psychological distress was assessed using the Kessler
Psychological Distress Scale（K6）for screening；a score of 13 points or higher was defined as psychological distress symptoms（PDs）. SAS version 9.3 and 9.4 were used for statistical analyses.
【Result 1】
We conducted a survey on PDs and intimate
partner violence（IPV）in the areas affected by
the Great East Japan Earthquake as well as social capital（SC）, which has received much attention after the disaster. SC is defined as characteristics of social organizations such as bonds（kizuna in Japanese）, trust and networks. The
subjects comprised approximately 7,500 pregnant women who responded to the questionnairefrom June 2011 and gave birth by December
2011；a comparison with subjects nationwide.

113【Method 2】
It has been reported that abnormal secretionof hormones such as glucocorticoid occurs due toperinatal mental health problems, and that theuse of psychotropic drugs, affects the fetus andadversely affects the behavioral development of
the child. Therefore, as an animal experimental
model of behavioral development from the fetal

period, we developed a fertile henʼs egg-embryochick system. Chick embryos hatch on egg age
day 21, and chick embryonic brain development
at egg age 14 days is equivalent to the third trimester in humans. Glucocorticoid receptor antagonist（mifepristone）, inhibitor of thyroid hormone biosynthesis（methimazole）, and sodium
valproate, and caffeine were administered toeggs（day 14 or 15）under conditions in which thetiming and dose did not increase the congenital
anomaly rate and the hatching rate was 80% or
higher. All groups were compared with the control group.
【Result 2】
Mifepristone and methimazole were shown todelay hatching, imprinting, aggregation, belongingness, and vocalization ability. Sodium valproate was shown to delay aggregation, belongingness, and vocalization ability. Caffeine promoted hatching behaviors. Behavioral development was not correlated with brain weight.
【Method 3】
We attempted clinical application to fetal development using a fetal electrocardiographic device, which we were the first to develop in theworld, with the aim of preemptive treatment for
fetal developmental abnormalities. We used thisdevice in a fertile henʼs egg-embryo-chick system to attempt new detection of embryonic brain
function development abnormalities.
【Result 3】
Methimazole was administered under thesame conditions as in Method 2, and results of examination of electrocardiography of the chickembryo performed on egg age day 19 reduced
the spectral power in the low frequency area.
The effects of glucocorticoid administration are
currently under analysis.

Symposium

The frequency of PDs was significant higher（5.5% vs. 3.0%）, physical IPV was higher（5.9%
vs. 1.5%）, feeling that most people were trustworthy was lower（24% vs. 33%）
, while feelingthat they had helpful neighbors was converselyhigh（69% vs. 57%）in the north coastal area of
Miyagi. Risk factors of psychological IPV in Miyagi, were disease or injury of someone close andchanges in the family structure that might be
attributed to the disaster. Risk factors for PDs
were IPV and being unable to contact close
trustworthy people as desired.
Previous study showed the possibility of prevention of PDs in pregnant women by diet suchas fermented foods, but the present study indicates that the intake of yogurt, lactic acid beverages, cheese, Japanese pickles, miso soup, or fermented soybeans was not significantly associated with PDs.
The use of psychotropic drugs by pregnant
women and risk of congenital anomalies havebeen reported in Europe and the United States,
but there have been no large-scale prospective
studies in Japan. The present study indicatesthat the use of selective serotonin reuptake inhibitors until the 12th gestational week was associated with urogenital abnormality in children（odd ratio 3.23）.
Moreover, there were no previous studies on
SC and the risk of complications of pregnancy. It
was revealed that the emotional support andneighborhood trust associated with the lower
prevalence of gestational diabetes.

114

The Best of the best：Symposium 2（Reproduction/Endocrinology, Perinatology and Womenʼs Healthcare） ST
The Latest Knowledge Obtained from the Prospective Study in the Reproduction/
Perinatology and the Prospect of Preemptive Medicine

4）Effects of Various Environments on the Perinatal Prognosisof Mothers and Infants
Symposium

Seiichi MOROKUMA
Kyushu University【Background】
Recently, there has been an increased interest

particulate matter（SPM）, nitrous oxide（NO2）,and sulfur dioxide（SO2）.

in environmental influences during pregnancy.

To assess environmental effects on pregnancy-

Although the environment encompasses a wide

induced hypertension, air pollution data includ-variety of aspects, these can be broadly divided

ing the mean concentration of air pollutants dur-

into many chemical substances including thoseing the 0-12 week gestation period was analyzed.

found in food and the atmosphere. Maternal life-

To assess pollutant exposure effects on placentastyle factors such as diet and sleep also play an

previa or placenta accrete occurrence, air pollu-

important role.

tion data including mean concentration of air pol-【Objective】

lutants during the 0-4 week gestation period（im-In this study, we investigated the association

plantation period）, and during the 5-12 week ges-

between air pollutant exposure as an externaltation period were analyzed. There were 821

environmental factor, and pregnancy-induced

mothers（1.7%）who suffered from placental

hypertension, placenta previa, placenta accreta,

abruption. To assess the effects of air pollutants

placental abruption, small for gestational age

on placental abruption occurrence, the mean con-

（SGA）occurrence, and fetal heart rate abnor-

centration of air pollutants from 5 days before

malities. It was assumed that hyperemesis ofdelivery was analyzed. To evaluate the correla-pregnancy included exposure to malnutrition

tion between SGA and pollutant exposure, theearly in pregnancy, and SGA was regarded asmean concentration of air pollutants during thethe outcome. We investigated the association be-

0-12 week gestation period was analyzed. SGA

tween these factors.

was defined as a birthweight below the 10th per-【Methods】

centile for the gestational age-specific standard.

Patient records were obtained on 47,835 moth-

Cases of false-positive fetal heart rate abnormali-

ers and their infants delivered in the Kyushu andties were defined as those diagnosed with abnor-

Okinawa regions. All charts included were regis-

mal fetal heart rate at

tered in the Japan Society of Obstetrics and Gy-an umbilical cord blood pH

necology Perinatal Database between 2005 andscore

2010. The air pollutant molecules investigated in-for early, mid, and late pregnancy were used forcluded photochemical oxidants（Ox）,suspended

this group.

!32 weeks gestation with
!7.2 and an Apgar!7 at 1 and 5 minutes. Air pollution data

115

1.01-1.23；Ox：OR=1.08, 95% CI=1.00-1.16）. Exposure to SPM was also associated with placenta

fixed data from the Japan Environment and Chil-accreta（excluding placenta previa）（OR=1.33,

drenʼs Study（JECS）carried out by the Environ-

95% CI=1.07-1.66）.There was no association withment Ministry. The fixed data included 10,228

exposure to SPM, Ox, and other pollutants dur-deliveries. The required information was avail-ing the 5-12 week gestation period（Environ Int.

able on a cohort of 8,631 mothers who had full-2016）. Exposure to SO2 2 days before birth wasterm singleton deliveries. The extent of hy-

associated with placental abruption（OR=1.4, 95%

peremesis gravida was assessed using patient

CI=1.1-1.8）. There was no association with expo-

questionnaires. Pregnant women were asked thesure on other days or to other pollutants（Epide-following question： Did you have morning

miology. 2016）. Exposure to Ox during the 0-12

sickness from conception until about week 12 ofweek gestation period was associated with SGA

the pregnancy? The answers were interpreted（OR=1.07, 95% CI=1.01-1.12）, but there was no

as the following：1=no, 2=just nausea, 3=vomit-

association with exposure to Ox at 13 weeks ges-ing but able to eat, 4=vomiting and unable to eat.

tation or with exposure to other pollutants（Envi-

It was assumed that those who answered 1, 2, orron Pollut. 2017）. Exposure to SPM during early

3 were able to eat, and for those who answered 4,

pregnancy was associated with a false-positive

it was assumed that they were unable to eat be-

fetal heart rate abnormality（OR=1.20；95% CI

cause of severe morning sickness. The body

=1.05-1.37）（Sci Rep. 2017）. Hyperemesis gravida

weight of patients was also taken in considera-

was not associated with SGA（OR=0.81, 95% CI=

tion. It was assumed that those who lost 5% of

0.39-1.66）.

body weight during early pregnancy suffered【Discussion】

from hyperemesis gravida. The association be-

Our study showed how air pollution affects thetween air pollution and hyperemesis gravida wasuterus and placenta. Because the air pollution ex-

investigated using various types of regression

tended across a wide area, the number of preg-

analysis.

nant women exposed was large. However, pre-【Results】

ventive measures are available, and education

Our study demonstrated that a high-level of

may help to decrease exposure. Learning more

exposure to Ox during the 0-12 week gestation

about the effects of pollutants on pregnancy will

period was associated with pregnancy-induced

have significant clinical implications within thehypertension［odds ratio（OR）=1.20, 95% confi-

field of obstetrics. By learning more, appropriate

dence interval（CI）=1.01-1.42）. There was no as-

preventative measure can be developed and im-sociation with exposure to other pollutants（Envi-plemented. Therefore, further research is war-ron Res. 2015）. Exposure to SPM and Ox during

ranted in this area to help improve our current

the 0-4 week gestation period was associatedunderstanding of the effects of air pollution onwith placenta previa（SPM：OR=1.12, 95% CI=

pregnant women and their newborns.

Symposium

The association between hyperemesis gravida
and SGA was investigated by using primary

116

Overseas Invited Lecture 1

Precision Medicine：New Frontier in Womenʼs Health
Linda Giudice
University of California, USA

Overseas
Invited Lecture

Precision medicine is an emerging approachcine, will involve new clinical and scientificfor disease prevention, novel diagnostics, and in-knowledge and paradigms, transdisciplinary

dividualized treatments based on a personʼshealthcare teams, novel research collaborations

genes, environment, and lifestyle. Big scienceand workflows, and innovative opportunities forand big data, new technologies, and clinical co-

educators and the next generation of healthcare

horts with deep phenotyping and bio specimens

providers and investigators. Womenʼs Precision

for analyses comprise the basis of precision

Medicine has the promise of individualized

medicine, which is inextricably linked to social

therapies, diagnostics and prognostics to im-

and environmental determinants of health. It is

prove the health and well being of womenenvisioned that Womenʼs Precision Medicine, in-world wide.

!

tegrating womenʼs health and precision medi-

!

!

117

Linda Giudice
Linda C. Giudice, MD, PhD is Distinguished Professor, Chair Emerita, and the Robert B. Jaffe MD Endowed Professor in the
Reproductive Sciences in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California, San Francisco（UCSF）. She is a biochemist and reproductive endocrinologist specializing in endometriosis and infertility. Her research focuses on human endometrial function and regeneration, genetics and epigenetics of endometriosis, placental uterine interactions relevant to pregnancy outcomes, and evaluating the evidence of environmental impacts on reproductive health and human development. She has mentored over 250 students, fellows and faculty, authored > 300 peer
reviewed publications, and is co editor of 7 textbooks on womenʼs health, reproductive environmental health, endocrinology, endometrium and endometriosis. She is Past President of the American Society for Reproductive Medicine, the Society for Gynecologic Investigation, and the World Endometriosis Society, and is President elect of the International Federation of Fertility Societies, and Chair of the International Federation of Gynecology and Obstetrics（FIGO）Reproductive andDevelopmental Environmental Health Working Group. Dr. Giudice is on the UCSF Steering Committee on Womenʼs Precision Medicine, the March of Dimes Scientific Advisory Council, and is an elected member of the U.S. National Academy ofMedicine and the U.S. National Academy of Inventors.

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Overseas
Invited Lecture

118

Overseas Invited Lecture 2!

Genetics of Pre eclampsia
Hannele Laivuori1,2,3,4
Tampere University Hospital, Finland1,
University of Tampere, Finland2,
University of Helsinki, Finland3,
University of Helsinki and Helsinki University Hospital, Finland4

Overseas
Invited Lecture!

Pre eclampsia has its origins in early preg-quency variants in FLT1 that may protect from

nancy long before the onset of its signs andpre eclampsia. These variants are enriched in a!

!

symptoms. The genetic basis of pre eclampsia

Finnish population and may also protect fromand its link with increased lifetime risk of cardio-

heart failure in later life. Identification of rare/

vascular diseases are impcompletely understood.

low frequency variants associated with pre ec-

According to the epidemiological studies mater-

lampsia in both previously identified loci andnal and paternal genes affect the risk. The Inter-

novel loci may be easier in founder populations.

thPregGen consortium funded by the EU 7

Centrally collected medical, prescription andFramework Programme has studied many thou-

many other national registries may disclose newsands of women affected by pre eclampsia fromgenotype phenotype relationships. Any newWestern Europe and Central Asia, together withgene discovery will highlight a known pathway

their partners and offspring, using genome wideor reveal a new biochemical pathway in theassociation screening（GWAS）. The consortium

pathogenic process leading to pre eclampsia andhas reported the first GWAS of offspring frommay also help identifying individuals withpre eclamptic pregnancies and discovery of thehigher risk for later cardiovascular disease. A

first genome wide significant susceptibility lo-

successful strategy of combining genetic factors

!

!

!

!

!

!

!

!

!

cus near the fms related tyrosine kinase geneand non genetic factors in early pregnancy for（FLT1） encoding fms like tyrosine kinase 1 im-risk prediction of pre eclampsia would be a ma-plicated in pre eclampsia. Using targeted exome

jor advance in healthcare.

!

!

!

sequencing we have found maternal low fre-

!

119

Hannele Laivuori
Hannele Laivuori M.D., Ph.D. is an associate professor at the Faculty of Medicine and Life Sciences, University of Tampere
and an assistant chief physician at the Department of Obstetrics and Gynecology, Tampere University Hospital, Finland.
She is board certified in Obstetrics and gynecology and in Clinical genetics. Professor Laivuori serves also as a clinical teamleader at the Institute for Molecular Medicine Finland（FIMM）,HiLIFE Unit, University of Helsinki in the FinnGen project.
It is an international large scale genomics public private partnership research project, which brings together Finnish biobanks, universities, hospital districts and international pharmaceutical companies. Professor Laivuori is scientifically recognized for her work on genetics of pre eclampsia. She has led the clinical translation arm of the InterPregGen project fundedby the EU 7th Framework programme, a largest Genetics of pre eclampsia study to date. She currently lists over 100 papers
published in the peer reviewed literature. She is regularly invited to lecture at international meetings. Professor Laivuori
is an active mentor having supervised several graduate students and postdoctoral fellows. She has also been active in improving careers of clinical medical researchers.

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Overseas
Invited Lecture

120

Overseas Invited Lecture 3!

Reducing the Rate of Preterm Birth Results of!

a State wide Implementation Program
John Newnham
The University of Western Australia, Australia

Overseas
Invited Lecture

Preterm birth（PTB）is the single greatest

women and their families based on print and so-

cause of death in the newborn period and a ma-!

cial media（known as thewholeninemonths ）.In

jor contributor to long term disability. Discover-the first full calendar year（2015）the rate of sin-

ing how to safely prevent early birth needs to begleton PTB state wide fell by 7.6% and the effectone of our highest priorities. In 2014, Western!!

continued down to the 28 31 week gestational

Australia introduced a state wide whole ofage group. In the stateʼs major tertiary level cen-population multi faceted PTB prevention pro-tre the PTB rate fell by 20% and was accompa-

gram based on seven interventions. These in-nied by a significant increase in births in the 39

cluded avoidance of non medically indicated late

week age group. There was no change in thepreterm/early term birth；routine measure-stillbirth rate. These findings have shown that ament of cervix length at mid pregnancy ultra-

comprehensive and multifaceted prevention pro-sound scans；vaginal progesterone for short-gram aimed at both health care practitioners andened cervix or prior history of early birth；ap-

the general public and using existing knowledge

propriate use of cerclage；smoking avoidance；

can significantly lower the rate of preterm birth.

and a dedicated new clinic. The new clinicalFurther research is required to expand the effectguidelines were promoted by a state wide out-

and to determine how the program can bereach program for all health care practitioners

adopted into other health care environments.

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and a public health campaign was introduced for

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121

John Newnham!

John Newnham is Professor of Obstetrics at The University of Western Australia（UWA）and is a sub specialist in Maternal
Fetal Medicine. He is Head of the UWA Division of Obstetrics and Gynaecology based at King Edward Memorial Hospitalin Perth and Chief Scientific Director of the Women and Infants Research Foundation.
His research interests focus on prevention of preterm birth and the early life origins of health and disease. He has initiatedmany clinical and laboratory research studies, including The Raine Study and the Western Australian Preterm Birth Prevention Initiative.

Overseas
Invited Lecture

122

Overseas Invited Lecture 4

Personalized Cancer Models for Discovery andDevelopment of Novel Therapeutic Targets
Christopher Kemp
Fred Hutchinson Cancer Research Center, USA

Overseas
Invited Lecture

A major goal of precision oncology is to util-

siRNA and drugs using patient tumor samples.

ized genomic information to inform patient care.

This functional data combined with genomic

While there are spectacular examples of success,analysis is used to distinguish driver from pas-

for the great majority of cancer patients,

senger mutations and identify novel drug targets

genomic information is insufficient to guide pa-

and potentially effective drugs specific to atient care or select effective therapeutic options.

given patient. We will describe applications of

We have developed an approach that employs

this approach to identify novel targets for cis-high throughput functional testing with both

platin resistant ovarian cancer.

123

Christopher Kemp
Christopher Kemp received an MS in Toxicology from Oregon State University and a PhD in Oncology from the Universityof Wisconsin. He did postdoctoral research at the Beatson Institute, University of Glasgow and has been a faculty at theFred Hutchinson Cancer Research Center for 23 years. He has made major discoveries in cancer genetics, including identifying p27/Kip1 and CTCF as haploinsufficient tumor suppressor genes. He has studied the interaction between Ras, p53
and Arf during tumor progression using mouse models. More recently his work is focused on identifying new cancer drug
targets using siRNA screening and patient relevant cancer models. This work has led to a successful clinical trial targeting
the WEE1 kinase in head and neck cancer patients.

Overseas
Invited Lecture

124

Overseas Invited Lecture 5

How Has Our Understanding of Abnormal Uterine Bleeding（AUB）
Changed during the Last Decade?
Rohana Haththotuwa1,2,3
Ninewells Care Mother and Baby Hospital, Sri Lanka1,
AOFOG2,
FIGO, Committee for Menstrual Disorders3

Overseas
Invited Lecture

Abnormal uterine bleeding（AUB）has been

The classification of causes has been done undera neglected area till recently. But during the last

the PALM（with structural abnormality）, COEIN

decade many changes have taken place regard-（without structural abnormality）classification.

ing, the cultural issues, terminology, classifica-

Further the structural abnormalities like polyps,tion of causes ＆ the investigations ＆ treatment

adenomyoses and leiomyoma are been sub clas-of AUB.

sified.

!

Culturally menstruation has been a taboo sub-Major changes have taken in the investiga-

ject, been plagued with myths, fears, misunder-

tions with the development of trans vaginal ＆ 3

standings which prevented women particularly

D ultra sound scans, CT Scanning, MRI ＆ Hys-in the developing countries from attending toteroscopy.

house hold activities, social functions and relig-

In the medical management choice of treat-ious places during menstruation. This resulted inment agents have increased during the recent

a delay in women seeking treatment for AUB.

past. These include anti fibrinolytics, COX in-

There has been a reduction of these myths andhibitors, newer oral contraceptives, Levonorg-

cultural issues over the years with the improve-

estril intra uterine system, GnRH agonists ＆ an-

ment in education.

tagonists, and Progesterone receptor modulators.

With regards to the nomenclature the terms

In the surgical side the need for hysterectomy

used were ill defined and there was no uniform-

due to AUB has markedly reduced due to the im-

ity around the world sometimes within the same!

proved medical therapy and the development ofinstitution there was no clear definition all

uterus sparing surgical procedures which in-round making it difficult to communicate. Under-

clude hysteroscopic polypectomy, endometrial

stand research publications, design clinical trials

ablation ＆ resection, adenomyomectomy andand to teach ＆ educate. So the confusing terms

uterine artery embolisatin.

!

like menorrhagia, metrorhagia, dysfunctional

These changes during the last decade has re-bleeding has been discarded and simple English

sulted in a marked improvement in the under-

terms using the frequency, regularity, duration

standing and management of AUB.

and volume to describe various forms of AUB.

125

Rohana Haththotuwa
Consultant Obstetrician ＆ Gynaecologist
Chairman, Ninewells CARE Mother ＆ Baby Hospital
Secretary General, Asia Oceania Federation of Obstetrics ＆ Gynaecology（AOFOG）
Chairman, Menstrual Disorders Committee, FIGO
Vice President, South Asian Federation of Obstetrics ＆ Gynaecology
Past President, Sri Lanka College of Obstetricians ＆ Gynaecologists
Past President, Menopause Society of Sri Lanka
Vice President, South Asian Federation of Menopause Societies

Country Representative Aspire（Asia Pacific Initiative in Reproductive Endocrinology ）Overseas
Invited Lecture

Treasurer, Asia Pacific Society for Infections in Gynaecology ＆ Obstetrics from 2010

126

Overseas Invited Lecture 6

Optimisation of Antenatal Steroid Therapy
Matthew Kemp
The University of Western Australia, Australia

Antenatal steroids are routinely given tosame dose of potent steroids as a 120 kg woman

women in anticipation of preterm delivery. The

in preterm labour at 34 weeksʼ gestation. Theremost common agents in clinical use today are be-is significant variation in the efficacy of antena-

Overseas
Invited Lecture!

tamethasone（as a combined preparation of ace-

tal steroid therapy, and on going debate remains

tate and phosphate）, betamethasone or dex-

around the use of repeat（aka rescue ）courses

amethasone phosphate. Antenatal steroids actof steroids, and the use of steroids in late pre-via the glucocorticoid receptor to drive preco-

term birth.

cious maturation of the preterm lung, resulting

Drawing on evidence from clinical and basic

in improved outcomes（chiefly reduced lung andscience studies, this paper will advance the argu-

brain injury）for preterm infants. Although ante-

ment that antenatal steroids can and should un-

natal steroids convey clear benefit when admin-dergo further, patient specific optimisation in an

istered appropriately, their use remains un opti-

effort to improve the efficacy and safety of thismised；as such, a 50 kg woman in preterm la-important therapy for preterm infants and theirbour at 26 weeksʼ gestation receives the exact

mothers.

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127

Matthew Kemp
Matt completed his undergraduate studies in New Zealand at Otago University. He holds PhDs in Medicine（University of
New South Wales）and Education（University of Western Australia）, and completed postdoctoral training at Oxford University with the support of an MRC Career Development Fellowship. He is presently employed as an Associate Professor（Research）in the Division of Obstetrics and Gynecology at the University of Western Australia.

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His research interests in perinatology are focused on improving outcomes for preterm infants, and include anti inflammatory and antibiotic therapies, antenatal steroid treatment optimisation, and the development of an artificial uterine life support platform for extremely preterm infants.
Mattʼs work has been supported by a range of national and international agencies including the National Health and Medical Research Council, the National Institutes of Health, the Bill and Melinda Gates Foundation, the Royal Society, the Ramaciotti Foundations and the Financial Markets Foundation for Children. He maintains an active research interest in evidence based graduate education and is presently completing the Program for Leadership Development at Harvard Business School.

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Overseas
Invited Lecture

128

Overseas Invited Lecture 7

A Search Engine of Personalized Treatments for Ovarian Cancer
Carla Grandori1,2，Franz X. Schaub1，Rachele Rosati2，Reid C. I. Shaw2，Hallie A. Swan1，
Michael J. Churchill1，Roland M. Watt1，Caroline Bridgwater1，
Stephanie A. T. Murphy1，Robert L. Diaz1，Vijayakrishna Gadi3，Chris J. Kemp3，
Shalini C. Pereira1
SEngine Precision Medicine, USA1,
Cure First, USA2,

Overseas
Invited LectureFred Hutchinson Cancer Research Center, USA3

tary set of metrics, resulting in a SPMTM score,【Background】
Ovarian cancer exhibits a distinct and uniquewhich weights both the sensitivity and unique-mosaic of genomic alterations, which rarely indi-

ness of each tumor response. The results are in-cating therapeutic choices. To advance a func-

tegrated with genomic data and reported to thetional approach to precision medicine we haveclinician to highlight treatment options.

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developed a high throughput assay that employs
organoid cultures derived from patient speci-【Results】

mens to directly determine drug responses to a

Thus far, SEngine has performed drug screen

comprehensive set of 131 oncology drugs. Herestudies with ＞150 cancer organoids from ＞20

we present the results obtained with this novel

tumor types and established high reproducibil-

test, named P.A.R.I.S. in analogy with Paris whoity. Results from several ovarian cancer speci-

defeated Achilles, by aiming precisely at its

mens will be presented. To facilitate communica-

weakness, to aid oncologists select personalized

tion of the test results, SEngine has developed antreatments.

in house application suite（SEngine Medicine!

APP）, consisting of interactive charts, statistical【Experimental Procedures】

analysis, and reactive reports which can be

Organoids are derived from surgical resec-

shared with oncologists and investigators. We

tions, biopsies or ascites and exposed to a librarywill discuss applications of the P.A.R.I.S. test toof clinically relevant drugs. The assay measuresaccelerate development of novel targeted drugs

cell viability and multi dose response curves are

and overcome drug resistance in ovarian cancer.

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evaluated and drug are ranked using a proprie-

129

Carla Grandori
Dr. Carla Grandori, MD, PhD. CEO of SEngine Precision Medicine and Scientific Director, Cure First.
I am a cancer researcher of >30 years, aiming to contribute to the discovery of less toxic treatments for cancer. I received
an MD degree in 1982 from the University of Rome, La Sapienza, followed by a PhD at the Rockefeller University in New
York under the guidance of Dr. Hanafusa, a pioneer of oncogenes. My research career continued at the Fred Hutchinson
Cancer Center, focused on the MYC oncogene and was complemented by industry experience at Rosetta Inpharmatics（asubsidiary of Merck）. Adopting the technology of high throughput RNAi screens my laboratory identified MYC synthetic
lethal genes as candidates for therapeutics. In 2009, I joined as director the Quellos High Throughput Screening（HTS）facility at the University of Washington, and awarded a Presidential Entrepreneurial Award from the UW. Our technology wasrecognized in 2013 with a prestigious grant from the Cancer Target Discovery and Development Network（CTD2, NCI）tocontinue the discovery of novel drug targets. In 2012, I co founded Cure First, a not for profit organization dedicated to accelerate research and delivery of personalized treatments for cancer. In 2015, I co founded and since led SEngine Precision
Medicine, advancing novel drugs and personalized treatments to the clinic.

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Overseas
Invited Lecture

130

Overseas Invited Lecture 8（Web Lecture）

Screening and Prevention of Preeclampsia
Kypros Nicolaides
King’s College London, UK

Overseas
Invited Lecture［CV］
Qualifications：1974 Biochemistry and Physiology BSc（1st classhonours）,Kingʼs College, London University.
1978 Medicine, MBBS, Kingʼs College Hospital,
London University.
1984 Obstetrics and Gynaecology, MRCOG.
2014 Obstetrics and Gynaecology, FRCOG.
Present post from 1992：
Professor of Fetal Medicine, Kingʼs College, London,Awards：1. Ian Donald Gold Award of the International Society Ultrasound in Obstetrics ＆ Gynecology, forHighest Contribution in Ultrasound, 1999
2. Eric Saling Award of the World Association ofPerinatal Medicine, for highest scientific contribution in Perinatal Medicine, 2001
3. Excellence in Letters, Culture and Science,
Government of Cyprus, 2004
4. Honorary Fellowship of the American Institute of Ultrasound in Medicine, USA 2004.
5. Maternity Prize of the European Associationof Perinatal Medicine, 2014.
6. Eardley Holland Gold Medal of the Royal College of Obstetricians and Gynaecologists, 2015.
7. Honorary Doctorate in Medicine：Universityof Athens in Greece（2005）, University of Warsaw in Poland（2009）, University of Bucharest in
Romania（2009）, University of Jinan in China（2010）,Spinoza Chair, University of Amsterdam,in the Netherlands（2010）,University of Olomouc
in Czechia 2011, University of Ioannina in Greece
2012, European University of Cyprus in Cyprus（2013）,University of Thessaly in Greece（2016）,
Aristotelion University of Thessaloniki in Greece（2017）.

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Scientific Activities：
・Published 1,378 peer review papers in Scientific Journals. He ranks 237th in the list of themost highly cited researchers, both living anddeceased. He ranks 1st amongst all Obstetricians!

and Gynaecologists. His h index is 142 and his
work has been cited 86,732 times.
・Edited several books and introduced internet
based courses for health care professionals andpatients in 20 languages.
・Supervised 52 research fellows who obtained
PhDs and MDs.
・Provided training in Fetal Medicine to morethan 500 doctors from 50 countries.
・Introduced new methods of fetal therapy, including intrauterine blood transfusions for fetal
anemia, thoraco amniotic shunting for drainageof pleural effusions, endoscopic laser surgery forsevere twin to twin transfusion syndrome andendoscopic tracheal occlusion for diaphragmatic
hernia.
・Described new methods of screening for fetal
abnormalities, including the lemon and banana
signs for spina bifida and nuchal translucency
for Downʼs syndrome which are now the accepted methods of screening throughout theworld.
・Introduced new approach for early screeningforpregnancy
complications,
including
preeclampsia, preterm birth, gestational diabetes, miscarriage and stillbirth, macrosomia andfetal growth restriction.
・Demonstrated the benefit of progesterone inprevention of preterm birth and aspirin in prevention of preeclampsia.

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Founder and Chairman of the Fetal Medicine
Foundation
This charity was set up in 1995. The main sourceof income is a private clinic which donates all its
profits to the charity. The aims are to promoteresearch and training in Fetal Medicine throughout the World. More than ￡22,000,000 have been
donated to finance the training of many doctors
from all over the world and to carry out major
multicentre studies on screening and preventionof preterm delivery and preeclampsia, which are
the leading causes of perinatal mortality.

131

MEMO

Overseas
Invited Lecture

132

Overseas Invited Lecture 9

Management of Preterm Labor, Delivery and Newborn at
National Hospitals in Cambodia
Sann Chan Soeung1，Koum Kanal1，Prak Somaly2，Seang Sody2，Chhun Samsophea3，
Im Sethika3，Soeung Sophornmony4，Siek Meng4，Chhea Chhorvann5，
Chau Darapheak5，Noriko Fujita6
Cambodian Society of Gynecology and Obstetrics, Cambodia1,

Overseas
Invited Lecture

National Maternal and Child Health Center, Cambodia2,
Calmette Hospital, Cambodia3,
Khmer Soviet Friendship Hospital, Cambodia4,
National Institute of Public Health, Cambodia5,
National Center for Global Health and Medicine, Japan6【Objectives】

women who received corticosteroid before deliv-

The study aims to review the current clinicalery was 43.6%. Among all preterm newborns

management of preterm labor delivery and new-

6.3% of them died. The proportion of newbornborn outcomes at three national hospitals indeath was more likely found among women who

Cambodia, the referral centers in the domain of

did not received corticosteroid（33.3% vs 83.3%

gynecology and obstetrics.

for ＜1,000g, 14.5% vs 55.6% for 1,000 1,499g and【Methods】

1.9% vs 9.5% for 1,500 1,999g）. Percentage of!

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Patient records on preterm delivery were re-newborn death was higher among women whoviewed by hospital staffs for three months period

came from the provinces than women living infrom August to October 2016. Maternal back-the capital Phnom Penh（3.9% vs 8.3%）. Womengroundofwho had induced labor newborn death havemother, laboratory test results, clinical manage-

higher than spontaneous vaginal delivery（4.6%

information,clinical

symptoms

ment, mode of delivery, postpartum, and new-vs 15.6%）.

born outcome were collected for statistical【Conclusion】

analysis at the National Institute of Public Health

Our data showed low percentage of corti-

Cambodia in December 2016.

costeroid use but proved efficiency to improve【Results】

the newborn outcomes among the referral hospi-

The total number of preterm delivery in three

tal in the capital Phnom Penh. Protocol for pre-national hospitals was 605 representing 11% ofterm labor delivery should be standardized andtotal number of deliveries. The percentage ofpromoted urgently in Cambodia.

133

Sann Chan Soeung
PROFESSION ：Medical Doctor：Professor of University of Medical Science in Phnom Penh, Cambodia
WORK EXPERIENCES：
1982：OB GY Ward at Kossamak Hospital
1999：Chief of Technical Bureau of the National Maternal and Child Health Center（NMCHC）
2000：Deputy Director of the NMCHC and Manager of National Immunization Program, Ministry of Health2015：Head of Scientific Committee of the Cambodian Society of Gynecology and Obstetrics

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Overseas
Invited Lecture

STUDIES：Management of Preterm Labor Delivery and Newborn at the National Hospitals in Cambodia（2016）
Evaluation of Maternal Neonatal Tetanus in Cambodia in collaboration with WHO and UNICEF（2013）
Evaluation of Measles in Cambodia in collaboration with WHO and UNICEF（2012）
Prevalence of chronic hepatitis B virus infection after implementation of a hepatitis B vaccination program among children in three province in Cambodia（2012）
The social determinants of health and health service access：an in depth study in four communities in Phnom Penh（2012）
Hepatitis B survey in Cambodia using rapid test（2009）

134

Overseas Invited Lecture 10

Prenatal Programming, Epigenetics and Transgenerational Outcomes
Stephen Matthews!

University of Toronto and The Lunenfeld Tanenbaum Research Institute, Sinai Health Systems, Canada

Overseas
Invited Lecture

The developing fetal brain is highly respon-

prefrontal cortex（PFC）, hippocampus and hypo-

sive to endocrine, nutritional and chemical cues.

thalamic paraventricular nucleus（PVN）.Effects

Glucocorticoids（GC）are critical for normal brain

are associated with altered function of the hypo-development and are tightly regulated at low

thalamic pituitary adrenal（HPA）and stress re-levels in the fetus for the majority of pregnancy.

lated behaviours in offspring, and these effects

Levels increase rapidly in late gestation. Thisare maintained in to adulthood. Most recently,

surge is critical for fetal lung development andwe have shown that the effects of GCs on epige-

maturation of other organ systems including the

netic/transcriptional landscapes, HPA function

brain. Fetal GC levels can be elevated earlier inand behaviours can extend across multiple gen-gestation as a result of maternal or fetal stress or

erations, and that this can occur via maternalmaternal treatment with synthetic GCs. The lat-and paternal transmission. Our findings have sig-

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ter occurs in cases of threatened preterm birthnificant implications for clinical practice, but（＞10% of all pregnancies）. Using an animalalso our fundamental understanding of themodel, we have shown that premature exposure

mechanisms by which the fetal endocrine envi-of the fetal brain to GC can lead to profoundronment impacts the developing brain leading tochanges in the epigenetic（DNA methylation,

life long modification of endocrine function andacetylation）and transcriptional landscapes in the

behaviours.

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135

Stephen Matthews
Stephen G. Matthews is Professor of Physiology, Obstetrics and Medicine at the University of Toronto and Director of Research at the Alliance for Human Development. Professor Matthews received his PhD from the University of Cambridge,
UK, was appointed to the University of Toronto in 1996 and served as Chair of the Department of Physiology from 20072014. He has secured over $25M in research funding and has published over 200 full papers. He has won a number of prestigious research prizes including The 2006 Mortyn Jones Memorial Medal, and The 2012 Presidentʼs Achievement Award
from the SRI（formerly SGI）
. Professor Matthews has served on Editorial Boards of several Journals including Endocrinology and Journal of Neuroendocrinology. He is a member of Council for SRI and DOHaD and has served as Scientific Program Chair for both Societies. In 2015, he co founded DOHaD Canada. His research is focused towards understanding how
the fetal environment affects developmental trajectories leading to modified neurologic and endocrine function. He has established that these effects can extend across multiple generations. With a focus on epigenetics, his research team is determining the molecular mechanisms by which such ʻprogrammingʼ can occur. In parallel, he is investigating drug and hormone transport mechanisms in the placenta and fetal brain, with a focus on protection of the fetus. Professor Matthews iscommitted to translating fundamental research. He is currently co leading large pregnancy intervention studies in India
and Africa focused towards improving maternal, infant and child health.

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Overseas
Invited Lecture

136

Overseas Invited Lecture 11

Gene Correction in Human Embryos
Shoukhrat Mitalipov
Center for Embryonic Cell and Gene Therapy, Oregon Health ＆ Science University, USA

Overseas
Invited Lecture

In vitro fertilization（IVF）represents a suc-tant paternal MYBPC3 locus, were efficiently re-cessful cell therapy approach for treatment of in-paired by homology directed repair（HDR）

fertility. However, IVF is increasingly utilizedmechanisms using the wild type maternal allele

for preimplantation genetic diagnosis（PGD）fol-

as a template. By modulating the cell cycle stage

lowed by embryo selection to prevent the trans-

at which CRISPR Cas9 was introduced, we were

mission of heritable human diseases. We recently

able to avoid mosaicism in embryos and achievesought to complement PGD by attempting to res-a high yield of homozygous embryos carrying

cue mutant embryos by correcting the heterozy-

the wild type MYBPC3 gene without evidence

gous deletion in MYBPC3 gene causing hy-of off target mutations. The efficiency, accuracy

pertrophic cardiomyopathy（HCM）. Our study

and safety of the approach presented suggest

demonstrated that in a substantial portion of het-that it has potential to be used for the correction

erozygous human embryos, CRISPR Cas9 in-of heritable mutations in human embryos.

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duced double strand breaks（DSBs）at the mu-

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137

Shoukhrat Mitalipov
Shoukhrat Mitalipov, Ph.D., directs the OHSU Center for Embryonic and Gene Therapy, where he is focused on developing
treatments to prevent the transmission of genetic disease from parent to child. Mitalipov is also a professor of biomedical
engineering and obstetrics, gynecology and pediatrics in the OHSU School of Medicine with appointments in the Oregon
National Primate Research Center and Knight Cardiovascular Institute. Mitalipov earned his Ph.D. in 1994 from the Research Center for Medical Genetics in Moscow. He arrived at OHSU in 1998 after conducting postdoctoral research in stem
cell and developmental biology at Utah State University.
In August 2017, Dr. Mitalipov and his colleagues published groundbreaking research in Nature demonstrating that thegene editing tool CRISPR can be effectively used to repair a disease causing mutation in a human embryo and prevent thedisease from being passed down to future generations. The focus of the study was the gene mutation that causes hypertrophic cardiomyopathy, a common inherited condition that can cause sudden cardiac death and heart failure. This is
the first time scientists have successfully tested the gene repair method on donated clinical quality human eggs. Results ofthis landmark research were reported in thousands of media outlets worldwide.

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Overseas
Invited Lecture

138

Overseas Invited Lecture 12

Evidence and Eminence in Secondary Prevention of Preterm Birth!An Overview Comparing Vaginal Progesterone,!

Cerclage and Cervical Pessary in Singleton and Twin Pregnancies
Birgit Arabin
Philipps University/Clara Angela Foundation, Germany

Overseas
Invited Lecture

Transvaginal sonography（TVS）is used fornancies with previous PTB and combined cervi-

secondary prevention of preterm birth（PTB）,

cal shortening in the current pregnancy. The

but the sensitivity is still low. Trials based on

short and long term outcome could not be im-

TVS show controversial results ― by addressing

proved, whereas maternal complications seemthe controversies we try to optimize transpar-increased. A cervical cerclage should not be indi-ency for clinicians who need to make decisionscated in twin pregnancies even not when they

on a daily basis.

have a short CL.

Vaginal progesterone may reduce PTB＜34

A cervical pessary in singleton pregnancies

weeks in screened singleton pregnancies. Up toseems to be effective in hands of experienced cli-

now, no positive long term effect could be dem-

nicians. Then it has been shown to prolong preg-

onstrated. It has no benefit to prolong pregnan-nancies and to reduce poor neonatal outcome.

cies after preterm contractions and in risk pa-

Mainly in twin pregnancies, pessary treatment

tients without cervical shortening. Randomized

seems to be promising compared to other options

controlled trials（RCTs）apart one non registeredwhen the therapy is started at early stages ofand non placebo controlled trial showed no

precocious

benefit in unselected or selected twin pregnan-

proven cost effectiveness and improved longcies. Meta analyses for singleton and twin preg-

term outcome.

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nancies still demonstrate conflicting results de-!

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cervical!

ripening.

StudieshaveComparative trials and a prospective meta!
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pendent on selection criteria.

analysis are in progress to better compare treat-

A cerclage is（only）indicated in singleton preg-

ment options in specific subgroups.

139

Birgit Arabin
Medical University
Medical Curriculum

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1971 1975 Albert Ludwig University Freiburg（Germany）
1975 1978 Free University Berlin
1978 1979 Research Fellow University Hospital Brussels and at theInstitute for Perinatal Medicine Berlin
1979 1985 Residency OBGYN Ruprecht Karl University Heidelberg
1985 1988 Assistent Professor Institute for Perinatal Medicine Berlin
1988 1993 Assistant Professor Free University Berlin
1992 1993 Lecturer/Studies School of Public Health Hannover
1993 2008 Consultant Perinatal Centre Zwolle NL
Subspecialist Maternal Fetal Medicine in Germany ＆ The Netherlands
Level III DEGUM Ultrasound/Germany
Lecturer Private University Witten Herdecke ＆ Humboldt University Berlin
2008 now Head of Prenatal/High risk pregnancyAcademic Perinatal Board
Philipps University Marburg Germany!

Organizations

References
Medical Interests

Awards!

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1988 Harris Birthright Center London/ Prof. Nicolaides
1991 Dep. of Prenatal Medicine Bonn/ Prof. Hansmann2008 Centre for Prenatal Therapy Poissy Paris/ Prof. Ville
Member/Board of Societies of Perinatal Medicine such as WAPM,
SMFM, ISUOG, IAPM, NVOG, DGGG, DGPM, DGPPM
Reviewer German Research Funding BMBF/several international journals!

Appr. 50 books/ book chapters, >100 peer reviewed papers, >500 international
lectures preferably on topics of Perinatal Medicine
Prevention of preterm birth, fetal growth, prenatal diagnosis, fetal programming,
twin pregnancy, public health concepts, national and international education andpostgraduate training, partnerships in the field of perinatal medicine
Staude Pfannestiel Price 1988,
Ambroise Pare Medal Int. Academy Perinatal Medicine 2005,
Award World Association Perinatal Medicine 2008,
Hackert Price Prenatal Medicine 2009,
Pschyrembel Medal 2013
Dexeus Medal 2015
Dr. honoris causa Sorbonne Paris 2016

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Varia
Other Interests!

1997 Founder Clara Angela Foundation Witten/Berlin http://clara angela.info
based on Dr. Arabin GmbH www.dr arabin.deMusic, literature and poetry, implication of humanity into political concepts, to live
a balanced life, to organize original meetings, to create an angel museum.

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Overseas
Invited Lecture

Sabbatical

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140

Overseas Invited Lecture 13

Ultrasound Grading of Cesarean Scar Pregnancies and Its Implication for
the Strategy of Management：Experience at a Single Medical Center
Chien-Nan Lee1,2National Taiwan University Hospital, Taiwan1,
President elect. the Federation of Asia and Oceania Perinatal Societies2【Objectives】

Overseas
Invited Lecture!

Seventy eight women received surgery, andA cesarean section pregnancy（CSP）is a preg-the complication rate was 12.8%（10/78）. Linearnancy in which the gestational sac is implanted

regression analysis demonstrated a significant

in the previous cesarean section scar. The clini-

association between the invasiveness of the op-

cal manifestations of CSP present a wide range

eration and the ultrasound grading. The main-of differences, and optimal management is yet tostream operation for grade I CSP was transcervi-

be defined. We propose an ultrasound grading

cal resection, while the majority of grade III andsystem and discuss its implications for the man-

IV patients required hysterotomy or hysterec-

agement of CSP.

tomy. Another 31 women received chemother-【Methods】

apy with methotrexate as their initial treatment.

This was an observational, retrospective co-

The success rate for chemotherapy was only

hort study. We enrolled 109 patients with the di-61.3%；the remaining patients had to receive

agnosis of CSP from our department and classi-

further surgery due to persistent CSP or heavy

fied these cases into four grades according to thebleeding during or after chemotherapy. Fifteen

implantation depth and the ultrasound morphol-patients（48.3%）
receiving chemotherapy sufferedogy. A gestational sac（GS）embedded in less thanfrom complications（mostly bleeding）. Among

one half thickness of the myometrium was cate-them, 7（22.6%）patients experienced bleeding ofgorized as grade I, and a GS embedded in more

more than 1,000 mL, while 10（32.3%）of these 31

than one half thickness was considered grade II.

patients required blood transfusions to stabilize.

In grade III CSP, the GS bulged out of the cesar-【Conclusions】!

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ean scar, and grade IV was defined as cases in

Our new ultrasonographic grading system

which the GS became an amorphous tumor withmay help determine the optimal surgical strat-rich vascularity at the site of a previous cesarean

egy for CSP. Chemotherapy with methotrexate

scar.

for CSP is not satisfactory and is associated with

【Results】

a high rate of complications.

141

Chien-Nan Lee!

Prof. Chien Nan Lee is the Professor and Attending Physician of Obstetrics, Department of Obstetrics and Gynecology, National Taiwan University Hospital. He is the Federation of Asia and Oceania Perinatal Societies of President. His special interests are ultrasound of fetal anomaly, high risk pregnancy and prenatal genetic diagnosis. He is one of the top experts on
those therapeutic area internationally.
Prof. Lee, as a professional obstetricians and a senior researcher, he published lots of clinical papers and train many young
obstetricians to make them become not only clinicians but also scholars in clinical researches.
Prof. Lee is continuously appointed as a medical consultant or advisor for ultrasound of fetal anomaly, high risk pregnancy
and prenatal genetic diagnosis. Also, he is frequently invited as an international speaker to share his valuable experiencesand expertise in many countries, recently, he was just invited to give lectures in Vietnam, Japan and China etc.

Overseas
Invited Lecture

142

Overseas Invited Lecture 14

Prevention of Preterm Birth：Progesterone vs Cerclage
Keun-Young Lee
Hallym University, Korea

There are 15 million babies delivered prema-

followed by either progesterone or cervical cer-

turely every year, and the incidence of preterm

clage. However, there is controversy about thebirth is rising. Each year 1.1 million babies die ofissue of progesterone vs cerclage for prevention

Overseas
Invited Lecturecomplications from preterm birth（PTB）, makingof PTB. We donʼt have sufficient data to deter-

PTB one of the important issues in the obstetrics

mine what the best treatment for PTB preven-field worldwide. Several studies have provention is, among progesterone vs cerclage vs cer-that the use of either progesterone or cervicalclage with progesterone. Several studies have in-cerclage is effective in the prevention of preterm

vestigated the use of vaginal progesterone after

delivery. Regarding progesterone, the exact

cerclage and pessary. Among the various routes

mechanism of its action in preventing PTB is un-of progesterone delivery, including intramuscu-

known, although several mechanisms are pro-lar, vaginal and oral, vaginal progesterone has

posed. In general, the evidence seems to favor

the advantages of easy access and satisfactory

two mechanisms：an anti inflammatory effectpatient compliance. Although expectant manage-

that counteracts the inflammatory process lead-ment is an alternative to using vaginal progester-ing to PTB, and a local increase in progesterone

one after cerclage for short cervical length, ran-in gestational tissues that counteracts the func-

domized studies and long term safety data aretional decrease in progesterone leading to PTB.

needed to establish consensus guidelines. Adju-

Regarding cervical cerclage, meanwhile, com-vant vaginal progesterone therapy with PEICC

pared to the case of no intervention it is associ-has been associated with reductions in SPTB,

ated with reductions in the rate of PTB at 37

low birthweight and neonatal intensive care unit

weeks of gestations and in perinatal mortality.

admission. I would also like to introduce my algo-

There are many different guidelines for prevent-rithm, based on my clinical experiences includ-ing PTB recommended by the ACOG, SMFM,

ing ultrasound indicated cerclage by Leeʼs cer-

SOGC, and NICE. Most of their regimens mix theclage balloon and my published papers.

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measurement of CL by transvaginal ultrasound

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143

Keun-Young Lee
Contact details：
Department of Obstetrics and Gynecology
Kangnam Sacred Heart Hospital
College of Medicine, Hallym University
Seoul
Korea
Current postion：Professor in the Department of Obstetrics and Gynecology, Vice President, Hallym University Medical
Center!

Primary speciality：Obstetrics and gynecology, and maternal fetal medicine
Clinal interest：Preterm Labour, cervical insufficiency

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Professor Lee is expert at performing rescue, transabdominal and ultrasound!
indicated cerclage procedures, and has devel-

oped a new method of emergency cerclage, as well as new diagnosis and treatment methods for cervical incompetence. He
made Leeʼs（uniconcave）cerclage balloon and have patened with the Korean, USA, Japanese government and EU .
He has a special interest in clinical and translational research for cervical insufficiency, particularly the pathophysiology ofcervical insufficiency and preterm labour, and has built up a large bank of biological samples, including cervical mucus, amniotic fluid, maternal serum and neonatal secretion.

Professor Lee has published more than 130 papers and received several awards, including awards from the Korean Societyof Ultrasound（2000）and Best Paper of the Year prize from the Korean Society of Obstetrics and Gynecology（2005）.
He is influential in Korea and internationally, and has been invited to speak at several international congress. Professor Lee
has authored many articles and several text book chapters in the field of cervical insufficiency. He has been worked as an
editorial board at several international journal of Obstetrics such as Maternal Fetal Neonatal Medicine.

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Patent：Leeʼs Cercalge Balloon
Publishied Use of a uniconcave balloon in emergency cerclage
American Journal of Obstetrics and Gynecology, 2015, 212：111 114
Korean Patent 10 117085
USA Patent 9,028,506 B
Japan Patent 5863717!

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Overseas
Invited Lecture

Biography：Keun Young Lee is a Professor in the Department of Obstetrics and Gynecology at the Hallym University College of Medicine, Seoul, Korea. He trained in medicine at Chung Ang University, Seoul, Korea, and obtained his PhD at
same institute. He has current position since 1997, and appointed Vice President of the Hallym University Medical Centerin 2010. He has previously been chairman of the department（2006 2014）and Director of the Kanganm Sacred Heart Hospital,（2006 2010）and was past President of the Korean Society for Maternal Fetal Medicine（2008 2010）.

144

AOFOG Program ：Cervical Cancer Screening in Asian Countries

1）Current Status and Issues of Cervical Cancer Screening in Japan
Kiyoshi Ito
Tohoku University / JSOG

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AOFOG
Program

In Japan, cervical cancer screening is con-eration. The effects of a free coupon program un-ducted as a national project, and early discovery

der financial support from the national govern-

had contributed to reduction of morbidity andment was limited. Secondly, no surveillance data

mortality rates for cervical cancer. Miyagi pre-exist at the national level. Third, cervical cancer

fecture is one of the first areas in Japan to be in-screening using either human papillomavirus

volved in mass screening for cervical cancer（HPV）testing alone or HPV testing combined

since the 1960ʼs. However, incidence rates forwith cytology is still not recommended for popu-

cervical cancer has recently been increasing es-lation based screening, although screening using

pecially among young women such as 20s andconventional and liquid based cytology is recom-

30s in Japan. In the national screening guideline,

mended. Finally, the proactive recommendation

cervical cancer screening is performed by cervi-

for HPV vaccinations by the government has

cal cytology（Pap smears）in women aged 20

been suspended since June 2013, following re-years and over every two years, although there

peated media reports of adverse events after theis no upper age limitation. At this present, there

vaccination. Thereafter, the rate of HPV vaccina-

are several problems existed in cervical cancer

tion decreased dramatically. I will overview thescreening and prevention program in Japan.

current status on cervical cancer screening andFirst of all, the rate of cervical cancer screening

prevention in Japan.

is extremely low especially among young gen-

!

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AOFOG Program ：Cervical Cancer Screening in Asian Countries2）Paradigm Change in Cervical Cancer Screening with HPV Testing
Young-Tak Kim
University of Ulsan, Asan Medical Center, Korea / AOFOG

In 2015, the American Cancer Society, Ameri-

Primary hrHPV screening has made an impor-can Society for Colposcopy and Cervical Pathol-tant scientific and clinical advance in cervicalogy, and the American Society for Clinical Pa-

cancer screening since it offers better reassur-

!

AOFOG
Programthology updated interim clinical guidance for use

ance of low cancer risk compared to cytology

of primary hrHPV testing for cervical cancer

only screening conducted at the same interval.

screening. That is based on grown evidence forPrimary hrHPV screening can be considered as

screening with primary hrHPV testing. Previ-an alternative to current cytology based screen-

ously approved US FDA labeling for hrHPV test-

ing approaches including cytology alone anding included triage of equivocal cytology（i.e.,

cotesting. Until now, there is lack of firm consen-

ASC US）and as an adjunct to cytology whensus about a well defined and evaluated strategy

screening women 30 years and older（cotesting）.

to manage hrHPV positive women, inadequate

However, a large prospectively conducted FDA

information to define appropriate screening in-registration trial of primary hrHPV screening

tervals for hrHPV negative women, and lack ofdemonstrated improved sensitivity against CIN2

data on testing errors due to specimen inade-

!

!

!

!

!

!

!

and CIN3 over cytology alone. In April 2014, thequacy and cost effectiveness. While there con-

FDA approved modified labeling of a hrHPV as-tinue to be numerous practical and research

say to include primary hrHPV screening forquestions, primary hrHPV testing has a potential

women 25 years and older. Data from ATHENA

to further reduce morbidity and mortality of cer-and other studies support the use of genotyping

vical cancer.

for HPV 16 and 18 as a way to triage hrHPV positive women.

147

Young-Tak Kim
Present Title and Affiliation：
Professor of Department of Obstetrics and Gynecology
Director, Asan Medical International
University of Ulsan, Asan Medical Center, Seoul, Korea
Education and Certification：
1981 M.D. College of Medicine, Yonsei University, Seoul, Korea
1991 Ph.D. Graduate School, Yonsei University, Seoul, Korea
Postgraduate Training：
1994 1995 Fellowship at the Dept. of Pathology, Johns Hopkins University Hospital, USA.
2003 2004 Visiting Professor, Ohio State University Hospital, USA!
!

Academic and Administrative Appointments：
2002：Secretary General, IXth Biennial Meeting of IGCS 2002
2002 2003：Member of Educational Committee of IGCS
2003 2004：Member of Developmental Committee of IGCS
2004 2005：Representative of Asia Oceania in Nominating Committee of IGCS
2005 2006：Secretary General of AOGIN
2007 2015：Council of Asia Oceania Federation of Obstetricians and gynecologists（AOFOG）
2007 2008：Cervix Committee Member of GOG
2009 2012：Chairman of Scientific Committee of KSOG
2014
Executive Board Member of Korean Society of Cancer
2015
Executive Council of FIGO
2015 Chairman of Oncology Committee of AOFOG
2016 Chairman of Educational Committee of AOGIN
2016 Member of Educational Committee of IGCS
2016 President of Korean Society of Gynecologic Oncology

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AOFOG
Program

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148

AOFOG Program ：Cervical Cancer Screening in Asian Countries3）Paradigm Change in Cervical Cancer Screening with HPV Testing
Yin-Ling Woo
University Malaya Medical Centre, Malaysia / AOFOG

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AOFOG
Program

Organized cervical screening in high resour-with many professional bodies clearly recom-

ced countries have led to significant reductions

mend HPV testing for cervical screening. In fact,

in new cases of cervical cancer. However, it is ac-

many high income countries are now in the proc-

knowledged that the implementation of Pap

ess of changing their well estalished cytology

smear programs in many countries have notbased programs into HPV testing based pro-been successful for the lack of highly skilled hu-

grams. The entire landscape of cervical cancer

man resources, infrastructure and other barriers

prevention is now changing and stakeholders

to screening. In the meantime, many countries

need to review the necessary steps and options

are now adopting HPV vaccination as primarythat will be appropriate for their setting. The ap-

prevention. This does not negate the need forplication of design thinking principles to cervicalcervical cancer screening but calls for a para-

screening should serve as a starting point in ad-

digm change. The 2013 WHO guidelines along

dressing the unmet needs.

!

149

Yin-Ling Woo
Professor Woo Yin Ling is a Consultant Gynaecological Oncologist in University Malaya Medical Centre, Kuala Lumpur.
She is a clinician scientist, having completed her specialist and subspecialty training in gynaecological oncology in the UK.
Professor Woo was a Royal College of O and G Gold medallist for the MRCOG. She was also awarded the Gordon Hamilton
Fairley Fellowship by Cancer Research UK to undertake her research in the area of human papillomavirus immunology
and was conferred her PhD by the University of Cambridge.

!

Professor Woo is now part of a multidisciplinary team in University Malaya Medical Centre involved in cancer service provision/ development and collaborative research. Her most recent undertaking involves applying the principles of design
thinking to cervical screening in Malaysia.

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AOFOG Program ：Cervical Cancer Screening in Asian Countries

4）AOFOG Initiatives for Cervical Cancer Control
in Low Resource Countries
Pisake Lumbiganon1,2
The Royal Thai College of Obstetricians and Gynaecologists, Thailand / AOFOG1,
Vice President, Asia Oceania Federation of Obstetrics and Gynecology2

Cervical cancer is one of the leading causes ofally the lack of effective secondary prevention

cancer death in women most of which occur inthat include adequate screening coverage and ef-

low to middle income countries. Unfortunately,

fective treatment of those women with positive

about half of cervical cancer cases in the world

tests.

!

AOFOG
Programoccur in Asian countries. Asian countries with

Asia and Oceania Federation of Obstetrics andhigh incidence of cervical cancer include Bangla-

Gynecology（AOFOG）is a regional professionaldesh, Cambodia, Indonesia, India, Myanmar, Phil-

organization responsible for improving repro-

ippines and Thailand.

ductive health in the region. At its recent execu-

HPV is the most common infection usually oc-

tive board and action plan meeting in Penang,

cur early in sexual life. A minority of HPV infec-

Malaysia AOFOG decided to initiate pilot pro-tions persist and may lead to cervical pre cancer

ject for cervical cancer control in Asia. Philip-in women. These pre cancer lesions if notpines and Thailand were selected to be the firsttreated properly, may progress to cancer 10 to 20

two countries to start comprehensive cervicalyears later. HPV vaccine has been recently

cancer control. International organizations suchlaunched in many countries but it will take more

as JHPIEGO and WHO were approached for pos-than 10 to 20 years before it can have significant

sible technical supports. Appropriate strategies

effect in cervical cancer control. Cervical cancer

for each country will be planned, implemented

is a treatable disease if detected in pre cancer orand evaluated.

!

!

!

early invasive stage. The main reason for is usu-

151

Pisake Lumbiganon
Pisake Lumbiganon is a Professor of Obstetrics and Gynecology, Convenor of Cochrane Thailand and Director of the
WHO Collaborating Centre on Research Synthesis in Reproductive Health based at Faculty of Medicine, Khon Kaen University, Thailand. He is also the President of the Royal Thai College of Obstetricians and Gynaecologists and the Vice President of Asia Oceania Federation of Obstetrics and Gynecology. He got his MD and Obstetrics and Gynaecology training
from Ramathibodi Hospital, Mahidol University in Thailand and Master of Sciences in Clinical Epidemiology from the University of Pennsylvania in the US. He has been involved with various WHO Reproductive Health Research projects including many multicentre randomized controlled trials. He has been convening the Thai Cochrane Network since its inception
in 2002. He has published more than 150 papers including many Cochrane reviews in various international journals. He wasawarded as the distinguished researcher in medical science by the National Research Council of Thailand in 2010. He was adean of the Faculty of Medicine at Khon Kaen University from 2009 to 2013. His main areas of interest includes maternaland perinatal health, evidence based practices, systematic review and meta analysis.

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Program152

AOFOG Program ：Cervical Cancer Screening in Asian Countries5）Cervical Cancer in Cambodia and Its Challenges
Koum Kanal1，Chhun Luon2，Sann Chan Soeung1
Cambodian Society of Gynecology and Obstetrics, Cambodia / AOFOG1,
NCD Bureau, MoH, Cambodia2

AOFOG
Program

Uterine cervical cancer is the most common
type of cancer among women and becomes a major public health concern in Cambodia. It is estimated that 1,500 women are newly diagnosed
cervical cancer cases and at least 900 women dieof cervical cancer each year.
Cambodian Ministry of Health（MOH）is increasingly giving priority to cervical cancerfrom 2005, The MOH Non Communicable Disease strategy（2012 2015）also emphasizes thehigh need to address cervical cancer prevention
and control. For its implementation, since 2012,
two screen and treat projects has been started tofind out the most effective strategy for the Cambodian context. One pilot project is using（VIA+
Cryotherapy）in several provinces under the collaboration with MOH and NGOs, and results to
be determined.
Another pilot has been conducted with the different implementation strategy（HPV test +LEEP）by SCGO with the collaboration of JSOG.
Targeting female factory workers, this projectuses a comprehensive approach, starting fromhealth education to increase awareness for cervical cancer, primary screening with HPV test, andsecondary check at national hospitals with colposcopy and early treatment with LEEP. First
screening was conducted and 31 female factory
workers participated in June 2017, with 4 casesof HPV test positive（positive rate of 12%）
. Registered female workers were about 20% of targeted people in the factory（older than 25 years
old, ever married）, but no one came for secondary check till September 2017. HPV test costs 5!

!

US$ per test, and it took only one month for laboratory technicians to handle HPV test properly
under the quality control with JSOG support.
Main challenges are to promote cervical cancer
screening and to connect first screening and secondary check.
HPV vaccine demonstration program was also
started since 2017. Core strategy of school vaccination is used with a target of 9 year old girls in
2 provinces and monitored by the MON National
Immunization Program.
MOH plans to update Standards Operational
Procedure on cervical cancer screen and treat
into National Standard Operating Procedures for
cervical cancer screening in Cambodia and finalize National Action Plan for Prevention ＆ Control of Cervical Cancer.
Challenges we need to overcome are Leadership and governance, Health care financing
Health Work Force, Medical products and technologies, information and research and service
delivery.
Conclusion：Aging population of Cambodia start
to increase. The incidence of cancer is indeed increasing and becoming a public health issue andan economic burden to society. It is necessary tohave a comprehensive intervention including appropriate strategy, appropriate human resources
and adequate system in the Cambodian context
and need more investment to boost more coverage of vaccination, screening and to open moreaccessibility to cancer treatment in the wholecountry.

!

153

Koum Kanal
President of CAMBODIAN Society of Gynecology and Obstetrics
Nationality: CAMBODIAN living in Phnom Penh, CAMBODIA as President of Cambodian Society of Gynecology and Obstetrics
Graduate as Medical Doctor in 1981 from Faculty of Medicine, University of Health Science in Phnom Penh, CAMBODIA
and Professor Hospitalo Practitioner University from University of Health Science, Phnom Penh, Cambodia in 2000.
Working as Director of National Maternal and Child Center from 2000 to 2011（till retired）.
Now Still as Vice Chair of the Gynecology and Obstetrics Department of the University of Health Science and The President of The Cambodian Society of Gynecology and Obstetrics, CAMBODIA.

AOFOGProgram

154

2nd J-K-T Joint Conference ①：1．Perinatology1）Acute Myometritis in Refractory Postpartum Hemorrhage：
The Underlying Pathology and the Development of Novel Treatment for!

Uterine type Amniotic Fluid Embolism
Naoaki Tamura
Hamamatsu University School of Medicine / JSOG

2nd J-K-T Joint
Conference

Postpartum hemorrhage is the main cause ofof unknown cause during pregnancy or soon af-maternal postpartum death over the world. It

ter delivery and required differentiation of amni-

may occur in various pathologies, such as abnor-

otic fluid embolism were registered following

mal placental attachment, birth canal laceration,

the entry criteria, and development of uterine at-uterine atony, and abnormal blood coagulation,

ony induced

but uterine atony is the most frequent cause ac-

hemorrhage was identified in many cases ac-

counting for 70% of cases. Although excess uter-counting for about 80%. For this condition, we

ine extension and fatigue of the uterine muscle

proposed a concept of uterine type amniotic

during pregnancy and delivery are known as thefluid embolism. Since complement activation, in-main inducers of uterine atony, it cannot be ex-crease in IL 8, and uterine edematous changes

plained by these conditions alone, and manyare observed in uterine type amniotic fluid em-

cases of postpartum hemorrhage are resistant tobolism, we hypothesized that immune reactions

treatment with compression of the uterus, suchin the maternal body cause local inflammation in

as circle massage and oxytocin administration.

the uterine muscle and induce treatment resis-

Why does this pathology of uterine contractile

tant postpartum hemorrhage. We would like todysfunction develop? In the project on serodiag-present our study based on uterine pathology

nosis of amniotic fluid embolism performed byand introduce clinical application of C1 esterase

our department in our country, patients who de-inhibitor for uterine edema due to anaphylactoid

velopedreaction.

cardiopulmonary

lethargy,

massive

bleeding, disseminated intravascular coagulation!

!

treatment resistant

postpartum

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156

2nd J-K-T Joint Conference ①：1．Perinatology2）Comparison of Various Markers for Intrauterine Growth Restriction/!!

Small for gestational Age Fetuses in the First Trimester
Chen-Yu Chen
MacKay Memorial Hospital / TAOG

Intrauterine growth restriction（IUGR）and

outcomes, the abilities of various markers to ac-!!

small for gestational age（SGA）fetuses are at in-

curately predict IUGR/SGA have been studied,creased risk of perinatal mortality and morbidity

such as biochemical serum markers, ultrasoundworldwide. Prophylaxis with aspirin during theand Doppler study of uterine and spiral arteries,

first or second trimesters and/or combined withand placental volume and vascularization.

heparin before conception, may reduce the incidence of IUGR/SGA in high risk groups.

Risk factors for IUGR/SGA are easy to assess
but have poor predictive value. The use of first

2nd J-K-T Joint
Conference

Despite improvement in the understanding oftrimester biochemical markers in combination

the pathophysiology, abilities in the first trimes-

with ultrasound markers is promising as a poten-

ter to precisely predict pregnant women who

tial screening tool. Modern assessments suggest

will develop IUGR/SGA are limited. While differ-

combined algorithms using these strategies, allent measures of placental dysfunction are associ-with the goal of a better prediction of IUGR/

ated with increased risk for adverse pregnancy

SGA.

157

Chen-Yu Chen
Department：Obstetrics and Gynecology
Affiliation：MacKay Memorial Hospital
Nationality：Taiwan*Education：
1. M.D., College of Medicine, National Cheng Kung University, Taiwan
2. Ph.D., Institute of Biomedical Engineering and College of Medicine, National Taiwan University, Taiwan*Current positions：
1. Attending Physician ＆ Director of Division of High Risk Pregnancy, Department of Obstetrics and Gynecology,
MacKay Memorial Hospital, Taiwan
2. Associate Professor, Department of Medicine, MacKay Medical College, Taiwan*Honors and Awards：
1. New Talent Award（Taiwan Society of Perinatology, 2012）
2. Distinguished Paper Award（Taiwan Society of Perinatology, 2013, 2014, 2015, and 2016）
3. Distinguished Paper Award（Association of Chemical Sensors in Taiwan, 2015, 2016 and 2017）*Research Interests：
1. High risk pregnancy
2. Fetal therapy
3. Biomedical engineering
4. Nanomedicine

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2nd J-K-T Joint Conference ①：1．Perinatology!

3）Maternal Anti Fetal Rejection As a New Mechanism of
Spontaneous Preterm Birth
JoonHo Lee
Yonsei University / KSOG

2nd J-K-T Joint
Conference

Preterm birth is defined as birth before 37

poglycemia, infantile death, cerebral palsy, men-complete weeks of gestation, which is one of thetal retardation, behavioral disorders in child-most important causes of neonatal mortality andhood, management of late preterm birth is re-morbidity. It is classified into three groups（ex-quired. However, mechanism of late preterm

tremely preterm birth, moderately preterm

birth is not yet established well, while intrauter-birth, and late preterm birth）according to theine infection/inflammation is a well known etiol-

gestational age at birth. As late preterm birth

ogy of extremely preterm birth. Recently, mater-（birth between 34 and 36 weeks of gestation）, ac-

nal anti fetal rejection has been proposed as acounting for more than 70% of preterm birth, is

new mechanism of spontaneous preterm birth,

associated with long term complications includ-especially late preterm birth, which will be dis-

ing neonatal respiratory distress syndrome, hy-cussed this time.

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159

JoonHo Lee
Assistant Professor
Division of Maternal Fetal Medicine
Department of Obstetrics and Gynecology
Yonsei University College of Medicine!

Education
1999 M.D. in Seoul National University College of Medicine
2007 M.S. in Seoul National University College of Medicine
2013 Ph.D. in Seoul National University College of Medicine

Postgraduate Training

!
!
!
2011!
2011
2012!20152016!

2000 2004
2007 20082009 2011

Residency training in the Dept. of OBGY, Seoul National University Hospital（SNUH）
Clinical ＆ Research Fellow in the Dept. of OBGY, SNUH
Research Associate in Perinatology Research Branch/NICHD/NIH/DHHS,
Hutzel Womenʼs Hospital/Wayne State University
Visiting Scholar in the Dept. of Periodontitis and Oral Medicine,
University of Michigan School of Dentistry
Assistant professor in the Dept. of OBGY, SNUH
Present position!

Lee J, Romero R, Dong Z, et al. Glycogen phosphorylase isoenzyme BB plasma concentration is elevated in pregnancy andpreterm preeclampsia. Hypertension. 2012；59（2）：274 282.

!

!

Lee J, Romero R, Xu Y, et al. A Signature of Maternal Anti fetal Rejection in Spontaneous Preterm Birth：Chronic Chorioamnionitis, Anti Human Leukocyte Antigen Antibodies, and C4d. PLoS One. 2011；6（2）：e16806.

!

2nd J-K-T Joint
Conference

Representative Bibliography
Lee J, Romero R, Lee KA, et al. Meconium aspiration syndrome：a role for fetal systemic inflammation. American Journalof Obstetrics and Gynecology. 2016；214（3）：366.e1 9.

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2nd J-K-T Joint Conference ①：2．Reproduction1）Current Status of Uterus Transplantation Research in Japan：
Towards Clinical Application
Iori Kisu，Kouij Banno，Yusuke Matoba，Masataka Adachi，Daisuke Aoki
Keio University / JSOG!

Uterus transplantation（UTx）has become andelivery after autologous UTx in non human pri-alternative to gestational surrogacy and adoption

mates in 2012. We have examined many issues

for women with uterine factor infertility. Bränn-

including immunological response and rejection

ström et al. achieved the first human delivery af-

in UTx and we believe UTx is possible from ater UTx in 2014 and to date a total of 8 babies

technical viewpoint with our experimental expe-

have been born after UTx from living donors.

rience and clinical data overseas.

This outcome attracted much attention world-

However, this procedure has many medical,

wide and many countries have recently preparedethical and social issues that require discussion

for UTx followed by Swedish team.

prior to clinical application. Moreover, UTx is

2nd J-K-T Joint
Conference

We launched UTx research in 2009 consider-still in the experimental stage overseas and theing that UTx may provide new hope to thesesafety and efficacy remain unclear despite sev-

Japanese women. The guidelines of the Interna-

eral clinical applications. Despite the many is-tional Federation of Gynecology and Obstetrics

sues to be resolved, this new organ transplanta-（FIGO）indicate that adequate studies in large

tion technology will provide new hope foranimals, including primates, should be conducted

women with uterine factor infertility and further

before clinical application. Therefore, we havedevelopment of the technology is important for

performed UTx research using cynomolgus ma-

future reproductive and gynecological medicine.

caque for this purpose, with the first successful

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2nd J-K-T Joint Conference ①：2．Reproduction!

2）Roles of Exosome Associated Glycosphingolipids
in Immune Tolerance of Embryo Implantation and Pregnancy
Hsien-Ming Wu
Chang Gung Memorial Hospital Linkou Medical Center / TAOG

Establishment of pregnancy requires synchro-healthy women undergoing pregnancy termina-

nized growth between the endometrium and thetion of a pregnancy at 6 to 12 wk gestation, af-blastocyst. Functional interaction between theseteroccurs both during the pre implantation phase

exosomes significantly induced macrophage M2

of embryo implantation and during placentation.

polarization. Moreover, isolated exosomes from

Pregnancy is a unique event in which a fetus, de-villus trophoblast cells were confirmed by trans-

spite being genetically and immunologically dif-mission electron microscopy images. Pretreat-

ferent from the mother, develops in the uterus.

ment with exosomes derived from villus tro-

Successful pregnancy implies avoidance of rejec-

phoblast cells of a normal pregnancy signifi-tion by the maternal immune system. Exosomes

cantly induced macrophage M2 polarization

released from the endometrium and the embryo

compared with anembryonic pregnancy throughare present in uterine fluid. These can transfer

M1 macrophage marker expression by qRTmiRNA, mRNAs, proteins and lipids between

PCR. We demonstrate that GSLs were significant

cells, thus providing endometrial embryo com-

expressed in exosomes derived from villus tro-

munication in the peri implantation period.

phoblast cells, indicating the GSLs have potential

Exosomes have been considered of critical im-

modulatory role on embryo implantation and de-portance for embryo implantation and program-cidual programming of human pregnancy. These

ming of human pregnancy. We examined that

represent a new concept regarding the immuno-

the!

2nd J-K-T Joint
Conference!

actionof!

!

informed

consent.

!

Pretreatment

with

!

glycosphingolipids（GSLs）inmodulatory capacity of exosomes from embryos

exosomes, and their role as preventing the em-and villi, suggesting that exosomes have poten-bryo from being attacked by the maternal im-tial modulatory role on embryo implantation andmune system. Human villus trophoblast cells

decidual programming of human pregnancy.

were isolated from the abortus tissue from163

Hsien-Ming Wu!

Hsien Ming Wu received M.D. degree from Taipei Medical University in 1996. He received his PhD from the Graduate Institute of Clinical Medical Science, Chang Gung University, Taiwan in 2009 for his thesis on Gonadotrophin releasing hormone（GnRH）signalings in intrauterine tissues. He trained as a postdoctoral research fellow in the University of British Columbia, Canada. He is presently working as an associate professor, clinician, teaching faculty, researcher and chief of Reproductive Endocrinology and Infertility in the Department of the Obstetrics and Gynecology of the Chang Gung Memorial
Hospital, Linkou Medical Center, Taiwan.

!

His research interests include reproductive endocrinology, GnRH system, infertility, and artificial reproductive treatment.
With over a hundred academic publications and presentations, Dr. Wu is a noted expert in the clinical management of infertility, IVF and other disorders of the reproductive system. Dr. Wu is the principal investigator for Ministry of Science andTechnology funded grants that have impacted infertility therapy in Taiwan.

!

!

Dr. Wu received a lot of awards, including the awards from Taiwan Society for Reproductive Medicine（TSRM）, Chien
Tien Hsu Cancer Research Foundation, the Infertility Foundation of the Taiwan, and FertiLink reproduction meeting.

2nd J-K-T Joint
Conference

164

2nd J-K-T Joint Conference ①：2．Reproduction3）Fertility Preservation in Gynecologic Cancer Patients
Chan Woo Park
Cheil General Hospital ＆ Women’s Healthcare Center, Dankook University College of Medicine / KSOG

Despite predominantly occurring in postmeno-noma, ovarian tumors of low malignancy, andpausal women, approximately 20% of gyne-some selected cases of unilateral ovarian carci-

cologic malignancies take place in women of re-noma（stage IA）. A conservative approach to fer-

productive age who have yet to complete family

tility involves sparing the uterus and a unilateralplanning. When broken down by subtype, 8% of

ovary during surgery. However, in cases of ad-

endometrial cancers, 12% of ovarian cancers, andvanced gynecologic malignancies, reproductive

40% of cervical cancers occur in patients duringorgans such as the uterus and ovaries must be

their childbearing years.

removed by radical surgery. The removal of re-

2nd J-K-T Joint
Conference

Improvements in cancer diagnosis and treat-productive organs through radical surgery

ment have resulted in an improved survival rate,

makes it difficult to consider future pregnancies.

allowing these patients to focus on their quality

A few reports have discussed ex vivo retrievalof life. Fertility preservation（FP）has become anin advanced stage gynecologic cancer patients.

important issue for cancer patients of reproductive age.

!

!

Herein, we report a case series of FP using invitro matured oocytes retrieved from macro-In gynecologic malignancies, fertility sparing

scopically normal ovarian tissue harvested dur-

surgery is a viable option for certain early stage

ing radical surgery, and live birth from in vitro

cancer patients, including those with early cervi-

fertilization after fertility sparing surgery forcal carcinoma, early endometrial adenocarci-

early stage gynecologic cancer patients.

!

!

!

165

Chan Woo Park
Associate Professor
Department of Obstetrics ＆ Gynecology
Cheil General Hospital ＆ Womenʼs Healthcare Center
Dankook University College of Medicine
Chanwoo Park, MD, PhD received his doctorate of medicine and PhD in medical science at Hallym University, Chuncheon,
Korea. He then went on to complete his internship and residency at the Kangdong Sacred Heart Hospital, Hallym University, Seoul, Korea. Dr. Parkʼs clinical fellowship was in reproductive endocrinology and infertility at Samsung Cheil Hospital, Seoul, Korea. During his career he spent a year as a research fellow at the Division of REI, Dept. of Ob/Gyn at theSouthwestern Medical Center, University of Texas, Dallas, TX, USA.

2nd J-K-T Joint
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166

2nd J-K-T Joint Conference ②：Overseas Invited Lecture

The Most Important Discoveries of the
Past Fifty Years in Gynecologic Pathology
Steven Silverberg
Professor Emeritus of Pathology, University of Maryland, USA

In commemoration of my 50th year as an aca-!

!

munohistochemistry in formalin fixed, paraffin

2nd J-K-T Joint
Conference

demic pathologist, I have compiled two lists ofembedded

importantgyne-Classification of 1973 and The Bethesda System

cologic pathology during those years. Both willof 1988；（3）HPV as a causative agent in devel-

be discussed in more detail in this lecture. The

opment of cervical, vaginal, and vulvar preinva-

list based on responses from ten distinguishedsive and invasive carcinomas；（4）endometrial

gynecologic pathologists is as follows：（1）roleatypical hyperplasia/intraepithelial carcinoma/of HPV in lower female genital cancers and pre-EIN as type 1 carcinoma precursor；（5）discov-cancers；（1）（tie）diagnostic immunohistochem-eries concerning

istry；（3）frequency of metastases to ovary/roleserous carcinomas, and（tie）vaginal clear cellof STIC；（4）uterine serous carcinoma；（5）AIS

adenocarcinoma and its relation to intrauterine

and gastric type cervical adenocarcinomas；（5）diethylstilbestrol（DES）administration. I hope（tie）aspects of molecular pathology/genomics.

that similar lists will emerge for gynecologic on-

My own list：（1）development of diagnostic im-

cology, endocrinology, and other subspecialties.

discoveries/publications

in!

tissuespecimens；（1）（ tie）WHO

ovarianandextraovarian

167

Steven Silverberg
Clinical Professor of Pathology
Education
A.B.
M.D.

Brooklyn College, Brooklyn, New YorkJohns Hopkins University, Baltimore, Maryland

1958
1962

Internship（medical）
Cornell Division Bellevue and Memorial Hospitals, New York

1962 1963

Residency（anatomic pathology）
Yale University, New Haven, CT

1963 1965

Fellowship（pathology）
Memorial Hospital for Cancer and Allied Diseases, New York, N.Y.

1965 1966!

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Certification
Diplomate, American Board of Pathology（certified in Anatomic Pathology）
Medical Licensures

1969

District of Columbia；Maryland, #D0051037（expires 9/30/13）

Major ResearchInterests
Differential diagnosis, epidemiology, natural history and prognostic markers of cancers and precancers of female
genital tract, breast, and prostate；development and standardization of diagnostic and prognostic algorithms；
investigation of cytopathologic/histopathologic correlations；study of variability in pathologic interpretations.

1966 1968

Employment History
Assistant Professor of Surgical Pathology, Medical College of Virginia, Richmond, VA
Associate Professor
Associate Professor of Pathology, University of Colorado Health Sciences Center, Denver, Colorado
Professor of Pathology
Professor of Pathology, George Washington University Medical Center, Washington, D.C.
Professor of Pathology, University of Maryland School of Medicine, Baltimore, MD
Clinical Professor, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD
Professor Emeritus, University of Maryland School of Medicine

1968 1971
1971 1972
1972 1978
1978 1981
1981 1996
1996 2003
1/04 6/30/08
7/2010

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Major Academic Tasks
Director of Pathology Residency Program, University of Maryland Medical System, Baltimore, MD
1997 2004
Medical Director of Pathologist Assistant Training Program, University of Maryland Medical System, Baltimore, MD
1999 2004
Director of Anatomic Pathology, University of Maryland Medical System, Baltimore, MD
1996 2004
Director of Anatomic Pathology, George Washington University, Washington DC
1981 1996
Director of Surgical Pathology, University of Colorado, Denver, Colorado
1972 1981
Executive Director, Colorado Regional Cancer Center, Denver, Colorado
1976 1980

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Professional Memberships
American Society for Clinical Pathology（Fellow）；
International Academy of Pathology；American Society of Cytopathology；Japanese American Society of Pathologists；
Washington Society of Pathologists；Arthur Purdy Stout Society of Surgical Pathologists；Phi Beta Kappa；Sigma Xi；International Society of Gynecological Pathologists；Society of Gynecologic Oncologists（Associate Member）；
International Gynecologic Cancer Society；Papanicolaou Society；Mid Atlantic Gynecologic Oncology Society；International Society of Breast Pathology；Association of Directors of Anatomic and Surgical Pathology；Maryland Society of Pathology!

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2nd J-K-T Joint
Conference

Military Service
Captain, USAF（MC）,Staff Pathologist, Tachikawa Air Base Hospital, Japan168

2nd J-K-T Joint Conference ②：3．Gynecology1）Integrated Analysis of Genomic and Transcriptomic Data in
Ovarian Clear Cell Carcinoma
Kosuke Yoshihara
Niigata University / JSOG

Clear cell carcinoma（CCC）is the second mosttected in 57% of CCC. In addition, 12 CCC sam-common subtype of ovarian carcinomas（OCs）inples（16%）had somatic mutations of HR associ-Japan accounting for about 25% of OCs. CCC

ated genes that might be biomarkers of PARP in-shows resistance to platinum based chemother-

hibitor sensitivity. Next, we ran Pipeline for

apy and hence development of new therapeutic

RNA sequencing Data Analysis（PRADA）to de-strategies based on molecular characteristics oftect therapeutic targetable fusion transcripts

CCC is urgently required. The aim of this study

with high confidence. In total, 151 fusion tran-

is to identify therapeutic molecular targets in

scripts with high confidence were detected in 61

CCC. We performed targeted sequencing of 25

CCC samples. Especially, 10 CCC samples had a!

2nd J-K-T Joint
Conference!

homologous recombination（HR）associated genes

kinase in frame fusion transcript which could be

including OC associated genes and RNA se-considered as therapeutic targets. This inte-

quencing for 74 and 61 CCC samples, respec-

grated molecular characterization provides atively. According to previous results, 74% of CCC

comprehensive foundation for developing CCC

harbored ARID1A somatic mutations, and coex-

precision medicine.

istent ARID1A and PIK3CA mutations were de-

169

MEMO

2nd J-K-T Joint
Conference

170

2nd J-K-T Joint Conference ②：3．Gynecology2）Discovery and Translation of Epigenetic Biomarker
in Womenʼs Cancers
Hung-Cheng Lai1,2
Shuang Ho Hospital / TAOG1,
Taipei Medical University, Taiwan2

Epigenetics is pervasive in almost every aspect of cancers. The pursuit of new diagnostics

testing of POU4F3/HPV（CONFENDENCE）has!

completed a multi center trial in Europe.

and therapeutics has been in high hopes since

The incidence of endometrial cancer is in-

the burgeoning of epigenetic phenomenon increasing worldwide. There are no screening

early 21st century. We have been exploring DNA

methods so far. We identified a panel of methyla-

methylation in gynecological cancers as an effort

tion biomarkers, and verified the feasibility of us-

to improve cancer screening and develop new

ing the methylation profile of cervical scrapings

therapies.

to detect endometrial cancer. By a panel of DNA

2nd J-K-T Joint
Conference!

The unsatisfactory cytology based Pap smear

methylation from cervical scrapings, we can de-and virus based HPV testing leaves the unmet

tect endometrial cancer with the sensitivity andneed for cervical cancer screening. By methylo-

specificity ＞90%. These molecular biomarkers

mic analysis, we discovered PAX1/ZNF582/

expand the scope of Pap smear, which has been

POU4F3 methylated in cervical cancer withused for more than half a century and is usedclinical applicability. In 2016, Taiwan FDA ap-

widely in developed countries with a high preva-!

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proved PAX1（Cervi M）as an adjunct testing forlence of uterine cancer. The transition to in vitro

cervical cancer screening. In addition, combined

diagnostics and a prospective trial is ongoing.

171

Hung-Cheng Lai
Professor
Chair, Department of OB/ GYN
School of Medicine, Taipei Medical University
Vice Superintendent, Chairman, Department of OB/ GYN, Shuang Ho Hospital, Taipei Medical University◎Education
・PhD, Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C. 2000.08 2003.02
・MD, National Defense Medical Center, Taipei, Taiwan, R.O.C. 1986.08 1993.07◎Professional Experiences
・Visiting Scholar, Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio,
U.S.A., 2005.08 2005.12
・Visiting Scholar, German Cancer Research Center（DKFZ）, Heidelberg, Germany, 2002.07 2002.08◎Expertise・Epigenetics and Biomarker・Cancer Stem Cells・Robotic Surgery◎International Grant Reviewer
・Italian Ministry of Health（MOH）,Italy
・United Arab Emirates University（UAEU）, United Arab Emirates
・Health and Medical Research Fund（HMRF）, Hong Kong
・Israel Science Foundation（ISF）, Israel・Dutch Cancer Society KWF Kankerbestrijding, Netherlands◎Editorial Board
・Editorial Board of the journal Gynecologic Oncology（official J. of Am. Society of Gynecology Oncology）
・Editorial Board of the journal Journal of Gynecologic Oncology（official J. of Asian Society of Gynecology Oncology）
・Associate editor of Taiwanese Journal of Obstetrics and Gynecology（official J. of Taiwan Association of Obstetrics and Gynecology）

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Conference

172

2nd J-K-T Joint Conference ②：3．Gynecology3）HOXB9 as a Potential Target Gene for Overcoming Platinum
Resistance in Mucinous Ovarian Cancer
Dong Hoon Suh
Seoul National University / KSOG

Although ovarian cancer is heterogeneoustively；expression of vimentin was decreased

with various histologic types, current treatment

while expression of E cadherin was increased；

guidelines are generally the same for all his-

SOX 2, Nanog, and Oct 4 also decreased in both

tologic types. Expression of HOX genes in epi-

cell lines after specific siRNA treatment. Whenthelial ovarian cancer（EOC）was known to be

injected with RMUG Sko HOXB9 and SKOV 3oe HOXB9

histology specific. We performed a series of inin mouse models, we clearly showed that the tu-

vitro and in vivo studies to find out a tailoredmors from RMUG Sko HOXB9 grew significantly

strategy of inhibiting HOXB9 expression for

slower than those from control. By contrast, theovercoming platinum resistance in mucinous

tumors from SKOV 3oe HOXB9 grew significantly

EOC. HOXA10 and HOXB9 showed exclusively

faster than those from control. After harvesting,high expression in SKOV 3 and RMUG S, re-the cells from the SKOV 3oe HOXB9 were character-

spectively. HOXA10 siRNA treatment made a!

ized with resistance to cisplatin and higher ex-significant decrease in cell viability of SKOV 3,

pression of vimentin than those form the control.

but not RMUG S. By contrast, HOXB9 siRNAOur findings suggest that platinum resistancetreatment made a significant decrease in cell vi-

of mucinous ovarian cancer might be defeated byability of RMUG S, but not SKOV 3. HOXA10

inhibiting HOXB9, which could be a target of tai-siRNA and HOXB9 siRNA treatments：in-lored strategy for overcoming the resistance tocreased the expression level of cleaved PARP

platinum in mucinous EOC.

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2nd J-K-T Joint
Conference

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and caspase 3 in SKOV 3 and RMUG S, respec-

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173

Dong Hoon Suh
Dong Hoon Suh is a clinical professor of the department of obstetrics and gynecology in Seoul National University Hospital.
He is a gynecologic oncology specialist.
He is one of the acting members of the Asian Society of Gynecologic Oncology, ASGO, particularly taking an active part inits official journal, Journal of Gynecologic Oncology as an associated editor. He has been also deeply involved in othermedical journal activities as a committee member for Planning and Evaluation of Korean Association of Medical Journal
Editors, KAMJE.

2nd J-K-T Joint
Conference174International Workshop for Junior Fellows（IWJF）：
1. Cross country Differences in Routine Prenatal Examinations!

1）Cross Country Differences in Routine Prenatal Examinations：
The US and Japan
Supraja Rajagopalan
Medical University of South California, USA
ACOG

The tenants of prenatal care are universal,

countries. I aim to do this by exploring the his-they are rooted in protecting mothers and theirtorical, cultural, and economic contexts of health-infants with the goal of reducing maternal andcare in each country. I will then apply each of

infant morbidity and mortality. The US and Ja-

these lenses to each prenatal care delivery sys-

pan are both strongly invested in this goal. Whiletem and to the specific components of prenatal

the two share many practices in prenatal care,examinations in practice. I will also discuss preg-there are also many differences. The goal of thisnancy outcomes in both countries as they relatepresentation is to highlight an understanding ofto these systems of practice.

the differences in prenatal care between the two

Junior Fellows

175International Workshop for Junior Fellows（IWJF）：
1. Cross country Differences in Routine Prenatal Examinations!

2）Routine Prenatal Examinations in Taiwan
Cleo Tsai
Cathay General Hospital, Taiwan
TAOG

Prenatal routines around the world generally

ing 24 to 28 gestation weeks.

follow a set guideline, but may vary a bit from

As most pregnant women tend to be con-place to place due to prevalent diseases particu-

cerned with the health and safety of their babies,

lar to a location or population group. The Na-

we also do offer a variety of self paid laboratory

tional Health Insurance system is unique to Tai-

exams. These include non invasive prenatal test-

wan. This system offers 10 prenatal visits includ-ing（NIPT）,early Downʼs screening, early predic-

ing lab tests, urinalysis, and one mid trimestertion for preeclampsia, spinal muscular atrophy

ultrasound scan to assess for fetal anomalies. An-（SMA）testing,other aspect particular to Taiwan is the in-screen, and array CGH. Level II ultrasound, 3D/4

creased prevalence of HBV and thalassemia car-D ultrasounds, and a series of further ultra-

riers, and general screening for these two dis-sounds to assess for fetal development andeases is done upon the first prenatal lab testing.

growth not included in the health exams can also

Amniocentesis is provided for patients with ad-

be performed upon patientʼs request.

!

! testing, TORCH

Fragile Xvanced maternal age or other high risk indications at 16 to 18 gestational weeks. Gestational
diabetes mellitus（GDM）is assessed as well dur-

Here, we present the current situation of the
pyramid of prenatal care in Taiwan.

Junior Fellows

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176

International Workshop for Junior Fellows（IWJF）：
1. Cross country Differences in Routine Prenatal Examinations!

!

3）The Current Status of the Guidelines of Non invasive Prenatal Testing（NIPT）in Japan, South Korea and Taiwan
Joseph J. Noh，Soo-Young Oh，Suk-Joo Choi，Cheong-Rae Roh，Jong-Hwa Kim
Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
KSOG【Purpose】
Non invasive prenatal testing（NIPT）for chromosomal aneuploidy became commercially available in Japan, South Korea and Taiwan in 2013.
We explored the current status of the development of guidelines in regards to NIPT use in thethree nations.
【Methods】
A PubMed search of the literature using thepertinent keywords was undertaken, and 15 journal articles published in the three nations werereviewed.
【Results】
In Japan, prenatal genetic screening is performed in less than 5% of all pregnancies and ismostly performed as second trimester maternal
serum screening. With a growing interest in prenatal screening in recent years however, the Japan Society of Obstetrics and Gynecology published clinical guidelines in 2013 recommending
NIPT for women who meet the following conditions：（1）the fetal ultrasound suggests the possibility of a fetal chromosomal abnormality；（2）maternal serum screening suggests the possibility of a fetal chromosomal abnormality；（3）aprevious pregnancy had a fetal chromosomal abnormality；（4）pregnancy occurs at an olderage；（5）trisomies 21 and 13 in the fetus are considered possible due to a balanced Robertsoniantranslocation in either parent. It also recommends undergoing NIPT only after receiving genetic counseling from an obstetrician and pediat-!

Junior Fellows!

ric genetic specialist or an approved genetic
counselor. These guidelines are similar to thosepublished by the American College of Obstetricians and Gynecologists and the Society for Maternal Fetal Medicine.
Guidelines similar to the Japanese that emphasize the use of the test in high risk pregnant
women as a screening method are currently being developed in South Korea, but there are no
official guidelines by professional societies or organizations in regards to the use of NIPT yet.
Taiwan is in similar conditions to South Korea.
In Taiwan, prenatal genetic screening has been
mandated by law since 1985, but at present, thefirst trimester combined test and second trimester quadruple test are the main tools for routine
prenatal care and it recently began integrating
NIPT in prenatal care.
【Conclusion】
The three nations are all avidly adopting the
NIPT in prenatal screening. Japan has been themost active not only in evaluating the performance of the test but also in providing clinicalguidelines that consider psychological and social
issues ensued from performing the test. It wasobserved in all three nations that a high proportion of pregnant women favored the introductionof the test in obstetrical care. Therefore, it seems
necessary for professional societies to establish
clear guidelines that take into account of the
ethical, legal, social and economic aspects of the
test.

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177

International Workshop for Junior Fellows（IWJF）：
1. Cross country Differences in Routine Prenatal Examinations!

!

4）Cross country Differences in Routine Prenatal Examinations
Sayaka Kawashita，Haruhisa Konishi，Mamoru Shigeta
JSOG

The latest maternal mortality rate in Japan isvanced medical institutions with massive man-

3.4 per 100,000 deliveries in 2015. That has been

power in collaboration with other departments

decreasing consistently since the 1980s and issuch as neonatology, anesthesiology and so forth.

sufficiently low. Furthermore, the perinatal mor-

One of the characteristics of prenatal examina-

tality rate is 3.6 per 1,000 live births. The demo-

tions in Japan is the high frequency of ultrasoundgraphic statistics reveal a high level of safety of

examinations. It is common practice to examine

pregnancy and childbirth in Japan. In this pres-fetal development and amniotic fluid volume byentation, we review our characteristic prenatal

ultrasonography every checkup. Detailed exami-

examinations compared with foreign countries.

nations focusing on organic diseases in fetuses

In Japan, municipalities take charge of mater-

have also been emphasized recently. Although a

nal and child health. Pregnant women usually go

review is necessary for the purpose of effective

to regular medical checkups using the public

utilization of limited medical resources, it is defi-

health system. We perform a total of 14 checkups

nitely useful for the discovery of fetal growth re-until delivery, once every 4 weeks until the 23rdstriction, large babies, non reassuring fetal

week, every 2 weeks until the 35th!

status and infant diseases that require postnatal
early treatment. In conclusion, the reduction ofmost identical throughout the entire nation. The

regional disparities by public expenditure andresult of the prenatal checkup is recorded in thethe established system of managing high riskmaternity passbook published by municipalities.

pregnancies lead to a high level of safety for

The passbook is systematically used through thepregnancy and childbirth in Japan.

duration of the pregnancy.

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In association with women s social advance-

Patients are usually managed at primary medi-

ment, the average age of first childbirth has been

cal institutions from the confirmation of intrau-

rising in Japan. There is a growing demand forterine pregnancy until delivery. However, we

prenatal diagnosis including non invasive prena-evaluate their perinatal risks such as complica-

tal genetic testing（NIPT）started in 2013. How-

tions and their course of pregnancy each time,

ever, some matters remain unresolved such as

and we decide whether to introduce them to ap-

shortage of genetic counselors and insufficient

propriate advanced medical institutions, namely

support systems for eligible patients.

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regional perinatal medical centers（191 centers

It is important for us to make further progressnationwide）and comprehensive perinatal medi-in prenatal management through examining our-cal centers（91 centers nationwide）. High risk

selves and learning from foreign countries on

pregnancies are managed at fully equipped ad-

this occasion.

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Junior Fellows

week andevery week after the 36th week. The content is al-178International Workshop for Junior Fellows（IWJF）：
2．Work life Balance for OB/GYN Doctors：Pregnancy and Parenthood with Careers!

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1）Work life Balance for OB/GYN Doctors：
Managing Pregnancy and Parenthood with Careers
Alison Dixon
Loyola University Medical Center, USA
ACOG!

Being a parent is difficult no matter what ca-

ing of reflections on work life balance in OB/

reer you choose. Balancing work life demands,

GYN from a group of American OB/GYN resi-

including pregnancy and parenting, is especiallydents and attendings. We will discuss overall

difficult in OB/GYN, with busy inpatient serv-

challenges in the field and some limitations spe-

ices and surgery schedules. This talk is a gather-cific to American work life balance.

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Junior Fellows

179International Workshop for Junior Fellows（IWJF）：
2．Work life Balance for OB/GYN Doctors：Pregnancy and Parenthood with Careers!

!

2）The Challenges of Work life Balance for Female Physicians in!

OB GYN versus Other Specialities：Managing Pregnancy andParenthood with Careers
Shu-Han You1，Chang-Chyi Jenq2,3
Chang Gung Memorial Hospital, Taiwan1,
Department of Nephrology, Chang Gung Memorial Hospital, Taiwan2,
Chang Gung Medical Education Research Centre, Taiwan3
TAOG【Background】【Results】
A total of 93 women physicians responded, 47（50.5%）and 40（43%）of whom thought more bar-peting in career and being a dedicated mother,riers in career and life, respectively compared

the issue of coordinating family and career be-with their male coworkers. Among 43 marriedcome important. Women physicians may encoun-

physicians, 23（53.5%）reported delayed family

ter more challenges in childbirth and parent-

planning and childbirth because of training.

hood, especially in women obstetricians and gy-

Twenty two women physicians had at least one

necologists（OB GYNs）. In this study, we as-

child and took 8 weeks maternity leave. Al-

sessed and compared experiences of managing

though 13 women（59%）were unsatisfied withwork life balance, pregnancy, childbirth, andthe short maternal leave, only 2（9%）had paren-parenthood between women OB GYNs andtal leave. Comparing women OB GYNs withother specialties.

other specialties, more OB GYNs chose to work

【Methods】

in medical centers and had more working hours

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An anonymous survey questionnaire including

and night shifts. However, the attitude towards

factors affecting specialty or workplace chosenfamily planning and maternal leave had no sig-

and childbearing timing, work life balance, andnificant difference.

satisfaction with the policy of maternal and pa-【Conclusions】!

!

rental leaves was mailed to 25 40 years female

Women physicians conflicted more challenges

physicians in the study institute. Mann Whitney

in workplace and delayed childbirth with dissat-

test was used to identify and compare the career

isfaction of 8 weeks of maternal leave. The study

and life choices and the difficulties in pregnancy

suggested more strategies to lessen the child-and parenthood with careers between womenbearing burden in training and practice.

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OB GYNs and other specialties.

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Junior Fellows

As the increasing numbers of female physicians and the pressure to choose between com-180

International Workshop for Junior Fellows（IWJF）：
2．Work life Balance for OB/GYN Doctors：Pregnancy and Parenthood with Careers!

3）Reality of Young Korean Doctorsʼ in Marriage, Childbirth,!

and Child rearing：A Comprehensive Interview Survey
Se Ik Kim，Maria Lee，Hee Seung Kim，Hyun Hoon Chung，Jae-Weon Kim，
Noh Hyun Park，Yong-Sang Song
Seoul National University College of Medicine, Korea
KSOG!

【Objective】

ber of 1.4（range, 1 2）
. Three female doctors andKorea is rapidly becoming an aging society be-

spouses of the two male doctors were pregnant

cause of its declining birth rate combined withat the time of survey. The reasons behind low

an increasing life expectancy. The total fertility

marriage and birth rates were various. Doctors

rate of the Korean women, at 1.24, is one of thecommonly responded that hospitalʼs welfare pro-lowest. This study aimed to investigate thegrams are insufficient：female doctors can use

young Korean doctorsʼ current state of marriage,

only three months on maternity leave. Married

childbirth, and child rearing.

doctors requested child care facilities in hospital.

【Methods】

In addition, many reported that they are not fi-!

Junior Fellows

A comprehensive interview survey was con-nancially stable enough to get married or raise aducted on trainee of the Department of Obstet-child, putting off marriage and/or childbirth un-rics and Gynecology in two institutional hospi-

til they finish training and get a secure job. Sometals, Seoul National University Hospital andyoung single doctors complained of lack of dat-

Seoul National University Bundang Hospital.

ing due to overwork.

Presently, 41 residents and 15 fellows work and【Conclusion】

all of them were enrolled.
【Results】

From the interview survey, we could recognize the young Korean doctorsʼ current state and

In total, 56 young doctors responded the sur-worrisome regarding marriage, childbirth, andvey（response rate, 100%）. Mean age was 31.8

child rearing. Young Korean doctors showed

years（range, 26.4 39.1）and male doctors ac-

low marriage and birth rates. Hospitalʼs welfare

counted for 14.3%；two are residents and six aresupports as well as Korean governmentʼs policies

fellows. Of the doctors, 23（41.1%）were married

which encourage young Korean doctors to get

and only 8（14.3%）gave birth with the mean num-married and to have more children are needed.

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181

International Workshop for Junior Fellows（IWJF）：
2．Work life Balance for OB/GYN Doctors：Pregnancy and Parenthood with Careers!

!

4）Actual Condition of Work life Balance of OB＆GY Doctors in Japan
Ranka Kanda，Naoyuki Iwahashi，Masumi Ishibashi
JSOG!

From the 1990s onward, the support of work!

To achieve a comfortable work life balance, itlife balance（harmonization of work and lifestyle）

is necessary to understand the diversity of life

has drawn much attention in Japan. To improve!

styles of individual doctors, and secure economic

female workersʼ work life balance is consideredstability, a healthy, enriched life, and availability

as one of the solution strategies to Japanʼs prob-of flexible and diversified working styles for alllems that include a declining birthrate and aging

doctors, not only for female doctors raising theirsociety.

children.

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To create a good work life balance for all

male and female has been decreasing year byworkers, the term IKUBOSS was generated inyear since its peak in 2010. The number of fe-

2013. IKU stands for ikuji , which means rais-

male doctors aged less than 40 has exceeded theing a child, and IKUBOSS means a supervisor

male doctors of the same generation since 2013.

who takes the initiative in creating a workplace

More female doctors tend to leave their positions

environment supportive of work life balance.

due to childbirth and childcare than male doc-

IKUBOSS is responsible for supporting the pri-tors. To avoid female doctors leaving their posi-vate lives and careers of subordinates, while also

tions, the Japanese Society of Obstetrics Gyne-

enjoying a work life balance fully, obtaining

cology has advocated the importance of work

profits for the organization, and solving the prob-

life balance.

lems of conflict between the supporter side and!

Many female doctors have to leave their posi-!

doctors who need support.

tions due to childbirth and childcare in Japan.

However, IKUBOSS is not yet appreciatedAnd after they return to work, they are obliged

in the OB＆GY field and there are quite a few

to limit their working hours, accept decreased in-senior supervisors who feel confused about thecome, and suspend their careers in order to raisepractice on the site. This is because the supervi-

their children. On the other hand, to support fe-

sors who are expected to play the role ofmale doctors raising their children with limited

IKUBOSS

work time, the other doctors have been burdened

doctors, and some senior supervisors do not un-with a heavy workload. As the current systems!

derstand the sense of values that places impor-of encouraging work life balance particularlytance on personal and family life, as well as at-

support female doctors during pregnancy ormosphere of workplace. There are few supervi-

child raising in Japan, other doctors feel unfair-sors who can serve as role models.

ness in the contents and volume of work and appraisal of their performances.

have too much work as OB＆GY!

We expect the work life balance of all OB＆
GY doctors to be improved.

Junior Fellows

The number of OB＆GY doctors in Japan, both

182

Luncheon Seminar 31

Are Environmental Toxics Affecting Reproductive Health Globally―What is the Evidence?
Linda Giudice
University of California, USA

The past 70 years have demonstrated an

critical windows of development have adverse

alarming global increase in developmental ab-effects on reproductive tract development andnormalities, intellectual disabilities, reproductivefunction through epigenetic and other mecha-

compromise, respiratory, endocrine and meta-

nisms, resulting in or exacerbating, e.g., male andbolic disorders, and cancer. As these changes

female infertility, endometriosis, polycystic ovar-

have occurred in a relatively short time frame, it

ian syndrome, uterine fibroids, and per term de-is unlikely that genetics is their sole cause, and it

livery. Additionally, disadvantaged populations

is likely that environmental factors are signifi-

have higher likelihood of living in contaminatedcant contributors. Globally, chemicals in agricul-

communities and higher risk occupations, aug-ture, pesticides, industrial waste, personal carementing their risks of poor reproductive out-

products, household cleaning agents, and nearly

comes. This lecture will review relevant dataubiquitous plastics, along with particulate mat-

supporting environmental toxics as putting

ter in indoor and outdoor air pollution are ofworld reproduction at risk and highlight how re-great concern. Human epidemiologic studies andproductive and other healthcare professionals

wildlife and laboratory data support risks andare well positioned to advocate for global solu-

plausible causation of these agents in human dis-

tions to prevent these growing harms to theease risk. Exposures to environmental toxics athealth of this and future generations.

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Luncheon
Seminar183

IS-AC-1-1

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IS-AC-1-2
Quantification of primordial follicle using optical coherence
tomography intended for investigating effective ovarian tissue transplantation Seido Takae1, Kosuke Tsukada2, Yorino
Sato1, Naoki Okamoto1, Chie Nishijima1, Nobuhito Yoshioka1,
Yodo Sugishita1, Yuki Horage1, Haruhiro Kondo1, Junichi
Hasegawa1, Kazuhiro Kawamura1, Nao Suzuki1 St. Marianna University School of Medicine 1, Keio University Graduate School of
Science and Technology 2
Objective Assessment of ovarian reserve on each ovarian tissue
will enhance the effect of ovarian tissue transplantation. Nevertheless, there are no established noninvasive techniques forquantification of primordial follicles in fresh ovarian tissue. Optical coherence tomography（OCT）is high resolution imaging
technique equivalent to microscope with near infrared ray（NIR）. In present study, we verified potency of OCT for clinicalapplication. Methods OCT with ovaries from each life stage
mice was performed to establish standard follicle images. To!

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The PGC 1α mediated pathway as a potential therapeutictarget in endometriosis Hisashi Kataoka, Taisuke Mori,
Fumitake Ito, Akemi Koshiba, Osamu Takaoka, Hiroyuki
Okimura, Eiko Maeda, Takuya Sugahara, Yosuke Tarumi,
Izumi Kusuki, Jo Kitawaki Kyoto Prefectural University of
Medicine
Objective Previously, we reported that PGC 1α stimulates
aromatase activity to promote local estrogen biosynthesis in
ovarian endometrioma. In this study, we investigated the potential of PGC 1α as a molecular target for endometriosis treatment. Methods Stromal cells（SCs）from ovarian endometrioma（OE, n=21）and normal endometrium（NE, n=8）tissue were cultured. The SCs were transfected with PGC 1α or knocked down
for PGC 1α using siRNA. The expression level of PGC 1α andother factors during endometriosis was examined by real time
PCR and western blotting. Cell proliferation was measured by
the WST 8 assay. Transcriptional activity was examined by aluciferase reporter assay. HX531, a selective Retinoid X Receptor（RXR）antagonist, was used post transfection with PGC 1α.
Results PGC 1α overexpression promoted the proliferation of
OESCs, but not of NESCs, in a time dependent manner（P＜0.01）. PGC 1α stimulated the expression of aromatase, IL 6,
IL 8, and VEGF（P＜0.05）. Phosphorylated IκB was observed
post transfection with PGC 1α. The expression of XIAP and survivin, inhibitors of apoptotic proteins, was also upregulated（P＜0.05）. HX531 suppressed the PGC 1α induced cell proliferation（P＜0.05）；this compound also suppressed the expressionof the factors listed above（P＜0.05）. Moreover, transcriptional
reporter activity was inhibited by HX531 in a dose dependent
manner（P＜0.05）. PGC 1α knockdown reduced the expression.
of aromatase, IL 6, IL 8, and anti apoptotic factors（P＜0.05）
The immunostaining intensity of RXR in OE was significantly
greater than that in NE. Conclusion PGC 1α plays importantroles during cell proliferation in endometriosis. Thus, the PGC 1
α mediated pathway could be a potential molecular target forendometriosis treatment.

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HSD3B1 and Androgenetic alopecia in polycystic ovarian syndrome women Yi-An Tu, Mei-Jou Chen National Taiwan University Hospital, Taiwan
Objective Androgenetic alopecia（AGA）is a common phenotype
in women with PCOS. However, the mechanism of AGA is still
unknown. HSD3B1（1245A＞C）has been mechanistically linked

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Uterine progesterone signaling is a mechanistic target for
metformin therapy in polycystic ovary syndrome Linus R
Shao1, Yuehui Zhang1,2, Min Hu1, Hakan Billig1 The Sahlgrenska
Academy at the University of Gothenburg, Sweden 1, First Affiliated Hospital, Heilongjiang University of Chinese Medicine,
China 2
Background Impaired progesterone（P4）signaling is linked to
endometrial dysfunction and infertility in women with polycystic ovary syndrome（PCOS）. However, the molecular mechanisms behind this association are not well characterized. Metformin is one of the primary therapeutic drugs for PCOS patients, where beneficial treatment of endometrial dysfunction isobserved clinically, but the effects of metformin on the regulation of the P4 signaling pathway are not fully understood. Objective The present study sought to establish how the P4 signaling
pathway is involved in improved uterine function in PCOS patients treated with metformin. Study design Differential expression of two progesterone receptor（PR）isoforms in endometria
samples from non PCOS and PCOS patients was observed. Using an established PCOS like rat model, which exhibits similar
pathological alterations of both uterine morphology and function, we determined the molecular mechanism underlying metformin induced alterations of P4 signaling molecules before andafter implantation. To determine whether metformin directly
regulates PR, we evaluated PR targeted and implantation related gene expression in an in vitro study of rat uterine tissues.
Results We found that in the absence of P4 or to sustained low
levels of P4, both uterine PR isoforms were elevated in PCOS patients and in PCOS like rats in vivo. This was positively associated with the high levels of estrogen receptor（ER）expression.
Consistent with mouse knockout studies, decreased or increased
expression of Fkbp52 and Ncoa2, two genes that contribute touterine P4 resistance, was observed in PCOS like rats before
and after implantation. Our data showed that metformin directly suppressed uterine PR isoform expression along with thecorrection of aberrant expression of PR targeted and implantation related genes in PCOS like rats. Abnormal cell specificregulation of PR and ER, paralleling the aberrant expression of
PR targeted and implantation related genes, was retained insome PCOS like rats with implantation failure. In addition,
while increased PR expression was associated with inhibition of
the MAPK/ERK/p38 signaling pathway, metformin treatment
mainly restored the MAPK/p38 signaling pathway in PCOS
like rat uterus. Conclusion Our results suggest that the P4 signaling pathway might constitute the target of metformin treatment in PCOS patients with uterine dysfunction.

verify the safety of OCT, outcome of in vitro fertilization（IVF）was compared among follicles from day3 mice ovaries irradiated stepwise NIR（60 to 250 mW/cm2）.Also, day3 mice ovaries with/without OCT were transplanted under kidney capsuleof host mice. Two weeks later, outcome of IVF with transplanted ovaries were confirmed, and newborns were bred. Finally, OCT was performed using human ovary tissues which obtained from two hematological disease girls who received ovarian tissue cryopreservation as fertility preservation. And follicle
count was performed with OCT as quantification of follicle numbers. Results The standard OCT images were established including primordial follicle. And NIR irradiation and OCT examination did not affect for IVF outcome. Furthermore, all of newborns were shown normal appearances including reproductive
ability. Finally, OCT images of human ovarian tissues were
well accorded with histological images. As the result of follicle
count, there were no significant differences between histology
and OCT（p=0.98）. Conclusion In present study, potency of OCT
for clinical application was demonstrated to quantify of follicles
aimed at effective ovarian tissue transplantation.

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to polycystic ovarian syndrome（PCOS）because it encodes analtered enzyme that augments dihydrotestosterone synthesis
from non gonadal precursors. We postulated that women inheriting the HSD3B1 1245C allele would exhibit specific phenotypic variances in PCOS. Methods Between 2004 and 2011, inthe single center, we included 472 women with PCOS and determined their HSD3B1 genotype and correlated genotype withphenotypic outcomes, including androgenetic alopecia, acne, hirsutism, obesity, hypertension, and laboratory evidence of androgen excess and dyslipidemia. Results We included and genotyped 472 PCOS patients. Androgenetic alopecia was significantly increased（p=0.046）in women with heterozygous variant
genotype（n=56, 23.2%）, compared to that with homozygous
wild type genotype（n=416, 13.5%）.In PCOS women with AGA,
we found significantly higher BMI（26.9 vs. 23.0 kg/m2, p＜
0.001）,lower sex hormone binding globulin（22.5 vs. 31.7 nmol/
L, p＜0.001）, higher free androgen index（9.6 vs. 8.4, p=0.034）,
and more hypertension（15.9 vs. 7.7%, p=0.037）. The frequency
of HSD3B1 1245C allele（0.076）in this PCOS cohort was similarin previous reported Asian ethnicity（0.072）. Conclusion Inheritance of the HSD3B1 1245C allele that enhances peripheral dihydrotestosterone synthesis is associated with AGA phenotype
in PCOS. This is the first study elucidating the possible genetic
contribution of AGA phenotype in PCOS women.

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Clinical outcomes and risk of recurrence among patients withvaginal intraepithelial neoplasia Mi-Kyung Kim1, In Ho Lee2,
Ki Heon Lee2 Ewha Womans University of Korea, Korea 1, Cheil
General Hospital and Womenʼs Healthcare Center, Dankook University of Korea, Korea 2
Objective To evaluate the clinical outcomes of vaginal intraepithelial neoplasia（VAIN）and to assess the risk of recurrence andprogression to invasive vaginal carcinoma. Methods A retrospective review of the clinicopathologic data and clinical outcomes was performed on patients who were diagnosed with
VAIN at a single center between January 2000 and July 2016.
Demographics, treatments, and clinical outcomes were abstracted from medical records. Results A total of 576 patientswith VAIN1 3 were included in the study analysis. The distribution of VAIN1 3 was as follows：VAIN1 31.1%, VAIN2 45.3%,
and VAIN3/in situ carcinoma（CIS）23.6%. In VAIN1 patients,
observation was performed in 29.1% of the cases and 48.8% obtained regression. In VAIN2+ patients, management included
observation（3.5%）, topical management（6.5%）, laser ablation（75.3%）, excision（14.1%）, and radiotherapy（0.5%）with the following rates of recurrence/progression：46.2%, 62.5%, 26.4%,
32.7%, and 0%, respectively. Four patients among VAIN3/CIS
patients（3.2%）developed invasive vaginal cancer during the follow up period with a median time to cancer diagnosis of 21.4
months（range, 5.0 44.8 months）.On multivariate analysis, highrisk HPV positivity and treatment method were found to be independent risk factors for recurrence and progression（p=0.003
and p=0.001）. Conclusion Patients with VAIN are at high risk ofrecurrence, but the risk of progression to vaginal cancer is relatively low. Laser or excision provides higher regression rate
than topical agent or observation, and high risk HPV positivity
is a risk factor for recurrence. Whatever the treatment method
is used, however, the high rate of recurrence warrants longterm follow up surveillance.

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Acceptability and thoughts about Multipurpose Human Papillomavirus Vaccines in Korean physicians and mothers ofAdolescent Girls：What to consider when introducing a new
vaccine Hyewon Seo, Jahyun Koo, Minjin Jeong, Keunho Lee,

Taechul Park, Jongsup Park, Chanjoo Kim Catholic Universityof Korea, Korea
Objective Cervical HPV infection is a common sexually transmitted infection. In Korea, given the high priority of preventing
HPV associated cervical disease including cancers, HPV vaccines were integrated into national vaccination programs in2016. The importance of vaccines is emerging as the age of firstsexual experience is getting younger. Multipurpose vaccines（MPVs）could be formulated to prevent multiple sexually transmitted infections. This study was five countriesʼ collaborative
study（Argentina, Malaysia, South Africa, South Korea, andSpain）on MPVs acceptability led by the US in 2013. We aimed
to assess the acceptability of hypothetical MPVs for STI prevention, And further, what to consider when introducing a new vaccine. Methods We conducted in depth interview with 30 physicians for the acceptability of MPVs. We conducted focus group
discussion（FGD）with the 31 mothers of adolescent daughter.
Focus group discussion（FGD）with 31 mothers of adolescent
girls was done in 4 groups according to their daughterʼs HPV
vaccination status and social status. One group was consistedwith mothers of vaccinated daughters and the other 3 groups
were mothers of un vaccinated daughters. Results We foundout the research about MPV showed 71% of the mothers preferred single purpose HPV vaccines over MPVs. too muchʼsounds too dangerousʼ sounds less effective and more expensiveʼ. Concerns about Safety and efficacy was common barriers
to accepting MPVs. More mothers of vaccinated girls have pros
for the MPV（vaccinated vs unvaccinated 37.5%［3/8］vs. 26.1%［6/23］）but it was not statistically significant. Providers havepositive attitude（62%）toward MPVs. expect less follow up vaccination loss convenient are the main reasons. They said thebiggest problem with introducing a new vaccine was its costand lack of publicity, mentioned television advertisement as themost effective way to promote. Conclusion Effective recommendation and guideline should be promoted in more detail at the
specialized subcommittee when we accept new vaccine, and allthese activities will need national support. Publicity and effort
will be needed to change the viewpoint on obstetrics and gynecology at the national level as well. If we give information to thepeople with sufficient understanding of the disease and to recognize the need for a vaccine, the introduction of new vaccines is
expected to be successful in the future.

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Contribution of T helper 17 in peripheral blood to expressionof PD L1 in ovarian cancer Aeri Aotsuka1, Yoko Matsumoto1,
Ayumi Taguchi2, Takahide Arimoto3, Juri Ogishima1, Akira
Kawata1, Katsutoshi Oda1, Kei Kawana4, Yutaka Osuga1,
Tomoyuki Fujii1 The University of Tokyo Hospital 1, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome
Hospital 2, Toranomon Hospital 3, Nihon University Itabashi Hospital 4
Objective The PD 1/PD L1 pathway has shown promisingclinical success as a cancer immunotherapy target. T helper 17
cells（Th17）inducing Interleukin 17（IL 17）are known as causeof autoimmune diseases. In this study, we aimed to analyze therole of Th17 in peripheral blood in the regulation of PD L1 expression in human ovarian cancer. Methods Blood samples of 30
ovarian cancer patients and 18 healthy controls（HC）were collected under approval of our institutional ethics committee. Ratio of Th17 in peripheral blood mononuclear cells（PBMCs）andexpression level of IL 6 in plasma were analyzed by multi color
flow cytometry and enzyme linked immunosorbent assay. Expression levels of PD L1 mRNA in PBMCs was quantified byreal time polymerase chain reaction. We refer to the clinical record of neutrophil to lymphocyte ratio（NLR）which can be a
prognostic marker in ovarian cancer. Results Flow cytometry

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Microsatellite instability is a potential biomarker for immune
checkpoint inhibitor（anti PD 1/PD L1 antibody）in endometrial cancer Hitomi Yamashita, Kentaro Nakayama,
Masako Ishikawa, Tomoka Ishibashi, Kohei Nakamura, Kaori
Ohnishi, Ruriko Ono, Hiroki Sasamori, Kouji Iida, Razia Sultana,
Toshiko Minamoto, Satoru Kyo Shimane University
Objective Tumor cells have immune escape mechanism and immune checkpoint inhibitor therapy（anti PD 1/PD L1 antibody）
has shown benefit in various cancers. Somatic mutations havethe potential to encode non self immunogenic antigens and lymphocytes infiltrate tumor cells in microsatellite instable（MSI）endometrial cancers. Therefore, immune checkpoint inhibitor therapy might be effective in MSI endometrial cancers.
Methods Mismatch repair protein（MLH1, PMS2, MSH2, andMSH6）, tumor infiltrating lymphocytes（CD8）, and PD 1/PD L
1 expression were assessed by immunohistochemistry in 60 patients with endometrial cancer. We examined whether MSI
status have enhanced immune microenvironment and become
the therapeutic effect predictor of PD 1/PD L1 immunotherapy
in endometrial cancer. Results Loss of mismatch repair protein（MSI group）was identified in 42（27.2%）of 154 patients withendometrial cancer. Expression of tumor infiltrating lymphocytes（CD8）and PD 1/PD L1 were significantly higher in MSI
group compared to MSS group（p=0.007, p=0.010 and p＜0.001）.
Conclusion These results suggested that immune checkpoint inhibitor（anti PD 1/PD L1 antibody）is effective in endometrial
cancers with MSI. MSI testing is likely to be a biomarker for
PD 1/PD L1 immunotherapy in endometrial cancer.

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Nationwide cohort study of the risk of major adverse cerebrovascular and cardiovascular events in the Asian womenwith endometriosis Hsin-Ju Chiang1, Kuo-Chung Lan1, Yao-Hsu
Yang2, Pei-Hsun Sung3 Kaohsiung Chang Gung Memorial Hospital, Taiwan 1, Department of Traditional Chinese Medicine,
Health Information and Epidemiology Laboratory, Chang Gung
Memorial Hospital, Taiwan 2, Division of Cardiology, Department
of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan 3
Background Emerging evidence shows growing cardiovascularrisk in a number of womenʼs disease. Based upon positive correlation of anti Müllerian hormone to cardiovascular disease in recent studies, we investigated the association between endometriosis and major adverse cerebro /cardio vascular events（MACCE）in an Asian population. Method Taiwan National
Health Insurance Research Database（NHIRD）was utilized forthis retrospective population based cohort study（1997 2013）.
A total of 17,543 patients with endometriosis and age between
18 and 50 years were identified from 1,000,000 general populations after excluding initially concomitant diagnoses of MACCE.
The MACCE was defined as major cardiovascular disease（ma-

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jor CVD, comprising myocardial infarction and heart failure）
and cerebrovascular accident（CVA, including ischemic andhemorrhagic strokes）.The comparison group（n=70,172）
without
endometriosis was selected matching study cohort with age,gender, income and urbanization in a 1：4 ratio. We compared
the demographic data, frequency of comorbidities, incidence ofand risk of MACCE between the disease and non diseasegroups. Results With a median follow up of 9.2 years, the endometriosis patients had significantly higher frequency and cumulative incidence of MACCE than non endometriosis counterparts（2.76% vs. 2.18%, p＜0.0001）. After adjusting with multivariate analysis, the patients with endometriosis had 1.17 foldgreater risk for future development of MACCE（95% CI 1.05
1.29, p=0.0053）. In further, the adjusted hazard ratios of endometriosis for major CVD and CVA were 1.19 and 1.16, respectively（all p＜0.04）. Apart from endometriosis, older age, lower
urbanization level, hypertension and diabetes were identified asrisk factors for MACCE occurrence as well. On the contrary,neither medication nor surgery for endometriosis increased therisk of MACCE. Conclusion The risk of MACCE including major CVD or CVA increases in the Asian women at reproductive
age. There is no concern of increasing MACCE risk regarding
medication and surgery for endometriosis.

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Mediator complex subunit 1（MED1）is a novel binding partnerof BRCA1 and regulates homologous recombination repair
Harunori Honjoh, Michihiro Tanikawa, Osamu Hiraike,
Katsutoshi Oda, Yoshiko Kawata, Machiko Kojima, Shinya Oki,
Kenbun Sone, Kazunori Nagasaka, Yoko Matsumoto, Yutaka
Osuga, Tomoyuki Fujii The University of Tokyo
Objective Homologous recombination（HR）is a major repair
pathway of DNA double strand breaks and closely correlatedwith carcinogenesis of breast and ovarian cancer. HR deficiency
has now been established as a therapeutic target. The aim of
this study was to elucidate functions of a novel HR factor, MED
1, and its association with BRCA1. Methods Novel HR candidate
genes, including MED1, were identified through genome widesiRNA screening. The complex formation of MED1 and BRCA1（the central integrator of HR and transcription）was analyzed
by immunoprecipitation and GST pull down assay. The role astranscription cofactors of BRCA1 was analyzed by luciferase assay. The roles in DNA damage response and HR pathway wereanalyzed by immunofluorescence and HR assay. Results Among
several HR candidate genes, we identified MED1 as a novel
binding partner of BRCA1, which binds to BRCT domain of
BRCA1. Luciferase assay showed MED1 potentiate the transcription ability of BRCT by 1.5 folds. In MED1 depleted cells,
recruitment of HR genes, such as RPA and γH2AX, to DNA
damage sites were severely impaired. HR assay showed strong
deficiency of HR in MED1 depleted cells. Conclusion We identified MED1 as a transcription cofactor in HR pathway. The impaired interaction of MED1 and BRCA1 may be an alternative
mechanism of HR deficiency in cancer cells.

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Lack of interval cytoreductive surgery after neoadjuvant
chemotherapy in peritoneal, ovarian, or fallopian tube cancer：a description of reasons and treatment outcomes
Myong Cheol Lim1,2, Snag-Soo Seo1, Sokbom Kang1, Sang-Yoon, Korea 1,
Park1, Robert E. Bristow2 National Cancer Center（NCC）
Irvine Medical Center, University of California, USA 2
Objective To investigate the reasons for lack of interval cytoreductive surgery and subsequent treatment outcomes of patientswith ovarian cancer who underwent neoadjuvant chemotherapy. Methods We conducted a retrospective study of women

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revealed that the ratio of Th17 of ovarian cancer patients weresignificantly higher（p =0.002）than HCs. The ratio of Th17 was
associated with NLR in ovarian cancer patients（p =0.023）.Moreover, Th17 and NLR were also correlated with concentration of. Quantitative realIL 6（p =0.003 and p =0.008, respectively）
time PCR analysis revealed that the expression of PD L1mRNA of ovarian cancer patients was not significantly distinct
from that in HCs. However, we observed that IL 17 induced
both PD L1 and IL 6 mRNA expressions with upregulation of
PD L1 protein expression in a human ovarian cancer cell line.
Conclusion Our data suggest that increase of Th17 ratio in
PBMCs contributes to the upregulation of PD L1, which maylead to immune tolerance in ovarian cancer.

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with advanced ovarian cancer who never had interval cytoreductive surgery, by using medical chart reviews between September 2001 and December 2015. Results Of 470 women who received neoadjuvant chemotherapy as an initial treatment, 110（23.4%）women did not undergo interval cytoreductive surgery.
Of the 110 women, 45（40.9%）and 65（59.1%）patients had stage
III and IV disease, respectively. The median age was 65.6 years（range, 30.6 86.4 years）. The main reason for not undergoing
the recommended interval cytoreductive surgery was patientrefusal（n=29；26.4%）. Other reasons included progressive disease after neoadjuvant chemotherapy（19.1%）, chronic illness
and/or old age（17.3%）, death during neoadjuvant chemotherapy（10.9%）, and persistent extraperitoneal disease（10.0%）.The median overall survival for these groups was 21.8, 16.7, 14.7, 9.7, and
0.9 months for patients who refused surgery, had chronic illness
and/or due to old age, had extraperitoneal disease, had progressive disease, and died during chemotherapy, respectively. In themultivariate analysis, age was the only prognostic factor for
women who did not undergo interval cytoreductive surgery.
Conclusion and Relevance Patientsʼ refusal to undergo interval
cytoreductive surgery was the main reason for the lack of surgery, resulting in a median overall survival of 21.8 months. The
survival benefit of an intentionally planned treatment package,
including interval cytoreductive surgery, needs to be carefully
discussed with patients before administration of neoadjuvant
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Differential localization of extracellular matrix related proteins in the uterine cervix of female pelvic organ prolapse
Aki Takase1, Akihiro Hamuro1, Masami Hayashi1, Natsuko
Yokoi1, Hiroko Katayama1, Takuya Misugi1, Akemi Nakano2,
Daisuke Tachibana1, Masayasu Koyama1 Osaka City University 1,
Department of Research Support Platform, Osaka City University 2
Objective Pelvic organ prolapse（POP）is multifactorial disorderwhich impairs the quality of the life of the elderly women. Although mechanical pelvic floor damage is a direct trigger of the
progression of POP, genetic and molecular biological pathogenesis of POP has not been clarified yet. Methods POP patients（n=29）were classified into two groups by with（n=13）or without
cervical elongation（n=16）by POP Q assessment. We investigated the expression of extracellular matrix（ECM）related proteins, elastin, fibulin 5（FBLN5）, integrin β1（ITGβ1）, lysyl oxidase like 1（LOXL1）and collagen in human vaginal mucosa（VM）,uterosacral ligament（USL）and uterine cervix（UC）. Samples were obtained during pelvic reconstructive surgery from
29 women suffering from POP under permission of institutional
IRB（2199）. Localization of ECM proteins were immunohistochemically evaluated and their mRNAs were quantified byreal time polymerase chain reaction technique and correlation
between mRNA level of each protein and severity of POP. Results FBLN5 and elastin were localized at lamina propria and fibromuscular layer of VM and USL. FBN5 gene expression was
positively correlated to the advance of POP in USL of cervicalelongation group, while negative correlation was observed inthose of normal cervix group. ITGβ1 and LOXL1 mRNAs fromUC samples significantly increased with POP Q staging in thecervical elongation group. Expression of elastin and collagenalso significantly increased in cervical elongation group. Conclusion The correlation between progression of POP andmRNAs of ECM related proteins was different from the existence of cervical elongation of POP. Differential expression of
ECM proteins will affect the phenotype of POP.

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The discovery of new biomarkers for preterm birth prediction Hyun Joo Shin, Young-Ah You, Eun Jin Kwon, JiEun Doo,Kyung Ju Lee, MiHye Park, Young Ju Kim Ewha Womans University Medical School, Korea
Objective We aimed to investigate biological biomarkers in maternal blood, amniotic membrane, amniotic fluid, urine, and vaginal discharge to prevent preterm birth. Methods To determine
the biomarkers for early detection of preterm delivery, 40 cytokines were measured with amniotic fluid of pregnant womenusing cytokine array and we screened cytokines of amniotic
fluid between preterm women and normal pregnant women.
Next, the 16S rRNA sequencing method using the next generation sequencing with urine, blood, and vaginal fluid in pregnant
women was used to compare metagenomes that differed between preterm and normal groups. Lastly, we identified thebiomarkers in maternal blood and amniotic membrane using
methylation array. After screening, we performed the experiments for the validation in large samples. Results After cytokine array in amniotic fluid, the 15 pro inflammatory cytokines（IL 1β, IL 6, IL 7, IL 8, TNF α, MMP3, MMP8, MMP9,
MIP 1α and MIP 1β）were significantly higher in preterm birthgroup. IL 10, IL 13, IL 15, IL 17α, and G CSF were significantly different among the 15 pro inflammatory analyzed by
ELISA. In urine metagenome of 73 non pregnant women and 74
pregnant women, Bacillus was increased about 374 times in maternal urine, and Lactobacillus and Atopobium was increased in
preterm women. Specially, premature babies born to motherswith increased Lactobacillus, Ureaplasma, Megashaera, Apotobium, Fusobacterium, Sneathia and Prevotella in the urine
showed diseases such as hyaline membrane disease, germinal
matrix hemorrhage, pneumomediastinum, respiratory distresssyndrome and urinary tract infection. We tried to findmetagenome related to preterm birth in maternal vaginal fluid.
In this study, it was found that Bacteriodes and Prevotella weresignificantly increased in vaginal fluid of preterm pregnant
women. One of the probiotics found in Kimchi and Lactobacillus
were significantly decreased in vaginal fluid of preterm pregnant women. Furthermore, IL 7 was correlated with a decreasein Lactobacillus and an increase in Bacteroides. After methylation array and experiments for validation, there were significant
differences in the methylation of the KIMB gene in the maternal
blood between preterm and normal groups and in the methylation of the KIMC and KIMD in the amnion（p＜0.05, respectively）.Conclusion We found several candidate biomarkers related to preterm birth in amniotic fluid, urine, urine, blood, andamniotic membrane. We are trying to do experiments to identify candidate markers in the population. In near future, we
hope the development of biomarker to predict preterm birth using non invasive method from pregnant women.

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Comparison of pregnancy outcome among nulliparas withand without microalbuminuria at the end of the second trimester Maryam Kashanian, Shohreh Bahasadri, Zahra Khosravi
Iran University of Medical Sciences, IranIntroduction Poor pregnancy outcome and complications during pregnancy such as pre eclampsia, preterm delivery, preterm premature rupture of membranes（PPROM）and intra uterine growth restriction（IUGR）, are very important and the finding of new methods for their prediction has always been a matter of serious concern. Objective To evaluate the rate of poor
pregnancy outcome among nulliparas who had microalbuminuria at the end of the second trimester of their pregnancy. Methods A prospective cohort study was performed on 490 nulliparous women who were at the end of the second trimester of

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with the occurrence of CCI in pregnant women with non primary CMV infection. Methods This study was approved by theinstitutional ethic boards, and written informed consent was obtained from all participants. One thousand two hundred andeighty seven pregnant women with non primary CMV infection were enrolled. Positive CMV IgG, avidity index ＞45% andnegative IgM were defined as non primary infection. Clinicalfactors assessed were as follows：hypertensive disorders, diseases requiring immunosuppressive medication, abnormal glucose tolerance, threatened premature labor, and multiple pregnancy etc. To determine risk factors for CCI, logistic regression
analyses were performed. Results Seven（0.5%）of the 1,287 pregnant women with non primary infection were found to havenewborns with CCI. Univariate logistic regression analyses
demonstrated that threatened premature labor（OR 10.6, 95%CI
2.0 55.0；p＜0.01）and multiple pregnancy（OR 7.1, 95%CI 1.4
37.4；p＜0.05）were associated with the occurrence of CCI. Multivariable logistic regression analyses revealed that threatenedpremature labor was a significant risk factor of CCI（OR 8.4, 95%
CI 1.5 48.1；p＜0.05）. Conclusion The present study demonstrated for the first time that the threatened preterm labor wasa risk factor for the occurrence of CCI from mothers with non
primary CMV infection.

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Causes and risk factors for singleton stillbirth in Japan：ananalysis using the Japan Society of Obstetrics and Gynecology Perinatal Database, 2013 2014 Rei Haruyama1, Naoyuki
Miyasaka2 The University of Tokyo 1, Tokyo Medical and Dental
University 2
Objective Although Japan has achieved one of the lowest perinatal mortality rates in the world, more than 80% is due to stillbirths after 22 weeks of gestation with one in 300 families experiencing fetal loss every year. This study aimed to assess causes
and risk factors for singleton stillbirth in Japan. Methods A retrospective cross sectional study was conducted using the Japan
Society of Obstetrics and Gynecology（JSOG）Perinatal Databasefrom January 2013 to December 2014. A total of 379,211 births
including 2,133 stillbirths were analyzed. Causes of death were
examined by the JSOG clinical death classification system andreclassified according to the level 1 categories of the Cause of
Death and Associated Conditions classification system by gestational age. A multi level Poisson regression model was used toassess the relationship between stillbirth and key maternal, fetal, and facility factors. Results Causes of death were unknown
in 25 45% of stillbirths. Among the known cause, placental abnormality accounted for the most, followed by umbilical cord abnormality and congenital malformation. Stillbirth risk was increased among small for gestational age infants（adjusted relative risk（ARR）：3.8, 95% confidence interval（CI）：3.3 4.3）andnulliparous women（ARR：1.2, 95% CI：1.1 1.3）
. By contrast,
maternal underweight, pregnancy induced hypertension andoligohydramnios showed a protective effect. Conclusion This
study suggests that stillbirths occurring among women withknown complications are likely already being prevented in Japan. Further reduction in stillbirths must target small sized fetuses and nulliparous women. Improved recording of the causal
pathways of stillbirths is also needed to explain stillbirths withunknown cause of death.

Pre pregnancy factors associated with development of hypertension in women with preeclampsia Hye Jin Choi1, Geum Joon
Cho1, Min Jung Oh1, Jong Heon Park2, Ki-Hoon Ahn1, Soon-CheolHong1, Hai-Joong Kim1, Sung Won Han2 Korea University, Korea 1, Big Data Steering Department, National Health Insurance
Service, Korea 2
Objective The aim of our study was to investigate the pre pregnancy characteristics that are risk factors for the developmentof hypertension（HTN）and identify pre pregnancy factors forthe development of HTN in women affected by preeclampsia intheir first pregnancy. Study design We enrolled 1,910 women
who had undergone a National Health Screening Examination
through the National Health Insurance Corporation between
2002 and 2003, and who had their first delivery affected by
preeclampsia in 2004. Women were classified as having HTN ifthey were newly diagnosed with HTN from 2005 through 2012.
Results After 8 years of follow up, 7.7%（148/1,910）of
preeclamptic women developed HTN. Using the Cox proportional hazards model, old age（hazard ratio［HR］3.92, 95% confidence interval［CI］2.47 6.23）, a family history of HTN（HR 2.28,
95% CI 1.46 3.58）, pre pregnancy obesity（HR 3.74, 95% CI 2.50
5.59）
, and high blood pressure（BP）（HR 2.78, 95% CI 1.85 4.19）,
were independently associated with the development of HTN.
Conclusion The results show the development of HTN in
preeclamptic women is related to pre pregnancy factors. Thissuggests that the monitoring and management of these factors
during pre pregnancy and/or early pregnancy may facilitate areduction in the likelihood of developing preeclampsia and HTN
in the future.

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Risk factors for congenital cytomegalovirus infection inpregnant women with non primary infection Akiko Uchida1,
Kenji Tanimura1, Shinya Tairaku1, Kana Ozaki1, Satoshi
Nagamata1, Mayumi Morizane1, Masashi Deguchi1, Yasuhiko
Ebina1, Ichiro Morioka1, Toshio Minematsu2, Hideto Yamada1
Kobe University Hospital 1, Aisenkai Nichinan Hospital 2
Objective Not only primary cytomegalovirus（CMV）infection
during pregnancy but also non primary infection can cause congenital CMV infection（CCI）. The aim of this prospective cohort
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Antenatal ultrasound findings and hemorrhagic outcomes insuspected abnormally invasive placenta Su Kyeong Kong,
Suk Young Kim, Eun Suk Seo, Mee Hyang Ko Gil Medical Center Gachon University, Korea
Abnormally invasive placenta（AIP）is a clinical term used todescribe a placenta that does not separate spontaneously at delivery and cannot be removed without causing high blood loss.
Because of potentially life threatening, accurate antenatal diagnosis in suspected AIP allows improved pregnancy outcomes.
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pregnancy. Urine tests for albuminuria and creatinine measurements were performed in all women and the albumin to creatinine ratio（ACR）was calculated. The women with microalbuminuria（exposed group）and those without microalbuminuria（nonexposed group）were monitored until the end of their pregnancy and compared for pregnancy outcome. Results Preterm
labor（57.9% versus 13.5%）, preeclampsia（50.0% versus 8.6%）,
intrauterine growth restriction（42.1% versus 6.4%）, and preterm premature rupture of membranes（31.6% versus 10.2%）
were significantly more common in the exposed group. The
rates of gestational diabetes did not differ significantly between
the 2 groups. In multivariate logistic regression analyses, microalbuminuria increased the risks for preterm labor（adjusted OR
2.4；95% CI 1.1 5.5, P=0.03）and preeclampsia（adjusted OR 9.5；
95% CI 4.6 19.3, P=0.001）. Conclusion Microalbuminuria at theend of the second trimester of pregnancy might increase therisks of preterm labor, preeclampsia, intrauterine growth restriction, and preterm premature rupture of membranes.

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ings and hemorrhagic outcomes in suspected AIP. Between 2016
and August. 2017, distribution of ultrasound signs and pregnancy outcome were examined in patients with suspected AIP.
We used the Pro forma for ultrasound reporting. The report include appropriate demographics and risk factors and ultrasoundsigns to evaluate AIP. There were 6 parameters of grayscale
and 4 parameters of color Doppler ultrasound. During this period 862 living singleton births had occurred and they had atleast one scan in our ultrasound unit. Finally 41 cases were enrolled in prospective observational study. The majority of patients had placental lacunae of grayscale parameters and subplacental hypervascularity of color doppler ultrasound. The
prevalence of loss of clear zone and all parameters of color doppler ultrasound was association with high blood loss at delivery.
There was a significant relationship between subplacental hypervascularity and blood loss（p=0.003）. Antenatal ultrasoundfindings has a clinical significance to predict high blood loss.
Further studies using a standardized approach in suspected
AIP to evaluate correlation between ultrasound sings and hemorrhagic outcomes are needed.

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Obstetric outcome and use of medications during pregnancy
with systemic lupus erythematosus, rheumatoid arthritis andinflammatory bowel disease in Japan；A nationwide retrospective descriptive study Sayaka Tsuda1, Azusa Sameshima1,
Haruna Kawaguchi2, Shintaro Makino3, Daisuke Fujita4, Shigeru
Saito1 University of Toyama 1, Osaka Medical Center and Research Institute for Maternal and Child Health 2, Juntendo University 3, Osaka Medical College 4
Objective To describe obstetric outcome and medications during pregnancy with systemic lupus erythematosus（SLE）, rheumatoid arthritis（RA）, Crohnʼs disease（CD）and ulcerative colitis（CD）. Methods We conducted questionnaire survey to thehospitals listed in the Japan Maternal Fetal Intensive Care Unit
Network. It inquired the number of the pregnancy with thosediseases for two years, obstetric outcome and medications. Results Among 69,810 deliveries, pregnancy with SLE, RA, CD and
UC were 282（0.4%）, 203（0.3%）,68（0.1%）and 302（0.4%）,respectively. Compared with before conception, the proportion of patients with active disease increased during pregnancy in SLE（4.8% vs 15.0%, p=0.003）but not in others. In SLE, incidence
rates of preterm delivery, preeclampsia（PE）, fetal growth restriction（FGR）and thromboembolism were higher than that ofgeneral population（9.6% vs 5.6% p=0.017, 14.4% vs 5.6% p=
0.0002, 11.2% vs 4.1% p＜0.0001, 2.7% vs 0.1% p＜0.0001）. Incidence rates of preterm delivery in RA and FGR in CD were alsosignificantly higher（12.9% vs 5.6% p=0.0002, 20.7% vs 4.1% p=
0.001）. Anti TNF inhibitors users during pregnancy were 0.0%
of SLE, 15.0% of RA, 65.5% of CD and 3.9% of UC. Immunosuppressive agents users were 19.3%, 2.9%, 17.2% and 3.3%, respectively. To estimate the birth rate, that of RA women was 42.2%（95% CI；24.1 60.2）of general population. Conclusion Frequency of obstetrical complications was the highest in SLE. We
showed that despite pregnancy increased the rate of active disease just in SLE but not in RA, CD and UC, the birth rate of RA
were fewer than that of general population in Japan.

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Antenatal anti arrhythmic treatment for fetal tachyarrhythmias：a prospective multicenter trial in Japan Takekazu
Miyoshi1, Haruhiko Sago2, Hitoshi Yoda3, Makio Shozu4, Shinji
Katsuragi1, Tomoaki Ikeda5 National Cerebral and Cardiovascular Center 1, National Center for Child Health and Development 2,
Toho University Omori Medical Center 3, Chiba University 4, Mie
University 5!

Objective To evaluate the efficacy and safety of the protocol defined transplacental treatment of fetal tachyarrhythmias. Methods This was a multicenter, single arm interventional study. A
total of 50 fetuses were enrolled at 15 Japanese institutions from
October 2010 to January 2017. The protocol defined treatment
was performed for singletons with sustained fetal tachyarrhythmia ＞180 bpm, with a diagnosis of supraventricular tachycardia（SVT）or atrial flutter（AFL）. Digoxin, sotalol, flecainide or
a combination was used for transplacental treatment. The primary endpoint was disappearance of fetal tachyarrhythmias.
Results SVT shortVA（n=17）,SVT longVA（n=4）and AFL（n=29）were diagnosed at 30.4±3.2 weeks of gestation. Fetal hydrops at diagnosis was found in 5 cases. Maternal adverse event
was observed in 43/50（86.0%）, however, each event was minor,
thus transplacental treatment could be continued. The treatment effect was analyzed in 49 cases excluding 1 case of dropout. Fetal tachyarrhythmia disappeared in 41/49（83.7%）；39/44（88.6%）of non hydropic and 2/5（40.0%）of hydropic fetuses.
Fetal demise was found in 2 cases；AFL with suspected Costello syndrome and advanced hydrops, and SVT shortVA（suspected ventricular tachycardia）with progression of fetal hydrops. Mean gestational age was 37.0±1.9 weeks and preterm
birth was 8/47（17.0%）. Neonatal tachyarrhythmia was found in
17/47（36.2%）. Conclusion Our protocol defined transplacental
treatment of fetal tachyarrhythmias is effective and tolerable inmore than 80% of cases. However, it is necessary to take noticeof serious fetal adverse events and recurrence of tachyarrhythmias after birth.

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Clinical significance of p53 binding protein 1 nuclear foci incervical squamous intraepithelial lesions Sayaka Kawashita,
Kiyonori Miura, Yuri Hasegawa, Takako Shimada, Michio
Kitajima, Hideaki Masuzaki Nagasaki University
Objective As p53 binding protein 1（53BP1）localizes at the sitesof DNA double strand breaks and forms nuclear foci（NF）, the
presence of 53BP1 NF can be considered as an indicator of endogenous genomic instability. We previously reported the numberof 53BP1 NF in cervical squamous intraepithelial lesions（SIL）
increased with tumor progression. In this study, to clarify thesignificance of 53BP1 NF in SILs, we analyzed the distributionof 53BP1 NF in a series of SILs and compared with the expression of P16, which is a useful diagnostic marker of SIL reflecting
the proliferative stress caused by HPV infection. Methods We
performed double label immunofluorescence for 53BP1 and P16
in 64 cases of SILs（CIN1：22 cases, CIN2：21 cases, and CIN3：
21 cases）. Correlation between the expressions of 53BP1 NF and
P16 in epithelial layers was analyzed. Results P16 was negativein 10 cases of SILs（15.6%）. In 54 cases of SILs with a positive expression of P16, a strong correlation between the expressions of
53BP1 NF and P16 was detected（P＜0.0001）, suggesting that
53BP1 NF could be a potential diagnostic marker for SILs as
well as p16. Furthermore, when 53BP1 NF was detected over 1/
3 layer of epithelium, the presence of SILs referring to ROC
curve showed highest sensitivity and specificity. Especially, fiveof 10 cases with a negative result of P16（50%）were diagnosed
as SILs correctly. Conclusion 53BP1 NF immunofluorescence!

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The expression of glucagon like peptide 1 receptor could bea novel biomarker of endometrial cancer possibly by stimulating autophagy via AMPK signaling pathway Ranka Kanda1,
Haruko Hiraike1, Yasuhiro Matsumoto1, Yuko Sasajima2,
Kazunori Nagasaka1, Osamu Hiraike3, Eiji Ryo1, Yutaka Osuga3,
Tomoyuki Fujii3, Takuya Ayabe1 Teikyo University 1, Department of Diagnostic Pathology, Teikyo University 2, The University of Tokyo 3
Objective A previous report suggested that glucagon like peptide 1 receptor（GLP 1R）agonist exenatide induced apoptosis
in endometrial cancer cells. However, pathophysiological role of
GLP 1R in endometrial cancer is not fully elucidated. Here, we
aimed to further investigate the effects of GLP 1R agonist liraglutide in endometrial cancer cells, and examined the association between GLP 1R expression and clinicopathological characters in endometrial cancer patients. Methods Ishikawa cells
were treated with liraglutide of different concentrations. Cell viability assay, colony formation assay, flow cytometry, Western
blotting, and immunofluorescence were used to assess the effects of liraglutide. The induction of autophagy was examinedby analyzing the expression levels of LC3 and p62, and the accumulation of autophagosome. Moreover, using tissue microarray,
we analyzed the GLP 1R expression status in 154 endometrial
cancer tissues by immunohistochemistry. Results In concordance with previous report, liraglutide inhibited the growth ofcancer cells in a dose dependent manner. We revealed that thetreatment with liraglutide significantly induced autophagy, andphosphorylated AMPK expression was elevated in Ishikawa
cells. The immunohistological analysis of GLP 1R revealed thatthe expression of GLP 1R was associated with positive estrogenand progesterone receptor status, and higher expression of
GLP 1R was significantly correlated with better progression
free survival. Conclusion The application of liraglutide to target
autophagy in endometrial cancer cells may provide a new potential treatment for endometrial cancer. Furthermore, higher
expression of GLP 1R may be associated with better prognosis
in endometrial cancer patients.

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The clinical prognostic correlation of CypB in epithelial
ovarian carcinoma patients Heng-Cheng Hsu1,2, Chi-An Chen2,
Chang-Yao Hsieh2, Wen-Fang Cheng2,3,4 National Taiwan University Hospital Hsin Chu Branch, Taiwan 1, College of Medicine,National Taiwan University, Taiwan 2, Graduate Institute ofClinical Medicine, College of Medicine, National Taiwan University, Taiwan 3, Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taiwan 4
Objective To invesitgate the role of CypB as a clinical prognostic biomarker for patients with epithelial ovarian carcinoma.
Methods We measured CypB expression with quantitative realtime polymerase chain reaction（qRT PCR）in 201 women with
EOC and 36 woman with normal/benign ovaries and evaluatedcorrelations between CypB expression, clinicopathological characteristics, and the outcomes of the patients. Results The expression of CypB was higher in cancerous tissues than in normal
tissues. The expression of CypB were especially elevated in patients with ovarian clear cell caricinoma（p＜0.001）,high grade（p＜0.001）, and lymph node metastasis（p=0.044）. Conclusion
The results suggest that CypB could be a potential marker topredict ovarian cancer cell type and be a predictor of lymph
node metastasis.

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The prognostic role of pre treatment complete blood countprofiling in early cervical cancer Joseph J. Noh, Chel Hun
Choi, Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae Samsung
Medical Center, Sungkyunkwan University School of Medicine,
Korea
Objective To investigate the prognostic role of pre treatmentcomplete blood count（CBC）profiling as a predictive marker ofsurvival, recurrence and death in early stage adenocarcinoma
and squamous cell carcinoma of the cervix. Methods The CBC
profiles of the patients from eight tertiary medical centers inSouth Korea who were treated surgically for early stage cervical cancer were reviewed. The blood samples were collected
within two weeks prior to the initial operation. Results A totalof 1,441 patients were included in the study and the median follow up was 58 months with a range of 3 181 months. They wereclassified according to the disease status no evidence of disease（NED）,hematogenous recurrence, lymphatic recurrence ordeath. Those who recurred within five years from the initial
treatment showed lower hemoglobin levels and higher plateletlevels in pre treatment CBC compared to the NED group（hemoglobin in g/dL, 12.4 vs. 12.7, p＜0.01；platelet in multiple of
103/microliter, 273 vs. 250, p＜0.01）. The patients who diedwithin five years from the initial treatment also showed lower
hemoglobin levels and lymphocyte percentage levels comparedto those who survived（hemoglobin in g/dL, 12.4 vs. 12.7, p＜
0.01；lymphocyte in percentage, 1.7 vs. 1.9, p＜0.01）. Furtheranalyses revealed that low hemoglobin and high platelet levels
were predictive markers of overall recurrence including both
hematogenous and lymphatic while low white blood cell（WBC）,
neutrophil levels and high platelet levels were predictive of hematogenous recurrence. Pre treatment low hemoglobin levels
were also shown as a prognostic marker of death in this population. Conclusion Pre treatment CBC profiling including WBC,hemoglobin, neutrophil, lymphocyte and platelet levels were
found to be a potential biomarker for survival prognosis in earlycervical cancer.

may be a potential diagnostic marker for SILs, especially in thecases with a negative result of P16.

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Laparoscopic cornuostomy versus cornual resection using hemostatic suture：interstitial ectopic pregnancy Bo Ram Yu,
Chul Hee Rheu, Jong Hyun Kim Chonbuk National University of
Korea, Korea
Objective To evaluate outcomes of two surgical management（cornuostomy, cornual resection）of interstitial ectopic pregnancies. Methods Retrospective case review of patients with cornual pregnancy which treated by laparoscopy. The charts ofthirty five patients managed by laparoscopic cornual resection
or cornuostomy at Chounbuk National University Hospital, Korea, from 2010 to 2017 were reviewed. The primary outcomes
were operation time, hemoglobin level difference after surgery,blood transfusion, postoperative methotrexate（MTX）injection,
postoperative acute complication（infection, bleeding, etc.）.The
secondary outcomes were pregnancy outcomes like full term delivery, another ectopic pregnancy, etc. The primary outcomes
were processed by paired t test. Results Seventeen patientswere treated by cornual resection using hemostatic suture. Sixteen patients were treated by cornuostomy using hemostatic suture. Between cornual resection group and cornuostomy group,
the values of operation time, hemoglobin level difference after
surgery, blood transfusion, postoperative MTX injection, postoperative acute complication（infection, bleeding, etc.）are statistically not significant. 1 case of continuous abdominal pain after
cornual resection was managed by bed rest ＆ pain killer only. 1
case of vaginal bleeding after cornuostomy which suspected asuterine subinvolution was treated by uterotonic agents. Only 1case of 21 unruptured interstitial ectopic pregnancys was transfused blood after cornual resection. Only 3 patients were pregnant after laparoscopy（one after cornual resection, two after
cornuostomy）. No one has recurred yet. Conclusion Cornual resection is not superior to cornuostomy with regard to postoperative outcomes. Cornuostomy would be considered as a first line
surgical treatment.

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JKT-YD-6!

Porphyromonas gingivalis lipopolysaccharide enhances inflammation in amniotic mesenchymal cells Haruhisa Konishi1,
Satoshi Urabe1, Yuko Teraoka1, Mutsumi Miyauchi2, Hiroshi
Miyoshi3, Takashi Takata2, Yoshiki Kudo1 Hiroshima University 1,
Department of Oral and Maxillofacial Pathobiology, Hiroshima
University 2, Hiroshima Prefectural Hospital 3
Objective Inflammation is known to induce preterm delivery.
We previously reported that mice with dental Porphyromonas
gingivalis（P.g ；a common pathogen of dental disease）infection
could be used as an effective model of preterm delivery. In thismodel, P.g colonies were observed in the fetal membrane, andinflammation on the fetal membrane is thought to be the maincause of preterm delivery as COX 2 and interleukin（IL）1b levels are highly upregulated. However, whether P.g induces inflammation in the fetal membrane remains unknown. We aimed
to investigate the association of P.g infection with the humanamniotic membrane in vitro. Methods Amniotic membranes
were obtained at normal delivery under protocols approved by
the Institutional Review Board in our hospital. The amniotic
membrane was isolated to epithelial cells（AEC）and amniotic
mesenchymal cell（AMC）with trypsin and collagenase, and primary cell cultures were carried out. Confluent cells were stimu（1ng, 10ng, 100ng, 1μg/
lated with P.g lipopolysaccharide（LPS）
ml, 12hours）.The mRNA expression of IL 1b, IL 8, and COX 2
were investigated by realtime RT PCR. Results Initially, themRNA expression of IL 1b, IL 8 was observed only in AMC,
and the mRNA expression of COX 2 was observed in both cells.
Following stimulation with P.g LPS, the expressions in AMC
were enhanced in a concentration dependent manner, and those

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in IL 1b, IL 8, and COX 2 were increased by 2.7, 3.7, and 3.6 foldwith 1μg/ml, respectively. By contrast, there were no significant changes in AEC. Conclusion P.g LPS might enhance inflammation in AMC, leading to preterm birth.

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Comparisons of the effects of estradiol valerate and medroxyprogesterone acetate versus tibolone on menopausal
symptoms, lower urinary tract symptoms and female sexualfunction：A preliminary report Pei-Ling Chen, Sheng-Mou
Hsiao Far Eastern Memorial Hospital, Taiwan
Objectives Treatment related effects are important for pretreatment counseling. Thus, our aim was to compare the effects
of different hormone therapies on menopausal symptoms, lower
urinary tract symptoms and sexual functions in women withmenopausal syndrome. Methods Between December 2012 andAugust 2017, women with menopausal syndrome were invited
to receive estradiol valerate（E2V, 1 mg）＆ medroxyprogesterone acetate（MPA, 2.5 mg）or tibolone（2.5 mg）per day. Women
who were willing to pay an extra fee took tibolone, which is notcovered by the National Health Insurance in Taiwan；others
got E2V/MPA. Results A total of 68 women had a follow up visit
after 1 monthʼs treatment, including E2V/MPA（n=39）and tibolone（n=29）. Thirty three women received a follow up visit
after 3 monthsʼ therapy, including E2V/MPA（n=22）and tibolone（n=11）. Baseline characteristics did not differ between the twogroups. At the visit after one month treatment, most domains ofmodified Greene Climacteric Scale and some domains of Female
Sexual Functional Index improved. Significant improvements indiastolic blood pressure were found in both groups. Besides, endometrial thickness did not increase in either group. However,the quality of life score of International Prostate Symptoms
Score improved with E2V/MPA treatment exclusively. At thethree month visit, most domains of modified Greene Climacteric Scale, as well as some domains of Female Sexual Functional Index and International Prostate Symptoms Score, improved after hormone therapy. However, dizziness was significantly reduced with tibolone, but not with E2V/MPA. Conclusions Both regimens give rise to similar improvements in menopausal symptoms. In addition, they both improve lower urinary
tract symptoms and some domains of female sexual functions. E2
V/MPA is superior in the improvement in quality of life affected by urinary symptoms, while tibolone has superiority inthe reduction of dizziness.

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The effectiveness of laparoscopic ultrasonography during
LM operation to reduce residual myomas Mamoru Shigeta,
Yasushi Kotani, Kiko Yamamoto, Masato Aoki, Shiro
Takamatsu, Yoshie Yo, Kosuke Murakami, Hisamitsu Takaya,
Masao Shimaoka, Takako Tobiume, Isao Tsuji, Noriomi
Matsumura Kindai University HospitalObjective LM（Laparoscopic Myomectomy）has been more often
performed than before. The problem of postoperative recurrence in both LM and OM（Open Myomectomy）sometimes occurs. In our prior retrospective study the cumulative recurrence
rates of 8 year after LM and OM operation were 76.2% and 59.6%
respectively. The postoperative recurrence rate of LM was significantly higher than that of OM. There is a possibility that thelack of palpation during operation in LM causes residual
myomas and results in the recurrent. Therefore we have used
LUS（Laparoscopic ultrasonography）to reduce residual myomas
since 2015. In this study, we will introduce the effectiveness of
LUS. Methods Between February 2015 and September 2016, in
LM after all the myomas detected by preoperative MRI were removed, with LUS we checked and removed residual myomas if

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JKT-YDany. We used LUS in 26 patients and examined the patient characteristics and surgical outcomes. Results In the patients who
underwent LM, 26 patients underwent LUS. The total number ofremoved myomas was 135. The mean number was 5.2 per patient. The mean diameter of the largest myoma was 68mm. In 6
out of the 26 patients, residual myomas were detected by LUS
and removed additionally（7 myomas were detected and all removed）. The mean diameter was 5.7mm and all the myomas
were less than 10mm. Conclusion The myomas that would beleft behind without LUS can be removed during operation. We
believe LUS will contribute to decreasing postoperative recurrence rate in LM.

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Comparison of MRI, PET CT, and frozen biopsy in theevaluation of lymph node status before fertility sparing radical trachelectomy in early stage cervical cancer Geon-Woo
Lee, Jeong-Yeol Park, Dae-Yeon Kim, Dae-Shik Suh, Jong-Hyeok
Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam University of Ulsan College of Medicine, Asan Medical Center, Korea
Objective Apply of frozen biopsy is more accurate than MRI or
PET CT when trachelectomy is performed in early cervicalcancer. Materials and Methods This was a retrospective study
including 132 young women with early stage cervical cancer
who tried fertility sparing laparoscopic or robotic radical trachelectomy between July 1, 2004 and April 30, 2017. All patients
underwent preoperative MRI and/or PET CT. Pelvic lymphadenectomy was performed during surgery, and all retrieved
lymph nodes were sent to frozen biopsy before proceeding radical trachelectomy. Paraaortic lymphadenectomy was performed
when metastasis was suspected in the paraaortic lymph node.
The diagnostic accuracy of MRI, PET CT, and frozen biopsy
was compared using McNemar test and logistic regression using generalized estimating equation. The final pathologic reporton lymph nodes was the gold standard for diagnosis. Results A
total number of retrieved lymph node stations was 697, andmean retrieved lymph nodes was 20（range 2 61）. Lymph nodes
were positive in 20 patients（14.3%）.Sixteen patients underwent
radical hysterectomy with lymphatic metastasis in frozen biopsy. In comparison between patients, there was significant difference in sensitivity（95.0% vs. 40.0%, P＜0.001）, specificity（100.0% vs. 80.0%, P＜0.001）, accuracy（99.2% vs. 73.8%, P＜
0.001）of frozen biopsy versus MRI. There was significant difference in specificity（100.0% vs. 84.3%, P＜0.001）,accuracy（99.2%
vs. 82.5%, P＜0.001）of frozen biopsy versus PET CT. Conclusion Although sensitivity is not statistically significant in PET
CT, lymph node metastasis is very important for prognosis.
Therefore, frozen biopsy of all retrieved lymph nodes during
surgery is still the best way to evaluate lymph node status before fertility sparing radical trachelectomy.

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The study about anti cancer mechanism of tetraarsenic oxide
in cervical cancer using cell line and PDX model Jeong-Won
Lee, Jun Hyeong Seo, Jee Youn Hong, Jihye Kim, Hyunjin Choi,
Jae Ryoung Hwang, Young-Jae Cho, Chel Hun Choi, Byoung-Gie
Kim, Duk-Soo Bae Samsung Medical Center, Sungkyunkwan
University School of Medicine, Korea
Objective Current standard therapy for advanced or recurrent
cervical cancer is combination chemotherapy with paclitaxel or
topotecan based on cisplatin chemotherapy. However, these
combination chemotherapy show only 27 36% response rate.
Therefore, there have been many efforts to discover other combination therapeutic agents for cervical cancer. Tetraarsenic oxide（TAO）showed the possibility of therapeutic effect in previous in vitro and in vivo studies with cervical cancer cell lines.
The purpose of this study was to investigate the anticancer effect of TAO in an in vivo study using patient derived xenograft（PDX）mouse model and reveal the mechanisms of TAO acting
on tumor cells. Methods We performed in vivo experimentswith subrenal injection of three different squamous cell carcinoma PDX models of uterine cervix. TAO was administered toeach group to compare the antitumor effect with control. We
also did in vitro studies using cervical cancer cell lines, in orderto understand the mechanism of anticancer effect of TAO. TAO
was treated with SiHa, HeLa and HUVEC cells, and western blot
was performed. In addition, to investigate the effect of TAO on
cell migration, we performed MMP2 and 9 ELISA assays using
HUVEC and SiHa cells. Results In vivo studies with PDX mouse!

model, all three showed significant tumor volume reduction in
TAO treated group. Furthermore, the tumor volume decreased
more significantly in cisplatin combination group than in single
agent and control group. In vitro studies with SiHa and HeLa
cells, TAO decreased the phosphorylation of Akt. In HUVEC
cells, TAO decrease VEGF receptor 1 expression. Furthermore,
the same results were obtained after processing with VEGF in
HUVEC cells. Also, MMP2 was decreased in HUVEC cells. Conclusion TAO reduces tumor volume in cervical cancer PDX
mice, which is more pronounced in the cisplatin combinationgroup. TAO inhibits phosphorylation of Akt and decreases
VEGF receptor 1 expression. However, these mechanisms differ
depending on the cell line. These results indicate the reductionof VEGF related signaling pathway plays an important role inanti cancer mechanism of TAO in cervical cancer.

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Increased myeloid derived suppressor cells during pregnancy
promotes cervical cancer progression Katsumi Kozasa1, Seiji
Mabuchi1, Naoko Komura1, Eriko Yokoi1, Akihiko Yoshimura1,
Hiromasa Kuroda2, Yuri Matsumoto1, Michiko Kodama1, KaeHashimoto1, Kenjiro Sawada1, Tadashi Kimura1 Osaka University 1, Kansai Rosai Hospital 2
Objective Myeloid derived suppressor cells（MDSC）wereknown to be involved in the progression of human malignancies
including cervical cancer（CC）.Recently it is reported that 17 βestradiol（E2）increase MDSC. It is also reported that women
diagnosed with cervical cancer during pregnancy may have an
increased mortality. We hypothesized that elevated E2 level
during pregnancy promotes cervical cancer progression by the
induction of MDSC. Methods BALB/c nude mice, subcutaneously inoculated with HeLa cells（known estrogen receptor
negative CC）, were impregnated and then, tumor growth andthe number of MDSC were examined. In order to investigate theeffect of pregnancy induced increment of E2 on the frequency of
MDSC and tumor growth, we carried out the following experiments. The effect of E2 on the differentiation of bone marrowcells into MDSC was examined by flow cytometry. We examined the effect of E2 on the STAT3 activation in MDSC by western blotting. We examined the effect of E2 on the suppressive effect of MDSC on the proliferation of CD8+ T cells by flow cytometry. Results The number of MDSC was increased in bonemarrow, peripheral blood mononuclear cells and tumor in pregnant mice. The tumor growth was also enhanced in pregnant
mice. E2, that is elevated during pregnancy, stimulated the differentiation of bone marrow cells into MDSC. E2 also enhanced
the STAT3 activation in MDSC and the suppressive effect of
MDSC on CD8+ T cells. Conclusion Pregnancy might promote
cervical cancer progression by the induction of MDSC.

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MicroRNAs in the cervical mucus are promising biomarkers
for cervical cancer and cervical neoplasia Satoshi Kawai,
Sayaka Ootani, Ryoko Ichikawa, Yutaka Torii, Eiji Nishio,
Takuma Fujii Fujita Health University
Objective MicroRNAs（miRNAs）play important roles in theregulation of gene expression during cervical carcinogenesis.
The aim of this study was to examine whether the detection of
specific miRNAs could be a biomarker for cervical cancer.
Methods Cervical mucus was collected using a cotton swab
from 230 patients with a normal cervix, cervical intraepithelial
neoplasia（CIN）, squamous cell carcinoma（SCC）, and adenocarcinoma（AD）, and cellular miRNA levels were quantified bymiRNA array and real time RT PCR. Cytology and human papillomavirus（HPV）infection statuses were also used as clinicalparameters. Results We found that four miRNAs（miR 126 3p,

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!20b!5p, !451a and !144!3p）were significantly upregulated in
SCC and AD compared with normal, and that their expression
levels correlated with the disease severity and with high!
risk
HPV infection. Receiver operating characteristic curve analyses
revealed that the area under the curve values for miR!126!
3p,!20b!5p, !451a, and !144!3p were 0.91, 0.94, 0.96, and 0.95, re-

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Reduced serum miR 100 as a potential biomarker for cervical cancer Zenta Yamanaka, Yuzo Nagamitu, Toru Sasaki,
Hirotaka Nishi Tokyo Medical University
Objective MicroRNAs（miRNAs）regulate various physiologicalactivities in living organisms. Recent studies have reported thatthe expression of miR 100 decreased in cervical cancer tissues.
In this study, we measured the expression level of miR 100 in
the sera and tissues of individuals with cervical cancer to investigate whether miR 100 can be used as a biomarker for cervicalcancer. Methods From April 2010 to April 2012, we extracted
total RNA from the sera and cervical tissues of 46 cervical cancer patients（CC）, 64 cervical intraepithelial neoplasm patients（CIN）, and 34 normal controls（NC）. The expression level ofmiR 100 was investigated in each sample using quantitative
real time RT PCR. The cutoff value of miR 100 in serum wasset based on a ROC curve. We also examined the correlations ofmiR 100 expression levels with clinicopathological factors andprognosis. Results The relative levels of miR 100 in serum were
5.32±3.39 in the NC, 3.93±2.52 in the CIN, and 1.84±1.72 in theCC, indicating that significantly lower levels were present in patients with CC（p＜0.001）. The levels of miR 100 in cervical tissues were also significantly lower. According to the ROC curve,
the AUC was 0.879, and the cutoff value was set at 2.451. The
level of miR 100 in the lymph node metastasis positive groupwas significantly lower than that in the negative group（0.98±
0.36 and 2.13±2.15, respectively；p＜0.01）. Also, cervical cancer
patients with lower miR 100 levels tended to have a poorer
prognosis than those with higher miR 100 levels in serum. Conclusion Serum miR 100 level may be used as a biomarker for
cervical cancer.

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HPV E1 is dispensable for low and high risk HPV maintenance and latent replication in keratinocytes but is necessary
for genome amplification Isao Murakami, Takashi Iwata,
Masaru Nakamura, Tohru Morisada, Kyoko Tanaka, Mamoru
Tanaka, Daisuke Aoki Keio University
Objective E1 and E2 play a direct role in viral replication. In
contrast, the E6, E7 and E5 proteins act indirectly to drive theinfected cell into cell cycle. To establish the minimal requirement of low and high risk viral proteins in genome maintenance and latency, we have developed a genome maintenancemodel system, and have compared replication mechanisms between low and high risk HPV. Methods Normal immortal
keratinocytes（NIKS）transfected wild type or mutated HPV11/
16 genomes were cultured pre or post confluence. Genome
copy number and viral gene expression were subsequently ana-

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Intra patient variation of human papillomavirus genomes revealed by deep sequencing Yusuke Hirose1, Yuri Tenjimbayashi1,
Mamiko Onuki1, Takeo Minaguchi2, Takashi Iwata3, Koji
Matsumoto1, Akihiko Sekizawa1 Showa University Hospital 1,
University of Tsukuba 2, Keio University 3
Objective Persistent infection with oncogenic HPV causes invasive cervical cancer（ICC）, accompanied with the accumulationof somatic mutations into the host genome. However, genetic
changes in the HPV genome during HPV infection and theirrelevance to cervical carcinogenesis are not fully understood.
The aim of this study was to investigate the intra patient variation of HPV genomes by performing deep sequencing analysisof the viral whole genome. Methods The whole genome of HPV
16, 52 and 58 was amplified by HPV type specific PCR from total cellular DNA of cervical exfoliated cells collected from CIN/
ICC patients, and subjected to deep sequencing on a MiSeq（Illumina）. The viral genome positions showing base substitutions ofmore than 0.5% read counts in the total read count at each position were determined for individual clinical specimens. Results
In total, 896 positions of base substitutions were detected
throughout HPV16/52/58 genomes from 118 patients samples（CIN1, n=47. CIN2/3, n=48. ICC, n=24）, with varying numbers
and frequencies for individual samples. Overall, C to T substitutions were predominantly detected across HPV types and histological grades, followed by C to A substitutions. The analysisof trinucleotide motifs covering substitution bases revealed that
TCW（W：A or T）, a preferred target sequence for APOBEC
proteins, was a primary site for C to T substitutions in HPV
genomes. Interestingly, the relative frequency of C to T substitutions decreased with lesion severity, whereas that of C to A
substitutions increased. Conclusion These results strongly imply that APOBEC proteins, cellular cytidine deaminases thatmediate antiviral immunity, are primarily involved in introducing mutations into the HPV genome, particularly in CIN1 lesions.

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Involvement of transcription factor HOXD9 in the malignant
phenotype of cervical cancer through direct binding to HPV
P97 promoter Naohiko Saiki, Takashi Iwata, Kohsei Tanaka,
Tomoko Iijima, Masaru Nakamura, Shigenori Hayashi, Tohru
Morisada, Kyoko Tanaka, Mamoru Tanaka, Daisuke Aoki Keio
University
Objective We previously showed that apoptosis is induced by

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spectively, for SCC compared with normal, and 089, 0.90, 0.94,
and 0.93, respectively, for SCC plus AD compared with normal,
showing high accuracy of cancer detection. When comparing
normal with CIN3 and worse, these values for miR 126 3p,
20b 5p, 451a, and 144 3p were 0.80, 0.82, 0.87, and 0.87, respectively, showing moderate accuracy. Real time RT PCR
analyses confirmed the expression of these four miRNAs in frozen tissues of cervical cancer. Conclusion miR 126 3p, 20b 5p,
451a, and 144 3p, which are upregulated in cervical mucusfrom cervical cancer and its precursor lesions, are promisingbiomarkers for cervical cancer detection.

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lyzed using qPCR. Results Both wild type HPV11 and HPV16
genomes were maintained during cell division, despite different
growth rates and patterns of transcription. However, HPV16
genome levels rose three fold post confluence, while in contrast,
HPV11 genome copy number declined dramatically. Both HPV
11 and HPV16 E1 deficient genomes were maintained pre confluence, reinforcing the emerging view that maintenance replication is E1 independent. Loss of functional E1 prevented HPV
16 confluence dependent genome amplification. Exogenous E6
and/or E7 expression recovered HPV11 replication post confluence, but was not sufficient to elevate HPV11 E1 deficient episomal copy number. Conclusion Our results show that both low
and high risk HPVs switch their replication mode from E1 independent replication to E1 dependent replication as cell density increases and cells commit to differentiate. Moreover, it appears that both of HPVs can replicate in the absence of the E1
viral helicase during genome maintenance, and during latent
replication in the basal layer. The methodologies and observations described here have implications for drug therapeuticstrategies designed to clear viral episomes.

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suppression of transcription factor HOXD9 in cervical cancer
cell lines, and that cell growth was also markedly inhibited. In
this study, we examined the genetic basis of these results. Methods（1）HOXD9 expression was suppressed by shRNA in cervical cancer cell lines SKG I and SKG IIIB. Changes in all genes
in the two cell lines were analyzed by microarray analysis andintracellular signals that changed in both lines were identified.
（2）HOXD9 expression was suppressed in SKG IIIB and Sihacell lines and expression of p53 at the gene and protein levels
was examined.（3）Luciferase assays using the HPV16 E6/7 genepromotor（P97 promoter）were performed to examine whether
HOXD9 induced E6/7 gene expression via the P97 promoter.
（4）A chromatin immunoprecipitation（CHIP）assay was performed to examine whether HOXD9 binds to the P97 promoter.
Results（1）P53 signaling was activated after suppression of
HOXD9 expression in SKG I and SKG IIIB cells.（2）P53 gene
expression did not change, while the P53 protein level was elevated in HOXD9 supressed SKG3B and Siha cells.（3）Luciferase
activity was significantly decreased after HOXD9 expression
was suppressed in SKG IIIB cells（p＜0.05）（. 4）In the CHIP assay in SiHa cells（HPV16 positive）, HOXD9 was shown to bindto the P97 promoter. Conclusion HOXD9 is involved in the malignant phenotype of cervical cancer through direct binding to P
97 promoters, which facilitates expression of E6/7 and promotes
degradation of P53.

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Antitumor effect of XCT790, an estrogen related receptor α
inverse agonist, on uterine endometrial cancer cells and a
xenograft mouse model Tetsuya Kokabu, Taisuke Mori,
Hiroshi Matsushima, Hisashi Kataoka, Kaori Yoriki, Haruo
Kuroboshi, Hiroshi Tatsumi, Morio Sawada, Jo Kitawaki Kyoto
Prefectural University of Medicine
Objective Estrogen related receptor（ERR）α is structurally
similar to estrogen receptors. We previously demonstrated tumor progression caused by ERRα in endometrial cancer. This
study investigated the efficacy of XCT790, a selective inverse
agonist of ERRα, on endometrial cancer. Methods HEC 1A and
KLE, endometrial cancer cells showing high ERRα expression,
were treated with XCT790. Xenograft model mice inoculatedwith HEC 1A were treated with XCT790. Cell proliferation wasmeasured with WST 8 and colony formation assays. Transcriptional activity was examined with a luciferase assay. The cell
cycle was examined with flow cytometry, fluorescent immunocytochemistry, and western blotting. The apoptotic effect wasdetermined with the caspase 3/7 assay. Results XCT790（1.25
10 μM）significantly inhibited ERRα induced transcriptional activity in a concentration dependent manner, regardless of the. XCT790 reupregulation of ERRα at mRNA level（P ＜0.01）
duced colony formation and suppressed cell proliferation in adose and time dependent manner without cytotoxicity（P ＜0.01）, and induced apoptosis supported by accumulation in the
sub G1 phase and stimulation of caspase 3/7 activity（P ＜0.01）.
Flow cytometry and fluorescent immunocytochemistry revealed that XCT790 caused cell cycle arrest at the mitotic
phase. Western blotting used to analyze induction of histone H3
phosphorylation after treatment with XCT790 demonstrated themitotic arrest. XCT790 in combination with paclitaxel produced
a synergistic inhibitory effect. Significant inhibition of tumor
growth without reduction of body weight was observed in a
. Concluxenograft mouse model treated with XCT790（P ＜0.01）
sion XCT790, a selective ERRα inverse agonist, may be a novel
therapeutic agent for endometrial cancer.

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A novel epigenetic therapy with inhibition of histone methyltransferase, SETD8, for endometrial cancer Shinya Oki1,
Kenbun Sone1, Katsutoshi Oda1, Asako Kukita1, MachikoKojima1, Michihiro Tanikawa1, Kazunori Nagasaka1, Yoko
Matsumoto2, Osamu Hiraike1, Yutaka Osuga1, Tomoyuki Fujii1
The University of Tokyo 1, Kanagawa Health Service Association 2
Objective Dysregulation of histone methyltransferases is known
to be associated with human cancers. One of the methyltransferase, SETD8, is a key regulator of DNA replication and its
overexpression is reported in various types of cancers. Here, weinvestigated the role of SETD8 expression and anti tumor effect of SETD8 inhibition in endometrial cancer. Methods
SETD8 expression was analyzed by quantitative real time PCR
in 52 clinical endometrial cancer specimens under informed consent and approval of our ethics committee. SETD8 was inhibitedby either knockdown of SETD8 with siRNA or treatment with
UNC0379, a selective SETD8 inhibitor, in 8 endometrial cancer
cell lines. The anti tumor effects were examined with immunoblotting, MTT assay, colony formation assay, cell cycle
analysis, and Annexin V FITC. Anti proliferative effect of UNC
0379 was assessed by combination with other anti cancer drugs（cisplatin or doxorubicin）. Results SETD8 expression was elevated in endometrial cancer specimens, compared with control（normal endometrium）（P＜0.05）. Knockdown of SETD8 by
siRNA induced significant growth suppression（90% of suppression）and caused G1 arrest in 8 endometrial cancer cell lines. In
addition, knockdown of SETD8 increased the number of apoptotic cells（15 35%）and reduced the level of H4K20 methylation,accompanied with gamma H2AX accumulation（DNA damage
marker）. UNC0379 suppressed cell proliferation（IC50：0.6 2.5
μM in MTT assay）by itself, and showed additive anti proliferative effects when combined with either doxorubicin or cisplatin.
Conclusion The present findings highlight that SETD8 overexpression is involved in endometrial cancer, and that SETD8
might be a promising epigenetic target against endometrial cancer.

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Long term outcomes of medroxyprogesterone acetate plus
metformin as fertility sparing treatment for atypical endometrial hyperplasia and endometrial cancer Akira
Mitsuhashi, Yuji Habu, Hirokazu Usui, Makio Shozu Chiba University
Objective This study aimed to analyze the long term outcomesof MPA plus metformin as fertility sparing treatment for atypical endometrial hyperplasia（AEH）and endometrial cancer（EC）. Methods We analyzed 56 patients（37 with EC and 19 withAEH）who underwent fertility sparing management using
MPA plus metformin. MPA（400 mg/day）and metformin（7502250 mg/day）were administered to achieve a complete response（CR）. Metformin was administered until conception,even after MPA discontinuation. We compared these patientswith 19 patients who received MPA alone. Results The body（mean, 30.5 kg/
mass index was ＞25 kg/m2 in 42 patients（75%）
m2；range, 19 51 kg/m2）.Fifty four（96.4%）showed CR within
18 months. The CR rates at 6, 8 9, 12 months were 58.9%, 80.4%,
and 89.3%, respectively. During a median follow up period of 57
months（range, 13 88 months）,relapse was confirmed in 7 of 54
patients（12.9%）who had achieved CR. Two patients who failed
to achieve CR and 3 of 7 recurrent patients underwent hysterectomy. Four of 7 patients with recurrence underwent re treatment with MPA, and all achieved CR. Relapse free survival in
all patients at 3 years was 44% in the MPA alone group and
85.4% in MPA+metformin group（p=0.003）. Conclusion The con-

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Genomic analysis of cell free DNA in plasma using NIPT
platform by massively parallel sequencing for a prognostic
factor：gynecological tumor associated copy number variants；a prospective study Makoto Nakabayashi1, Akihiro
Kawashima1, Hanako Shimizu2, Shingo Miyamoto1, Chiaki
Iitsuka1, Koji Matsumoto1, Akihiko Sekizawa1 Showa University 1,
National Cancer Center Hospital 2
Objective The discovery of circulating tumor DNA（ctDNA）
molecules has created a paradigm shift in tumor biomarker. In
the other hands, non invasive prenatal testing（NIPT）for detecting circulating cell free fetal DNA in maternal plasma has been
increasingly recognized as a valuable substitute to perceive fetal copy number variations（CNVs）.We hypothesized that CNVsof ctDNA detected by NIPT methods would be detectable in theplasma of gynecological cancer patients collected before primary surgery and be predictable for their recurrence. The aimsof this study were whether the use of NIPT platform for ctDNAin the plasma of gynecological cancer patients could serve as apredictive marker of patient outcome. Methods We used NIPT
platform to detect CNVs of ctDNA in the plasma of patientswith gynecological cancers. Samples were collected from 100
patients who underwent surgery at a single institution. Progression free survival（PFS）and overall survival（OS）were analyzed
according to the presence of CNVs of ctDNA. Results Amongthe 100 cases, CNVs of ctDNA was detected in 32 plasma sam-!
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The malicious role of immune reaction in Uterine Serous carcinoma Yuka Mise, Tsukasa Baba, Junzo Hamanishi, Kaoru
Abiko, Ryusuke Murakami, Noriomi Matsumura, Masaki
Mandai Kyoto University
Objective Uterine serous adenocarcinoma（USC）has the worst
prognosis in endometrial cancer exhibiting chemo resistant andprogressive property, and thereby a novel therapeutic strategy
has been desperately required. Recently, anti tumor immunity
evasion（ATIE）is known to play crucial roles in refractory cancers, but ATIE in USC has not been clarified so far due to lacking immunocompetent assessment models. The aims of thisstudy are to evaluate local immunological features of human
USCs and to develop an immuno competent mouse USC model
for future investigation. Methods Clinical samples from 42 surgically treated USC patients were served for clinicopathologicalanalysis. Tumor infiltrating CD8＋T cells（TILs）and CD33＋cells（MDSC）were counted and MDSC TIL ratio was calculated toassess tumor microenvironmental immunity. A mouse endometrial cancer cell line, ppp268, was established by conditional uterine deletion of Pten and Trp53 using the Cre/loxP approach, and murine cMyc was further introduced to develop
ppp268 cMyc cells for assessing immunocompetent tumorigenicity on C57BL6 mice. Results TILs were more frequently
observed in the center of tumor without recurrence（p＜0.05）.
Overall survival was significantly better in cases with low
MDSC TIL ratio. Immunocompetent tumorigenicity got superior by transduction of cMyc, and cMyc tumor exhibited highly
nuclear atypia and glandular structure mimicking USC. In
cMyc tumors, MDSCs were more frequently observed（p＜0.05）,
and MDSC TIL ratio was also high. Conclusion TILs and
MDSCs are prognostic factors of human USC. ppp268 cMyc
cells can be designated as a mouse USC mimicking cell line suitable for investigating a new therapeutic strategy conquering
ATIE.

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Surgical technique and outcomes of uterus retrieval frombrain dead multi organ donors：a preclinical research of human living uterine transplantation Gaowen Chen1, Yifeng
Wang1, Xiangyuan Li2, Youhong Zheng1, Xiaoxuan Li1, Ying
Zhu1, Zengying Cui1, Chenyuan Hao1 Zhujiang Hospital, Southern
Medical University, China 1, Department of Reproductive Medical Center, Guangdong Women and Children Hospital, China 2
Objective To evaluate the surgical technique and outcomes of
deceased donor uterine transplantation, which is a preclinicalresearch of human living uterine transplantation. Methods
From May, 2015 to August, 2017, four uterine retrieval procedures, characterized with radical hysterectomy and uterine vascular pedicles dissection, were performed in multi organ brain
dead donors. The uterus was the third authorized organ after
the kidney and liver retrieval procedures. The uterine pedicles
included the uterus, ovarians, fallopain tubes, the upper one
third of the vagina and internal iliac vessels or external iliac
vessels. The perfusion of the uterus was conducted after the retrieval for evaluating the availability, followed by histopathological examination of the harvested uterus per 30 minutes.

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Screening of Endometrial Cancer Using Cervical Swab Ling
Lim1, Yuh-Cheng Yang1, Chao-Chih Wu2, Yun-Ting Hsu2,
Chih-Long Chang1,2,3 MacKay Memorial Hospital, Taiwan 1,
MacKay Memorial Hospital, Department of Medical Research,
Taiwan 2, MacKay Medical College, Taiwan 3
Objective The Papanicolaou test
（Pap test）
reduced cervical cancer since it was introduced in screening program in 1991. However, cervical cancer remains the only gynecologic cancer thatis screenable till now. Endometrial cancer is the most common
gynecologic cancer in developed countries. It is often discovered only when patients presented with symptom of vaginal
bleeding and had underwent invasive procedure to extract tissues from endometrium. Our study aims to establish a screening
tool for endometrial cancer based on current infrastructure using cervical swab. Methods Fresh tissues from 108 endometrial
cancer patients were screened for gene mutations. Besides,
white blood cells of 60 of these patients were collected as control. The gene mutations were determined by capture probes
and next generation sequencing（NGS）. Afterwards, a panel ofmutated genes was established through data processing. Subsequently, this panel of mutated genes was tested in cells obtained
from cervical swabs of 138 endometrial cancer patients and 50
healthy participants by amplicon based multiplex polymerase
chain reaction and NGS. All participants were enrolled from two
medical centers in Taiwan. Results A total of 1,635 amplicons
from 36 genes were determined as final markers for screeningof endometrial cancer. The detection rate for endometrial cancer was 86% when validating the panel genes using cervicalswab in 188 cases. However, up to 14% of the normal cases were
found to have gene mutations. Conclusion In conclusion, ourdata indicated that screening of endometrial cancer might befeasible using cervical swab. However, further investigation isneeded to improve the specificity of the test. Furthermore, cost
reduction of this screening test is necessary to enhance its accessibility.

ples. Patients with CNVs of ctDNA had a significantly poorer
prognosis in all stages concerning PFS（P=0.002）and OS（P=0.043）, and even in early stages concerning PFS（P=0.034）Conclusion We proved that the existence of CNVs of ctDNA in
plasma samples could be a powerful predictor of poor survival
in patients with gynecological cancer. Accordingly, CNVs of
ctDNA detection might be a promising approach for the management of gynecological cancer.

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Results Since the uterine vein was quite difficult to identify anddissect in the first two case, which result in the rupture of triple
uterine veins. Therefore, the uterine venous vessels, including
uterine vein connected with internal iliac vein, and internal iliac
arteries as well as uterine arteries were selected as vasculargrafts and dissected sucesssfully in the last two cases. The last
two harvested uteri could be perfused with the mixture of 4 degree heparinized physiological saline through each artery following shortening the surgical time. Mean（SD）operative timewas 68.7±9.3 mins（60 85 mins, n=4）
. Conclusion Our preliminary experience indicated that the uterus could be retrieved
from the brain dead multi organ donors and transplanted to therecipient. The attempt of purely dissecting the uterine veinsshould be replaced by dissection of internal iliac vein.

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Analysis of paternal contribution of genetic partial hydatidiform mole using subtraction B allele frequency plotting of
SNP array Hirokazu Usui, Asuka Sato, Makio Shozu Chiba University
Objective Partial hydatidiform mole（PHM）is genetically diandric monogynic triploid. Two haploids of paternal contribution
are estimated. The aim of this study is to elucidate the clarify
the detailed paternal contribution of PHM, especially which did
not have three allelic loci in short tandem repeat（STR）polymorphism analysis. Methods The paired genomic DNA of eightcases of genetic PHM diagnosed by STR analysis and their maternal blood were analyzed using single nucleotide polymorphism（SNP）array（Illumina HumanCore v1.0）to get the log
R ratio and B allele frequency（BAF）parameters. We developed
the subtraction BAF plotting, which could estimate their paternal haploid contribution. Further, the SNP array data were explored with subtraction BAF plotting. Results Four PHM cases
showed two paternal haploid contributions and one maternal
contribution. Centromeric region analysis indicated that two paternal haploids were from two mature sperms but not a diploid
sperm. The rest of four cases without three allelic loci on STR
analysis were confirmed as triploid. They showed the mono haploid of paternal contribution（self duplication）and one maternal
haploid. Conclusion We developed the new method as a subtraction BAF plotting. We identified the diandric monogynic triploid PHM with the paternal contribution from one mature
sperm. This methodology could be applied to determine the parental origin of trisomy and to analyze the villous samples withmaternal contamination.

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Genomic landscape of ovarian clear cell carcinoma via next
generation sequencing Se Ik Kim, Maria Lee, Hee Seung Kim,
Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang
Song Seoul National University College of Medicine, Korea
Objective To obtain whole exome sequencing（WES）data of
OCCC via next generation sequencing（NGS）technique.
Genomic profiles were compared between EMS associated
OCCC（EMS OCCC）and non EMS associated OCCC（Non
EMS OCCC）. Methods We used serum samples and cancer tissues collected from the female patients who were diagnosed
with OCCC between 2012 and 2016, and stored at the Seoul National University Hospital Human Biobank. In total, 15 patientswere enrolled：5 were pathologically confirmed EMS OCCC
cases and the other 10 were Non EMS OCCC cases. We performed WES for 15 OCCC tissues with matched serum samples,and analyzed NGS data for comprehensive genomic characterization of OCCC. Results OCCC was characterized by complex
genomic alterations, with a median of 178 exonic mutations（range, 111 25,798）and a median of 343.0（range, 43.0 1,820.0）so-

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Gene Methylation Panel of CDH1, DLEC1 and SFRP5 as Prognostic Marker in Advanced Epithelial Ovarian Cancer
Ying-Cheng Chiang1, Wen-Fang Cheng1, Chi-An Chen1,
Heng-Cheng Hsu2 National Taiwan University Hospital, Taiwan 1, National Taiwan University Hospital, Hsin Chu Branch,Taiwan 2
Background Aberrant gene methylation is crucial in carcinogenesis and related to the clinical outcomes. This study aimed
to investigate the prognostic value of the gene methylation
panel（CDH1, DLEC1 and SFRP5）in the advanced epithelial
ovarian cancer. Methods Totally 177 epithelial ovarian cancer
specimens were evaluated by methylation specific polymerase
chain reaction and capillary electrophoresis. The correlation ofgene methylation and clinico pathological parameters wereanalyzed. The panel was also validated by TCGA dataset. Results Patients with tumor recurrence had higher frequency of
two or more methylated genes（37.8% versus 12%, p=0.001, Chi
square test）than patients without tumor recurrence. Chemo resistant patients had higher frequency of two or more methylated genes（43.3% versus 22.7%, p=0.004, Chi square test）than
chemo sensitive patients. The patients with two or more methylated genes had a significantly shorter disease free survival（DFS）（p＜0.001, log rank test）and overall survival（OS）（p=0.001, log rank test）than those with only one or no gene methylation. In multivariate Cox regression, two or more methylated
genes was independent factor for recurrence（HR：1.79［1.192.69］, p=0.005）and death（HR：1.96［1.26 3.06］, p=0.003）. In theTCGA dataset, patients with two or three methylated genes hada significantly shorter DFS（p=0.023, log rank test）and OS（p=0.003, log rank test）than those with only one or no gene methylation. Conclusion Our gene methylation panel can be a prognostic biomarker of advanced epithelial ovarian cancer.

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matic copy number variations per tumor sample. Top three statistically recurrent somatic mutations were PIK3CA, ARID1A,
and KRAS. Somatic copy number alterations were frequently
detected on the region of MUC1, GATA2, NTRK1, and ATM.
And we also identified that significantly altered pathways included cell proliferation/survival（PI3K AKT pathway, TP53
pathway and ERBB2 pathway）in 87% and chromatin remodeling in 47% of tumors. However, we could not find the staticallydifference between EMS OCCC and Non EMS OCCC groups
on genetic alteration analyses. Conclusion We successfully obtained genomic landscape of 15 patients with OCCC. We identified a potential therapeutic target in most tumors for the treatment of OCCC. Further studies with whole transcriptome sequencing to discover the effect of genetic alterations are warranted.

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GSTP1 rs1695 is a predictive indicator of both hematological
toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin Tomoko Yoshihama1, Akira Hirasawa1,
Hiroyuki Nomura1, Tomoko Akahane1, Fumio Kataoka1, Wataru
Yamagami1, Taisei Mushiroda2, Mamoru Tanaka1, Daisuke Aoki1
Keio University 1, RIKEN 2
Objective To identify genetic variants that are associated with
toxicity and/or efficacy of paclitaxel plus carboplatin combination chemotherapy（TC therapy）,so that we are able to predictthe likelihood of severe toxicity or efficacy in patients before
treatment. Methods In a retrospective case control study, we
analyzed 320 patients who had received TC therapy for gynecological cancers（ovarian, fallopian tube, peritoneal, uterine, andcervical cancers）and collected their germline DNA from archived samples. We performed a comprehensive pharmaco-

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Inactivation of ZNF671 by DNA methylation is closely associated with early recurrence of serous ovarian cancer Shoko
Mase1, Ryutaro Nishikawa1, Atsushi Arakawa1, Mayumi
Sugiura1, Yutaka Kondo2 Nagoya City University 1, Nagoya University, Department of Cancer Biology 2
Objective The aim of this study is to examine epigenetic alterations, which are associated with early recurrence of SOCs.
Methods We use TCGA database to identify the methylated
genes in early recurrence of SOCs. We analyze DNA methylation of the identified gene in our SOC cohort and perform thefunctional analysis of the identified gene using SOC cell lines.
Results We analyzed DNA methylation using Infinium 27K dataof 209 SOCs in The Cancer Genome Atlas：51 showed early（＜
12 months）and 158 showed late（＞12 months）recurrence, respectively. Among 14,475 genes, we identified 11 genes whichwere differentially methylated between the two groups. ZNF671
was the most frequently methylated in the early recurrencegroup and showed inverse correlation between DNA methylation status and gene expression. In validation group of SOCs（n=85）,the sensitivity of this marker for detection of early recurrence was 82.1%（DNA methylation cut off was 10.85%）.And patients with high methylation of ZNF671 significantly showedworse overall survival compared with those who with low methylation（p＜0.05）. Inhibition of DNA methyltransferase by 5
aza 2 deoxycytidine induced ZNF671 expression in SOC celllines（JHOS 2, JHOS 4, OVCAR3）. Further, inhibition of ZNF
671 by siRNA increased cell proliferation as well as invasion
and migration in SOC cell lines. Conclusion Our data indicatedthat ZNF671 may act as a tumor suppressor and that methylation of this gene might be a useful biomarker for prediction ofearly recurrence of SOCs.

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MiR 522 modulates paclitaxel resistance in ovarian cancer
cells Mayuko Miyamoto, Kenjiro Sawada, Akihiko Yoshimura,Erika Nakatsuka, Michiko Kodama, Kae Hashimoto, Seiji
Mabuchi, Tadashi Kimura Osaka University
Objective The overcome of paclitaxel resistance is a critical issue in ovarian cancer treatment. The aim of this study is to identify key microRNAs（miRNAs）which regulate paclitaxel resistance and to pursue those potential as therapeutic targets. Methods Using two serous ovarian cancer cell lines, SKVO3ip1 andHeyA8, paclitaxel resistant cell lines were established by a continuous exposure of paclitaxel. The miRNA PCR arrays were!
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performed and miR 522 was found to be one of downregulated
miRNAs in paclitaxel resistant cell lines. The expression levelof miR 522 was analyzed among 7 ovarian cancer cells and therelationship between miR 522 and IC50 value of paclitaxel was
examined. The effect of miR 522 on paclitaxel resistance wasassessed by transducing the precursor miRNA into ovarian cancer cells. Using lazor microdisection techniche, the precise carcinoma tissues were extracted from paraffine embedded materials and the expression level of miR 522 was examined by realtime miRNA PCR. Results In paclitaxel resistant cell lines（HAC2, KOC7C, OVISE, RMG 1, RMG 2）,of which IC50 values
were higher than 50nM, the expression level of miR 522 wasdown regulated than paclitaxel sensitive SKOV3ip1 cells（0.003,
0.627, 0.608, 0.009, and 0.066, respectively）. In vitro cell viability
assay revealed that transduction of miR 522 into paclitaxel resistant SKOV3ip1 cells sensitized resistant cells to paclitaxel. In
paclitaxel resistant clear cell carcinoma, miR 522 expression
was significantly down regulated compared with contralateral
normal ovary（0.042）. Conclusion MiR 522 modulated sensitization to paclitaxel in ovarian cancer cells and can be considered
as a therapeutic target to overcome paclitaxel resistance.

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Elevated level of serum miR 1290 is correlated with highgrade serous epithelial ovarian cancer and can be a potential
biomarker Masaki Kobayashi, Kenjiro Sawada, Aasa Shimizu,
Mayuko Miyamoto, Kyoso Ishida, Akihiko Yoshimura, Erika
Nakatsuka, Koji Nakamura, Michiko Kodama, Kae Hashimoto,
Seiji Mabuchi, Tadashi Kimura Osaka University
Objective There is a critical need for improved diagnostic
markers detecting ovarian high grade serous ovarian cancer（HGSOC）. MicroRNAs（miRNAs）stably exist in circulating
blood, reflecting tissue conditions and present in circulating microvesicles like exosomes. The aim of this study is to identify
which miRNAs are highly produced from HGSOCs and analyze
whether serum miRNA can discriminate HGSOC patients fromhealthy controls. Methods Secreted exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted.
miRNA microarray was performed and several elevated miRNAs specific to HGSOCs were picked up. Among these, we focused on miR 1290. Serum from 71 pre operative, 46 post operative ovarian cancer patients and 13 healthy controls weregathered and its expression levels were detected by quantitative real time PCR. Further, CA125 value of each patient wascollected and the potential of miR 1290 as a novel biomarker examined. Results In HGSOC patients, miR 1290 emerged overexpressed compared to healthy controls（3.52 fold）unlike othertypes of epithelial cell ovarian cancer patients. In advanced
stage HGSOC patients, its expression was higher than that inearly stage（4.23 VS 1.58；P=0.23）. Its expression significantly
decreased after operation（5.87 to 1.17；P＜0.01）, indicating that
this miRNA is produced from cancer tissues. ROC analysis
showed that at the cut off of 1.61, the sensitivity and specificity
were 63% and 85% respectively for detecting HGSOCs（AUC=
0.71）. Combining CA125 and miR 1290 values, AUC value significantly improved（0.972 to 1.00）. Conclusion Serum miR 1290
can be a potential diagnostic biomarker for HGSOC.

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IS-WS-4-1
Cyberknife Therapy for Locally Recurrent Gynecologic Cancers After External beam Radiation Therapy Courtney
Griffiths1, Roseanna Valant1, Jonathan Haas1, David Ebling1,
Melissa Fazzari1, Jeanine Villella2, Eva Chalas1, Edward Jimenez1
NYU Winthrop University Hospital, USA 1, Lenox Hill Hospital,
USA 2
Objective Management of locally recurrent gynecologic cancers!

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genomic analysis by targeted resequencing of 100 pharmacogenes using next generation sequencer. For all 1,188 genotyped
variants with minor allele frequency 0.001 and missing genotype rate ＜10%, case control association studies and survival
analyses were conducted. Next, we assessed 5 year progression free survival（PFS）
and overall survival（OS）in 56 advanced
ovarian cancer patients who had received tri weekly TC therapy as a first line chemotherapy. Results GSTP1 （glutathione
S transferase P1）rs1695 showed the smallest p value for hematotoxicity association, and the A allele（wild type）had a significantly higher risk of severe hematotoxicity（neutropenia G4,
thrombocytopenia G3 and anemia G3）than the G allele（variant type）did（p=0.00034, odds ratio=5.71（95% confidence interval：1.77 18.44））. In a prognosis analysis, patients with GSTP1
rs1695 AA genotype showed significantly better PFS（p=0.00070）and OS（p=0.0012）than those with the AG or GG genotype did. Conclusion Our study indicates that the GSTP1 rs1695
AA genotype is associated with both severe hematotoxicity andhigh efficacy of TC therapy, identifying a possible prognostic indicator for patients with TC therapy.

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following external beam radiation（RT）presents a therapeutic
dilemma. Treatment options usually involve an exenterative
procedure or palliative chemotherapy due to the risk of toxicity
with re irradiation. This study aims to analyze the efficacy ofre irradiation using Cyberknife for local recurrences. Methods
A retrospective chart review of patients treated with Cyberknife at NYU Winthrop between 2005 2015, identified 29 patients with prior RT and locally recurrent gynecologic cancer：
endometrial（n=22）, cervix（n=1）, ovary（n=2）and vulvar（n=4）. Recurrences were radiologically confirmed. Median dose ofpelvic RT given prior to the recurrences was 60 Gy and the median Cyberknife dose delivered was 25 Gy. Kaplan Meier estimates for progression free（PFS）and overall survival（OS）were
calculated. Associations between survival was determined using Cox proportional hazards regression models. Results 27 of
the 29 patients had follow up data and were included. Mediantime between primary RT and Cyberknife treatment was 24months. Seventeen recurrences were located in the central pelvis, 4 in the pelvic sidewall, and 9 in the PA region. Median follow up was 13.7 months. Overall response rate to Cyberknife at
12 months was 89（9 complete response, 8 partial response, and7 stable disease）. The median PFS and OS were 11.7 months and20.5 months, respectively. Only 6 in field disease progressions
were observed. Conclusion Our results suggest that use of Cyberknife for locally recurrent gynecologic cancers in a prior radiated field can be an effective non surgical salvage option providing local control with acceptable toxicity.

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Lovastatin induced KLF2, KLF6 and RHOB genes and preferentially led to viability reduction of cisplatin resistant cells
Chiho Koi, Tomoko Kurita, Taeko Ueda, Seiji Kagami, Toshinori
Kawagoe, Toru Hachisuga University of Occupational and Environmental HealthObjective Recently, statin has been reported to have an antitumor activity and also pointed out the association with drug resistance. We investigated the antitumor activity of statins in cisplatin resistant cells and elucidated the mechanism. Methods（1）We performed the cell viability of 7 statins in cisplatin resistant HCP4 and PCDP5 cells compared with parent Hela and PC3
cells by WST 8 assay. We also examined cell cycle analysis after treatment to Hela and HCP4 cells with lovastatin.（2）We investigated cDNA microarray analysis with HCP4 cells treatedor untreated 1uM lovastatin, and we focused on KLF2, KLF6,
and RHOB genes thought to be tumor suppressor genes. We examined whether statins induced these genes by real time PCR,
and evaluated the effect on cell survival and cell cycle due tooverexpression of these genes, by cell counting and cell cycle
analysis, respectively. Results（1）HCP4 cells and PCDP5 cells
were 20.8 33.4 fold more resistant to cisplatin but 1.02 68.3 foldmore sensitive to 7 statins. Lovastatin significantly increased
the sub G1 population of HCP4 cells more rapidly and to greater
extent than in Hela cells.（2）KLF2, KLF6, and RHOB genes
were induced by a low concentration of lovastatin in HCP4 cells
compared with Hela cells. Overexpression of these genes led to
viability reduction. Cell cycle analysis revealed that KLF2 and
RHOB significantly induced an increase in the populations of
sub G1. Conclusion It was suggested that stains induced tumor
suppressor genes such as KLF2, KLF6, and RHOB and sensitized cisplatin resistant cells with low concentration.

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Frzb is induced by RAS MAPK signaling and contributes totransformation Ichiro Onoyama, Keisuke Kodama, Hiroshi
Yagi, Masafumi Yasunaga, Tatsuhiro Ohgami, Kazuo Asanoma,
Kenzo Sonoda, Kiyoko Kato Kyushu University HospitalObjective RAS MAPK signaling is aberrantly activated in variety kinds of human cancers. In gynecologic oncology field,
KRAS activating mutation is one of the most frequent alterations reported in ovarian cancers and endometrial cancers. However, KRAS mutation alone cannot transform normal cells andneeds another oncogene activation and/or tumor suppressor
genes inactivation for carcinogenesis. To fully understand RAS
MAPK downstream signaling pathways we performed RNA sequencing using mouse embryonic fibroblasts（MEFs）isolated
from BrafV600E knock in mice, and tried to find unknown pathways that promote or suppress carcinogenesis. Methods MEFs
are isolated from BrafV600E knock in mice, and analyzed themwith RNA sequencing. Upregulated or downregulated genes
are validated with MEFs from BrafV600E and KrasG12D
knock in mice, and biological significance of those genes were
investigated with knockdown experiments. Results We have
got many genes with their expressions increased or decreased
after BrafV600E activation from RNA sequencing analysis, andfocused on Frzb among the validated genes, because oncogenic
Braf and Kras induced massive expression of Frzb two or three
weeks after activation of each oncogene. KrasG12D knock in
MEFs with Frzb knockdown showed suppressed cell growth
and reduced focus formation ability, indicating that Frzb induced by Kras activation would plays a role in carcinogenesis.
Conclusion Frzb was induced by oncogenic Kras activation, andcould contribute to carcinogenesis in Kras activated cells. Besides Frzb, the expression of many genes which are not known
to be involved in RAS MAPK pathway, changed following oncogenic Kras activation. RAS MAPK signaling has been studied
vigorously so far, however, it is still worth investigating thosegenes to understand the pathway.

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Anticancer effect by curcumin is both associated with caspase dependent and caspase independent cell death in gynecological cancer cells Tzefang Wong, Atsushi Uekawa, Shiho
Kuji, Norihito Yoshioka, Tatsuru Ohara, Imari Deura, Akiko
Tozawa, Nao Suzuki St. Marianna University School of Medicine
Objective Curcumin is widely reported to have a vast repertoireof molecular targets within the cell, despite its low toxicity innormal cells. As curcuminʼs multitude targets within the cell
was touted to circumvent resistance to treatment, we chose
three distinct pathways within cancer that have shown to contribute to resistance to standard clinical therapies when eitherof which was inhibited, i.e. the RAS MEK ERK1/2, PIK3CA
AKT mTOR and JAK2 Stat3 pathways. Association with both
caspase independent and classical apoptosis was also investigated. Methods Gynecological cancer cell lines RMG I, RMG V,
SNG II, SNG M, HeLa and SiHa were used. Curcumin wasadded to cultured cells and IC50 were derived from cell proliferation assays using alamarBlue（manufactured by Bio Rad）,
based on the protocol provided. Western blots were performed
to detect apoptotic markers such as cleaved PARP and cleaved
caspases, phosphorylated kinases and other pathway markers.
Results Curcumin inhibits cell proliferation in a dose dependent manner. Lower IC50 seems to be associated with a higher
AKT activity, as shown by AKT phosphorylation. Cervical cancer cell lines, HeLa and SiHa, tend to show caspase independent cell death, whereas the endometrial cancer（SNG II and
SNG M）and ovarian cancer cell lines（RMG I and RMG V）tend
to show both caspase dependent and independent apoptosis.
Conclusion Resistance to standard cytotoxic chemotherapy andmolecular targeted treatment is an urgent problem. This investigation aims to fine tune our understanding on curcuminʼsmechanism of action, therefore will potentially prove（or dis-

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prove）the usefulness of curcumin for cancer treatment.

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Trends in maternal mortality in Mongolia in year 2016
Munkhtsetseg Davaatseren1, Yanjinsuren Darmaa1, Enkhtsetseg
Jamsranjav1, Bolormaa Narantuya2, Buyanjargal Yadamsuren2,
Bolorchimeg Baldandorj1, Amartuvshin Tumenjargal1 Mongolian National University of Medical Sciences, Mongolia 1, Ministry of Health, Mongolia 2
Aim Maternal mortality remains a major challenge to healthsystems in Mongolia. In this study, we investigated the causes ofmaternal death in 2016, Mongolia. Methods We retrospectively
analyzed 38 maternal mortality cases in 2016. The information
was obtained from pregnancy observation card, birth history,
verbal autopsy study, and reports of the chief expert of the Ministry Health for Obstetrics and Gynecology. Results In the year
2016, there were 72,000 deliveries in Mongolia. The overall maternal mortality ratio（MMR）was 26.0 per 100,000 live births in2015 and increased significantly to 48.6 per 100,000 live births in
2016. Further, seven（18.4%）of maternity died at home without
any healthcare service. However, our antenatal care rate was
76.3%. Among the 38 cases, there were 22（57.9%）direct maternal deaths and 16（42.1%）indirect. The main causes of directmaternal deaths were in a category of amniotic fluid embolism（n=8, 36.4%）, and sepsis（n=7, 31.8%）. In the indirect causes ofmaternal deaths, most often were a cardiovascular disorder（n=5, 31.3%）, neurological disorders（n=4, 25%）
, followed by respiratory system disease was two（n=2, 12.5%）. Most of the maternal
deaths were in age group 30 34 years old（n=16, 42.1%）. Conclu-!

IS-WS-5-2
Factors affecting maternal and neonatal morbidity plannedfor cesarean delivery Young Mi Jung, Su Ah Kim, Ji Hyun
Ahn, Jina Youm, Seung Mi Lee, Chan-Wook Park, Joong Shin
Park, Jong Kwan Jun Seoul National University College of Medicine, Korea
Objective Previous studies have indicated that the risk of adverse neonatal outcomes in term cesarean deliveries（CD）increases progressively as gestational age（GA）at birth declines.
So it has recently been recommended to perform CD after 39
weeks of gestation. We analyzed factors affecting maternal andneonatal morbidity in term cesarean section. Methods The relationship between the GA, maternal age, indication of CD,
whether elective or emergent and adverse neonatal/maternal
outcomes were compared in 1,035 term pregnant women who
were booked for CD. Adverse neonatal outcomes were definedas the presence of mortality, adverse respiratory outcomes, sepsis, hypoglycemia, seizures, necrotizing enterocolitis, hypoxic
ischemic encephalopathy, cardiopulmonary resuscitation, cord
pH＜7, 5min AS below 3, admission to NICU, or prolonged hospitalization. Adverse maternal outcomes included a primary composite of death, uterine atony, need for transfusion, uterine artery embolization, peripartum hysterectomy, cystostomy, broad
ligament hematoma, uterine artery ligation, uterine rupture,wound dehiscence, admission to ICU, endometritis, thromboembolic complications, or postoperative ileus. Results 1）The frequency of adverse neonatal and maternal outcomes were 5%（52/1,035）, and 6%
（61/1,035）
in all CD. 2）Neonatal complications
decreased as the GA increased in all patients. 3）The maternal
age and whether the cesarean section was an emergency orscheduled were the two factors that adversely affect maternal
outcomes. Conclusion The risk of neonatal complications decreased as the GA increased. But GA was not related with adverse maternal outcome. Maternal age and whether elective or
emergent were the factors related with adverse maternal outcome. The risk of emergency CD increased as the GA̲planned
increased, so clinicians should remember when planning thedate of elective CD.

IS-WS-5-3
How do we reduce further maternal deaths in Japan?：Recommendations from the Maternal Death Exploratory Committee Junichi Hasegawa1, Hiroaki Tanaka2, Shinji Katsuragi2,
Kazuhiro Osato2, Takeshi Murakoshi2, Masahiko Nakata2,
Masamitsu Nakamura2, Jun Yoshimatsu2, Akihiko Sekizawa2,
Isamu Ishiwata2, Tomoaki Ikeda2 St. Marianna University Schoolof Medicine 1, The Maternal Death Exploratory Committee in Japan 2
Objective To clarify the problems related to maternal deaths inJapan, we made recommendation for further reduction of maternal deaths. Methods Descriptive study was performed in maternal death registration system established by the Japan Association of Obstetricians and Gynecologists（JAOG）. Women who
died during pregnancy or within a year after delivery between
2010 and 2016 throughout Japan（n=277）were analyzed. This
study was approved by institutional ethical board. Results Maternal deaths were frequently caused by obstetric hemorrhage（23%）, stroke（15%）, amniotic fluid embolism（13%）, cardiovascular disease（10%）and pulmonary disease（8%）. The committee considered that it was impossible to prevent death in 51% of

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The spliceosome U2 snRNP factors promote genome stability
through distinct mechanisms；transcription of repair factors
and R loop processing Michihiro Tanikawa1, Osamu Hiraike2,
Katsutoshi Oda2, Harunori Honjoh2, Machiko Kojima2, Shinya
Oki2, Kenbun Sone1, Kazunori Nagasaka1, Yoko Matsumoto1,
Yutaka Osuga2, Tomoyuki Fujii2 The University of Tokyo 1,
Graduate School of Medicine, The University of Tokyo 2
Objective Whole exome sequencing in various cancers identified recurrent somatic mutations in U2 snRNP components ofthe spliceosome. Accumulating evidences have implied that the
spliceosome plays an important role in genome stability and
DNA repair processes. The aim of this study is to clarify thefunctions of U2 snRNP splicing factors, especially SNRPA1（Small Nuclear Ribonucleoprotein Polypeptide A1）in DNA
damage repair（DDR）pathway. Methods SNRPA1 and othersplicing factors were identified as Homologous Recombination（HR）repair genes by genome wide screens. Each splicing factor was depleted by siRNA knockdown and their functions in
DNA repair were analyzed by HR assay, immunofluorescence,real time laser micro irradiation and comet assay. R loop formations, deleterious transcription by product for the genome,
were also analyzed. Results HR assay showed strong HR deficiencies in splicing factorʼs depleted cells. In these cells, accumulation of BRCA1 and Rad51 to DNA damage sites were severely impaired. Live cell imaging showed recruitment of
SNRPA1 to laser induced DNA damage sites, indicating its direct involvement to DNA damage repair. Comet assay showedthat depletion of SNRPA1 markedly caused DNA damage. Immunofluorescence detected R loop formation in splicing factors
depleted cells as cause of DNA damage. Conclusion Recruiting
HR factors to DNA damage sites and R loop processing wereidentified as novel tumor suppressive function of the spliceosome U2 snRNP factors. Our data also suggest U2 snRNP of
spliceosome can be therapeutic target in HR deficient cancers（i.
e. BRCAness）.

sion Available data showed that the leading causes of maternalmortality are amniotic fluid embolism, sepsis, and cardiovascular disorders. Besides, recent changes in mortality distribution
highlight current characteristics of pregnancy care in Mongolia
and may help identify strategies for future improvement.

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the cases due to their severity especially in cases of amniotic
fluid embolism and stroke. In contrast, half of the deaths due toobstetric hemorrhage were considered possible to prevent withquick response or enough medical resource. Frequency of
epidural labor analgesia in the subjects was as same as that in
population in Japan（5%）. Whereas only a death was associatedwith analgesia itself, obstetric hemorrhage involved by instrumental delivery was strongly associated with deaths. 10% of thesubjects had got pregnant by ART, however one third of themhad already had severe complications before ART. Suicide wasreported only 5% of the subjects, however this incidence is estimated lower than certain population. Conclusion Recommendations for further reduction of maternal deaths in Japan include
to improve primary care for patients with maternal hemorrhage, longitudinal mental care from pregnant to puerperal period, and pre conceptional evaluations for each complicationand care.

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Prevention of hypothermia is important in early mother infant skin to skin contact Kentaro Kurasawa1, Yoshinobu
Sugo1, Mizuha Odagami1, Shigeru Aoki2, Etsuko Miyagi1 Yokohama City University 1, Yokohama City University Medical Center 2
Objective The points of attention in Early Mother Infant Skin
to Skin Contact was published in 2012. We describe the current
status of implementing early mother infant skin to skin contact in Japan and identify factors associated with suddenchanges in the conditions of newborns. Methods The Maternaland Child Health Division of the Ministry of Health, Labour andWelfare conducted a questionnaire survey focusing on earlymother infant skin to skin contact during the early neonatal
period in full term infants born in 2014. The questionnaire wasdelivered to 2,839 maternity facilities throughout Japan. Replies
were obtained from 1,680 facilities（60.4%）, and 627,593 deliveries were analyzed based on the responses obtained. Results The
proportions of facilities implementing early mother infant skinto skin contact overall and in accordance with the Points of Attention in Early Mother Infant Skin to Skin Contact were
88.2% and 36.0%, respectively. Early mother infant skin to skincontact time is most often less than 30 minutes（38.9%）. The
number of events of sudden change requiring resuscitation including positive pressure ventilation during early mother infant skin to skin contact was 149（0.027%）. Of these 149 events,
97（65.1%）occurred within 10 minutes after birth. There was no
association between the event occurrence rate and facility types（p=0.56）, although fewer events were observed in the generaland regional prenatal care centers. In addition, the event rate
was significantly lower in facilities providing hypothermia prevention（p＜0.01）. Conclusion All newborns may show suddenchanges, necessitating careful observation of mothers and children. Prevention of hypothermia in newborns contribute to reducing the risk of needing urgent care.

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Population based trends and risk factors of early and late
onset preeclampsia in Taiwan 2001 2014 Shu-Han You,
Hsien-Ming Wu, Pao-Hsien Chu, Ting-Ting Chung, Chang-Fu
Kuo Chang Gung Memorial Hospital, Taiwan
Objective Preeclampsia is strongly correlated with maternal
and fetal complications in pregnancy, especially the early onset（＜34 weeks of gestation）preeclampsia, which contributes topoorer pregnancy outcomes. Besides, the incidences between
early and late onset of preeclampsia were differed among populations. The established risk factors of preeclampsia included
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diabetes mellitus. In this study, we evaluated the incidences,
trends, and risk factors of early and late onset preeclampsia in
Taiwan. Methods The population based prospective cohort
study included all ＞20 weeks singleton deliveries in Taiwan
from 2001 to 2014（n=2,884,347）according to the Taiwanese
Birth Register. The preeclampsia was determined from hospitalrecords, reporting to National Health Insurance Research Database. The standardized preeclampsia incidence was adjusted
based on the age distribution in 2014, the trends were analyzed
through Joinpoint Trend Analysis Software, and multivariate logistic regression was used to evaluate the adjusted relative
risks（ARR）of clinical factors of early and late onset
preeclampsia. Results The total incidence of preeclampsia increased from 1.11 to 1.69% with the early onset from 0.47 to
0.83% and late onset from 0.66 to 0.89%, respectively during thestudy period. The significant annual percentage change wasnoted in early onset preeclampsia, especially from 2012 to 2014（22.5%/year；95% confidence interval［CI］, 7.5 39.6%）. Advanced maternal age, primiparity, previous stroke, diabetes mellitus, chronic hypertension, and hyperthyroidism were associated higher risk of preeclampsia. Comparing early versus late
onset disease, two groups were similar to clinical risk factors,
and chronic hypertension had stronger association with early
onset preeclampsia（ARR, 16.8；95%CI, 15.7 18.0）. Conclusion
The incidences of early and late onset preeclampsia were increasing between 2001 and 2014 in Taiwan, especially early onset preeclampsia. Pregnant women who were advanced maternal age, primiparity, or had stroke, diabetes mellitus, chronic hypertension, or hyperthyroidism should be aware of higher riskof early and late onset preeclampsia, particularly in womenwith chronic hypertension.

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EEG changes and sleep/wakefulness behaviors in Pregnancy
Associated Hypertensive mice Haruna Komiya, Hiromi
Hamada, Miyuki Mayumi, Yuko Nagai, Rena Ohara, Hiroya
Yagi, Mana Obata, Toyomi Satoh University of Tsukuba
Objective We reported the quantitative/qualitative sleepchange during pregnancy in mice at the annual congress lastyear. Based on these results, we further investigate the effect of
EEG changes and sleep/wakefulness behaviors on acute andsever hypertension during late pregnancy using PAH（Pregnancy Associated Hypertensive）mice, Renin Angiotensin
transgenic mice. Methods Human angiotensinogen expressing
female mice and C57BL/6 female mice are the subjects. At theage of 9 12 weeks, EEG/EMG recording electrodes were implanted to the skull and neck muscle. After the recovery and acclimation periods, we recorded the basal sleep state. Next, wemated the human angiotensinogen expressing female mice andwild type female mice with human renin expressing male mice
and wild type male mice, respectively. The recordings were restarted after the confirmation of vaginal plug. We evaluated 4days for early, mid, late pregnancy and 2 days for postpartum.
Furthermore, we injected Evans blue to the tail vein and removed the brains in late pregnancy to investigate the BBB permeability. Results PAH mice exhibited markedly abnormal vigilance states with a generalized slowing of EEG and a drastic decrease in REM sleep during late pregnancy, making it impossible to determine wakefulness and NREMS. Half of the PAH
mice shows convulsive seizure conceived as eclampsia. Thesechanges are returned to normal immediately after delivery. All
PAH mice exhibited multiple leakages of Evans blue. Conclusion PAH mice exhibited a general slowing of EEG accompanied with BBB disruption. This study also suggest the PAH
mice as an animal model for eclampsia

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Possible involvemet of RAGE in Hypertensive Disorders ofPregnancy Juria Akasaka, Taihei Tsunemi, Kazutoshi Nakano,Shunsuke Onishi, Mai Kimura, Kenji Ogawa, Chiharu
Yoshimoto, Toshiyuki Sado, Hiroshi Kobayashi Nara Medical
University
Objective Obesity and diabetes mellitus are risk factors of Hypertensive Disorders of Pregnancy（HDP）. RAGE is one of themost important receptor related in diabetes mellitus. In thisstudy we investigate the involvement of RAGE in HDP. Methods We used primary human preadipocyte and induced theminto adipocyte. We cultured adipocyte with medium which contains 10% patientʼs serum. We used serum of preeclampsia patients（referred to as PE group）, and serum of normal pregnancy
as a control group（referred to as NP group）. After culture, wecollected adipocyte for analysis of mRNA expression and collected supernatant for measurement of protein expression. Results Using real time PCR, we analyzed mRNA expression of
adipocyte（about TNFα, IFNγ, IL 6, IL 17A）. IL 6 mRNA expression was elevated after 6 and 12 hours culture in PE gourp
compared to NP group. Using ELISA, it was also revealed that
IL 6 protein expression is elevated in supernatant of PE groupcompared to NP group. Focusing on IL 6, we furthermore analized mRNA expression of HMBG1, RAGE, CCL2. Hereupon, we
comfirmed that mRNA expression of IL 6 are related to those of
HMGB1, RAGE and CCL2. We hypothesize the pathway that
HMGB1 elevation cause RAGE elevation and finally cause IL 6
and CCL2 elevation. So using SW872 as human adipocyte cultivated cell line, stimulating SW872 with AGE and HMGB1 leadto elevation of mRNA expression of IL 6 and CCLS. But whensiRAGE is introduced, stimulating with AGE and HMGB1 didnʼt

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Endoplasmic reticulum chaperone calreticulin plays a keyrole in human placental development Naoyuki Iwahashi1,
Madoka Yamamoto1, Yoshito Ihara2, Kazuhiko Ino1 Wakayama
Medical University Hospital 1, Department of Biochemistry,
Wakayama Medical University Hospital 2
Objective Calreticulin（CRT）,a molecular chaperone in the endoplasmic reticulum, plays a variety of roles in cell growth, differentiation, and apoptosis. The objective of this study was to investigate the expression and functions of CRT in human placenta, utilizing the human trophoblast cell lines, in which CRT
gene expression was knocked down. Methods Expression of
CRT was examined in human placenta and trophoblast celllines, such as HTR8/SVneo and BeWo. Stable CRT knockdown
HTR8/SVneo and BeWo cell lines were established, and the effect of CRT downregulation was investigated in respects of cellproliferation, invasion, adhesion, and/or differentiation. This
study was approved by the institutional ethics boards, and theinformed consent was obtained from all patients. Results In
western blotting, CRT was strongly expressed in human placenta throughout pregnancy and in trophoblast cell lines. In immunohistochemistry, CRT was mainly expressed in extravillous
trophoblasts cells in the first trimester placenta, and in syncytiotrophoblasts in the third trimester placenta. In human placenta, the CRT expression levels in fetal growth restrictiongroup were significantly lower than those in control group in
the third trimester. On the other hand, in HTR8/SVneo cells,
knockdown of CRT expression suppressed matrigel invasion
and the adhesion to fibronectin via the alteration of integrin signaling. Furthermore, in BeWo cells, forskolin induced expression of β hCG was significantly suppressed by the CRT knockdown. Conclusion The results suggest that CRT is involved incell invasion and β hCG expression in trophoblasts. The decrease in CRT expression in fetal growth restriction might beinvolved in the dysfunction of placental development.

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IS-WS-6-2
Effectiveness of Nifedipine in threatened preterm labor：arandomized trial Chatchanawadee Na Nan, Srisuda Songthamwat,
Metha Songthamwat Udon Thani Hospital, Thailand
Objective Threatened preterm labor is the condition which ispremature regular uterine contraction at least 1 time in 10 minutes persist for more than 30 minutes before 37 complete weeks
of gestation without dilatation of cervix. In the preterm laborwith cervical dilatation, the effectiveness of tocolytic wasproven. However, in threatened preterm labor, the efficacy of
Nifedipine has not yet been well studied. This study aimed toevaluate the effectiveness of Nifedipine versus placebo for inhibiting uterine contraction in threatened preterm labor. Methods A randomized, double blind, placebo controlled study of 206
threatened preterm labor participants were randomly allocatedinto Nifedipine and placebo groups. Results After 90 minutes oftreatment, 88.3% of the Nifedipine group and 69.9% of the placebo group had no uterine contraction（P＜0.001）. Nifedipine
achieved successful treatment in 77.6% of the participants compared with 49.5% in placebo group（P＜0.001）.The remainder ofparticipants from both groups needed the second line tocolytic
drug. Of these 9.7% of the Nifedipine group delivered in 48hours
compare with 12.6% in the placebo group（P＞0.05）. Mean gestation age at delivery and neonatal complications of both groups

May 12 Sat.
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Attenuation of angiotensin II induced preeclamptic symptoms by recombinant thrombomodulin in mice ― a novel
therapeutic approach for preeclampsia Hiroko Oda, Takeshi
Nagamatsu, Takayuki Iriyama, Yutaka Osuga, Tomoyuki Fujii
The University of Tokyo
Objective Endothelial dysfunction is known to be a factor of
pathoetiology in preeclampsia（PE）. Recombinant thrombomodulin（rTm）is reported to have anti inflammatory functionthat could modify endothelial damage. We examined the efficacy of rTm administration in a mouse model of PE. Methods
The osmotic pump was implanted in the pregnant mice or nonpregnant female mice. Angiotensin2（Ang2）was continuously
injected for 7 days from pc 10 to 17 using the osmotic pump.
rTm was administered intraperitoneally for 4 days from pc 13 to
16. In the control mice, saline was administered during the same
period. Blood pressure（BP）was monitored daily. Blood andurine samples were collected before and after rTm or saline injection. On pc 17, the mice were sacrificed. The fetuses and placentas were excised. Results Continuous infusion of Ang2 induced the symptoms mimicking human PE. Significant elevation of BP was confirmed from day 3 after of Ang2 infusion. Hypertension was more obvious in the pregnant mice than the nonpregnant control. Occurrence of proteinuria was limited to pregnant mice. Ang2 infusion caused growth restriction in the fetuses. Administration of rTm significantly attenuated all of thethree symptoms of PE. On pc 17, the difference between rTmgroup and the non treated control were as follows, SBP（mmHg）；rTm：149±21 vs control：199±15, p＜0.001, proteinurea（mg/g CRE）
；rTm：40±13 control：78±12, p＜0.001,
and fetal weight（g）；rTm：0.7±0.07 control：0.61±0.05, p＜
0.001. Conclusion rTm attenuated Ang2 induced PE symptoms
in the mouse model. Our findings suggest that rTm might be anovel approach for the therapy of PE.

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cause mRNA elevation of IL 6 and CCL2. Conclusion In this experiment we revealed that in human adipocyte, AGE and HMGB
1 leads to raise of IL 6 and CCL2 through RAGE. It is possiblethat PE patient serum contains RAGE ligands and play an important role in HDP onset.

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were not significantly different. Conclusion Nifedipine has ahigher success rate in inhibiting threatened preterm contraction. However, 60 90 minutes observation before starting tocolytic drug can reduce unnecessary treatment without affecting
the outcome.

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Involvement of apoptosis signal regulating kinase1（ASK1）
MAPK pathway in inflammation induced preterm birth
Midori Yoshikawa, Takayuki Iriyama, Kensuke Suzuki, Taiki
Samejima, Tatsuya Fujii, Kazuki Morita, Takeshi Nagamatsu,
Yutaka Osuga, Tomoyuki Fujii The University of Tokyo
Objective Oxidative stress is closely associated with the pathophysiology of preterm birth. Apoptosis signal regulating kinase
1（ASK1）,a member of mitogen activated protein kinase kinasekinase（MAPKKK）, controls oxidative stress induced cellularresponses including inflammation by regulating JNK and p38
MAPK pathways. Here, we aimed to investigate the roles of
ASK1 JNK/p38 MAPK pathways in preterm birth. Methods
Lipopolysaccharide（LPS）was injected transvaginally into cervices of pregnant ASK1 deficient（ASK1 / ）and wild type（WT）mice on day 15 of gestation. Human amniotic epithelial
cells（hAEC）isolated from human term placenta were treatedwith hydrogen peroxide. The research protocol was approvedby the Institutional Committee. Results ASK1 / displayed asignificantly lower incidence of delivery（7/17=41%）at 24 hours
following LPS injection when compared with WT（11/15=73%）（p＜0.05）. Kaplan Meier analysis revealed that the incidence ofdelivery within 48 hours following LPS injection was significantly lower in ASK1 / as compared with WT（p＜0.05）. Immunoblotting analysis showed that LPS injection induced theactivation of ASK1 in the cervix, myometrium, and placenta of
WT. LPS induced phosphorylation levels of JNK and p38 in thecervix, myometrium, and placenta were decreased in ASK1 / ,compared with WT. In human primary culture of placental
membranes, we found that ASK1 was activated in response tohydrogen peroxide in hAEC. Conclusion Our results suggested
that ASK1 could play a pivotal role in inflammation induced
preterm birth through the activation of JNK and p38 pathways.
ASK1 might be a novel therapeutic target for preterm birth.

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IS-WS-6-4
Amniotic fluid macrophages help the healing of ruptured amnion via epithelial mesenchymal transition（EMT）Haruta
Mogami1, Yosuke Kawamura1, Shingo Io1, Mai Sato1, Hiroshi
Takai1, Yoshitsugu Chigusa1, Eiji Kondoh1, Masaki Mandai1,
Ruth Ann Word2 Kyoto University 1, UT Southwestern Medical
Center, USA 2
Objective pPROM is a major cause of preterm birth. However, asmall proportion of women remain undelivered after pPROM
and spontaneous sealing of the membranes occurs occasionally.
Here, we investigated mechanisms of healing of ruptured membrane. Methods Fetal membranes of pregnant mice were punctured with a sterile 26G or 20G needle by laparotomy on 15dpc.
Ruptured membrane was compared to intact control at eachtime point. All procedures were approved by the Ethics Committee and Animal Research Committee of our institution. Results In the model of non infectious pPROM by 26G, 83% healed
spontaneously within 24h and 98% within 72h, whereas in rupture by 20G, only 7% healed spontaneously within 24h and 50%
within 72h. Histologically, massive migration of mesenchymal
cells was observed in healing site of amnion. In scanning electron microscope, flap like structure of amnion was formed at
rupture site, and then rupture was completely covered by epithelial cells after 48h. In immunofluorescence, F4/80 positive
macrophages were recruited from amniotic fluid to wounded

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amnion, and IL 1β and TNF were released. Vimentin positivemesenchymal cells have appeared in the epithelial layer of healing amnion, which suggested the existence of EMT. In vitro, IL
1β and TNF stimulated the migration of human amnion epithelial cells in scratch assay, and E cadherin positive epithelial
cells were changed to vimentin positive mesenchymal cells in
the wounded center. Conclusion Amniotic fluid derived macrophages move to ruptured amnion, releasing IL 1β and TNF,
which stimulate EMT of amnion epithelial cells and help thehealing of the ruptured amnion.

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IS-WS-6-5!

Anti inflammatory effect of progesterone suppresses the enhancement of inflammatory cytokines on fetal membrane in apreterm birth mouse model with chronic dental infection
Yuko Teraoka1, Satoshi Urabe1, Haruhisa Konishi1, Mutsumi
Miyauchi2, Hiroshi Miyoshi3, Takashi Takata2, Yoshiki Kudo1 Hiroshima University 1, Department of Oral and Maxillofacial
Pathobiology, Hiroshima University 2, Hiroshima Prefectural
Hospital 3
Objective Progesterone（P4）is important in maintaining pregnancy via its anti inflammatory effect in the myometrium：
however, this effect is poorly understood in the fetal membrane.
We previously reported that mice with dental Porphyromonas
gingivalis （P.g ）infection could be useful as a model of preterm
birth. In this model, inflammation in the fetal membrane via
toll like receptor 2 is thought to result in preterm birth, as thelevel of IL 1 β is highly up regulated. We investigated whether
P4 prevented preterm birth and the effects of P4 on the fetal
membrane. Methods P.g mice were injected subcutaneously
with（P.g +P4 mice）or without（P.g mice）1 mg of P4 daily atdays 15.5 to 17.5 of gestation. We observed the mice in these gestational periods. Western blot analysis was performed for detection of NF κB and MAPK on the fetal membrane at day 18 ofgestation. We also evaluated inflammatory cytokines（IL 1 β,IL 8, TNF α）at the same tissues using RT PCR. Results The
average gestational period was 20.4 days in P.g +P4 mice and18.3 days in P.g mice. The enhancement of NF κB and MAPK
expression levels was decreased in P.g +P4 mice, comparedwith in P.g mice. Treatment with P4 significantly reduced theenhancement of the expression of IL 1 β, IL 8, and TNF α by
88%, 76% and 59%, respectively. Conclusion P4 prevented preterm birth by suppressing the activation of inflammatory signaling pathways in the fetal membrane of a chronic inflammationinduced preterm birth mouse model.

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Prevention of LPS induced preterm labor by the lack of CX3
CL1 CX3CR1 interaction in mice Mika Mizoguchi, Tamaki
Yahata, Madoka Yamamoto, Sawako Minami, Kazuhiko Ino
Wakayama Medical University
Objective We explored the pathological roles of CX3CL1（fractalkine）and its receptor CX3CR1 in preterm labor（PTL）using!
Cx3cr1 !/（KO）mice. Methods Pregnant C57BL/6（WT）and KO
mice were injected i.p. 25μg LPS at gestational day（gd）15.5 andobserved until labor followed by the evaluation of PTL rate. Gestational tissues and serum were collected at 6 hrs after LPS. The
rate of PTL, count of immune cells, and inflammatory cytokines
were compared between WT and KO mice. Anti CX3CL1 Abs
were injected to WT mice at 3 hrs after LPS. Results In bothmice and human PTL, serum CX3CL1 level was significantly increased. The rate of PTL was significantly inhibited in KO mice,compared with WT ones. Moreover, the lack of CX3CR1 reduced macrophage recruitment into uterus and gene expressionof Il1b, Il6, Tnfa and Ptgs2 . Macrophages were the main cellular source of these cytokines and COX 2. The exogenous

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CX3CL1 augmented gene expression of l1b, Il6, Tnfa and Ptgs2
in WT peritoneal macrophages. Finally, anti CX3CL1 Ab significantly reduced the rate of preterm labor in WT mice. Conclusion Collectively, these observations suggested that CX3CL
1 CX3CR1 axis would play detrimental roles in LPS induced
PTL through macrophage recruitment and eventually inflammatory cytokine production. Thus, CX3CL1 CX3CR1 systems
might be a therapeutic target of PTL.

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Comparison of One Step Versus Two Step Screening for Gestational Diabetes Mellitus and Adverse Obstetrical Outcomesat a Single Tertiary Center in Taiwan Cleo Tsai, Mei-Leng
Cheong, Li-Ching Chen, Ming-Song Tsai Cathay General Hospital, Taipei Branch, Taiwan
Objective To compare the incidence of gestational diabetes mellitus（GDM）diagnosed by the one step or two step screening
method during 24 to 28 weeks of gestation and its associated adverse obstetrical outcomes. Materials and Methods From January 2000 to August 2017, the medical records of 23,517 singleton
pregnancies were reviewed retrospectively at Cathay General
Hospital, Taiwan. Data for GDM diagnosed by the one step International Association of Diabetes and Pregnancy study groups（IADPSG）method or the two step Carpenter and Coustan（CC）
criteria were collected. Outcomes including cesarean delivery,
macrosomia, large for gestational age（LGA）,intrauterine fetal
demise（IUFD）,and preeclampsia were compared between thetwo groups. Results The incidence of GDM using the one step
criteria（9.21%）had a 2.73 fold increase when compared to thetwo step criteria（3.37%）. After implementation of the one step
criteria as institutional guidelines since August 2012, decreases
in cesarean delivery rate（46.7% to 40.5%, p＜0.05）, macrosomia

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IS-WS-7-1!

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Anti cancer effect of axitinib in ovarian cancer Myeong Seon
Kim, Jihye Kim, Seon Mi Kim, Ji Young Hong, E Sun Paik,
Tae-Joong Kim, Chel Hun Choi, Byoung-Gie Kim, Duk-Soo Bae,Jeong-Won Lee Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
Objective Axitinib（InlytaⓇ）is a small molecule tyrosine kinase
inhibitor developed by Pfizer. It is known that the primarymechanism of axitinib is related to vascular endothelial growth
factor receptor 2（VEGFR2）, which is dependent on tumor associated angiogenesis. We aimed to investigate the anti cancer effect of axitinib alone or combined with chemotherapeutic drugs
against human ovarian cancer cells. Methods We treated axitinib in ovarian cancer cells（A2780, HeyA8, A2780 cis, HeyA8
MDR, ES2, RMG1）to evaluate the effect on cell proliferation using MTT assay. To check the VEGFR2, ERK, AKT and Bcl 2level and the apoptosis according to Axitinib treatment, we performed the Western blot and ELISA in ovarian cancer cell line.
In addition, in vivo therapy experiments of axitinib were doneusing xenografts using A2780 and RMG1 in nude mice. Tumor
cells were injected i.p., the mice（n=10 per group）were randomly assigned to two treatment groups：0.5% methyl cellulose（control）, oral axitinib 30mg/kg twice daily. Moreover, we performed the in vivo therapy experiment in patient derived
xenograft model（PDX）of ovarian clear cell carcinoma（CCC）toconfirm these effects. Results Axitinib significantly inhibitedthe cell survival and increased the apoptosis in ovarian cancer
cells. Combination treatment of cells with axitinib and cisplatin/
paclitaxel significantly inhibited the cell growth and increased
the apoptosis compared to the single agent treatment in chemo
resistant ovarian cancer cells. In in vivo experiments, axitinib
significantly decreased the tumor weight in xenograft models of
established cell lines（A2780, RMG1）and a PDX model for CCC
compared to control. Moreover, the immunohistochemical analysis using in vivo tumor samples showed that axitinib treatedgroup increased apoptosis revealed by TUNEL assay comparedwith control. Conclusion We found that axitinib have anti cancer effects in ovarian cancer cells via inhibition of VEGFR signal to cell proliferation and apoptosis through in vitro and invivo tests. Also, our results indicated that combined therapy
with axitinib and chemotherapeutic drugs could significantly
enhance the ovarian cancer cell growth inhibitory effect. We
plan further studies using xenograft model for combination effect of axitinib and chemotherapeutic drugs.

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IS-WS-7-3

May 12 Sat.
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Elimination of Mother to Child Transmission of Human Immunodeficiency Virus：11 Year Experience in a Single Center in Taiwan Huang Kuan-Ying, Li Yi-Ping, Shi Chung-Ching,
Lee Chien-Nan, Lin Shin-Yu, Ho Hong-Nerng National Taiwan
University Hospital, Taiwan
Background A prenatal opt out human immunodeficiency virus（HIV）screening program in Taiwan has started since 2005.
By the end of 2014, the screening rate was approximately 99%.
However, after the opt out HIV screening program, only 13
cases of MTCT of HIV infection were diagnosed in Taiwan；an
MTCT rate of 3.2%. Here we describe clinical management of
the HIV infected mother and MTCT rate in National Taiwan
University Hospital after the opt out HIV screening program
was started. Methods Retrospective charts of pregnant women
infected with HIV managed at NTUH, Taipei, Taiwan, from2005 to December 2016, were reviewed. HIV infection status
was available for 39 infants born to HIV infected mothers. Results There were 50 pregnant HIV infected women with 57
parities in NTUH from 2005 to December 2016. Fifty seven living infants were born. However, 18 parities were excluded because of missing data. Maternal antiviral treatment was administered in 92% parities（37/39 infants）.Only one child（1/39）wasfound to be positive for an HIV antibody test at 18 months, but
this child showed definitive HIV exclusion at 20 months after aseries of tests without antiviral treatment. The MTCT rate waszero. Conclusion Successful implementation of available perinatal HIV intervention dramatically reduced the vertical transmission rate. The MTCT rate was zero in NTUH after the opt out
HIV screening program. However, as an HIV referral center,several efforts need to be made for achieving the World HealthOrganization criteria of elimination vertical transmission of HIV
to lower than 2% in Taiwan.

（6.7% to 1.8%, p＜0.05）, LGA（15.0% to 6.0%, p＜0.05）, and hypertensive disorders（9.4% to 5.6%, p＜0.05）were observed. Our dataalso showed an increase in vaginal delivery rate（49.4% to 57.8%,
p＜0.05）in women with GDM diagnosed by the one step
method. Conclusion The one step screening method was associated with a higher incidence of GDM when compared to thetwo step criteria. However, decreases in adverse obstetricaloutcomes in our population were observed after encouragementof diet control and regular exercise. GDM is a category of highrisk pregnancy that all obstetricians should carefully manage
and treat accordingly to reduce the risks of adverse pregnancy
outcomes.

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Machine Learning guided Staging in Patients with Epithelial
Ovarian Cancer E Sun Paik1, Jeong-Yeol Park2, Ju-Hyun Kim2,
Jihye Kim1, Chel Hun Choi1, Byoung-Gie Kim1, Duk-Soo Bae1,
Sung Wook Seo3, Jeong-Won Lee1,3 Samsung Medical Center,
Sungkyunkwan University School of Medicine, Korea 1, Univer-︶204
sity of Ulsan College of Medicine, Asan Medical Center, Korea 2,
Samsung Advanced Institute for Health Sciences ＆ Technology, Sungkyunkwan University School of Medicine, Korea 3
Purpose We aimed to use the machine learning classifier, gradient boosting（GB）, to predict survival outcomes for epithelial
ovarian cancer（EOC）patients using all of available clinical variables. Methods Clinical variables including serial CA 125 level
in EOC patients from two hospitals were analyzed retrospectively for training/internal validation（Samsung Medical Center,
n=1,128）and external validation（Asan Medical Center, n=229）.
The GB model was optimized using validation data. The performance of final model was tested over external validation set.
ROC curves of survival probability were compared to the Cox
proportional hazard regression analysis（CoxPHR）model annually over five years after the surgery. Results Of initial 34 covariates generated, 19 covariates were optimized for GB model.
We used second year survival data as target value with thehighest area under the curve（AUC）. During internal validation,
the AUC of the GB model for predicting second year overall survival was 0.830（95% C.I.：0.802 0.853）, which was more accurate than CoxPHR（AUC of 0.668（95% C.I.：0.617 0.719））.On external validation, GB model also showed higher AUC of 0.816（95% C.I.：0.739 0.892）for second year survival after surgery,which was better than the CoxPHR model（AUC of 0.597（95%C.I.：0.474 0.719））.A new staging system according to survival
probability scores of the GB model identified four distinct prognostic subgroups that classified patients. Conclusion Our new
GB guided staging system accurately identified prognostic subgroups of patients with EOC. This approach would be useful for
better estimation of individual outcomes of EOC patients.

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Trends and comparative analysis of patients with end stage
ovarian cancer who have received active palliative chemotherapy for the past 10 years Jeong-Yeol Park, Dae-Yeon Kim,
Dae-Shik Suh, Jong-Hyeok Kim, Yong-Man Kim, Tae-Kyu Jang,
Young-Tak Kim, Joo-Hyun Nam Asan Medical Center, University of Ulsan College of Medicine, Korea
Objective We analyzed the pattern of chemotherapy for the last
6 months of patients with end stage ovarian cancer who havebeen aggressively treated with palliative chemotherapy for the
past 10 years. Methods We retrospectively analyzed the patients who died after performing active palliative chemotherapy
with end stage ovarian cancer at Asan Medical Center from2006 to 2015. From 2006 to 2010 and from 2011 to 2015, we divided into two groups. Based on the electronic medical records,
the demographic and basic characteristics of the patients, admission for the last 6 months, invasive procedures, and the timeof final chemotherapy were confirmed. Results A total of 111 patients with ovarian cancer were eligible for this study. 57 patients died from 2006 to 2010, and 54 patients died from 2011 to2015. The mean number of hospitalizations during the last 6months was 4.33（2006 2010）vs. 5.69 times（2011 2015）（p=0.041）
and mean number of palliative chemotherapy was 3.88（20062010）vs. 5.06 times（2011 2015）.（P=0.002）The proportion ofpatients undergoing invasive procedures was 35.1%（20/57,
2006 2010）vs. 53.7%（29/54, 2011 2015）（. p=0.048）The numberof palliative chemotherapy and the rate of invasive procedures
have increased in patients with end stage ovarian cancer forthe recent 5 years compared to 2006 to 2010. Conclusion Gynecology oncologists need to evaluate whether active palliative
chemotherapy improves patient quality of life at every time and
if not helpful, should communicate with patients and caregivers
about when to stop the palliative chemotherapy.

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IS-WS-7-5!

Carcinoma associated mesothelial cells orchestrate progression of peritoneal dissemination and acquired platinum resistance in epithelial ovarian cancer Masato Yoshihara1, Hiroaki
Kajiyama1, Mai Sugiyama2, Yoshihiro Koya2, Shiro Suzuki1,
Fumitaka Kikkawa1 Nagoya University 1, Bell Research Center,
Nagoya University 2
Objective Based on the seed and soil theory, we evaluated interaction of epithelial ovarian cancer cells（EOCs：seed）andmesothelial cells（MCs：soil）, and analyzed how they promotetumor microenvironment with innovative experimental models
and various in silico omics analyses under approval of ethicalcommittee. Methods We compared adhesion and proliferation of
EOCs co cultured with carcinoma associated MCs（CAMs）andnon activated MCs by human omentum ex vivo assay and invivo imaging system using a mouse dissemination model. We established an in vitro peritoneal metastatic invasion model andvisualized fluorescent labeled cell behavior by 3D construction.
Proteome analysis was used to reveal the feature of CAMs. Cell
viability of EOCs co cultured with CAMs were evaluated by
apoptosis detection assay and transcriptome analysis was performed to pursue detailed mechanism. Results The EMT related characteristics were observed in CAMs and its relevancewas confirmed by proteome analysis. The growth factor array（ascites；n=17）concluded that CAMs were mainly generated
by TGF β1. Adhesion and proliferation of EOCs on CAMs wereincreased both in vitro, ex vivo, and in vivo assay. As for invasion, the 3D construction imaging demonstrated that EOCs invaded with CAMs into extracellular matrix beneath the layer ofMCs（846μm vs. 261μm, p＜0.05）. Moreover, we found acquired
platinum resistance in EOCs co cultured with CAMs by apoptosis detection assay（24.6% vs. 9.93%, p＜0.05）. Transcriptome
analysis suggested PI3K/Akt pathway played a crucial role in
EOCs induced by stimulation of CAMs. Conclusion Our results
suggest tumor microenvironment enhanced by mutual association with EOCs and CAMs promotes progression of peritoneal
dissemination and acquired platinum resistance in EOCs.

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IS-WS-7-6
Bisphosphonates, new candidate of drug repositioning forovarian cancer Yusuke Kobayashi, Kouji Banno, Haruko
Kunitomi, Yusuke Matoba, Moito Iijima, Takashi Takeda, Miho
Iida, Kanako Nakamura, Kosuke Tsuji, Eiichiro Tominaga,
Mamoru Tanaka, Daisuke Aoki Keio University
Objective Rapid advances in pharmacotherapy and bioinformatics develop drug repositioning that includes re investigating or
recycling of existing drugs for new indications. We have previously demonstrated an antitumor effect of statins, antidyslipidemic drugs, on ovarian cancer in vitro and in vivo. Bisphosphonates are commonly used as antiosteoporotic drugs, and inhibit mevalonate pathway as same as statins. Antitumor effectsof the bisphosphonate were examined in this study. Methods
Cell counts after administration of alendronate, a second generation bisphosphonate, were performed to examine inhibitory
ability on growth of SKOV3 and OVCAR5 ovarian cancer cells.
Autophagy expression was evaluated by western blot. The potential antitumor effect was examined in vivo using transgenic
ovarian cancer model mice. The proliferative activity with Ki
67 and quantification of STICs with STIC associated marker,
laminin C1 were evaluated in tissue section by immunohistochemistry. Results Alendronate exhibited concentration dependent inhibition of growth of these cells. Vacuolation was
found in cells in a time dependent, and concentration dependent expression of autophagy marker, LC3A and LC3B, were induced by alendronate. Treatment with alendronate significantly
reduced the total tumor mass in the female reproductive tract,

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based on the organ weight. The proliferative activity with Ki 67
was significantly decreased in the alendronate treated micecompared with that of the control group. The rate of laminin C
1 positive tubal epithelial cells in alendronate treated mice wasalso significantly reduced compared with that of the control
group. Conclusion Alendronate induces autophagy and has an
inhibitory effect on cell growth in vitro and an antitumor effectin vivo. Drug repositioning targeting mevalonate pathway forovarian cancer deserves consideration for clinical application.

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IS-WS-8-2!

The role of angiopoietin like protein 2 in serous ovarian carcinoma with peritoneal dissemination Yuko Takeshita, Isao
Sakaguchi, Hidetaka Katabuchi Kumamoto University
Objective It has been reported that Angiopoietin like protein 2（ANGPTL2）is a secretory protein, which is induced from cells
under various stress conditions, and also involved in carcinogenesis in skin tissue as well as cancer invasion and metastasis
in breast and lung cancer. In this study, we examined the role of
ANGPTL2 in peritoneal dissemination of serous ovarian carcinoma. Methods We firstly established ANGPTL2 overexpressing cells derived from a human serous ovarian carcinoma cellline, SKOV3. Next, we administered ANGPTL2 overexpressing
cells and control cells intraperitoneally to immunodeficient
mice, respectively and evaluated the formation of peritoneal dissemination and survival time between two groups. In addition,
we performed RT PCR array focusing on cell motility to examine the key factor of peritoneal dissemination. Results In vivo

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May 12 Sat.
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The therapeutic effects of iPS cell derived myeloid cells producing interferon beta on human ovarian cancer cells in mice
Yuko Imamura1, Hironori Tashiro2, Junko Tsuboki1, Kiyomi
Takaishi1, Takashi Ohba1, Hidetaka Katabuchi1 Kumamoto University 1, Faculty of Life Sciences, Kumamoto University 2
Objective The microenvironment of metastatic ovarian cancer
includes fibroblasts, mesothelial cells, and immune cells withmacrophages, the most abundant cell type. Macrophages influence pro tumorigenic properties. In this study, we focused on
examining the cell to cell interactions between macrophages
and ovarian cancer cells. We examine the mechanism and therapeutic effects of interferon beta, produced by induced pluripotent stem（iPS ML/IFN β）cell derived myelomonocytic cells,
on metastatic ovarian cancer cells. Methods The human ovariancancer cell lines were cultured in the presence or absence of recombinant human IFN α, IFN β, IFN γ, TNF α, and TRAIL.
We then established a xenograft model of ovarian cancer metastasis human ovarian cancer cells into the peritoneal cavity ofmice. After disseminated tumor formed in the abdomen, IFN β
was administered by intraperitoneal injection. SKOV3 and ES2
cells were cultured with or without iPS ML/IFN β. The injection of iPS ML/IFN β caused the expression of several macrophage markers, including CD11b and CD68. After a three day
incubation period, luminescence was measured. SCID mice were
injected with luciferase expressing SKOV3 cells. Mice with established tumors were randomly divided into control and treatment groups. The mice in the treatment group were injectedwith iPS ML/IFN β. All mice underwent a bioluminescenceanalysis. Results Both IFN α and IFN β resulted in a decreasein the number of live SKOV3 and ES2 cells in vitro. IFN β
showed a clear inhibitory effect on ascites accumulation in vivo.
iPS ML/IFN β significantly inhibited the growth of disseminated ovarian cancer cells in vitro and in vivo, and also successfully reduced ascites in vivo. Conclusion This study suggeststhat iPS ML/IFN β has therapeutic potential in patients withmetastatic ovarian cancer.

analysis, the number of disseminated nodules in the group ofmice transplanted with ANGPTL2 overexpressing cells waslarger than the number in the control group significantly（p＜0.01）. Survival time was significantly shortened in the group ofmice treated with ANGPTL2 overexpressing cells compared tocontrol group（p＜0.05）. In RT PCR analysis, the expressions of
MMP1 and MMP13 increased significantly in ANGPTL2 overexpressing cells（p＜0.001, respectively）, and an increase of
dipeptidyl peptidase 4（DPP4）expression in the cells was also
detected by RT PCR array. Conclusion It is proved that
ANGPTL2 expression in serous ovarian carcinoma can promote
peritoneal dissemination in vivo analysis and that the expression of ANGPTL2 in serous ovarian carcinoma might contributeto cell motility in peritoneal dissemination through upregulating the expressions of MMPs and DPP4.

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IS-WS-8-3!

Unmasking ovarian chemoresistant cancer cells by TSA or 5
AZA reveals new candidates miRNAs involved in chemoresistance development Mohamed Hassan1,2,3, Amr Waly2, Hidemichi
Watari3, Noriaki Sakuragi3, Sherif El-Khamisy2 Faculty of Science, Port Said University, Egypt 1, Center for Genomics, Zewail
City for Science and Tech., Egypt 2, Hokkaido University 3
Objective Ovarian cancer is the most frequent cause of mortality in female gynecological maligancies. The current therapeutic agents face high rate of resistance, pressing the need fornovel therapeutics. Methods Here, we studied the comparative
microarray profiling between the ovarian cancer cells, KF andtheir taxane resistance counterparts, KF TX before and after
treatment with the epigenetic modulators TsA or 5AZA, to get
novel players involved in ovarian chemoresistance and themechanism of their expression. After microarray profiling,
Quantitative PCR was used to validate the expression of thosemiRNAs dowregulated in KF TX and re expressed after TsA
or 5AZA treatment. Results We found that miR 7 5p, miR 204
3p, miR 205 5p, miR 365a, miR 387g, miR 501 5p, miR505 3 ,miR 1236, miR 3195, miR 3613, miR 3652, miR 4286, miR 4526
and miR 8071 were the most downregulated miRNAs（morethan two folds change）in the chemoresistant cells（more than
two folds）.Of those miRNAs, only miR 204 3p and miR 501 5p
were upregulated under TsA treatment, while miR 7 5p, miR
204 3p, miR 365a, miR 4286, miR 4526 and miR 8071 wereupregulated after 5AZA treatment in KF TX cells. Conclusion
Histone modification study confirmed the promoter acetylationof those miR 501 5p, however DNA methylation of those genes
affected by 5AZA, using promoter bisulfate sequencing, confirmed their promoter methylation. Interestingly, combinationof TsA and/or 5AZA with taxane significantly restored chemosensitivity as confirmed by viability assay and clonogenic assay.
Pathway analysis indicated the major pathways affected by epigenentic changed of miRNA in the chemoresisitant ovarian cancer cells. Taken together, our data not only introduced novel
suppressors, downregulated during chemoresistance, players in
TX resistance but also revealed the mechanism of their downregulation.

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IS-WS-8-4!

Tumor suppressive roles of MARK3 in high grade serous
ovariancarcinomas
Hidenori Machino1, Syuzo Kaneko2,
Kenbun Sone1, Asako Kukita1, Shinya Oki1, Michihiro
Tanikawa1, Kazunori Nagasaka1, Yoko Matsumoto1, Katsutoshi
Oda1, Yutaka Osuga1, Tomoyuki Fujii1, Ryuji Hamamoto2 The
University of Tokyo 1, National Cancer Center Research Institute 2
Objective High grade serous ovarian carcinoma（HGSOC）is themost aggressive histological type, causing approximately 70% of

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death by ovarian cancer. The purpose of this study is to identify
novel candidate molecular targets and to clarify their functionsin HGSOC. Methods We analyzed publicly available microarraydatasets to identify genes, which are dysregulated and associated with prognosis in HGSOC. We then focused on a microtubule affinity regulating kinase 3（MARK3）gene and performed
functional analysis by RT PCR, in vitro kinase assay and cellline based assays, using doxycycline inducible cell lines. Results By analyzing two independent datasets, we identified 6
overlapping genes whose expression was dysregulated in
HGSOC. Of them, MARK3 was significantly downregulated in
HGSOC cell lines and tissues, and downregulation of MARK3
was associated with poor progression free survival（p＜0.0001）.
In silico analysis and chemical screening revealed that themechanisms to repress MARK3 expression in HGSOC are copy
number deletion and histone de acetylation. MARK3 overexpression significantly inhibited tumor proliferation in vitro.
MARK3 increased the ratio of cells in the G2/M phase by inhibiting CDC25s activities. Conclusion Our data suggests MARK3
is a novel tumor suppressive checkpoint kinase and its downregulation causes tumor proliferation. Dysregulation of MARK3
and CDC25s axis may be a potential therapeutic target against
HGSOC.

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IS-WS-8-5
Identification of somatic genetic alterations in ovarian clear
cell carcinoma with next generation sequencing Yusuke
Shibuya, Hideki Tokunaga, Bin Li, Nobuo Yaegashi Tohoku University HospitalObjective Ovarian clear cell carcinoma（OCCC）is the most refractory subtype of ovarian cancer and more prevalent in Japanese than Caucasians（25% and 5% of all ovarian cancer, respectively）.The objective of this study is to discover the genomic alterations that may cause OCCC and effective molecular targets
for chemotherapy. Methods Paired genomic DNAs of 48 OCCC
tissues and corresponding non cancerous tissues were extracted from formalin fixed, paraffin embedded specimens collected between 2007 and 2015 at our hospital. All specimens underwent exome sequencing and the somatic genetic alterations
were identified. Results We divided the cases into three clusters
based on the mutation spectra. Clinical characteristics such asage of onset and endometriosis are similar among the clusters
but one cluster shows mutations related to APOBEC activation,
indicating its contribution to subset of OCCC cases. There arethree hypermutated cases（showing 12 fold or higher somatic
mutations than the other 45 cases）and they have germline andsomatic mismatch repair gene alterations. The frequently mu, PPP2R1A
tated genes are ARID1A （66.7%）, PIK3CA （50%）（18.8%）and KRAS（16.7%）. Somatic mutations important for selection of chemotherapeutic agents, such as BRAF, ERBB2,PDGFRB, PGR, and KRAS are found in 27.1% of OCCC cases, indicating clinical importance of exome analysis for OCCC. Conclusion Our study suggests that the genetic instability causedby either mismatch repair defect or activation of APOBEC play
critical roles in OCCC carcinogenesis.

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IS-WS-8-6
The novel JNK inhibitor AS602801 inhibits ovarian cancer
stem cells in vitro and in vivo Hirotsugu Sakaki, Manabu
Seino, Takeshi Sudo, Tsuyoshi Ohta, Satoru Nagase Yamagata
University HospitalObjective Our recent study released that JNKs（c Jun NH2 terminal kinases）is a key molecule in the maintenance of ovariancancer stem cells. A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor,
in the treatment of inflammatory endometriosis is complete. We!

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are now examining whether AS602801 acts against human ovarian cancer stem cells in vitro and in vivo. Methods Using ovarian cancer stem cells derived from A2780 human ovarian cancer
cell line, We examined the effect of AS602801 on the viability as
well as on the self renewal and tumor initiating capacity. We
examined the anti cancer stem cells effect of AS602801 by trypan blue as a vital dye. We next examined the effect of AS
602801 on self renewal capacity by the expression of stem cellmarkers with immunoblot assay and flow cytometric assay. We
also evaluated sphere formation ability as self renewal capacity.
Lastly, we examined the effect of AS602801 on tumor initiating
capacity by ex vivo assay. Results In vitro, AS602801 exhibited
cytotoxicity against both serum cultured non stem cancer cells
and cancer stem cells derived from human ovarian cancer atconcentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self renewal andtumor initiating capacity of cancer stem cells surviving AS
602801 treatment. Conclusion These findings suggest AS602801
is a promising anti ovarian cancer stem cell agent, and further
investigation of the utility of AS602801 in the treatment of cancer seems warranted.

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IS-WS-9-1
Zfp371 is a novel DNA repair gene responsible for genome
stability during mitosis Seiji Ogawa1, Mitsutoshi Yamada1,
Toshio Hamatani1, Hidenori Akutsu2, Akihiro Umezawa2,
Mamoru Tanaka1, Daisuke Aoki1 Keio University 1, Departmentof Reproductive Biology, National Center for Child Health andDevelopment 2
Objective Chromosomal abnormalities are major obstacle to theassisted reproductive technology（ART）. We have previously
demonstrated that Zfp371 , which was identified by in silico
analysis, expressed in preimplantation embryos, testis and embryonic stem cells（ESCs）, and Zfp371 knockout somatic cells
exhibited several different types of chromosomal abnormalities
such as chromosome gap, derivative chromosomes, gain or lossof chromosome, and Robertsonian translocation. Zfp371 is reported to correlate with Rad51 and Brca1 , implying its role of
DNA repair. Here we used Zfp371 knockout mouse to elucidate
the etiology of chromosomal abnormalities and clinical phenotype. Methods Zfp371 deficient ESCs（KO ESCs）were derived
from homozygous. To test DNA stress response, KO ESCs irradiated with a dose of 4 Gy γ ray were stained by a marker of
DNA damage, phosphorylated（Ser139）histone H2A.X（γH2AX）.
Protein complex immunoprecipitation（Co IP）using the protein
extracted from ESCs was performed to analyze protein protein
interactions. Teratoma assay was performed to evaluate pluripotency. Results Irradiated KO ESCs showed significantly increased numbers of γH2AX foci（3.6 per cell）relative to wild
ESCs（1.8 per cell）（p＜0.05）. Global transcriptional analysis
showed elevated expression of DNA repair genes, Rad51l3 andBard1 in Zfp371 homozygous ES cells. Histone H1.1, H1.2 andH1.4 were detected as the proteins bound with Zfp371 . KO
ESCs differentiated into choriocarcinoma. Conclusion These results suggest that the absence of Zfp371 results in elevatedlevel of DNA damage, an accumulation of chromosomal abnormalities and eventually carcinogenesis. This is the first reportthat zygotic gene, Zfp371 , plays a role in DNA repair and is responsible for genome stability.

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IS-WS-9-2
The function of PTENP1 in implantation Masashi Takamura
Hudson Institute of Medical Research, Australia
Objective Embryo implantation failure is a major cause of infertility. While IVF is an important intervention of implantation
failure, the critical regulators remain to be defined. The role of

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IS-WS-9-3
C/EBPβ, but not Hif1α, regulates Vegf gene expression in
granulosa cells undergoing luteinization during ovulation after the LH surge in female rats Masahiro Shinagawa, Isao
Tamura, Ryo Maekawa, Yuichiro Shirafuta, Maki Okada,Toshiaki Taketani, Hiromi Asada, Hiroshi Tamura, Norihiro
Sugino Yamaguchi University
Objective Vascular endothelial growth factor（Vegf）expression
is increased in granulosa cells（GCs）undergoing luteinization
after the LH surge and Vegf plays an important role in rapid
vascularization after the LH surge, which contributes to corpus
luteum formation. We investigated transcriptional regulation of
Vegf in GCs undergoing luteinization. Especially, we focused ontranscription factors, HIF1α and C/EBPβ, which are involved inangiogenesis. Methods GCs were obtained from rats treatedwith equine chorionic gonadotropin（CG）before（0h）and 4, 8,
12, 24h after human（h）CG injection. 1）Vegf mRNA levels（RTPCR）, 2）HIF1α and C/EBPβ protein expressions（Western blot）,
3）binding activities of C/EBPβ to the Vegf promoter region（ChIP assay）,4）transcriptional activity of C/EBPβ binding site
（Luciferase assay）,5）histone modifications（ChIP assay）andchromatin structure（FAIRE qPCR）in the Vegf promoter region were analyzed. Results 1）Vegf mRNA levels were gradually increased and reached a peak at 12h. 2）HIF1α protein expressions were not detected. The protein levels of C/EBPβ wereincreased at 12h. 3）The binding activities of C/EBPβ were increased at 12h. 4）C/EBPβ binding site of the Vegf promoter had
a transcriptional activity. 5）The levels of H3K9me3 and H3K27
me3, which are transcription repressive markers, were significantly decreased at 12h, and the chromatin structure became
looser compared with 0h. Conclusion We found for the first timethat C/EBPβ, but not HIF1α, regulates Vegf gene expression bybinding to and altering the chromatin structure of the promoter
region in GCs undergoing luteinization after the LH surge.

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Activation of Endoplasmic Reticulum Stress in Granulosa
Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis Nozomi Takahashi1, Miyuki Harada1,
Yasushi Hirota1, Osamu Yoshino2, Gentaro Izumi1, Tetsuya

Hirata1, Kaori Koga1, Osamu Hiraike1, Yutaka Osuga1, Tomoyuki
Fujii1 The University of Tokyo 1, University of Toyama 2
Objective Given the emerging role of unfolded protein response（UPR）, activated by endoplasmic reticulum（ER）stress, in regulating tissue fibrosis, we hypothesize that ER stress is activatedin granulosa cells（GCs）of PCOS patients, and that activated ER
stress induces ovarian fibrosis by modulating pro fibrotic
growth factor expression in GCs. Methods The study was approved by IRB. mRNA expression of UPR genes and transforming growth factor（TGF）β1 in GCs from PCOS patients were
examined by quantitative RT PCR（qPCR）. Ovarian fibrosis andexpression of UPR and TGF β1 in the ovary of PCOS patientswere examined by Masson trichrome staining（MT）and immunohistochemistry（IHC）. The effects of ER stress inducers andinhibitors on mRNA and protein expression of TGF β1 in cultured human GCs were examined by qPCR and ELISA. The effects of ER stress inhibitors on ovarian fibrosis and ovarian expression of TGF β1 in PCOS mouse model were examined byMT, qPCR, and IHC. Results ER stress was activated in GCs of
PCOS patients and PCOS mouse model, accompanied by interstitial fibrosis and an increase in TGF β1 expression in GCs. ER
stress inducers increased the expression of TGF β1 in humanGCs, which was abrogated by a treatment with an ER stress inhibitor. ER stress inhibitors decreased interstitial fibrosis andcollagen deposition in PCOS mouse ovaries, accompanied by areduction in TGF β1 expression in GCs. Conclusion ER stress in
GCs of PCOS patients contributes to the induction of pro fibrotic growth factors during ovarian fibrosis, and that ER stress
may serve as a therapeutic target in PCOS.

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IS-WS-9-5
M2 macrophages play an essential role for successful implantation in mice Yosuke Ono1, Osamu Yoshino1, Mutsumi Kobayashi1,
Masami Ito1, Azusa Sameshima1, Tomoko Shima1, Yasushi
Hirota2, Akitoshi Nakashima1, Shigeru Saito1 University of
Toyama 1, The University of Tokyo 2
Objective Macrophages（Mφs）play important roles for implantation. Mφs are classified into M1 and M2 Mφs. However it is unknown which type of Mφs play essential roles in implantation.
We investigated the role of M2 Mφs in implantation using CD
206 DTR mice. Methods The localization of CD206+ M2Mφs inuterus was studied by immunohistochemical staining. To deplete M2Mφ, diphtheria toxin（DT）was injected before prior to
implantation period in CD206 DTR female B6 mice mated with
Balb/c male mice. Decidualization was studied by Ki 67 staining and HE staining on day 3.5. Implantation related mRNAs
were evaluated by qPCR on E4.5. Results In WT, CD206+ M2
Mφs were accumulated in uterine stromal lesion at implantation
period. In CD206 DTR mice, the number of implantation was
significantly lower compared to that of WT（1.6±3.6 vs 8.0±
0.7；p＜0.01）,although the serum levels of estradiol and progesterone were similar to those in WT. Furthermore, decidualization at E3.5 such as Ki 67+ stromal cells were completely impaired in CD206 DTR mice. And the mRNAs level of implantation related genes such as LIF, IL 10, Foxp3, IL 15 on E4.5 in
CD206 DTR mice were significantly reduced（p＜0.01）compared to WT, while the implantation failure related TNF αmRNA was increased（p＜0.05）. In M2Mφ depleted mice, breakdown of tolerance by decreased IL 10 and Foxp3, reduced NK
cell differentiation by decreased IL 15, and increased inflammation by accelerated TNF α could reduce the implantation essential cytokine, LIF expression resulting in implantation failure.
Conclusion M2 Mφs are essential for successful implantation.

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IS-WS-9-6
Analysis of obstetric complications and outcomes related to

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long non coding（lnc）RNA in embryo implantation has beenpoorly defined. We identified that the lncRNA, PTENP1（Phosphatase And Tensin Homolog Pseudogene 1）,was reduced inprimary human endometrial epithelial cells（HEEC）
treated withhuman blastocyst conditioned media（BCM）from embryos that
did not implant suggesting a role in implantation. We aimed toinvestigate the function of PTENP1 in embryo adhesion to endometrium, the initiating event of embryo implantation. Methods 1. PTENP1 and PTEN expression in endometrial tissue
across the menstrual cycle（N=8）
was investigated by RT qPCR.
2. PTENP1 was localized in human endometrium using in situ
hybridization（N=5）. 3. A trophoblast cell line（HTR8）spheroid
adhesion assay was used to model implantation（N=4）. 4. miRNA
PCR array and fluidigm analysis was used to determine PTENP
1 targets in HEEC. Results 1. PTENP1 and PTEN levels did notchange across the menstrual cycle. 2. Luminal epithelium
showed the highest expression in mid secretary phase. PTENP
1 was maximal in the stroma in late secretary phase. 3. PTENP
1 silenced HEEC showed less adhesion（reduced by 21±4.0%,
P＜0.001）4. PTENP1 knockdown in HEEC the reduction of 100
miRs. miR 590 3p was augmented after knockdown（2.28±0.23
fold, p＜0.05）. miR 590 3p mimic reduced adhesion（0.58±0.06
fold p＜0.001）. Fluidigm analysis detected reduction of LIF,
RHOA, ALCAM after knockdown. Conclusion Endometrial
PTENP1 has pivotal role in successful implantation.

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singleton pregnancy after embryo transfer using a large
scale perinatal registry in Japan Yusuke Kurokawa, Yutaka
Kozuma, Toshiyuki Yoshizato, Tatsuyuki Kakuma, Kimio
Ushijima Kurume University HospitalObjective The aim of this study was to determine the obstetriccomplications and outcomes related to the singleton pregnancy
after embryo transfer（ET）using the large scale perinatal database in Japan. Methods The subjects were 215,659 cases of singleton pregnancy delivery at ＞22 weeksʼ gestation of the perinatal registry database of the Japan Society of Obstetrics andGynecology between January and December 2015. There were
16,600 cases of pregnancies after ET（ET group）and 199,059
cases of spontaneous conceptions（SC group）without ovulationinduction, artificial insemination with husbandʼs semen or ET.
After patientsʼ background characteristics extracted from a univariate analysis between both groups, a multivariate logistic regression analysis was performed to determine obstetric complications and outcomes related to ET. The significance was set at
P＜0.05. Results The independent factors related to the singleton pregnancy after ET were maternal and fetal complications
including pregnancy induced hypertension（OR：1.18, 95% CI：
1.09 1.27）, atonic bleeding（OR：1.37, 95% CI：1.28 1.46）,blood
loss at delivery（OR：2.79, 95% CI：1.50 4.93）and placenta andcord abnormalities including placenta previa（OR：1.28, 95%
CI：1.13 1.45）, low lying placenta（OR：1.27, 95% CI：1.09
1.47）,placenta accreta（OR：3.23, 95% CI：2.73 3.84）,velamentous cord insertion（OR：2.14, 95% CI：1.88 2.41）, and marginal
cord insertion（OR：1.44, 95% CI：1.35 1.55）. Conclusion The
extracted factors were in part related to abnormal implantation,
which remains to be elucidated whether ET itself or the maternal background necessary for ET is associated.

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IS-WS-9-7!

Mdm2 p53 axis is a key machinery of ovulation Hirofumi
Haraguchi, Yasushi Hirota, Leona Matsumoto, Mitsunori
Matsuo, Takehiro Hiraoka, Shun Akaeda, Tomoki Tanaka,
Yutaka Osuga, Tomoyuki Fujii The University of Tokyo HospitalObjective Physiological roles of tumor suppressor p53 in theovary remain unclear. Mdm2 is the negative regulator of p53,
and Mdm2 deletion increases p53 expression. We establishedmice of ovarian Mdm2 deficiency to clarify the influence of excessive p53 on ovarian function. Methods We generated micewith deletion of ovarian Mdm2（KO）and Mdm2/p53（DKO）byusing Pgr Cre mice. These mice were mated with wild typefertile males, and reproductive phenotype of KO and DKO mice
were evaluated. Microarray analysis and qPCR using mouse cumulus cells（CC）, and ChIP assay using human granulosa cellline were performed. Results KO mice were infertile due to ovulation failure. In KO mice with superovulation treatment, cumulus cell oocyte complex（COC）expansion and oocyte maturation
were compromised, and numbers of ovulated eggs were markedly decreased. In contrast, DKO were fertile with normal COC
expansion and ovulation. Expression of orphan nuclear receptor
steroidogenic factor 1（SF1）, a well known regulator of ovarianfunction, in CC was not reduced in DKO mice but in KO mice. In
addition, p53 was recruited to an SF1 promoter region upon exposure to Nutlin 3, an Mdm2 inhibitor. Conclusion Ovarian deficiency of Mdm2 caused infertility due to ovulation failure via p
53 induction, and Mdm2 p53 axis in ovarian granulosa cells
regulated SF1 transcriptionally, indicating the importance ofovarian Mdm2 p53 SF1 pathway in female fertility. Our findings might help better understanding of human infertility, since
p53 inducers such as smoking, obesity, aging, chemotherapy andradiotherapy are linked to the disruption of ovarian function
and infertility.

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IS-WS-9-8
A National Survey of Cryopreservation of Embryos, Oocytes,
and Ovarian Tissue for Cancer Patients Miyuki Harada1,
Yuko Sanada1, Mayuko Kanatani1, Gentaro Izumi1, Tetsuya
Hirata1, Nao Suzuki2, Kenichiro Morishige3, Minoru Irahara4,
Daisuke Aoki5, Yutaka Osuga1, Tomoyuki Fujii1 The Universityof Tokyo 1, St. Marianna University School of Medicine 2, Gifu University 3, Tokushima University 4, Keio University 5
Objective To determine the reality of cryopreservation of embryos, oocytes, and ovarian tissue in childhood, adolescent, andyoung adult cancer patients in Japan. Methods Six hundred andthirteen JSOG certified ART institutions were sent questionnaires on the experience of cryopreservation for cancer patients
between Jan. 2011 and Dec. 2015. Subsequently, the institutions
conducting the cryopreservation for cancer patients were sent
the second questionnaires. The present survey was conducted
as a part of the AMED project Development of the infrastructure of oncofertility in Japan and the research protocol was approved by local IRB. Results We received 481 replies（78.5% of
613 institutions）.Among them, 126（26.2%）conducted the cryopreservation for cancer patients. At 108 institutions replied tothe second questionnaires（recovery rate：85.7%）, 1,085 cases ofembryo or oocyte cryopreservation and 122 cases of tissue cryopreservation were conducted. More than 70% of them werebreast cancer patients, followed by patients with hematologicalmalignancy. The median number of patients in each institution
was 4 and 2 for breast cancer and hematological malignancy, respectively. Indication for cryopreservation and age limitation
varied between institutions. Three hundred and sixteen embryos and 19 oocytes were already thawed and transferred withresulting pregnancies, while no pregnancy was observed in 7
cases undergoing ovarian tissue transfer. Conclusion The present study shows that over 1,000 embryos or oocytes and over
100 ovarian tissues were cryopreserved for cancer patients inJapan. It is urgently needed to establish a national registration
system to evaluate the safety and efficacy of the current management.

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IS-WS-10-1
Comprehensive analysis of trophoblast lineage cells from human induced pluripotent stem cells（hiPSCs） Nanae
Tsuchida1, Hidenori Akutsu2, Junya Kojima1, Hiroe Ito1, Naoaki
Kuji1, Keiichi Isaka1, Hirotaka Nishi1 Tokyo Medical University 1,
National Research Institute for Child Health and Development 2
Objective Human induced pluripotent stem cells（hiPSCs）
treated with bone morphogenetic protein 4（BMP4）can differentiate into extra embryonic tissue. However, the differentiatedcells are heterogeneous, which include trophoblast（TB）and
mesoderm lineage cells. In order to gain further understandingof early TB differentiation, we collected TB cells using a pan
trophoblast marker, KRT7, and performed comprehensive gene
expression analysis. Methods Four types of hiPSCs（menstrual
blood, two types of uterine endometrium and placental artery
endothelium）from four patients were investigated. The hiPSCs
were treated with 50ng/ml of BMP4 and differentiated into TB
lineage cells. Next, we performed immunofluorescence analysis
to confirm the expression of KRT7. We collected KRT7 positive
cells using flow cytometry and performed microarray analysis
to examine the transcriptome states. We further carried out
gene ontology and pathway analysis to compare the gene expression patterns of hiPSCs and differentiated TB lineage cells.
Results KRT7 was expressed in the BMP4 mediated differentiated cells. Microarray analysis demonstrated that 833 upregulated genes were commonly expressed in all the four hiPSC
groups. Of the 259 upregulated genes commonly expressed in
the four differentiated groups, some TB specific genes, such as

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CGA, CGB, and syncytin2, were identified. Cluster analysis revealed that most gene clusters were divided into two groups：
hiPSCs and KRT7 positive cells. Conclusion To the best of ourknowledge, this is a first report of comprehensive gene expression analysis of TB lineage cells derived from different types of
hiPSCs. The results suggest that the upregulated genes may
play an important role in early placental development.

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The hemodynamic influence of twin twin transfusion syndrome on diastolic function in recipient twins：Insight into
pathophysiology Mayumi Takano1, Masahiko Nakata1, Sumito
Nagasaki1, Junya Sakuma2, Sadanori Kasai2, Rei Ueyama1, Eijiro
Hayata2, Ayako Oji2, Toshimitsu Maemura2, Mineto Morita1 Toho
University 1, Toho University Omori Medical Center 2
Objective This study was aimed to assess the ventricular fillingpressure in twin twin transfusion syndrome（TTTS）and the impact of fetoscopic laser photocoagulation（FLP）by using E/eʼwith Dual gate Doppler method. The relationship between recipientʼs amniotic fluid N terminal prohormone brain type natriuretic peptide（NT proBNP）and E/eʼ was also investigated.
Methods This is a prospective study involving TTTS patients
who underwent FLP for TTTS between 2015 and 2017. Ultrasonography was performed within 24 hours before and 4 7 days

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Fetal baroreceptor activity in preterm fetal sheep withlipopolysaccharide induced endotoxemia Hyo Kyozuka,
Tsuyoshi Hiraiwa, Shun Yasuda, Keiya Fujimori Fukushima
Medical University
Objective The aim of this study was to investigate the effect oflipopolysaccharide（LPS）induced endotoxemia on fetal baroreceptor activity in chronically instrumented preterm fetal sheep.
Methods The changes in fetal baroreceptor activity were measured in six chronically instrumented preterm fetal sheep atdays 111 120. Endotoxemia was induced by LPS injection into
the amniotic cavity on postoperative days 5 and 6. Fetal baroreceptor activity and fetal heart rate（FHR）were each measured
during three phases（A, control phase；B, acute phase；and 3,
fetal acidosis phase）. Baroreceptor activity was determined by
the ratio of fetal FHR decrease to mean arterial pressure increase. Results Severe chorioamnionitis was confirmed histologically in all cases. Baroreceptor activity was measured a total number of 136 times in this experiment（A, n=63；B, n=54；
and C, n=19）. There was no significant difference regarding
FHR at the time of phenylephrine injection at 3 points（A, 172［3.3］bpm, B, 176［4.3］bpm, and C, 162［4.7］bpm. p=0.14）. However, the baroreceptor activity showed significant differences at
3 points（A, 2.7［0.2］；B, 2.5［0.2］；and C, 1.6［0.1］.p＜0.05）. Post
hoc test showed that baroreceptor activity in the fetal acidosis
phase significantly decreased compared to that in the control
phase. Conclusion Baroreceptor activity decreased without
FHR change during fetal deterioration induced by LPS. These
data suggest that intra uterine infection may mask variable decelerations or late decelerations

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Trial for a new fetal assessment by ultrasound guided photoacoustic measurement of placental oxygen saturation
Kiguna Sei, Hidenori Sasa, Kenichi Furuya National Defense
Medical College
Objective The sensitivity for fetal hypoxia of fetal heart rate
（FHR）monitoring has been questioned. Blood oxygen saturationin placenta（PlO2）might provide more objective information
about fetal oxygenation than FHR. We performed real time
low invasive measurement of PlO2 by ultrasound guided photoacoustic（PA）technique. Methods Established hypoxia rabbit
model was applied to seven pregnant rabbits in 28 gestationalday. Fetal hypoxia was made by changing maternal respiration
rate and normal, hypoxia, and recovery phase were set. Continuous observation of FHR, fetal tissue oxygen saturation by nearinfrared spectroscopy（NIRS）, and PlO2 by PA technique were
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Analyses of FHR parameters and dynamics in normal fetuses
according to reactivity related to fetal movement Jeongkyu
Hoh, Eun Saem Choi, Ji Hyun Keum, Young-Sun Park Hanyang
University of Korea, Korea
Introduction The reactive non stress test（NST）notice the increase of fetal heart rate（FHR）by more than 15 beats/min for
longer than 15 seconds following fetal movements, but FHR dynamics according to reactivity related to fetal movement have
not yet been identified. Objective To compare and analyze differences in antepartal FHR parameters, non linear indices andpregnancy outcomes in fetuses proven to be normal after delivery according to the reactivity as a result of NST and fetal
movement（FM）. Methodology/process We surveyed 3,295
NST data acquired using a computerized FHR analysis system.
First, subjects were divided into two groups by the reactivity asa result of NST（reactive（R）cases, n=1,720 vs non reactive（NR）
cases, n=1,575）. Second, each two groups were divided into
three groups according to FM：group1（NR, FM=0）, group2（NR, FM=1）, group3（NR, FM＞=2）, group4（R, FM=0）, group
5（R, FM=1）, and group6（R, FM＞=2）.Neonatal outcomes werecompared, and FHR parameters analyzed using computerized
fetal monitoring system. Non linear analysis was performed using approximate entropy, ApEn；sample entropy；SampEn,
and correlation dimension；CD. Results/outcome FHR parameters（mean FHR, FHR variability, Acceleration, and Deceleration）of group3 were the highest among NR groups（p＜0.01）,
and FHR parameters of group6 were the highest among R
groups（p＜0.01）. The correlation coefficients between FM andFHR parameters were statistically significant（p＜0.01, respectively）. However, nonlinear indices among NR group（ApEn,group1=0.92±0.13 vs. group2=0.92±0.13 vs. group3=0.91±
0.14；p＞0.05）and those among R group（ApEn, group4=0.88±0.16 vs. group5=0.89±0.15 vs. group6=0.89±0.15；p＞0.05）
were not statistically different. The correlation coefficients between FM and nonlinear indices were not statistically significant（p＞0.05, respectively）. There were no statistically significant differences of perinatal outcomes among 6 groups. Conclusion The heart rate dynamics of fetuses are not affected by fetal
movement and they are coincidence with fetal and perinatal
outcomes.

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after FLP. The Z score for E/eʼ was calculated by using reference ranges of our previous study. Amniotic fluid samples wereobtained from recipientʼs sac at the time of FLP, and NT
proBNP/total protein ratio was assessed. Results There were 34
cases. Left ventricular（LV）E/eʼ of recipients in stage 1, 2 was. RV E/eʼ of resignificantly higher than that of donors（p ＜0.05）
cipients was elevated in stage 3d and 3r than where in stage 1, 2
. Amniotic fluid NT proBNP was elevated in 3d and（p ＜0.05）, and significantly higher NT proBNP
3r, respectively（p ＜0.05）
was observed if recipientʼs RV E/eʼ was more than 1.5 of Zscore（3,475 ng/g vs. 530 ng/g, p =0.008）.Both LV and RV E/eʼ
. Conof recipients significantly decreased after FLP（p ＜0.05）
clusion Recipient heart demonstrates the increase of fillingpressure in LV at first, followed by the increase in RV, which isresulted in amniotic fluid NT proBNP elevation. FLP decreased
these elevated biventricular filling pressure within a week, reflecting improvement of pathophysiology of TTTS in recipients.

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est（ROI）was set in placenta and maternal tissue. Oxygen saturation of each ROI was calculated from PA signals by the external standard method whose accuracy was proved in our previous study. Results The real time PA measurement was successfully performed. The average PlO2 in the normal phase was 57.8
±13.9%, which corresponded to the data in literatures. The recovery of PlO2 in the recovery phase was observed by PA technique while maternal tissue oxygen saturation and the other index by FHR and NIRS deteriorated. Conclusion The result demonstrated that PlO2 might reflect fetal blood information directly because PA technique could extract the data of placenta
due to its high spatial resolution. PA imaging technique can beapplied to objetvs such as umbilical vessels and fetal sagittal sinus by transvaginal detect. PA imaging would be a new device
for quantitative fetal assessment and analysis of fetal physiology.

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IS-WS-10-6
Fetal microglia changes by maternal immune activation
Kana Ozaki1, Hiroaki Wake2, Hideto Yamada1 Kobe University 1,
Division of Neuroscience, Kobe University 2
Objective Maternal immune activation（MIA）triggers developmental disorders and psychiatric diseases, but the mechanism of
MIA for affecting on the fetal brain has not been elucidated. In
this research, we focused on microglia, sole immune cell in central nervous system, and revealed the difference of motility andmorphology of microglia between brain with MIA and wild type（WT）in live fetal mice, using in vivo two photon microscope.
We furthermore showed the neuronal firing alteration in postnatal mice from MIA mice associated with the changes of fetal microglia. Methods Pregnant mice, of which fetal microglia were
specifically labelled by GFP, were intraperitoneally injectedwith 10mg/kg of polyinosinic polycytidylic acid［poly（I：C）］
at embryonic days 15（E15）to cause MIA. GFP labelled microglia were visualized with two photon microscope, and their dynamic changes were analyzed at E17 in live fetuses. After image
acquisition, fetal brains were fixed and sectioned to analyze distribution and morphology of microglia. Results The velocity offetal microglia was increased after poly（I：C）injection in vivo .
The cell body area（52.4±18.1 μm2）of microglia with MIA（n=155）was smaller（p=1.59×10!40）than that（90.4±22.5 μm2）of
WT（n=127）. The process length（95.9±42.0 μm）of microglia
with MIA（n=23）was longer（p=0.0085）than that（70.4±34.1μm）of WT（n=31）. These data suggest microglia of MIA mice
have more matured phenotype of their motility and morphology.
Conclusion MIA may be causally associated with developmental disorders and psychiatric diseases through changes in function and morphology of fetal brain microglia.

IS-WS-10-7
Mesenchymal stem cell can induce offspringʼs immune tolerance against non inherited antigens in murine Maternal to
Fetal microchimeric model Aiko Okada1, Masayuki Endo1, Kei
Sasano1, Yoko Kawanishi1, Takao Owa1, Etsuko Kajimoto1,
Hiroko Tanaka1, Aiko Kakigano1, Kazuya Mimura1, Takuji
Tomimatsu1, Katsuto Tamai2, Tadashi Kimura1 Osaka University 1, Stem Cell Therapy Science, Osaka University 2
Objective Recent studies revealed that there are mutual cell migrations including hematopoietic stem cells（HSCs）and mesenchymal stem cells（MSCs）through the placenta between motherand fetus. In this study, we investigated allogenicl MSCs can induce immune tolerance in utero to proteins specifically expressed in MSCs and their lineages. Methods We evaluated immune reaction after syngeneic skin graft in three chimeric models. The recipient was C57BL/6（WTB6）mice. As donor cells,
we firstly used HSCs, MSCs and Lineage positive（Lin+）cells,!

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which are not stem cells, isolated from bone marrow cells（BMCs）of C57BL/6TgN（act EGFP）（B6GFP）mice, which all
express GFP.The second donor HSCs and MSCs were isolated
from BMCs of PDGFRa H2BGFP mice, which only express GFP
in MSCs, but not in HSCs. These cells were injected intravenously into neonatal recipient mice. Finally, we applied a mouse
F1 backcross bleeding model（B6 males x PDGFRa H2BGFP females）, as maternal to fetal microchymeric model. Results In
B6GFP model, HSCs and MSCs transplantation induced both humoral and cell mediated immune tolerance against GFP, but
Lin+ cells didnʼt. In PDGFRa H2BGFP model, MSCs transplantation induced both humoral and cell mediated immune tolerance against GFP, but HSCs didnʼt. In F1 model, successful engraftment was observed in 15% of the recipient mice until 20
weeks. Conclusion It is necessary to be exposed stem cells suchas HSCs or MSCs, rather than non stem cells to induce immune
tolerance. Furthermore, MSCs rather than other stem cells
should present to induce immune tolerance in utero to proteinsspecifically expressed in MSCs and their lineages.

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The impact of the Great East Japan Earthquake on obstetriccomplications：results from the Fukushima Health Management
SurveyTsuyoshi Murata, Hyo Kyozuka, Tsuyoshi
Hiraiwa, Shun Yasuda, Akiko Yamaguchi, Keiya Fujimori
Fukushima Medical University
Objective This study aimed to assess the effects of the Great
East Japan Earthquake on obstetric complications. Methods We
used the results of the Fukushima Health Management Survey.
Pregnant women were divided into three groups according totheir residence during the disaster（affected area：n=2,207, middle area：n=5,183, and less affected area：n=933）. Adjusted
odds ratios（aORs）for preterm birth（PTB）＜37 weeks, threatened PTB, low birth weight＜2,500g, pregnancy induced hypertension（PIH）, and gestational diabetes mellitus（GDM）were
calculated using a logistic regression model. Leaving residence
area and trimester at the time of the disaster were used as reference. Results The affected area was not a significant factor for
any obstetric complications. However, the middle area was related to LBW＜2,500g（aOR：0.74, p＜0.05）and GDM（aOR：2.50,
p＜0.05）compared to the less affected area, after accounting forseveral factors. With regard to maternal gestational age, being
in the second trimester at the disaster was a significant risk factor for threatened PTB（aOR：1.84, p＜0.05）when compared tothe pregnancies conceived after the disaster. Similarly, being in
the third trimester at the disaster was a significant risk factor
for PIH（aOR：1.80, p＜0.05）. Conclusion Living in the affectedarea at the disaster was not a significant risk factor for obstetriccomplications. However, maternal gestational age at the time ofthe disaster may affect the occurrence of obstetric complications.

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IS-WS-10-9
Efficacy of maternal screening and perinatal prevention program for hepatitis B Tokuro Shirakawa1, Yuuki Sasagawa1,
Masashi Deguchi1, Kenji Tanimura1, Mayumi Morizane1, Ichiro
Morioka2, Hideto Yamada1 Kobe University 1, Department of Pediatrics, Kobe University 2
Objective The aim of this study is to assess the effect of maternal screening for HBV and perinatal HBV prevention program.
Methods With approvals from institutional ethics boards, thisstudy was performed prospectively. 3,102 pregnant women delivered at our hospital between Jul. 1, 2008 and Jun. 30, 2015 andtheir neonates were participated in this study. HBs antigen（HBsAg）was measured during the first trimester as a maternal
screening. HBe antigen（HBeAg）was measured for the HBsAg

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IS-WS-11-1
Amenorrhea in female athletes deteriorates bone microarchitecture of cortex Yuriko Kitajima1, Shizuka Ogawa2, Naoko
Murakami1, Michio Kitajima1, Kiyonori Miura1, Hideaki
Masuzaki1 Nagasaki University 1, Marusan Ai Co., LTD 2
Objective Young female athletes may suffer from disturbed energy availability, hypothalamic amenorrhea, lower bone density,
which are designated as female athlete triad. In this study, weevaluated the microstructure of bone using HR pQCT in female
athletes. Methods Nineteen female long distance runners or
rhythmic gymnastics athletes and 29 non athlete（control）withcomparable age（15 23y）were allocated for this study. We performed questionnaire survey to obtain menstrual history. Bonedensity of lumbar and femur was measured by dual energy x
ray absorptiometry（DXA）. Bone microarchitecture of radius
and tibia was measured by HR pQCT. Results Although theheight were not significantly different, BMI in athletes were significantly lower than control（18.4 vs. 20.6kg/m2, p＜0.01）. Ageof menarche in athletes was significantly older than control（14.5
vs. 12.9y, p＜0.01）.In addition, 73.7% of athletes showed irregular menstrual cycles despite 6.9% in control（p＜0.01）. Bone density of lumbar and femur measured by DXA were not significantly different in each group. Cortical bone density in radius
and in tibia were significantly lower in athletes than control（880.4 vs. 920.9mg/cm3, p＜0.03；935.2 vs. 956.5mg/cm3, p＜0.01,
respectively）, but not trabecular bone density. Cortical porosityof athletes was significantly increased comparing to control inradius（0.34 vs. 0.2%, p=0.01）. Cortical thickness of athletes was
significantly thinner than control in radius（0.93 vs. 1.05mm, p＜0.02）. Conclusion Even the bone density measured by DXA
may not show significant changes, bone microarchitecture ofcortex can be deteriorated in amenorrheic athletes. HR pQCT
may be useful to evaluate the bone stiffness of female athletes.

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Bone mineral density in premenopausal women is associatedwith antioxidant nutrient intake Tamami Odai, Masakazu
Terauchi, Asuka Hirose, Naoyuki Miyasaka Tokyo Medical and
Dental University
Objective Although the intake of calcium, vitamins D, and K are
known to be positively associated with bone mineral density（BMD）,the effects of other nutrients on BMD are yet to be elucidated. The aim of the current study was to investigate the relationship between the consumption of a variety of nutrientsand BMD in middle aged women. Methods In 279 middle aged
women, lumbar spine BMD（L2 4）was measured with dual energy X ray absorptiometry（DEXA）, and the dietary habitswere assessed with brief type self administered diet history
questionnaire（B DHQ）from 2009 to 2016. 117 women treatedwith estrogen or anti osteoporosis drugs were excluded. Divid-

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ing the remaining 162 women（204 DEXA measurements）into
pre and postmenopausal groups, the correlation between their
BMD and the intake of 97 nutrients were investigated separately. Results 47 women（48 DEXA measurements）were premenopausal and 117 women（156 DEXA measurements）were
postmenopausal. Their average age（years）was 49.3±2.8 and58.5±7.6（mean±SD）,and the BMD（g/cm2）was 1.123±0.180
and 0.988±0.148, respectively. The daily intake amount of calcium, α tocopherol, and cryptoxanthin was positively correlatedwith BMD in premenopausal women（r=0.2958, 0.3136, 0.3826, p＜0.05）, but not in postmenopausal women. Conclusion Oxidative stress has been linked to bone loss through the increase inbone resorption and the formation of abnormal collagen crosslinks. In the current study, we found that BMD in premenopausal women were associated with not only calcium but also
antioxidant nutrients, namely α tocopherol and cryptoxanthin.
This result suggests that the health diet rich in antioxidant nutrients may contribute to the preservation of bone mass inwomen before menopause.

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The Evaluation of Efficiency of CRISPR/Cas9 System in Generating Fibulin 5 Knockout Mice Kohei Kitada1, Masami
Hayashi2, Aki Takase2, Natsuko Yokoi2, Hiroko Katayama2,
Akihiro Hamuro2, Akemi Nakano2, Takuya Misugi2, Daisuke
Tachibana2, Masayasu Koyama2 Izumiotsu Municipal Hospital 1,
Osaka City University 2
Objective The aim of this study was to generate fibulin 5
knockout mice, which were known for the model of pelvic organ
prolapse, by CRISPR/Cas9 system and to evaluate the efficiencyof this method. Methods To design single guided RNA for
CRISPR/Cas9 system, we selected Cas9 target sites in thefibulin 5 gene. We searched for 20 nucleotide sequences infibulin 5 gene followed by the protospacer adjacent motif（PAM）sequence（NGG）after the translational start site（ATG）.
C57BL/6 female mice were superovulated and mated with C57
BL/6 males, and fertilized embryos were collected from the oviduct. The pronuclear stage embryos were injected with pX330
plasmid and single guided RNA. The embryos were cultivatedthen transferred into the oviducts of pseudopregnant ICR females. We extracted DNA from mouse tail and analyze genotype by DNA sequencing. Results We obtained 29 mice（16 maleand 13 female）, and gene mutation of fibulin 5 was introducedin 58.6% of mice（17/29, 8 male and 9 female）. In the fibulin 5
gene mutation mice, homozygous mutation was found in 53%（9/17）. We chose 2 female mice which had homozygous typefibulin 5 mutation and mated with C57BL/6 male mice. Afterdelivery, rectal prolapse was found in all mice. Conclusion
Fibulin 5 gene mutation mice ware obtained efficiently by
CRISPR/Cas9 system and almost half of mutation mice were homozygous mutation.

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IS-WS-11-4!

A genome wide association study identifies 10 new susceptibility loci for uterine leiomyoma in Japanese population
Kensuke Sakai1, Akira Hirasawa2, Wataru Yamagami2,
Nobuyuki Susumu3, Mamoru Tanaka2, Daisuke Aoki2, Koichi
Matsuda1 The Institute of Medical Science, The University ofTokyo 1, Keio University 2, International University of Health andWelfare 3
Objective Uterine leiomyoma is a common benign gynecologic
tumor occurring up to 30% of women population. Nevertheless,the pathogenesis of this tumor still stays unclear. We conducteda genome wide association study to elucidate the pathogenesis.
Methods In this study, we conducted a genome wide association study in which 951,117 SNPs were analyzed in 5,720 indi-!

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positive patients. All neonates delivered from HBsAg positive
women were given HBIG and HB vaccine based on the Japanese
HBV prevention program after birth. Results Of 3,102 pregnant
women, 33 were positive for HBs antigen. 10 of the 33 were positive for HBe antigen. Two exacerbation cases were observed
among the patient with positive for HBeAg, HBsAg and HBeAg,
AST, ALT and HBV DNA titers increased in both exacerbation
cases. HBV prevention program was accomplished for all neonates, and consequently, vertical infection was not observed.
Conclusion We find that perinatal HBV prevention program isso effective. HBsAg, HBeAg, AST, ALT and HBV DNA titers
seem useful for evaluating patient,s condition, but it seems difficult to predict exacerbation by these factors. Careful follow up
is necessary to exclude exacerbation, for the women with
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viduals with clinically diagnosed uterine leiomyoma and 17,492
female controls in the screening stage. After the quality controlof the genotyping data and the imputation using 1,000 Genome
project phase 1 dataset, we further analyzed the association of
7,521,072 SNPs. A total of 3,830 SNPs with P＜1×10!4 in the firstscreening were further analyzed using an independent casecontrol set consisting of 8,026 individuals with previous historyof uterine leiomyoma and 52,824 controls those were genotyped
with illumina Omni express exome BeadChip. A meta analysisof the screening step and the replication step identified 13
genomic loci with P value of ＜5×10!8（genome wide significance）. Results Three genomic loci（chromosome 10, 11, 22）
were previously reported, and we identified 10 novel loci：chromosome 1, 2, 3, 4, 5, 7, 8, 12 and 13. One SNP on ch 1 is locatedwithin the estrogen receptor（ER）binding site. Because estrogenis known to be the most critical regulator of leiomyoma, thisSNP could potentially regulate target genes and play an important role in the pathogenesis of uterine leiomyoma. Conclusion
These 13 genomic loci should contribute to elucidate the pathogenesis of uterine leiomyoma.

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IS-WS-11-5
A novel approach to treat endometriosis via targeting epithelial mesenchymal transition Hirotaka Masuda1, Masataka
Furuya2, Tetsuo Maruyama1, Fumie Miki1, Satomi Katakura1,
Yushi Yoshimasa1, Sayaka Uchida1, Hiroshi Uchida1, Tomoka
Takao1, Hidetaka Katabuchi3, Mamoru Tanaka1, Daisuke Aoki1
Keio University 1, Rose Ladies Clinic 2, Kumamoto University 3
Objective Endometriosis shares some malignant features suchas invasion and metastasis despite its benignancy. These features are thought to be involved in epithelial mesenchymaltransition（EMT）. This study sought to investigate EMT statuses in endometriosis and drug potency of an EMT inhibitor.
Methods Ten endometriosis, nine adenomyosis and seventeen
non endometriosis patients undergoing surgery for benign indications were recruited. We examined the expression of E cadherin, N cadherin, vimentin and EMT induced transcriptional
factors（Snail and ZEB1）
in epithelium of each type of endometriotic lesions and normal endometria by immunohistochemical
scoring. The western blot analysis was employed to assess EMT
induction of TNFα and TGFβ on cultured endometrial epithelial
cells（cEECs）. An inhibitory effect of an EMT inhibitor was
evaluated by wound healing assay. Results N cadherin and
Snail were preferentially expressed in deep infiltrating endometriosis（DIE）and ovarian endometrioma（OVE）. Vimentin
expression level was significantly higher in eutopic endometria
of endometriosis patients compared to non endometriosis
women. E cadherin staining showed isolated/scattered pattern
in DIE and adenomyosis. ZEB1 was only expressed in endometriotic lesions, especially DIE and adenomyosis, but not in
eutopic endometria. Western blot analysis demonstrated cadherin switch in cEECs, which indicated EMT was easily provoked by TNFα and TGFβ in cEECs. Wound healing assay revealed that the EMT inhibitor reduced the migration ability ofcEECs. Conclusion The differential EMT status of each endometriotic lesion may indicate different etiology or pathophysiology according to the type of lesions. The EMT inhibitor could
be the first non hormonal drug without anovulatory effect,
which confers tremendous benefits to infertility women.

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zonokuchi
Objective To evaluate the use of a hysteroscopic morcellator
system in terms of the operating time, surgeonʼs convenience,and effect on patients in comparison with the performance of
conventional electrosurgical resection in the hysteroscopic resection of submucosal uterine fibroids. Methods Patients undergoing hysteroscopic resection of submucosal uterine fibroids
were randomly allocated to undergo either hysteroscopic morcellation or electrosurgical resection after obtaining the approval from the institutional review board. The primary outcome was the operating time. Secondary outcomes were the removal success, fluid deficit, convenience associated with thetechnique, visibility of the operative field, recurrence of the patientʼs chief complaint, and adverse events. Results Ten women
were randomly allocated to either the morcellation arm（n=5）orthe electrosurgical resection arm（n=5）from November 2015 toNovember 2016. The fibroids were completely removed in all
patients（100%）of the morcellation arm and in two patients（40%）of the electrosurgical resection arm. The average operating time（15.8 minutes vs. 27.7 minutes, P=0.149）tended to belower in the morcellation arm than in the electrosurgical resection arm. Surgeonsʼ subjective evaluation measured on a 10 cm
visual analog scale was higher in the morcellation arm than in
the electrosurgical resection arm in terms of ease of removal（8.4
vs. 6.2, P=0.010）and visibility of the operative field（8.8 vs. 5.7,
P=0.010）. Conclusion In the resection of submucosal uterine fibroids, the use of a hysteroscopic morcellator system in comparison with electrosurgical resection received a higher evaluation score from surgeons, and may shorten operating time.

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IS-WS-11-6
Intraoperative and postoperative clinical evaluation for hysteroscopic resection of submucosal uterine fibroids with ahysteroscopic morcellator system Akira Tsuchiya, Yasunori
Komatsu, Michiko Honda, Hiroko Tsuchiya, Reiko Matsuyama,
Akihisa Fujimoto, Osamu Nishii Teikyo University Hospital, Mi-

IS-WS-11-7
Expression of Müllerian inhibiting substance receptor and antiproliferative effects of MIS on human adenomyosis tissue
Youn Jee Chung, Jae Yen Song, Young Sin Han, Soo Hyun Sim,
Hyun Hee Cho, Hyejin Hwang, Mee Ran Kim, Jang Heub Kim
The Catholic University of Korea, Korea
Objective Müllerian inhibiting Substance（MIS）is known to not
only act as a regulator of female reproductive function but also
inhibits the growth of Müllerian duct derived tumors. But therole of MIS in adenomyosis is unclear. Therefore, this study is
aimed to confirm the expression of MISRII and effects of MIS on
adenomyosis. Methods We gathered the tissues from the 30 patients who had hysterectomy for adenomyosis. We performed
immunohistochemistry with rabbit polyclonal anti human MISRII antibody. The cultured cells were exposed to MIS and MTT
assay. Induction of cell cycle and apoptosis was also observed in
the cells treated with MIS as measured by using DNA PI staining and annexin V binding. The cells were analyzed on a flowcytometer. We evaluated the expression of proteins which is related apoptosis and cell cycle arrest in adenomyosis. Results
MISRII was stained in adenomyosis tissues and The expression
level of MISRII was in the order of weakly, mild, strong positive
and negative. The cultured adenomyosis cells treated with MIS
for 48 and 96 hours significantly exhibited growth inhibition
14.59%, 26.6%（P＜0.05）. It will perform experiments for thechanges in cell cycle distribution and apoptosis related in ashort time. Conclusion The expression of MISRII has difference
between myometrial tissue and adenomyosis. MIS induces G0G1
cellcycle arrest and apoptosis of adenomyosis. These finding
suggest that MIS has a greater role on adenomyosis thanmyometrium in cellcycle inhibition and apoptosis. Therefore,
MIS could be used as a biological modifier or therapeutic agent
for the treatment of adenomyosis.

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Selective cytotoxic effect of non thermal micro DBD plasma
Byung Su Kwon, Hyun Nyung Jo, Kim Yoon Hwa, Ka Yeong
Yun, Sieun Han, Ki Hyung Kim, Dong Soo Suh Pusan National
University Hospital, Korea
Non thermal plasma has been extensively researched as a newcancer treatment technology. We investigated the selective cytotoxic effects of non thermal micro dielectric barrier discharge（micro DBD）plasma in cervical cancer cells. Two human cervical cancer cell lines（HeLa and SiHa）and one humanfibroblast（HFB）cell line were treated with micro DBD plasma.
All cells underwent apoptotic death induced by plasma in adose dependent manner. The plasma showed selective inhibition of cell proliferation in cervical cancer cells compared to
HFBs. The selective effects of the plasma were also observed
between the different cervical cancer cell lines. Plasma treatment significantly inhibited the proliferation of SiHa cells incomparison to HeLa cells. The changes in gene expression weresignificant in the cervical cancer cells in comparison to HFBs.
Among the cancer cells, apoptosis related genes were significantly enriched in SiHa cells. These changes were consistent
with the differential cytotoxic effects observed in different celllines.

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Whole genome analysis of human papillomavirus genotypes
52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer Yuri
Tenjimbayashi1, Yusuke Hirose1, Mamiko Onuki1, Sari Nakao2,
Takashi Iwata3, Koji Matsumoto1, Akihiko Sekizawa1 Showa University 1, University of Tsukuba 2, Keio University 3
Objective HPV52/58 are frequently detected in patients with
CIN and invasive cervical cancer（ICC）in East Asian countries
including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than

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Mieap induces cell death via non canonical mitophagy in human cervical cancer Makoto Yamamoto, Shizuka Yamada,Hideaki Tsuyoshi, Makoto Orisaka, Tetsuji Kurokawa, Yoshio
Yoshida University of Fukui
Objective Canonical mitophagy plays a pivotal role in mitochondrial quality control, which is mediated by the Parkin/Pink1
mediated macroautophagy. Recently, we discovered non canonical mitophagy that is induced by Mieap. Overexpression ofMieap induces large vacuole structures（designated MIV：
Mieap induced vacuole）. MIV eats and degrades cancer specific unhealthy mitochondria. This non canonical mitophagy
leads to cancer cell death via the ROS production and caspase
activation. To clarify the role of Mieap mediated non canonicalmitophagy in cervical cancer, this study was carried out. Methods A total of 70 patients with cervical cancer underwent immunohistochemistry to assess Mieap protein expression. Using
HeLa cells, Mieap was overexpressed by adenovirus infection,and cell death was examined by caspase assay and cytochromec immunostaining. Results Immunohistochemistry of 70 cervicalcancer patients indicated that high level of Mieap expression
was frequently detected in premalignant lesions and early stage
cancers, but not in advanced and invasion cancers. Enforced expression of exogenous Mieap in HeLa cells induced MIVs andcell death. Activation of caspase 3 and 9 were observed, but notthat of caspase 8. In immunofluorescence experiment, cytochrome c was released from the mitochondria throughout thecytoplasm and nucleus of the dying HeLa cell. Conclusion In
cervical cancer clinical specimens, early stage cancer tends toMieap positive. Mieap mediated non canonical mitophagy induces cell death of HeLa cells via mitochondrial apoptotic pathway. These results suggest that Mieap mediated non canonicalmitophagy plays a critical role in cervical cancer tumor suppression via cell death.

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Establishment of a patient derived orthotopic Xenograft（PDOX）model of HER 2 positive cervical cancer expressing
the clinical metastatic pattern Takuya Murata1, Robert
Hoffman2, Mitsuru Shiota1, Koichiro Shimoya1 Kawasaki Medical
School 1, US San Diego Medical Center, USA 2
Objective Patient derived xenograft（PDX）mouse models of!!

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Compare the levels of IL 2, IL 6, IL 10 and IFN γ in cervicallesions tissues and serum of Uyghur and Han women
Mayinuer Niyazi, Gulan Tuohetimulati, Suray Husayin The Peopleʼs Hospital of Xinjiang Uighur Autonomous Region, China
Objective To test the IL 2, IL 6, IL 10, IFN γ and（HPV）L1 inserum from Han and Uyghur screened with HPV（＋）. Methods
The data gathered Uyghur at the Peopleʼs Hospital of Xinjiang
Uyghur Autonomous Region from August of 2013 to June of2015, cervical erosion was determined by HC 2, HPV DNA, andHPV typing technique. the factors analyzed by means of Logistic Regression Analysis, which were severed into several
groups of cervicitis, CIN1, CIN2 3 and cervical carcinoma. The
levels of IL 2, IL 6, IL 10 and IFN γ in serums and cervical tissues was measured. ELISA and Immunocytochemical and IHCA
were applied to inspect 197 specimens with positive HPV. Results The IFN γ in cervical tissues was inversely proportional
to the severity of cervical lesions while the IL 10 was in proportion to cervical lesions, which can be inferred that descended
with an increase of severity of cervical lesions while the otherclimbed up with the severity of that, both had a statistical significance（P＜0.05）. The IL 2 and IFN γ with different grades ofcervical lesions declined with an increase of the severity of cervical lesions while the IL 6 and IL 10 was opposite, which went
up with the severity of cervical lesions, both showed a statisticalsignificance（P＜0.05）. The comparison between Han and Uyghur no statistical differences（P＞0.05）. Conclusion The IL 2
and IFN γ with different grades of cervical lesions declinedwith an increase of the severity of cervical lesions, the IL 6 andIL 10 was opposite to this.

10% differences between complete genome sequences of thesame HPV genotype. However, variations of viral genome sequences have not been fully examined for HPV52/58. The aim of
this study was to investigate genetic variations of HPV52/58
prevalent among Japanese women by analyzing the viralwhole genome sequences. Methods The entire genomic regionof HPV52/58 was amplified by long range PCR with total cellular DNA extracted from cervical exfoliated cells isolated fromJapanese patients with CIN or ICC. The amplified DNA was
subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole genome sequences to assign variant
lineages/sublineages to the HPV52/58 isolates. Results Among
52 isolates of HPV52, 50 isolates belonged to lineage B and two
isolates belonged to lineage A. Among 48 isolates of HPV58, 47
isolates belonged to lineage A and one isolate belonged to lineage C. SNPs specific for individual variant lineages were determined throughout the viral genome based on multiple sequencealignments of the Japanese HPV52/58 isolates and reference
HPV52/58 genomes. Conclusion Among the HPV52/58 positive
specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 andlineage A for HPV58 across histological categories.

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cancer are emerging as an important potential aid to personalized cancer therapy. Subcutaneous transplantation（patient derived subcutaneous xenograft；PDSX）is often used because itis easy to transplant but rarely metastasize. Unlike PDSX, thepatient derived orthotropic xenograft（PDOX）model is known
to metastasize and correlate with what it occurred to cancer patient. HER 2 positive uterine cervical carcinoma consisted of
42% of 136 uterine cervical carcinoma cases in the most recent
report. Its biological feature is not well understood. Methods
The PDSX and PDOX was performed to 10 and 8 nude mice respectively. Growth of primary tumor, tumor take rate, sites andrate of metastasis, histological comparison of primary and metastatic tissue was performed. Results Metastasis was detected
in 4 of 8 nude mice in cased of PDOX but no metastasis was detected in case of PDSX. The sites of metastasis after surgical orthotropic implantation in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph
node metastasis reflecting the metastatic pattern in the donorpatient. Primary tumors and metastases in the nude mice hadhistological structures similar to the original tumor and were
stained by an anti HER 2 antibody in the same pattern as thepatientʼs cancer. Conclusion PDOX model reflect well with cancer patient clinical feature and has a potential to be a goodmodel to achieve personalized cancer therapy.

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CDX2 expression and cancer progression in cervical cancer
Suguru Nosaka, Iemasa Koh, Eiji Hirata, Yoshiki Kudo Hiroshima University
Objective In cervical adenocarcinoma, detection at the stage of
precancerous lesions is difficult, and invasion or metastasis isfrequently detected even at the early stage. Patients with cervical adenocarcinoma have a poorer prognosis than dose withsquamous cell carcinoma, because of resistance to chemotherapy and radiotherapy contributing to high recurrence rates. We
previously reported that in ovarian mucinous adenocarcinoma,
the transcription factor caudal type homeobox 2（CDX2）expression is positive and it transcriptionally regulates multidrug resistance 1（MDR1）expression, leading to drug resistance. We reported that CDX2 expression was observed in tissue specimensof adenocarcinoma in situ（AIS）and intestinal type mucinous
adenocarcinoma. We therefore have examined relation between
CDX2 expression in cytologic specimen and tissue specimen inuterine cervical neoplasia. Methods We applied immunochemical staining to clinical specimens of cervical neoplasia, and examined the correlation between cytochemical staining and histochemical staining. Results In tissue specimens, CDX2 expression was positive at a high rate in AIS sample, and at half in intestinal type mucinous adenocarcinoma sample. CDX2 expression was also positive in cytologic specimens from patients
whose tissue samples are positive for CDX2. Conclusion Our
data suggest that CDX2 expression may influence cancer progression in intestinal type mucinous cervical adenocarcinoma
and that expression of CDX2 in cytologic specimen can be anovel marker for the diagnosis of intestinal type mucinous adenocarcinoma.

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Tumor derived G CSF induces Tumor associated neutrophils（TANs）and suppresses the activation of T cell in cervical cancer microenvironment Naoko Komura, Seiji Mabuchi,
Eriko Yokoi, Katsumi Kozasa, Michiko Kodama, Kae Hashimoto,
Kenjiro Sawada, Tadashi Kimura Osaka University
Objective To investigate the mechanism by which tumor associated neutrophils（TANs）are induced in cervical cancer microenvironment, we conducted in vitro and in vivo analyses.

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Methods［1］The baseline characteristics of FIGO stages IB IVB
cervical cancer patients treated with definitive radiotherapy between January 1996 and December 2011 were collected. We
evaluated the relationships between intratumoral CD66b+ TAN
density and tumor G CSF expression by immunohistochemistry.［2］By inoculating G CSF expressing or Mock expressing
cervical cancer cells into nude mice, we investigated whether
tumor derived G CSF induces TANs in cervical cancer microenvironment using flow cytometry. Finally, using TANs obtained from tumor bearing mice, immunosuppressive activityof TANs was assessed by T cell suppression assay. Results Intratumoral TAN density was positively correlated with the intensity of tumor G CSF expression in cervical cancer patients（p＜0.05）. In mice studies, TANs were more frequently observed in tumor and peripheral blood of G CSF expressing
cells bearing mice than in Mock expressing cells bearing mice
（p＜0.05）. When co incubated, TANs isolated from G CSF expressing cervical cancer bearing mice significantly inhibitedthe proliferation of CD8+T cell in vitro. Conclusion Tumor derived G CSF induces TANs and suppresses the activation of T
cell in cervical cancer microenvironment.

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The clinicopathological characteristics and PD L1 expression in neuroendocrine carcinoma of the cervix Yukihiro
Hirata1, Hirokazu Ozone1, Youko Nagayoshi2, Chikage Narui2,
Hiromi Komazaki3, Noriko Yamaguchi4, Hirokuni Takano2,
Aikou Okamoto2 The Jikei University Kashiwa Hospital 1, The
Jikei University Hospital 2, The Jikei University Katsushika
Medical Center 3, The Jikei Daisan Hospital 4
Objective Neuroendocrine carcinomas of the cervix（NECC）arecharacterized by a high mitotic rate, necrosis, frequent lymphovascular space involvement and a more aggressive clinicalcourse. Clinical treatment relies on operation, chemotherapy
and radiotherapy；relapses are frequent. The Programmed
death ligand 1（PD L1）pathway is a major target of anti tumour immunotherapy. Aberrant PD L1 expression may cause
local immune suppression in NECC. Here, we studied the clinicopathological characteristics and PD L1 expression in NECC.
Methods Tissue specimens were obtained from 15 patients with
NECC who were diagnosed at our hospital from 2007 to 2016.
PD L1 protein expression were analyzed by immunohistochemistry using monoclonal antibodies（E1L3N）. Results We identified a total of 942 patients in cervical cancer including 15（1.5%）
with NECC. FIGO staging was as follows：Stage IB1, n=5；
stage IB2, n=2；stage IIB, n=3；stage IVB, n=5. 10 patientswere pure neuroendocrine carcinoma, 5 patients were mixed
adenoneurocrine carcinoma. The median survival duration was
15 months（range, 1 44）, survival was worse for NECC compared to squamous cell carcinoma and adenocarcinoma. PD L1
positivity was observed in 60% of the NECC. No correlations
were observed between the clinical parameters and PD L1 protein expression. The PFS and OS did not correlate significantlywith PD L1expression. Conclusion We found that NECC is arare and aggressive type of cervical cancer that is generally associated with poor survival. Further studies of PD L1may generate insights into the biological characteristics that drive theclinical behavior of NECC.

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Research on early warning factors of cervical carcinomas
and precancerous lesions Suray Husayin, Gulan Tuohetamurat,
Mayineur Niyazi The Peopleʼs Hospital of Xinjiang Uighur
Autonomous Region, China
Objective To evaluate the capsid protein in cells and exfoliatedcells, the genetic load of HPV16 DNA L1, E6/E7 in cells, the ex-

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A neast case control study on type specifice persistent HPV
infection in Uyghur women Gulan Tuohetimulati, Mayinuer
Niyazi The Peopleʼs Hospital of Xinjiang Uighur Autonomous
Region, China
Objective To investigate the feature of type specifice persistent HPV infection and the associated risk factors in Uyghur
women. Methods From September 2012 to August 2013, Uyghur
women. Who underwent opportunistic screening for cervicalcancer at the Peopleʼs Hospital of Xinjiang Uyghur Autonomous
Region were recruited during the baseline irestigation. After
tasting for HPV infection and genotyping, 300 women with enrolled in the nested case control study, information came fromthe sample subjects interviewed using questionnaires and follow up associated risk factors in Uyghur women study. Results
The type specific persistent HPV infection rate was 25.50%（65/255）. The top five most common HPV types were HPV16（48.80%）, HPV18（31.03%）, HPV58（28.30%）, HPV52（23.40%）,
HPV45（21.43%）. The risk of type specific persistent HPV infection was increased 4.81 fold for HPV16 compared with non
HPV16. Compared with transient HPV infection, menopause andnot using condoms were risk factors for persistent HPV infection. Having menopause and not using condoms. Regular sceaning and close follow up be carried out in the high risk population. Conclusion The risk factors for persistent HPV infection
for Uyghur women included having HPV16 infection, having
menopause and not using condoms. Regular sceaning and close
follow up be carried out in this high risk population.

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IIIB/IVA cervical cancer patients. Methods We reviewed the
medical records of FIGO stage IIIB/IVA cervical cancer patients（n=30）who had been intended to be treated with TC
based CCRT followed by consolidation chemotherapy（TC
CCRT group）from April 2012 May 2016. Patients who had beentreated with CCRT involving a single platinum agent（CCRT
group；n=52）or definitive radiotherapy alone（RT group；n=74）from January 1997 September 2012 were also identified andused as historical controls. Survival was calculated using the
Kaplan Meier method and compared using the log rank test.
Results Of the 30 patients included in the TC CCRT group, 22
patients（73.3%）completed the planned TC based CCRT. The
most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was themost common acute grade 3/4 non hematological toxicity. Aftera median follow up of 35 months, 9 patients（30.0%）had developed recurrent disease. The patientsʼ estimated 3 year progression free survival（PFS）and overall survival（OS）rates were
67.9% and 90.8%, respectively. In comparisons with historicalcontrol groups, the survival outcomes of TC CCRT group was
significantly superior to CCRT group in terms of OS（p=0.011）and significantly superior to RT group in terms of both
PFS（p=0.009）and OS（p＜0.001）.Conclusion TC based CCRT
followed by consolidation chemotherapy is safe and effective. A
randomized controlled study needs to be conducted to further
evaluate the efficacy of this multimodal approach in this patient
population.

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Chemoradiotherapy followed by consolidation chemotherapy
involving paclitaxel and carboplatin and in FIGO stage IIIB/IVA cervical cancer patients Hiroko Shimura, Seiji Mabuchi,
Tsuyoshi Takiuchi, Yuri Matsumoto, Michiko Kodama, Eiji
Kobayashi, Kae Hashimoto, Yutaka Ueda, Kenjiro Sawada,
Takuji Tomimatsu, Kiyoshi Yoshino, Tadashi Kimura Osaka
University
Objective To evaluate the efficacy and toxicity of paclitaxel
plus carboplatin（TC）based concurrent chemoradiotherapy（CCRT）followed by consolidation chemotherapy in the International Federation of Gynecology and Obstetrics（FIGO）stage

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ISP-2-4
Phase I study of multiple epitope peptide vaccination in patients with recurrent or persistent cervical cancer Yuji Ikeda,
Akira Kurosaki, Yuichi Imai, Shoji Nagao, Daisuke Shintani,
Akira Yabuno, Keiichi Fujiwara, Kosei Hasegawa Saitama Medical University International Medical Center
Objective Cancer immunotherapy is recently established as the
fourth cancer therapy ．In this study, we conducted a phase I
dose escalation study trial using a mixture of five peptides tovaccinate cervical cancer patients with HLA A*2402. Methods
The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were
evaluations of immunological responses and clinical efficacy. All
patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy.
Peptides derived from forkhead box protein M1（FOXM1）, maternal embryonic leucine zipper kinase（MELK）,holliday junction recognition protein, and vascular endothelial growth factor
receptors 1 and 2 were administered to nine patients in a threepatient cohort design, with doses of 0.5, 1, or 2 mg of each of theindividual peptides in a mixture with incomplete Freundʼs adjuvant. Results The major adverse events were anemia and injection site reactions, which were seen in 77.8%（7/9）and 66.7%（6/9）of patients, respectively. Grade 3 anemia was observed in one
patient. No dose limiting toxicity of the vaccine was observed.
Seven（78%）patients achieved stable disease, and the medianprogression free survival was 3 months. Interferon γ ELISPOT
assays for each of the five antigens showed that eight（89%）andseven（78%）patients had high T cell responses to FOXM1 and
MELK, respectively. Conclusion We demonstrated that thisfive peptide vaccine was tolerable, and that FOXM1 and MELK
could be promising targets for immunotherapy in patients withcervical cancer.

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ISP-2-5
Neoadjuvant intraarterial chemotherapy using an original
four lumen double balloon catheter for locally advanced
uterinecervicalcancerTomohito Tanaka, Hiromitsu!

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pression of HPV16L1, HPVE6/E7 Protein, HPV E6/E7mRNA in
the progress of cervical erosion between Han and Uyghur
women. Methods Data gathered at our hospital from August of2013 to June of 2015, the type and infection of cervical erosion
was determined by HC 2HPV DNA. Patient were severed into
cervicitis, CIN1, CIN2 3 and cervical carcinoma groups. Immunocytochemical and IHCA were applied to inspect the capsid
protein in cervical exfoliated cells and tissues towards 197
specimens with positive HPV, RT PCR and western blot weretesed genes and protein of HPV16DNA L1, DNA E6, DNA E7,
ELISA was tested the antibody HPV16L1 in serums. APTIMA
was executed to have an HPV E6/E7 mRNA inspection uponcervical lesions. Results the positive rate of HPV L1 in tissues
and exfoliated cell outlined a declining trend, which demonstrated statistical significance.（P＜0.05）. antibody HPV16L1 inserums ascending with the severity of cervical lesions, whichhave statistical significance（P＜0.05）.No statistical significancebetween Han and Uyghur（P＜0.05）. Both HPV16E6/E7 protein
and HPVE6/E7mRNA in cervical upgraded with an aggregation
the severity of cervical lesions, both conferred statistical significance（P＜0.05）. PPV was measured at 72.88% while NPV
equaled to 81.02%. AP was 76.14%. Conclusion HPVL1 protein
and HPVE6/E7mRNA expected a marker for predicting the severity of cervical lesions in Uygur.

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Tsuchihashi, Shinichi Terada, Misa Nunode, Hiromi Konishi,
Natsuho Nakamura, Keisuke Ashihara, Kazuya Maeda, Saha
Yoo, Hiroshi Sasaki, Yoshito Terai, Masahide Ohmichi Osaka
Medical College
Objective We report the balloon occluded arterial infusion therapy with original four lumen double balloon catheter（4L DB）,
which enable to efficient injection of an anticancer agent at ahigh concentration to target spot, for patients with locally advanced uterine cervical cancer. Methods One hundred andforty three patients with locally advanced cervical cancer
treated with neoadjuvant
intraarterial
chemotherapy（NAIAC）or primary radical hysterectomy（PRH）were retrospectively assessed. The patients in NAIAC group were received irinotecan 70 mg/m2 intravenously on day 1 and 8 andcisplatin 70 mg/m2 intraarterially using 4L DB on day 2 of a 21
day course, and two courses were performed in principle. Radical hysterectomy was performed within 6 weeks after NAIAC.
Results Ninety four patients were treated with NAIAC and 49
patients had PRH. In NAIAC group, 88 patients had 2 courses of
NAIAC, 6 patients had 1 course of NAIAC and 88 had radical
hysterectomy. The response rate of NAIAC was 92.6%. Fourteen patients（14.6%）had no evidence of cancer cells on pathologic diagnoses. The medium follow up was 26 months and25 months, respectively. NAIAC group had higher 2 year progression free survival than PRH group（76.7% vs. 57.1%, p=0.03）,
however, overall survival was not different significantly. The
relative risk for recurrence was higher in patients with lymph
node metastasis（4.31；95% CI, 2.23 8.43）and lower in those with
NAIAC（0.30；95% CI, 0.14 0.68）. Conclusion Our results with
NAIAC using 4L DB catheter in locally advanced cervical cancer indicates beneficial effects on primary lesions and improves
progression free survival.

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Comparison of adjuvant therapy for node positive clinicalstage IB IIB cervical cancer：systemic chemotherapy versus
pelvic irradiation Hideki Tokunaga1, Muneaki Shimada1, Koji
Matsuo2, Yoichi Aoki3, Masaru Sakamoto4, Nobuhiro
Takeshima5, Hisaya Fujiwara6, Takashi Matsumoto7, Mikio
Mikami8, Nobuo Yaegashi1, Toru Sugiyama9 Tohoku University 1,
University of Southern California, USA 2, University of the
Ryukyus 3, Sasaki Foundation Kyoundo Hospital 4, Japanese Foundation for Cancer Research 5, Chugoku Rosai Hospital 6, Ehime
University 7, Tokai University 8, Iwate Medical University 9
Objective To examine survival outcomes and recurrence patterns of women with node positive stage IB IIB cervical cancer
who received only postoperative systemic chemotherapy afterradical hysterectomy as compared to those women who received radiation based therapy. Methods This was a nation
wide retrospective study in Japan examining women who underwent radical hysterectomy for clinical stage IB IIB cervicalcancer with pelvic and/or para aortic lymph node metastasis
between 2004 and 2008. Time to recurrence or death and patterns of disease recurrence were compared based upon the adjuvant treatment pattern：whole pelvic radiotherapy alone（n=253）,concurrent chemo radiotherapy（CCRT, n=502）, and chemotherapy alone（n=319）.Results Women who received chemotherapy alone had similar recurrence（5 year rates, 36.6% versus
34.1%）and mortality（24.7% versus 21.8%）compared to those
who received CCRT on multivariate analysis. Chemotherapy
treatment was independently associated with decreased risk of
distant recurrence（5 year cumulative rates, 19.2% versus
24.6%）but increased risk of local recurrence（23.9% versus
14.3%）compared to CCRT. Non squamous histology, parametrial involvement, and high lymph node ratio were independent predictors for local recurrence, and presence of multiple
risk factors was associated with high 5 year cumulative local

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recurrence rate in the chemotherapy group：no risk factor
3.9%, single factor 14.2 22.1%, and multiple risk factors 27.8
71.9%（P＜0.001）. Conclusion Systemic chemotherapy may be aseffective a postoperative treatment as radiation based therapy
in node positive high risk stage IB IIB cervical cancer. Whentumor exhibits certain risk factors, chemotherapy alone is likely
insufficient for local control and adding pelvic irradiation to systemic chemotherapy is recommended in this subgroup.

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ISP-2-7
Effectiveness of adjuvant systemic chemotherapy for intermediate risk stage IB cervical cancer Takamichi Minato1,
Muneaki Shimada1, Koji Matsuo2, Harushige Yokota3, Toyomi
Satoh4, Hidetaka Katabuchi5, Shoji Komada6, Hiroshi Sasaki7,
Noriomi Matsumura8, Mikio Mikami9, Nobuo Yaegashi1, Toru
Sugiyama10 Tohoku University Hospital 1, University of Southern
California, USA 2, Saitama Cancer Center 3, University ofTsukuba 4, Kumamoto University 5, Niigata Cancer Center Hospital 6, The Jikei University Kashiwa Hospital 7, Kyoto University 8,
Tokai University 9, Iwate Medical University 10
Objective To examine the effectiveness of systemic chemotherapy after radical hysterectomy for women with intermediaterisk stage IB cervical cancer. Methods This is a retrospective
analysis of a previously organized nation wide cohort study examining 6,003 women with stage IB IIB cervical cancer who underwent radical hysterectomy between 2004 and 2008 in Japan.
Survival of 555 women with stage IB cervical cancer with intermediate risk group（deep stromal invasion 50%, large tumor
size 4cm, and lympho vascular space invasion［LVSI］）were examined based on adjuvant therapy patterns：chemotherapy
alone（n=223, 40.2%）, concurrent chemo radiotherapy（n=172,
31.0%）, and radiotherapy alone（n=160, 28.8%）. Results The mostcommon intermediate risk pattern was LVSI with deep stromalinvasion（n=216, 38.5%）. The most common chemotherapy
choice was taxane/platinum doublet（52.2%）.Women with adenocarcinoma/adenosquamous histology were more likely to receive chemotherapy（P=0.03）, and intermediate risk pattern
was not associated with chemotherapy use（P=0.11）.Women received systemic chemotherapy had disease free survival（5year rate, 88.1% versus 90.2%, adjusted hazard ratio（HR）0.98,
95% confidence interval（CI）0.52 1.83, P=0.94）and cause specific survival（95.4% versus 94.8%, adjusted HR 0.85, 95%CI 0.34
2.07, P=0.71）similar to those who received concurrent chemoradiotherapy on multivariable analysis. Similar results wereseen among 329 women with multiple intermediate risk factors（5 year rates for DFS, chemotherapy versus concurrent
chemo radiotherapy, 87.1% versus 90.2%, P=0.86；and CSS
94.6% versus 93.4%, P=0.82）. Cumulative local recurrence（P=0.77）and distant recurrence（P=0.94）risks were similar acrossthe adjuvant therapy types. Conclusion Our study suggests thatsystemic chemotherapy may be an alternative treatment choice
for adjuvant therapy in stage IB cervical cancer with an intermediate risk factor.

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Paclitaxel plus cisplatin as adjuvant chemotherapy after radical hysterectomy for intermediate and high risk stage IB
IIB cervical cancer Yuta Inoue, Takeshi Fukuda, Masahiro
Shimomura, Hiroaki Matsubara, Mari Kasai, Yasunori
Hashiguchi, Tomoyuki Ichimura, Tomoyo Yasui, Toshiyuki
Sumi Osaka City University
Objective The aim of the present study was to evaluate the efficacy and safety of paclitaxel plus cisplatin（TP）as adjuvant chemotherapy after radical hysterectomy for intermediate andhigh risk stage IB IIB cervical cancer. Methods Thirty eightpatients with intermediate and high risk stage IB IIB cervical

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ISP-2-9
The comparison of CCRT protocols composed of different
chemotherapy regimens for the patients with locally advanced cervical squamous cell carcinoma Yoshifumi Nakao1,
Asako Fukuda1, Takako Hikari1, Yukihiko Nakayama1, Satoshi
Nishiyama1, Katsuyuki Hanashima2, Mariko Hashiguchi2,
Masatoshi Yokoyama1 Saga University 1, Saga University Graduate School of Medical Science 2
Objective To evaluate response and short time survival in patients with locally advanced squamous cell carcinoma of theuterine cervix who underwent historically different chemotherapy protocol with the same irradiation procedure. Methods A
review of patients with locally advanced squamous cell cervicalcancer who underwent definitive CCRT in the single institution.
Chemotherapy included 2 monthly doses of intra arterial infusion with cisplatin（50 mg/m2）and mitomycin C（10 mg/body）（MPia CCRT）or weekly intra venous infusions with cisplatin（CDDPiv CCRT）. Both groups were irradi（40 mg/m2/week）
ated to the whole pelvis and high dose rate brachytherapy inthe same policy. From 2006 to 2012, 76 patients were treatedwith MPia CCRT. From 2012 to 2015, 46 patients were treatedwith CDDPiv CCRT. Patient distribution of each group according to the FIGO stage was as follows：8 and 7 stage IB2, 6 and
13 stage IIA, 42 and 10 stage IIB, 3 and 2 stage IIIA, 16 and 12
stage IIIB and 1 and 2 stage IVA respectively. Radiologicallymph node involvement except paraaortic nodes was present
in 61.8% and 47.8%. The radiological response, pathological response, overall and disease free survival were assessed. Results
CR ratio and response rate showed 84.2%（64/76）and 98.7%（75/76）in MPia CCRT group and 81.8%（36/44）100%（44/44）in
CDDPiv CCRT group respectively. In the median follow up duration（68.5 months and 30.5 months）, the 2 year disease free
and overall survival 76.3% and 85.1%, and 70.3% and 86.7% respectively. Conclusion Different chemotherapy regimens administered with identical radiation protocol showed the statistically similar responses and short time survivals in patients withlocally advanced cervical squamous cell carcinoma.

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ISP-3-1
Posttreatemt HPV genotyping for recurrent high grade cervical intraepithelial neoplasias Chan Joo Kim1, SeoHye Won1,
Keun Ho Lee2, TaeChul Park3, JongSup Park2 St. Paulʼs Hospital,
The Catholic University of Korea, Korea 1, Seoul St. Maryʼs Hospital. The Catholic University of Korea, Korea 2, Uijeongbu St.
Maryʼs Hospital, The Catholic University of Korea, Medical Col-lege, Korea 3
Objective Risk of recurrent CIN and CIS remains elevated foryears following treatment of CIN3 and CIS. The role of HPV
genotyping on subsequent risk of CIN2+ was evaluated. Methods This study was conducted on 66 patients with CIN3 and CIS
after LEEP conization at the St Paulʼs Hospital of the Catholic
University of Korea. Pathologic diagnosis of cervix were confirmed with colposcopic guided biopsy or LEEP procedure. Pap
smear and HPV genotyping were performed before surgery andevery 3 6 month. We used HPV genotyping with Anyplex II
HPV test. This test differentiates between 19 HPV HR types（16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 26, 53, 69, 73,82）and 9 low risk HPV types. Results The mean age was 46.33
years. The most frequent HPV types were HPV 16（17 cases,
25.8%）, HPV 58（9 cases；13.6%）and HPV 52/ 33（7 cases；
10.6%）. Women with single and multiple HPV type was 43（65.2%）and 19（28.8%）.Median follow up was 16 month. Proportion of young women under 34 years old was 20（30.3%）and nulliparity was 23（34.8%）. High risk HPV types during follow up
was found in 20 cases（30.3%）. Among them, only one womenwith persistent HPV 52 received total hysterectomy. Final pathology of cervix showed CIN 3 on one focus. Conclusion HPV
infection is not completely eradicated by LEEP in patients with
CIN3/CIS. HPV persistence using HPV genotyping after LEEP
can identify women at greatest risk of posttreatment CIN 2+ lesions.

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ISP-3-2
HPV subtyping according to the tissue biopsy of the cervix ofthe uterine at an institution Eunseop Song, Hwa Yeon Choi,
Haesun Joo, Eunye Jo, Hyungeun Choi, Shina Jang, Sukyung
Jung Inha University of Korea, Korea
Objective To analyze the HPV typing according to the pathology of uterine cervix at an institution. Methods Medical records
had been reviewed retrospectively at an institution. The result
and time of the biopsies were reviewed. Results There were 441
biopsies from 2001 to 2016. There were 117 patients with CIN 1,
43 with CIN 2, 114 with CIN 3 and 167 with squamous cell carcinoma（SCC）. At CIN 1, the frequency of HPV were 50%, and at
CIN 2, 72%, and at CIN 3, 97%, and at SCC, 98%. The frequencyof HPV 16, 18 and 16, 18, 31, 33, 45, 52, 58 at CIN 1 were 57% and71%, at CIN 2 were 50% and 60%, at CIN 3 were 47% and 74%
and at SCC, 72% and 94%. Conclusion The rate of High Risk
HPV type according to the biopsy were 50% at CIN 1, 72% at
CIN2, 97% at CIN 3 and 98 at squamous cell carcinoma. Amongthe patient with identified HPV type, the rate of 2 types（16 and/or 18）and 7 types（16, 18, 31, 33, 45, 52, and 58）were 57% and 71%
at CIN 1and 50% and 60 at CIN 2 and 47% and 74% at CIN 3, and
72% and 94% at squamous cell carcinoma. This data may helpful
to prepare and expect the potency of the vaccination of HPV.

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Outcomes of patients diagnosed with atypical glandular cells（AGC）in a single institution experience Mie Tanaka, Kiyoshi
Yoshino, Akiko Okazawa, Tsuyoshi Takiuchi, Michiko Kodama,
Kae Hashimoto, Eiji Kobayashi, Seiji Mabuchi, Yutaka Ueda,
Takuji Tomimatsu, Kenjiro Sawada, Tadashi Kimura Osaka
University
Objective This study aimed to investigate the outcomes of patients diagnosed with atypical glandular cells（AGC）and determine the clinical management for them. Methods We retrospectively reviewed the outcomes of patients with AGC from January 2010 to August 2017 in our institution. Results 195 patientswere diagnosed with AGC during the study period. Amongthem, the final diagnosis was as follows：endometrial cancer 73（37.4%）, cervical cancer 41（21.0%）, cervical intraepithelial neo-!

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cancer treated with radical hysterectomy received adjuvant TP（135mg/m2 paclitaxel and 50mg/m2 cisplatin, six courses for thepatients who had lymph node metastasis and three courses forthe others.）（TP group）. Adverse events and disease free survival were investigated. The outcome was compared with thatfor 40 patients who received adjuvant radiotherapy or concurrent chemoradiotherapy（RT group）.This study was approvedby the Ethics Committee in our facility. Results The completion
rate of TP was 97.1%. One year disease free survival was 89.5%
for the patients who received adjuvant chemotherapy. There
was no significant difference in disease free survival between
two groups（P=0.873）. Grade 3 and 4 adverse effects were identified as 15 neutropenia in TP group, 5 neutropenia, 4 diarrhea, 1
lymph edema, 3 ileus, 1 vesicovaginal fisutula and 1 rectovaginal
fistula in RT group. As for grade 3 and 4 adverse events, neutropenia was significantly more frequent in the TP group（P=0.004）
and diarrhea was significantly more frequent in the RT group（P=0.045）. Conclusion TP might be an effective and safe adjuvant
therapy after radical hysterectomy for intermediate and highrisk stage IB IIB cervical cancer.

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plasia 3（CIN3）13（6.7%）, adenocarcionoma in situ（AIS）4（2.1%）,
CIN3+AIS 3（1.5%）, cervical intraepithelial neoplasia 1（CIN1）or
cervical intraepithelial neoplasia 2（CIN2）7（3.6%）, complex endometrial hyperplasia with atypia 2（1.0%）, ovarian cancer 7（3.6%）, peritoneal cancer+CIN2 1（0.5%）, other malignant lesions 3（1.5%）, and benign lesion 14（7.2%）.24 patients（12.3%）
had no lesions and the outcomes were unclear in 2 patients. Of
all cases diagnosed as AGC, 64.1% had malignant lesions. Conclusion Patients diagnosed as AGC were high risk for malignancy. Most of them located in the uterus, biopsies of cervix under colposcopy, from endometrium and conization if necessary
should be carried out. It was rare, but abdominal cancer coexisted with cervical AGC, so that careful imaging analysis of abdominal cavity such as with MRI can be considered if physician
suspects malignancies.

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The pathological investigation of parametrial invasion to diminish type III radical hysterectomy for stage IB IIA cervical cancers Fuminori Ito1, Atsushi Sugiura1, Kana Iwai2, Yuki
Yamada2, Yasuhito Tanase2, Ryuji Kawaguchi2, Shinji Toyoda1,
Yoshio Itani1, Hiroshi Kobayashi2, Tsunekazu Kita1 Nara Prefecture General Medical Center 1, Nara Medical University 2
Objective To assess the adequate conditions of type II radical
hysterectomy（RH II）for stage IB1 to IIA2 cervical cancers inorder to reduce postoperative complications by avoiding typeIII radical hysterectomy（RH III）.Methods The relationship between pathological parametrial invasion（PMI）and other prognostic factors was retrospectively investigated in cases performed with RH III for stage IB1 to IIB cervical cancers in two
tertiary institutions, from November 2006 to May 2017. Chi
square test was used as univariate analysis and multiple logistic
regression analysis as multivariate analysis. Results One hundred forty cases were preoperatively diagnosed as stage IB1 in
54 cases, IB2 in 32, IIA in 17, IIB in 35 and IVB in 2. Thirty cases（21.4%）were revealed histologically with PMI. In univariate
analysis, elder age（＞50 yo）, large tumor（＞30mm）and common
iliac lymph node metastasis were the significant risk factors for
PMI. In multivariate analysis, all three factors were extracted as
the significant risk factors for PMI with p values 0.012, 0.020,
0.019, respectively. Combination of these three factors could estimate PMI with high sensitivity（90.9%）and negative predictive
value（96.3%）in stage IB1 to IIA2 cases. These results mean RH
II might be enough for 26.2% of IB1 to IIA2 cases with an only
3.7% risk of pathological PMI. Conclusion RH II nor RH III
could be enough for stage IB1 to IIA2 cervical cancers, with age
younger than 50 years, with tumor size smaller than 30mm, andin addition, without metastasis to common iliac lymph nodes
proved by intraoperative frozen section.

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Lymph node metastasis of stage IA1 uterine cervicalsquamous cell carcinoma：case report Kana Sekigawa1, Ichiro
Ono2, Keijiro Sumori2, Hidenori Umeki3, Yoshiaki Somekawa3,
Mikiko Tsugata3, Aya Osonoi3, Hironori Asada1, Shuji
Takemoto1, Satoshi Asai1 Shin yurigaoka General Hospital 1,
Ome Municipal General Hospital 2, JA Toride Medical Center 3
Lymph node metastasis of stageIA1 uterine cervial squamouscell carcinoma（SCC）is very rare. In this report we will present
two cases in which we detected post surgical lymph node metastasis. In our first case was a 63 year old women who was diagnosed with cervical microinvasive squamous cell carcinoma
following a regular uterine cervical cancer check up. We performed conization. The diagnosis was SCC stageIA1, the mass
depth was 3mm, the length was 6mm and LVSI was negative.
We added total abdominal hysterectomy（TAH）and bilateral

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salpingectomy（BLS）. Twenty two months after the first surgery, increasing para aortic lymph node was detected by CT,
and she underwent pelvic lymphadenectomy and para aortic
lymphadenectomy. Second case was a 74 year old woman. Hydrometra had been detected and the fluid had been suctioned,
but soon reaccumulated. Since her abdominal pain had beenworsing we preformed TLH and BLS. The diagnosis of the uterine cervix was SCC stageIA1, the mass depth was under 1mm
and the length was 2mm and LVSI was negative. Fourteenmonths after the first operation inguinal lymph node had been
palped, and we removed it which was diagnosed with SCC.
There were twenty two SCC IA1 cases in two hospitals between 1996 and 2016, but only these two cases（9%）had relapsed.
In both cases LVSI was negative even by immunostaining. Image testing for stage IA1 uterine cervical SCC is not standard
during routine exam, but we must remember the potential forpost surgical metastasis and consider image testing logical addition to follow up after initial surgery.

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Leukocytosis as an initial sign of aggressive growth of granulocyte colony stimulating factor producing cervical cancer
Ai Yoshida, Kyousuke Takeuchi, Mamiko Sawada, Akiko
Takeda, Makoto Sugimoto Kobe Medical Center
Introduction Granulocyte colony stimulating factor（G CSF）
induced leukemoid reaction is a rare paraneoplastic syndromein cervical carcinoma, with rapid tumor progression and poor
prognosis. We report three cases of G CSF producing
squamous cell carcinoma of the cervix, where leukocytosis led
to diagnosis and the disease and its recurrence. Cases A 57
year old woman underwent radical hysterectomy for cervicalcarcinoma. No leukocytosis was noted. The patient was treatedwith concurrent chemoradiation therapy. One month after radiation therapy the patient developed fever without evidence of
infection, and laboratory data showed leukocytosis（18,540/μL；
90% neutrophils）. Serum G CSF was 125.2 pg/mL. The specimens found at surgery were focally positive for G CSF. A 58
year old woman had high fever. The biopsy specimens at cervix
demonstrated a squamous cell carcinoma. The cytoplasm of thetumor cells was positive for G CSF. Laboratory data showed severe leukocytosis（22,540/μL；93% neutrophils）and 58.2 pg/mL
of G CSF. Intensive irradiation and chemotherapy provided
temporary remission. An 80 year old woman had exploratory
laparotomy under the diagnosis of colonic perforation, and perforated pyometra and advanced cervical carcinoma were diagnosed. Antibiotics therapy was performed. However, leukocytosis（31,300/μL；85% neutrophils）continued, regardless of improvement of other inflammatory findings. The cytoplasm of thetumor cells at cervix was positive for G CSF. After radiation
leukocyte count and G CSF levels were decreased. Discussion
The possible existence of G CSF producing carcinoma should
be considered in cases of cervical carcinoma with remarkableleukocytosis and neutrophilia, but without obvious infection.
White blood cell count should be closely followed as part of themonitoring of disease activity.

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Retrospective study of metastatic size and recurrence pattern
for lymph node positive cervical cancer patients Tomoyuki
Nagai, Hideki Tokunaga, Masafumi Toyoshima, Muneaki
Shimada, Hitoshi Niikura, Nobuo Yaegashi Tohoku University
Hospital
Objective To evaluate the clinicopathological features in thelymph node positive cervical cancer patients. Methods FIGO IA
2 IIB cervical cancer patients who underwent surgery from2012 to 2017 in our hospital and had histologically metastatic

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Squamous cell carcinoma of the cervix with superficial
spreading to the endometrium：A case report Shuhei Abe,
Kiyonori Miura, Noriko Miyashita, Toru Murakami, Yuri
Hasegawa, Atsushi Yoshida, Hideaki Masuzaki Nagasaki University
Commonly, cervical squamous cell carcinoma（SCC）can directly
invade the uterine wall with or without parametrial involvement and/or by lymphatic invasion. The superficial spreading
to the endometrium replacing it without myometrial invasion isvery uncommon, with fewer than 30 cases reported in the literature. The author reports a case of cervical SCC with superficial
spread. A 69 year old female（G 2 P 2）presented with abnormal
cytological and histological finding of cervix（HSIL and CIN3）7
years ago. However, she did not get cervical conisation. She admitted a local hospital with itching sensation of the vulva andatypical genital bleeding since the last three months and was introduced to our hospital because of further examination for abnormal cytology（ASC H）. Cervical cytology, endometrial cytology, cervical biopsy and endometrial curretage revealed SCC.
There was CIN3 with gland involvement by cervical conisationand no mass lesion detected by imaging such as US/CT/MRI.
The patient was diagnosed as cervical SCC（FIGO stage IA1 byendometrial curettage sample）. A semi radical hysterectomy
with bilateral salpingo oophorectomy and pelvic lymph nodedissection was performed. Microscopically, the cervical lesion
revealed features of CIN3（carcinoma in situ）extending up andlining the endometrial surface without myometrial invasion. In
this case, the superficial spreading SCC of cervix involved theentire the endometrial surface without myometrial invasion. Although the FIGO staging system has ignored such a condition,
as this case is rare phenomenon, more case studies are necessary to clarify the conclusion regarding treatment and prognosis of this condition.

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ISP-3-9metastasis of the pelvic lymph node. Results Nineteen cases（47.5%）showed a high signal intensity on DW MRI and only 5cases（12.5%）showed metastasis positive in pelvic lymph nodes.
The sensitivity, specificity, positive predictive value, and negative predictive value of DW MRI for pelvic lymph node metastases were 80.0%, 57.1%, 21.1%, and 95.2%（20/21）, respectively.
Of 21 cases with low signal intensity on DW MRI, only 1 casewas revealed with lymph node metastasis. The average sizes ofmetastasis negative and metastasis positive lymph nodes withhigh signal intensity on DW MRI were 11.9 mm and 13.1 mm,
respectively. The median tumor sizes of metastasis negativeand metastasis positive were 28.1 mm and 33.7 mm, respectively. Conclusion Our findings suggest that we cannot predicta metastasis of pelvic lymph node with a high signal intensity
on DW MRI. But we can probably omit pelvic lymph node dissections in patients without high signal intensity on DW MRI of
the pelvic lymph node.

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Usefulness of diffusion weighted MRI（DW MRI）in the detection of lymph node metastases in patients with uterine cervical cancer Yoshinori Takeda, Atsushi Sugiura, Shoichiro
Yamanaka, Sayuri Morita, Hitomi Sugimoto, Satoko Ishibashi,
Fuminori Ito, Hitoshi Hirano, Shinji Toyoda, Yoshio Itani,
Tsunekazu Kita Nara Prefecture General Medical Center
Objective A high signal intensity on preoperative DW MRI is
widely relied upon for the diagnosis of malignant gynecologicaltumors. In this retrospective study, we investigated the effectiveness of this diagnostic method on detecting pelvic lymph
node metastases in patients with uterine cervical cancer, who
underwent pelvic lymph node dissections. Methods We studied
40 patients diagnosed with uterine cervical cancer, who underwent pelvic lymph node dissections between December 2013
and March 2017. We tried to clarify an association between asignal intensity on preoperative DW MRI and the pathological

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Clinical Features of High grade Neuroendocrine Carcinomaof the Uterine Cervix：a single institute retrospective reviewof 21 cases Yoko Furutake, Kaoru Abiko, Taito Miyamoto,
Yoshimi Kitawaki, Ryusuke Murakami, Miyuki Ito, Akihito
Horie, Junzo Hamanishi, Tsukasa Baba, Masaki Mandai Kyoto
University
Objective High grade neuroendocrine carcinoma（NEC）of theuterine cervix is aggressive, and its prognosis is extremely poor.
Due to the rarity of the disease, the optimal treatment strategy
is yet to be clear. In this study, we retrospectively investigatedclinical features and treatment of NEC. Methods Patients with adiagnosis of NEC treated at our hospital between 2005 and 2016
were included. Clinical and pathological data were collectedfrom the clinical records. Results The median age at the diagnosis was 45（range, 27 83 years）. 15 patients had small cell and 6
had large cell neuroendocrine carcinoma. FIGO stage was I in
12 patients, II in 1, III in 1, and IV in 7, respectively. 2 year and5 year survival rates were 80.0% and 42.9%（FIGO I II）, 57.1%
and 12.5%（FIGO III IV）.In 13 stage I II patients, all but one underwent radical hysterectomy. 5 patients underwent neoadjuvant chemotherapy consisting of 2 courses of cisplatin/irinotecan（PI）, and 4 of them obtained partial response, and 1 obtained
stable disease. 10 patients received adjuvant therapy. 22% ofstage IB1 patients and all stage IB2 II patients experienced relapse. Among stage IV patients, none obtained clinical response
after 6 cycles of PI. In recurrent cases, 1 patient obtained partial
response（PR）using abraxane, and 1 patient obtained PR using
cisplatin/etoposide（PE） CCRT followed by PE. No patient obtained clinical response with paclitaxel/carboplatin（TC）. Conclusion The prognosis of NEC is dismal even in early stages.
Some chemotherapy regimens other than standard TC showedclinical response. Specialized treatment strategy is required to
improve outcomes.

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Decreased expression of nuclear receptor coactivator 6 maycorrelate with the progression and less differentiation of human endometrioid adenocarcinoma Norikazu Watanabe, Jun
Kawagoe, Hizuru Yamatani, Seiji Tsutsumi, Satoru Nagase
Yamagata University HospitalObjective Nuclear receptor coactivator 6（Ncoa6）is one of thecoactivators that regulate transcriptional activities of estrogen
receptor α（ERα）. In mice, the knock out of Ncoa6 facilitates thegrowth of endometrial carcinoma. However, the function of
Ncoa6 in human endometrium and in endometrial cancer remains unclear. We therefore investigated the relationship between the expression levels of Ncoa6 and the clinical character-!

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positive lymph node were analyzed. We evaluated overall survival and progression free survival, recurrence pattern, size ofmetastatic lymph node, and operative procedure（with or without sentinel lymph node mapping）.Results Thirty patients had
positive lymph node metastases and 6 patients had recurrence.
Four of six patients experienced lymph node recurrence. Fourpatients had only with micrometastases but 2/4 recurred. In patients using sentinel lymph node（SLN）mapping, 7/9 found
lymph node metastases only in SLN. None with SLN mapping
patients recurred. Conclusion Cervical cancer patients with micrometastases have a same risk compared with macrometastases patients. Using sentinel lymph node mapping may probably
reduce the risk of lymph node recurrence.

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istics of endometrial cancer. Methods Pathological samples ofhuman endometrioid adenocarcinomas were obtained from patients who underwent surgery between 2009 and 2011. The expression of Ncoa6 in each sample was studied using immunohistochemistry, and classified into three groups：negative（0%Ncoa6 positive cells）；weak（1% to 49% Ncoa6 positive cells）；
and positive（＞50% Ncoa6 positive cells）. Statistical analysis
was performed to reveal the relationship between patient clinical status, including grade and staging of cancer, and Ncoa6 expression. Authorization was obtained from the appropriate ethics committee for this study. Results Ninety eight patients werestudied：50 with Grade（G）1, 35 with G2, and 13 with G3 cancer.
Compared with 100% positive cells in the normal endometrium,
the ratio of negative cells increased with cancer grade；specifically, 14% in G1, 17% in G2, and 38% in G3. The proportion of patients with advanced stage（stage III IV）was significantly
higher in the negative than in the positive group（odds ratio,
5.11；95% CI, 1.13 23.1）. Conclusion Expression of Ncoa6 is decreased in endometrioid carcinoma. Decreased expression of
Ncoa6 may be associated with cancer progression.

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There is a possibility that DUSP6 contributes to one of thestem like cell phenotypes in uterine endometrial cancer
Masaya Kato, Ichiro Onoyama, Sachiko Yoshida, Natsuko
Yokota, Teruhiko Kawamura, Keiko Kawamura, Keisuke
Kodama, Hiroshi Yagi, Kazuo Asanoma, Kenzo Sonoda, Kiyoko

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Estrogen related receptor α induces epithelial mesenchymaltransition through the cancer stromal interaction in endometrial cancer Kaori Yoriki, Taisuke Mori, Tetsuya Kokabu,
Shiori Umemura, Hiroshi Matsushima, Jo Kitawaki Kyoto Prefectural University of Medicine
Objective Estrogen related receptor（ERR）α shows structuralsimilarities with estrogen receptors. We previously demonstrated the tumor promoting action of ERRα in endometrial cancer. However, little is known about the detailed underlying
mechanism. In this study, we investigated whether ERRα in co
operation with peroxisome proliferator activated receptor γ
coactivator（PGC）1α, could participate in epithelial mesenchymal transition（EMT）through the cancer stromal interaction
in endometrial cancer. Methods Endometrial cancer cell lines,
Ishikawa and HEC 1A, transfected with ERRα/PGC 1α orknocked down for ERRα using siRNA, were co cultured withhuman endometrial stromal cells（T HESCs）and mono cultured
with/without transforming growth factor（TGF）β. The expression of EMT related factors including Snail, ZEB 1, andVimentin, was measured by quantitative PCR and E cadherin
expression was examined by western blotting. Migration and invasion capabilities were evaluated by Matrigel invasion assay.
Results The co culture experiments showed that the expression of EMT related factors was upregulated in cancer cells
transfected with ERRα/PGC 1α（P＜0.01）and TGF β expression was significantly induced in T HESCs（P＜0.01）. In themono culture system, ERRα/PGC 1α overexpression significantly stimulated the expression of EMT related factors after；however, it decreased E cadherin
TGF β exposure（P＜0.01）
expression at the protein level. ERRα knockdown suppressed
the expression of EMT related factors in the presence of TGF
β whereas E cadherin expression remained unchanged. Invasion assay revealed that ERRα knockdown attenuated the migration and invasion abilities stimulated by TGF β（P＜0.01）.
Conclusion These findings suggest that ERRα might be a potential target for inhibiting TGF β induced EMT through the cancer stromal interaction in endometrial cancer.

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Kato Kyushu University
Objective Caner stem cells（CSCs）are defined as a subset of tumor cells that can reconstitute cancer tissues and which areconsidered to be responsible for cancer progression, metastasis
and therapeutic resistance. To clarify the molecular mechanism
integrating the stemness of uterine endometrial cancer cells, wehave focused on dual specificity phosphatase 6（DUSP6）, because our previous data showed that DUSP6 is specifically expressed in CSC like cells although it is epigenetically silenced
in differentiated tumor cells. Methods To analyze DUSP6 functions associated with the stemness of tumor cells, human DUSP6
was overexpressed in uterine endometrial cancer cell lines（Hec1）. We assessed the signaling pathways, ALDH1（CSCs marker）,
the pluripotency associated factors and cell survival in hypoxic
condition. Results DUSP6 suppressed Erk1/2 activity via
dephosphorylation while it promoted Akt phsphorylation. DUSP
6 overexpressed cells showed higher expression of ALDH1 andpluripotency associated factors compared with control cells. Although DUSP6 suppressed cell proliferation in normoxic condition, it did not inhibit cell growth in hypoxic condition. Conclusion There is a possibility that DUSP6 contributes to one of thestem like cell phenotypes in uterine endometrial cancer by acquiring hypoxic resistance. DUSP6 might be a new target intherapeutic strategies for endometrial cancers.

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The high expression of claudin 6 is a poor prognostic factor
in uterine endometrial cancer Manabu Kojima1, Shu Soeda1,
Shinji Nomura1, Takafumi Watanabe1, Toshifumi Takahashi1,
Hideki Mizunuma1, Hideki Chiba2, Keiya Fujimori1 Fukushima
Medical University Hospital 1, Department of Basic Pathology,
Fukushima Medical University Hospital 2
Objective Among the claudin（Cldn）family that are transmembrane protein of tight junctions, Cldn6 is expressed in various
epithelial cells during fetal period, but not in any types of adultcells. Cldn6 is also detected in a part of lung, stomach, ovarian,and uterine endometrial adenocarcinomas, as well as in a significant part of germ cell tumors, but its functional relevance incancers is largely unknown. Here, we demonstrated the clinicopathological significance of cldn6 expression in uterine endometrial cancers（UEC）. Methods The Cldn6 expression was
evaluated by immunohistochemistry in paraffin embedded cancer tissues resected from 141 UEC cases, and semi quantitatively scored Cldn6 expression by the immunoreactive scoring
method（score 0, 1+, 2+, 3+）. We next determined whether Cldn
6 expression score was correlated with clinicopathological factors. And we produced a strain of CLDN6 overexpressing cells
from the ECC 1 endometrial carcinoma cell line and compared
their proliferation potential with those of the parent cell line in
Brdu and scratch assay. Results Of 141 UEC cases, 105, 14, 12, 10
cases exhibited Cldn6 score 0, 1+, 2+, 3+, respectively. 5 year
OS rates in Cldn6 score 3+ group were significantly lower thanscore 0/1+/2+ groups（5 year OS, 30.0% vs 89.3%, P＜0.001）.
The frequencies of clinical stage III/IV, non endometrioid adenocarcinoma, histological grade 3, lymphnode metastasis, distant metastasis were significantly higher in Cldn6 score 3+
group than those in score 0/1+/2+ groups. In Brdu and scratch
assay, we found that the proliferation potential of the tumor
cells was significantly elevated in the CLDN6 overexpressing
cell strain. Conclusion In UEC, high Cldn6 expression is a very
poor prognostic factor.

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Characterization of a cell line（NOMH 2）originating froma human uterine serous carcinoma Takashi Yamada Osaka
Medical College

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The usefulness of transcervical needle biopsy in uterine bodytumors Shunpei Kato, Iemasa Koh, Satoshi Urabe, Norifumi
Tanaka, Maki Hyodo, Eiji Hirata, Yoshiki Kudo Hiroshima University HospitalObjective It is important to assess malignant disease in the decision on a treatment strategy for uterine body tumors. However,myometrial tumors are often difficult to diagnose by means ofendometrial cytology or histology. Therefore, we examined theusefulness of transcervical needle biopsy for histopathologic diagnosis. Subjects and Methods Of 104 patients who had undergone needle biopsy for uterine tumors, 58 underwent hysterectomy at our Hospital between 2006 and 2016. We compared preoperative needle biopsy and postoperative histopathology findings in these 58 patients. Eleven patients diagnosed with malignant uterine body tumors were further examined retrospectively. We also examined adverse events associated with all 104
needle biopsies. Results The diagnostic accuracy for detecting
malignancy was 97%（56/58 patients）. Of 11 patients diagnosed
with malignant uterine body tumors, 9 underwent endometrial
cytology. The results were negative for 6 of these patients. Histological types matched in 7 of 11 cases, when comparing needle
biopsy and postoperative histopathological findings. Two cases
were diagnosed as malignant out of the 4 cases in which histological types did not match. Adverse events associated withneedle biopsy were pain and fever, which were observed in 26%（27/104）and 10%（10/104）cases, respectively. Almost all occurrences were mild and improved at follow up. Conclusion Histopathology by needle biopsy may be useful based on its high diagnostic accuracy and safety in cases where malignant uterine
body tumors are suspected and diagnosis via endometrial cytology or histology are difficult.

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Survival analyses based on tumor microenvironment profile
in endometrial carcinoma Shuang Zhang, Takeo Minaguchi,
Ayumi Shikama, Shuling Liu, Bouchra Lachkar, Nobutaka
Tasaka, Azusa Akiyama, Manabu Sakurai, Sari Nakao, Hiroyuki
Ochi, Toyomi Satoh University of Tsukuba

Objective Tumor microenvironment（TME）including the immune checkpoint system reportedly contributes to prognosis insome kind of tumors. The aim of this study was to investigate
the prognostic impact of TME profile in endometrial carcinoma.
Methods We performed immunohistochemical evaluations of
TME biomarkers, PD L1, CD8, CD68, and VEGF, in 221 endometrial carcinomas. Overall survival（OS）was comparedbased on the evaluations. Univariate and multivariate analysesof prognostic factors for OS were conducted. Results High staining index of PD L1 in tumor cells showed trends toward better
OS（p=0.059）. High VEGF staining index in tumor cells was significantly associated with worse OS（p=0.019）. High PD L1 intumor surrounding immune cells showed significant associations with CD8+ tumor infiltrating lymphocyte count, CD68+
tumor associated macrophage count, and microsatellite instability（p=0.0000003, 0.00001, and 0.0056）, and showed trends towards shorter treatment free interval after adjuvant chemotherapy（p=0.21）. Univariate analysis of prognostic factors
showed that high PD L1 in tumor cells was significant for better OS, and high PD L1 in tumor surrounding immune cells,
older age, advanced FIGO stage, non endometrioid histology,
deep myometrial invasion, and positive lymphovascular spaceinvasion（LVI）were significant for worse OS（p=0.007, 0.043,
0.000006, 0.000000002, 0.0000001, 0.000007, and 0.0001）. Subsequent multivariate analysis revealed that high PD L1 in tumor
cells, older age, advanced stage, non endometrioid histology,
and positive LVI were significant and independent prognostic
factors（p=0.017, 0.003, 0.0004, 0.001, and 0.038）. Conclusion Our
findings indicate that PD L1 mediated immune checkpoint system may be contributing to prognosis through regulating TMEin endometrial carcinoma, suggesting that inhibitors targeting
this system may be efficacious for the subset of patients withthe disease.

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Nanopore sequencing to uncover complex isoforms indicating
lymph node metastasis for endometrial cancer patients
Yosuke Ito, Yasuhisa Terao, Emiko Yoshida, Satoru Takeda Juntendo University HospitalObjective In a previous study, we found molecular biomarkers
that enable prediction of lymph node metastasis of endometrial
cancer by using CAGE（Cap Analysis Gene Expression）.One of
the markers is RNA molecules derived from TACC2 gene, a tumor suppressor. While eight isoforms are reported in TACC2 locus, we discovered that the maker RNAs are transcribed by anovel promoter. Our effort to identify its entire structure by using conventional cloning coupled with Sanger sequencing resulted in a series of distinct isoforms. While this unexpectedcomplexity is quite interesting in terms of transcription and its
regulation, it raises an important question in the aspect of application as clinical application：which isoform is the moststrongly associated with lymph node metastasis. Methods Oxford Nanopore technology（MinION）to sequence amplicons prepared from the TACC2 locus. The technology enables us to determine long nucleotide sequences（from 6 bases to over 100kbases）with single molecule, while a conventional Sanger sequencer determines 1kbp and a typical next generation sequencer in Illumina determines 〜300 bases. Results We obtained 2,211,504 sequences from amplicons of the TACC2ʼs novel
isoform（i.e. starting from the novel 1st exon）. The number ofreads are 147,434 fold larger than the one of our previous sequencing by Sanger sequencer. Conclusion The data set provides us an unique opportunity to confirm the isoforms identified previously, and to explore further novel isoforms.

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Objective Cell lines are very useful for clinical and basic research. Due to the scarcity of information, the establishment of auterine malignant tumor cell line with distinctive characteristics is particularly important to study this disease. Thus, thisstudy was undertaken to establish and characterize a new human serous carcinoma of the uterine corpus. Methods The cellline NOMH 2 was established from a uterine tumor of a 65
year old woman. Features of the cell line studied included morphology, chromosome analysis, heterotransplantation, tumor
markers, and chemosensitivity. Results This cell line has grown
well for 23 years and has been subcultured more than 50 times.
Monolayer cultured cells are polygonal in shape and appeared
to be epithelial showing a tendency to pile up without contact
inhibition. The doubling time was 149 hours, the saturation density was 2.4×104/cm2, the plating efficiency was 13.4% and themitotic index was 0.5%. The chromosomal number shows aneuploidy and the modal chromosomal number was in the hypohexaploid range. The cells could be transplanted into the subcutis of nude mice and produced tumors resembling the original
tumor. NOMH 2 cells（2×106/5ml）produced tissue polypeptide
antigen（TPA）, 1,500 U/mL；CA125；100 U/mL；CA19 9, 86
U/mL during 5 days in culture media. The cells were sensitiveto actinomycin D, cisplatin, carboplatin, mitomycin C by MTT
assay. Point mutations were found in MLH 1 and TP53 gene.
Conclusion NOMH 2 would be very useful for basic research ofuterine serous carcinoma.

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Dysadherin regulates cell invasion and might be an independent prognostic factor in uterine endometrial cancer Kyoko
Akashi, Taisuke Mori, Hiroshi Matsushima, Kaori Yoriki,
Tetsuya Kokabu, Haruo Kuroboshi, Morio Sawada, Hiroshi
Tatsumi, Jo Kitawaki Kyoto Prefectural University of Medicine
Objective Dysadherin, one of membrane glycoproteins, is inversely correlated with the expression of E cadherin and an unfavorable prognostic factor and in some kinds of cancer. However, the significance of dysadherin in uterine endometrial cancer still remains unexamined. The aim of this study is to examine the expression and the function of dysadherin in uterine endometrial cancer. Methods Specimens from patients with endometrial cancer were immunochemically stained with E cadherin and dysadherin. A quantitative PCR. Matrigel invasion/
migration assay, and scratch assay were performed in endometrial cancer cell lines, Ishikawa less expressing dysadherin, and KLE cells higher expressing dysadherin, transfectedwith dysadherin plasmid and knocked down for dysadherin forsiRNA. Results The research protocol was approved by the Institutional Review Board. Eighty five specimens from patientswith endometrial cancer were examined. Dysadherin was
highly expressed in 22.4%（19/85 cases）,while E cadhrein was
in 54.1%（46/85）. There was no inverse association in the expression of dysadherin with E cadherin. Dysadherin expression was
significantly associated with lymphatic metastasis and vascularinvasion. Kaplan Meier analysis revealed dysadherin expression was inversely correlated with progression free survival. In
vitro experiment, dysadherin overexpression stimulated invasion and migration in Ishikawa cells, regardless of the proliferative capacity. On the hand, dysadherin knockdown reduced invasiveness and cell motility of KLE cells. Conclusion Dysadherin could regulate invasiveness and cell motility leading to be
an unfavorable prognosis factor in uterine endometrial cancer.

Over expression of Carbonyl reductase 1 induces MET bysuppressing transforming growth factor beta signaling inuterine leiomyosarcoma cells Takuya Kajimura, Shun Sato,
Kengo Nakashima, Toshiaki Taketani, Koutarou Sueoka,
Norihiro Sugino Yamaguchi University
Objective Carbonyl reductase 1（CBR1）is an NADPH dependent, mostly monomeric, cytosolic enzyme. We reported that
CBR1 suppresses epithelial mesenchymal transition（EMT）in
uterine cervical squamous cell carcinoma. Uterine sarcoma is
one of high grade malignancy tumor. This study investigatedwhether CBR1 induces mesenchymal to epithelial transition（MET）in uterine sarcoma and inhibits sarcomaʼs malignant behaviors. Methods（1）We established the clone of uterine leiomyosrcoma cell line, SKN, in which CBR1 was over expressed,and expressions of EMT related markers and TGFβ which iswell known to induce EMT were analyzed by Western blot and
RT PCR.（2）To investigated whether TGFβ actually induces
EMT in the CBR1 overexpression cells, the cells were treatedwith TGFβ（10 ng/ml）for 4 days. Furthermore, to investigatedwhether suppression of TGFβ signaling induces MET, SKN
cells were treated with TGFβ receptor blocker（SB431542,
10 μM）for 24 h. Results（1）In the CBR1 overexpression cells,
expressions of epithelial markers of EMT（E cadherin, cytokeratin）were increased while mesenchymal markers（N cadherin,
fibronectin）were decreased, and also TGFβ was decreased, indicating that CBR1 induces MET with the decrease in TGFβ.（2）TGFβ decreased E cadherin expression with the increase insnail, a transcription factor to suppress E cadherin. TGFβ receptor blocker increased E cadherin expression with the decrease in snail expression of the TGFβ signaling induces MET.
Conclusion CBR1 induces MET by suppressing the TGFβ signaling, which may inhibit the malignant behaviors in uterine
leiomyosarcoma. This study provides a novel therapeutic strategy targeting CBR1 for uterine leiomyosarcoma.

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The role of myeloid derived suppressor cells（MDSC）in the
induction of endometrial cancer stem cells（CSC） Eriko
Yokoi, Seiji Mabuchi, Naoko Komura, Katsumi Kozasa,
Hiromasa Kuroda, Yuri Matsumoto, Michiko Kodama, KaeHashimoto, Kenjiro Sawada, Tadashi Kimura Osaka University
Objective To investigate the role of MDSC and 17β estradiol（E2）in the induction of CSC in endometrial cancer. Methods
CSC was defined as cells with high aldehyde dehydrogenase（ALDH）1 activity. 1）Tumor samples and clinical data from surgically treated endometrial carcinoma cases treated from January 2000 to March 2016 were collected. Then, the relationshipbetween the immunoreactivities for G CSF, CD33, or ALDH1 intumor, pretreatment white blood cell（WBC）counts, and their
prognosis were examined. 2）G CSF expressing and Mock expressing endometrial carcinoma cell lines were established.
Cells were subcutaneously inoculated into nude mice. The frequencies of MDSC and CSC in tumors were examined by flow
cytometry. 3）MDSC isolated from tumor bearing mice were
co cultured with endometrial carcinoma cell line in the presence or absence of E2. Then the frequencies of CSC were examined. Results 1）A positive correlation was demonstrated between the immunoreactivities for G CSF, ALDH1, CD33（MDSC
marker）,and pretreatment WBC count. 2）Increased MDSC and
CSC were observed in G CSF expressing endometrial cancer
cell derived tumors. 3）MDSC induces CSC through the production of PGE2. E2 enhanced the activity of MDSC to induce CSC.
Conclusion MDSC induced by tumor derived G CSF, together
with E2, promote CSC expansion via the production of PGE2.

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Prolactin contributes to the cell proliferation of type 1 endometrial cancer by the regulation of prolactin receptor andestrogen
receptor
via
MAPK
signaling
pathway
Erdenebaatar Chimeddulam1, Munekage Yamaguchi1, Fumitaka
Saito1, Hironori Tashiro2, Hidetaka Katabuchi1 Kumamoto University 1, School of Health Science, Kumamoto University 2
Objective Elevated levels of serum prolactin have been reported to contribute to the tumorigenesis of organs expressing
prolactin receptor（PRLR）. We previously reported that the expressions of PRLR and pJAK2 in cancer cells were significantly
increased in hyperprolactinemic patients with type 1 endometrial cancer（EC）in the 69th annual congress of Japan Society of Obstetrics and Gynecology. This study aims to elucidate
the effect of prolactin on type 1 EC cell lines. Methods Prolactin
and/or estradiol（E2）were added in culture mediums of EC celllines（Ishikawa cells and HEC 1）. The proliferative ability ofcell lines was assessed using MTS assay. The expressions of
PRLR, pJak2, pERK1/2, pMEK1/2, and estrogen receptor alpha（ER α）were evaluated using western blotting. AG490（JAK2 inhibitor）or U0126（MEK1/2 inhibitor）were administered to assess the effect of prolactin on the downstream pathway of PRLR.
Results MTS assay showed that the proliferative ability of EC
cell lines was significantly increased after adding prolactin and/or E2. The administration of both prolactin and E2 was most effective on the proliferative ability. Western blotting revealed
that the expressions of PRLR, pJAK2, pERK1/2, pMEK1/2, andER α in cell lines were increased after adding prolactin. The
concomitant administration of AG490 or U0126 inhibited the increased expressions of those proteins. Conclusion Prolactin

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modulates the expression of PRLR and ER α in type 1 EC cells
via MAPK signaling. This mechanism may contribute to enhancing their proliferation particularly after adding both prolactin and E2. Anti prolactin drug may be a treatment option forpremenopausal women with type 1 EC especially who desirepreserving fertility.

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Genetic and epigenetic characterization of young onset endometrial cancer Takeshi Makabe1, Eri Arai2, Akira Hirasawa1,
Wataru Yamagami1, Nobuyuki Susumu3, Mamoru Tanaka1,
Daisuke Aoki1, Yae Kanai2 Keio University 1, Department of Pathology, Keio University 2, International University of Health andWelfare 3
Objective This study aimed to clarify the genetic and epigenetic features of young onset endometrial cancer. Methods Targeted sequencing of 50 tumor related genes and single CpG
resolution genome wide DNA methylation analysis were performed using the Ion AmpliSeq Cancer HotSpot Panel v2 andthe Infinium MethylationEPIC BeadChip, respectively, for 31
samples of normal control endometrium（C）from patients without endometrial cancer, 34 samples of endometrial cancer frompatients aged 40 years or less（YE）, and 40 samples of endometrial cancer from patients elder than 40 years of age（OE）.
Results There were distinct differences in non synonymous
driver mutations between the YE and OE samples. Principal
component analysis revealed distinct DNA methylation profilesof endometrial cancers that differed from those of C samples.
There were significant differences in the levels of DNA methylation at 1,034 CpG sites between YE and OE samples, and thesewere considered to potentially create differences in the expression levels of tumor related genes, such as those participating in
the cell cycle and autophagy. Unsupervised hierarchical clustering analysis of YE specific DNA methylation profiles clustered
the YE samples into Clusters YA（n=22）and YB（n=12）.Clinicopathologically less aggressive tumors tended to be accumulated in Cluster YB. Eleven marker CpG sites discriminated YB
samples from YA samples with 100% sensitivity and specificity.
Conclusion Genetically and epigenetically different pathways
may participate in the development of YEs and OEs. During
treatment of YE patients, 11 CpG sites act as biomarkers for predicting patients amenable to fertility preservation.

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A long non coding RNA LUCAT1 mediates taxane resistance acquisition in ovarian cancer Satoshi Tamauchi, Hiroaki
Kajiyama, Nobuhisa Yoshikawa, Fumi Utsumi, Shiro Suzuki,
Fumitaka Kikkawa Nagoya University
Objective Recently, long non coding RNAs（lncRNAs）have
been recognized as key factors of several malignancies. In addition, anticancer drug resistance including taxane is one of thebiggest problems in cancer treatment. However, the relationship between lncRNA and taxane resistance has not been reported so far. In this study, we aimed to clarify the relation between lncRNAs and taxane resistance acquisition. Methods A
microarray was used to identify lncRNA candidates relatingtaxane resistance, which analyzed gene expression changes in 3
couples of paclitaxel resistant cell lines and control cell lines.
For lncRNAs whose expression changed more than 2 fold, functional analysis was performed. Results The microarray revealed
that expression of three lncRNAs were increased, and one wasdecreased more than 2 fold. Of these, knockdown of a lncRNA
LUCAT1 significantly reduced taxane resistance in ovarian. LUCAT1 might not only procancer cell lines in vitro（p＜0.05）
mot drug excretion, but also induce microtubule instability andpromote taxane resistance. LUCAT1 knockdown also reduced

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CXCL10 works as a tumor promoter in tumor microenvironment in ovarian cancer Juri Ogishima1, Ayumi Taguchi1, Kei
Kawana2, Mitsuyo Yoshida1, Akira Kawata1, Masakazu Sato1,
Kensuke Tomio1, Katsuyuki Adachi1, Takeshi Nagamatsu1,
Katsutoshi Oda1, Yutaka Osuga1, Tomoyuki Fujii1 The Universityof Tokyo 1, Nihon University 2
Objective CXCL10 is a chemokine which attracts activated T
cells into inflammatory environment, however the relationshipbetween its expression and tumor progression remains unclear.
We investigated prognostic impact and effects on tumor microenvironment（TME）of CXCL10 in ovarian cancer. Methods
Ovarian cancer specimens（RNA and paraffin sections）were obtained from 50 patients under informed consent and approval of
our ethics committee, for cDNA microarray analysis and immunohistochemical staining of CXCL10. Correlation between
CXCL10 expression and clinicopathological findings was assessed with focus on neutrophil to lymphocyte ratio. Mice wereintraperitoneally injected with KRAS transfected murine ovarian cancer cell line, ID8 KRAS. Concentration of CXCL10 in ascites was assessed by specific ELISA. DC and T cell subsets
were assessed by flow cytometry. Results The level of CXCL10
in tumor was significantly higher in serous carcinomas, compared to endometrioid or clear cell carcinomas（serous：746.7±219.6, endometrioid：582.0±479.4, clear cell：360.6±135.9,
Wilcoxon test, p＜0.05）. Immunohistochemistory revealed
CXCL10 was mainly expressed in cancer cells, not in stromalcells. Overall and progression free survival were significantly
lower in CXCL10 high group, compared to CXCL10 low group（log rank test：p=0.02, p=0.01, respectively）. Neutrophil tolymphocyte ratio was significantly higher in CXCL10 highgroup, compared to CXCL10 low group. In vivo, expression of
CXCL10 in ascites was significantly increased accompaniedwith decreased number of cDCs and Tim 3+PD 1+CD8+ exhausted T cells along with tumor progression. Conclusion
Higher level of CXCL10 was associated with poor prognosis in
ovarian cancer. CXCL10 might modulate TME and promote tumor progression.

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CXCL17, as a key regulator of microenvironment, promotes
peritoneal dissemination in ovarian cancer Akira Kawata1,
Ayumi Taguchi1, Juri Ogishima1, Mitsuyo Yoshida1, Hiroe
Nakamura1, Masakazu Sato1, Kensuke Tomio1, Katsuyuki
Adachi1, Katsutoshi Oda1, Kei Kawana2, Yutaka Osuga1,
Tomoyuki Fujii1 The University of Tokyo 1, Nihon University 2
Objective Tumor Associated Macrophage（TAM）and Myeloid
derived suppressor cell（MDSC）are known to promote anchorage independent proliferation of cancer cells via activation of
EGF/FGF signaling. In ovarian cancer, spheroid formation ofcancer cells is essential for progression of peritoneal dissemination. We herein investigated the association of CXCL17, a
chemokine, with TAM and MDSC, and its role on spheroid formation in ovarian cancer progression. Methods Mice were intraperitoneally injected with a KRAS transfected mouse ovarian cancer cell line, ID8 KRAS, under approval of institutional
ethics committees. Spheroid formation was assessed in vitro under EGF/FGF treatment. cDNA microarray was analyzed for 2
D cultured or 3D cultured tumor cells in vitro . In vivo timecourse analysis of tumor microenvironment（TME）such as
TAM and MDSC, was investigated using flow cytometry. We

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ability of cell proliferation（p＜0.05）. Conclusion We identified
the novel lncRNA LUCAT1 involved in taxane resistance inovarian cancer. Taxane resistance is also a serious problem inother malignancies, and further investigation is required.

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evaluated effects of CXCL17 level on tumor progression and alteration of TME with a CXCL17 knockdown cell line（shCXCL
17 ID8KRAS）established by shRNA technique. Results EGF/
FGF treatment markedly promoted spheroid formation in vitro .
In 3D condition, 1,653 genes were upregulated, compared to 2D
condition. Especially, CXCL17 expression was increased by 8times. CXCL17 was also upregulated in peritoneal floating cancer cells in vivo . MDSC fraction was significantly increased
along with the tumor progression（control vs ID8 KRAS：0.3%
vs 8.6%）. shCXCL17 ID8KRAS significantly suppressed tumor
progression, accompanied with decreased number of MDSCs in
ascites. Conclusion Our findings suggest that transformationinduced chemokine, CXCL17, may promote peritoneal dissemination in ovarian cancer, mainly through spheroid formation via
CXCL17 attracted MDSCs and EGF/FGF signaling.

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Antisense oligo nucleotide of Annexin A4 improves platinum
resistance in ovarian clear cell carcinoma Reisa Kakubari,
Satoshi Nakagawa, Eiji Kobayashi, Shinya Matsuzaki, Yutaka
Ueda, Kiyoshi Yoshino, Tadashi Kimura Osaka University
Objective Annexin A4 is overexpressed in ovarian clear cell
carcinoma（OCC）and contributes to chemoresistance. Our object is to develop the antisense oligonucleotides（ASOs）targeting Annexin A4 to improve chemosensitivity in OCC. Methods
We used ASO targeting mRNA of Annexin A4 with 2,4 bridged
nucleic acid. Gene suppression efficiency of Annexin A4 in
ASO transfected cell line was analyzed by real time PCR in vitro. In 16 types of ASOs targeting Annexin A4, 2 ASOs hadstrong gene suppression effect. We analyzed suppression of Annexin A4 in ASO transfected RMG I, OVISE cell lines（CCC）invitro. Drug resistance for platinum was analyzed with IC50 values and intracellular accumulation of platinum. We used ICR
nu/nu mice subcutaneously xenografted with CCC cell lines toassess the improvement of platinum resistance in vivo and also
determined the adverse event of ASO against the tumor infiltrated macrophages and NK cells by FACS analysis. Intraperitoneal injection of cisplatin 3mg/kg after intratumoral administration of ASO 1mg/kg each twice a week were given to
xenografted mice and tumor volumes were monitored. Results
Annexin A4 ASO effectively suppressed Annexin A4 expression in vitro. As we expected, Annexin A4 ASO transfected
cells were significantly resistant to cisplatin（IC50=3.3μM）compared control（IC50=5.2μM）in RMG 1 cell line. Intracellular
platinum accumulation increased in Annexin A4 ASO transfection cell. Intratumoral administration of Annexin A4 ASO significantly improved platinum sensitivity in vivo. Conclusion
Annexin A4 ASO improved chemosensitivity by suppressing
Annexin A4 expression both in vitro and in vivo. Targeting Annexin A4 by ASO would be a promising therapeutic option forchemoresistant OCC.

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Histone methyltransferases are the candidate therapeutic targets in high grade serous ovarian carcinoma（HGSC）Asako
Kukita, Kenbun Sone, Katsutoshi Oda, Hidenori Machino,
Machiko Kojima, Shinya Oki, Michihiro Tanikawa, Kazunori
Nagasaka, Yoko Matsumoto, Osamu Hiraike, Yutaka Osuga,
Tomoyuki Fujii The University of Tokyo
Objective Dysregulation of histone methylation could be involved in human carcinogenesis. Several histone methyltransferases have been reported to be overexpressed in various typesof cancers. However, there have been no reports of comprehensive analysis of histone methyltransferases in HGSC. The aim of
this study is to elucidate the dysregulation of methyltransferases in HGSC. Methods We screened 9 methyltransferases,!

which are reported as overexpressed in other human cancers.
We analyzed the expression of these genes by quantitative realtime PCR（q PCR）with 39 clinical specimens of HGSC. Written
informed consent was obtained from all participants and thisstudy was approved by our ethics committee. We performed
knockdown experiments using siRNA against histone methyltransferases and control siRNA（siNC）in HGSC cell lines. The
anti tumor effects were examined with immunoblotting, MTT
assay, cell cycle analysis, and Annexin V FITC. Results Q PCR
revealed that 6 out of 9 methyltransferases（including）were
overexpressed in clinical HGSC specimens（P＜0.01）, comparedwith a normal ovarian tissue specimen. In addition, knockdownof several histone methyltransferases using specific siRNAs resulted in growth suppression and apoptosis induction of HGSC
cells, accompanied by attenuation of histone methylation. Conclusion The present findings highlight that overexpressed histone methyltransferases are involved in HGSC tumorigenesis
and that several histone methyltransferases might be novel candidates for treating HGSC.

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Clinicopathological characteristics of clear cell ovarian carcinomas without any mutations in ARID1A and PIK3CA
Akira Nishijima1, Katsutoshi Oda1, Kosei Hasegawa2, KayoAsada1, Akira Kurosaki2, Takahiro Koso1, Aki Miyasaka2, Yuji
Ikeda2, Keiichi Fujiwara2, Yutaka Osuga1, Tomoyuki Fujii1 The
University of Tokyo 1, Saitama Medical University International
Medical Center 2
Objective Approximately 50% of clear cell ovarian carcinomas（CCOC）harbor mutations of ARID1A and PIK3CA, and coexistence of these mutations is frequent. However, the biologicalcharacteristics of CCOC which lacks mutations in ARID1A andPIK3CA（ double negative genotype）have not been fully understood. We aimed to clarify the clinico pathological characteristics of double negative CCOC. Methods We performed
whole exome sequencing in 78 CCOC surgical specimens underinformed consent and approval of our ethics committee. We analyzed the clinicopathological characteristics of double negative group, and pathologically reviewed all the double negative CCOC samples. Results We identified ARID1A and/or PIK
3CA mutations in 57 CCOC samples, which classified 21 tumors
as double negative group. The double negative group
showed significantly poor progression free survival（p=0.0052
by Log rank test）,with higher ratio of TP53 mutations（29%）,
compared with the other group（1.8%）（p=0.0012 by Fisherʼs exact test）. Pathological review revealed that six out of 21（28%）
double negative group partially contained components which
are suspicious of high grade serous carcinomas（ SC likegroup）.TP53 was mutated in 3 of 6 SC like group（50%）andin 2 of 15（13%）in the remaining 15 samples（ non SC likegroup）（p=0.11）. High grade nuclear atypia（Grade 3）was morecommon in SC like group, compared with the non SC
like group（83% vs 33%, p=0.063）. Conclusion Genotyping by
mutational status of ARID1A and PIK3CA may be useful toidentify CCOC with more aggressive biology. Our data suggestthat double negative CCOC includes certain tumors with biological similarity to high grade serous carcinomas with TP53
mutations.

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Ultrasound based logistic regression model LR2 versus magnetic resonance imaging for discriminating between benign
and malignant adnexal masses：a prospective study Kanae
Shimada1, Koji Matsumoto1, Takashi Mimura1, Chiaki Iitsuka1,
Shingo Miyamoto1, Tetsuya Ishikawa1, Mamiko Onuki1,
Kiyotake Ichizuka1, Hajime Tsunoda2, Akihiko Sekizawa1 Showa

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Combination of MDM2 inhibitor, DS 3032b, and mTOR inhibitor, everolimus, exerts antitumor effect in ovarian andrenal clear cell carcinomas Yoshiko Kawata, Kazunori
Nagasaka, Katsutoshi Oda, Shinya Oki, Makoto Takeuchi,
Chinami Makii, Michihiro Tanikawa, Kenbun Sone, Yoko
Matsumoto, Yutaka Osuga, Tomoyuki Fujii The University ofTokyo
Objective Both MDM2 overexpression and activation of mTOR
pathway are frequent in clear cell carcinomas of the ovary andkidney. We aimed to clarify anti tumor effect of inhibition of
MDM2 and mTOR in ovarian and renal clear cell carcinomas
with wild type p53. Methods We investigated the effect ofeither MDM2 inhibitor（DS 3032b）or mTOR inhibitor（everolimus）in 8 ovarian（OVISE, OVTOKO, RMG 1, JHOC7,
OVMANA, JHOC9, ES2, SKOV3）and 2 renal（Caki 1, Caki2）cell clear cell carcinoma lines. The cell viability was evaluated by MTT assay and flow cytometry. In vivo anti tumor effect was investigated by oral administration of（i）DS 3032b at
50 mg/kg/day,（ii）everolimus at 5 mg/kg/day, or（iii）combination of these two drugs for 3 weeks in mouse xenograft models.
Results Dose dependent suppression of cell proliferation by
DS 3032b was observed only in cells with wild type p53（Median IC50：181.8 nM）,while sensitivity to everolimus was generally observed in clear cell carcinoma cells, regardless of p53 mutational status（Median IC50：728.6 nM）.The IC50 values of DS
3032b were drastically decreased when combined with 1 nM of
everolimus. Combination of DS 3032b and everolimus increased
the ratio of apoptotic cells in wild type p53 cancer cells. In
mouse xenograft models, oral administration of combination
DS 3032b and everolimus significantly suppressed the tumor
growth, compared with each single agent alone（p＜0.05）. Conclusion Our data suggest that co targeting MDM2 and mTOR
signaling might be a promising novel therapy for wt p53 clear
cell carcinomas of both ovary and kidney.

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ISP-6-9The impact of UGT1A1 genotype upon prognoses of the patients with ovarian clear cell carcinomas a historically controlled
study
Masashi Takano1, Tomoyuki Yoshikawa1,
Morikazu Miyamoto2, Tadashi Aoyama2, Hiroaki Soyama2,
Kento Kato2, Takahiro Sakamoto2, Kazuki Takasaki2, Mika
Kuwahara2, Tomoko Goto2, Hidenori Sasa2, Kenichi Furuya2 Department of Tumor Chemotherapy, National Defense Medical
College Hospital 1, National Defense Medical College Hospital 2
Objective Genotyping of UGT1A1*28 and *6 was supported bynational insurances since 2008 in Japan, however, there still exists argument over clinical application of the genotyping. The
aim of the study was to evaluate the clinical significance of UGT
1A1 upon prognoses of the patients with ovarian clear cell carcinomas. Methods Medical records of the patients with ovarian
clear cell carcinoma that met inclusion criteria were reviewed（UGT group）：（a）those whose UTG1A1 genotype were available,（b）those treated with irinotecan based therapy. For historical control group（Non UGT group）, the patients treatedwith irinotecan based therapy without UGT1A1 genotyping
were evaluated. The study protocol was approved by the IRB of
our hospital. Results A total of 17 cases with UGT group and 37
cases with non UGT group patients were analyzed. There wereno significant difference clinical parameters including age,stage distribution. UGT group included 8 cases with wild type,
8 cases with hetero type, and one case with homo type genotype. There was no significant difference of progression freesurvival in stage I patients between UGT group and non UGTgroup. Among UGT group Stage I patients, recurrence was observed in 67%（2/3）in wild type cases, and 14%（1/7）in hetero/homo type patients（p=0.097）. Additionally, G4 hematologic toxicities were frequently observed in hetero/homo type patients.
Conclusion Although significance was not observed, recurrence
was frequently observed in the patients with UGT1A1 wild
type patients compared with UGT1A1 hetero/homo type patients. The doses of irinotecan based therapy might be lower for
the UGT1A1 wild type patients with ovarian clear cell carcinomas, although further studies are needed to confirm the results.

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CRISPR/Cas9 mediated genome editing and efficient PD L1
disruption on tumor cells promote antitumor immunity andsuppress ovarian cancer progression in a mouse model
Tamaki Yahata, Naoyuki Iwahashi, Mika Mizoguchi, Madoka
Yamamoto, Noriyuki Sasaki, Michihisa Shiro, Yasushi Mabuchi,
Wakayama
Shigetaka Yagi, Sawako Minami, Kazuhiko Ino
Medical University
Objective Programmed cell death ligand 1（PD L1）on tumor
cells unfavorably impacts patient prognosis. However, the functional roles of PD L1 in ovarian cancer progression remain unclear. In this study, we examined the pathophysiological roles of
PD L1 in ovarian cancer. Methods Under the approval of institutional committee, PD L1 was genetically disrupted in murine
ovarian cancer cell lines, ID8 and HM 1, using CRISPR/Cas9
mediated genome editing. The generated PD L1 knockout（KO）
ovarian cancer cells and control cells were intraperitoneally inoculated into syngeneic mice, and survival time and tumor dissemination were evaluated. Moreover, intratumoral lymphocyte
recruitment and cytokine levels were analyzed by immunohistochemistry and RT PCR. Results The survival time was significantly longer in PD L1 KO ID8 inoculated group comparedwith control group. The tumor weight and ascites volume weresignificantly reduced in PD L1 KO ID8 and PD L1 KO HM 1
groups compared with control groups. Immunohistochemically,
the number of intratumoral CD4+ T cells, CD8+ T cells, and NK
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University 1, NTT Medical Center Tokyo 2
Objective The diagnostic performances of the International
Ovarian Tumor Analysis（IOTA）ultrasound based logistic regression model（LR2）and magnetic resonance imaging（MRI）
in discriminating between benign and malignant adnexal
masses have not been directly compared in a single study. Methods Using IOTA LR2 model and subjective interpretation of
MRI findings by experienced radiologists, 265 consecutive patients with adnexal masses were preoperatively evaluated in
two hospitals between February 2014 and December 2015. Definitive histologic diagnosis of excised tissues was used as a gold
standard. Results From the 265 study subjects, 54（20.4%）tumors were histologically diagnosed as malignant（including 11
borderline and 3 metastatic tumors）.Preoperative diagnoses ofmalignant tumors showed 91.7% total agreement between IOTA
LR2 and MRI, with a kappa value of 0.77（95% confidence interval［CI］：0.68 0.86）. Sensitivity of IOTA LR2（0.94, 95% CI：
0.85 0.98）for predicting malignant tumors was similar to that of
MRI（0.96, 95% CI：0.87 0.99；P=0.99）, while specificity of
IOTA LR2（0.98, 95% CI：0.95 0.99）was significantly higher
than that of MRI（0.91, 95% CI：0.87 0.95；P=0.002）. Combined
IOTA LR2 and MRI results gave the greatest sensitivity（1.00,
95% CI 0.93 1.00）and had similar specificity（0.91, 95% CI 0.860.94）to MRI. Conclusion The IOTA LR2 model had a similarsensitivity to MRI for discriminating between benign and malignant tumors and a higher specificity compared with MRI. Ourfindings suggest that IOTA LR2 model, either alone or in conjunction with MRI, should be included in preoperative evaluation of adnexal masses.

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groups compared with in control groups. In contrast, the number of regulatory T cells was significantly reduced in PDL1 KO
groups. The intratumoral gene expression of IFN γ, TNF α, IL
2, and IL 12a was significantly higher, whereas IL 10, VEGFa,
and MMP9 were significantly reduced in PDL1 KO ID8 groupcompared with control. Conclusion CRISPR/Cas9 mediatedPD L1 disruption promoted antitumor immunity by increasing
tumor infiltrating lymphocytes and modulating cytokine production, thereby suppressing ovarian cancer progression. Thissuggests that PD L1 targeted therapy by genome editing may
be a novel therapeutic strategy for ovarian cancer.

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Exosomal miR 99a 5p is upregulated in ovarian cancer patientsʼ sera and enhance PAI 1 expression in neighboring
peritoneal mesothelial cells to facilitate cancer invasion
Akihiko Yoshimura, Kenjiro Sawada, Koji Nakamura, Aasa
Shimizu, Masaki Kobayashi, Mayuko Miyamoto, Erika
Nakatsuka, Michiko Kodama, Kae Hashimoto, Seiji Mabuchi,
Tadashi Kimura Osaka University
Objective RNA containing exosomes in circulating blood are
emerging as potential target for disease diagnosis. The purposeof this study was to identify which miRNAs are highly produced
from ovarian cancer（OC）, to analyze whether serum miRNAcan detect OC, and to examine the functional role of these miRNAs. Methods Using miRNA microarray, we found that several
miRNAs including miR 99a 5p were specifically elevated in
exosomes derived from OC. Expression level of serum miR 99a
5p of 58 patients with OC, 26 patients with benign ovarian tumor and 20 healthy controls were determined by miRNA qRTPCR. To examine the role of miR 99a 5p in peritoneal dissemination, human peritoneal mesothelial cells（HPMCs）were transfected with miR 99a 5p mimic and the effect of cell invasion
and proliferation was analyzed. Proteomic analysis with transfected HPMC was performed using tandem mass tag method.
Results Serum miR 99a 5p levels were significantly increasedin OC patients compared with those with benign tumor andhealthy controls（2.1 fold and 4.0 fold, respectively）. ROC analysis showed that using a cut off of 1.57, the sensitivity and specificity were 78% and 68% respectively for detecting OC（AUC0.78）. The cell invasion was significantly increased through
HPMCs transfected with miR 99a 5p compared with negative
control. Plasminogen activator inhibitor 1（PAI 1）expression
was increased in HPMCs transfected with miR 99a 5p. Conclusion Serum miR 99a 5p was increased in OC patients and has
the potential to predict OC. Exosomal miR 99a 5p promotes cell
invasion by affecting HPMCs through PAI 1 upregulation.

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Induction of anti VEGF therapy resistance by upregulated
expression of microseminoprotein （ MSMP ） Takashi
Mitamura Hokkaido University HospitalObjective Anti VEGF therapy has demonstrated efficacy intreating human metastatic cancers, but therapeutic resistance isa practical limitation and most tumors eventually become unresponsive. Methods To identify microenvironmental factors underlying the resistance of cancer to anti angiogenesis therapy,
we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti VEGF therapy（B20antibody）developed. Results We found that expression of the
microseminoprotein, prostate associated（MSMP）gene was substantially upregulated in resistant compared to control tumors.
MSMP secretion from cancer cells was induced by hypoxia, triggering MAPK signaling in endothelial cells to promote tube formation in vitro. Recruitment of the transcriptional repressor
CTCF to the MSMP enhancer region was decreased by histone

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acetylation under hypoxic conditions in cancer cells. MSMP
siRNA, delivered in vivo using the DOPC nanoliposomes restored tumor sensitivity to anti VEGF therapy. In ovarian cancer patients treated with bevacizumab, Increased expression of
MSMP was associated with significantly reduced disease freesurvival in ovarian cancer patients given bevacizumab. Conclusion These findings imply that MSMP inhibition combined withthe use of anti angiogenesis drugs may be a new strategy toovercome resistance to anti angiogenesis therapy.

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Genomic alterations of tumor related pathways suppresses a
mitochondrial function through the activation of PDK2 inovarian clear cell carcinoma Sachiko Kitamura, Ken
Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo
Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
Kyoto University
Objective Although various molecular targeting therapies havebeen developed, cancer cells can survive for escaping from targeting the specific pathway. Targeting metabolism is an attractive strategy to overcome this problem because tumor related
pathways regulate metabolism. We previously reported cancer
specific metabolism regulated by HNF1B pathway and the activation of KRAS PIK3CA AKT1 PTEN and MYC CDK2/4 RB
1 pathways in ovarian clear cell carcinoma（OCCC）. The aim of
this study is to identify universal metabolic targets induced bygenomic alterations which render chemoresistance in OCCC.
Methods 39 OCCC clinical samples and 13 OCCC cell lines wereanalyzed by whole exome sequencing and gene expression microarray. Immunohistochemistry, cell viability assay, apoptosis
assay and in vivo a mouse xenograft model experiements wereconducted. Results Chromosome（chr）17q21 24 was significantly amplified in recurrent cases and the genes associatedwith mitochondrion were significantly enriched in chr17q21 24
amplified cases. Cell viability assay revealed chr17q21 24 amplification correlated with resistance to cisplatin. Pyruvate dehydrogenase kinase 2（PDK2）located on chr17q21 regulates pyruvate entering into TCA cycle in mitochondrion. Inhibitors targeting the pathway in PIK3CA AKT, MDM2 TP53 or MYC
RB1 reduced PDK2 expression. Immunohistochemistry showed
high PDK2 expression was associated with poor prognosis.
Knock down of PDK2 by short hairpin targeting PDK2 and theinhibitor, dichloroacetate（DCA）, increased cisplatin sensitivity
by upregulation of mitochondrial ROS production. A mouse
xenograft model showed DCA synergically inhibited tumor
growth with cisplatin. Conclusion Genomic alterations of tumor related pathways leading to upregulation of PDK2 expression rendered OCCC platinum resistance. Targeting metabolism such as PDK2 is a new therapeutic strategy for OCCC.

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Role of RNA chaperones in ovarian cancer metastasis Mahy
Egiz1, Kazuyuki Kitatani2, Masafumi Toyoshima1, Masumi
Ishibashi1, Shogo Shigeta1, Junko Minato1, Nobuo Yaegashi1 Tohoku University 1, Tohoku Medical Megabank Organization 2
Objective The lethality of ovarian carcinoma primarily stems
from the inability to detect the disease at an early, organ confined stage, and the lack of effective therapies for advanced
stage disease. Ovarian cancer metastasis requires many cellular
processes such as cellular ability to form lamellipodia, to migrate from the primary site and to invade surrounding tissues.
La related protein（LARP）4 was described as one of the novel
regulators for cytoskeletal organization, cell morphology andmigration. Here, we report on LARP4 role in epithelial ovariancancer progression. Methods SKOV3 cells were transfectedwith siRNA directed against LARP4, lamellipodia determined

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CD141 Dendritic cells in ovarian cancer microenvironment
Rin Mizuno, Kaoru Abiko, Tsukasa Baba, Junzo Hamanishi,
Ryusuke Murakami, Masaki Mandai Kyoto University
Objective Patients with higher CD8+ T cell numbers in the ovarian tumor exhibit better prognosis, but the functions of CD8+ T
cells are inhibited in the tumor environment by various factors.
Dendritic cell（DC）mediated cross presentation of exogenous
antigens to CD8+ T cells is necessary for inducing antitumor immunity. The aim of this study is to investigate the function ofDCs, especially CD141+ DCs reported to traffic tumor antigens.
Methods The immunostaining of anti CD141 and ant CD8 inparaffin embedded sections of ovarian cancer clinical samples
was performed to evaluate CD141+ DC and CD8+ T cells. The
number of cells was counted at x400 magnification and the average number of five areas was determined. We evaluated the CD
141+ DC in relations with CD8+ T cells and clinical background.
Results The numbers of CD141+ DC was significantly high in advanced cases（clinical stage I.II vs III.IV, p＜0.05）.Progression
free survival of the patients with higher number of CD141+ DC
tended to be longer than that of the patients with lower numbers（p=0.13）. Patients with higher number of CD141+ DC
tended to have more CD8+ T cells in stroma of the ovarian tumor（p=0.08）. Conclusion Tumor infiltrating CD141+ DC in
ovarian cancer may play important role in uprising anti tumor
immunity by CD8+ T cells.

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A Machine Learning Algorithm Using Blood Biomarkers for
Diagnostic and Prognostic Prediction in Epithelial Ovarian
Cancer Junya Tabata1, Nozomu Yanaihara1, Chihiro Goto1, Yuka
Akiyama1, Ryosuke Saito1, Hiromi Komazaki1, Yasushi Iida1,
Motoaki Saito1, Hirokuni Takano1, Seiji Isonishi1, Eiryo
Kawakami2, Aikou Okamoto1 The Jikei University School of
Medicine 1, RIKEN 2
Objective We aimed to develop an ovarian cancer specific predictive algorithm for the pretreatment estimation of clinicalstage, histotypes, and prognosis of patients with epithelial ovarian cancer（EOC）based on machine learning from multiple
biomarkers available from peripheral blood tests. Methods We
analyzed 334 patients with EOC and 101 patients with benign
ovarian tumors who were treated between 2010 and 2017. We
retrospectively investigated 38 parameters from pretreatment
peripheral blood tests. Either one of four supervised machinelearning classifiers including Bayesian, Neural networks, Random forests, and support vector machines was subjected to a
training and test approach. Results Machine learning basedclassification could distinguish EOC from benign tumors at a
precision of 91% predictive value. However, the preciseness of
predicted staging and histotypes were 77% and 58%, respectively. Values for platelet, fibrinogen, and hemoglobin, in addition to tumor markers, were central factors for classifying histotype. Furthermore, using Random Survival Forests analysis, we
identified factors（total protein, C reactive protein, carbohy-!

drate antigen 125, lactate dehydrogenase, blood urea nitrogen,and albumin）strongly associated with prognosis in patientswith EOC. Supervised clustering analysis based on these factors
identified two distinct clusters in which patient,s survival statistically differed. Conclusion It may be possible to select personalized treatment options by stratifying the prognosis of pretreatment patients with EOC using machine learning based predictive algorithms.

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with confocal microscopy, cell migration assessed by transwell
assay, Rho proteins expression was detected by western blotting. Furthermore, metastatic potential in xenograft model was
determined by counting metastatic nodules in the peritoneum.
Results LARP4 knockdown significantly increased lamellipodia
formation and cell migration. LARP4 knockdown upregulated
Rho family proteins expression. Furthermore, in a LARP4 depleted xenograft model there was a significant increase in metastatic nodules number. Conclusion LARP4 is proposed toserve as a metastasis suppressor protein in ovarian cancer. Rho
family is a possible target for LARP4.

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Diagnosis of early stage ovarian clear cell carcinoma（CCC）and endometrioid carcinoma（EMC） the combination
assay of A2160（Alpha chain of Complement 4 Binding Protein with Fully Sialylated Glycans）and C4BP with all typesof glycans（ALL C4BP） Masaru Hayashi, Hiroko Machida,
Tetsuji Iida, Masae Ikeda, Masako Shida, Takeshi Hirasawa,
Mikio Mikami Tokai University HospitalObjective For detecting early stage CCC, we developed thenovel marker A2160, which can be potentially applied for themonitoring of endometrioma patients（Gynecol Oncol. 2015；
139：520 8）. To upgrade the diagnostic utility of A2160 between endometrioma, early stage CCC and EMC, we tried to examine the combination assay of A2160 and ALL C4BP（COMB）.
Methods A total of 62 patients who had CCC（n=38）or EMC（n=14）or endometrioma（n=10）were enrolled in the study from2009 to 2014. Serum A2160 was measured by LC MS（Liquid
chromatography mass spectrometry）, and ALL C4BP values
were measured by ELISA. Diagnostic accuracy of the combination of A2160 and ALL C4BP（COMB）was compared by AUC.
The COMB value was statistically calculated by the formula,
COMB=［A2160］
×2.0 ［All C4BP］. Results COMB was significantly higher in early stage of CCC and EMC than in en. Diagnostic accuracy ofdometrioma（p＜4.8×10!5 and p＜0.003）
COMB to distinguish early stage CCC from endometrioma washigher than that of A2160 or ALL C4BP only：AUC for ALL C
4BP, A2160 only versus COMB, 82, 90, versus 92%. Diagnostic
accuracy of COMB to distinguish early stage EMC from endometrioma was higher than that of A2160 or ALL C4BP only：
AUC for ALL C4BP, A2160 only versus COMB, 81, 80, versus
86%. Conclusion This combination assay can potentially be applied for monitoring of endometrioma patients and make theearly diagnosis of CCC and EMC possible.

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Ex vivo chemosensitivity assay using patient derived spheroids of ovarian cancer Yu Ito1, Satoshi Kubota2, Yumiko
Kiyohara3, Shinya Matsuzaki1, Eiji Kobayashi1, Toshihiro
Kimura3, Yutaka Ueda1, Kiyoshi Yoshino1, Shoji Kamiura3,
Tadashi Kimura1, Masahiro Inoue3 Osaka University 1, ResearchCenter, Osaka Medical Center for Cancer and Cardiovascular
Diseases 2, Osaka Medical Center for Cancer and Cardiovascular
Diseases 3
Objective The aim of this study is to evaluate the clinical relevance of a newly developed chemosensitivity assay in ovariancancer. Methods We previously developed cancer tissue originated spheroid（CTOS）method, a primary 3D culture system toprepare cancer cells from patient tumors. In this study, we conducted sensitivity assay for paclitaxel and carboplatin using
CTOSs from ovarian cancer. Single CTOS was placed in one
well of a 96 well plate, and five CTOS were examined for one
dose of each drug. After 7 days of culture, CTOS viability wasevaluated by measuring intracellular ATP levels, corrected by
the CTOS size at day 0. Results We prepared CTOSs from 45
ovarian cancer. The overall success rate of CTOS formation andculture was 100%（45 out of 45）. Characteristics of the original
tumors were well retained in CTOS. Among these 45 cases, pa-

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tients diagnosed with FIGO Stage IC IV and underwent TC
chemotherapy were 32 cases. The overall success rate of sensitivity assay was 90.6%（29 out of 32）. The success of the sensitivity assay depended on the amount of specimen. There were substantial differences in sensitivity among the CTOSs from different patients. These results might reflect the clinical diversity inchemosensitivity to paclitaxel and carboplatin among patients.
In some cases, the assay results corresponded with their clinicalcourses. Conclusion We are assessing the correlation between
ex vivo sensitivity assay and clinical patient response. Sensitivity assays using CTOS from ovarian cancer might be useful in
precision medicine.

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these histone methyltransferases in OCCC cell lines. Results Q
PCR revealed that 2 histone methyltransferases（SMYD2 and
WHSC1）were significantly overexpressed in clinical OCCC
specimens, compared with normal ovarian tissues（p＜0.05）.
Knockdown of either SMYD2 or WHSC1 induces growth suppression and apoptosis in OCCC cell lines through attenuation ofhistone methylation of H3K4, H3K36. Conclusion Our results
suggest that overexpression of SMYD2 and WHSC1 is involvedin the cell growth of OCCC. Further functional studies may affirm the importance of SMYD2 and WHSC1as a promisingtherapeutic target for OCCC.

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Lysosomal function estimated through the autophagic features in ovarian carcinoma Koji Kumagai, Masahiro Sakai,
Takayoshi Maeda Osaka Railway HospitalObjective Many cancer cells increase the number of lysosomes
to maintain homeostasis by the degradation and recycling of essential nutrients. Ovarian cancer has 2 major distinct subtypes：high grade serous carcinoma（HGSC）and clear cell carcinoma（CCC）. Recent reports demonstrate that autophagic tumor stroma provide recycled nutrients for cancer cell metabolism. In this study, we estimated the lysosomal function throughthe autophagic features in ovarian HGSC and CCC. Methods
This study was approved by the institutional ethics committee.
We evaluated the expression of microtubule associated protein
1 light chain 3（LC3）and pan cathepsin（panCat）, 2 representative proteins of early and late stage autophagy（i.e. autophagosome and autolysosome）, respectively, by immunohistochemical analysis of paraffin embedded HGSC and CCC tissue
sections. Then we speculated the lysosomal function in thosecarcinomas. Results The average age of the patients with HGSC
（n=6）and CCC（n=6）was 73 and 60 years, respectively, and thenumber of cases of FIGO clinical stage I, II, III, and IV tumors
was 0, 0, 6, 0 and 4, 0, 2, 0, respectively. Consequently, 2 patientswith HGSC and 2 with CCC died of the disease. Strong LC3 andpanCat expression was detected in the tumor stromal cells of
83%（5/6）and 100%（6/6）of patients with HGSC and 66%（4/6）and 50%（3/6）of patients with CCC. These data suggested
the lysosomal involvement between the early and late stage
autophagy both in HGSC and in CCC. Conclusion We estimate
the lysosomal involvement between the early and late stage
autophagy in HGSC and CCC.

The mechanism of ceramide nanoliposomes induced necroptosis in ovarian cancer Xuewei Zhang1, Kazuyuki Kitatani2,
Masafumi Toyoshima1, Masumi Ishibashi1, Shogo Shigeta1,
Junko Minato1, Nobuo Yaegashi1 Tohoku University 1, Tohoku
Medical Megabank Organization 2
Objective Ceramides are bioactive lipids that mediate cell deathin cancer and ceramide based therapy has been proposed forcancer treatment. The most representative ceramide formulation is ceramide nanoliposomes（CNL）that have been preclinically studied. However, the effect of CNL in ovarian cancer isstill unclear. Thus, we investigated the therapeutic efficacy andsignaling mechanisms of the CNL in refractory ovarian cancer.
Methods Cell viability was measured by Cell Titer Glo Kit. Cell
death was determined by Annexin V/7 amino actiomycin D
assay. The proteins involved in apoptosis and necroptosis weredetected by immunostaining. Results Treatment of ovarian cancer cells with CNL decreased the number of living cells. Surprisingly, CNL treatment predominantly induced necrosis, but not
apoptosis. Necrosis is also programmed like apoptosis. Necroptosis, the best characterized form of regulated necrosis, is mediated with regulatory proteins such as protein kinase receptor
interacting protein kinase（RIPK）1, RIPK3 and pseudokinase
mixed lineage kinase domain like（MLKL）. Importantly, dying
cells exhibit activation of MLKL as evidenced by oligomerization and relocalization to the blebbing membranes. Knock downof MLKL with siRNA abolished CNL induced cell death. Mechanistically, ceramide was revealed to interact with MLKL in abinding assay, suggesting MLKL as a novel pro necroptotic target for ceramide. Conclusion CNL is suggested to serve as atherapeutic reagent that inducing MLKL dependent necroptosis in ovarian cancer.

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ISP-8-4Overexpression of histone methyltransferases is involved in
the proliferation of ovarian clear cell carcinomas MachikoKojima, Kenbun Sone, Katsutoshi Oda, Asako Kukita, Hidenori
Machino, Shinya Oki, Michihiro Tanikawa, Kazunori Nagasaka,
Yoko Matsumoto, Osamu Hiraike, Yutaka Osuga, Tomoyuki
Fujii The University of Tokyo HospitalObjective Dysregulation of histone methylation is involved in
the development and progression of cancer. Several histone
methyltransferases have been reported to be overexpressed invarious types of cancers. Meanwhile, there are no reports ofcomprehensive analysis of histone methyltransferases in ovarian clear cell carcinomas（OCCC）. We investigated the involvement of histone methyltransferases in OCCC and evaluatedtheir therapeutic potential. Methods We screened 9 histone
methyltransferases, which were reported to be overexpressedin human cancer. We analyzed expression of these genes byquantitative real time PCR（q PCR）
, in 23 clinical OCCC specimens under informed consent and approval of our ethics committee. Anti tumor effect of histone methyltransferases wasevaluated by knockdown experiments using siRNAs against

GEP oncogene induces epithelial mesenchymal transition
through LATS1 down regulation in ovarian cancer Hiroshi
Yagi, Ichiro Onoyama, Kazuo Asanoma, Keisuke Kodama,
Masafumi Yasunaga, Tatsuhiro Ohgami, Kenzo Sonoda, Kiyoko
Kato Kyushu University
Objective Gα12/13, heterotrimeric G proteins, encoded by GEP oncogene, are implicated in the progression of several human cancers. However, the underlying mechanisms by which GEP oncogene promote cancer progression has not been fully elucidated.
We herein evaluated downstream targets of GEP oncogene thatare implicated in ovarian cancer progression. Methods To examine the effect of Gα13 activation on ovarian cancer cells, weemployed constitutively active mutant of Gα13（Gα13QL）or synthetic biology approach using a GPCR activated solely by artificial ligands（RASSL）.Morphological change, protein expression
profiles and intracellular signaling pathways were analyzed. Results Regarding both in cell morphology and protein expression
profile, Gα13 activation induced epithelial mesenchymal transition（EMT）like phenotypes. Cycloheximide chase assay revealed that LATS1 degradation mediated by Gα13 was involved

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in EMT like phenotype of ovarian cancer cells. Conclusion Gα13
activation may contribute to EMT like phenotypical change
through LATS1 degradation in ovarian cancer.

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Expression of epithelial cell adhesion molecule and CD44 variant 6 is a predictive biomarker of chemoresistance and prognosis in epithelial ovarian cancer Yashiro Motooka1, Takeshi
Motohara1, Kiyomi Takaishi1, Fumitaka Saito1, Isao Sakaguchi1,
Ritsuo Honda1, Takashi Ohba1, Hironori Tashiro2, Hidetaka
Katabuchi1 Kumamoto University 1, School of Health Science, Kumamoto University 2
Objective Cancer stem cell（CSC）are associated with chemoresistance and poor prognosis. Epithelial cell adhesion molecule（EpCAM）or CD44 variant 6（CD44v6）are over expressed insome epithelial cancers. We examined the involvement of EpCAM and CD44v6 in clinical outcomes of epithelial ovarian cancer patients. Methods The expression of EpCAM and CD44v6
was examined by immunohistochemical analysis using primaryovarian cancer specimens from 167 patients. The relationshipbetween expression level of EpCAM and/or CD44v6 and prognosis of patients was assessed. In addition, we studied the association between the expression patterns of EpCAM and CD44v6
and the resistance to platinum agents in in vitro assays. Results
We found that EpCAM/CD44v6 double positive epithelial ovarian cancer patients had poorer survival than single positive or
double negative counterparts. We also found that EpCAM/CD
44v6 double positive patients have a lower probability of achieving overall responsive rate after first line adjuvant chemotherapy than the EpCAM negative patients, and also that EpCAM/
CD44v6 positive patients have the worst overall responsive rate
than single positive or double negative counterparts. Consistent
with clinical findings, in in vitro assays, the subpopulation of Ep-!

ISP-8-7
Ferroptosis induced by erastin in RAS mutant ovarian cancer
cells
Motoki Takenaka, Minako Mori, Yoko Ueda, Kyoko
Kikuno, Kenichiro Morishige Gifu University HospitalObjective Although apoptosis has been thought as the principal
mechanism of cell death in chemotherapy, other forms of nonapoptotic death also has been noted. The oncogenic RAS selective lethal small molecule erastin triggers a unique iron dependent form of cell death termed ferroptosis. This mechanism
is expected to induce eradication of chemotherapeutic resistantcancer cells. In this study we demonstrate this new form of cell
death in ovarian cancer cells. Methods The clear cell epithelial
ovarian cancer cell lines, TOV21G（RAS mutant type）and KOC（RAS wild type）were treated with erastin and deferoxamine（DFO）.The results of cell proliferation were measured by using
Premix WST 1 Cell Proliferation Assay System（Takara）. The
glutathione（GSH）concentrations were determined with the
GSSG/GSH Quantification Kit（Dojindo）and the expression of
glutathione peroxidase（GPx4）was identified by using a westernblot. Results Erastin dose dependently inhibited growth in
TOV21G cells, but not KOC cells. DFO rescued growth inhibition induced by erastin in TOV21G cells. The GSH level was reduced by erastin and this reduction was not rescued by DFO. In
addition, the basal level of GSH in TOV21G cells was lower than
KOC cells. The expression of GPx4 was reduced by erastin andthis reduction was not rescued by DFO. Conclusion Ferroptosis
was induced by erastin in RAS mutant ovarian cancer cells. Although erastin induced cell death by reducing the level of GSH,
DFO rescued this cell death by another pathway. The sensitivity to erastin might depends on the basal level of GSH in cells.

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Efficacy and toxicity of PEGylated liposomal doxorubicin forrecurrent ovarian cancer according to number of previous
chemotherapy regimens：Comparison with gemcitabine
Yoshifumi Takahashi, Yuji Takei, Shizuo Machida, Akiyo
Taneichi, Suzuyo Takahashi, Takahiro Yoshiba, Hiroyuki
Morisawa, Chikako Yoshida, Kouhei Tamura, Yasushi Saga,
Hiroyuki Fujiwara, Shigeki Matsubara Jichi Medical University
Objective PEGylated liposomal doxorubicin（PLD）is one of thesecond line chemotherapy regimens for platinum resistant recurrent ovarian cancer, but in clinical practice, PLD is often selected for third line or higher regimens. We previously reported that the disease control rate of gemcitabine（GEM）
tended to decrease as the number of previous chemotherapy
regimens increased, without an increase in toxicity. However,there is no report on the efficacy and toxicity of PLD based on
the number of previous chemotherapy regimens. The purpose ofthis study was to clarify this point in comparison with GEM.
Methods We retrospectively reviewed the medical records ofpatients at our institution with epithelial ovarian cancer who
underwent two or more cycles of single agent PLD therapy between July 2009 and March 2017. We used our reported data on
GEM for the comparison analysis. Results Seventy eight patients were enrolled in this study. The overall response rate was
19%, and the disease control rate（DCR）was 54%. The DCR ofone, two, three, and ＞three previous chemotherapy regimens
were 54%, 49%, 64%, and 67%, respectively. Grade 3/4 neutropenia and anemia occurred in 59% and 13%, respectively. When

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Regulation of Reg IV expression and prediction of response
to 5 fluorouracil by CDX2 in ovarian mucinous carcinoma
Iemasa Koh, Eiji Hirata, Suguru Nosaka, Yoshiki Kudo Hiroshima University
Objective Ovarian mucinous carcinoma is a disease with a poor
prognosis and a low response rate to chemotherapy. REG4 ,which encodes the Reg IV protein, is a potent activator of theepidermal growth factor receptor（EGFR）/AKT/activator protein 1（AP 1）signaling pathway. Reg IV is overexpressed in several human cancers, and is involved in apoptosis inhibition, as
well as in resistance to 5 fluorouracil（5 FU）. Ovarian mucinous
carcinoma has also been found to be associated with the overexpression of Reg IV, and we have confirmed the regulation of Reg
IV expression by CDX2. Therefore, we have examined the effectof 5 FU and anti EGFR treatment by profiling CDX2 and Reg
IV expression. Methods We examined the changes in Reg IV expression in response to CDX2 overexpression in OMC 3 cells,
which display relatively low endogenous CDX2 among ovarian
mucinous carcinoma cell lines. In addition, using this cell line,
we confirmed an effect of 5 FU and anti EGFR treatment（cetuximab）by cytotoxicity assay（MTS assay）.Results CDX2
overexpression in OMC 3 cells resulted in upregulation of Reg
IV expression. OMC 3 cells ectopically expressing CDX2 displayed 5 FU sensitivity through overactive apoptosis, but sensitivity to 5 FU in combination with cetuximab was not increased. Conclusion CDX2 regulates the expression of Reg IV,
but any combined effect involving an anti EGFR antibody ispoor. However, the sensitivity to 5 FU is high in ovarian mucinous carcinoma cells expressing CDX2. Therefore, our study
suggests the potential of novel chemotherapy regimens using 5
FU in the treatment of ovarian mucinous carcinoma.

CAM/CD44v6 double positive cells showed higher viability inresponse to platinum agents in comparison with single positiveor double negative cells. Conclusion We demonstrated that expression of EpCAM and CD44v6 is a predictive biomarker ofchemotherapeutic response and unfavorable prognosis in ovarian cancer patients.

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the number of previous regimens was limited to 3 or more, theDCR for PLD was significantly higher than that for GEM（65%vs 31%, p=0.038）.Conclusion The DCR did not decrease with anincrease in the number of previous chemotherapy regimens.
When the number of previous regimens was high, the DCR of
PLD was higher than that for GEM. Adverse events were tolerated with both regimens.

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Interleukin 34 is a promising prognostic biomarker in ovariancancers
Hiraku Endo1, Nao Suzuki1, Akiko Tozawa1,
Hidemichi Watari2, Tatsuya Kato2, Yosuke Konno2, Daisuke
Endo2, Hiroshi Asano2, Hisamori Kato4, Ken-ichiro Seino3 St. Marianna University School of Medicine 1, Hokkaido University 2,
Hokkaido University Institute for Genetic Medicine 3, Kanagawa
Cancer Center 4
Objective Despite several advances in the treatment of ovariancancers, most patients suffer recurrence even after full remission following first line therapy, which significantly impact patientʼs prognosis. Prognostic assessment depends clinically on
few biomarkers, which still have many disadvantages regarding
sensitivity, specificity and reliability. Thus, it is of great importance to identify new biomarkers that help to monitor response
to cancer therapy and predict recurrence in ovarian cancer patients. Interleukin 34（IL 34）has been suggested previously to
act as an important factor that contributes to resistance against
cytotoxic chemotherapy. Also, it correlates with poor prognosis
when highly expressed in lung cancers, based on our previous
report. In present study, we examined the possible involvementof IL 34 in chemoresistance and recurrence in ovarian cancers.
Methods We checked expression of IL 34 in several ovariancancer cell lines and clinical samples from chemotherapy untreated or treated ovarian cancer patients using RT PCR, IHC
and Ion AmpliSeq targeted sequencing analysis. And present
study is performed under approval of multicenter research ethics committees. Results IL 34 was found to be expressed in
ovarian cancer cell lines, in addition to a subset of ovarian cancer patients. IL 34 expression was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines in addition to clinicalsamples from chemotherapy treated ovarian cancer patients.
Importantly, high IL 34 expression correlated with worse progression free survival（PFS）in ovarian cancer patients（P=0.0421）.Conclusion These findings suggest a high usefulness of
IL 34 as a prognostic biomarker that helps to predict and monitor disease recurrence.

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SPIO method for the diagnosis of pelvic lymph node metastasis
Kosuke Murakami, Ayako Suzuki, Hanako Sato, Risa
Fujishima, Masato Aoki, Shiro Takamatsu, Yoshie Yo, Akiko
Kanto, Hisamitsu Takaya, Takako Tobiume, Hidekatsu Nakai,
Noriomi Matsumura Kindai University
Objective Lymph node（LN）metastasis in uterine cervical andendometrial cancer is a significant risk factor of recurrence. To
determine appropriate therapeutic strategy, precise evaluationof LN metastasis is important. The aim of this study is to develop more accurate imaging and pathological methods for pelvic LN metastasis. Methods We studied cervical and endometrial cancer cases which were planed pelvic LN dissection
from February 2016. We injected Super Paramagnetic Iron Oxide（SPIO）into uterine cervix, and took T2* weighted image of
MRI. Normal LN takes SPIO and is enhanced, but metastatic LN
does not. After surgery, we pathologically examined thinly
sliced LNs which reacted strongly to iron staining. This study
was approved by institutional review board, and we got informed consent from all patients. Results All of 27 patients did

not have adverse events. For patient base, accuracy was 89%（24/27 cases）, sensitivity was 80%, specificity was 91%, positive
predictive value was 67%, negative predictive value was 95%.
There was a 10mm short axis diameter LN, but it could be diagnosed no metastasis accurately. For 5 9mm short axis diameterbut easy to notice, accuracy was 85%（23/27 nodes）, and 6mm
and 8mm LN metastasis could be diagnosed. We could detectiron staining positive LNs, and evaluate them retrospectively as
sentinel LNs. Conclusion Local injection of SPIO in uterine cervix were performed safely. SPIO enhanced MRI and immunopathological investigation by iron staining may be useful for diagnosis of pelvic LN metastasis of uterine cervical and endometrial cancer.

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Discrimination of malignant transformation from benign endometriosis using near infrared approach Yuki Yamada,
Chiharu Yoshimoto, Kenji Ogawa, Naoki Kawahara, Ryuji
Kawaguchi, Toshiyuki Sado, Hiroshi Kobayashi Nara Medical
University
Objective Endometriosis is known to increase the risk of ovarian cancer. Iron and hemoglobin（Hb）species in the cyst fluid
can be used as markers of malignant transformation in benign
ovarian endometriosis（OE）.The aim of this study was to investigate the discrimination of malignant transformation from OE
using near infrared approach in the ex vivo study. Methods In asingle center retrospective study, we collected the cyst fluid
samples from patients with OE（n=34）and endometriosis associated ovarian cancer（EAOC）（n=12）between February 2013
and January 2015. The light reflected from each cyst fluid（achange in luminance, δL（cd/m2））was spectrally measured bya near infrared CCD camera with band path filter（800 nm）.
Cyst fluid level of Hb（g/dL）was converted from heme levels inall patients. The value of δL and Hb for the diagnosis of malignant transformation was assessed by receiver operating characteristic（ROC）curve analysis. Results The δL in EAOC is significantly lower than that in OE（14.4±10.8 versus 29.6±5.0［mean±SD］,p＜0.001）. A positive correlation between the δL and Hblevel in cyst fluid was observed from regression analysis results.
The diagnosis sensitivity and specificity for δL were 83.3% and94.1% at the cutoff value of 21.5 cd/m2 with the area under the
ROC of 0.897. Conclusion This ex vivo study potentially provides a powerful near infrared approach for quantitative discrimination between EAOC and benign OE with high sensitivity and specificity. Our study lays a foundation for future clinical approaches.

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Pathogenic KRAS mutation was frequently found in endometrial polyp with whole exome sequencing Takashi
Takeda1, Kouji Banno1, Masataka Adachi1, Megumi Yanokura1,
Arata Kobayashi1, Mayuka Anko1, Asako Sera1, Yusuke
Kobayashi1, Eiichiro Tominaga1, Kenjiro Kosaki2, Mamoru
Tanaka1, Daisuke Aoki1 Keio University 1, Center for Medical Genetics, Keio University 2
Objective Endometrial polyp is a common disease for women in
reproductive age, however a molecular mechanism of endometrial polyp is still unclear. Next generation sequencer
makes whole exome analysis and detection of gene mutationeasier. We analyzed endometrial polyp by next generation sequencer with the goal to reveal a driver gene of endometrial
polyp. Methods After an approval of ethics committee and written informed consent, 4 cases of endometrial polyp who werepremenopausal, did not take medicine and had transcervical resection of endometrium were recruited. DNA was extracted
from endometrial polyp as a tumor tissue and peripheral blood

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Evaluation of safety and diagnostic concordance for flexible
hysteroscopy in 1,591 outpatient cases Kosuke Tsuji, Yusuke
Kobayashi, Kouji Banno, Kanako Nakamura, Arata Kobayashi,
Takayuki Takahashi, Takuro Hirano, Haruko Kunitomi, Wataru
Yamagami, Eiichiro Tominaga, Mamoru Tanaka, Daisuke Aoki
Keio University
Objective There have been few large studies concerning thesafety and diagnostic concordance rates of outpatient flexible
hysteroscopy. In our institution, outpatient hysteroscopy has
been routinely and educationally applied to intrauterine lesions；thus, we retrospectively investigated outpatient flexible
hysteroscopy cases at our institution. Methods Fifteen hundred
ninety one cases of outpatient flexible hysteroscopy conducted
at our institution during the previous 5 years（2012 2016）wereretrospectively analyzed considering the clinical background,complications, and diagnostic concordance rates. Results The
diagnosis before outpatient flexible hysteroscopy included 540
cases of benign disorders（317 endometrial polyps, 168 myomas,
and 55 endometrial hyperplasia）, 355 atypical endometrial hyperplasia, 570 endometrial cancers, and 126 others. There wereno major complications including uterine perforation. Only onecase（0.06%）was diagnosed as septic shock derived from intrauterine infection, in which the patient had been receiving immunosuppressive drugs. Three hundred eighty two cases diagnosed as benign disorders through outpatient flexible hysteroscopy underwent operation, and the diagnostic concordance
rate was 70.4%（269 cases）. However, this included 14 cases（3.7%）which were diagnosed as malignant disorders postoperatively. In preoperative endometrial cancer cases, the sensitivity
and specificity for diagnosis of cervical invasion was 39.4% and90.8%, and positive intraoperative ascites cytology possibly
caused by outpatient hysteroscopy was seen in only one patient.
Conclusion Outpatient flexible hysteroscopy had high safety
and almost negligible effect on ascites cytology. Although outpatient hysteroscopy had a high diagnostic rate, there were limitations in diagnosing malignancies by this procedure alone, so it
is important that the diagnosis is determined by multidisciplinary approaches.

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Influence of adverse effects on quality of life of survivors ofgynecologic
cancer
Keiichiro Nakamura, Naoyuki Ida,
Masayuki Saijo, Junko Haraga, Takeshi Nishida, Chikako
Ogawa, Tomoyuki Kusumoto, Hisashi Masuyama Okayama University
Objective The objective of this observational study was to investigate correlations between adverse effects（lower extremity

lymphedema［LEL］, dysuria, severe gastrointestinal symptoms［SGS］, and Peripheral motor neuropathy［PMN］/Peripheral
sensory neuropathy［PSN］）and quality of life（QOL）（physical
well being［PWB］, social well being［SWB］, emotional well being［EWB］, and functional well being［FWB］）at least 3 year
after treatment（post treatment 1）, over 3 years post treatment（post treatment 2）of with patients with gynecologic cancer（GC）. Methods From January to August 2017, questionnaire responses and clinical data of 215 patients with GC were collected
and assessed by treatment received. The χ2 test was used to determine the significance of correlations. Results Participants
with LEL had significantly poorer QOL than those without it in
the domains of PWB at post treatment1（p=0.006）. SGS had significantly poorer QOL than those without it in the domains of
PWB at post treatment1（p=0.034）and post treatment 2（p=0.009）, and FWB at post treatment1（p=0.038）. Moreover, patients with PMN/PSN had significantly poorer QOL than those
without it in the domains of EWB at post treatment1（p=0.046）.
Conclusion Poorer QOL in emotional, physical and functional
domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical
therapy not only on survival but also on the QOL of survivors.

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ISP-9-6
Application of hysteroscopic transcervical resection for cervical proliferative disorder diagnostic method Kensuke
Hamamura, Yayoi Sugimori, Youko Fujiura, Sumire Ishii, Asako
Kumagai, Kanako Murata, Yukari Kitagawa, Yota Shimanuki,
Syozo Matsuoka, Daiki Ogishima Juntendo University Nerima
Hospital
Objective Cervical conization has been widely performed to diagnose of cervical proliferative disorders presenting with multiple cysts, however, this method might not provide enough tissue
to diagnose because the tumor lesion is often located at the internal os. We applied hysteroscopic transcervical resection（TCR）for a cervical biopsy method. This study aimed to compare the clinical/histological results of TCR with conization andto confirm usefulness of TCR biopsy for diagnosis of cervicalcystic tumor. Methods We retrospectively studied 11 patientswith large amount of vaginal discharge and cervical multicystic
lesions in MRI who visited our hospital between April 2007 andAugust 2017. These patients underwent conization, TCR,（orboth）for diagnosis. Conization was selected including the cases
regarded as suspicious of malignancy and TCR was selected forlobularendocervical glandular hyperplasia（LEGH）suspectedcases by endocervical cytology. Results Conization or TCR
method was performed for 5 or 7 patients respectively. Bothwere done for one case. There was no statistical difference in
two methods（conization：TCR）about operative duration（average；22.8min：25.4min）and amount of blood loss（average,
21g：15.5g）.Postoperative complication did not occurred in any
cases. Conization provided appropriate diagnosis for malignancy, but provided insufficient tissue to detected tumor pathologically in two benign cases. All TCR cases obtained enoughtissue for pathological diagnosis, and three of them were revealed LEGH after hysterectomy. Conclusion Cervical biopsy
using TCR was applicable for cervical tumor diagnosis withhigh safety and accuracy. It may useful for the case which could
not be diagnosed with conization.

ISP-9-7
Relation between intracardiac thrombus and advanced cancer：Report of two cases Yasuka Miyakuni, Wakako Mouri,
Yasuho Yanagihara, Ryosuke Shibui, Kyoko Oshina, Atsuko
Yamada, Aya Otsuka, Akari Koizumi, Izumi Suzuki, Takafumi
Ujihira, Michio Nojima, Koyo Yoshida Juntendo University

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lymphocytes as a normal tissue. Whole exome was analyzed by
next generation sequencer and derived candidate gene by thesubtraction of gene mutation in tumor and normal samples.
Then, we recruited totally 21 cases of endometrial polyp and additionally analyzed the extracted candidate gene by PCR rSSO
（reverse sequence specific oligonucleotide）method. Results
Among 4 cases who were analyzed subtraction of whole exome,
2 cases had pathogenic mutation in exon2 of KRAS （p.G12V, p.
G13C）. Additional KRAS analysis revealed 7 of 21 cases（33.3%）
had mutation in exon2 of KRAS （p.G12V, p.G12D, p.G13C）.
These mutation cases tended to have more endometrial polyps
which were preoperatively checked in outpatient hysteroscopy（4.1±3.4 vs 1.7±0.9, p=0.088）.Conclusion Endometrial polyp isa benign tumor, however it had pathogenic mutation in exon2（codon 12,13）of KRAS with the similar frequency to that of endometrial cancer. This result indicates that KRAS may be adriver gene of endometrial polyp.

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Urayasu Hospital
Cancer associated thrombosis is a significant cause of death inpatients with cancer. Although deep venous thrombosis and pulmonary embolism（PE）are commonly encountered, little has
been reported on intracardiac thrombus. We report two cancer
patients who died after suffering intracardiac thrombus. Case
1：50 year old woman presented with dyspnea and chest pain,
and was diagnosed with PE and sick sinus syndrome, and she
was suspected of ovarian cancer. She got cardiac pacemaker implantation and started treatment with anticoagulant. She underwent bilateral salpingo oophorectomy and was diagnosed withovarian cancer, stage IIIC, and received adjuvant chemotherapy. After 1 year and 2 months, thrombosis of left subclavian
vein and left internal jugular vein and progression of cancer
were found. Then she chose to take only palliative care and anticoagulant. Two months later, right atrial thrombi was detected
and she passed away three months later. Case 2：84 year old
female was diagnosed cervical cancer, stage IIB, and went
through concurrent chemoradiotherapy. She had been taken
novel oral anticoagulant（NOAC）for paroxysmal atrial fibrillation, but genital bleeding made her stop to take NOAC. After
three years, the cancer spread to the lungs and liver, and she
was admitted with complains of dyspnea and diagnosed left ventricular thrombus and renal infarction. She died before one
month had passed since the diagnosis. Thrombotic events arereported to be the second cause of death in cancer patients andaggressiveness of cancer reflects on thrombotic events. When
we recognize the progression of cancer, we should be carefulwith thrombosis.

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ISP-9-8
Consideration of outpatient mammary gland at our hospital
Takako Kawakita, Yuri Kadota, Kana Kasai, Kanako Yoshida,
Takeshi Kato, Masato Nishimura, Minoru Irahara Tokushima
University
Objective It has been reported that HRT affects breast cancer
although its risk is low, and breast cancer screening in HRT,LEP is recommended. In this issue, we examined breast cancer
screening examinees in our department retrospectively and examined the usefulness of breast cancer screening for gynecologic disease patients. Methods We studied breast cancer examinees in our department from August 2016 to July 2017 retrospectively. Results There were 89 examinees, 44 check ups during HRT, and 45 other screenings during gynecological treatment. Median age was 54 years old（29 81 years old）
, medical
examiners in their thirties were undergoing HRT therapy aftercancer surgery（4 cases）, oral administration of LEP（5 cases）.
At 40 years of age or older, it was medical examination during
HRT therapy or during treatment of other diseases. 20.4% during HRT administration showed increased mammary gland concentration. Two out of 44 patients undergoing HRT admitted fibroadenoma of breast, but one patient did not show any significant change in continuing HRT. In one case there was a tendency to reduction. We also admitted a case of breast cancer discovery in a screening before HRT. In this study, no onset ofbreast cancer was observed during HRT. Conclusion In
womenʼs lifestyle, HRT is an important treatment option. Periodical health examination during HRT is thought to be a trigger
for breast cancer screening examination.

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ISP-9-9
A retrospective study for the effectiveness and the safety ofchemotherapy for elderly gynecologic cancer patients
Mihoko Aoki1, Yukihide Ota1, Mikiko Sato1, Natsuko Kamiya1,
Yukio Suzuki1, Yuichi Imai1, Tae Mogami2, Naho Ruiz Yokota1,
Tatsuya Matsunaga1, Etsuko Miyagi1 Yokohama City University

Hospital 1, Kanagawa Cancer Center 2
Objective The purposes of this study were to evaluate the effectiveness and safety of chemotherapy and to identify pre treatment risk factors in elderly gynecologic cancer patients. Methods We assessed the medical courses of the patients with theage over 74 years who were diagnosed gynecologic cancer inour department between 2011 and 2015. The correlation between variety of clinicopathological factors and overall survivalof the patients were analyzed using Log rank test. Results The
number of the study subjects were 105（range：75 92 yearsold）.Chemotherapy was considered for 70 patients（73%）. Only30 patients（39%）received chemotherapy. Among them, 9（30%）
patients accomplished the planned therapy, 11（36%）needed anticancer agent reduction and 10（33%）stopped the chemotherapy. The disease control rates were 100%, 81%, 40%, respectively. A few life threatening events occurred, but the chemotherapy was feasible for most of cases. Twenty six（37%）patients who decided not to receive chemotherapy had no particular reason other than the elderly. The log rank test of the 70 patients revealed significant correlations between the overall survival and pre treatment performance status, falls risk assessment score, nourishment status and high CRP. Conclusion Chemotherapy was beneficial for appropriately selected elderly gynecologic cancer patients. Considering that significant numberof the patients did not receive chemotherapy with no convincing reason, proper pre treatment assessment is required to select the patients who would benefit chemotherapy.

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ISP-10-1
Primary vaginal gestational trophoblastic neoplasia treatedwith uterine angiographic embolization and chemotherapy
Maria Concepcion Cenizal1, Angelica Anne Chua1,2, Leo Francis
Aquilizan1,2 St. Lukeʼs Medical Center, Philippines 1, St. Lukeʼs
Medical Center Global City, Philippines 2
Gestational trophoblastic neoplasia in general is a rare condition, much so is primary extrauterine gestational trophoblastic
neoplasia. The incidence of gestational trophoblastic neoplasia
varies in different regions of the world. In the Philippines, local
data showed that incidence of gestational trophoblastic neoplasia remained to be almost constant at 22.4 per 40,000 pregnancies. However, incidence of primary extrauterine gestational
trophoblastic neoplasia was not mentioned. To date, there are
only 2 cases of primary vaginal choriocarcinoma and 1 case of
primary vulvar choriocarcinoma reported in literature. This is acase of a 26 year old gravida 1 para 0（0 0 1 0）who came in for
profuse vaginal bleeding. Serum beta human chorionic gonadotropin was elevated and ultrasonographic study showed a hypervascular vaginal mass and an empty uterus. Patient was diagnosed with primary vaginal gestational trophoblastic neoplasia and was started with combination chemotherapy. However,during the course of chemotherapy, profuse vaginal bleeding
was noted which was controlled by angiographic embolizationof the uterine arteries. The patient tolerated the procedure andcompleted cycles of Etoposide, Methotrexate, Actinomycin D,
Cyclophosphamide and Vincristine（EMACO）. She had a complete remission of the tumor and had two successful subsequentpregnancies. Primary vaginal gestational trophoblastic neoplasia is a rare condition that warrants high index of suspicion.
Combined chemotherapy with EMACO is the cornerstone oftreatment. Angiographic embolization is a minimally invasive
procedure that is safe and effective in managing acute hemorrhage among patients with gestational trophoblastic neoplasia.

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ISP-10-2
The Mole that Created a Hole：A Case of an Invasive Mole
with Uterine Perforation in a Primigravid Lugie

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ISP-10-3
Prognostic effect of ABO blood groups in patients with androgenetic complete hydatidiform moles Asuka Sato1,
Hirokazu Usui1, Yuji Habu1, Ayumu Matsuoka2, Kyoko
Nishikimi2, Shinichi Tate2, Akira Mitsuhashi1, Makio Shozu1
Chiba University 1, Chiba University Hospital 2
Objective The association between ABO blood groups and gestational trophoblastic disease is still unclear, although it has
been discussed since the 1970s. This study aimed to evaluate theeffect of ABO blood groups on the prognosis of molar pregnancy
by enrolling only subjects with genetically diagnosed complete
hydatidiform moles（CHMs）. Methods This was an observational cohort study of 206 patients who primarily underwent an
operation for suspected molar pregnancy between January 2007
and February 2016. Among the patients, 132 were diagnosed ashaving CHMs according to multiplex short tandem repeat polymorphism analysis. The ABO blood groups of patients were determined serologically. The incidence of gestational trophoblastic neoplasia（GTN）was compared based on ABO blood groups.
Results Of the patients, 54（41%）, 28（21%）, 11（8%）, and 39（30%）
were classified as types A, B, AB, and O, respectively. The distribution was approximately equal to that of the general Japanese population. The overall incidence of GTN was 17.4%（23/132）.GTN occurred in 15%（8/54）,21%（6/28）,36%（4/11）,and
13%（5/39）of the type A, B, AB, and O patients, respectively.
The incidence of GTN in patients with A and B antigens tended
to be higher（p=0.062, Cochran Armitage trend test）. Conclusion Patients with blood type O had a tendency not to develop
GTN. The hypothesis is that immunological rejection against A
and B antigens could play an important role in eliminating thetrophoblastic cells after a molar pregnancy. Further study isneeded to prove the relationship between ABO compatibility
and the occurrence of GTN.

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Primary choriocarcinoma of the mesentery in a pregnancy
woman：A case report Misaki Ozawa1, Masakazu Kitagawa1,
Tamina Kino2, Ayasa Hashimoto1, Eri Uchida1, Asuna Yumori1,
Kimiko Enomoto2, Yukiko Okada1, Shigeru Aoki2, Etsuko
Miyagi3, Hideya Sakakibara1 Yokohama City University Medical
Center 1, Department of Obstetrics, Yokohama City University
Medical Center 2, Yokohama City University 3
Choriocarcinoma usually develops subsequently after pregnancy and cases developing during pregnancy are very few. As
our knowledge, this is the first report of primary choriocarcinoma of the mesentery in a pregnant woman. She was 40 year
old woman, gravida 2（induced abortion）, para 0 and had been
diagnosed with schizophrenia. She had been pregnant spontaneously and health checkups started in another hospital. From 1sttrimester, 6 cm mass in adnexal area was detected and had been
observed as an ovarian tumor or a uterine subserosal myoma.
MRI scan at 31 weeks of pregnancy revealed that the mass enlarged to 10 cm, showing high signal intensity on T1 weighted
images and heterogeneous signal intensity on T2 weighted images. Because of exacerbation of schizophrenia, she was referredto our hospital at 35 weeks. A cesarean section was performed
at 37 weeks due to poor control of preeclampsia and schizophrenia. Observing intra abdominal cavity, bilateral adnexae werenormal. The origin of the tumor existed in sigmoidal mesentery
and severe adhesion was seen between the tumor and sigmoid
colon, and tumor resection with colectomy was performed subsequently. By immunohistochemical analysis, it was diagnosed
as choriocarcinoma of the mesentery. No cancer cells could befound in her placenta. Final diagnosis was primary choriocarcinoma of the mesentery, stage IV, and FIGO scoring was 15
points. Preoperative serum hCG level was 1,445,000 mIU/mL.
We have been performing chemotherapy comprised ofmethotrexate, actinomycin D and etoposide after operation, so
serum hCG level has decreased and finally been unable to be detected.

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Treatment of choriocarcinoma with 4 day methotrexate,
etoposide and actinomycin D regimen：a single center experience Eiko Yamamoto1, Shizuka Sato2, Kaoru Niimi3, Kimihiro
Nishino3, Kenichi Nakamura3, Yoshiki Ikeda3, Fumitaka
Kikkawa3 Department of Medical Adminst, Nagoya University 1,
Nagoya Memorial Hospital 2, Nagoya University 3
Objective The aim of this study was to examine the efficacy andsafety of 4 day methotrexate, etoposide and actinomycin D（MEA）regimen for treatment of choriocarcinoma. Methods
Thirty patients of choriocarcinoma had treatment with 4 day
MEA regimen between January 1999 and December 2015. Retrospective analysis was performed on the outcomes and adverse
effects. This study was approved by the ethics committee of thehospital. Results The mean age was 35.8 years old. The diagnoses of 30 patients were pathological choriocarcinoma in 12, clinical choriocarcinoma in 17 and non gestational choriocarcinoma
in one. Twenty five patients（83.3%）had 4 day MEA as thefirst line regimen and five patients had other regimens previously. Twenty four patients（80.0%）achieved complete remission and 3 patients（10%）relapsed followed by cured by 4 day
MEA. Of 6 patients who developed drug resistance, three patients were completely cured by surgery, radiotherapy and theother regimen, and three patients died of choriocarcinoma. The
remission rate as the first and the secondary therapies were88.0% and 44.0%, respectively. The adverse effects were nausea（64.2%）, stomatitis（61.5%）,leukocytopenia（G3 4, 49.7%）, anemia（G2 3, 24.0%）, and hepatoxicity（G2 3, 13.6%）. Among patients in the reproductive age, 15 patients recovered natural cy-

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Testado-Ouano, Angelita Teotico Manila Central University Ultrasound Services Incorporated, Philippines
Invasive mole is a condition where molar pregnancy partial orcomplete hydatidiform mole invades the myometrium. The occurrence of an invasive mole following a nonmolar pregnancy isvery rare and most rare is an invasive mole without antecedent
pregnancy. Presented here is a case of a 29 years old, primigravid, who was admitted for hypogastric pain with a positive
pregnancy test. Transvaginal ultrasound revealed an enlarged
uterus with a complex mass at the fundal area without visible
intact myometrium and massive hemoperitoneum suggestive ofa gestational trophoblastic tumor with suspicious uterine perforation versus ruptured interstitial pregnancy. Serum B hCG
was elevated 311, 413 mIU/ml. Patient then underwent exploratory laparotomy. Intraoperatively, the uterus was symmetrically enlarged with smooth serosa. There was 1 2 cm rupture
with active bleeding noted at the fundal area with a spongy
mass. On cut section of the uterus, a poorly circumscribed mass
was seen infiltrating the myometrium. The endometrium wassmooth. Both fallopian tubes and ovaries were grossly normal,
and there was hemoperitoneum of 2 liters. Total abdominal hysterectomy and bilateral salpingectomy were done. Repeat serum B hCG was 44,660 mIU/ml. Histopathology result revealed
chorionic villi invading the myometrium suggestive of an invasive mole. Patient was discharged improved with final diagnosis
of gestational trophoblastic neoplasia（invasive mole）stage 1,
low risk（WHO score of 4）. The case aims to emphasize thesonographic appearance of the different trophoblastic neoplasias as well as the difficulty surrounding the management of invasive mole with complication in a primigravid.

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cles after hormone treatment. Eleven patients hoped for childbearing, and five patients had nine conceptions with the resultsof two spontaneous abortion and seven term live births with noanomaly. Conclusion The total remission ratio of 4 day MEA
was almost the same as those of 5 day MEA and EMA/CO. Adverse effects, including reproductive status, were acceptable byusing supportive therapy.

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ISP-10-6
The Usefulness of genetic analysis for differential diagnosis
between complete and partial hydatidiform moles Noriko
Miyashita, Yuri Hasegawa, Ai Higashijima, Shuhei Abe,
Atsushi Yoshida, Kiyonori Miura, Hideaki Masuzaki Nagasaki
University
Objective It is difficult to differentiate complete and partial hydatidiform moles by image findings. Hydatidiform moles havebeen diagnosed by pathological examination. We performed genetic diagnosis for hydatidiform moles to clarify if hydatidiform
mole is complete or partial. Methods From 2013 to 2017, we diagnosed 10 cases of complete hydatidiform moles and 4 cases ofpartial moles by pathological examination. In 14 cases, 4 cases
were obtained after receiving written informed consent to getpatientʼs and their husbandʼs blood samples and the tissues ofhydatidiform moles. We performed genetic analysis of cystic
villi and patientʼs and their husbandʼs blood samples by shorttandem repeat PCR. Results One case was diagnosed partial hydatidiform mole by pathological examination. In this case, p57（Kip2）immunohistochemistry was found at the partial nuclei oftrophoblast and stromal cells of the villi. However, as genetic
analysis of cystic villi showed that the cystic villi had paternal
homozygosity. Finally, we diagnosed this case as complete hydatidiform mole. Three cases were diagnosed as complete hydatidiform moles by both pathological examination and genetic
analysis. Conclusion Genetic analysis of hydatidiform mole isuseful technique for the differential diagnosis between complete
and partial hydatidiform mole.

ISP-10-7
Three cases of complete hydatidiform mole coexistent with alive twin fetus Hikari Yoshizawa, Yasuhiko Ebina, Hitomi
Imafuku, Kaho Suzuki, Senn Wakahashi, Yoshiya Miyahara,
Masashi Deguchi, Hideto Yamada Kobe University
Complete hydatidiform mole coexisting with a live twin fetus（CHMCF）is very rare, occurring in 1/20,000 1/100,000 pregnancy. We report 3 cases of NHMCF. The median age was 24
years（range 24 39）. Diagnosis of complete hydatidiform mole
was obtained by histopathology and immunohistochemistry.
The gestational weeks at diagnosis were 12 14 weeks gestation.
Two of three women became pregnant after administration ofovulation inducer. Maternal complications were severe hyperemesis gravidarum（n=1）and genital bleeding（n=2）. Pregnancies were terminated in 14 and 15 weeks in 2 women because of the patientʼs request. One woman was diagnosed asclinical invasive mole 20 days after termination and received
methotrexate/actinomycin D therapy. The other woman intended to continue the pregnancy, but pregnancy was terminated at 21 weeks gestation due to lung metastasis. Her serum
hCG decreased rapidly after methotrexate treatment and metastasis to lung disappeared. The overall rate of GTD was 67%. In
the cases with CHMCF we experienced, the incidence of GTD
was considerably high. Even if pregnancy was terminated in thefirst trimester, strict check for GTD is crucial.

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The change of maternal cardiac function in twin pregnant
women
Mayu Ukai, Eiji Yoshida, Takuji Ueno, Takuma

Yamada, Takehiko Takeda, Sho Tano, Kaname Uno, Teppei
Suzuki, Toko Harata, Yasuyuki Kishigami, Hidenori Oguchi
TOYOTA Memorial HospitalObjective Twin pregnant women have 20% higher cardiac output and 10 to 20% greater increase in plasma volume than singleton pregnant women. These physiological changes impose
considerable stress. The aim of this study was to reveal thechanges in cardiac function in twin pregnant women comparedwith singleton pregnant women. Methods This study was a prospective cohort study from January 2010 to February 2016.
Echocardiography and BNP levels were examined at early, middle, and late pregnancy, within 5 days after delivery, and at one
month postpartum. Left ventricular ejection fraction（LVEF）＜
55% was defined as systolic dysfunction. Early transmitral velocity/early diastolic velocity of the mitral annulus（E/Ea）＞15
was defined diastolic dysfunction. Results A total of 142 twin
pregnant women and 44 singleton pregnant women were enrolled. Twenty one twin pregnant women were excluded due topreeclampsia or cardiovascular disease. LVEF were not significantly different in both twin and singleton pregnant women. E/
Ea and BNP did not deteriorate in singleton pregnant women. In
twin pregnant women, E/Ea elevation was observed at latepregnancy（9.6±2.8, p＜0.01）and within 5 days after delivery（9.7±2.2, p＜0.01）compared with early and middle pregnancy.
BNP elevation was much higher in twin pregnant women thansingleton pregnant women in late pregnancy（43.4±8.8, p＜0.01）
and early postpartum（46.9±8.0, p＜0.05）. Conclusion Twin
pregnant women have a risk of cardiac functional deterioration.
Late pregnancy and early postpartum should be considered ashigh risk periods for maternal cardiac dysfunction.

ISP-11-2
Pregnancy outcomes of MD twins Miki Nishizawa, Koichiro
Kido, Rina Sakurai, Takayuki Ichinose, Shigenari Namai,
Rintaro Kishimoto, Yasuhiro Matsumoto, Haruko Hiraike,
Masahiro Shiba, Yukifumi Sasamori, Eiji Ryo, Takuya Ayabe
Teikyo University
Objective FLP is effective for twin to twin transfusion syndrome（TTTS）. In MD twins, however, poor pregnancy outcomes are also caused by similar situations such as twin anemia polycythemia sequence, twin amniotic fluid discordance,and selective fetal growth restriction, which are not eligible for
FLP. We analyzed medical records, and tried to draw some suggestions to expand FLP indications. Methods Forty three MD
pregnancies from 2013 through 2016 at our hospital were analyzed retrospectively based on the medical records. Results
There were 27 MD twins of normal amnion without FGR（control group；CG）, and 16 cases which are suspected of TTTS andsimilar situations（suspected group；SG）. The mean delivery
week were 33.7 vs 35.9（SG vs CG）（p＜0.01）. The mean Apgar
scores of the first twin at 1 min were 6.5 vs 7.7（SG vs CG）
（p＜
0.01）
, and that of the second twin were 6.7 vs 7.9（SG vs CG）（p＜0.01）. There were two cases of TTTS in the SG group, one occurred at 28 weeks of gestation and the other deteriorated fromTAPS at 31 weeks of gestation, both of them yielded low APSs.
Conclusion Pregnancy ended earlier in SG than in CG. Babies in
SG showed lower APSs, but have shown no neurological complications at the latest follow up. The current management for MD
twins seemed effective to prevent neurological complications.
Some TTTS, however, occurred after the present deadline of
FLP, or 26 weeks. Study to expand FLP indication is expected.

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Clinical significance of pregnancy in Japanese women aged 15
years Asako Watanabe, Asako Saso, Naofumi Okuda, Sayuri
Kondo, Marie Ito, Miwa Miyazaki, Yoshie Shibata, Zuisei

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vaginal）. Incidences of maternal and fetal adverse outcomes
were also analyzed. The Fisherʼs test was used to analyze categorical variables. Findings were considered statistically significant if p＜0.05 for all outcomes. Results There were 3,781
women who met criteria, which included 17（0.45%）women who
were age ＞45 years at the time of delivery. Rates of cesareandelivery differed by age group（31.1%, 20 34years；39.1%, 35 39
years；42.4%,40 44years；58.8%, ＞45 years）. Compared to thereference group, women age＞45 years were significantly more
likely to undergo a cesarean delivery（OR 3.17；95% CI,1.20 8.36,
p＜0.02）, experience severe maternal morbidity（11.76% vs1.82%；OR=7.18；95% CI, 1.59 32.41, p＜0.05）and blood transfusion（11.76% vs 1.61%；OR=8.17；95% CI, 1.80 37.03, p＜0.05）.
Conclusion Compared to non AMA women, extremely AMA
women experience significantly increased rates of cesarean delivery and maternal risks. Extremely AMA women should be informed about these risks.

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Pregnancy after fertility preservation with high dose medroxyprogesterone acetate：Three cases of obstetric complications Karin Imaizumi, Hyo Kyozuka, Satoshi Suzuki, Daisuke
Suzuki, Akiko Yamaguchi, Shu Soeda, Takafumi Watanabe,
Keiya Fujimori Fukushima Medical University
High dose medroxyprogesterone acetate（MPA）
therapy is a fertility preserving treatment for early stage endometrial cancer
or atypical endometrial hyperplasia. However, obstetric complications after MPA therapy are not well known. Here, we report
3 cases of obstetric complications after fertility preservation
therapy using MPA. Case 1：A 35 year old woman was referred to our hospital for the management of threatened preterm birth at 23 weeks. The patient had preterm premature rupture of membrane（pPROM）at 29 weeks despite use of several
tocolytic agents. Caesarean section（CS）was performed after acourse of antenatal corticosteroids. Severe inflammation of theplacenta and umbilical cord was histologically confirmed. Case
2：A 41 year old woman underwent CS because of arrest of labor at 41 weeks in our hospital. The placenta was difficult to remove. Because of postpartum hemorrhage, abdominal total hysterectomy was performed soon after the delivery. Histologicalexamination revealed placenta increta and intrauterine inflammation. Case 3：A 35 year old woman was referred to our hospital for the management of pPROM at 26 weeks. CS was performed after a course of antenatal corticosteroids. An attempt
was made to remove the placenta；however, manual removal
was unsuccessful because the partial placenta adhered to theuterine wall at the fundus. Placenta accreta was clinically diagnosed. Conservative management for placenta accreta was selected as the course of action.

Ultrasound study of fetal movements in singleton and twin
pregnancies at 12 to 19 weeks Mohamed Aboellail1, Kenji
Kanenishi1, Nobuhiro Mori1, Junko Noguchi2, Toshiyuki Hata1 Kagawa University 1, Kagawa Prefectural College of Health Sciences 2
Objective To evaluate fetal behavioral differences between singleton and twin fetuses before 20 weeks of gestation using four
dimensional（4D）ultrasound. Methods 4D ultrasound was used
to examine fetal movements in 58 singleton and 48 twin normal
fetuses at 12 to 19 weeks. The frequencies of eight fetal movements were assessed through 15 minutes recordings. The fetuses were divided into two gestational age groups（12 to 13 and
14 to 19 weeks）to evaluate the changes with advancing gestation in twin versus singleton fetuses. Results Arm and general
movements were the most frequent movements in singleton fetuses, whereas only general movement was significantly more
frequent than the other seven fetal movements in twin fetuses
at 12 to 13 weeks. At 14 to 19 weeks, frequencies of arm and leg
movements were significantly higher than those of the other six
movements in singleton fetuses, while only arm movement wassignificantly more frequent than the other fetal movements in
twin fetuses. Comparisons of fetal movements between singleton and twin fetuses revealed that only arm movement showeda significant difference at 12 to 13 weeks, while the frequencies
of all movements in singleton fetuses were significantly higher
than those in twin fetuses at 14 to 19 weeks. Conclusion Our results suggest that the limitation of available space and crowdingof twin fetuses with advancing gestation may have a marked impact on twin fetal movements compared with singleton fetuses,
even in the first half of pregnancy.

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Pregnancy outcome of extremely advanced maternal age
Tomoyuki Sekizuka, Masayuki Yamaguchi, Kazufumi Haino,
Ryo Tamura, Kunihiko Yoshida, Mina Itsukaichi, Taro Nonaka,
Koichi Takakuwa, Takayuki Enomoto Niigata University Medical and Dental HospitalObjective To evaluate pregnancy outcome in women of extremely advanced maternal age（＞45 years）in our hospital.
Methods This is a retrospective study of all women delivering
singletons births in our hospital from 2006 to 2015. Data wereextracted from maternal registry of our hospital. Women withmultiple gestation, stillbirth and whose records lacked were excluded. We compared non advanced maternal age women（nonAMA women；age 20 34 years, reference group）to advanced
maternal age women（AMA women；age 35 39, 40 44 and＞45
years）.The primary outcome was route of delivery（cesarean vs

The effect of trimester specific gestational weight gain on
the risk of light for date in Japanese women stratified by themethods to calculate trimester specific gestational weightgain Takuhiro Yamada1, Tadahiko Uesato1, Tadashi Uesato1,
Eiji Imaizumi1, Kazuhiro Fujita1, Jutaro Fujita1, Chisato Mori2
Aiwa Hospital 1, Department of Bioenvironmental Medicine,
Chiba University 2
Objective To investigate associations between trimester specific gestational weight gain（GWG）and fetal birth weight.
Methods The term singleton 24,517 births were analyzed retrospectively. We calculated the odds ratio of light for date
（LFD）among women who were low weight gain in each trimester. We also calculated the adjusted odds ratio with maternalage, parity, height, body mass index（BMI）, infant sex andweight gain in other trimesters using multivariate logistic re-

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Hayashi, Shunji Suzuki Japanese Red Cross Katsushika Maternity HospitalObjective We examined the clinical characteristics and obstetric outcomes in pregnancies in Japanese women aged 15 years.
Methods The present study was a retrospective investigation of
all Japanese women with singleton pregnancies who gave birth
beyond 22 weeksʼ gestation aged 15 years old between 2002 and2016 at our institute（n=56）. Results Of the 56 women, 7（13%）gave birth without visiting prenatal care. Adverse obstetric outcomes were not observed in the pregnancies in women
aged 15 years；however various social and economic problems
regarding pregnancy in these women were observed. In addition, the rate of more serious social problems such as insulted
state with their parents and unknown pregnant partners washigher significantly in women without prenatal care than that inwomen received prenatal care. Conclusion Adequate social support is needed for the young pregnant women.

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gression. Then we calculated the adjusted odds ratio of LFD by
BMI category. Results The mean（standard deviation）1st trimester specific GWG rate was 50.1（161.5）g/w, and the 2nd was
367.9（123.4）g/w, and the 3rd was 356.5（151.3）g/w. Low weightgain both in the 2nd and in the 3rd trimester significantly increased the risk of LFD. In the crude model low weight gain in
the 1st trimester did not increase the risk of LFD, but in the adjusted model, low weight gain in the 1st trimester significantly
increased the risk of LFD. In low and normal BMI groups low
weight gain in the 2nd and in the 3rd trimester significantly increased the risk of LFD. In high BMI group low weight gain
only in the 2nd trimester increased the risk of LFD. Conclusion
Low weight gain in the 2nd trimester affected the risk of LFD
the most. Low weight gain in the 3rd trimester had higher riskof LFD than the 1st trimester. The effects of trimester specific
GWG on the risk of LFD differed by BMI groups.

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ISP-11-8!

The clientʼs attitude survey after invasive or non invasive
prenatal testing Mie Tahara, Hiroaki Nakamura, Atsushi
Matsuki, Maya Komori, Takako Matsuki, Sachiyo Nishimoto,
Kazuharu Tanaka, Osamu Nakamoto Osaka City General HospitalObjective In Japan, Non Invasive Prenatal Testing（NIPT）has
been performed for many pregnant women from April, 2013.
The differences about clientʼs attitude between invasive andnon invasive testing are unknown. Therefore, we report here
using the questionnaires. Methods Under the permission of ethics committee, we asked 1,352 clients after prenatal testing using questionnaire from March, 2015 to August, 2017. Four questions are 1. Did you understand about your results? 2. Did you
feel your anxiety was resolved? 3. In future, if you get pregnant
again, do you want to receive same prenatal testing? 4. If possible, please let us know your opinion. Data were analyzed using
Fishersʼ exact test. Results We collected 1,337 answers（411 ofamniocentesis, AC and 926 of NIPT）. 1. 89% of AC and 95% of
NIPT clients answered understood very well . 2. 75% of AC and
68% of NIPT clients answered extremely resolved . 3. 65% of
AC and 70% of NIPT client answered agree . 4. Of the 345 described clients, 70% of AC and 65% NIPT clients were satisfied,but 20% and 30% clients were dissatisfied, respectively. Conclusion From this attitude survey, although same genetic counseling, the attitude of clients after invasive or non invasive study
were dfferent. NIPT is safe but expensive, and the informationof the test is limited more than invasive tests.

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ISP-11-9
An investigation of the benefits of first trimester ultrasoundscreening combined with second trimester maternal serum
screening Yumi Araki, Maki Hyodo, Norifumi Tanaka, Tomomi
Yamazaki, Yoshiki Kudo Hiroshima University
Objective Maternal serum screening（MSS）is used for trisomy
21 and 18. However, many women who have false positive results feel anxiety and undergo invasive procedures unnecessarily. In our hospital, first trimester ultrasound screening is also
performed in all cases of MSS. We investigated the benefits ofcombining these exams. Methods From 2015 to 2016, 192 pregnant women underwent first trimester ultrasound screening
and second trimester MSS. On ultrasound screening, fetal
nuchal translucency thickness ＞3 mm and/or hypoplasia（including absence）of nasal bone were considered positive findings. We studied the correlation of these screening results andoutcomes. Results Six（3.1%）cases were positive in both exams,
with 3 cases diagnosed as chromosomal abnormalities. One of
the 3 cases was trisomy 18 and the other 2 were trisomy 21. In
33（17.2%）positive cases only on MSS, 16 women who underwent!

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non invasive prenatal testing（NIPT）or amniocentesis had
negative or normal findings. The other 17 women and the 131
who had negative results in both exams were satisfied by theseresults and decided to continue their pregnancies without further examination. In 22（11.5%）positive cases only on ultrasoundscreening, 5 cases were diagnosed with fetal abnormalities suchas trisomy 13, Noonan syndrome, polycystic kidney disease, cleidocranial dysplasia, and multiple congenital malformation syndrome. Conclusion Using first trimester ultrasound screening,
trisomy 21 and 18 can be screened more precisely than only
MSS, and more fetal abnormalities can be screened. Additionally, ultrasound screening before MSS could reduce the numberof women who feel anxiety and undergo invasive procedures unnecessarily.

ISP-12-1
Immunoglobulin fetal therapy for symptomatic congenital cytomegalovirus infection Yutoku Shi1, Kenji Tanimura1, Akiko
Uchida1, Mizuki Uenaka1, Mayumi Morizane1, Masashi Deguchi1,
Yasuhiko Ebina1, Ichiro Morioka2, Hideto Yamada1 Kobe University 1, Department of Pediatrics, Kobe University 2
Objective Approximately 90% of the surviving infants withsymptomatic congenital cytomegalovirus（CMV）infection（CCI）
have severe neurological sequelae. We aimed to assess the efficacy of fetal therapy with immunoglobulin（Ig）of a high titeranti CMV antibody for symptomatic CCI. Methods This study
was approved by the institutional ethic boards, and written informed consent was obtained from all participants. Motherswith fetuses of symptomatic CCI received Ig injection into the
fetal peritoneal cavity（Fip）or intravenous Ig injection into maternal blood（Miv）. Results Twelve fetuses received fetal therapy（Fip 1, Miv 5, and Fip+Miv 6）from 2009 to 2017. After Ig fetal therapy, ultrasound examinations and CMV DNA PCR tests
demonstrated the following changes：ascites disappearance of
8.3%（1/12）, improvement in fetal growth restriction of 33.3%（4/12）, and the disappearance of CMV DNA in fetal ascites of 8.3%
（1/12）. The survival rate was 83%（10/12）. In the 7 surviving infants whose neurological outcomes were evaluated at age of 12months or later, 2（28.5%）developed severe or mild sequelae, 2（28.5%）had unilateral hearing difficulty only, and 3（42.9%）developed normally. Conclusion Ig fetal therapy may be effective
for reducing the incidence and severity of sequelae in symptomatic CCI infants.

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Anti cytomegalovirus IgM titer for congenital infection in
first trimester pregnancy with primary infection Kuniaki
Toriyabe1, Fumihiro Morikawa2, Toshio Minematsu3, Asa
Kitamura1, Kyoko Shimada1, Michiko Kubo1, Masafumi Nii1,
Kayo Tanaka1, Hiroaki Tanaka1, Kazuhiro Osato1, Yuki
Kamimoto1, Tomoaki Ikeda1 Mie University Hospital 1, Mie Association of Obstetricians and Gynecologists 2, Aisenkai Nichinan
Hospital 3
Objective We evaluated cytomegalovirus（CMV）immunoglobulin M（IgM）titer in first trimester pregnant women with primary infection as a predictive factor for congenital infection in a
multi center prospective cohort study. Methods Maternal CMV
antibody screening during the first trimester was conducted
prospectively at 16 centers in Japan between September 2013
and September 2015. Pregnant women with primary infection
underwent testing for fetal congenital infection by real time polymerase chain reaction on CMV DNA. We investigated thepositive predictive value of CMV IgM titer levels for congenital
infection in first trimester pregnant women with a positive/
borderline IgG, positive IgM, and low IgG avidity（IgG avidity
index of 35.0% or less）result. Results We identified six（8.6%）

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Biphasic MCA PSV elevation in a case of congenital cytomegalovirus infection Sho Tano, Eiji Yoshida, Hatsuo Isogai,
Takuji Ueno, Takuma Yamada, Takehiko Takeda, Kaname Uno,
Mayu Ukai, Teppei Suzuki, Toko Harata, Yasuyuki Kishigami,
Hidenori Oguchi Perinatal Medical Center, TOYOTA Memorial
Hospital
Introduction Congenital cytomegalovirus（CMV）infection is theleading cause of nonhereditary sensorineural hearing loss andneurodevelopmental impairment. The nervous system is one of
the main targets of congenital CMV infection, but the infectious
dynamics of CMV in vivo brain has not been sufficiently studied. Although it is difficult to evaluate inflammation of the fetus
in uterus, it is reported that the middle cerebral arterial peaksystolic velocity（MCA PSV）correlates with the inflammatory
response. We reported a case of congenital CMV infection without fetal anemia, in which MCA PSV was elevated to biphasic
in uterus. Case A 28 year old pregnant woman, gravida 2, para
1, had no infectious episodes. At 26 week of pregnancy, fetus
MCA PSV increased to 77.7 cm/sec, but there was no other abnormality. After that, once the MCA PSV remained in the normal range, the ventricular enlargement was recognized from 30
weeks of gestation, and MCA PSV increased after 34 weeks ofpregnancy. She has labor in 39 weeks of pregnancy, delivering
2,590 g of boy without anemia. He was diagnosed as congenital
CMV infection and took valganciclovir. Now 2 years old, there
are no abnormalities except for speech developmental disorderdue to sensorineural hearing loss. Discussion The biphasic increase in MCA PSV in our case may have been affected by the
biological properties of CMV. CMV is a member of the herpes
virus family, and has latency and reactivation properties. CMV
shifts to the latent phase within one month after infection andreactivates later. This characteristic is useful for ultrasound diagnosis.

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ISP-12-4
Prediction of functional pulmonary hypoplasia using MRI
Junya Sakuma, Mayumi Takano, Sadanori Kasai, Sumito
Nagasaki, Eijiro Hayata, Ayako Oji, Toshimitsu Maemura,
Yukiko Katagiri, Masahiko Nakata, Mineto Morita Toho University Omori Medical Center
Objective The aim of this study was to investigate the utility offetal lung to liver signal intensity ratio calculated by MRI for
the prediction of functional pulmonary hypoplasia. Methods We
retrospectively analyzed 63 pregnancies who underwent MRI
between April 2011 and August 2017. Single shot turbo spinecho sequence was used for analyzed. On the fetal coronary
plane of T2 weghited images, each signal intensity of lung andliver was measured, and the ratio of lung to liver signal intensity（LLSIR）was calculated. Pulmonary hypoplasia was defined
as follows：the neonates were required mandatory ventilation

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or died due to respiratory trouble expect for prematurity. Results The median gestational age at MRI was 33 weeks（range：
27 35 weeks）. There were 52 pulmonary hypoplasia cases,
LLSIR of pulmonary hypoplasia group was significantly lower
than that of without pulmonary hypoplasia group（1.83（range：
1.35 2.23）vs 2.44（range：1.92 4.63）, p＜0.001）. Using ROC curve
analysis, a threshold of 1.93 for LLSIR had 91% sensitivity, 73%
specificity, 100% positive predictive value, and 98% negative
predictive value for the prediction of neonatal respiratory disorder. Conclusion LLSIR of fetuses complicated with neonatal respiratory disorder was significantly lower than that of normal
pulmonary function, and LLSIR seems to be useful MRI parameter to predict fetal functional pulmonary hypoplasia. This result
indicates that low LLSIR might reflect the characteristics of hypoplastic lung structures.

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ISP-12-5
Measuring fetal lung volume through fetal MRI imaging
prior to ex utero intrapartum treatment（EXIT）for fetal airway occlusion and stenosis could contribute to EXIT success：a retrospective multicenter joint study Satoshi Dohi1,
Kiyotake Ichizuka1, Ryu Matsuoka2, Kohei Seo1, Masaaki
Nagatsuka1, Akihiko Sekizawa2 Showa University Northern
Yokohama Hospital 1, Showa University Hospital 2
Objective We used a multicenter joint study to verify whether
fetal MRI imaging performed prior to ex utero intrapartum
treatment（EXIT）helps to predict postpartum pulmonary hypoplasia. Methods In a questionnaire survey of 174 perinatal
centers in the Kanto region of Japan, we received 114 responses（response rate 65.5%）, of which 13 cases of EXIT performed for
fetal airway occlusion/stenosis from 2005 2016 were used forthis study. Fetal pulmonary volume in the EXIT cases wasmeasured from the fetal MRI images using medical imaging
analysis software；differences between cases reporting neonatal mortality and those reporting survival were studied. Results
Airway management was achieved for all 13 cases where EXIT
was performed. Rate of survival after birth was 84.6%（11/13
cases）, with two cases of neonatal mortality. The causes of neonatal mortality were pulmonary hypoplasia（one case）and otocephaly（one case）. Based on a test for outliers（Smirnov andGrubbs test）in the 11 cases where fetal MRI imaging（including
the two cases of fetal mortality）was available and analyzed inthis study, it was statistically found that fetal pulmonary hyperplasia was an obvious outlier（p=0.031）. Definitive signs of pulmonary hypoplasia were not noted in the case with otocephaly.
Conclusion Pulmonary hypoplasia can be quantitatively confirmed through fetal MRI, which may also provide informationon the indication for EXIT. Due to the small sample populationin this study, a statistical investigation based on a larger sample
size, such as a nation wide survey, is required to validate thesefindings.

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ISP-12-6
Prediction of the severity of lung hypoplasia in congenital
diaphragmatic hernia Yuka Yamamoto1, Yojiro Maruyama2,
Atsuo Itakura2, Michio Nojima1, Koyo Yoshida1 Juntendo University Urayasu Hospital 1, Juntendo University Hospital, Juntendo
University 2
Objective Congenital diaphragmatic hernia（CDH）is a challenging lesion complicated to lung hypoplasia（LH）. The evaluationof LH is important for the perinatal counseling and postnatal
plan for the treatment strategies, however the accurate evaluation of LH has been under investigation. The purpose of thisstudy was to seek the better ultrasound parameters to evaluate
the LH in fetal CDH. Methods We collected 31 prenatal diagnosed CDH fetuses in our institutes from 2012 to 2017 Septem-

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cases of congenital infection among 70 pregnant women withpositive/borderline IgG, positive IgM, and IgG avidity index of
35.0% or less and eleven（39.3%）among 28 women with IgG and/or IgM seroconversion after an initial negative IgG and negative
IgM result. Keeping 100% sensitivity for the former six congenital infection cases, positive predictive values of IgM titer levelfor congenital infection were 8.6%（IgM titer of 1.21 or more）,
11.8%（2.00 or more）, 15.0%（4.00 or more）, 17.1%（6.00 or more）,
respectively. An IgM titer level of 6.00 or more showed the highest positive predictive value for congenital infection in first trimester pregnant women with a positive/borderline IgG, positive IgM, and low IgG avidity result. Conclusion High titer of
CMV IgM during the first trimester in pregnant women withprimary infection is a predictive factor for congenital infection.

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ber. Pulmonary arterial（PA）size, observed/expected lung area/
head circumference ratio（o/e LHR）and PA Doppler parameterssuch as acceleration/ejection time ratio（AT/ET）, peak early
diastolic reverse flow（PEDRF）and pulsatility index（PI）were
measured. PA size was converted to z score. Perinatal outcome
including the survival and duration of intubation was evaluated.
Results PA z score in contralateral PA was significant smallerin lethal group compared to survivor group（p＜0.05）. Therewas a decreased trend of AT/ET in lethal group compared tosurvivors（p=0.05）. However, there were no significant differences in PEDRF or PI. o/e LHR was significantly lower in lethalgroup compared to the survivors（p＜0.01）. Interestingly, the duration of intubation related to AT/ET ratio rather than o/e LHR
or PA z score. Conclusion The risk of death in infants with
CDH related to o/e LHR and contralateral PA z score. The
prognosis of morbidity about LH may more relate to AT/ET in
PA.

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ISP-12-7
A case of prenatal diagnosis of congenital hiatal hernia Moe
Yorozu, Naoki Okimoto, Kao Fukui, Naomi Oooka, Mizuho
Yoshida, Saya Tsukahara, Satoko Masahiro, Yoko Tateishi,
Kazumasa Kumazawa, Katsuhiko Tada Okayama Medical Center
Prenatal diagnosis of congenital hiatal hernia（HCC）is uncommon and is not considered in the differential diagnosis of prenatal abnormal sonographic findings of cystic chest anomalies. It isalso difficult to differentiate HCC from bochdalek hernia. We report a case prenatally diagnosed as HCC. A 30 year old woman
was referred at 35 weeks of gestation for fetal sonographic
evaluation due to a cystic mass in the fetal thorax and suspectedof bochdalek hernia. Sonographic examination revealed a cystic
structure behind the heart and the stomach of the fetus was not
visualized in the abdominal cavity. The cystic mass in the thorax was then suspected as the stomach. The heart appeared normally located but slightly shifted anteriorly, without mediastinal shift, and the lungs appeared to be of normal echogenicity
and volume. Based on these findings, the stomach was suspected
to be located specifically into the mediastinum and HCC was thepossible diagnosis. At 36 weeks of gestation, the sonographic examination revealed the stomach was visible in the abdominal
cavity. The sagittal section showed a small stomach located below the diaphragm that continues into the mediastinum. Magnetic Resonance Imaging of the fetus was performed at 36
weeks of gestation and reassured that the reduction of the lungvolume was to be slight. At 39 weeks of gestation, A 2,944g male
was born spontaneously and the pulmonary status of the newborn was entirely normal. The postdelivery chest radiography
confirmed the prenatal diagnosis. HCC should be considered in
the differential diagnosis of fetal cystic chest anomalies.

ISP-12-8
A case of fetal megalocystis and oligohydramnios with bladder size reduction and amniotic fluid volume improvement
during the second trimester Eriko Iwane, Minoru Mitani,
Hazuki Iwata, Kanae Kashiwazaki, Masakazu Katou, Aika
Korai, Kana Maruta, Misato Akiyama, Hidefumi Tashiro,Tokyo
Masami Wada, Yoshiyuki Nakajima, Naoki Masaoka
Womenʼs Medical University Yachiyo Medical Center
Currently, fetal urinary tract abnormalities can be diagnosed
relatively easily using ultrasound in early pregnancy. We report
the case of a fetus diagnosed with megalocystis, oligohydramnios, and bilateral hydronephrosis during the first trimester,whose bladder size was reduced. The amniotic fluid volume improved during the second trimester. The presence of urachal
remnants was suspected after birth. A 33 year old primiparous! !

woman. Abdominal ultrasonography at 12 gestational weeks,
performed at another hospital, raised a suspicion of megalocystis and fetal bladder outlet obstruction. After that oligohydramnios and bilateral hydronephrosis were diagnosed. At 23 gestational weeks, the fetal bladder was reduced in size and amniotic
fluid volume was improved. At 31 gestational weeks, she consulted our hospital due to moving house. Abdominal ultrasonography was performed；the scrotum and penis were identified, but we could not confirm the status of the bladder andurine outflow tract. At 38 gestational weeks, she delivered bycesarean section due to breech presentation. The male neonate
weighed 2,498 g, and Apgar scores were 3/5. He had a small penis and constriction of the urethra, and his testes could not be
palpated in the scrotum. Due to urine leakage around the umbilicus, we suspected urachal remnants. Ultrasonography
showed bilateral renal cysts and a hydroureter. We used a
guidewire to insert a 3 Fr feeding tube, and urine excretion occurred. If megalocystis improves, bladder rupture and reopening of the urethral closure may be considered. Because spontaneous resolution of urachal remnants is relatively rare, we report our case with a literature review.

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ISP-12-9
Familial campomelic dysplasia due to maternal germinal mosaicism Daisuke Higeta1, Takeshi Takagi2, Takashi Minegishi1
Gunma University Hospital 1, Gunma Childrenʼs Medical Center 2
Campomelic dysplasia（CD）is an autosomal dominant skeletal
dysplasia caused by heterozygous SOX9 mutations. Most patients are sporadic due to a de novo mutation. Familial occurrence of CD is very rare. We report on a family with CD caused
by maternal germinal mosaicism. Two siblings（the first andthird children）showed the classic CD phenotype with a novel
SOX9 mutation（c.441delC, p.N147fsX182）. Radiological examination of the mother showed mild skeletal changes, such as narrow ilia and elbow dislocation. Then, her somatic mosaicism of
the mutation was ascertained. In the next pregnancy, she underwent a prenatal molecular analysis with amniocentesis, yielding
a normal result, and gave birth to a healthy fourth child. This is
the first report of molecularly confirmed maternal germinal mosaicism for a SOX9 mutation. We suggest that a meticulous
clinical examination of the parents, even if they are superficiallyhealthy, is needed to avoid overlooking germinal mosaicism of
SOX9 mutations.

ISP-12-10
14 cases of fetal skeletal dysplasia：accuracy of prenatal diagnosis Miyoko Waratani, Yukiko Tanaka, Aki Mabuchi, Jo
Kitawaki Kyoto Prefectural University of Medicine
Objective Fetal skeletal dysplasia comprises disorders of prenatal onset that can be diagnosed in the antenatal period. These
disorders are characterized by underdeveloped bone and cartilage. Although the diagnostic rate has increased with the widespread use of ultrasound, prenatal diagnosis is complicated, because the description of the phenotype is often inconclusive.
Skeletal dysplasia mostly refers to monogenic disorders；thus,
a definitive diagnosis is possible through the identification of amutation in the defective gene. We report the results of our investigation of prenatal and definitive postnatal diagnoses in 14
cases of fetal skeletal dysplasia. Methods For cases in whichskeletal dysplasia was suspected in the antenatal period, we refined the diagnosis by performing prenatal 3 dimensional computed tomography and magnetic resonance imaging. We compared the postnatal definitive diagnosis with the prenatal diagnosis. Results There were thanatophoric dysplasia, osteogenesis
imperfecta, campomelic dysplasia, Desbuquois syndrome,achondroplasia（including 1 case with trisomy 21）, hypochondro-

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ISP-13-1
Repairing fetal membranes using elastomeric sealant in vivo
mouse model Yosuke Kawamura, Eiji Kondoh, Shingo Io, Mai
Sato, Hiroshi Takai, Yoshitsugu Chigusa, Haruta Mogami,
Masaki Mandai Kyoto University
Objective Although preterm premature rupture of membranes（pPROM）is associated with adverse pregnancy outcomes, there
is no effective treatment. The aim of this study was to evaluate
the sealing and healing capacity of elastomeric sealant in mousesterile pPROM model. Methods Murine uterus and fetal membranes were punctured with a 20 gauge needle at 15 days post
coitum（dpc）by laparotomy. After puncture, elastomeric sealant,
a viscous diisocyanated prepolymer, or phosphate buffered saline（PBS）was injected between membrane and myometrium.
At 18 dpc, rupture size was measured under microscope and fetal membranes were collected. We conducted histological andgene expression analysis of the membrane. Results Rupture sizeof choriodecidua became significantly smaller by sealant injection than PBS（0.45±0.19 vs 1.43±0.16 mm, P ＜0.01, n=14 and20, respectively）. Rupture size of amnion tended to be smaller
by sealant, although it did not reach statistical significance（0.4. mRNA expression of wound±0.194 vs 0.74±0.186 mm, P =0.23）
healing growth factors, Egf , Fgf2 , and Tgfb3 was increased insealant group compared to PBS（x3.1, x2.6, x1.8, respectively, P＜0.05）. In addition, Mmp9 , and Il10 mRNA were increased by. Conclusion Elassealant（x3.5, x4.6, respectively, P ＜0.05）
tomeric sealant assists healing of ruptured fetal membranes by
releasing growth factors and remodeling extracellular matrix.

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An ex vivo model and case report using intracervical elastomeric sealant for previable spontaneous premature ruptureof the membranes Eiji Kondoh, Junzo Hamanishi, Shingo Io,
Yoshitsugu Chigusa, Yoshihide Inayama, Haruta Mogami,
Yosuke Kawamura, Noriomi Matsumura, Masaki Mandai Kyoto
University
Objective To study an ex vivo model for sealing the uterine cervical canal and to report our experience with an intracervicalelastomeric sealant for treatment of previable premature rupture of the membranes（PROM）. Methods The sealant, which
has been used as a hemostatic agent for arterial anastomosis,
was applied to the cervix of uteruses removed for benign gynecological disease. Normal saline was administrated into the exvivo uterine cavity through a catheter using a pressure infusion
bag. We investigated whether the application of the sealantcould prevent the leakage of normal saline from the cervical canal. This technique was then applied to a case of previable spontaneous PROM occurring at 19 weeks gestation. Results The
sealant was effective in preventing fluid loss from the ex vivo
uterine cavity even under conditions of infusion bag pressure
beyond 150 mmHg. The intracervical sealant treatment, combined with cervical cerclage, prevented rapid decrease of theamniotic fluid volume after amnioinfusion in the case of previ-able PROM, leading to prolongation of the pregnancy until 25
weeks gestation. The infant survived without severe sequelae.
The study was approved by the ethics committee. Conclusion
Intracervical elastomeric sealant can stop fluid leakage completely in an ex vivo model. Although the in vivo application requires improvement in practical use, the sealant would help increase amniotic fluid volume and improve outcomes of pregnancy complicated with previable PROM.

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Development of a prognostic/diagnostic examination systemof preterm birth, targeting serum galectin 3 Satoshi Urabe1,
Haruhisa Konishi1, Yuko Teraoka1, Hiroshi Miyoshi2, Mutsumi
Miyauchi3, Takashi Takata3, Yoshiki Kudo1 Hiroshima University 1, Hiroshima Prefectural Hospital 2, Department of Oral andMaxillofacial Pathobiology, Hiroshima University 3
Objective Preterm birth（PTB）is a leading cause of neonatal
morbidity and mortality. We confirmed that a Porphyromonas
gingivalis（P.g. ）dental infection induced PTB mouse model
showed 2 days of PTB. In the placenta, P.g. was detected；
moreover, galectin 3（Gal 3）, an immune regulator, was significantly upregulated in the placenta, amniotic fluid, and serum.
The purpose of this study was to establish a screening and/or
monitoring system targeting serum Gal 3 levels in pregnant
women at a high risk of PTB. Methods Following institutional
review board approval and attainment of informed consent, we
examined Gal 3 levels in maternal blood samples and their association with PTB. We carried out a case control study that included 106 puerperae who experienced a spontaneous delivery：21 cases（premature）and 85 controls（full term）. Results
We confirmed that serum Gal 3 level in cases of spontaneous
PTB（71% of cases of PTB）is higher than that in cases of fullterm birth in every gestation period. Moreover, pregnant
women with serum Gal 3 levels greater than 15 ng/mL had aparticularly high risk of PTB. Conclusion In this study, we demonstrated that Gal 3 could be a potential biomarker of PTB. We
will next perform a large scale clinical evaluation study to clarify the usefulness of serum Gal 3 level for the prediction/diagnosis of PTB.

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Analysis of bacterial floral profile of the amniotic fluid in thecases of intra amniotic inflammation using next generation
sequencer Tsuyoshi Yamasaki1, Takashi Horinouchi2, Toshiyuki
Yoshizato2, Kimio Ushijima2, Ryoko Kawatsu3, Hidetoshi Honda3
Kyushu Medical Center 1, Kurume University 2, Human Micriobial Laboratory, Biogenomics, Co., Ltd. 3
Objective To analyze the amniotic fluid（AF）bacterial floral
profile in the cases of intra amniotic inflammation（IAI）using
next generation sequencer. Methods Subjects consisted of 46 patients with threatened premature labor at ＜34 weeks gestation
at our center with amniocentesis performed for bacterial culture. Maternal venous white blood cell（WBC）count, C reactive
protein（CRP）and AF interleukin（IL）6 levels were simultaneously measured. Analyzed were 17 cases, with 9 cases in thecontrol group having WBC of ＜12,000/μL, CRP of ＜0.5 mg/dL
and AF IL 6 level of ＜2,600 pg/mL, and 7 cases in the IAI
group, with AF IL 6 level of ＞2,600 pg/mL. After microbial
genomic DNA was extracted, the V1 V2 regions of the16S ribosomal RNA gene were amplified and 3,000 reads were randomly
chosen. The strains was classified by operational taxonomic unit
analysis and determined based on the reference database, while
the composition ratio was calculated as the percentage of thenumber of reads in each strain. Results In the control group, thetop five strains were all the same. In the top three strains, Fusobacterium sp. 2̲1̲31 , Staphylococcus haemolyticus , and Fuso-

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plasia, Elis van Creveld syndrome, and 2（siblings）with hypophosphatasia（HPP）. In 1 case, definitive postnatal diagnosis differed from the prenatal diagnosis, and definitive diagnosis in another case was made through DNA testing following intrauterine death. In a patient with Desbuquois syndrome and HPP, adefinitive diagnosis had been made in a sibling through DNA
testing；thus, the diagnosis was easy following prenatal detection. Conclusion In order to identify the defective gene andmake a definitive diagnosis, it is necessary to narrow down thetarget gene through precise clinical diagnosis. Establishing
more accurate clinical diagnoses should be the goal of futurestudies.

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bacterium periodonticum were found in this order. In the IAI
group, while 6 cases showed similar profile as the control 2 patients indicated a different composition among the top 5 strains,
including Faecalibacterium prausnitzii , Bacteroides massiliensis and Atopobium vaginae , of which only trace amounts were
contained in the control group. Conclusion Differences in thebacterial flora in the amniotic fluid may be related to intra amniotic inflammation.

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ISP-13-5!

Risk factors for preterm birth in ureaplasma infected pregnant women with preterm labor Erina Hashimoto, Ai Kouno,
Takuo Nakayama, Hiromitsu Azuma, Chuyu Hayashi, Go
Ichikawa, Atsushi Komatsu, Yasuji Miyagawa, Shinichi Takada,Fumihisa Chishima, Kei Kawana Nihon University Itabashi HospitalObjective High level of ureaplasma infection to the vagina in
pregnant women can be a risk factor for preterm birth and someprevious studies show treatment of ureaplasma positive womenwith preterm prelabor rupture of membrane（PROM）by antibiotics for ureaplasma may prolong the pregnancy. We here examined the risk factors for preterm birth in pregnant womenwith ureaplasma infection to the vagina. Methods Under approval by Ethical committee in our hospital, we investigated retrospectively medical records for 56 pregnant women who were
hospitalized due to preterm labor in our hospital in 2017. Ureaplasma（paruvum/urealiticum）test of the vaginal swab wasdone for all cases. All ureaplasma positive cases were treatedby azithromycin（1g×1）when diagnosed as positive（24 34 gestational weeks）. All cases were treated by tocolytic agents regardless of positivity for ureaplasma. Results Positive rate ofureaplasma in the vagina among women with preterm laborwas 27%（15/56）. Preterm birth rate in ureaplasma positive
cases was clearly higher than that in ureaplasma negative（47%vs 15%, p=0.0275）.The rate of other microbial infection in ureaplasma positive cases was higher than that in ureaplasma
negative（40% vs. 10%, p=0.0163）. logistic regression multivariate analysis showed numbers of white blood cell（WBC）was independent risk factor for preterm birth with marginal significant（p=0.08）. Conclusion Ureaplasma infection was associatedwith preterm birth even though treatment by antibiotics forureaplasma. Ureaplasma positive women were likely to complicate other microbial infections. Taken together with logistic
analysis, ureaplasma based infection and inflammation in thevagina might be critical for preterm birth.

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The association of progranulin level controlled by progesterone with cervical maturation Taiki Samejima, Takeshi
Nagamatsu, Takayuki Iriyama, Yutaka Osuga, Tomoyuki Fujii
The University of Tokyo HospitalObjective Protease system is a key to tissue remodeling processof the uterine cervix. Progranulin, a secretory protein, exerts
anti protease activities, contributing to tissue repairing processes. This study aimed to investigate the involvement of cervical progranulin in the process of cervical maturation. Methods
This study was conducted under the approval of the ethics committee in our facility. From 166 women in uncomplicated pregnancy at 24 26 weeks of gestation, cervical mucus was collected
and the cervical length（CL）was measured by transvaginal ultrasonography. Neutrophil elastase and progranulin protein levels in the mucus samples were measured by ELISA. The correlation of those substances with CL was analyzed. mRNA expression of cervical progranulin was measured in two mouse models；a preterm birth model by administration of a progesterone
receptor antagonist, RU486 and a delayed birth model by exces-

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Time series Analysis of Life logs to Predict Hypertensive
Disorders of Pregnancy in Maternity Log Study Takafumi
Yamauchi1, Daisuke Ochi1, Yoshiki Tsunemoto2, Maiko Wagata3,
Yuki Harada4, Riu Yamashita5, Osamu Tanabe4, Nobuo
Yaegashi6, Masao Nagasaki4, Junichi Sugawara3 NTT DOCOMO,
INC./Tohoku University 1, NTT DOCOMO, INC. 2, Department ofCommunity Medical Supports, Tohoku University Tohoku
Medical Megabank Organization 3, Department of Integrative
Genomics, Tohoku University Tohoku Medical Megabank Organization 4, Department of Biobank, Tohoku University Tohoku
Medical Megabank Organization 5, Tohoku University Hospital 6
Objective Pregnancy complications including hypertensive disorders of pregnancy（HDP）are multifactorial diseases causedby complex interactions of genetic and environmental factors.
Therefore, analyses of both factors are important to develop
methods of early detection and prevention of such diseases.
However, most of the previous researches have used self reportquestionnaires to collect information on environmental factors,
and had limitations in the frequency of data acquisition and theobjectivity of the information. Methods We are conducting aprospective cohort study Maternity Log Study of pregnant
women. By using a smart phone and monitoring devices, participants（n=302）upload daily life logs including biometric information on more than 20 items such as household blood pressure, as
well as lifestyle information on more than 10 items such ashours of sleep. Furthermore, we collected specimens such as
blood, saliva, and urine of participants for multi omics analyses.
In this presentation, we report differences in life logs between
an HDP（n=17）and control（n=124）groups. Results We foundsignificant differences in several items of life logs between thetwo groups. For example, the HDP group experienced larger
numbers of days with palpitation after the 28th week of gestation. Next, we established prediction models using several life
logs. A leave one out cross validation demonstrated the specificity of 0.82, and the sensitivity of 0.88 at the 24th week. Conclusion By the analyses of daily life logs during pregnancy, we
identified candidate life log markers for HDP. On the presentation, it will be also reported whether the predictive performanceis further improved by combining maternal omics data withlife logs.

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ISP-13-6!

sive progesterone administration. Results The progranulin levelof the cervical mucus in women with CL＞=35 mm（n=142）wassignificantly higher than that in women with CL＜35 mm（n=24）；（58.9 vs 34.4 ng/mg, p＞0.05）. No remarkable difference
between these two groups was observed in the cervical neutrophil elastase levels. While RU486 treatment reduced the expression of cervical progranulin, exogenous progesterone administration enhanced the expression of cervical progranulin. Conclusion Our findings suggest the possibility that anti proteaseactivity of progranulin is controlled by progesterone and is involved in the regulation of cervical maturation.

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Prediction of Hypertensive Disorders of Pregnancy by Using
Genetic Information in Maternity Log Study Yoshiki
Tsunemoto1, Daisuke Ochi2, Takafumi Yamauchi2, Riu
Yamashita3, Maiko Wagata4, Yuki Harada5, Osamu Tanabe5,
Nobuo Yaegashi6, Masao Nagasaki5, Junichi Sugawara4 NTT DOCOMO, INC. 1, NTT DOCOMO, INC./Tohoku University Tohoku
Medical Megabank Organization 2, Department of Biobank, Tohoku University Tohoku Medical Megabank Organization 3, Department of Community Medical Supports, Tohoku University
Tohoku Medical Megabank Organization 4, Department of Integrative Genomics, Tohoku University Tohoku Medical

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Characteristic changes of the circadian rhythm by ambulatory blood pressure monitoring seen in preeclamptic women
Yoshikatsu Suzuki, Tamao Yamamoto, Hiroshi Matsushita,
Kazushi Watanabe, Akihiko Wakatsuki Aichi Medical University
Objective Blood pressure（BP）shows circadian rhythm similar
to Cosine curve by ambulatory BP monitoring（ABPM）. BP ishigher in the afternoon and lower at midnight. Hypertension
shows blunt nocturnal BP fall and reversed circadian BP
rhythm due to disturbance in sympathetic system. We investigated the characteristic changes of circadian rhythm in womenwith hypertensive disorders of pregnancy（HDP）, especiallypreeclampsia（PE）by ABPM. Methods In 106 pregnant women
showed hypertension by clinic BP, 24 hour ABPM diagnosed
with HDP（n=79）, including PE（n=43）and gestational hypertension（GH, n=36）, and white coat hypertension（WCH, n=27）. Circadian rhythm was investigated for 1）fall of nighttime as dipper, non dipper or riser, 2）and percent rhythm（PR：multiple
regression）and acrophase（maximal BP time）by Cosinor
method. This study was approved by ethics of local committee.
Results Mean systolic BP（SBP）and diastolic BP（DBP）in PE
and GH was higher than in WCH. The riser in SBP was seen in
21in PE, 15 in GH and 0 in WCH. The PR of both BPs in threegroups was similar, while, the PR of pulse was lower in PE（0.24±0.18 for PE vs 0.33±0.17 for GH and 0.33±0.21）. In PR more
than0.16, the acrophase of SBP in 57% of PE, 40% of GH and 0%
of WCH were shifted to evening or night. Conclusion Characteristic changes in PE was reduction of PR in BP as well as pulse
and shifted acrophase. The pathogenesis of PE might be involved in not only vascular dysfunction but also sympathetic
disorders.

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Cardiac dysfunction in patients with preeclampsia Eiji
Yoshida, Risa Yoshimoto, Takuji Ueno, Takuma Yamada,
Takehiko Takeda, Sho Tano, Kaname Uno, Mayu Ukai, Teppei
Suzuki, Toko Harata, Yasuyuki Kishigami, Hidenori Oguchi

Perinatal Medical Center, TOYOTA Memorial HospitalObjective Some preeclampsia patients develop left ventricular
diastolic dysfunction（LVdD）.However, few studies have illustrated prognostic factors for LVdD. We aimed to reveal the risk
factors associated with LVdD in patients with preeclampsia.
Methods This was a single center prospective cohort study. Single pregnant women with preeclampsia who delivered at our
hospital between November 2011 and January 2015 were eligible. Echocardiography was conducted in 99 patients before delivery and in 163 patients a few days after delivery. Early transmitral velocity/early diastolic velocity of the mitral annulus（E/Ea）＞15 was defined as LVdD. Logistic regression analysis was
conducted to examine risk factors of LVdD. Results Age＞35,
plasma BNP＞100 pg/mL, blood loss＞1,000 mL, plasma creatinine＞0.7 mg/dL and severe preeclampsia（systolic BP＞160
mmHg or diastolic BP＞110 mmHg）were included as independent variables for the analysis of LVdD. E/Ea＞15 was detected
in 12（12.1%）patients before delivery and in 16（9.8%）patients
after delivery. While BNP＞100 pg/mL was a risk factor of
LVdD before delivery（OR=4.114, 95%CI=1.023 16.549, p=0.046）,
this was not an independent risk factor of LVdD after delivery（OR=2.396, 95%CI=0.681 8.431, p=0.173）. Maternal age＞35 wasa risk factor after delivery（OR=6.002；95%CI=1.536 23.464；p=0.01）.Blood loss＞1,000 mL, plasma creatinine＞0.7 mg/dL andsevere preeclampsia did not associate with LVdD. Conclusion
LVdD was detected even after delivery. While BNP＞100 pg/
mL was the risk factor of LVdD before delivery, it was not an independent risk factor of LVdD after delivery.

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Maternal cardiac function in patients with preeclampsia compared with normal pregnant women Takuma Yamada,
Takehiko Takeda, Kaname Uno, Sho Tano, Michinori Mayama,
Mayu Ukai, Teppei Suzuki, Toko Harata, Yasuyuki Kishigami,
Hidenori Oguchi TOYOTA Memorial HospitalObjective Preeclampsia is a risk factor of peripartum cardiomyopathy and increases the risks of cardiovascular diseases.
The aim of this study was to examine maternal cardiac function
in patients with preeclampsia during peripartum period. Methods Patients with preeclampsia were enrolled in this study from2010 to 2016. Echocardiography was conducted three times；
late stage of pregnancy, early and one month postpartum. In thesame period, pregnant women without high BP took echocardiography as a control group. Results Eighty seven patientswith severe preeclampsia and 51 patients with mild preeclampsia were compared with 36 normal pregnant women. Left ventricular ejection fraction（LVEF）was not significantly different
among three groups. Though LV diastolic parameter, which wasmeasured by early transmitral velocity/early diastolic velocityof the mitral annulus E/E,, became worse in mild group at latepregnancy, the cardiac parameters were not significantly different in normal pregnant after delivery. At late pregnancy, E/E,,
left ventricular（LV）diameter and LV wall thickness deteriorated in severe group compared with other groups. These deteriorations were shown after delivery, even at one month postpartum. Conclusion Maternal cardiac function of mild
preeclampsia became normal in early postpartum. On the other
hand, severe preeclamptic patients experienced cardiac
changes and these deteriorations did not recover completely atearly and even one month postpartum. These changes are assumed to correlate with future onset of cardiovascular diseases.

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Long term outcomes of infants delivered between 24 and 34
weeks of gestation in women with early onset hypertensive
disorders of pregnancies（HDP）Junsuke Muraoka1, Masanao!

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Megabank Organization 5, Tohoku University Hospital 6
Objective Hypertensive Disorders of Pregnancy（HDP）is a major cause of maternal and fetal death. HDP is caused by complex
interactions of genetic and environmental factors. Initially, we
focused exclusively on genetic factors in HDP on the way to the
future analysis of the complex interactions of both genetic andenvironmental factors. Methods In this study, we used wholegenome sequence data obtained from 24 HDP group and 278
control group. We first compiled 166 HDP associated genes
from public databases and several researches with HDP meta
analysis. We cataloged all the common SNPs in those HDP associate genes with the minor allele frequency（MAF）＞0.01 in our
samples. From them, we selected SNPs potentially useful for
prediction of HDP based on the CADD score that represents thedeleteriousness of single nucleotide variants, and 10 SNPs highest in the CADD score in each gene were selected. We then performed prediction of HDP by using the adaptive elastic net, andthe results were evaluated by the leave one out method. Results The sensitivity and specificity of this model was 0.22 and
0.75, respectively, when only the SNPs of MAF＞0.05 in our samples were used. However, when only the SNPs of MAF＞0.1
were used, the sensitivity fell to 0.00. Conclusion The results
suggest that it is difficult to predict HDP only by the genetic information. However, the prediction accuracy may be improvedby increasing the number of samples. In future, we also try to
improve the accuracy by using both genetic and environmental
factors.

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Oohashi1, Kaori Michikata2, Yohei Maki2, Koutarou Doi2,
Yasuyuki Kawagoe2, Yuki Kodama2, Masatoki Kaneko2, Hiroshi
Sameshima2 Miyazaki Medical Association Hospital 1, Universityof Miyazaki Hospital 2
Objective To assess the long term outcomes of infants in early
onset HDPs and its antepartum fetal heart rate patterns correlated to the outcomes. Methods A retrospective, observational
study was performed involving singleton, non anomalous 282 infants born between 24 and 34 weeks of gestation at a tertiary
center for a 13 year period（2003 2015）, focusing on antenatalmanagement including administration of antenatal corticosteroid and magnesium sulfate, fetal heart rate monitoring, mode ofdelivery, birth weight and its percentile, and infants outcome.
Cases with intrapartum unavoidable events including placental
abruption（n=17）and prolapse of umbilical cord（n=2）are excluded. Poor outcome included neonatal death（ND）, cerebral
palsy（CP）, and developmental disorders（DD）at 2 year old.
Results Excluded 34 loss of follow up infants, we enrolled 229
cases, in which 34 cases with HDPs and 195 cases without HDPs.
In early onset HDPs, nine infants（16%）resulted in poor outcome including one case of ND, three cases of CP, and five casesof DD. Minimal baseline variability associated with late decelerations of antepartum FHR monitoring patterns had tendency
to result in poor neurological outcomes compared to any otherabnormal FHR patterns. Conclusion Antepartum FHR patterns
including minimal baseline variability associated with late decelerations may be risk factor for neurological sequela in early
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The difference of the activated prorenin concentration between pregnant women with or without hypertensive disorderof pregnancy Shoko Tamada, Kazumasa Tani, Jota Maki,
Takeshi Eguchi, Takashi Mitsui, Eriko Eto, Kei Hayata, Hisashi
Masuyama Okayama University
Objective The activated prorenin has an important role in thetissue RAS. The purpose of this study was to reveal the difference of activated prorenin concentration between pregnant
women who developed hypertension disorder of pregnancy andnormal pregnant women. Methods The subjects were 7 pregnant women who developed HDP and 30 normal pregnant
women in Okayama University Hospital. The activated proreninconcentration was measured with the plasma sampled in thefirst, second and third trimesters of pregnancy and umbilicalcord blood by ELISA and compared between pregnant women
who developed HDP and normal pregnant women. This study
was approved by the Institutional Ethical Review Board of
Okayama University Graduate School of Medicine, Dentistry
and Pharmaceutical Sciences. Results The activated proreninconcentration in pregnant women who developed HDP on thesecond trimester was 573.6±71.9 pg/ml, and that on the third
trimester was 733.3±211.1 pg/ml. The activated prorenin concentration in normal pregnant on the second trimester was
1,170.2±251.1 pg/ml, and that on the third trimester was 1,089.7±386.0 pg/ml. The activated prorenin concentration in pregnant women who developed HDP was significantly lower thanthat in normal pregnant women throughout the second andthird trimesters of pregnancy. Conclusion Activated proreninconcentration in pregnant women who developed HDP waslower than that in normal pregnant women. Reduction of blood
activated prorenin concentration in pregnant women who developed HDP may reduce vasodilatation by AT2 required during
pregnancy and may be involved in placental blood flow failure.

ISP-15-1

for gestational age infants among pregnant women without
gestational diabetes Dittakarn Boriboonhirunsarn, Prasert
Sunsaneevithayakul Siriraj Hospital, Thailand
Objectives To compare incidence of large for gestational age（LGA）between women with false positive and normal glucose
challenge test（GCT）, and to evaluate factors associated with
LGA. Methods A retrospective cohort study included 480 pregnant women at risk for gestational diabetes（GDM）；160 withfalse positive GCT and 320 with normal GCT results. Incidenceof LGA and other pregnancy outcomes were compared between
normal and false positive GCT groups. Possible associated factors for LGA were evaluated by comparing various characteristics with those with appropriate for gestational age（AGA）infants. Results Women with false positive GCT were significantly older and more likely to be multiparous, and less likely togain weight greater than recommendation. Incidence of LGA
were comparable between false positive and normal GCTgroups（15.6% vs. 13.1%, p=0.456）. Other pregnancy outcomes
were also comparable. Logistic regression analysis showed thatpre pregnancy underweight significantly reduced the risk of
LGA（adjusted OR 0.25, 95%CI 0.07 0.87, p=0.029）while second
trimester weight gain＞7 kg significantly increased the risk of
LGA（adjusted OR 3.13, 95%CI 1.67 5.89, p＜0.001）. Conclusion
The risk of LGA was only slightly higher among women withfalse positive GCT. Pre pregnancy underweight reduced therisk of LGA while second trimester weight gain＞7 kg increased
the risk of LGA.

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Relationship between 50 g glucose challenge test and large!

Prevalence of false positive 50 g glucose challenge test andrelationship with adverse pregnancy outcomes Auakarn
Thananyai, Dittakarn Boriboonhirunsarn, Tachjaree Panchalee
Siriraj Hospital, Thailand
Objective To determine the prevalence of false positive resultsof 50 g GCT for early GDM screening and relationship withpregnancy outcomes. Methods A total of 500 singleton pregnancy who were at risk for GDM and received 50 g GCT for
GDM screening before 20 weeks of gestation were included.
Women with abnormal 50 g GCT received 100 g OGTT for
GDM diagnosis. Data were extracted from medical records, including baseline characteristics, GDM risk factors, 50 g GCT
and 100 g OGTT results, obstetric data, and pregnancy outcomes. Prevalence of false positive results of 50 g GCT and
GDM were estimated. Various baseline characteristics and pregnancy outcomes were compared between women with normal
GCT, false positive GCT, and GDM. Results Mean age was 33.4
years, mean BMI was 22.9 kg/m2, and 45.6% were nulliparous.
Common GDM risks were age＞30 years（81.6%）,family historyof DM（30.4%）, and overweight/obesity（24.6%）. Mean GA at
GDM screening was 9.8 weeks. Normal 50 g GCT was found in
243 women（48.6%）. The other 257 women underwent 100 g
OGTT and 187（37.4%）had false positive GCT results（normal
100 g OGTT）and 70（14%）had GDM. Women with GDM hadsignificantly higher age, BMI, and more likely to be overweightor obese than those with normal and false positive GCT（p＜0.05）. Gestational weight gain were comparable between normal
and false positive GCT but it was significantly greater thanGDM（p＜0.001）. A significant trend of increasing in the rate of
LGA was observed in normal GCT, false positive GCT, and GDMgroup（14.4%, 21.9%, and 25.7%, respectively, p=0.013）. Conclusion Prevalence of false positive GCT was 37.4%. Women withfalse positive GCT were at increased risk of LGA.

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Determination of an Optimal 50 g Oral Glucose Challenge
Test Cutoff Value to Screen for Gestational Diabetes Mellitus

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ISP-15-4
Present condition and problems of gestational diabetes mellitus care in our prefecture Naoto Yonetani, Takashi Kaji,
Atsuko Hichijo, Minoru Irahara Tokushima University
Objective The objective was to clarify the present condition andproblems of gestational diabetes mellitus（GDM）care in our prefecture. Methods A self administered questionnaire survey related to GDM was conducted for all birthing facilities in our prefecture. The number of singleton births in 2018, among which
the number of GDM patients, the screening method of glycometabolism abnormality, the management during pregnancy andpuerperium, the explanation about the future risk of developing
diabetes were investigated. Results All 18 facilities（9 hospitals
and 9 clinics）responded. The total number of singleton births
was 5,969, among which 113 GDM patients delivered. The incidence of GDM was 1.9%, which was well below the assumed incidence at the new GDM diagnostic criteria（7 to 8%）. One hospital and 3 clinics did not establish criteria for positive screening
in the first trimester. In 6 hospitals all patients with GDM werereferred to the internal medicine. In 3 hospitals and 2 clinics all
patients had 75gOGTT during puerperium, and in five hospitals
and 4 clinics all patients were explained about the future risk of
diabetes. Conclusion The incidence of GDM in our prefecture
was low. It was considered as one of the factors that screening
criteria were not established at any facilities. The frequency
with internal medicine physician involvement was high, we considered that the survey about the management method of physicians was also necessary. Furthermore, the improvement of
postpartum educational methods was also desired.

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ISP-15-5Glycemic and metabolic features in gestational diabetes：singleton versus twin pregnancies Yohei Akiba, Kei Miyakoshi,
Yu Sato, Satoru Ikenoue, Yoshifumi Kasuga, Daigo Ochiai,
Tadashi Matsumoto, Mamoru Tanaka, Daisuke Aoki Keio University
Objective The information on clinical features of gestational diabetes（GDM）in twin pregnancies is limited. The aim of thisstudy was to compare the severity of dysglycemia between twinand singleton pregnancies with GDM（T GDM and S GDM）.
Methods We reviewed GDM women who underwent perinatal
care from 2011 to 2016 in our hospital. During the study period,
all GDM women underwent dietary management and self monitoring of blood glucose measurements. Insulin administration

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was initiated when dietary treatment did not achieve the glycemic goal. The glycemic and metabolic characteristics were compared between T GDM and S GDM, as follows：gestational
week at the diagnosis of GDM, 75g oral glucose tolerance test
（OGTT）results, HbA1c, insulin secretion（i.e. insulinogenic index［IGI］and Insulin Secretion Sensitivity Index 2［ISSI 2］）,
and insulin requirement before delivery. Results Of 3,322 deliveries（twin, n=123；singleton, n=3,199）,there were 471 womenwith GDM（T GDM, n=20；S GDM, n=451）.The rate of one abnormal OGTT value in T GDM was similar to that in S GDM（71% vs 60%）. There were no significant differences in gestational week and levels of HbA1c at diagnosis, levels of IGI and
ISSI 2 between T GDM and S GDM（median, 24 weeks vs 17
weeks, 5.3% vs 5.2%, 0.94 vs 0.79, 1.85 vs 1.97, respectively）.The
rate of insulin treatment and a median dosage of insulin needed
before delivery was comparable between the two groups（TGDM vs S GDM：32% vs 45% and 13 vs 14 unit/day）. Conclusion Our data indicated that women with T GDM was similar to
those with in the severity of glucose intolerance.

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Efficacy of the risk scoring system to triage patients withgestational diabetes Hiroshi Yamashita, Megumi Koga, Ichiro
Yasuhi, Satoshi Isokawa, Noriko Odani, So Sugimi, Yasushi
Umezaki, Sachie Suga, Masashi Fukuda, Nobuko Kusuda Nagasaki Medical Center
Objective We have originally developed a risk scoring system
to triage patients with gestational diabetes（GDM）, depend on
their perinatal risk. Our aim was to demonstrate whether therisk scoring system was effective for predicting of high risk
GDM patients to triage intensive care. Methods This is a prospective study including singleton pregnant women with GDM
between 2015 2017. In the scoring system（10 points in total）, we
allocated 4 points to each risk factor；fasting PG=or ＞84 mg/
dL at diagnosis, prepregnancy body mass index=or ＞24 kg/m2,
and 1 point to；=or ＞2 abnormal values of OGTT, age=or ＞40
years. We defined the score 0, 1 2, and=or ＞4 as Category 1, 2,
and 3, respectively. We also defined high risk GDM as requiring
insulin=or ＞20 U/day and/or having a large for gestationalage infant. We evaluated the association between the categories
and the high risk GDM. Results Among 162 women, we found
48（30%）high risk GDM patients. By the scoring system, 53（33%）, 21（13%）and 88（54%）were categorized as Category
1, 2, and 3, respectively. The prevalence of high risk GDM were
13.2%, 33.3%, and 38.6%, respectively. In comparison with Category 1（reference）, Category 3 was significantly associated withhigh risk GDM with an odds ratio of 4.14（95%CI 1.76 11.0, p＜
0.01）. Conclusion The risk scoring system was confirmed as effective in this prospective study. Patients with GDM in Category 3 need more intensive care, while those in Category 1 may
require less intensive management in the clinic type care system.

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Epigenetic modifications of well controlled gestational diabetes on cord blood using genome wide methylation analysis
Yoshifumi Kasuga1,2, Kei Miyakoshi1, Yu Sato1, Toshimitsu
Otani1, Yohei Akiba1, Marie Fukutake1, Satoru Ikenoue1, Daigo
Ochiai1, Tadashi Matsumoto1, Kenichiro Hata3, Mamoru
Tanaka1, Daisuke Aoki1 Keio University 1, Kawasaki Municipal
Hospital 2, National Research Institute for Child Health and Development 3
Objective Epigenetic modifications associated with maternal
hyperglycemia are assumed to mediate the susceptibility of
metabolic disorders of the offspring. To date, however, the information on epigenetic influence on offspring in well controlled!

May 11 Fri.
ISP

Sakiko Matsuoka, Tatsuya Fukami, Miho Ando, Sumie
Nakamura, Yoko To, Takahiro Koyanagi, Maki Goto, Haruhiko
Kondo, Hiroshi Tsujioka, Fuyuki Eguchi Aso Iizuka HospitalObjective The aim of this study was to evaluate the cutoff valueof 50 g oral glucose challenge test for the screening of gestational diabetes mellitus. Methods 843 patients were analyzed using 50g GCT during 18 to 24 weeks of gestation. We set the cutoff value of blood glucose at 130 mg/dl and positive patients sequentially underwent 75g OGTT. Other patients also underwent
75g OGTT if consent for the test was available. Gestational diabetes mellitus（GDM）is/was diagnosed on the International Diabetes in Pregnancy Consensus Group（IADPCG）criteria. Results
381 patients were positive for the 130mg/dl cutoff value and 115
patients were diagnosed with GDM. 50g GCT negative patients
numbered 462 and the 45 of them who agreed to our trial underwent 75g OGTT, of which 8 patients were diagnosed with GDM.
ROC curve revealed the cutoff value of blood glucose for 50g
GCT as 129mg/dl（sensitivity：94%, specificity：64%, area under the curve：0.83, p＞0.05）. Conclusion We propose that thecutoff value of 50g GCT should be 130 mg/dl in the screening of
GDM.

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gestational diabetes mellitus（w GDM）is limited. The aim of
this study was to investigate genome wide methylation variation in cord blood from offspring born to mothers with w
GDM. Methods Umbilical cord blood samples were collectedfrom singleton term neonates born to Japanese mothers with w
GDM（n=165）or normal glucose tolerance（NGT, n=61）from2011 to 2016. All GDM women underwent dietary management
and self monitoring of blood glucose measurements. Insulin administration was initiated when dietary treatment did notachieve the glycemic goal. Genome wide DNA methylation
over 850k CpG sites in cord blood was compared between the
GDM and NGT groups using Illumina Infinium MethylationEPIC Beadchip（EPIC array）.We scaled individual arrays tohave the same median absolute deviation using limma package
in R. Results There were no differences in maternal gestational
weight gain（8.6kg vs 8.3kg）,birthweight（3,014g vs 2,988g）,sex（male：54% vs 56%）, heavy for date（birthweight＞90%tile：
16% vs 15%）and small for date（birthweight＜10%tile：1% vs3%）between the w GDM and NGT groups. The EPIC arraydemonstrated no significant epigenetic differences between thetwo groups. Even if stratified by fetal sex, pregestational weightcategory, or heavy for date neonates, there were no differentially methylated loci associated with w GDM. Conclusion
Genome wide methylation analysis demonstrated no significant
methylation differences in cord blood from offspring born tomother with w GDM, compared to those with NGT.

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Purpose We are reporting on a monochorionic diamniotic（MD）
twin pregnancy complicated by type I diabetes in which glucose level was controlled by Sensor Augmented Pump（SAP）
therapy and led to vaginal delivery. Case The patient was a 38
year old woman, gravida 3 para 1 who developed type I diabetes at 28 years and was on insulin therapy. She conceived MD
twins naturally while she was being considered for switching toinsulin pump due to poor glycemic control, and SAP therapy
was initiated at 6 weeks of gestation. The MD twins were progressing normally without amniotic fluid imbalance or abnormal blood flow. Gestational hypertension and proteinuria wasobserved at 31 weeks, which required in hospital management.
However, she had uterine contractions on admission, whichwere inhibited with magnesium sulfate. Blood pressure was stable within the normal to mildly hypertensive range and proteinuria did not worsen. Glucose levels were well controlled withcarbohydrate counting to adjust insulin dosage. Labor was induced at 37 weeks and 0 days and both babies were deliveredvaginally. The first infant weighed 3,324 g, Apgar score 8/10
and the second infant weighed 2,644 g, Apgar score 8/10. The respective glucose levels of the two babies at birth were 71 mg/dl
and 73 mg/dl. During induction of labor, the motherʼs glucose
level was controlled between 100 to 120 mg/dl. Conclusion Glucose level was well controlled during pregnancy and delivery
with SAP therapy in a MD twin pregnancy complicated with
type I diabetes, and was managed without major perinatal complications.

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ISP-15-10

Is the therapeutic intervention during early pregnancy effective in women with gestational diabetes diagnosed before 20
weeksʼ gestation? Noriko Odani, Sachie Suga, Ichiro Yasuhi,
Hiroshi Yamashita, Satoshi Isokawa, Megumi Koga, So Sugimi,
Masashi Fukuda, Nobuko Kusuda Nagasaki Medical Center
Objective It is unclear whether the therapeutic intervention for
women diagnosed as having gestational diabetes（GDM）during
early gestation. In this preliminary study, we aimed to demonstrate whether therapeutic intervention before 20 weeksʼ gestation was effective in women with GDM diagnosed during earlypregnancy. Methods This is a prospective study including
women diagnosed as GDM by 75 g glucose tolerance test
（OGTT）before 20 weeks. Those women did not have any therapeutic intervention except for regular prenatal care, and had thesecond OGTT between 24 to 26 weeks. We excluded womenwith fasting plasma glucose（PG）＜110 mg/dl or obese womenwith fasting PG of 92 109 mg/dl. Results We included 12 subjects（36±5 years；prepregnancy body mass index 24±5）, including 4 obese women. They had the first OGTT at 15±2
weeks；PGs during the OGTT were 86±8, 174±24, and 162±27mg/dl at fasting, 1 hr, and 2 hr, respectively. The second
OGTT were performed at 25±1 weeks；the PGs during the test
were 80±8, 144±27, and 134±29, respectively. By the second
OGTT, only three women（25%）were diagnosed as GDM and theother had normal results. They delivered of infants with birthweight of 2,840±544 g, without any macrosomia, at 38±2 weeks.
Conclusion In this preliminary study, three quarters of women
diagnosed as GDM during early gestation showed normal results at the repeat OGTT during midpregnancy without any
therapeutic intervention before 20 weeksʼ gestation. We suggestthat the therapeutic intervention during early pregnancy may
not be useful rather over treatment.

Correlation of early pregnancy body mass index, waist circumference and waist to hip ratio to gestational diabetes
mellitus Kathryn Bautista, Marie Catheleen Santiago Manila
Central University, Philippines
Introduction Anthropometric measurements taken in earlypregnancy can predict increased risk of gestational diabetes
mellitus（GDM）.Body mass index（BMI）may be a limited measure of total obesity because the association of diabetes with central obesity is stronger than the association with general fat.
Thus, alternative measures that reflect abdominal adiposity,
such as waist circumference, waist hip ratio, have been suggested, because increased visceral adipose tissue is associatedwith metabolic abnormalities that predispose to GDM. Objective To determine the correlation of body mass index, waist circumference and waist to hip ratio to the development of GDM.
Methods Measurments for height, weight, waist circumference
and hip circumference were done at the first prenatal visit
among 56 patients between 4 12 weeks age of gestation. Diagnosis of Gestational Diabetes Mellitus was made with fasting blood
glucose and 75g oral glucose tolerance test. Results Results
showed that BMI, and waist to hip ratio（WHR）were significantly associated with GDM. For this study, a cut off value of ＞
23 kg/m2 for GDM, and a waist to hip ratio of ＞/= 0.80 weresignificantly associated with GDM. Results revealed that WHR
is the most sensitive parameter to rule out GDM. Conclusion
There is a progressive increase in GDM risk above a BMI of 23
kg/m2（OR 2.14；95% CI 1.02, 4.76）with no apparent increase inrisk for GDM among underweight women（BMI＜18.5 kg/m2）.
There is a progressive increase in GDM risk above a WHR of＞/= 0.8. There is no significant association between GDM andwaist circumference.

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ISP-16-1

Monochorionic diamniotic twin pregnancy complicated bytype I diabetes treated with SAP therapy for blood sugar control Miho Kondo, Aki Mabuchi, Miyoko Waratani, Jo Kitawaki
Kyoto Prefectural University of Medicine

The Missing Link：A Case of Hydrops Fetalis in Alpha Thalassemia Ivy Karen Romero, Angelita Reyes-Teotico Manila
Central University Filemon D. Tanchoco Medical Foundation
Hospital, Philippines

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Clinical characteristics of women developing perinatal venous thromboembolism under standardized prophylaxis management following JSOG guideline Misako Kuramochi,
Takeshi Nagamatsu, Eri Inoue, Hitomi Furuya, Takahiro
Seyama, Toshio Nakayama, Takayuki Iriyama, Yutaka Osuga,
Tomoyuki Fujii The University of Tokyo HospitalObjective Venous thromboembolism（VTE）is a life threatening
complication in perinatal period. This study aimed to reveal
clinical characteristics of women developing VTE in perinatal
periods to gain knowledge for better management for VTE prevention. Methods This study was conducted under approval of
our facility ethics committee. The cases developing VTE inperinatal period were isolated among the women managed in
our hospital from 2002 to 2016（n=17 out of 11,896 deliveries,
0.14%）. During the observational period, the prophylaxis using
unfractionated heparin was conducted for the women with apast history of VTE and with thrombophilia confirmed before
conception risk. Pneumatic device was used for all the cases
having cesarean section. The clinical data associated with theincidence of VTE were analyzed by reviewing the medical records of the VTE cases. Results VTE occurred in the first trimester（n=9/17, 53%）
, in the second trimester（n=2/17, 12%）,in
the third trimester（n=1/17, 6%）, and in postpartum（n=5/17,
29%）. The cases developing VTE during the first trimester
were characterized by advanced maternal age at 35 or over（n=7/9, 78%）and hyperemesis requiring hospitalization（n=3/9,
33%）. There was no case developing VTE under heparin administration. Conclusion Advanced maternal age and hyperemesis would be risk factors for VTE in the first trimester.
Considering relatively high frequency of VTE in the first trimester even under the so far conducted VTE prevention management, it is necessary to establish a new prevention approachto evaluate VTE risk in early pregnancy.

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Preeclampsia in Pregnancies with Systematic Lupus Erythe-matosus Hiroyo Meguro1, Hyo Kyozuka1, Makiho Ishibashi1,
Satoshi Suzuki1, Daisuke Suzuki2, Akiko Yamaguchi1, Mikio
Tanaka3, Keiya Fujimori1 Fukushima Medical University 1,
Fukushima Medical Center for Children and Women 2, Ohta
Nishinouti Hospital 3
Objective The aim of this study was to identify factors associated with preeclampsia（PE）in pregnancies with systematic lupus erythematosus（SLE）. Methods We retrospectively conducted a case control study at two medical centers inFukushima Prefecture between 2006 and 2017. Clinical information, including immunological data obtained during the first trimester and pregnancy outcomes, were reviewed. Pregnancies
with SLE were divided into two groups（Case：pregnancy with
PE；Control：Pregnancy without PE）. Then, clinical information obtained during the first trimester was compared. A p＜
0.05 was assumed to indicate significance. Results 35 pregnancies with SLE were identified during the period. Among the 35
pregnancies, preterm birth and low birth weight（i.e.,＜2,500g）occurred in 31.4% and 42.9%, respectively. PE was observed in
9 cases（25.7%）. Immunological data obtained during the first trimester revealed that the incidence of depressed levels of CH50,
C3, C4, and anti SSA antibody was significant higher in PE
cases than in controls（77.8% vs 21.7%, 77.8% vs 9.1%, 77.8% vs27.3%, and 100% vs 45.0%, respectively）. The rates of anemia
and thrombocytopenia were not significantly different between
the two groups. Conclusion Pregnancy with SLE was related toobstetric complications. Immunological data obtained during
the first trimester is useful for predicting the occurrence of PE
in SLE pregnancy.

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Postpartum thrombotic microangiopathy occurring secondary to systemic lupus erythematosus：a case report
Kenichiro Hirotani, Saki Kido, Takahiro Nakano, Masahiro
Hachisuga, Nobuhiro Hidaka, Yasuyuki Fujita, Kiyoko Kato Kyushu University
A 32 year old woman, gravida 1 para 0, was referred at 14
weeksʼ gestation with the diagnosis of pregnancy with systemic
lupus erythematosus（SLE）.SLE was controlled by administration of prednisolone, azathioprine, and cyclosporine during pregnancy. At 37 weeksʼ gestation, she was admitted to our hospitalfor premature rupture of membrane, and underwent inductionof labor. Vacuum extraction was performed due to increased
blood pressure in the second stage of labor, and manual removalof the placenta was needed. Six hours after delivery, she demonstrated severe anemia, thrombocytopenia, and hypofibrinogenemia. Estimated blood loss was 400g, indicating hemorrhagic disseminated intravascular coagulation（DIC）；therefore, transfusion therapy was performed. Twelve hours after delivery, blood
tests revealed elevated liver enzymes, lactate dehydrogenase（LDH）, and serum creatinine levels, suggesting hemolysis, elevated liver enzymes, low platelet count（HELLP）syndrome.
However, after the peak out of elevated liver enzymes andLDH, normalized coagulopathy, thrombocytopenia and renal injury worsened. Blood microscopy showed red cell fragments,suggesting thrombotic microangiopathy（TMA）；we subsequently ceased transfusion therapy. Shiga toxin producing Escherichia coli results were negative, and the activity of
ADAMTS13 was more than 95%；therefore, we diagnosed her
with secondary TMA based on SLE. She was treated by plasma
exchange, hemodialysis, steroid pulse therapy, and immunosuppressive agent administration, and discharged at 6 weeks after
delivery. Postpartum thrombocytopenia and hemolytic anemia
are common in DIC or HELLP syndrome. If thrombocytopenia
and renal injury are prolonged after delivery despite normalization of coagulopathy or liver enzymes, other TMAs should beconsidered.

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Hemoglobin is the oxygen carrying component of RBCs. Its
structure consists of a tetramer of globin polypeptide chains：apair of alpha like and a pair of beta like chains. Normally, globin chain synthesis is balanced. Each newly synthesized alphaor non alpha globin chain will have an available partner to pairwith however, problems do arise when there is a missing link.
This a case of a 21 year old, primigravid, pregnant for 28 5/7
weeks, referred to our institution for fetal cardiac anomaly. Ultrasound at 21 2/7 weeks age of gestation revealed fetal cardiomegaly, ASD, beginning ascites with hydrothorax. Anemia
with decreased RBC indices was also noted. Iron supplementation was done, but anemia persisted. In our institution, biometry
was compatible with age；placentomegaly, fetal hydrops（ascites, pericardial effusion）were noted. Fetal echocardiography
showed cardiomegaly, right atrial enlargement and normal outflow tracts. MCA Doppler revealed a peak systolic velocity of 52
cms/sec, equivalent to 1.4 MoM, indicative of mild to moderate
anemia. Administration of corticosteroids was done. Patient andher partner underwent hemoglobin electrophoresis revealing
Alpha Thalassemia trait. Cordocentesis and intrauterine fetaltransfusion were done, however at 31 weeks, fetal monitoring
showed non reassuring fetal status. Cesarean section was done
and delivered to a live, baby boy, BW 1,500g, Apgar score of 1, 1,
1, Ballardʼs score of 32 weeks. Unfortunately, despite fetal resuscitation, baby succumbed. We can therefore say that prompt diagnosis of maternal condition is important so that proper management may be instituted and possibly decrease neonatal morbidity and mortality.

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A case of treatment resistant idiopathic thrombocytopenic
purpura during pregnancy Maki Okada, Ryo Maekawa,
Haruka Takagi, Masahiro Shinagawa, Lifa Lee, Hiroshi Tamura,
Norihiro Sugino Yamaguchi University Hospital
Idiopathic thrombocytopenic purpura（ITP）is an acquired
thrombocytopenia without other clear cause of the thrombocytopenia. In general, patients with ITP experience a reduction ofplatelet counts during pregnancy. We report a severe case of
ITP which was getting worse during pregnancy. A 30 year old
pregnant woman, gravida 0 para 0, had purpura and hematuria
with a low platelet count of 0.1×104/μL at 16 weeks of gestation.
She was admitted to our hospital for further evaluation of thethrombocytopenia. She had a lot of petechiae, ecchymosis andpurpura in her skin and oral mucous membrane. After the exclusion of all other causes of thrombocytopenia by several tests
including a bone marrow examination, she was diagnosis as ITP.
She was treated with prednisolone and intravenous immunoglobulin（IVIG）. These therapies were not effective to increase
persistently the platelet count to the enough level. Even platelettransfusion didnʼt increase the platelet count. Because of the severity and treatment resistance, splenectomy was performed at
25 weeks of gestation. The platelet count was temporarily increased, but it decreased again shortly. Since it was difficult tokeep the platelet count enough to continue the pregnancy, she
received a caesarean section at 34 weeks of gestation together
with intensive treatments with IVIG and platelet transfusion.
After the caesarean section, the platelet count increased to thenormal level. When any treatments are not effective to increase
the platelet count in such a severe ITP case, a termination ofpregnancy would be an only therapeutic option.

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ARDS due to H3N2 Influenza A occurring in the second trimester of pregnancy：A case report Yuri Sasaki, Akihiko
Kikuchi, Gen Haba, Hideyuki Chida, Hiroki Onoue, Tomonobu
Kanasugi, Chizuko Isurugi, Rie Oyama, Toru Sugiyama Iwate
Medical University
Many pregnant women had serious complications from theH1N1 pandemic 2009 worldwide. However, there have been noreports of ARDS due to H3N2 influenza during pregnancy inEnglish literature. We herein report such a case. A 41 year old
primigravida woman was admitted to our hospital at 24 weeks
gestation for threatened premature labor. She became pregnant
by in vitro fertilization with no other medical history. She wasvaccinated against seasonal influenza one month before admission. Although there was no sign of infection on admission, shedeveloped a fever on the second day and respiratory distress on
the third day. Chest X ray and CT showed clinical pictures of
ARDS. Emergency caesarean section was performed because
her respiratory condition deteriorated despite intubation. Influenza rapid tests at 12 hours and 24 hours after the onset of her
fever were both negative. H3N2 influenza infection was finallyconfirmed several weeks later by a serological test done on thefirst day of her symptoms. General intensive care after cesareandelivery rapidly improved her general condition without extracorporeal circulation nor administration of anti influenza medication. On the other hand, her infant died for complications due
to immaturity on the 48th day after birth. Our case indicatedthat even a healthy pregnant woman can rapidly develop ARDS
due to influenza infection. Based on our experience, immediate
termination of pregnancy might be quite essential for rescuingsuch a patient from critical respiratory conditions.

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Analysis of pregnant women with syphilis Hidenori Sasa,

Masaya Nakatsuka, Takahiro Natsuyama, Takahiro Sakamoto,
Haruka Kawauchi, Hiroaki Soyama, Morikazu Miyamoto,Kiguna Sei, Masashi Takano, Kenichi Furuya National Defense
Medical College
Objective The pregnant women with syphilis infection havebeen increased in recent years. We report the diagnosis andmanagement of pregnant women with syphilis. Methods Six patients with syphilis were analyzed in our hospital for the past
four years. Laboratory data, treatment, maternal and neonatal
outcome were investigated for six pregnant women with syphilis. Results They were infected from their partner or unknown
person and the time of the syphilis infection was unclear in allcases. The values of RPR and TPLA were high in two cases, andmoderate in four cases. Ampicillin or amoxicillin were administered for 12 weeks in all cases. Three pregnant women withoutsyphilis lesion were delivered uneventfully and their neonates
were not infected with syphilis. Three pregnancies with head or
genital lesions of syphilis terminated in artificial abortion for
the economic reason and were diagnosed as the second stage ofsyphilis. Conclusion There was no maternal fetal infection ofsyphilis in our case because of early treatment for maternal
syphilis. It is necessary to diagnose and treat early for increasing number of maternal syphilis infection.

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ISP-16-8!

The meaning of Methicillin resistant Staphylococcus aureus（MRSA）colonization in pregnant women；a prospective cohort study Jumpei Ogura, Koji Yamanoi, Yoshihide Inayama,
Tsutomu Ohara, Mie Sakai, Haruka Suzuki, Koh Suginami
Toyooka HospitalObjective Methicillin resistant Staphylococcus aureus（MRSA）
infection is a great concern. The objective of this prospective cohort study is to assess the effect of maternal MRSA colonizationon the clinical events in the perinatal period. Methods For thisprospective cohort study, pregnant women were enrolled at 32
to 36 weeks gestation. Nasal and vaginal swabs for culture wereobtained at enrollment. We followed up their clinical events inthe perinatal period, such as preterm birth, premature ruptureof membrane, Apgar score, umbilical artery pH, vertical transmission of MRSA at delivery, fetal MRSA skin and soft tissue infection（SSI）and admission to NICU, etc. We also investigatedmaternal backgrounds, such as number of para, their careersand complications during pregnancy. Results From September
2016 to August 2017, 598 pregnant women and their 606 newborns were enrolled. Maternal MRSA colonization occurred in
33 pregnant women（M group；5.5%）, and did not occur in 565
pregnant women（non M group）.Among clinical events in theperinatal period, vertical MRSA transmission at delivery and fetal MRSA SSI occurred significantly higher in M group than in
non M group（12% vs 0.003%；RR 13.793［95%CI：7.07〜26.9］,
6% vs 0%；RR 19.5［13.8〜27.5］）. Among maternal backgrounds,
the frequency of usage of antibiotics during pregnancy, healthprovider and multi paras were significantly higher in the M
group compared to those in the non M group（p＜0.05, respectively）.Conclusion Maternal MRSA colonization is a significant
risk of vertical transmission of MRSA and fetal MRSA SSI in
the perinatal period. This is an ongoing study.

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Acute Appendicitis during Pregnancy Misako Hideshima,
Masatoshi Yokoyama, Yoshifumi Nakao, Hiroaki Nakahashi,
Tomoko Yamamoto, Makiko Kurihara, Satoko Tsuda, Satoshi
Nishiyama Saga University HospitalObjective Acute appendicitis during pregnancy is the mostcommon complication requiring surgical treatment. The subjective and objective signs of appendicitis are different during

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Obstetrical and perinatal outcomes of the chemotherapy inbreast and cervical cancer during pregnancy Mee Hyang Ko,
Suk Young Kim, Kyung Joo Cho, Su Kyeong Kong, Sun Young
Jung Gachon University of Korea, Korea
Recent trend for women to delay childbearing, we expect morecases of cancer to be diagnosed during pregnancy. We had experienced two cases of pregnant women with breast cancer andone case of cervical cancer who had administrated to cancer
chemotherapy during pregnancy. Two cases was diagnosed thepregnancy associated breast cancer at first trimester of gestation and took surgical excision and lymph node dissection confirmed intraductal carcinoma histologically. They had administrated chemotherapy during second trimester. One case, at 37+2
weeks of gestation, had delivered repeat cesarean section maleweighting 3,870g with normal Apgar score. After delivery she
had taken additional 4 cycles of chemotherapy. The other casealso had taken surgery and chemotherapy and now she is 34
weeks of gestation without any obstetrical and fetal adverse
events. In one case of cervical cancer, she had visited for vaginal
bleeding and had found about 5 cm in size exophytic mass oncervix and confirmed was with squamous cell carcinoma by tissue biopsy. She had undergone carboplatin monotherapy for two
cycles until 30 weeks of gestation. She had occurred preeclampsia and had performed cesarean section at 33+1 weeks of gestation. After 1 week later, she underwent radical abdominal hysterectomy and lymph node dissection for treatment of cervicalcancer. Chemotherapy use in pregnancy, an extensive discussion must be undertaken with the patient and her family andmultidisciplinary team of physicians. Discussion should include
the benefits and the risks involved based limited data of chemotherapy use during pregnancy.

ISP-17-2
Successful Heterotopic Pregnancy with Prior Radical Trachelectomy after TCIC with MTX Treatment Eun-Jee
Whang, Kyong-No Lee, Keun-Young Lee Kangnam Sacred Heart
Hospital of Hallym University of Korea, Korea
Background Heterotopic pregnancy with cervical incompetence is very uncommon. And yet there is no definite treatment

for cervical incompetence occurring after radical trachelectomy. We are reporting a rare and novel case of a following invitro fertilization（IVF）combined intrauterine pregnancy andinterstitial pregnancy which was successfully treated withmaintenance of the pregnancy to term. Case We report a case of
a 32 year old woman with heterotopic interstitial pregnancy
combined with intrauterine pregnancy at 8 weeks of gestation,
who had radical trachelectomy in the past. For her extremely
short or almost absent cervix, transabdominal cervicoisthmic
cerclage（TCIC）was performed with ultrasound guided injection of methotrexate（MTX）to terminate the interstitial gestation while preserving the intrauterine gestation. The final outcome was the birth of healthy newborn at 38 weeks of gestation.
Conclusion The heterotopic interstitial pregnancy was successfully aborted, and the intrauterine pregnancy was successfully
maintatiend until 38weeks of gestation. There is no standardized treatment for heterotopic pregnancy with cervical incompetence occurring after radical trachelectomy. TCIC with local
injection of MTX can be performed successfully for treatment
of interstitial heterotopic pregnancy in patients who have wants
to preserve the intrauterine gestation. This case illustrates amultidisciplinary approach that may be useful as a template insimilar situations.

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Obstetrical prognosis of patients treated by vaginal radical
trachelectomy during pregnancy Takafumi Kuroda, Shinichi
Ishioka, Mina Umemoto, Tadahi Okada, Kaoru Noro, Hazuki
Kashiwagi, Miseon Kim, Kyoko Isoyama, Masahito Mizuuchi,
Miyuki Morishita, Tsuyoshi Baba, Tsuyoshi Saito Sapporo Medical University
Objective Radical tracheletomy（RT）with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who desire their fertility. However
this operative method is at high risk for the following pregnancy due to its radicality. We investigated retrospectively theobstetrical prognosis of patients treated by vaginal RT during
pregnancy. Methods We have performed vaginal RT for four
pregnant patients with uterine cervical cancer whose FIGO
stage were IB1 according to the method by Dargent et al. Results Patientsʼ age ranged from 30 to 34, and all patients were
nulligravida. They were diagnosed as uterine cervical cancer at
11 25 weeks of pregnancy. And following 1 5 weeks later, vaginal RT was performed for them between 16 and 18 weeks ofpregnancy without any troubles. Three of them continued theirpregnancies till 34 weeks or longer gestation under our following up schedule published before. One patient terminated at 26
weeks gestation due to a focal recurrence of the cervical cancer.
Conclusion Application of RT for pregnant patients can be achallenge for both gynecologic oncologists and obstetricians.
However, expansion of vaginal RT for pregnant patients withuterine cervical cancer could be a practical option for them.

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Clinical features and the management of pregnancy associated breast cancer：Retrospective analysis of 8 patients
Tadahi Okada, Shinichi Ishioka, Hazuki Kashiwagi, Kyoko
Isoyama, Takafumi Kuroda, Masahito Mizuuchi, Miyuki
Morishita, Mizue Teramoto, Tsuyoshi Baba, Tsuyoshi Saito Sapporo Medical University Hospital
The number of pregnant patients with breast cancer is increasing with the increase of the number of breast cancer patientsamong the younger generation. To better understand this situation, we conducted retrospective analysis of 8 pregnant patients with breast cancer treated in our department between
January 2011 and March 2016, using medical charts. The aver-May 11 Fri.
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pregnancy in comparison to non pregnant individuals. As a result, this condition is difficult to diagnose during pregnancy,
which in turn exposes the fetus and mother to an increased riskof mortality. We report cases in which we diagnosed acute appendicitis during pregnancy and describe its clinical presentation, diagnostic methods, and management and outcomes. We
also review relevant reports. Methods The clinical data of fivepregnant women who were diagnosed as acute appendicitis at
our hospital from April, 2007 to July, 2017 were collected retrospectively. Results The age of women ranged between 23 and 40
years（median：32 years）.Two cases occurred during the firsttrimester, one occurred during the second trimester, and the remaining two occurred during the third trimester. The mean gestational age was 16 weeks（range：6 35 weeks）. Three of thefive cases underwent appendectomy, one underwent laparoscopic surgery, and two underwent open surgery, including one
case of operated appendectomy after child delivery via a cesarean operation. All but one case, which involved an artificial
abortion, were managed successfully without severe fetal complications or loss. Conclusion Among these cases, those that received prompt treatment exhibited good maternal and fetal
prognoses. Acute appendicitis during pregnancy involves perforation or diffuse peritonitis, and is associated with severe fetal
complications and loss. Therefore, early diagnosis and treatment
is essential.

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age age of the patients was 36.5 years（range：32 to 42 years）, In
all patients, the reason for tumor detection was awareness of atumor nodule in self examination. The clinical stages of the patients were stage 0 I for 3 patients, stage II or higher for 4 patients, and recurrent cancer for 1 patient. The median time ofdelivery for the patients was 33 weeks（range：31w0d 40w0d）.
Seven of the patients underwent cesarean section, and 1 patientdelivered vaginally. The timing of the operation for the breast
cancer was before delivery（median 23 weeks）for 5 patients, atthe same time as cesarean section for 1 patient, and 2 weeks after delivery for 1 patient. Six of the patients remain free of disease, one is under treatment due to recurrent cancer, and one
died of the disease. Early detection of the cancer via self examination, and early operative treatment are important for pregnant patients with breast cancer. It is also important to decide
the most appropriate timing of delivery to start postoperative
treatment of the cancer as soon as possible based on the pathological results for the cancer, with collaboration among obstetricians, neonatologists, and oncologists.

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A case of colorectal cancer during pregnancy Miho Saito,
Hironobu Hyodo, Naoya Tsujimoto, Satoshi Nitta, Yuki
Taketani, Saho Fujino, Etsuko Saito, Fusako Sue, Midori
Funakura, Sorahiro Sunagawa, Takahiro Kasamatsu, Koji Kugu
Tokyo Metropolitan Bokutoh Hospital
Colorectal cancer during pregnancy is relatively rare and is difficult to be diagnosed because the symptoms such as nausea,
vomiting, constipation, abdominal pain are quite common andradiographic imaging examination may tend to be avoided during pregnancy. A 30 year old woman primigravida was referred to our hospital from a primary clinic in the 28 weeks for
suspect of torsion of an ovarian tumor. Her complaint was abdominal pain, constipation and diarrhea. Computed tomography
showed a tumor of sigmoid colon, multiple liver tumor, enlarged
ovaries and swollen lymphnodes and colonoscopy revealed anulcerative mass in the sigmoid colon. The biopsy confirmed adenocarcinoma, which suggested the fourth stage of colon cancer.
Considering a risk of intestinal obstruction, resection of the tumor following to c section was conducted at 31 weeks and a
1,692 g healthy female infant was delivered. In the operation,
metastasis to the both ovaries, dissemination to the uterine serosa, and rupture of the abscess was confirmed. The ovaries andthe uterus were resected together with the tumor and the colon.
Adjuvant chemotherapy with oxaliplatine, 5 FU, leucovorin
was conducted nine days after the operation. Colorectal cancer
during pregnancy is often diagnosed in advanced stage because
the symptom may be non specific during pregnancy and because the diagnostic method may be limited. It is very important to prepare for that the tumor may establish abscess and an
emergent operation may sometimes be required for preventing
intestinal obstruction or peritonitis, and that the lesion may be
so extended that may require adnexectomy and hysterectomy.

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Primary intramedullary spinal cord tumour in pregnancy：A
case report Kyoko Fujii, Makoto Orisaka, Makoto Yamamoto,Koji Nishijima, Yoshio Yoshida University of Fukui Hospital
Introduction Primary spinal cord tumours can lead to severe
neurological complications and even death. Pregnant womenoften complain of discomfort of the lower limbs, which is usuallycaused by sciatica. Here we present the case of a pregnant
woman, who was initially considered to have sciatica, but was finally diagnosed with a primary intramedullary spinal cord tumour. Case Presentation A 28 year old pregnant woman presented to our hospital with inexplicable numbness in her lower! !

limbs. She was initially considered to have sciatica, but acute deterioration of neurological symptoms and plane MRI findings
suggested malignancy. The patient was finally diagnosed with a
primary intramedullary spinal cord tumour at the C3 Th5 region. An emergency caesarean section was performed, after
which the spinal cord lesion was evaluated using contrast enhanced MRI, 18F FDG PET/CT, and spinal angiography, andfurther treatment was initiated. However, while the patientʼs
spinal cord tumour surgery was performed in early postpartum,her neurological symptoms remained unchanged. Discussion
Because of the low incidence of spinal cord tumours during
pregnancy, no definite reports have been published on the treatment of pregnant patients with spinal cord tumours. Althoughsafe imaging tests during pregnancy are limited, intervention insuch patients should be performed as early as possible to avoid
irreversible neurological deterioration.

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A pregnancy with adenomyosis：A case report Ayaka
Tachibana, Rie Yanagihara, Takako Kawakita, Takeshi Iwasa,
Kanako Yoshida, Minoru Irahara Tokushima University Hospital
We report a pregnancy with adenomyosis complicated. A 39
yaars old woman was diagnosed with adenomyosis because theright and posterior wall of uterus were observed thickening of 7
cm, and it was introduced to our institution due to imminent
abortion at gestational week 16. She was admitted and started
continuous infusion of isoxsuprine hydrochloride. We changed
to ritodrine hydrochloride at gestational week 16 but foundlower abdominal pain enhancement, WBC 10,900/μl, CRP 2.99
mg/dl, ABPC 2g/day administration started. After that, FMOX
2g/day was administered and the inflammatory response improved. Since antibiotic was discontinued but lower abdominal
pain was prolonged, we observed that after administration of
acetaminophen and pentazocine, it became pregnancy hypertensive syndrome（PIH）from gestational week 34, and blood pressure rise（180/90mmHg）was confirmed. Because of severe PIH
and pelvic position, cesarean section was performed on gestational week 37. Because of adhesion placenta, the total bleeding
volume was 3,600ml and blood transfusion（RCC 6units, FFP 6
units）was performed. On the fifth postoperative day, blood pressure rise was observed and administration of nifedipine 20mg/
day was started. Nifedipine administration was sustained after
discharging on the 7th postoperative day, but it stopped after 3
months of delivery. Retained placenta was observed at 1 monthcheckup, blood flow wasǹt observed by ultrasonography and
MRI, so it was taken as follow up observation. Even after 1 year
after parturition, the mass remained, and 1 year 5 months after
delivery, it was resected by hysteroscopic surgery. The mass
was a placenta accompanied by calcification and hyalinization
by pathological examination.

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Current circumstance of the care for pregnancy complicatedwith adult congenital heart disease at a non specialized tertiary perinatal center Hironobu Hyodo, Satoshi Nitta, Naoya
Tsujimoto, Saho Fujino, Miho Saito, Norihiko Nakazato, Etsuko
Saito, Midori Funakura, Sorahiro Sunagawa, Takahiro
Kasamatsu, Koji Kugu Tokyo Metropolitan Bokutoh HospitalObjective Prognosis of congenital heart disease has been improved remarkably and many women with the disease have become able to reach to the reproductive age. The pregnant
women of adult congenital heart disease（ACHD）has been therefore increasing and most of them have uneventful pregnancy.
However, cardiac function and condition are diverse even in thesame disease and the care for them are therefore different from!

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and suffering cardiorespiratory arrest at 38 weeks gestation.
Her current pregnancy was uneventful until 37 weeks gestation
when BP elevations and dyspnea were noted. Hours prior, she
had BP of 160/110mmHg and difficulty of breathing. Few minutes prior, patient was unconscious with zero vital signs. CPR
was started, intubation done, and epinephrine given. The fetus
was evaluated and noted to have bradycardia. The decision wasmade to perform peri mortem cesarean delivery at the ER. A
midline abdominal incision was made to gain access to the uterine cavity and a female infant was delivered with Apgar of 0, 2,
6. The neonate was intubated, ventilated and chest compressions started, however died after 2 days. There was spontaneous
return of cardiac output after delivery. After the operation, thepatient was transferred to ICU for further ventilation andinotropic support and is still surviving 47 days after delivery
and now at GCS 7. CPR was unresponsive until cesarean section
was instituted, thus, PMCD is necessary for successful resuscitation for the mother.

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ISP-18-2

Pregnant women with low TSH and normal FT4 in earlypregnancy may have relatively low risk of preterm delivery
Masahiro Shiba, Koichiro Kido, Youhei Nagaya, Michiharu Seto,
Rina Sakurai, Shigenari Namai, Rintaro Kishimoto, Haruko
Hiraike, Yasuhiro Matsumoto, Yukifumi Sasamori, Eiji Ryo,
Takuya Ayabe Teikyo University
Objective In early pregnancy, due to gestational transient thyrotoxicosis, TSH value of pregnant women with normal thyroid
function often seem to be low. On the contrary, that of pregnant
women with hypothyroidism, which might relate to preterm delivery, may seem to be normal in early gestation. Thus our aim
is to investigate whether pregnant women with low TSH in
early pregnancy show relatively low risk of preterm delivery ornot. Methods Outcomes of 2,173 pregnant women who delivered
singleton infant at 22 weeks of gestation or later were investigated retrospectively. TSH value less than 0.5 μIU/ml was defined as low TSH. Preterm delivery rate was estimated by Chi
squared test. Informed consent was obtained from all participants. Results The whole rate of preterm delivery was 15.3%（333 of 2,173 cases）. The rate of pregnant women with low TSH
and normal FT4 in early pregnancy was 18.7%（407 of 2,173
cases）. The rate of preterm delivery among the pregnant
women with and without low TSH and normal FT4 at earlypregnancy” was 9.1%（37 of 407 cases）and 16.8%（296 of 1,766
cases）, respectively（p＜0.05）. Conclusion Pregnant womenwith low TSH and normal FT4 in early pregnancy may haverelatively low risk of preterm delivery. Many factors give effecton preterm delivery, and our data contain many high risk pregnancy cases. Further investigation is required to reveal the realeffect of thyroid function on preterm delivery.

Perimortem Cesarean Section（PMCS）successful maternal
resuscitation of out hospital onset cardiopulmonary arrest, acase report Chiyori Sakamoto, Susumu Miyashita, Shoko
Ochiai, Emi Motegi, Tatsuya Kuno, Kazumi Tada, Ichio
Fukasawa Dokkyo Medical University Hospital
Case A 36 year old pregnant woman, 2 gravida 1 para, wastransferred to our critical medical center on 38 weeks becauseof unconsciousness. She was complicated with WPW syndrome
but needed no medication. She complained precordial oppression and fell down suddenly at her house. Her husband immediately brought her to our institute 19 minutes after the onset.
Ventricular flutter（VF）was recorded at presentation and ACLS
protocol was activated. Prolonged fetal bradycardia was also
noted. PMCS was decided and carried out promptly. A male infant was born with APGAR Score of 0（1min）,0（5min）and 2（10min）at 38 minutes after the onset. Chest compression was
discontinued with support of ECMO after 50 minutes of the delivery. She needed intensive care for impaired cardiac function,
coagulopathy and postpartum bleeding before the suspension of
ECMO on day 3, and for post cardiac arrest syndrome（PCAS）including renal failure before discharge on day 49 without major neurological sequela. There was no laboratory test result suggesting amniotic fluid embolism. The neonate had resuscitation, hypothermia therapy and needed continuous mechanical ventilation for 35 days but hypoxic encephalopathy was getting obvious. Discussion We encountered this case incidentally
just before describing a PMCS protocol. PMCS itself was carriedout smoothly and we could resuscitate the patient successfully.
Several points were raised including the launch timing of
ECMO, neonatal care, postpartum coagulopathy, multi organ
failure and rehabilitation for disuse extremities. A series of multidisciplinary meeting for debriefing of clinical action was essential to complete the PMCS protocol in our institute.

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In The Nick of Time A perimortem cesarean delivery following
pulmonarycongestionandpre eclampsia
Adeline Rose T. Escartin, Charisse P. Guerrero Manila Central
University FDTMF Hospital, Philippines
Cardio pulmonary arrest occurs rarely in pregnancy and involves two patients：mother and fetus. Prompt cardio pulmonary resuscitation and intervention can save both. Adequate
chest compression and displacement of the gravid uterus off thevenous return from the lower extremities are proven to improvematernal oxygenation. Peri mortem cesarean delivery is a legitimate medical intervention in successfully salvaging themother and the fetus. Emptying of the uterus improves maternal physiology and effectiveness of cardiopulmonary resuscitation. A 24 year old, g1p0, was brought to the ER, unconscious

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A retrospective cohort analysis of retained products of conception with vascularity after second trimester abortion；incidence, outcomes in expectant management, and characteristic ultrasonographic features leading to future severe hemorrhage
Naoya Akiba1, Takayuki Iriyama2, Hitomi Furuya2,
Takahiro Seyama2, Rieko Shitara2, Toshio Nakayama2, Takeshi
Nagamatsu1, Yutaka Osuga1, Tomoyuki Fujii1 The University ofTokyo 1, The University of Tokyo Hospital 2
Objective The aim of this study was to investigate the incidence
and spontaneous outcomes of retained products of conception（RPOC）with vascularity detected by ultrasonography after sec-!

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case by case. Experience of the care of many cases should be accumulated and shared in order to provide high quality management. Methods The medical records of pregnancy in the ACHD
women that managed at a tertiary perinatal center from 2010 to2017 were reviewed. The situation of the management, theevaluation, the medication, and the strategy during and after
pregnancy were investigated. Results Forty one cases and fifty
pregnancies were identified. VSD was the most major disease.
All of them were in NYHA 1 at the first visit and none of themhad cardiac events during and after pregnancy. A severe AS
case was referred to the specialized institute for the care andthe therapeutic approach based on more experience of ACHD.
Conclusion It is possible that a pregnant woman with ACHD in
NYHA 1 with no remarkable symptom may get worse in heart
condition as the pregnancy progress. As ACHD has diverse condition even in the same disease, individual evaluation is very important and the most appropriate management should be provided.

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ond trimester abortion, and to identify the sonographic features
related to the development of severe hemorrhage. Methods This
was a retrospective cohort study on 103 cases after second trimester medical abortion managed at our institute between 2014
and 2016 under the approval of our ethics committee. RPOC
with vascularity was defined by the presence of hyperechoic focus with blood flow by grey scale and color Doppler transvaginal ultrasonography. The vascularity of RPOC was assessed bycategorizing cases as follows；type1：vascularity confined to
endometrium, type2：vascularity reaching ＜1/2 myometrium,
type3：vascularity reaching ＞1/2 myometrium. Results
Among a total of 103 cases, 19 cases（18.4%）were diagnosed as
RPOC with vascularity. All cases were managed expectantly,
and 5 cases（26.3%）eventually failed expectant management due
to severe hemorrhage treated by uterine artery embolization
and/or blood transfusion. Of them, 80%（4/5）of cases with type3 developed severe hemorrhage as compared with 7.1%（1/14）ofcases with type1/type2（p＜0.05, chi square test）. Cases inwhich expectant management failed showed the significantly
larger maximum linear size of RPOC（43.0±12.0 mm vs 20.7±8.3mm, p＜0.01, Mann Whitney U test）. Conclusion Our results
suggested that the incidence of RPOC with vascularity is substantially high in cases after second trimester abortion, and thedegree of vascularity and the size of RPOC are associated withthe development of spontaneous severe hemorrhage.

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The relationship of anesthetic amount with the prolonged second stage of labor and malrotation in labor analgesia HitomiAndo, Shintaro Makino, Jun Takeda, Yojiro Maruyama, Atsuo
Itakura, Satoru Takeda Juntendo University
Objective Forceps delivery rate increased as the labor analgesia
rate increased in our facility. To reveal the influence of local anesthetic on the prolonged second stage of labor and malrotation,
the use amount of local anesthetic was examined. Methods A
retrospective chart review from April 2017 to June 2017 was
conducted. Term cephalic singleton pregnancies who had delivery with combined spinal epidural analgia were considered asinclusion criteria. The local anesthetic amount on the first stageof labor（1st）, on the second stage of labor（2nd）,during wholelabor（WL）, and during labor per minute（WL/M）were compared between prolonged second stage of labor and without prolonged labor, and malrotation and without malrotation. The prolonged second stage of labor was defined more than 3 hours. Results During the study period, 173 cases were met the inclusion
criteria. Among them, 28.3% had prolonged second stage of labor, and 19.0% had malrotation. The amount of local anesthetic
during WL and 2nd were significantly larger in prolonged second stage group（99.0ml vs. 66.0ml, 47.5ml vs. 20.9ml：p＜0.05, respectively）. No differences were found on 1st（52.0ml vs. 45.7
ml：p=0.43）, and WL/M（0.16ml vs. 0.17ml：p=0.6）.For the malrotation, WL, 1st, and 2nd had significantly larger amount of anesthetic（98.2ml vs. 70.0ml, 62.9ml vs. 43.8ml, 35.3ml vs. 26.7ml：p＜0.05, respectively）. However, no difference was found in WL/
M（0.18ml vs. 0.16ml：p=0.3）.Conclusion There was no correlation factor of the prolonged second stage of labor and fetal headmalrotation except for the total amount of local anesthetic.

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ISP-18-5
Perinatal maternal cases of disturbance of consciousness
transferred to our facility Yoshihiro Kuritani1, Takahide
Maenaka1, Michihide Maeda1, Yukako Oi1, Naoya Shigeta1,
Yangsil Chang1, Hiroaki Tsubouchi1, Kayoko Shikado1, Takeshi
Yokoi2, Kazuhide Ogita1 Rinku General Medical Center 1, Kaizuka
City Hospital 2
Introduction Our facility is a tertiary medical center, accepting

on average 20 perinatal emergency cases per year. From 2011 to2017 we have had 17 cases of disturbance of consciousness, 8 epilepsy（47.1%）, 4 cerebral infarction（23.5%）, 2 cerebral hemorrhage（11.8%）and 3 eclampsia（17.6%）cases. We show three representative cases below. Case1 A 30s, primipara, 38 gestational
weeks was transferred for sensory disturbance of left upper
limb. Head MRI showed atherothrombotic infarction of right parietal lobe. Induced labor was planned but her infarction got
worsen in the process. Then, cesarean section was performed.
The antiplatelet agent was administered after the operation. No
subsequent complication was seen. Case2 A 20s, multipara, 35
gestational weeks was transferred for transient loss of consciousness and headache. Motor disturbance of bilateral lower
limbs was observed. Head CT showed the rupture of aortic
aneurysm of right anterior cerebral artery. Termination by cesarean section was performed to ease cerebral vascular treatment. On postoperative day 2, stent placement and coil embolization were performed. Anticoagulant and antiplatelet agentswere administerd. No subsequent complication was seen. Case3
A 30s, multipara, 37 gestational weeks was transferred for seizure soon after her delivery. Head MRI showed PRES. We diagnosed eclampsia with HELLP syndrome. No medical treatment
was added after arriving at our facility. Conclusion All cases
had good prognosis because of early diagnosis and treatment. It
might be important to transfer patients with cerebral events assoon as possible to a facility where CT, MRI and neurosurgery
are available in an emergency.

ISP-18-6
The challenge to quantify the uterine contraction；usabilityof handheld muscle hardness meter（HMH meter）and its clinical application to obstetric bleeding management Kenji Imai,
Tomomi Kotani, Teruyuki Mizutani, Yuri Niwa, Asuka Tachi,
Masataka Nomoto, Yukako Iitani, Mayo Miura, YoshinoriMoriyama, Takafumi Ushida, Tomoko Nakano, Fumitaka
Kikkawa Nagoya University
Objective To report a new method to easily and objectively
quantify the uterine contraction during cesarean section（CS）
with handheld muscle hardness meter（HMH meter）. Methods
Under Institutional Review Board approval and informed consent, a total of 34 term pregnant women who underwent elective
CS were recruited. HMH meter could measure tissue hardness
with a few seconds contact time. With the HMH meter, wemeasured the uterine hardness twice in each CS；Time A=immediately after placental separation and Time B=just before abdominal closure. Each measurement was conducted at 2 standardized points；Point A=fundus uteri and Point B=corpus
uteri. Also, the operator subjectively judged the uterine contraction into 3 grades；weak, normal, strong. Results HMH meter
could clearly quantify the subjective judgments of uterine contraction, especially at Point A（weak；47.9±1.96, normal；59.3±0.85, strong；64.0±0.92, p＜0.001）. Simple linear regression
revealed that the measurements at Time A were significantly
correlated with the amount of intraoperative hemorrhage（Point
A；r= 0.64, p＜0.001, Point B；r= 0.44, p=0.017, respectively）.
Massive intraoperative hemorrhage（＞1,000 mL）occurred in
58.8%（10/17）of cases with HMH meter ＜60 at Time A andPoint A, whereas in 5.9%（1/17）of cases with HMH meter ＞60
at the same time and point（p=0.002）. Conclusion These results
showed the feasibility of HMH meter for the quantification ofuterine contraction, and HMH meter ＞60 might be proposed asa novel criteria for management of uterine atony.

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For 10 years prospective study：trial of labor after cesarean（TOLAC）versus repetitive cesarean based on informed

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choice Kaname Uno, Eiji Yoshida, Hatsuo Isogai, Takuji Ueno,
Takuma Yamada, Takehiko Takeda, Sho Tano, Mayu Ukai,
Teppei Suzuki, Toko Harata, Yasuyuki Kishigami, Hidenori
Oguchi Perinatal Medical Center, TOYOTA Memorial HospitalObjective Though the successful rate of trial of labor after cesarean（TOLAC）is reported 60 80%. In Japan, most patients eligible for TOLAC undergo elective repetitive cesarean delivery（ERCD）. To reveal the benefits and risks of TOLAC, we conducted 10 year prospective study. Methods From 2005 to 2016,
patients who had undertaken CS were enrolled in this study. Patients who met our criteria chose their delivery way after being
explained the risks and benefits of both TOLAC and ERCD. Ourcriteria were only one previous lower segment transverse CS,
singleton vertex presentation and no history of myomectomy.
We collected the maternal and neonatal data at delivery and maternal backgrounds to identify more eligible patients. Results A
total of 982 patients with prior CS were enrolled, and 311 patients were excluded because of still birth before labor, severe
preeclampsia and not meeting our criteria. 671 patients could
choose their desirable delivery way. In these patients, 433 patients（64.5%）chose TOLAC. Of 433 patients, 395 patients（91.2%）succeeded in vaginal delivery and 2（0.45%）had uterine
rupture. There was no significant difference in Apgar score at 5
minutes（p=0.56）. The amount of bleeding at delivery in TOLAC
group were significantly less than ERCD group（p=0.01）. No maternal and neonatal deaths and sequels were occurred. Conclusion If the risks and benefits of both TOLAC and ERCD are explained, over half of patients choose TOLAC as their desirable
way. TOLAC was thought to be a reasonable way of delivery
and the choice of TOLAC should be offered for suitable candidates.

Shinichi Takada, Fumihisa Chishima, Kei Kawana Nihon University Itabashi HospitalObjective Since placenta accreta is a life threatening complication of placenta previa at caesarean section（C/S）, pre operative
assessment of placenta is important. Risk factors for placenta accreta are well reported. We here examined which risk factors
are the most useful to predict placenta accreta. Methods A retrospective study on pregnant women with placenta previa wasdesigned under approval by ethical committee in our hospital.
29 women with total placenta previa underwent C/S for delivery in our hospital. Typical images of placenta accreta（lacunae,
loss of clear zone, and paracervical varix）were evaluated by
MRI and ultrasonography（US）and scored（0 2 for MRI and 0
3 for US）pre operatively. Placenta accreta was diagnosed pathologically. Comparison in clinical factors between placenta accreta（n=10）and non accreta（n=19）groups was made by several statistical methods. Results Previous uterine surgery correlated strongly with placenta accreta（p=0.005）whereas age, gestational weeks, alert bleeding, position of placenta did not correlate. Univariate analysis showed US score, but not MRI, correlated strongly with placenta accreta（p=0.001）. Multi variate logistic regression analysis revealed that previous uterine surgery was an independent risk factor for placenta accreta（p=0.03）and high US score was also important risk factor with marginal significance（p=0.08）. ROC curve showed combination ofprevious uterine surgery and US score predicted placenta accreta with high accuracy（p＜0.001）. Conclusion For womenwith placenta previa, US was more useful for prediction of placenta accreta rather than MRI. Placenta accreta can be predicted preoperatively by combination of previous uterine surgery and US findings.

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ISP-19-2

Induction of labor with metreurynter at or after 39 weeks ofgestation in women with one previous cesarean delivery increases the likelihood of failed trial of labor after cesareandelivery Kento Misawa1, Madoka Furuhashi2, Yoshiaki Maseki1,
Atsuko Tezuka1 Japanese Red Cross Nagoya Daiichi Hospital 1,
Nagara Medical Center 2
Objective To elucidate the safety and efficacy of metreurynter
as an induction tool for women with one previous cesarean delivery. Methods A database was reviewed to identify womenwith singleton and vertex pregnancies who underwent trial oflabor after one cesarean delivery（TOLAC）at or after 39 weeks
of gestation between the years 2010 and 2016. Results Fifty one
women underwent induction of labor, and 230 women had spontaneous onset of labor pain. Successful TOLAC was observed in
95.2%（219/230）and 74.5%（38/51）of women with spontaneous
onset of labor pain and induction, respectively（p＜0.001）. A caseof uterine rupture was seen in a woman with induction, where
the baby was born dead by cesarean section. Women with induction of labor were less likely to have successful TOLAC（adjusted odds ratio 0.21 and 95% confidence interval 0.07 0.65）
compared with women with spontaneous onset of labor. Vacuum extraction（23.7% vs 6.8%, p＜0.001）and amniotomy（55.3%
vs 33.3%, p=0.010）were more frequent in women who had successful TOLAC withinduction than those with spontaneous onset of labor. Conclusion Induction with metreurynter decreases
the success of TOLAC but is satisfactory in clinical practicebased on its success rate and safety.

The usefulness of preoperative autologous blood donation before caesarean section of placenta previa based on SBOE（thesurgical blood order equation） Junki Imaizumi, Sumika
Matsui, Atsuko Hichijo, Naoto Yonetani, Takeshi Iwasa,
Takashi Kaji, Minoru Irahara Tokushima University
Objective Autologous blood donation has been performed forcase with high risk of excessive bleeding. However, because it isdifficult to preoperatively predict the amount of bleeding, excess amount of blood has tended to be stored for obstetric surgery, and high discard ratio is one of the problems to be solved.
In this study, we retrospectively evaluated whether the discarding rate and allogeneic blood transfusion rate can be reduced using SBOE. Methods From January 1st, 2013 to June 30th, 2017,40 pregnant women with placenta previa underwent preoperative autologous blood donation. The volume of autologous blood
donation, intraoperative bleeding, volume of autologous bloodtransfusion, discard ratio and volume of allogeneic blood transfusion were analyzed. In addition, necessary blood volume wasretrospectively calculated by SBOE in each case and it wascompared with actual date. Results 75% women underwent autologous blood transfusion. The autologous blood discard ratio
was 42%, whereas 7.5% women underwent allogeneic bloodtransfusion. If autologous blood was collected based on SBOE,
the assumed discard ratios would be 38%, and 35% women
would undergo allogenic blood transfusion. Conclusion Autologous blood donation seems to be effective for avoiding allogeneic blood transfusion. However, the discard ratio is high andsome patients would be needed to undergo allogeneic bloodtransfusion besides autologous blood due to excessive bleeding.
If SBOE is used to determine the necessary volume of autologous blood collection, it is concerned that the case needed for allogeneic blood transfusion may be increased. Thus, SBOE
seemed to be less useful in case with placenta previa.

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Which risk factor is the most useful to predict placenta accreta pre operatively?：a retrospective study on placenta
previa Hiromitsu Azuma, Ai Kouno, Takuo Nakayama, Chuyu
Hayashi, Go Ichikawa, Atsushi Komatsu, Yasuji Miyagawa,

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Shigetaka Matsunaga2, Eishin Nakamura2, Kouki Samejima2,
Hiroko Masuko1, Yukiko Mikami1, Sumiko Era1, Yoshihisa Ono1,
Yasushi Takai2, Masahiro Saitoh1, Kazunori Baba1, Hiroyuki
Seki1 Center for Maternal, Fetal and Neonatal Medicine, Saitama
Medical University Saitama Medical Center 1, Saitama Medical
Center Saitama Medical University 2
Objective Preoperative autologous blood donation（PAD）is considered to be an effective method for avoiding allogeneic bloodtransfusion. Recently, high rejection rate of PAD is regarded asa serous problem. Therefore, we investigated optimal PAD volume for avoiding allogeneic blood transfusion in patients withplacenta previa and low lying placenta retrospectively. Methods
Of the 383 patients who underwent PAD from 2008 to 2013, we
examined 269 patients with placenta previa and low lying placenta by reviewing medical chart. One bag of PAD volume wasdetermined as 300 ml for a pregnant woman, the cases enrolledwere stratified by PAD volume every 300 ml, and compared thefrequency of allogeneic blood transfusion. Results PAD wasused for 124 patients（46.1%）and allogeneic blood was transfused to 12 cases（4.5%）. The rejection volume of PAD was
23,940 ml（70.5%）per year in average. The allogeneic bloodtransfusion rate was significantly higher in the 300 ml PAD
group than in the other groups（17.2%, 1.69%, 3.82%, 0% in 300,
600, 900, 1,200 ml PAD groups, respectively, p＜0.05）. The cutoff value of PAD for avoiding allogeneic blood transfusion wasdetermined as 300 ml by receiver operating characteristic
analysis, and the odds ratio of
300ml PAD in multivariate
analysis was 14.278（p=0.0303）. Conclusion 600 ml or moreamount of PAD showed no difference in the rate of allogeneic
blood transfusion. To minimize the rejection rate, the optimal
amount of PAD for the patients with placenta previa and low lying placenta is considered to be 600 ml（300 ml twice）.

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ISP-19-4
Placenta accreta following hysteroscopic lysis of adhesions
caused by Ashermanʼs syndrome Yuko Sonan1, Shigeru Aoki1,
Tamaki Cho1, Yuriko Yamamoto1, Soichiro Obata1, Azusa
Tochio1, Mio Takami1, Kimiko Enomoto1, Michi Kasai1, Junko
Kasai1, Etsuko Miyagi2 Yokohama City University Medical Center 1, Yokohama City University Hospital 2
Ashermanʼs syndrome is defined as partial or complete obstruction of the uterine cavity primarily caused by intrauterine procedures and infections. Hysteroscopic adhesiolysis is commonlyused to treat Ashermanʼs syndrome. Although the frequency ofplacenta accreta is known to increase with pregnancy after hysteroscopic adhesiolysis, precise data remain unknown. Here, wereport a case of placenta accreta following hysteroscopic lysis ofadhesions caused by Ashermanʼs syndrome, and review the literature on placenta accreta following hysteroscopic adhesiolysis. The patient is a 40 year old primipara who underwent underwent hysteroscopic myomectomy for 1 3 cm submucosal fibroids located in the uterine fundus. Ashermanʼs syndrome wassuspected after the patient exhibited secondary hypomenorrhea
10 months after surgery. Eight months after diagnosis, the patient underwent hysteroscopic adhesiolysis. Seven years after
hysteroscopic adhesiolysis, the patient became pregnant
through IVF. The course of pregnancy was uneventful thereafter, and an elective cesarean section was performed at 38 weeks
and 2 days of gestation because of a breech presentation. The
placenta remained firmly adherent to the uterine wall, and although there was almost no bleeding from the uterine cavity, cesarean hysterectomy was performed. The operative time was
101 minutes, while the total blood loss was 1,584 ml. Blood trans-

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fusion was not required. Placenta increta was confirmed basedon postpartum histological findings. The postoperative course
was uneventful, and the patient was discharged in good healthon the 7th postpartum day. It is necessary to consider placenta
accreta as a complication of pregnancies after hysteroscopic adhesiolysis for Ashermanʼs syndrome, particularly in those conceived using IVF.

ISP-19-5
Risk factors for the placenta with velamentous umbilicalcord insertion among term singleton ART pregnancies
Satoshi Furuya1, Takashi Yamaguchi2, Tamaki Kagawa2,
Kiyoshi Kubonoya1, Ken Kubonoya1 Kubonoya Ob/Gyn Clinic 1,
Kubonoya IVF Clinic 2
Objective The placenta with velamentous umbilical cord insertion（VCI）is a rare pathologic condition that is supposed to increase the risk of perinatal complications. In this research we
examined the ART conceived cases for the purpose of identifying the ART associated risk factors that might affect the incidence of the placenta with VCI. Methods We reviewed the records of 551 consecutive singleton term labor and delivery
ART conceived cases, from January 2010 to August 2017. Our
study population was divided into two categories as follows：cases with VCI（Group A：n=31）, and cases without VCI（Group
B：n=520）. Odds ratios（OR）for VCI, 95% confidence intervals（CI）, and significance of the odds ratio were calculated according to ART related variables, using multivariate logistic regression. Results The incidence of VCI in our study population was
5.6%（31/551）. The rate of delivery necessitating emergency C
section or operative vaginal delivery in Group A（58%, 18/31）
was higher than in Group B（36%, 189/520）. Blastocyst transfer（OR：6.63, 95%CI：1.55 28.28, P=0.01）and female fetus（OR：2.69, 95%CI：1.18 6.15, P=0.02）significantly increased the likelihood of developing the placenta with VCI. Maternal age, parity,
fertilization method（conventional IVF or ICSI）, and type of embryo（fresh embryo or frozen thaw embryo）did not affect the incidence of the placenta with VCI. Conclusion As velamentous
umbilical cord insertion often brings about serious obstetriccomplications, ART pregnancies achieved by blastocyst transfer and female fetus are optimal candidates for checking up andidentifying the umbilical cord insertion site more proactively
during routine obstetric ultrasound examinations.

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ISP-19-6
The importance of fetal/placental weight ratio for the evaluation of small for date Toshiya Itoh1, Yoshio Matsuda2, Hiroaki
Itoh1, Toshiyuki Uchida1, Kazunao Suzuki1, Kazuhiro Sugihara1,
Masaki Ogawa3, Naohiro Kanayama1 Hamamatsu University
School of Medicine Hospital 1, Mishima General Hospital 2, Tokyo
Womenʼs Medical University Hospital 3
Objective To clarify the importance of fetal/placental weightratio（F/P）as well as placental weight（PW）for the evaluationof small for date（SFD）. Methods From 93,034 placentas/infantsof mothers vaginally delivered a singleton infant（Japan Perinatal Registry Network database 2013）, SFD（n=3,379）was chosen
according to infantʼs weight referring to the Japanese neonatal
growth chart（Itabashi, 2010）. PW and F/P Z scores based on thestandard curves of a sex , parity and gestational age specific
PW and F/P（Ogawa ＆ Matsuda, 2016）were calculated. The
population was classified into 9 blocks according to the combination of low vs. middle vs. high i）PW Z score and ii）F/P Z
score. In both i）and ii）, ±1.28 standard deviations in the Zscores was used for classifying low vs. middle vs. high, with 3×
3 making 9 blocks. Block I（high PW Z score and low F/P Z
score）is considered as inappropriately heavy placenta. Results（1）All cases distributed into 6 blocks：11.7% in Block A, 40% in

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ISP-19-7
Placental mesenchymal dysplasia with severe fetal growth restriction in one side of placenta of dichorionic diamniotic
twin pregnancy Shoko Jitsumori, Michihisa Shiro, Nami Ota,
Sawako Minami, Kazuhiko Ino Wakayama Medical University
Placental mesenchymal dysplasia（PMD）is a rare condition ofswelling stem villi and placentomegaly without trophoblast proliferation. We report an extremely rare case of PMD with FGR
fetus in one side of placenta of DD twin pregnancy. A 24 year
old para 1 female was referred to our hospital at 24+1 weeksʼ
gestation of DD twin with one fetal FGR and placental anomaly.
Ultrasound examination revealed only one fetus was FGR（ 2.6
SD）and multiple cysts in the ipsilateral placenta. Maternal serum hCG level was within the reference range（44,084 mIU/mL）
and we clinically diagnosed PMD. There were no ultrasoundfindings of characteristics of BWS in the FGR. MRI at 32 weeksʼ
gestation showed cystic lesion in the placenta of FGR. Because
development of biparietal diameter of FGR fetus was restricted（ 4.5SD）,we performed cesarean section at 32+5 weeksʼ gestation. The both neonates were females, weighed 1,799g（ 0.1
SD）and 1,215g（ 2.5SD）.The weight of twin placenta was 1066
g（above 90th percentile）. There were prominent enlarged chorionic vessels on the placental surface of the small for gestational age（SGA）birth. The lesion of PMD was showed in about
37% of the SGA side of placenta. Microscopic examination revealed large swelling stem villi and increase of stromal cells
without trophoblast proliferation. Immunohistochemically, expression of p57kip2 was lost in the stromal cells and trophoblastsof swelling stem villi. It was suggested that PMD occurred in
one placenta of DD twin, leading to early onset FGR.

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ISP-19-8
A case report of chorioamniotic membrane separation withchorionic hematoma and inflammation Kumiko Nakata,
Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi,
Sawako Minami, Kazuhiko Ino Wakayama Medical University
Hospital
The amnion and chorion usually fuse between 14 and 16 weeks
of pregnancy. Chorioamniotic membrane separation（CMS）canlead to preterm delivery, premature rupture of the membrane
and fetal death. As CMS is rare, there have been few reports,
and management for CMS has yet to be determined. We report apatient with CMS with chorionic hematoma. A 29 year old
woman was hospitalized for lower abdominal pain, cervicallength shortening and genital bleeding at 15 weeks of pregnancy. Laboratory data indicated inflammation, and she received antibiotics and tocolysis. Chorionic hematoma, followed
by CMS at 16 weeks were observed on ultrasound. She wastransported to our hospital at 19 weeks 6 days of pregnancy.
Soon after, the amniotic cavity became narrower, and the fetus
became wrapped by the amniotic membrane. We considered
continuation of pregnancy to be difficult because of severe pulmonary hypoplasia and the complications resulting from contracture of the fetus. The fetus was stillborn at 21 weeks 3 days
gestation. Macroscopically, the fetus was wrapped in a thin film
and had limb contracture, but other obvious anomalies were notobserved. Pathological examination demonstrated CMS with hematoma and diffuse inflammation. This case was like chronic! !

abruption oligohydramnios sequence（CAOS）.

ISP-20-1
Practical applications of uterine compression sutures Jun
Takeda, Shintaro Makino, Atsuo Itakura, Satoru Takeda Juntendo University
Objective Postpartum hemorrhage is one of the leading causesof maternal morbidity and mortality. Several hemostatic surgical techniques during cesarean section have been reported previously. Among them, compression sutures are a relatively easy
and effective way of achieving hemostasis during cesarean section. However, in particular cases, it is difficult to achieve hemostasis only with the compression sutures. Methods For the original method of the compression sutures, threads were placed
through the anterior wall and posterior wall of the uterus andcompress the uterine cavity by apposing the anterior and posterior walls. Three cases needed contrivances to achieve hemostasis and to act against complication as practical applications ofcompression sutures. Results As the practical applications of
this technique, one case needed medical and wider compression
suture due to effaced cervix, who had cesarean section during
the trial of labor for low lying placenta. One case needed removal of the compression sutures thread for uterine isthmus
ischemia due to excessive reduction of uterine blood supply.
One case applied only uterine isthmus vertical compression sutures for severe uterine atony；however, decrease of uterine
corpus blood flow with ligating anastomosis of arcuate or/andradial arteries between ascending and descending uterine arteries helped to achieve hemostasis. Conclusion Some contrivances
aided compression sutures for the reliable hemostasis and minimal invasive procedure.

ISP-20-2
Transabdominal Cervical Cerclage via Laparotomy：5 cases
Yuri Hasegawa, Atsushi Yoshida, Ai Higashijima, Shuhei Abe,
Kiyonori Miura, Hideaki Masuzaki Nagasaki University
Objective We estimated the obstetrical outcomes in 5 cases oftransabdominal cervical cerclage（TAC）via laparotomy. Methods From 2014 to 2017, we performed TAC via laparotomy in 5
pregnant women with cervical incompetence. They were diagnosed cervical incompetence at 8 to 13 weeks gestation. Four
pregnant women have been performed conization for CervicalIntraepithelial Neoplasia（CIN）or micro invasive cervical carcinoma. One pregnant woman had transvaginal cervical cerclageat previous pregnancy, but cervical laceration had been happened. TAC was performed at 10 to 14 weeks gestation. As theobstetrical outcomes, operation time, blood loss, length of hospital stay, gestation at delivery, birth weight of neonates and Apgar Score were estimated. Results The average of operation
time was 112.4（74 153）minutes, blood loss was 80.6（5 270）
grams and length of hospital stay was 16.6（7 29）days, respectively. In all cases, there were not severe complications during
operations. Two women delivered healthy babies by cesarean
section at term. Their birth weight was 3,168 grams and 3,298
grams. Apgar Score of 5 minutes was 8 and 9, respectively. Conclusion TAC could be recommended as safe procedure for thecases of transvaginal cervical cerclage impossible.

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ISP-20-3
Analgesic effect of regular intravenous administration of
acetaminophen for pain due to post cesarean delivery：a retrospective study Keiko Yabuzaki, Hiroaki Aoki, Miki Muto,
Akihiro Hasegawa, Tomona Matsuoka, Michihiro Yamamura,
Haruhiko Udagawa, Yuki Ito, Kazuhiro Kajiwara, Osamu
Samura, Aikou Okamoto The Jikei University HospitalObjective Multimodal analgesia is recommended for postopera-!

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Block D, 37.6% in Block E（both PW and F/P Z scores are middle）, 0.5% in Block G, 9.9% in Block H, and 0.3% in Block I.（2）Minimum perinatal death rate was 10.2/1,000 in Block E. Conclusion Inappropriately heavy placenta is very rare in SFD.
Perinatal mortality rate is the lowest in Block E as balanced
growth of placenta and infant. Measuring not only PW but F/P
are important and helpful for the evaluation of SFD.

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tive pain management. To control further pain due to post cesarean delivery, we started prescribing the regular administration of intravenous acetaminophen since July 2016. The objective of this study was to evaluate whether the regular administration of intravenous acetaminophen reduces the need for additional analgesic drugs. Methods We performed a retrospective
chart review of women who underwent cesarean delivery withspinal anesthesia containing intrathecal morphine from July
2015 to June 2017. Patients in the first group received an intravenous analgesic drug as needed from July 2015 to June 2016.
Patients in the second group received intravenous acetaminophen（1,000 mg every 6 hours）postoperatively with otherintravenous analgesic drugs as needed from July 2016 to June
2017. The primary outcome was the number of additional analgesic medications administered until oral medication was taken.
The secondary outcome was the Numerical Rating Scale（NRS）score for pain. Outcome measures between the groups
were compared using the t test for continuous variables and χ2
test for ordinal variables. Results Four hundred eleven patientswere analyzed（first group, 183；second group, 228）. The proportion of patients requiring additional analgesic medications
was significantly lower in the second group than in the firstgroup（22.8%［52］vs. 60.7%［111］, p＜0.0001）. One hundred
twenty four（54.4%）and 84（45.9%）patients in the second andfirst groups, respectively, had mild pain（NRS score 0 3）（p=
0.0924）. Conclusion The regular intravenous administration of
acetaminophen following cesarean delivery increases the drug
analgesic effect and reduces the number of additional analgesic
drugs administered.

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ISP-20-4
The efficacy of uterine compression suture as a procedure in
the management of primary atonic bleeding：a historical cohort study Masaaki Sawada, Shinya Matsuzaki, Tatsuya
Miyake, Aiko Kakigano, Tsuyoshi Takiuchi, Kazuya Mimura,
Keiichi Kumasawa, Masayuki Endo, Takuji Tomimatsu,
Tadashi Kimura Osaka University
Objective Uterine compression suture（UCS）is recognized asa useful procedure in the management of atonic bleeding. However, appropriate hemorrhage volume to perform UCS is notwell understood. Our institution policy was to use UCS only incesarean deliveries（CD）and when atonic bleeding persistedwith an estimated blood loss of ＞1,500 mL. Although the strategy used to control atonic bleeding depends on the clinicians
preference, UCS was performed more commonly during CD after August 2013. We performed a historical cohort study to assess the efficacy of UCS for atonic bleeding（＞1,500 mL）during
CD before（period A）and after August 2013（period B）. Methods
In a retrospective analysis, data from CD patients with at least
1,500 mL of atonic bleeding between January 2010 and December 2016 were reviewed（expect placenta previa cases）. Data on
surgical outcomes were compared between period A and B. Results Data from 128 patients were included in this study（64 patients in both period A and B）. There was no significant difference in baseline characteristics between period A and B. UCS
was performed more commonly in period B than in period A［6/64（9.3%）vs 25/64（39.0%）；P=0.0001］.However, the surgicaloutcome of CD, such as mean intraoperative bleeding（2,307mL
vs 2,306 mL；P=0.32）,the rate of transfusion［27/64（42.2%）vs30/64（46.9%）；P=0.72］, and the rate of uterine preservation［62/64（96.9%）vs 58/64（90.6%）；P=0.27］,was not significantly
improved. Conclusion Our indication of UCS for atonic bleeding
during CD did not improve the surgical outcome.

ISP-20-5
Two cases of Vertical Rupture at Side Wall of the Uterine

Cervix：Unusual Clinical Courses and How the Ruptures
were Repaired Yasunori Fukuoka, Hiroki Kato, Takashi
Shibata, Satoshi Nakago, Tetsuya Oishi, Fumikazu Kotsuji,
Hisato Tokuda, Sayoko Hosono, Tomoki Kotera, Shota Asano,
Shigeki Nishikawa, Noriaki Iiduka Takatsuki General HospitalObjective We encountered two cases of vertical laceration at
sidewall of uterine cervix. Both patients were 35 y.o. primipara
and undertook induction labor with epidural anesthesia. We report unusual clinical courses of them and how the uterine
wound was repaired. Case case 1：The patient was performed
vacuum extraction with Kristeller method. 5days later, she visited us for lower abdominal pain. CT showed free air leaking
from the uterine cavity to extraperitoneal space, suggestinguterine rupture. When the broad ligament was opened, verticallaceration appeared at the sidewall of uterine cervix. After trimming necrotic tissue, fresh muscle layer was sutured. MRI after
a year showed perfect repair of the wound. case2：After 30hours of labor induction, she undertook caesarian section. Fivedays later, she explained lower abdominal pain. MRI suggested
laceration of left side wall of the uterine cervix andhemoretroperitoneum. Since false aneurysm of the uterine artery was suspected, we performed UAE and then uterine rupture was repaired as case1. 12days later, recurrence of retroperitoneal abscess was diagnosed. A small hole leading to the abscess was found at left side wall of the uterine cervix by the
probing using a specillum. By washing the abscess with serinefor 38 days, it was vanished. MRI taken a year later showed perfect repair of the wound. Conclusion Violent physical birr underepidural anesthesia might produce this type of rupture. It is possible that UAE inhibited wound healing, so UAE should be
avoided when repair the rupture is considered.

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ISP-20-6
The efficacy of a new combined uterine compression suturetechnique for severe postpartum hemorrhage Hasumi Tomita,
Masatoshi Saito, Tomoko Uehara, Yasuhiro Kurosawa, Sayaka
Ooshio, Michiyo Kurakata, Tetsuro Hoshiai, Hidekazu Nishigori,Nobuo Yaegashi Tohoku University HospitalObjective Many studies had reported that uterine compression
suture（UCS）was effective for postpartum hemorrhage（PPH）.
In these studies, UCS was performed mainly during caesarean
section. The aim of the current study was to reveal the effectiveness of our new UCS technique（combination of Haymanʼssutures and parallel vertical compression sutures）for severe
PPH occurred in other situations. Methods Patients who had severe PPH not responding to conservative treatment, and underwent UCS in our hospital between January 2015 and August
2017 were included. Patients who underwent uterine compression sutures during caesarean section were excluded. We retrospectively examined the medical record of these patients toevaluate the efficacy of our UCS technique. Results 15 women
were included in this study, 7 women were after vaginal delivery（included 3 vacuum deliveries）and 8 women were after caesarean section. Mean blood loss before UCS was 2,920g（range
1,400 5,000g）, and all cases required blood transfusion. In allcases, our UCS was successful, and the uterus preserved. Mean
blood loss during operation was 1,727g（range 157 4,529g）,and
mean operation time was 96minutes（range 58 177minutes）.
One case needed uterine artery ligation because of artery injury
during caesarean section, but other cases did not need other surgical treatment. None of the women developed complications related to the procedure. Conclusion Our uterine compression suture technique might be very effective and safety treatment forsevere PPH.

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ISP-20-8
The experience of CIABO（common iliac artery balloon occlusion ） Shotaro Kai, Takahiro Nakano, Saki Kido, Masahiro
Hachisuga, Nobuhiro Hidaka, Yasuyuki Fujita, Kiyoko Kato Kyushu University HospitalIn our hospital, before cesarean section we insert common iliac
artery balloon to occlude and reduce the bleeding for patients at
risk for massive bleeding such as placenta accreta, cesareanscar pregnancy, cervico isthmic pregnancy. If the bleeding is
uncontrolled, we perform total hysterectomy after cesarean section. We experienced 11 cases inserted common iliac artery balloon from January 2013 through August 2017 and review retrospectively. The cases with balloon occlusion was 7 cases and resulted in hysterectomy. Occlusion time was 11 to 20 minutes.
Blood loss was 2,200 to 6,758g. They were received homologous
or autologous transfusion, Operation time was 140 to 262 minutes. One case had thrombosis at extra iliac artery, she needed
anticoagulant therapy by heparin. CIABO may be effective for
reducing blood loss and transfusion, but also has risks of severe
complications. Therefore we should consider the indication ofthis procedure.

ISP-21-1
Novel function of a transcription factor WT1 in regulating
decidualization in human endometrial stromal cells and its
molecular mechanism Isao Tamura, Haruka Takagi, Yuichiro
Shirafuta, Yumiko Mihara, Masahiro Shinagawa, Ryo Maekawa,Toshiaki Taketani, Hiromi Asada, Hiroshi Tamura, Norihiro
Sugino Yamaguchi University
Objective The Wilmsʼ tumor suppressor gene（WT1）encodes
an essential transcription factor regulating urogenital development. However, the function of WT1 in human endometrium isunclear. The present study examined the involvement of WT1
in the regulation of IGF binding protein 1（IGFBP 1）andprolactin（PRL）, which are specific markers of decidualization,

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ISP-21-2
Bone morphogenic protein 4（BMP4）is required for establishment of an adequate uterine decidualization and vascularization to support normal pregnancy Takashi Nagashima,
Manami Ishida, Kei Tanaka, Miho Matsushima, Yukiko
Matsuzawa, Tomoko Izawa, Seishi Furukawa, Yoichi
Kobayashi, Mitsutoshi Iwashita Kyorin University
Objective Bone morphogenetic proteins（BMPs）,known to regulate a variety of cellular functions, are members of transforming
growth factor β（TGF β）superfamily and thought to play a
critical role in female reproduction. To define the physiologicalrole of BMP4 in female reproduction, we used conditional knockout（cKO）strategies to generate female mice lacking functional
BMP4 in different type of the female reproductive tract. Methods Of note, mutant embryos homozygous for a Bmp4 null allele（Bmp4 !/!）die during gastrulation. To overcome the early embryonic lethality, we generated Bmp4 cKO models using Cre
mediated recombination under the control of Anti Müllerian
hormone receptor type 2（AMHR2）and progesterone receptor（PGR）to conditionally disrupt Bmp4 gene in the ovary（Bmp4
cKO（Amhr2 ））and uterus（Bmp4 cKO（Pgr ））. Results Though
Bmp4 cKO（Amhr2 ）mice showed normal fertility, Bmp4 cKO（Pgr ）mice showed severe subfertility. However, implantationand early placental/fetal development were normal, mid gestational abnormalities were detected in decidualization of Bmp4
cKO（Pgr ）uteri, resulted from defective proliferation and differentiation of uterine stromal cells. Additionally, vascularization
defect was detected in decidual Bmp4 cKO（Pgr ）uteri, causedby reduction of blood vessel formation, leading to fetal growth
retardation and loss of the fetus before birth. Conclusion In ourprevious reports, we showed similar abnormalities in pregnant
Bmpr2 cKO（Pgr ）mice, which demonstrated decidualizationand vascularization defects resulted in fetal growth retardation,
placental abruption, and female infertility. Therefore, our findings indicate that BMP4 is one of the key ligands for uterine
BMPR2 during placentation and is indispensable for the establishment of an adequate uterine environment to support normal
pregnancy.

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ISP-21-3
Possible Role of Neurotensin and CRH in the Feedback Regu-

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Usefulness of vertical compression suture for placenta previa
in caesarean section Tomoko Uehara, Masatoshi Saito, Hasumi
Tomita, Yasuhiro Kurosawa, Sayaka Ooshio, Tetsuro Hoshiai,
Hidekazu Nishigori, Nobuo Yaegashi Tohoku University HospitalObjective Sometime, it is difficult to control bleeding from thecervical side after placenta delivery in caesarean section of placenta previa. To reduce massive hemorrhage, various methods
such as gauze packing have been suggested, but there is no certain method. Since 2013, we has used vertical compression suture（VCS）for that situation and obtained favorable outcomes.
So, the aim of current study was to investigate the availability of
VCS for C section of placenta previa. Methods 85 patients who
diagnosed as placenta previa from June 2013 to June 2017 were
eligible to current study and divided into two groups, VCS
group（n=31）and non VCS group（n=54）. The volume of total
blood loss, operation time, the time from delivery to the end ofoperation（D E period）,postoperative labo data and postoperative hospital day were analyzed retrospectively. Results There
was no significant difference between two groups in the total
blood loss（1,548±573 g vs. 1,395±611 g, p=0.26）.Operation timewas 60.7±16.9 min in VCS group and 47.7±14.5 min in non VCS
group（p＜0.05）. D E period of VCS was significantly longer
compared with non VCS（54.0±16.3 min vs. 41.5±12.4 min, p＜0.05）.No significant differences were observed in postoperativevalue of WBC, CRP and Hb and postoperative hospital day in
two groups. Conclusion This data showed that VCS is one of theconvenient and valid methods to control bleeding in caesarean
section of placenta previa with minimal invasion.

in human endometrial stromal cells（ESCs）undergoing decidualization. Methods ESCs isolated from proliferative phase endometrium were incubated with cAMP to induce decidualization. mRNA expressions were examined by qPCR. The recruitment of transcription factors was examined by ChIP assay.
Knockdown was performed by siRNA. Genome editing was performed using CRISPR/Cas9 system. Results cAMP increased
WT1 expression with the inductions of IGFBP1 and PRL.
Knockdown of WT1 inhibited the expressions of IGFBP1 and
PRL. cAMP also induced the recruitment of WT1 to the
IGFBP 1 and PRL promoters. To investigate the regulation
mechanism of WT1, we focused on C/EBPβ, a gene that regulates many gene expressions during decidualization. Knockdown of C/EBPβ decreased cAMP increased WT1 expression.
cAMP increased the recruitment of C/EBPβ to the WT1 enhancer that is located 14,000 bp downstream from the transcription
start site. To test the endogenous function of the WT1 enhancer
region on WT1 expression, the endogenous WT1 enhancer region was deleted by genome editing technique. The increase of
WT1 expression by cAMP was not observed in the enhancer
deleted clones. Conclusion The present study shows the novelrole of WT1 in regulating decidualization in human ESCs. C/
EBPβ regulates WT1 expression by binding to the novel enhancer region, which is identified by genome editing technique.

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lation by Estradiol：A Study Using Hypothalamic ARC and
AVPV Cell Models Tuvshintugs Tumurbaatar, HaruhikoKanasaki, Aki Oride, Tomomi Hara, Hiroe Okada, Satoru Kyo
Shimane University
Objective Hypothalamic kisspeptin（encoded by Kiss 1 gene）
control the release and synthesis of GnRH through kisspetin receptor（Kiss1R）within the GnRH neurons. In rodent, kisspeptin
neurons within the arcuate nucleus（ARC）are the center for
negative feedback by 17β estradiol（E2）, whereas those in theanteroventral periventricular（AVPV）are defined as the centerof positive feedback. These conclusions are based on the observations that Kiss 1 expression in the ARC is inhibited by E2,
whereas AVPV Kiss 1 expression is stimulated by E2. In thisstudy, we examined the involvement of neurotensin（NT）andcorticotropin releasing hormone（CRH）in the kisspeptin mediated feedback control by E2. Methods mHypoA 50 and mHypoA 55 cells were used as cell models for AVPV and ARC kisspeptin neurons, respectively. Expression levels of kisspeptinmRNA were measured by real time RT PCR. Results Kiss 1
gene expression in mHypoA 50 cells was upregulated by E2,
whereas it was downregulated by E2 under certain conditions
in mHypoA 55 cells. NT was expressed and its expression was
upregulated in the presence of E2 in both cell models. Stimulation of mHypoA 50 cells with NT increased Kiss 1 mRNA expression, whereas NT significantly reduced Kiss 1 expression
in mHypoA 55 cells. CRH was also expressed in these cells andwas also upregulated by E2. CRH stimulated Kiss 1 gene expression in mHypoA 50 cells, but it reduced Kiss 1 expression
in mHypoA 55 cells. Conclusion Our observations using hypothalamic AVPV and ARC cell models suggest that NT and CRH
have divergent effects on Kiss 1 gene expression under the influence of E2 in both hypothalamic regions. These neuropeptides might be involved in E2 induced feedback mechanisms.

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ISP-21-4!!

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14 3 3 sigma is a novel Basonuclin1 binding protein in oocyte
Motomasa Ihara, Masahito Tachibana, Takashi Kuno, Ayako
Fujimine, Keiko Tanaka, Saori Igeta, Emi Yokoyama, Masumi
Ishibashi, Zen Watanabe, Naomi Shiga, Nobuo Yaegashi Tohoku
University HospitalObjective There are multiple factors related to infertility. The
loss of zinc finger transcription factor Basonuclin1（Bnc1）
causes meiosis arrest at methaphase II during oocyte maturation. In order to find out a part of mechanism for meiosis abnormality in oocyte, novel Bnc1 binding proteins have been explored. Methods Lysates of 10,000 GV stage oocytes of adultmice, and 293 cells were immuno precipitated with couplingbeads using anti Bnc1 or rabbit serum, and analyzed with mass
spectrometry, independently. The data were analyzed by sequence alignment using Mascot and Sequest algorithms. Protein
database utilized Swiss Plot. One of the proteins identified as anovel Bnc1 binding protein from both oocyte and 293 cell data,
was cloned using mouse ovary cDNA. The GFP tagged Bnc1
binding protein and Bnc1 His Myc were immune precipitatedwith anti GFP antibody and analyzed with western blotting.
The endogenous target protein in oocyte was immunostained
and observed with confocal laser scanning microscopy. Results
56 candidates from oocytes, and 80 candidates from 293 cells
were identified as more than 2 of Σ# PSMs（peptide spectrum
matches）by MS analysis. Of these, 14 3 3sigma（Σ# PSMs=
3）was identified from oocyte and 14 3 3epsilon（Σ# PSMs=
1,666）was identified from 293 cells. Bnc1 was specifically immune precipitated with GFP 14 3 3sigma. Selective GPER（Gprotein coupled estrogen receptor）agonist enhanced endogenous nuclear localization of 14 3 3sigma in oocyte. Conclusion
14 3 3 family proteins induce cross talk with various signaltransductions though protein complex formation. 14 3 3sigma

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was identified as a novel Bnc1 binding protein. It is implicatedthat Bnc1 may possibly regulate various signal transduction
through 14 3 3sigma.

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ISP-21-5!

Genome wide gene expression analysis in mouse granulosa
cells undergoing luteinization during ovulation Yuichiro
Shirafuta, Isao Tamura, Haruka Takagi, Yumiko Mihara,
Masahiro Shinagawa, Maki Okada, Lifa Lee, Ryo Maekawa,
Hiromi Asada, Toshiaki Taketani, Hiroshi Tamura, Norihiro
Sugino Yamaguchi University
Objective Dramatic changes of gene expressions occur in granulosa cells（GCs）undergoing luteinization during ovulation after
the LH surge. Here, we genome widely investigated thechanges in mRNA expressions in mice GCs undergoing luteinization during ovulation. Methods 3 week old immature mice
were injected with equine chorionic gonadotropin（CG）（4IU）followed by human CG（5IU）. The ovaries were removed, luteinized GCs were obtained before（0h）and 4, 12h after hCG injection, and mRNA was isolated. To investigate the genome
wide mRNA expression, RNA sequencing was performed. Gene
expression values were calculated as fragment per kilobase ofexon unit per million mapped reads（FPKM）. The genes whose
FPKM values increased or decreased more than 2 fold by hCG
injection were defined as differentially expressed genes. The
roles of those genes were analyzed by Gene ontology analysis
and KEGG pathway analysis. Results（1）2,592 genes were up
regulated 4h after hCG injection. They were associated with angiogenesis, cholesterol metabolism, progesterone production,
histone modifications, and epithelial mesenchymal transition（EMT）. EMT may be involved in the changes of cell morphology form granulosa cells to luteal cells. These rapid changes ofgene expression may be regulated by epigenetic mechanisms；
histone modifications.（2）1,831 genes were up regulated 12h after hCG injection, and some of them were associated with protection of cells from DNA damage. Conclusion Genome wide
gene expression analysis using RNA sequencing revealed that
rapid changes of gene expression occur in GCs immediately after hCG injection, which contribute to corpus luteum formation
through various physiological functions.

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ISP-21-6!

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Mitochondria eating protein is essential for sperm function,
but not oocyte quality, in in vitro fertilization Makoto
Orisaka, Makoto Yamamoto, Yoshio Yoshida University of
Fukui
Objective Mitochondria eating protein（Mieap）is a key regulator of mitochondrial quality control system in cells. Although
Mieap plays a critical role in maintaining healthy mitochondria
in various pathophysiological states, its role in reproduction is
unknown. Methods In vitro fertilization（IVF）was conductedby using sperm from male wild type（WT sperm）and Mieap
knockout（Mieap KO sperm）mice, and oocytes from female
WT（WT oocytes）and Mieap KO（Mieap KO oocytes）mice.
The developed blastocysts were transferred into the uterus ofpseudopregnant female mice. Data expressed as percentages
were analyzed using Fisherʼs exact test. Results Mieap KO
sperm exhibited reduced motility and increased morphologicalabnormalities. The number of Mieap KO oocytes after ovarian
stimulation was identical to that of WT oocytes. The fertilization rate and percentage of 4 cell embryos/2 cell embryos weresignificantly lower between Mieap KO sperm and WT oocytes（41.5%［174/419］and 55.2%［96/174］, respectively）and Mieap
KO sperm and Mieap KO oocytes（29.9%［53/177］and 66.0%［33/53］, respectively）, than between WT sperm and WT oocytes（76.8%［413/538］and 94.9%［392/413］, respectively）and

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specifically on the surface of LDs, we generated mRNA which
encoded fusion protein of p62 and LD binding domain, and microinjected it into the cytoplasm of 1 cell embryos to induceforced lipophagy after fertilization. These lipophagy induced
embryos were further cultured and analyzed. Results In the
lipophagy induced embryos, LDs were clustered and translocated to the cell periphery, where autophagosomes and lysosomes were abundant. Induction of forced lipophagy caused a
reduction in LD size and number, and decreased the triglyceride level throughout embryonic development. We confirmedthat the lipophagy induction was dependent on autophagic activity. Finally, we found that the lipophagy induction decreases
the developmental ability reaching to the blastocyst stage. Conclusion We demonstrate that the lipophagy induction decreases
the developmental potential, indicating that proper amount of
LDs is essential for preimplantation embryo development in
mice.

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ISP-21-7
Identification of the genes associated with endometrial cellaging Teruhiko Kawamura, Ichiro Onoyama, Keiko Kawamura,
Natsuko Yokota, Kana Hiasa, Katsuko Egashira, Kiyoko Kato
Kyushu University
Objective As the age of reproduction among women is extended, the infertility rate has increased and the birth rate has
declined. We assume that not only aging of oocyte but also endometrium, cause infertility, but the mechanism of endometrial
cell aging is unknown. In the present study, we try to identify
the genes associated with endometrial cell aging. Methods We
purified total RNA from murine uteri resected from C57BL/6 at
5, 8 and over 60 weeks of age and the klotho mouse at 5 weeks ofage, which is known as a model of progeria, and analyzed themwith RNA sequencing and bioinformatics analysis including
cluster dendrogram, Gene ontology analysis and Pathway analysis. We validated the expression of candidate genes by real time
PCR. All mouse experiments were approved by the animal ethics committee. Results In cluster dendrogram, gene expression
profile of klotho mice is similar to young mice, but not aged
mice. We detected continuously changing 6 up regulated genes
and 5 down regulated genes with aging. In global comparison ofyoung mice with aged mice, ALDH1a and KLF4, which arestemness markers, were downregulated with aging. Pathway
analysis demonstrated that the genes involved in the pathway
associated with the cell cycle or mitosis are downregulated withaging. Among the differentially expressed genes, the expressionof IL17 receptor was validated and confirmed its upregulation.
Conclusion We identified several genes as markers of endometrial cell aging.

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ISP-21-8
Forced lipophagy reveals that lipid droplets are required forthe development of preimplantation embryos in mice
Takayuki Tatsumi1, Atsushi Yamamoto3, Toshiro Kubota4,
Naoyuki Miyasaka1, Satoshi Tsukamoto2 Tokyo Medical and
Dental University 1, National Institute for Quantum and Radiological Science and Technology 2, Dokkyo Medical University
Saitama Medical Center 3, Tokyo Kyosai Hospital 4
Objective Although large amount of lipid droplets（LDs）are accumulated during oogenesis, the physiological function of LDs
after fertilization remains largely unknown. Previously, we demonstrated that autophagy is highly activated after fertilization,and that autophagy deficient embryos are lethal before implantation. Although autophagy is basically a non selective degradation pathway, recent studies have revealed the existence of selective autophagy. We established a novel technique that could
reduce LDs artificially, which we called forced lipophagy, andadopted this technique for the mouse fertilized embryo to examine the relationships between the reduction of LDs and the development of preimplantation embryos. Methods p62（alsoknown as Sqstm1）, that is essential for selective autophagy, wasused as autophagy adapter for LD degradation. To express p62

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ISP-21-9!

HAND2 regulates IL 15 in human endometrium during progesterone induced decidualization Hiromi Murata, Naoko
Kida, Takeharu Kido, Maiko Kobayashi, Yoji Hisamatsu,
Toshiko Ono, Sonoko Okada, Tomoko Tsuzuki, Hidetaka Okada
Kansai Medical University
Objective Heart and neural crest derivatives expressed transcript2（HAND2）is a key transcription factor during progesterone induced endometrial decidualization. The present study
was undertaken in order to understand the mechanism underlying HAND2 regulates decidualization of human endometrium,
putting its focus on Interleukin 15（IL 15）which contributes tomaturation of uterine natural killer（uNK）cells. Methods This
study was approved by the institutional review board. Informed
consent was obtained from each patient. Human endometrial tissues were collected from 24 patients who underwent hysterectomies with regular menstrual cycles. Cultured hESCs weretreated with estradiol（E2）and medroxyprogesterone（MPA）for
2 h 12 d, and HAND2 siRNA transfected hESCs were cultured
in the presence of E2+MPA for 3 d. HAND2 and IL 15 mRNA
expression change were analyzed by real time PCR. Moreover,total RNA was extracted from endometrial tissues which werefrozen in liquid nitrogen as soon as were collected, and the
HAND2 and IL 15 mRNA levels were measured. Results The
expression of IL 15 mRNA increased later than the induction of
HAND2 mRNA in cultured hESCs primed with E2+MPA. IL 15mRNA expression in hESCs treated with E2+MPA for 3 d decreased with siRNA knockdown of HAND2 compared with control. Furthermore, there existed a statistically significant positive correlation between the mRNA levels of HAND2 and IL 15
in human endometrium. Both of HAND2 and IL 15 mRNA expression of the endometrium during secretory phase were significantly higher than those during proliferative phase. Conclusion This study suggests that HAND2 regulates IL 15 in humanendometrium during progesterone induced decidualization.

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ISP-22-1
New Strategies of preimplantation genetic haplotyping forpatients with de novo mutation and couples with no available
DNA samples from family members Junko Maki, Suguru Sato,
Kou Sueoka, Kenji Sato, Hiroshi Semba, Yuki Mizuguchi,
Nobuhiko Higuchi, Mamoru Tanaka, Daisuke Aoki Keio University
Objective The scarcity of template DNA is a leading cause of
misdiagnosis in preimplantation genetic diagnosis（PGD）using
direct analysis of mutations. To overcome this limitation, indirect linkage analysis using polymorphic markers should be performed. We aimed to establish a novel PGD strategy that is ef-

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WT sperm and Mieap KO oocytes（83.7%［144/172］and 96.5%［139/144］, respectively）. Live birth rate after blastocyst transfer was comparable among embryos from WT sperm and WT
oocytes（17.8%［21/118］）, WT sperm and Mieap KO oocytes（18.8%［15/80］）,Mieap KO sperm and WT oocytes（23.5%［4/17］）,and Mieap KO sperm and Mieap KO oocytes（20.0%［5/25］）. Conclusion Mieap, a key regulator of mitochondrial quality control, is required for sperm motility and structural integrity. Mieap KO sperm increased 2 cell stage block of embryossuggesting that the down regulation of Mieap in sperm induces
oxidative stress in embryos during IVF. Mieap is not essential
for oocyte quality nor implantation of blastocysts.

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fective for patients with de novo mutations or when affected
DNA samples from deceased family members are not available.
Methods Family 1）Both parents were carriers of the short rib
polydactyly syndrome, a lethal recessive skeletal disease. As
blood samples of the affected proband had been depleted in theanalyses by foreign institutions, we extracted DNA from dried
umbilical cord preserved according to the Japanese traditions.
Family 2）The patient had a de novo mutation for myotonic dystrophy, where the causative mutation was not identified in family members. We performed PGD on the basis of the results of adirect analysis coupled with a linkage analysis using DNA derived from poorly developed embryos subject to discard. Results Family 1）The average quantity of DNA from a dried umbilical cord was 20.1 μg/100 mg, sufficient for identifying linkage markers for haplotyping. Family 2）All the cells from twopoorly developed embryos consisting of 7 and 4 blastomeres, respectively, were subjected to whole genome amplification on
day 5, followed by a multi locus analysis of short tandem repeat
markers. Family haplotypes were constructed successfully.
Conclusion We established a robust PGD system for cases
where mutated DNA samples from affected family members
are no longer available or not present originally.

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ISP-22-2
Incidence and predictive factors for complete fertilization
failure in in vitro fertilization treatment cycles：a retrospective cohort study using the assisted reproductive technology
registry of Japan Toshifumi Takahashi1, Ryota Suganuma2,
Keiya Fujimori2, Hideki Mizunuma1 Fukushima Medical Centerfor Children and Women Fukushima Medical University 1,
Fukushima Medical University 2
Objective The purpose of this study was to evaluate the incidence and predictive factors for complete fertilization failure（CFF）in patients undergoing in vitro fertilization（IVF）treatment cycles. Methods The present study was a retrospective cohort study approved by the ethical committee on human subjects. The data analyzed in this study were part of the Japanese
assisted reproductive technology（ART）registry database. We
analyzed the data of 220,065 fresh cycles of IVF with one ormore oocytes retrieved. An instance of CFF was defined as zero
fertilized oocytes obtained. The IVF cycles with CFF and with
one or more oocytes fertilized were compared with each otherto determine predictive factors for CFF using multivariate logistic regression analyses. Results The number of IVF cycles
with CFF was 29,076（13.2%）. On the multivariate analysis, oocyte number（odds ratio［OR］：0.78, 95% confidence interval［CI］：0.77 0.79）and sperm motility（OR：0.99, 95% CI：0.98
0.99）were the independent predictive factors for CFF. The percentages of CFF cycles in terms of one, two, three, four, and fiveoocytes retrieved were 34.2%, 15.3%, 8.6%, 6.0%, and 4.6%, respectively. The efficacy of oocyte number and sperm motility
for predicting CFF was evaluated using receiver operating
characteristic curves. The areas under the curves for oocyte
number and sperm motility were 0.79 and 0.59, respectively.
Conclusion Predictive factors for IVF cycles with CFF might
be related with a specific oocyte number and sperm motility.
These results provide information that may be useful for counseling patients prior to their undergoing ART treatments.

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portant factor affecting fertilization and subsequent early embryo development. PUFAs are essential fatty acids that are notsynthesised in the body, but are utilised as an energy source forprocesses from oocyte nuclear maturation to embryonic development. Objective is to clarify the concentration of polyunsaturated fatty acids（PUFAs）in the follicular fluid affect fertilization and the quality of embryos. Methods A prospective study
was conducted on 28 women eligible for in vitro fertilizationand embryo transfer between August 2015 and December 2016.
Twenty eight serum and 140 follicle fluid samples were collected and analysed. This study was approved by the clinical research ethics investigation committee in our institution. PUFAs
fractions from the serum and follicular fluid were analysed using gas chromatography. Two millilitres of follicular fluid wascollected from six consecutive follicles of each patient. Each individual follicle was aspirated independently and matched to an
oocyte gr owing in this particular follicular milieu. Results The
concentration of γ Linolenic acid, an n 6 type PUFA, in the follicular fluid of fertilised oocytes was significantly higher thanthat in the follicular fluid of non fertilised oocytes（1.1 vs 0.9, p=0.007）. Similarly, the concentrations of EPA and docosapentaenoic acid, which are n 3 type PUFAs, in the follicular fluid of
fertilised oocytes were significantly lower than those in the follicular fluid of non fertilised oocytes. Conclusion The concentration of PUFAs in the follicular fluid plays an important role infertilisation.

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ISP-22-3
Polyunsaturated fatty acid concentration in the human follicular fluid may affect fertilization Keiko Mekaru, Maho
Miyagi, Kozue Akamine, Chiaki Heshiki, Yoichi Aoki Universityof the Ryukyus
Objective The metabolite composition of the follicular fluid,which represents the intrafollicular environment, may be an im-

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ISP-22-4
Does variable luteal support according to the serum progesterone level at the embryo transfer improve the clinical pregnancy rate of natural frozen thawed embryo transfer?
Takuhiko Ichiyama, Motoharu Ohno, Takashi Yamaguchi,
Motoi Nagayoshi, Atsushi Tanaka Saint Mother HospitalObjective To verify the clinical usefulness of the variable luteal
support according to the serum progesterone levels in the cycleof natural frozen thawed embryo transfer. Methods 1. 993 patients under 39 years old participated in 1,280 frozen thawedtransfer natural cycles from January 2015 to August 2017. They
were divided into two groups, with variable luteal support（VLS）in 351 cycles and no luteal support in 929 cycles（NLS）.
The two groups were further divided into five froups according
to the progesterone levels（ng/ml）：GroupA（Progesterone＜=5）, GroupB（5＜Progesterone＜=10）, GroupC（10＜Progesterone＜=15）, GroupD（15＜Progesterone＜=20）, GroupE（20＜Progesterone）. 2. In the VLS group, progesterone suppositories were
given according to the serum progesterone levels at the embryotransfer of the 5th day from the spontaneous ovulation. 3. In the
NLS group, no luteal support was given regardless of the progesterone levels. Results Pregnancy rate（VLS vs NLS）：
GroupA（50%（8/16）vs 33%（2/6））,GroupB（45%（45/101）vs40%（21/53））,GroupC（45%（94/208）vs 47%（99/211））,GroupD（55%（12/22）vs 40%（149/368））,GroupE（50%（2/4）vs 47%（136/291））.Miscarriage rate：GroupA（25%（2/8）vs 50%（1/2））, GroupB（18%（8/45）vs 19%（4/21））, GroupC（17%（16/94）vs 15%（15/99））, GroupD（25%（3/12）vs 19%（28/149））,
GroupE（0%（0/2）vs 20%（27/136））. Conclusion There wereno statistically significant differences between the VLS andNLS groups. Variable luteal support according to serum progesterone level in natural frozen thawed embryo transfer showed
no beneficial effect for improving the clinical outcome.

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ISP-22-5
Egg activation of sperm factor, phospholipase C zeta 1（PLCZ
1）as future clinical applications Takashi Yamaguchi1,
Takuhiko Ichiyama1, Motoharu Ohno1, Motoi Nagayoshi1,
Atsushi Tanaka1, Keiji Kuroda2 Saint Mother Hospital 1, Juntendo

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ISP-22-6
An analysis of follicular oxidative stress and oocyte development in ART treatment cycle Hiromi Terao, Osamu Hiraike,
Nana Akino, Harunori Honjoh, Mana Hirano, Miyuki Harada,
Tetsuya Hirata, Yasushi Hirota, Kaori Koga, Tomoyuki Fujii,
Yutaka Osuga The University of Tokyo
Objective Oxidative stress is defined as an imbalance between
the production of free radicals and the ability of the body tocounteract or detoxify their harmful effects through neutralization by antioxidants. This study was conducted to clarify influence of the oxidative stress on the development of oocytes.
Methods Under the approval of IRB and patientʼs consent, follicular fluid of patients who underwent ICSI treatment in the
Hospital were collected. The ovum was fertilized and individually cultured, and the development status was recorded. The follicular fluid corresponding to the ovum was analyzed by measuring the oxidative stress marker such as the reactive oxygen
metabolites（d ROMs test）and the antioxidant marker（BAP
test）. Results We collected 107 follicular fluid from 57 patients.
The age of participants was 37.89±4.54, and the number of theovum collected was 5.648±4.23. The fertilization rate of theovum judged by the presence of 2 pronucleus in Day 1 was
71.0%. Although the age, AMH, the number of ovum collected
and the embryonic development did not show significant correlation with oxidative stress markers, the value of d ROMs test
was significantly elevated in abnormal fertilization group（508.77±129.15）than that of normal fertilization group（398.06±108.70 p＜0.001）. Conclusion We found that the oxidative
stress in follicular fluid mainly influenced on fertilization rate of
the ovum, and the correlation of BAP test with several biomarkers should be further investigated.

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ISP-22-7
Progesterone/estradiol ratio as a predictor of obtaining usable blastocyst in clomiphene IVF cycle Kenichiro Watanabe,
Yoshimitsu Kuwabara, Mirei Yonezawa, Shuichi Ono, Tomoko
Ichikawa, Shigeo Akira, Toshiyuki Takeshita Nippon Medical
SchoolObjective To examine the relationship between the outcome ofobtaining usable blastocyst（3 BB or more）in clomiphene IVF
cycle and the serum progesterone（P4）/estradiol（E2）ratio which
is an indicator of early luteinization. Methods In 367 patients
who underwent clomiphene IVF cycle from January 2013 toJune 2015, the serum P4/E2 ratio at two days before the egg collection was calculated. The data was separated into 300 cycles
in the usable embryo acquisition group（Group A）, 38 cycles inwhich the oocyte could be picked up but did not result in obtaining usable embryos（Group B）, and 29 cycles for which the follicle was pierced but the eggs could not be obtained（Group C）Results The P4/E2 ratio was significantly lower in group A（3.9±
0.1×10!4）than in group B（5.5±0.7×10!4）and C（7.9±1.5×10!4）（Mean±S. E. M., A vs B；p ＜0.01, A vs C；p ＜0.0001）.The ROC
curve was drawn for the effective embryo obtained group（A）,
and for the effective embryo un acquired group（B+C）, the
AUC was 0.69, the cut off point of effective embryo acquisitionwas 3.5×10!4（if E2=1,000 pg, P=0.35 ng/ml）,the sensitivity was
80.6%, and the specificity was 52.33%. Conclusion The P4/E2 ratio is considered to be a predictor of usable embryo acquisitionin the clomiphene IVF cycle.

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ISP-23-1!

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Polycystic ovarian morphology in reproductive aged Thai
women with polycystic ovary syndrome Vichuta Unalome,
Thanyarat Wongwananurak Siriraj Hospital, Mahidol University, Thailand
Objectives To determine the prevalence and factors associatedof polycystic ovarian morphology（PCOM）in reproductive Thai
woman with polycystic ovary syndrome（PCOS）. Study design
Cross sectional study. Subject Thai PCOS 143 woman diagnosed
by Revised Rotterdam criteria who attended at Gynecologic Endocrinology Unit, Department of Obstetrics and Gynecology,
Siriraj Hospital during February 2016 to May 2017. Methods
The participants were interviewed and examined for weight,
height, waist circumference and blood pressure. Blood sample
were drawn for fasting plasma glucose, lipid profile, testosterone, and 2 hour post loading 75 glucose tolerance test（OGTT）.
Transvaginal or transrectal ultrasonography was performed toevaluate PCOM. Results Mean age and BMI of population were25.2±5.3 years old and 24.3±6.0 kg/m2. Clinical presentation
showed 77.6% had acne and 64.3% had hirsutism. The blood test
revealed 16.1% had abnormal OGTT in these 5.6% had diabetes
mellitus. Mean total testosterone was 0.47±0.1 ng/mL. The
overall prevalence of PCOM was 55.2%. Prevalence of PCOM byovarian follicle, ovarian volume was 36.4% and 42% respectively.
Mean follicle number per ovary, follicle number per cross section and ovarian volume were 20.0±9.5 follicles, 8.3±3.1 follicles, 7.9±3.0 cm3 respectively. Univariate analysis of clinicalpredictor founded that no associated factor with PCOM. Conclusion The overall prevalence of PCOM in Thai woman with
PCOS was 55.2%. There was no significance predictor associated with PCOM.

ISP-23-2
The effect of androgen on secondary follicle development
might be species specific Yuya Fujibe, Tsuyoshi Baba, Sachiko
Nagao, Tsuyoshi Saito Sapporo Medical University HospitalObjective Excess androgen is thought to play a key role in thepathogenesis of polycystic ovary syndrome（PCOS）.Several animal models exposed to androgens are used to examine the effects of androgens on follicle development. However, experimental animals exposed to androgens do not completely mimic
PCOS. In addition, extremely high level of androgen exposure infemale to male transsexualism does not cause PCOS like phenotype. We therefore investigated the effects of various dose of

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University 2
Objective In this study, to establish the best egg activation
method and improve development rates after ICSI or ROSI, we
compared the pattern of［Ca2＋］i elevation after stimulation bycytosolic aspiration, electrical stimulation, ionomycin treatment
and human PLCZ1 RNA injection. We found that the pattern of
Ca2＋oscillations after hPLCZ1 RNA injection exhibited similar
characteristics to that after ICSI treatment. Methods M II oocytes were incubated in 4μM Fluo 8H AM in SPS medium andoptimal RNA concentrations for oocyte activation were examined by injecting various concentrations of in vitro transcribed
hPLCZ1 RNA by conventional Piezo ICSI methods into the human M II oocytes. After injection, the rate of pronucleus（PN）
and polar body（PB）formation was checked and the intracellular
Ca2＋ concentrations were monitored by fluorescent Ca2＋ indicator among four groups；（A）electrical stimulation,（B）Mechanical stimulation,（C）Ionomycin,（D）hPLCZ1 RNA. Results Fromthe pattern of Ca2＋ concentrations and PN formation rate, optimal concentration of hPLCZ1 RNA to activate human oocytes
was 100 ng/μl. The duration and interspike intervals of Ca2＋ oscillations were similar to that of ICSI. And we also compared theeffect among 3 groups（A, C, D）in ROSI cycles. Group D showed
higher embryonic development without significant differences.
Conclusion hPLCZ1 has the ability to generate ideal and physiological egg activation, leading to subsequent embryo development. In the future, for clinical application, the safety of hPLCZ1
injection to human health should be examined in more detail.

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androgen on mice follicle development and compared with ourprevious study of nonhuman primate models. Methods Secondary follicles from 6 week old female ICR mice（n=3）were isolated and assigned to 4 culture conditions：1）control（33 ng/
ml FSH）；2）dihydrotestosterone（DHT）50 ng/ml；3）DHT
500 ng/ml；and DHT 1,250 ng/ml. Follicles were cultured at
37˚C in a 5% CO2 environment for two weeks. Follicle survival
and follicle diameters were determined. Results Follicle survival rates in control, DHT 50, DHT 500, and DHT 1,250 groups
were 83±8%, 49±7%, 45±5%, and 54±13%, respectively（p=0.057）.Follicle diameter at day13 in each group are 218.3±33.4μm, 236.7±10.7μm, 181.2±47.5μm, and 253.7±19.7μm, respectively（p=0.52）. Conclusion In our previous study using macaque, at the preantral stage, DHT can replace FSH action topromote follicle survival rate, but in rodents, androgen does notseem to support secondary follicle survival. In addition, the dose
escalation of DHT does not alter folliculogenesis in rodents. The
effects of androgens on secondary follicle development might bespecies dependent.

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ISP-23-3
Large uterine myoma with erythropoietin messenger RNA
and erythrocytosis Takafumi Kohama Keiju Medical Center
Background Erythrocytosis reported in association with a uterine myoma is well known as the myomas erythrocytosis syndrome. Although several etiologies for this syndrome have been
forth, altered erythropoietin production is the most likely towhich there are few cases reported. Case A 28 year old, gravida
0, para 0, with a chef complaint of infertility, presented with a
34 36 weeks gestation sized, solitary, degenerated uterine
myoma and erythrocytosis. After Gn RH agonist treatment, amyomectomy was performed and the tumor analyzed by reverse transcription polymerase chain reaction（PCR）with specific erythropoietin primer with erythropoietin mRNA was observed. Randomly selected 8 cases of uterine myoma from thepatients with no finding of erythrositosis were analyzed in thesame way for the control at the same time. Conclusion Our finding suggests that erythropoietin production by myomas mightcause erythrocytosis in the myomatous erythrocytosis syndrome. After the surgery, she had 2 pregnancies, showing no abnormalities all the courses of pregnancy and delivery（cesarean
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ISP-23-4!

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Application of Computer Aided Sperm Analysis（CASA）for
Sperm Immobilization Test Yu Wakimoto1, Atsushi Fukui1,
Akiko Hasegawa1, Yukiko Sugiyama1, Yuji Ukita1, Minoru
Shigeta2, Hiroaki Shibahara1 The Hospital of Hyogo College ofMedicine 1, Fuchu Nozomi Clinic 2
Objective Complement dependent sperm immobilizing test
（SIT）and quantitative SIT have been used as a useful tool for
diagnosis to female infertility in clinical sites. These tests are
subjective judgement of the operator due to counting motile
sperm by eye. It is possible to evaluate objectively data on
sperm motility using computer aided sperm analysis（CASA）
instruments. In this study, we developed a novel method of SIT
and quantitative SIT using CASA. Methods 78 serum samples
and motile sperm by a swim up method were prepared. Mixtures of 10 μL of serum, 1 μL of the sperm suspension, and 2 μLof complement were incubated. We compared the classicalmethod counting sperm by eye of a highly skilled embryologist
with a novel method counting sperm using CASA through thechamber slides. The mixtures were incubated respectively on
Terasakis microplates in the classical method and after being
applied to chamber slides in the novel method. Sperm motility
was measured after one hour incubation in both methods. Re-

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sults The results of SIT were completely same in both methods.
25 of 78 samples tested were positive and 53 samples were negative. In case sperm immobilizing value was 2 or higher, the values of SI50 were determined and closely correlated with highco efficiency in both methods（r=0.84）. Conclusion We showedthat it is possible to perform SIT and quantitative SIT in thenovel method using CASA presented here.

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A successful pregnancy in a patient with 46,XY pure gonadal
dysgenesis after transfer of a frozen thawed embryo derived
from donor oocytes Misato Ukita, Yuji Ukita, Yukiko
Sugiyama, Toru Kato, Kayoko Harada, Hideaki Sawai, Hiroaki
Shibahara The Hospital of Hyogo College of Medicine
Background The 46, XY pure gonadal dysgenesis（PGD）is one
of atypical sex disorders and named after Swyer, who first described this syndrome. Swyer patients（approximately 1：
30,000）have a male genotype（46, XY）but reveal no male gonadal differentiation. They show sex reversal with normal female external genitalia and a vagina. However, the uterus ismostly hypoplastic and the Fallopian tubes are rudimentary anddysfunctional. Here we report a successful pregnancy in a patient with PGD after transfer of frozen thawed embryo derived
from donor oocytes. Case A 27 years old female presented withprimary amenorrhea. Physical examination revealed a phenotypic female with a normal vagina and cervix, no clitoral enlargement and other evidence of virilization. The uterus accepted it by a ultrasonography, but the both ovaries were indistinct. Her serum FSH level was 75.71mlU/mL, LH level was
11.68mlU/mL, and testosterone level was 0.09ng/dL. A karyotype performed on peripheral leukocytes analyzed 100 cells, allof which contained a 46, XY chromosome. Laparoscopic surgery
revealed an infantile uterus, hypoplastic Fallopian tubes, and bilateral streak gonads, which were excised. Pathologic examination documented only fibrous tissue. Six years later she conceived after transfer of a frozen thawed embryo derived fromdonor oocytes at USA. She delivered a normal male infant
weighing 2,780g with Apgar scores of 8 and 9 at 1 and 5 minutes
by Cesarean section after her 37 weeks of pregnancy due to partial placenta previa.

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Determining the safe cut off point for preimplantation genetic diagnosis（PGD）of mitochondrial DNA（mtDNA）disorders Yuki Mizuguchi, Kou Sueoka, Suguru Sato, Junko Maki,
Kenji Sato, Mamoru Tanaka, Daisuke Aoki Keio University
Objective mtDNA disorders are usually heteroplasmic, withcells harbouring both wild type and mutated mtDNA. Prerequisites for PGD of mtDNA disorders are that the mutant load
has；1）correlation between tissues and cells, 2）no time dependent change, 3）correlation with phenotype. The most difficult problem of PGD for mtDNA disorders is the inability to determine the cut off point for embryo transfer. Too stringent criterion would lead to a loss of a presumably healthy embryo. We
aimed to determine the safe cut off point for PGD of mtDNA
disorders. Methods Four cases of Leigh encelaphalopathy havebeen approved by the hospital and Japan Society of Obstetrics
and Gynecology（JSOG）ethical committees. Amongst those,
PGD was carried out with 2 cases with m.8993T＞G mutation.
Results The number of transferrable/biopsied embryos were；case 1（0/1）, case 2（1/8）. None of these cases have resulted insuccessful pregnancy. For the m.8993T＞G mutation, the chanceof having an affected offspring is highly unlikely when the mutant load is below 20% and in most cases the threshold for a severe clinical outcome is 90%. When setting a cut off point；1）
mutant load below the carrier, 2）preventing the loss of healthy

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Establishment of female athlete outpatient in our hospital andcurrent problems for female athlete triad Sayaka Nose-Ogura,
Osamu Hiraike, Akari Nakazawa, Kaoru Morishima, Mana
Hirano, Mayuko Kanatani, Miyuki Harada, Tomoyuki Fujii,
Yutaka Osuga The University of Tokyo HospitalObjective Recently, it has been well recognized a set of healthproblems occurs for female athletes. After recognition of female
athlete triad（FAT）in 1992 and its update in 2007, low energy
availability, functional hypothalamic amenorrhea, and osteoporosis have been keenly attracting attention and our hospital established an outpatient for female athletes in April 2017. Herein
we report the current status of the outpatient. Methods Underapproval of IRB and patients consent, we retrospectively reviewed the medical records from April to September in 2017 toreveal the clinical characteristics of female athletes. Results Total number of cases was 145（26 in international level and 49 innational level）and average age of participants was 21.5. Athletes who visited for menstrual cycle control with the aim ofconditioning were 9（12%）. Forty patients（66.7%）were diagnosed as menstrual dysfunction（39 secondary amenorrhea, 1
primary amenorrhea, and 10 oligoamenorrhea）accompanying
with low energy availability, and they were consulted to sports
dietary specialist and four patients with apparent eating disorder were consulted to sports psychiatrist. Conclusion As expected, the most frequent disease in female athletes who visited
our hospital was amenorrhea due to low energy availability. We
should note that amenorrheic athletes may be complicated byeating disorder, and cooperation with sports dietitian and sports
psychiatrist is mandatory.

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Of 5 patients desired for baby, 4 became pregnant and all gavebirth at term（3 caesarean section and one vaginal）. Conclusion
OHVIRA syndrome and related diseases involved variety ofanomalies. Physician should be aware of those varieties of phenotypes and symptoms for accurate diagnosis and individualized management.

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ISP-23-8What is OHVIRA syndrome? The Müllerian duct anomaly
and unilateral renal agenesis in our 17 cases Takashi Kuno,
Zen Watanabe, Saori Igeta, Keiko Tanaka, Ayako Fujimine, Emi
Yokoyama, Masumi Ishibashi, Naomi Shiga, Motomasa Ihara,
Junichi Sugawara, Masahito Tachibana, Nobuo Yaegashi Tohoku University Hospital
Introduction OHVIRA syndrome was first described in 2007
and is emerging a generic term for diseases that merge uterine
anomalies with unilateral obstructed vagina and ipsilateral renal abnormality. OHVIRA syndrome and related diseases varyin phenotype and symptoms due to variety of congenital anomaly of Müllerian duct associated mesonephric duct anomaly. We
investigated 17 cases of the Müllerian duct anomaly and unilateral renal agenesis in our hospital. Methods Patient age at first
visit, symptoms, classification of female genital tract malformations, laterality of renal hemiagenesis, surgical interventions, endometriosis, pregnancy and delivery style were investigated for
those of 17 cases from 2002 to 2017. Results The median age ofpatients at first visit was 16 years. Chief complaints were as follows；5 with dysmenorrhea, 2 with associated abdominal pain, 4with desire for baby, and others. The laterality of renal hemiagenesis was 7 right and 10 left cases. In almost all 13 surgicalcases, the vaginal septectomy was performed. The operation
was performed for 8 cases in early adolescence and for 5 casesin adulthood. The combined laparoscopy was performed for 8
out of 13 cases and the pelvic endometriosis was revealed in 5.

Serum AMH levels in adolescent and young women under 25
years with irregular menstrual cycles Akari Watanabe,Michio Kitajima, Yuriko Kitajima, Ozora Tsukamoto, Naoko
Murakami, Ken Taniguchi, Kiyonori Miura, Hideaki Masuzaki
Nagasaki University HospitalObjective Serum AMH levels have been introduced to infertility care to predict responsiveness for controlled ovarian stimulations. They also may be useful in the diagnosis of premature
ovarian insufficiency（POI）and polycystic ovarian syndrome（PCOS）, though, its value is uncertain in young women under
25 years of age. In this study, we evaluated clinical significanceof serum AMH levels in women under 25years who showed irregular menstrual cycles from various reasons. Methods From
July 2011 to March 2017, women who visited our department
due to menstrual disturbances were recruited. Women withovarian tumor, endometriosis, and under hormonal therapy
were excluded. Menstrual disturbances were classified as POI,
PCOS, and hypothalamic from endocrinological examinations.
Serum AMH levels were measured by ELISA. The relationshipbetween serum AMH levels and clinical features are evaluated.
Results Fifty three women were enroled. In five idiopathic POI
patients, serum AMH were all undetectable, Mean serum AMH
levels were 0.23±0.26ng/mL in eight iatrogenic POI patients. In
obese PCOS（n=7）and non obese PCOS（n=8）patients, serum
AMH levels were 11.4±4.07ng/mL and 14.3±7.14ng/mL, respectively. In hypothalamic amenorrhea（n=25）, two out of fiveathletes, two out of three women in wasting state, such as cancer, and one out of seven weight loss women showed serum
AMH levels below 1.5ng/mL and significantly lower thanamenorrheic women with unknown causes（n=10, 6.58±3.37ng/
mL）. Conclusion Young women with hypothalamic amenorrhea
due to systemic exhaustions may show low serum AMH values,
which may need careful interpretations of the results.

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Association of eicosapentaenoic acid（EPA）to arachidonicacid（AA）ratio with second trimester miscarriage Nobuko
Mimura, Takeshi Nagamatsu, Rieko Shitara, Hitomi Furuya,
Aki Hara, Takahiro Seyama, Toshio Nakayama, Takayuki
Iriyama, Yutaka Osuga, Tomoyuki Fujii The University of Tokyo HospitalObjective Eicosapentaenoic acid（EPA）
to arachidonic acid（AA）
ratio is a representative marker to evaluate dietary intake balance of omega 3 and omega 6 fatty acids. This study aimed toinvestigate the relevance of serum EPA/AA ratio to thepathoetiology of recurrent miscarriage（RM）. Methods This
study was conducted under approval of our facility ethics committee. Medical records of 772 women visiting our special clinic
for RM from Nov. 2010 to Jul. 2017 were retrospectively reviewed. In addition to routine screening tests for RM, serum
EPA/AA ratio was examined. The women without specificcausal factors identified were divided into two age groups；thewomen at age ＞=35（group A, n=470）and the women at age＜35（group B, n=248）.The relevance of EPA/AA ratio to theirpast history of miscarriage was analyzed. Results There was nocorrelation between the past miscarriage number and EPA/AA
ratio in both groups. In group B, EPA/AA ratio was significantly lower in the women with a history of second trimester!

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embryos, 3）prevention of the disease, are taken into consideration. The JSOG ethical committee proposed that mutant load below 80% would be feasible so we set our cut off point at 45% taking patients desire in consideration. Conclusion Although there
is no definite cut off level for PGD of mtDNA disorders, lower
mutant load below 20% is likely to be a safe and efficient cut off
point.

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miscarriage（0.18±0.10, n=33）compared with the women without it（0.24±0.14, n=215）（p=0.02）. This phenomenon was more
obvious in the women who experienced the second trimester
miscarriage resulting from cervical incompetency and chorioamnionitis（EPA/AA ratio=0.11±0.03, n=6）
. No remarkableassociation of EPA/AA ratio with the history of second trimester miscarriage was observed in group A. Conclusion Low
omega 3/omega 6 intake would be a hidden factor associatedthe pathoetiology of the second trimester miscarriage among
unexplained RM women at age ＜35.

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ISP-24-2
DomainV of β2GPI has very high affinity with MHC class II
Yuuki Sasagawa1, Kenji Tanimura1, Satoko Morikami2, Masashi
Deguchi1, Yasuhiko Ebina1, Hideto Yamada1, Hisashi Arase3
Kobe University 1, Kobe City Nishi Kobe Medical Center 2, Osaka
University Immunology Frontier Research Center 3
Objective Antiphospholipid syndrome（APS）is an autoimmune
disorder characterized by thrombosis and/or pregnancy complications. β2 glycoprotein I（β2GPI）complexed with phospholipid
is known to be the major target for autoantibodies in APS. β2
GPI associated with HLA class II molecules is the major autoantibody target in antiphospholipid syndrome. β2GPI is composedwith 5 domains. It is suggested that autoantibodies bind to domain I of β2GPI, whereas phospholipids bind to domain V. In thisstudy, we analyzed how autoantibodies recognize β2GPI/HLA
class II complex. Methods We made domain deletion mutants of
β2GPI. Using these mutants of β2GPI, we analyzed the domainsof β2GPI to associate with HLA class II molecules using celllines, latex beads and SDS PAGE. Results We found that the domain V of β2GPI is responsible to the association with HLAclass II molecules. On the other hand, autoantibodies preferentially bound to the domain I of β2GPI. These results suggest thatthe binding region of β2GPI to phospholipids and HLA class II
molecules is similar. Conclusion These studies provide important information to understand how HLA class II molecules are
involved in the pathogenesis of antiphosipholid syndrome.

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Reevaluation of the RPL management based on the villus
chromosomal analysis after miscarriage despite previous
treatment Ai Sakamoto1, Hirofumi Matsuoka1, Shiho Fujita1,
Kotaro Kubo1, Toru Hasegawa1, Sayoko Kotani1, Yasuhiko
Kamada1, Mikiya Nakatsuka2, Hisashi Masuyama1 Okayama University 1, Okayama University Graduate School of Health Sciences 2
Objective In our hospital, outpatients with RPL（recurrent pregnancy loss）are examined for risk factors of miscarriage which
include autoimmunological, endocrine, and coagulation factors.
Based on the results, a treatment plan was developed for subsequent pregnancies. When miscarriages occurred despite themanagement, chorionic villus chromosomal analysis was conducted after obtaining a consent to ascertain the cause of pregnancy loss. Methods Women with singleton pregnancies, whowere treated for RPL and underwent a chorionic villus chromosomal analysis after miscarriage at our hospital from January
2006 to April 2017（158 cases）were analysed retrospectively.
Fourteen cases associated with parental chromosomal translocation were excluded. Results Out of 44 cases（27.8%）showing normal karyotype, subsequent pregnancies were recorded in 18
cases. Fetal morphological abnormalities were not detacted during the previous pregnancies in 14 cases, they were managedwith a method strengthened from previous treatments. As a result, 15 cases（83.3%）were able to deliver babies. However, repeated miscarriages with normal karyotype were recorded in 2
cases. In addition, 98 cases（62.0%）showed abnormal karyotype,and 56 cases out of the above group achieved following pregnancies and managed with the same treatments. As a result, 49
cases（87.5%）were able to deliver babies. Conclusion By ascertaining the cause of miscarriage and reevaluating the management, high rate of delivering a baby was achieved on subsequent pregnancies. This data is expected to help the patientswith RPL understand the importance of villus chromosomal
analysis after miscarriage.

ISP-24-4
Induction and clearance of decidual senescent cells in cycling
human endometrium Yojiro Maruyama, Keiji Kuroda, Keisuke
Murakami, Atsuo Itakura, Satoru Takeda Juntendo University
Objective Immune clearance of accumulating senescent cells
followed by stem cell activation and repair maintains homeostasis of many ageing tissues. To examine it is happened in endometrial stromal cells（EnSCs）, we checked cellular senescence and immune clearance in vivo and in vitro. Methods
EnSCs and immune cells are isolated from endometrial biopsies.
Decidualization is induced by progesterone and cAMP. Results
Here we show that cyclic decidualization of the human endometrium triggers cellular senescence in a subpopulation of
EnSCs, characterized by accumulation of senescence associatedβ galactosidase, heterochromatin formation, epigenetic changes
and induction of a complex pro inflammatory response. Treatment of primary cultures with rapamycin, a selective mTOR inhibitor, abrogated senescence but also blocked induction of decidual markers genes（PRL and IGFBP1）. However, selective ablation of senescent cells with dasatinib, a senolytic drug, had noeffect on subsequent induction of PRL or IGFBP1 in primary
EnSCs but attenuated the decidual pro inflammatory secretory
response and resulted in loss of clonal endometrial mesenchymal stem cells（eMSCs）.Further, we demonstrate that IL15 activated uterine NK（uNK）cells target and clear senescent EnSCs
both in vitro and in vivo. Taken together, these observations
demonstrate that the intense endometrial remodelling underpinning the mid luteal window of implantation involves inductionof a senescence associated pro inflammatory response. Activated uNK cells then clear senescent EnSCs, which in turn triggers differentiation of eMSCs as the decidual process unfolds.
Conclusion Our results suggest that imbalance of eMSCs, decidual senescent cells and uNK cells may be a major cause of reproductive failure.

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ISP-24-5
The distribution of etiology and therapy outcomes of recurrent pregnancy loss at our recurrent pregnancy loss clinic
Maho Miyaji, Masashi Deguchi, Kenji Tanimura, Mayumi
Morizane, Yasuhiko Ebina, Hideto Yamada Kobe University
Hospital
Objective The aim of this cohort study was to reveal etiology/
risk factor and pregnancy outcome in women with recurrent
pregnancy loss（RPL）. Methods The institutional ethic boards
approved this study. Three hundred forty five women with
RPL who consecutively visited our hospital between June 2009
and July 2015 were enrolled, and their etiologies/risk factors of
RPL were assessed. Pregnancy outcomes were evaluated, andcompared among 283 women with each etiology/risk factor of
RPL. High natural killer（NK）cell activity, luteal insufficiency
or positive anti phosphatidylethanolamine antibody was considered unexplained etiology/risk factor. All patients received
standard therapies before and during pregnancy. Results Of 283
patients, 257 patients became pregnant, and pregnancy rate was91%）. A total of 163 women had explained etiology/risk of RPL,
while 182 women had unexplained etiology/risk. Pregnancy
rate（67%）in women with uterine abnormality was lower than

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Subclinical hypothroidism in women with reccurent pregnancy loss Kotaro Kubo1, Yasuhiko Kamada1, Yuri Miyahara1,
Hirofumi Matsuoka1, Shiho Fujita1, Toru Hasegawa1, Ai
Sakamoto1, Sayoko Kotani1, Mikiya Nakatsuka2, Hisashi
Masuyama1 Okayama University 1, Okayama University Graduate School of Health Sciences 2
Objective Thyroid dysfunction is associated with various obstetrical complications. The guidelines of the American Thyroid
Association 2011 remarked that thyroid autoantibody positive
women were high risk for miscarriage and subclinical hypothyroidism during pregnancy. But management of subclinical hypothyroidism women with recurrent pregnancy loss（RPL）remains to be established. We evaluated the thyroid function in
RPL women with anti thyroid autoantibodies including anti
thyroglobulin antibodies（TgAb）and anti thyroid peroxidase
antibodies（TPOAb）. Methods Four hundred and twenty one
women with RPL（Age, 36.0±4.4, mean±S.D.）, who visited RPL
clinic in our hospital from April 2013 to December 2016 were enrolled into the study after informed consent. Women who havealready received medical treatment for thyroid dysfunction
were excluded in this study. Thyroid function（free T4, TSH）
and anti thyroid autoantibodies（TgAb, TPOAb）were examined
before pregnancy and during early pregnancy with other routine examinations. Results Prevalence of hyperthyroidism, subclinical hypothyroidism（TSH＞2.5 μU/mL）, and hypothyroidism（TSH＞10 μU/mL）were 0.7%, 17.1%, and 0.7%, respectively.
Prevalence of TgAb or TPOAb in RPL women was 16.3% or
8.3%, respectively. Two hundred and sixty women became pregnant in study duration, fifty six（21.5%）were newly discovered
as subclinical hypothyroidism at early pregnancy. In RPL
women, serum TSH levels were significantly elevated at earlypregnancy compared with TSH levels before they became pregnant. Conclusion In certain ratio of RPL women were newly diagnosed as subclinical hypothyroidism at early pregnancy. And
it may be necessary for them to be treated for newly developed
thyroid dysfunction. It is important to evaluate the thyroid function in RPL women at early pregnancy.

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ISP-24-7
Studies on the outcome of pregnancies which had continued
after the immunosuppressive and anticoagulation therapy forpatients with reproductive failure who are positive for anti
phospholipid antibodies （ APLs ） Taro Nonaka, Makiko
Takahashi, Kunihiko Yoshida, Koichi Takakuwa, Takayuki
Enomoto Niigata University Medical and Dental HospitalObjective To investigate the outcome of pregnancies which had
continued after the immunosuppressive and anticoagulation
therapy for patients with reproductive failure who are positive
for APLs. Methods We treated patients with recurrent fetal miscarriages positive for APLs using Saireito, which has similar
pharmacologic effect as corticosteroid hormone, as immunosuppressive therapy, and low dose aspirin as anticoagulation ther-!

apy. In cases with a high titer of APLs, prednisolone was administered from the early stage of pregnancy. The pregnancy had
continued in 110 cases after these therapy. The gestational
weeks of delivery（GW）, the body weight（BW）of infants, aswell as major complications, were analyzed in these patients. As
control, the pregnancy outcome was analyzed in 243 cases withno complication. Results Of 110 cases, the pregnancy had terminated before 37 WG（32 36WG）in 9 cases. And the pregnancy
had terminated at term in 101（91.8%）, which was not significantly different compared with that in control（209/243, 86.0%,
by Chi square test）. The average WG of delivery in study population and control was 38W5D±2W4D and 38W4D±2W3D, respectively（n.s. by non paired t test）. The average BW of infants born to the patients in the study population and control
was 2,959±465g and 2,904±583g, respectively（n.s. by nonpaired t test）. There was also no significant difference concerning the major complications between two groups. Conclusion
The outcome of pregnancies, especially the condition of infants
who were born to patients after the immunosuppressive and anticoagulation therapy, was not significantly different comparedwith normal population.

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A case of germline mosaicism detected in infertile man with a
47, XYY karyotype Kentaro Kai1, Atsushi Tanaka2, Yuichi
Furukawa1, Satoshi Eto1, Tomoko Oishi1, Yoko Aoyagi1 Nakatsu
Municipal Hospital 1, St. Mother Hospital 2
Introduction 47, XYY syndrome occurs in 1 out of 1,000 live
male births and is caused by the presence of an extra copy of
the Y chromosome in each of a male,s cells. Most individuals
with this syndrome were diagnosed as teenagers, and their appearance, intelligence, sexual development, and fertility are usually normal, but learning disabilities may be present. We report
here a 39 year old man with 47, XYY syndrome who is presenting with infertility. Case A 39 year old Japanese man was seenin our hospital because of infertility. He was 178 cm tall（+1.35
SD）, a high school graduate, and a service station operator.
Multiple semen tests showed oligospermia. His 39 year old wife
had a history of unexplained recurrent pregnancy loss：two
spontaneous miscarriages in the first trimester. A fourth roundof artificial insemination and a couple,s karyotype analysis were
simultaneously performed in parallel. Subsequently, his wife became pregnant, and his chromosomal karyotype of 47, XYY wasdiscovered. After genetic counseling, he underwent fluorescence in situ hybridization analysis of sperm, which showed no
disomy XY and YY based on 500 sperm counts. He was diagnosed as a germline mosaic 47, XYY karyotype, and the couple
did not undergo additional prenatal genetic testing. His wife
continued to take aspirin alone and gave birth to a girl of 3,032 g
at 37 weeks. Conclusion The diverse clinical presentations of 47,
XYY syndrome and controversial academic findings on infertility in people with this syndrome made the counseling difficult.
Accurate diagnosis of this constitutional karyotype is a valuable
aid in counseling.

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The Effects of Five year Hormone Therapy, Alendronate,
Tibolone, and Raloxifene on Bone Mineral Density in Postmenopausal Women （ Second Study ） Hoe-Saeng Yang,
Mi-Woon Kim Dongguk University of Korea, Korea
Objective To evaluate the effects of ten year hormone therapy,
tibolone, alendronate and raloxifene on bone mineral density（BMD）in postmenopausal women. Methods We studied 348
postmenopausal women who had visited the menopausal clinicof Dongguk university hospital between January 2001 and December 2010. These patients were divided into estrogen therapy!

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that（89%）in women without it（p＜0.01）. Pregnancy rate（98%）
and live birth rate（94%）in women with PS deficiency was
higher than those（86%, 76%）in women without it（p＜0.01）. Livebirth rate（58%）in women with high NK cell activity was lower
than that（86%）in women without it（p＜0.01）. Conclusion Pregnancy rate in women with uterine abnormality was low, while
pregnancy rate and live birth rate in women with PS deficiency
was high. Live birth rate in women with high NK cell activity
was found to be low. These results provide useful information
for clinical practitioners. Alternative therapy such as immunoglobulin might improve the pregnancy outcome of patient with
NK.

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（ET）
（n=51）, estrogen progesterone therapy（EPT）（n=84）, tibolone（n=70）, alendronate（n=82）and raloxifene（n=61）groups.
The mean patients age, height, weight and body mass index
were 55.28+3.34（range of 45 67）years, 157+5cm, 60.12+7.22kg
and 24.18+6.37, respectively. We evaluated BMD by measuring
lumbar spines（L1 4）and femoral neck at baseline, 1, 2, 3, 4 and5 years after treatment. Results The BMD of the femoral neckincreased significantly in the alendronate group by 6.6, 7.4, 7.9,
8.3 and 8.5% at 1, 2, 3, 4, and 5 years after treatment initiation, respectively. It increased in the EPT group by 3.4 and 2.5% at 1
and 2 years after, respectively. It increased in the tibolone group
by 2.2 and 2.7% at 1 and 2 years after, respectively. It increasedby 2.1% in the raloxifene group at 2 years after. The BMD of thelumbar spine increased significantly in the alendronate groupby 3.4, 5.7, 5.3, 5.3 and 4.7% at 1, 2, 3, 4, and 5 years after treatment initiation, respectively. It increased by 1.2% in the EPT
group at 1 year after. It increased by 1.4% in the raloxifene
group at 1 year after. Conclusion Thus, these findings suggestthat alendronate is most effective in improving the BMD levels.
In postmenopausal women, any treatment with hormone therapy, alendronate, tibolone or raloxifene increases bone mineraldensity in the femoral neck and lumbar spines.

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apy, salpingo oophorectomy or ovarian cystectomy is commonly performed, but ovarian surgery results in a decreased
ovarian reserve. Beneficial effects of the ovary to prevent osteopenia are known but the relation with remaining ovaries andrisk of osteopenia remains unclear. Methods Under the approvalof IRB and patientʼs consent, patients in their 40s attending ourdepartment with present or history of endometrioma were retrospectively reviewed. Demographic data and blood samplingtests were recorded, and the relation with bone mineral density（BMD）was analyzed. Results In this study, 173 patients aged
40 53 were enrolled and 137 had a history of ovarian surgery.
Among them, 6 patients（3.5%）had Young Adult Mean（YAM）
levels lower than 80%, and 78 patients with 2 remaining ovaries
and 54 patients with 1 remaining ovary were selected in thisstudy. Although BMD between 2 groups showed no significant
difference, the former exhibited higher levels of AMH, E2 and
FSH, and decreased level of TRACP 5b and BAP. Conclusion
Our results indicate that preserving both ovaries leads to higher
ovarian reserve, thus it could result in lowering the risks of osteoporosis in the future, and changes over the years should be
required.

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Polysaccharide isolated from Hyuganatsu orange that suppressed rat osteoclast formation should be an arabinogalactan Masatoshi Yamaguchi, Hiroko Hata, Hiroshi Sameshima University of Miyazaki HospitalObjective Recently, we reported polysaccharide derived from
Hyuganatsu orange containing drink suppressed TRACP5blevel of postmenopausal women. In this study, we sought to findan information of characteristics of polysaccharide. Methods 1）
In HPTLC analysis, a few possible peak were identified in highmolecular weight area. We collected each peak. Collected suppression activity for rat osteoclast formation was measured ineach fraction. 2）Optical density of IR and UV area were measured with spectrophotometer. 3）Nuclear resonance spectrum
was analyzed 4）Sugar structure was analyzed with methylation
analysis method. Results 1）Suppression activity of osteoclast
formation was identified in single peak. Therefore, this peak
was analyzed. 2）There was no peak in UV spectrophotometry,suggesting this peak did not contains polyphenol. IR spectrophotometry indicated this peak contains polysaccharide. 3）NMR
spectrum suggested polysaccharide. 4）With methylation analysis, 6 type of methylated sugar（1,3,5 tri O acetyl 2,4,6 tri O
methlhexitol, 1,3,4 tri O acetyl 2,5 di O methylpentitol, 1,4,5
tri O acetyl 2,3, di O methylpentiol, 2,3,6 tri O methyl D
galactopyranose, 2,3,6 tri O methyl D galactopyyranose and1,3,4,6 tetra O acetyl 2,4 di O methyhexitol）were identified.
methylation analysis suggested that ＞ 3 Gal（1 ＞chain ismain structure. And ＞3）Ara（ 1 ＞ or ＞5）Ara 1 ＞ side
chain is divided from 6 position. Therefore, we concluded that
this polysaccharide is arabinogalactan. Conclusion Polysaccharide isolated from Hyuganatsu orange that suppressed rat osteoclast formation should be an arabinogalactan.

A study to evaluate the impact of surgical menopause on bonemetabolism in women below 50 years of age Kanae Matsuno,
Kazu Ueda, Chihiro Goto, Yoko Nagayoshi, Ayako Kawabata,
Asuka Morikawa, Kazuaki Takahashi, Satoshi Yanagida,
Nozomu Yanaihara, Kyosuke Yamada, Naoki Kamiya, Aikou
Okamoto The Jikei University HospitalObjective Oophorectomy is often required for premenopausal
women to treat gynecological cancer. Increased bone resorption
is an adverse sequela that increases the patientʼs risk for fracture. In this study, we assessed the risk of acquiring osteopenia
or osteoporosis after surgical menopause in 27 women who had
oophorectomies performed at our hospital. Methods We measured bone mineral density（BMD）and bone metabolic markers（BAP, TRACP 5b）in 27 women treated for gynecologic cancer
by oophorectomy in the last decade. For 8 patients who we identified to have osteopenia, we received informed consent, begantreatment, and followed their response. Results The median investigation period was 17 months（range：2 115 month）and the
median age at the time of operation was 39 years（range：28 47
years）.We identified 8 patients（30%）to have osteopenia and 1（3%）to have osteoporosis by BMD. There was a significant increase in the median time since oophorectomy between patientswith a disorder of bone metabolism and those without, 54
months and 12 months respectively（p =.0445）. There was atrend for TRACP 5b levels to increase with time. BMD levels
increased and TRACP 5b levels decreased in all 8 cases of osteopenia after treatment with a bone resorption inhibitor. Conclusion Our data suggests the risk of developing a disorder ofbone metabolism increases over time in patients with surgicalmenopause. Additionally, early administration of a bone resorption inhibitor may partially restore normal BMD and bonemarkers in high risk osteopenic patients.

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The relation of remaining ovaries and risk of osteopenia：aretrospective study in patients with ovarian endometrioma
Nana Akino, Osamu Hiraike, Hiromi Terao, Harunori Honjoh,
Mana Hirano, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota,
Kaori Koga, Tomoyuki Fujii, Yutaka Osuga The University ofTokyo
Objective Endometriosis is a common disease in reproductive
aged female. Treatment of ovarian endometrioma can be a matter of concern since concomitant with ovarian suppression ther-

Investigation of long term use of bisphosphonate Emi
Motegi, Yoshiko Mochizuki, Wakana Soeda, Ichio Fukasawa
Dokkyo Medical University
Objective Bisphosphonates are drugs for osteoporosis with highfracture prevention effect and widely used. But bisphosphonates have adverse effects of osteonecrosis of the jaw（ONJ）
and atypical femoral fractures（AFF）. Therefore, recently it has
been proposed to consider the setting of the optimum use period
and the drug holiday period. However, in the treatment of osteo-! !! ! ! !!
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Undernourishment in utero programs CIDEA ＆ CIDEC
genes expression and deteriorates hepatic stetatosis：Role ofendoplasmic reticulum （ ER ） stress Jeenat Urmi, Keiko
Muramatsu, Yukiko Kohmura, Hiroaki Itoh, Naohiro Kanayama
Hamamatsu University School of Medicine
Objective Undernourishment in utero deteriorates hepatosteatosis（HS）in later life. Cell Death Inducing DFFA Like Effector A and C（CIDEA and CIDEC）are present in the membraneof endoplasmic reticulum（ER）and enhance lipid droplet（LD）
growth deteriorating HS. We investigated the effect of undernourishment in utero on hepatic LD size, and the gene expression of CIDEA/C genes by using mice animal model. Methods
Sampling of blood and liver of CN57Bl mice（n=16）aged 22
weeks, pups（NN；n=8）
obtained from dams with ad libitum andpups（UN；n=8）from dams with 40% caloric restriction. Pups
were fed high fat diet throughout 17 to 22weeks with vehicle（Veh）or Tauroursodeoxycholic acid（TUDCA, ER stress alleviator）.Oil Red O staining was used to assess diameter（μm）andarea（μm 2）of the hepatic LD and mRNA was used for micro array and quantitative PCR. Results UN in utero enlarged LD
area by 2.5 fold（p＜0.01）compared to NN concomitant with theupregulation of 38 genes（NN vs UN；Fold change ＞2 or＜ 2,
p＜0.05）. CIDEA/C genes were highly expressed（Fold change
11.5 ＆ 5.6, p＜0.001, respectively）confirmed by quantitative
PCR. ER stress alleviation, by TUDCA administration not only
reduced expression of these genes but also reduced the size ofLD significantly. Conclusion We propose that UN in utero programs hepatic ER stress integration in later life and deteriorates hepatosteatosis（HS）by activation of CIDEA and CIDEC
genes expression.

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ticipated in a cohort study（n=1,336, normal glucose tolerance（NGT）；n=1,685, PD；n=252, T2D）. Among them, 1,033 subjects visited the three year follow up. Each of the 75 metabolites profiled on fasting plasma samples using capillary electrophoresis mass spectrometry was assessed for associations withdiabetic status cross sectionally, and the impact of metabolite
concentrations on PD development was assessed using logistic
regression analyses. This study was approved by the ethics
committee of our institute and written informed consent was obtained from each subject. Results A total of 23 plasma metabolites were significantly increased in PD compared with NGT after adjustment for confounders. They included branched chainamino acids（BCAAs）：valine（200.4μM, 205.2μM, p＜0.01）,isoleucine（50.8μM, 52.7μM, p＜0.01）,leucine（102.7μM, 105.6μM, p＜0.01）；and aromatic amino acids（AAAs）：tyrosine（59.4μM,
60.8μM, p＜0.01）,phenylalanine（51.6μM, 52.7μM, p＜0.01）.Concentrations of these metabolites were further increased in T2D
subjects. Logistic analyses revealed insignificant associations
with the prediction of PD. Conclusion Metabolites such as
BCAAs and AAAs are altered in individuals with PD/T2D
among postmenopausal women in Japan.

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ISP-25-8
The risk of dyslipidemia after a cystectomy or oophorectomy
in endometriosis Mana Hirano, Osamu Hiraike, Nana Akino,
Hiromi Terao, Harunori Honjoh, Michihiro Tanikawa, Miyuki
Harada, Tetsuya Hirata, Yasushi Hirota, Kaori Koga, Tomoyuki
Fujii, Yutaka Osuga The University of Tokyo HospitalObjective Endometriosis causes heavy burden for women, and
10 30% of reproductive aged women suffer from endometriosis.
The treatment of ovarian endometrioma consists of surgery
and/or hormonal therapy and it often results in a decreased
ovarian reserve. Herein we evaluate the risk of dyslipidemia of
patients with history of ovarian cystectomy and/or oophorectomy in endometriosis. Methods After IRBʼs approval and informed consents of patients, we reviewed outpatients at over 40
years old with a history of endometriosis without familial history of dyslipidemia. We examined BMI, blood tests（TC, TG,
LDL）, and CAVI（cardio ankle vascular index）.Results In thisstudy, 173 patients aged 40 53 were enrolled. These patients
had a history of ovarian surgery, and these participants withdata of CAVI were finally selected. Thus we reviewed 91 patients, and 52 patients possess 2 ovaries and 39 patients possess
1 ovary. Although average BMI of 2 groups were comparable,
patients with two ovaries showed the lower level of CAVI, TC,
LDL, TG than with 1 ovary. In particular, the value of TC（195±33 vs 220±35 mg/dL, p=0.001）and LDL（115±25 vs 132±36
mg/dL, p=0.016）were significantly lower. Conclusion Remaining 2 ovaries at surgery is effective in improving lipid metabolism, and it may have beneficial effects to prevent future arteriosclerosis.

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ISP-26-1

Metabolomic profiling of prediabetes and diabetes among
Japanese postmenopausal women Miho Iida1, Toru Takebayashi2,
Haruko Kunitomi1, Yusuke Matoba1, Keiko Watanabe1, Hayato
Iseki1, Asako Sera1, Yusuke Kobayashi1, Eiichiro Tominaga1,
Kouji Banno1, Mamoru Tanaka1, Daisuke Aoki1 Keio University 1,
Department of Preventive Medicine and Public Health, Keio
University 2
Objective Prediabetes（PD）is the precursor condition of type2 diabetes（T2D）,and early identification contributes to the prevention of further diseases. In this study, we performed metabolomics profiling in Japanese postmenopausal women to
identify key plasma compounds associated with PD. Methods
Subjects were 3,273 naturally postmenopausal women who par-Abdominal palpation with Ou MC manipulation for womenwith acute abdomen Ming Cheh Ou1,2, Dennis Ou3, Chung Chu
Pang4 Taipei City Hospital, Taiwan 1, Taipei Medical University,
Taiwan 2, Oxford University, Taiwan 3, Su Women Hospital, Taiwan 4
Objective Abdominal palpation with Ou MC manipulation（APOM；AJEM, 2012）has showed to be more sensitive than bimanual pelvic examination for the diagnosis of pelvic inflammatory disease in women with acute abdomen. This study demonstrated APOM with Ou MC decrescendo phenomenon（OuDP；
Cancer Res, 2016）for diagnostic reliability for women withacute abdomen causing muscle guarding or diffuse pain. Methods 113 women with acute abdomen attending an emergency

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porosis, there is no clear criteria to stop the drug. We investigated retrospectively for osteoporotic patients using long termbisphosphonates. Methods We investigated retrospectively thechanges in bone mineral density（BMD）, fluctuation of boneturnover markers, and side effects about the patients usingbisphosphonates for over 5 years. Results There were 20 casesof bisphosphonates taken over 5 years, 11.3% of patients treatedwith osteoporosis. Their average age was 68.4 years old, the average use period was 9.6 years. One case showed a history of
fracture at the beginning of therapy. There were no cases of
new fractures, ONJ and AFF during the management period.
The mean lumbar spine BMD increase rate for 5 years after taking the bisphosphonates was 5.8%. In the latest BMD there were
15 patients with T score＜ 2.5. Bone resorption markers remained within the normal range in long term users. Conclusion
The majority of patients using bisphosphonates for a long time
had significantly reduced BMD. It is necessary to determine thedrug holiday, or the continuation by reference to the value ofbone turnover markers and FRAX in patients with osteopenia.

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department received AP and APOM. Of the 113 women, 91 hadpelvic organ disease, whereas 21 had nonpelvic organ disease
and 1 had pelvic and nonpelvic organ disease concurrently. Results Excluding the case with concurrent pelvic and nonpelvic
organ disease, the sensitivity of APOM for the diagnosis of pelvic organ disease was significantly greater than that of AP（P=.003）. APOM also showed greater specificity of excluding pelvic organ disease than did AP（P=.003）. APOM with OuDP performed for 37.2% of patients with muscle guarding or diffuse
pain demonstrated diseased organ location compatible with final diagnosis showed. Conclusion The delimitation by APOM asa separation zone may allow positional recognition of the tenderness with decreased overlap of signs. In cases with muscle
guarding or diffuse pain, APOM effectively located tenderness
with OuDP induced with contralateral hand of the examiner bypressing the hand in a chopping gesture along a line from thesubumbilicus to the femoral arterial canal of the inguinal area to
induce a zone of alleviated pain under the hand.

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ISP-26-2
Inhibitory Effects of Lactobacillus Culture Supernatants on
Candida albicans Yuko Matsuda1, Daiki Ogishima1, Satoru
Takeda2 Juntendo University Nerima Hospital 1, Juntendo University 2
Objective Vulvovaginal candidiasis（VVC）is an infection of thevaginal mucous membrane caused by Candida albicans . C. albicans exists as a yeast and/or in hyphal form, and forms a
biofilm on the vaginal mucosa. The healthy vaginal microbiome
comprises predominantly Lactobacillus , the presence of which
inhibits pathogen invasion. In this study, we assessed themechanisms underlying the inhibitory effects of Lactobacillus
culture supernatants on C. albicans budded to hyphal form
transition（BHT）,biofilm formation, and adhesion to HeLa cells.
Methods C. albicans cells were cultured with L. gasseri or L.
crispatus supernatants under BHT and biofilm formation inducing conditions. Inhibitory effects on biofilm formation were
determined by 2,3 bis（2 methoxy 4 nitro 5 sulfophenyl）5［（phenyl amino）carbonyl］2H tetrazolium hydroxide（XTT）
reduction assay. The expression levels of BHT and biofilm formation associated genes were determined by RT qPCR. Inhibition of C. albicans adhesion to HeLa cells by the supernatants
was evaluated by enumerating viable C. albicans cells. Results
Lactobacillus supernatants inhibited C. albicans hyphae andbiofilm formation. The expression of BHT and biofilm formation associated genes was downregulated, and C. albicans adhesion to HeLa cells was inhibited, in the presence of Lactobacillus
supernatants. Conclusion Culture supernatants of L. gasseriand L. crispatus , commonly found in the vaginas of healthy
Japanese women, inhibit C. albicans biofilm formation by downregulating biofilm formation related genes and C. albicans adhesion to HeLa cells. These findings support the notion that Lactobacillus metabolites may be useful alternatives to antifungal
drugs for the management of VVC.

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of Invasive Candidiasis 2013, four days of Fosfluconazole 400
mg/day were administered intravenously, followed by 14 daysof Micafungin 50mg/day intravenously. Five months later, sheconceived again with IUI. The culture of the vaginal discharge
was performed at 7 weeks of pregnancy, followed by once amonth of the culture. Candida species were not detected in all
the examinations. A uterine cervical polyp causing bleeding
was resected on 26 weeks of pregnancy. No other abnormal episodes were observed during pregnancy. Under epidural anesthesia, she delivered a female baby by vacuum extraction because of non reassuring fetal status on 39 weeks 1 days of pregnancy. The birth weight was 2,504g and Apgar score was 9（1min）and 10（5 min）. Both the mother and the newborn were
healthy and discharged from our hospital five days after the delivery. It should be thought that the treatment for Candida
glabrata with Fosfluconazole and Micafungin was effective
even after a serious infectious abortion and maternal fungemia.

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Successful treatment of Candida glabrata after infectious
abortion and maternal fungemia resulting in the next normal
pregnancy Megumi Oh, Takahiro Yamashita, Haruka Mitsui,
Eiji Shuri, Nobuko Akamata, Nagisa Yasumizu, Shinichiro
Yabe, Yukiko Kawana, Yoshiharu Takeda, Tomoko Adachi,
Takashi Okai, Masao Nakabayashi Aiiku Hospital
The case was 37 years old, G0P0. She conceived with intrauterine insemination（IUI）, but the pregnancy ended in infectious
abortion in 19 weeks gestation. Candida glabrata was detectedon the surface of the placenta and in her blood. Following the
JSMM Clinical Practice Guidelines for Diagnosis and Treatment

Abdominal tuberculosis a major cause of infertility in developing countries Sanjay Chaube, Mahendra Bhusari, Jyoti
Chaube St. Judeʼs Hospital, India
Infertility a major social and psychological problem for women.
Tuberculodis is a major health problem in developing countries
due to poor socioechonomic status. The scenario of root cause isvariable. A study of 128 patients of infertility over a period ofseven years revealed pelvic tuberculosis leading to tubal block amajor cause of infertility in the patiets in developing country.

ISP-26-5
A case report of pelvic inflammatory disease due to Streptococcus pneumoniae Miho Ando, Tatsuya Fukami, Sakiko
Matsuoka, Sumie Nakamura, Takahiro Koyanagi, Yoko To,
Maki Goto, Haruhiko Kondo, Hiroshi Tsujioka, Fuyuki Eguchi
Aso Iizuka Hospital
Streptococcus pneumoniae is one of the normal bacterial florasof the upper respiratory tract. Peritonitis occurred by streptococcus pneumoniae is uncommon disease defined as the infection in the abdominal cavity despite the absence of an obvious
source of infection. The occurrence of it in young healthy
women is very rare. It occurs mostly in patients with portal hypertension such as liver cirrhosis and those with nephrotic syndrome and HIV infection. We experienced a case of 48 year old
woman with Tubo Ovarian abscess. Although she had no particular history but hypertension and hyperlipidemia, it proved
to be caused by streptococcus pneumonia. The specimen was
cultured inside blood, which means it was an invasive pneumococcal disease（IPD）so we made a report to the local health center. We started treating with a broad antibacterial drugs andthe inflammatory reaction improved in two weeks of hospitalization. Peritonitis and pelvic inflammatory disease in adults arerare phenotype of symptoms for streptococcus pneumoniae related disease. Streptococcus pneumoniae represents a common
pathogen associated with high morbidity and mortality aroundthe world. There are only few studies about this infection and it
is poorly understood. We suggest that everyone should take into
consideration of pelvic inflammatory disease caused by streptococcus pneumonia when we perform medical examinations. We
will show the case with the review of the literature.

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Human CD134（OX40）expressed on T cells plays a key rolefor human herpesvirus 6B replication after umbilical cord
blood transplantation Satoshi Nagamata1, Yasuko Mori2, Hideto
Yamada1 Kobe University 1, Division of Clinical Virology, Kobe
University Graduate School of Medicine 2

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Diagnosis and treatment of the adnexal actinomycosis mimicking an advanced epithelial ovarian cancer Seok-Mo Kim,
U Chul Ju, Woo Dae Kang Chonnam National University, Korea
Objectives Adnexal actinomycosis can mimic advanced epithelial ovarian cancer（EOC）. Although histopathologic confirmation is required for diagnosis, it is often impossible. Methods
Among 79 cases suspected to actinomyosis more than EOC inpelvis MRI, 35 cases without histopathologic confirmation were
included in this study. We compared those to 108 cases of stage
II/III EOC. Patients with actinomycosis were treated with antibiotics for 6 months or more and took imaging every 3 months.
Results The median age of patients with actinomycosis was 48
years（range, 27 68）and 74.3% were premenopausal. 91.4% had
a history of intrauterine device（IUD）during a mean of 8.7 years（range, 3 20）. The mean serum WBC, CRP, and CA 125 level
were 14,330/mm2（range, 4,100 30,100）,9.7 mg/dL（range, 0 27）,
and 38.0 U/mL（range, 7 135）, respectively. In MRI, the mean
size of adnexal masses was 6.8 cm（range, 4 12）and all had noor small amount of ascites. Lymph node enlargement（＞ 0.5cm）
and hydronephrosis were presented in 48.6% and 57.1%, respectively. After 6 months, 77.1% showed complete remission andthe remaining also showed 3 to 4cm mass. Multivariate analysis
revealed that IUD history（OR=15.055；95% CI, 4.690 48.330；p＜0.001）, WBC＞10,800/mm2（6.566；2.774 15.539；p＜0.001）,
CA 125＜ 105 U/mL（19.171；7.535 83.182；p＜0.001）,size＜10cm（7.867；1.080 57.294；p＜0.001）,presence of hydronephrosis（5.182；1.807 14.861；p=0.008）, and no or small amount of ascites（7.135；1.681 30.291；p=0.002）were predictive factors ofadnexal actinomycosis compared to EOC. Conclusion If patientswith adnexal actinomycosis mimicking EOC in MRI have IUD
history, serum WBC beyond normal range, serum CA 125
within 3 times normal range, mass＜10 cm, hydronephrosis, andno or small amount of ascites, antibiotics can be a proper treatment without surgical intervention.

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ISP-27-1

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Systemic and local status of myeloid derived suppressor cells（MDSC）in endometriosis patients Erina Satake, Kaori Koga,

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ISP-26-7!

Arisa Takeuchi, Tomoko Makabe, Ayumi Taguchi, Gentaro
Izumi, Masashi Takamura, Yutaka Osuga, Tomoyuki Fujii The
University of Tokyo
Objective Myeloid derived suppressor cells（MDSC）are recently identified heterogeneous population of immature myeloid
cells. They suppress both innate and adaptive immunity,
thereby enhance various pathological settings such as inflammation and cancer. The main subsets of MDSC are mononuclear MDSC（M MDSC）and polymorphonuclear MDSC（PMNMDSC）. In endometriosis, it has been previously shown that the
depletion of PMN MDSC in the mouse model reduced the number of lesions；however, the status of MDSC in endometriosis
patients is not known. To determine the systemic and local
status of MDSC in endometriosis patients, we conducted following studies. Methods Under IRB approval and informed consents, peripheral blood mononuclear cells（PBMC）and peritoneal fluid MC（PFMC）were collected from the control（n=13）
and endometriosis patients（n=13）, and the numbers of M
MDSC（CD33+, HLA DR!/low, CD14+, CD15!）and PMN MDSC（CD33+, HLA DR!/low, CD14!, CD15+）were counted by flow cytometry. The percentages of M MDSC, PMN MDSC and total MDSC
were compared between the groups. Results In PBMC, percentages of PMN MDSC and total MDSC were significantly higher
in endometriosis group（3.0% vs 7.9%, 9.9% vs 15.4%, the control
vs endometriosis group, PMN MDSC, total MDSC, respectively,
p＜0.05）, while the percentage of M MDSC was not different between groups（7.0% vs 7.5%）. In PFMC, the percentages of neither M MDSC nor PMN MDSC were different between groups.
Conclusion Our study found that MDSC, especially PMN
MDSC were enhanced systemically in endometriosis patients.
Together with our previous findings, PMN MDSC may contribute to the pathogenesis of endometriosis, although further studies are warranted.

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ISP-27-2!

SR 16234, a novel selective estrogen receptor modulator, forpain symptoms with endometriosis：an open label clinical
trial Tasuku Harada1, Ikuko Ota2, Fuminori Taniguchi1 Tottori
University 1, Kurashiki Heisei Hospital 2
Objective SR 16234 is a selective estrogen receptor modulator（SERM）structurally different from approved SERM and has reported to have estrogen receptor（ER）α antagonistic activity
and strong affinity with a weak partial agonistic activity to ERβ.
SR 16234 showed strong inhibitory effects on transplanted endometrial cysts in endometriosis model of rat and mouse. In thisclinical trial, efficacy and safety of SR 16234 have been evaluated in endometriosis patients. Methods This trial was an open
label single arm clinical trial. Ten patients with dysmenorrhea
and pelvic pain associated with endometriosis and adenomyosis
were enrolled in this trial with written informed consent, andreceived 40 mg of SR 16234 once a daily for 12 weeks. The primary endpoint was the visual analogue scale（VAS）of pelvic
pain. The secondary endpoints included dysmenorrhea score,
pelvic pain score, objective observations（stiffness of Douglas
pouch, limitation of uterine movement, size of ovarian chocolate
cysts, thickness of endometrium, and serum CA125 concentration）and safety. Results After oral administration of SR 16234
40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas pouch, limitation of uterine movement comparing with the baseline values. Conclusion
The present trial suggested that a selective estrogen receptor
modulator could be used for treatment of pain associated withendometriosis for the first time.

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Objective CD134（OX40）, which is a cellular receptor for humanherpesvirus 6B（HHV 6B）and expresses on activated T cells,
may play a key role for HHV 6B replication after allogeneic hematopoietic stem cell transplantation（allo HSCT）.Several studies have shown that umbilical cord blood transplantation（UCBT）is a strong risk factor for HHV 6B reactivation and encephalitis. Methods We measured the percentage of CD134
positive cells within T cells and viral copy number of HHV 6B
after allo HSCT, including UCBT. The correlation between CD
134 and HHV 6B viral load was then statistically analyzed. Results Twenty three patients after allo HSCT were enrolled.
HHV 6B reactivation occurred in 11 of 23 patients（47.8%）. CD
134 expression was seen on T cells and was coincident with thetime of peak viral load. The percentage of CD134 positive cells
decreased significantly when HHV 6B DNA disappeared（p=. In the patients af0.005 in CD4+ T cells, p=0.02 in CD8+ T cells）
ter UCBT, the HHV 6B viral load varied with the percentage ofCD134 positive cells. In the comparison between the HHV 6B
reactivation group and non reactivation group, maximum percentages of CD134 positive cells among CD4+ T cells in reactivation group were significantly higher than those in non reactivation group（p=0.04）. Conclusion This is the first study to showthat a correlation of CD134 expression on T cells with HHV 6B
replication after allo HSCT. The results possibly indicate that
CD134 on T cells plays a key role for HHV 6B replication after
allo HSCT, especially in UCBT.

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Expression pattern of membrane proteins in endometrial
stromal cells from women with endometriosis SayaYamashita1, Kae Hashimoto1, Akihiko Yoshimura1, Ikuko
Sawada2, Yuri Matsumoto1, Michiko Kodama1, Seiji Mabuchi1,
Kenjiro Sawada1, Tadashi Kimura1 Osaka University 1, Itami City
Hospital 2
Objective Endometriosis affects women during their reproductive years, and can impact all aspects of their lives. The transplantation of an endometrial fragment during menstruation toectopic sites is probably the most widely accepted mechanism
for endometriosis. However, how endometrial cells, although
they are not cancer cells, can adhere to the peritoneal surface
and invade the underlying tissues is not fully understood. In thecurrent study, we have focused on the membrane proteins of endometrial stromal cells and investigated their role in the pathogenesis of endometriosis. Methods The eutopic endometrial
stromal cells were collected from patients undergoing hysterectomy for endometriosis and for other benign reasons. The expression patterns of membrane proteins were compared, using
iTRAQ. We identified the protein whose expression was higher
in the eutopic endometrium of women with endometriosis thanthose without endometriosis. We also performed protein analysis by immunohistochemistry and western blotting. Results By
iTRAQ comparison, the eutopic endometrium from patientswith endometriosis showed stronger expression of several molecules including galectin 3. Immunohistochemical analysis revealed immunoreactive score according to Remmele was 6.4±
1.6 and 2.6±1.4 respectively. Western blotting also showed a significantly higher expression of galectin 3 in the cells from endometriosis patients. Conclusion Expression of galectin 3 increased significantly in the eutopic endometrium of womenwith endometriosis. We are trying to demonstrate the functionof galectin 3 to the endometrial stromal cell adhesion, as well as
migration and proliferation.

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ISP-27-4!

CXCL12 CXCR4 axis is enhanced in endometriosis via
prostaglandin E2（PGE2） Tomoko Makabe, Kaori Koga, Erina
Satake, Arisa Takeuchi, Ayumi Taguchi, Fusako Sue, Mariko
Miyashita, Gentaro Izumi, Masashi Takamura, Yutaka Osuga,
Tomoyuki Fujii The University of Tokyo
Objective Chemokine CXCL12 and its receptor CXCR4 are
known to play a role in cancer progression, both by activating
cancer cells and inducing immunosuppressive cells. We hypothesized that CXCL12 CXCR4 axis is also enhanced in endometriosis, and prostaglandin E2（PGE2）is involved in the enhancement. Methods Under informed consents, peritoneal fluids（PF）were collected from the control and endometriosis patients. 1）Concentrations of CXCL12 in PF were measured using
ELISA（18 control, 31 endometriosis）. 2）Peritoneal macrophages（PM）were isolated using CD14 MACS selection. mRNA was extracted and expressions of CXCR4 and PGE2 receptors（EP2,
EP4）were measured using qRT PCR（11 control, 6 endometriosis）.3）PM were stimulated with PGE2（100 nM）in the absenceor presence of EP2 antagonist（PF 04418948, 100 nM）or EP4 antagonist（CL 042794, 100 nM）for 24h, and CXCR4 mRNA expression was measured. Results 1）Concentration of CXCL12 in PF
was significantly higher in endometriosis（p＜0.05）. 2）mRNA
expressions of CXCR4 and EP2 in PM ware significantly higher
in endometriosis（p＜0.05）, whereas mRNA expression of EP4
was slightly but not significantly higher in endometriosis. 3）
PGE2 significantly increased CXCR4 mRNA expression in PM（15.0±3.0 fold, p＜0.01）. Both EP2 and EP4 antagonist decreased
PGE2 induced CXCR4 expression to 87.7±15.4%（p＜0.05）and
65.2±15.3%（p＜0.01）, respectively. Conclusion CXCL12 CXCR4

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axis is enhanced in the peritoneal cavity of endometriosis, andPGE2 seems to be involved in this enhancement. Therefore, PGE2
can be therapeutic targets for endometriosis.

ISP-27-5!

Bradykinin system is involved in endometriosis related pain
through endothelin 1 production Osamu Yoshino1, Mutsumi
Kobayashi1, Yosuke Ono1, Akihisa Nakashima1, Akiko
UniversityofHasegawa2, Yutaka Osuga2, Shigeru Saito1
Toyama 1, The University of Tokyo 2
Objective The mechanism of pain production in endometriosis
remains unknown. Bradykinin（BK）,one of the most algogenic
substances, is also known as an inflammatory mediator. In thepresent study, we evaluated whether BK is involved in endometriosis related pain. Methods Endometriotic lesions wereused for immunohistochemistoy. Primary cultures of endometriotic stromal cells（ESC）were stimulated with IL 1β and/or BK.
Quantitative PCR was used to evaluate the mRNA expressionsof BK receptors（BKR）and endothelin 1, which causes neuropathic pain. The concentration of endothelin 1 in cystic fluid ofendometrioma or non endometrioma was measured with
ELISA. The conditioned medium of ESC stimulated with IL 1β
and/or BK was injected intraplantarly in mice, and evaluatedwhether pain related licking behavior was elicited. Results The
expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showedthat IL 1β induced 4±0.2 fold increase of BKR mRNA on ESC（P＜0.01）. Activation of these receptors by BK significantly induced endothelin 1 expression in ESC, which was negated completely by HOE 140, a BKR antagonist. The cystic fluid of endometrioma contained higher amount of endothelin 1（median
22 pg/ml, range 0 324 pg/ml）compared to non endometrioma（0 pg/ml, range 0 10 pg/ml）significantly（P＜0.01）. Intraplantar
injection of the conditioned medium of ESC treated with IL 1β
and BK significantly induced licking behavior, which was suppressed with BQ 123, an endothelin receptor antagonist. Conclusion The present study demonstrated the presence and thefunction of the BK axis in endometriosis, and established potential new therapy targets for endometriosis related pain.

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Dienogest improves decreased chemotaxis of peritoneal natural killer cells from women with endometriosis Chiaki
Izumiya1, Shimpei Yamamoto1, Takashi Ushiwaka1, Tamami
Tsuzuki1, Kayo Taniguchi1, Masanori Nakakuki2, Nagamasa
Maeda1 Kochi Medical School 1, MOCHIDA PHARMACEUTICAL CO., LTD. 2
Objective The immunologic suppression is considered as one ofthe pathogenesis of endometriosis. We have been investigatedthe behavior of peritoneal natural killer（NK）cells from womenwith endometriosis by time lapse imaging system. According to
the previous investigation, in women with endometriosis, peritoneal NK cells function was decreased compared to without endometriosis. In this paper, we investigated the immunologicaleffects of Dienogest（DNG）, an oral anti endometriosis progestin, on chemotaxis of peritoneal NK cells in women with endometriosis. Methods The effects of DNG on PF cells fromwomen with endometriosis were compared to without endometriosis（control）. We investigated cell movement speed andalso pseudo pod formation of peritoneal NK cells by time lapse
imaging under microscope incubator. The cell movement
speeds were measured twice before and after administration of
DNG（10!7 mol/L）. Results The cell movement speed and frequency of pseudo pod formation of NK cells from women withendometriosis was significantly decreased compared to control.
There was significantly positive correlation between cell move-

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Epidemiology and Recent Treatment of Leiomyomas in Korean Women Hyejin Hwang1, Minkyung Lee1, Hyunkyung Kim1,
Younjee Chung1, Soohyun Sim1, Youngsin Han1, Kyunghee
Chae2, Mira Kim2, Sukil Kim2, Meeran Kim1 The Catholic University of Korea, Korea 1, Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Korea 2
Objective The purpose of this study is to investigate epidemiology of uterine leiomyoma in general population. Methods Korean National Health Insurance Service（KNHIS）sample cohort
dataset which were collected during 2002 2013. Patients withuterine leiomyoma were identified by ICD 10 and intervention
codes for the Korean health insurance. Results A total of 50,884
women aged 15 54 were selected from the KNHIS cohort database, which included approximately 1 million individuals. The
incidence had increased all over the age. The age group 45 49
showed highest incidence for the years. In 2012, the incidence ofage group 45 49 was 2.97%. The total number of surgical treatment and intervention was increased from 561 in 2002 to 1,137 in
2011. The treatment percentage of all diagnosed patient was decreased（28.51% in 2002 to 13.81% in 2013）. Only the treatment
percentage of 20 24 age group was increased（5.00% in 2002 to
7.10% in 2013）.Of all treatment, the proportion of myomectomy
was increased 2.22 fold（22% in 2002 to 49% in 2013）while theproportion of hysterectomy was decreased 0.57 fold（78% in 2002
to 45% in 2013）constantly. Conclusion This study showed a significant trend towards an increase in diagnosis for uterine leiomyoma in Korean women with time. Particularly, we found thatthe trend of surgical treatment moved to fertility preservation
among Korean women. This study has meaningful in regard ofgeneral population based epidemiology study in asian women.

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Disturbed WNT/β catenin Signaling under Serum Starvationand Hypoxia Induces Adipocytic Transdifferentiation in Human Uterine Leiomyoma Cells Hiroshi Harada, Taeko Ueda,
Tomoko Kurita, Seiji Kagami, Toshinori Kawagoe, Yusuke
Matsuura, Toru Hachisuga University of Occupational and Environmental HealthObjective Fatty metamorphosis is known as an uncommon alteration in uterine leiomyoma（i.e. lipoleiomyoma）, the pathogenetic mechanisms underlying this phenomenon remain poorly
understood. Because a conditional deletion of β catenin, a majortransducer of the canonical Wingless/integrated（WNT）pathway, in the developing mouse uterus can induce adipogenesis in
the myometrium, it is hypothesized that disrupted WNT/β catenin signaling may be also involved in the development of fat
cells within uterine leiomyoma. Our goal was to induce the adipocytic transdifferentiation in human leiomyoma cells by the inhibition of the WNT/β catenin signaling. Methods Tumor samples were obtained from seven individuals at the time of surgery for uterine leiomyoma（range, 33 to 49 years）.We treatedcultured leiomyoma cells with a potent tankyrase inhibitor（XAV939）that can antagonize β catenin by stimulating its degradation, in a serum starved and hypoxic culture condition

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without additional adipogenesis inducing agents or supplements. After two weeks treatment, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells, andshowed increasing accumulation in a time dependent manner.
Results Using real time reverse transcriptional PCR asays, themarker genes of differentiated fat cells such as ADIPOQ and
PLIN were highly expressed in leiomyoma cells that weretreated with XAV939 under hypoxia and serum starvation,
whereas the immunohistochemical expression of desmin was
down regulated, which is in line with the switch in differentiation. Conclusion Our study demonstrates that the disturbance of
canonical WNT/β catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells.

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Diffuse type adenomyosis is associated with the high incidence of pregnancy complications Ayako Hashimoto1,
Takayuki Iriyama1, Rieko Shitara1, Hitomi Furuya1, Takahiro
Seyama1, Toshio Nakayama1, Akito Miyauchi2, Osamu Nishii3,
Takeshi Nagamatsu1, Yutaka Osuga1, Tomoyuki Fujii1 The University of Tokyo 1, Japanese Red Cross Medical Center 2, Teikyo
University Hospital, Mizonokuchi 3
Objective It has been reported that adenomyosis is associatedwith the increased incidence of obstetrics complications, including hypertensive disorders of pregnancy（HDP）, second trimester miscarriage, placental malposition, and preterm birth. In thisstudy, we aimed to examine the difference in the impact onpregnancy outcomes between adenomyosis subtypes, diffuse
and focal types. Methods This study was conducted under approval of our facility ethical committee. Ninety four singleton
pregnancy cases complicated with adenomyosis that had been
diagnosed by magnetic resonance imaging（MRI）and/or transvaginal ultrasonography（TVS）and were perinatally managed
in three hospitals from 2000 to 2016 were included in this study.
All cases were retrospectively subcategorized based on thefindings of MRI and/or TVS as follows；focal type：confined lesion which is embedded within the myometrium, diffuse type：extensive lesion reaching throughout the uterine musculature.
The incidence of obstetrical complications was examined. Results Among a total 94 cases, 49 cases（52%）and 45 cases（48%）
were subcategorized as diffuse and focal type respectively. Diffuse type cases were more likely to develop HDP with statisticalsignificance when compared with focal type cases（34.6% vs.
15.5%；p＜0.05, OR 2.8, chi square test）. The incidence of otherobstetrical complications including second trimester miscarriage and placental malposition exhibited increased tendency indiffuse type cases. Conclusion Among adenomyosis complicated pregnant women who display increased risk for obstetrical complications, patients with diffuse type adenomyosis require even more careful and intensive perinatal management.

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Hypoxia induced gene expression profile of uterine leiomyoma under extracellular matrix free conditions Hiroshi
Ishikawa1, Tetsuji Nishiwaki2, Makio Shozu1 Chiba University 1,
Chiba Aoba Municipal Hospital 2
Objective Uterine leiomyoma is characterized by large amountsof extracellular matrix（ECM）and broad avascular area, bothof which may induce hypoxia in the leiomyoma cells. We recently identified hypoxia induced hypoxia inducible factor 1 α（HIF 1 α）expression in uterine leiomyoma cells. To further
clarify hypoxic response in these cells, we explored hypoxia induced gene expression profile of uterine leiomyoma in the absence of ECM, which is possible to modify microenvironment of
this tumor. Methods IRB at our facility approved all experimen-

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ment speeds and frequency of pseudo pod formation of NK
cells. The cell movement speeds of both macrophages and lymphocytes were not significantly difference between with andwithout endometriosis. After DNG administration, the cell
movement speeds of only peritoneal NK cells from women withendometriosis were increased to the same level as in controls.
Conclusion DNG may improve the cell movement speed of NK
cells in women with endometriosis；suggesting that DNG may
improve the chemotaxis of NK cells and also improve the immunological peritoneal environment in women with endometriosis.

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tal protocols, and written consents were obtained from participants. We cultured primary leiomyoma and myometrial cells obtained from surgical specimens under hypoxia（1% oxygen）andnormoxia for 12 hours（n=3）, and then extracted total RNA. We
performed exhaustive cDNA microarray analysis using these
specimens, and also performed qPCR for the validation of the
microarray data using other specimens（n=10）. Results Pathway
analysis and subsequent validation qPCR revealed that hypoxia
significantly up regulated HIF responsive gene expressions（LDHA , SLC2A1 , ENO1 , ENO2 , HK2 , PDK1 , and PFKFB3 ）inuterine leiomyoma cells. Gene Ontology analysis revealed thathypoxia significantly up regulated metabolic and catabolic
process of glucose, hexose, and monosaccharide, glycolysis, andglucose binding in these cells. Conclusion Hypoxia significantly
up regulated HIF responsive gene expressions and glycolysis
related biological process in uterine leiomyoma cells under
ECM free conditions. These results may indicate fundamental
hypoxic response in uterine leiomyoma.

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ISP-28-5
The use of the apparent diffusion coefficient（ADC）value fordifferentiating leiomyosarcoma from leiomyoma variants
Mai Nishimura, Sachiko Matsumoto, Yasuhiro Ohara, Kaoru
Minowa, Risa Tsunematsu, Kanako Takimoto, Kazuaki Imai,
Yoko Tsuzuki, Hajime Ota, Yoshiyuki Fukushi, Shinichiro
Wada, Takafumi Fujino Teine Keijinkai HospitalObjective Most of leiomyosarcoma（LMS）and leiomyoma variants（LMV）display high intensity on diffuse weighted imaging
of magnetic resonance imaging（MRI）, however, differentiating
LMS from LMV preoperatively is sometimes difficult. The objective of our study was to investigate the clinical usefulness of
the apparent diffusion coefficient（ADC）value for preoperative
differentiation between uterine LMS and LMV. Methods
Thirty five patients were diagnosed with LMS or LMV pathologically in our hospital from 2013 to 2016. Twenty eight patients were LMV and 7 patients were LMS. All patients underwent 1.5 T MRI preoperatively. Results The mean ADC valueof the patients with LMV was 1.173±0.231（×10!3mm2/s）andthat of the LMS was 0.880±0.1222（×10!3mm2/s）. The mean
ADC value was significantly lower in LMS than LMV（p=0.0029）. With the exclusion of 3 apparently advanced stage
LMS patients, the highest ADC value of the LMS was 0.829 andthe lowest ADC value of the LMV was 0.849. Based on the receiver operation characteristic（ROC）curve analysis, the optimal ADC value for minimizing the false negative rate was 1.092（sensitivity；100%, specificity；53.6%）. Conclusion Preoperative measurement of the ADC value is useful for differentiating
LMS from LMV.

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ISP-29-1
Three cases of retained products of conception treated withhysteroscopic surgery following uterine artery embolization
Teppei Ichikawa1, Yoshinobu Hamada1, Kohei Nemoto1, Mao
Hisamatsu1, Nobuhiko Yamashita1, Shin Onota2, Atsushi
Yamamoto2, Akiko Fujii3, Manabu Nakata4, Kouhei Sugimoto2,
Shuichi Sakamoto1, Satoshi Takakura1 Dokkyo Medical University Saitama Medical Center 1, Dokkyo Medical University Reproduction Center 2, Department of Pathology, Dokkyo Medical
University 3, Department of Radiology, Dokkyo Medical University 4
Introduction Retained products of conception（RPOC）are intrauterine tissuees that persist after miscarriage or pregnancy
termination. Hysteroscopic transcervical resection（TCR）is effective for RPOC. However, in cases of hypervascular RPOC,
TCR may cause massive bleeding. We report three cases of hypervascular RPOC treated with TCR following uterine artery

embolization（UAE）for preventing massive bleeding. Case1
Forty years old woman G1P1（vaginal delivery1）underwent artificial abortion at 19 weeks of pregnancy. Ultrasonography
showed intrauterine mass 45mm size 41 days after that, suggestive of RPOC. Curettage was performed but massive bleeding
occurred. Bleeding was controlled with UAE. TCR was performed 2 days after UAE. Case2 Thirty three years old woman
G3P2（vaginal delivery2, miscarriage1）presented with irregularvaginal bleeding for more 2 months after vaginal delivery at 40
weeks of pregnancy. Ultrasonography and color doppler showed
intrauterine mass 17 mm size with hypervascularity, suggestiveof hypervascular RPOC. After expectant management, RPOC
was unchanged. TCR was performed 1 day after UAE. Case3
Thirty one year old woman G2P1（vaginal delivery1, miscarriage1）presented with irregular vaginal bleeding for more 3months after curettage for miscarriage at 7 weeks of pregnancy.
Ultrasonography and color doppler showed intrauterine mass 20
mm size with hypervascularity, suggestive of either hypervascular RPOC or trophoblastic diseases. TCR was performed on
the day of UAE. In all three cases, RPOC were removed by TCR
without massive bleeding and pathologically diagnosed chorionic villi, and postoperative periods were uneventful. Conclusion TCR following UAE may be effective in treatment of hypervascular RPOC.

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Laparoscopic Hysterectomy in Large Myoma Uteri by Using
Lee Huang Point Mayuko Komori, Takehiko Tsuchiya, Eijiro
Hayata, Yuko Hayashi, Tomoko Taniguchi, Yusuke Fukuda,
Toshimitsu Maemura, Yukiko Katagiri, Masahiko Nakata,
Mineto Morita Toho University Omori Medical Center
Objective The Lee Huang point was developed as the site for
insertion of the primary trocar midway between the xiphoidprocess and the umbilicus. Its location provided the laparoscopist a central anatomical view compatible with the practice ofhead to foot orientation of laparoscopic surgery. Since then, theapplication of the Lee Huang point has expanded to various gynecologic laparoscopic surgeries. To present cases of laparoscopic hysterectomy in large myoma uteri by using Lee Huang
point. Methods In five patients with large myoma uteri, Lee Huang point was used as primary 12mm trocar. Patients wereplaced in a dorsal lithotomy position. The arms are tucked at thesides and a foam mattress is situated directly under the patient
to prevent sliding during steep Trendelenburg. Results The average value of amount of bleeding was 370 ml（120 680 ml）. The
average of surgical time was 161 minutes（138 198 minutes）.
The average weight of the specimen was 1,125 gram（847 1,468
gram）. The postoperative course of all patients was good. Pathology anatomy results were fit with leiomyoma. Conclusion
Lee Huang point approach offers wide access to abdominal cavity, proper visual angle and increase work space. Lee Huang
Point was very useful in laparoscopic surgery of patients withlarge myoma uteri.

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ISP-29-3
Six ideas to provide accurate histopathological diagnosis for
specimens extracted by power morcellation during total laparoscopic
hysterectomy
Yoji Hisamatsu, Akiko Ikuta,
Takeharu Kido, Naoko Kida, Maiko Kobayashi, Hiromi Murata,
Hideharu Kanzaki, Masato Kita, Hidetaka Okada Kansai Medical University
Because surgical specimens extracted by power morcellation
during total laparoscopic hysterectomy（TLH）are small, anatomical location of uterus is macroscopically indistinct. Histopathological diagnosis of specimens is obtained by power morcellation is difficult to confirm compare with that by total abdomi-

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Spray type adhesion prevention barrier, how to use andshort term report Masato Kita, Yusuke Butsuhara, Takuya
Yokoe, Takeharu Kido, Hiromi Murata, Tomomi Mizokami,
Tomoo Yoshimura, Hidetaka Okada Kansai Medical University
Objective From January 2017, spray type adhesion prevention
barrier, developed in Japan became clinically available. Methods We used this barrier in total 81 cases, including 55 Laparoscopies and 26 open surgeries. Mean age was 47.5 years old. And
average period of postoperative monitoring was 6 months. Results Postoperative complications included no intraabdominal
infections and no surgical wound dehiscence. One case ofsubileus occurred but it was ovarian cancer case with peritonitis carcinomatosa, received neoadjuvant chemotherapy and tumor debulking surgery. She was treated with nothing per os andgastric tube for 3days. She fully recovered and no recurrence
occurred. We checked postoperative uterine intestines adhesion of some cases by transvaginal sonography. In these cases,
we usually had observed postoperative adhesion if treated byconventional sheet type adhesion preventing materials. But by
this barrier, almost all cases had no postoperative adhesion, andileus or subileus case were decreasing in our institute. Conclusion This barrier may compensate for shortcomings, including
difficult to apply, easily removed, cannot cover wide area, of previous adhesion prevention agents No remarkable postoperativecomplication Clinical outcome of postoperative adhesion prevention was satisfactory.

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ISP-29-5
Utility of continuous sutures by STRATAFIXⓇ for closing
vaginal stump in total laparoscopic hysterectomy Shintaro
Yanazume1, Shinichi Togami1, Mika Fukuda1, Masaki Kamio1,
Noriko Karakida2, Shunichiro Ota2 Kagoshima University Hospital 1, Kagoshima Medical Center 2
Objective STRATAFIXⓇ（SF）is an antibacterial monofilament
absorbable suture which has multiple small anchors on thestring surface. We report the application of SF on the closure ofvaginal stump in TLH, and compare it to conventional sutures.
Methods SF suture procedures were as follows. The needle wasinserted into the 6 oʼclock position of the vaginal wall and exitedfrom the right vaginal cuff to affix its tab at the tail end. Reverse
handlings of the needle from vesical side to dorsal side were

performed from the 3 to 9 oʼclock position. For duplicated stumpclosure, backstitching from 9 to 3 oʼclock were similarly added.
We evaluated the procedure difficulties and complications of SF（n=14）, compared with conventional sutures（n=21）from August, 2016. Results SF and conventional sutures were enrolled.
Characteristics were almost even in each group. The mediantime of closing vaginal cuff was 12.5 minutes and 14.8 minutes,
respectively（p=0.373）. Particularly, closure by operators without experience using SF was 6.3 minutes shorter than using conventional sutures. Complications including organ injury, bleeding, wound separation, and pain did not occur in both groups.
Conclusion SF has the potential benefits of stronger and fasterclosure than conventional sutures in closing vaginal cuff during
TLH. Beginners particularly can obtain benefit from its easierprocedure.

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Hand Assisted In Bag Morcellation with the Inside Retractor Technique Yoichi Aoki, Hiroyuki Kanao, Kohei Omatsu,
Maki Matoda, Terumi Tanigawa, Tsuyoshi Hisa, Syuhei
Okamoto, Takeru Sugihara, Makiko Omi, Nobuhiro Takeshima
Cancer Institute HospitalObjective Electromechanical morcellation is familiar to laparoscopic gynecologic surgeons. Several in bag morcellation techniques were developed, but there is a risk of leakage with thetrocar piercing method. We introduced a new technique for safe
Hand Assisted In Bag Morcellation with the Inside Retractor.
Methods The method of hand assisted morcellation has been reported in various literature. However, bag damage caused byslicing the scalpel is considered a problem. Many method introduced use retractors on outside of the bag. However, we introduce a method of installing a retractor inside the bag. Thismethod is highly likely to prevent the bag from being damagedby the scalpel. Results Hand assisted in bag morcellation was
performed in 2 patients undergoing laparoscopic myomectomy
and in 2 patients undergoing total laparoscopic hysterectomy.
Median patient age was 44 years（range：30 71 years）, median
BMI was 21.6（range：19.8 30.7）, Mean operation time was 187.2
min（range, 164 220 min）,mean estimated blood loss was 246.2
ml（range, 10 575 ml）, mean specimen weight was 217 g（range,
42 546 g）.Upon physiological saline testing, no bag leakage wasdiscovered in any case. No postoperative complications werenoted during follow up at the outpatient clinic, and no patient
required re operation. Conclusion Preventing specimen leakage from the bag is the most important purpose of our novel
technique because bag breakage should be avoided at all costs.
Our method may allow the safe collection of specimens with theuse of conventional equipment. We plan to accumulate cases in
the future and aim to generalize the technique.

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Proper device usage in total laparoscopic hysterectomy：A
retrospective analysis in single institute Kenro Chikazawa,
Ken Imai, Yuko Irie, Shigetane Sasaki, Junko Ushijima, Sachiho
Netsu, Isao Horiuchi, Tomoyuki Kuwata, Kenjiro Takagi, Ryo
Konno Jichi Medical University Saitama Medical Center
Objective We retrospectively reviewed the usage of advanced
bipolar/ultrasonic scalpel for laparoscopic hysterectomy toidentify the most useful device and to understand how to properly use it. Methods The medical records of 341 women who underwent total laparoscopic hysterectomy（TLH）at our institute,
between October 2014 and November 2016 were retrospectively
reviewed. Data on operating times, bleeding, and uterine weight
were collected. Results Devices used were the Ligasure Blunt
tip（Medtronic, Tokyo, Japan）, ENSEAL TRIO/G2,（Johnson ＆Johnson, Tokyo, Japan）, HARMONIC ACE/ACE+（Johnson ＆May 11 Fri.
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nal hysterectomy or by vaginal manual morcellation. To improve this problem, we take 6 ideas for the perioperative period.
Our procedures are as follows：1. Cytological examination forthe cervix and endometrium are performed before operation toeliminate the presence of malignancy. If the result of that is notnegative, histopathological examination by cervical biopsy or
endometrial curettage is added. 2. The bilateral fallopian tubes
are amputated from uterus and are extracted subsequently. 3.
The endometrium is curetted. 4. Indigocarmine is injected in theuterine cavity aim to stain endometrium indigoblue. 3 and 4 ofprocedure will occasionally reveal the unsuspected presence ofmalignant neoplasm of cervix and endometrium. 5. The cervix is
amputated from uterine body in vaginal canal. 6. The uterine
body is morcellated by power morcellation in abdominal cavity.
The extracted specimens are separated staining indigoblue or
not；former can be considered as the specimens around endometrium, and later can be as the other, including myometrium
or uterine serosa. The procedures from 3 to 5 take less than 10
minutes, and the technique is very easy. Even if occult uterus
malignant tumor is confirmed after operation, we can preventthe oversight of malignancy. This procedure may be useful forincreasing the accuracy of histopathological examination formorcellated specimens.

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Johnson, Tokyo, Japan）,and THUNDERBEAT（OLYMPUS, Tokyo, Japan）. Bleeding was similar in each group, but tended tobe higher with the HARMONIC. There were no significant differences among the 4 devices regarding the operating time, but
the THUNDERBEAT tended towards a shorter operative time.
Finally, LIGASURE was associated with significantly heavier
uterine weight, which was preselected based on pelvic examination. Conclusion This study suggests that LIGASURE is safe devices to use for TLH of large uteri. Moreover, THUNDERBEAT
might shorten the operative time in TLH.

ISP-29-8
Contained Morcellation for laparoscopic surgery Using a Tissue Isolation Bag（MorSafe）Atsuko Yamada, Iwaho Kikuchi,
Wakako Mouri, Yasuho Yanagihara, Kyoko Oshina, Akari
Koizumi, Izumi Suzuki, Takafumi Ujihira, Yuka Yamamoto,
Tsuyoshi Ota, Michio Nojima, Koyo Yoshida Juntendo University Urayasu Hospital
In April 2014, the FDA released a statement discouraging theuse of laparoscopic morcellation during hysterectomy andmyomectomy. Morcellation has come fragmentation and intraperitoneal dissemination of leiomyosarcomas, with upstaging of
the disease and worsened outcomes. We describe the use of atissue isolation bag designed for a 2 port morcellation technique. Nine patients underwent in bag morcellation of myomaswith a tissue isolation bag（MorSafe）between November 2016
and Augest 2017. This technique involved placing the myomas
into the isolation bag within the abdomen, exteriorizing the tailend of the bag, insufflating the bag within the peritoneal cavity,and morcellating the myomas under vision. The mean operative
time was LM 112.6 minutes（range 64 187 minutes）, TLH 173
minutes（range 159 190 minutes）. The average specimen weightwas 320.5 g（range 70 490 g）,the mean time for specimen introduction into the bag was 17.6 minutes（range 10 22 minutes）,
and mean time for morcellation and bag removal was 15.8 minute（range 5 23minutes）. Our morcellation within a bag perfumed no bag related complications. This method of morcellation is safe technique and feasible, reliable, reproducible.

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ISP-30-1!

Long term oncologic and reproductive outcomes of a fertility sparing management using high dose medroxyprogesterone acetate（MPA）for endometrial adenocarcinoma or atypical endometrial hyperplasia Emi Yokoyama, Naomi Shiga,
Takashi Kuno, Shoko Sakurada, Masumi Ishibashi, Zen
Watanabe, Hideki Tokunaga, Masahito Tachibana, Hitoshi
Niikura, Kiyoshi Ito, Nobuo Yaegashi Tohoku University HospitalObjective High dose medroxyprogesterone acetate（MPA）therapy is a fertility sparing treatment, for well differentiated endometrioid adenocarcinoma（EA）or atypical endometrial hyperplasia（AEH）. Even though it is aimed to a fertility sparing
treatment, little is known of its relationship in their oncologic
outcomes and fertility. To verify the current strategy, we retrospectively analyzed the long term oncologic and reproductive
outcomes of high dose MPA therapy for EA or AEH. Methods
We analyzed 22 patients with stage IA, grade 1, EA（EAgroup）,
and 20 patients with AEH（AEH group）who underwent fertility sparing management using MPA（600mg/day）at our Hospital from April 1998 to August 2017. Results In EA group, 13 patients（59.1%）achieved complete response（CR）, and 7 patients（53.8%）of them experienced recurrence after median follow up
time of 14.3 months. 7 patients（31.8%）who failed to achieve CR
underwent surgical management. 4 patients of EA group underwent fertility treatment and 2 patients of them become pregnant. 1 patient had one live birth and 1 patient is during pregnancy. In AEH group, 17 patients（85%）achieved CR, and 12 patients（70.6%）of them experienced recurrence after median follow up time of 16.9 months. 1 patients（5%）who failed to achieve
CR underwent surgical management. 3 patients of AEH group
become pregnant. 2 patients had two live births and 1 patient
had a spontaneous abortion. Conclusion High dose MPA therapy can be considered for the purpose of enabling patients topreserve their fertility. However, the rate of recurrence wasconsiderably high. Early intervention of fertility specialist isrecommended for the purpose of pregnancy.

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ISP-29-9
Examination of the Efficacy of Combination Therapy with
DOAC and Fondaparinux in Gynecology Patients with Venous
Thromboembolism Norihito Yoshioka, Noriyuki Yokomichi,
Takahiro Akama, Haruka Imai, Yuko Nagasawa, Shiho Kuji,
Imari Deura, Tatsuru Ohara, Akiko Tozawa, Junichi Hasegawa,
Nao Suzuki St. Marianna University School of Medicine
Objective In recent years, several researchers have conductedstudies on the effectiveness of combination therapy with fondaparinux（FPX）and direct oral anticoagulant（DOAC）for thetreatment of venous thromboembolism（VTE）. We performed
the examination about the utility of the VTE treatment by FPX
and DOAC. Methods The subjects were divided into threegroups according to their treatment period and method. GroupA of 39 gynecology patients received heparin treatment for
VTE between February 2009 and December 2011, and initiatedwarfarin from day four. Group B of 64 patients received FPX 7.5
mg/day for seven days between January 2012 and March 2016,
and initiated warfarin from day four. Group C of 25 patients received FPX 7.5 mg/day for four days between April 2016 andJuly 2017, and started oral DOAC treatment. We conducted D
dimer tests on the day of discovery, day three, and day seven tocompare the changes in values. Results The D dimer values of
day three reduced from the day of discovery are significantly
different between groups A and B and between groups A and C.
The D dimer values of day seven reduced from day three are
significantly different between groups A and C. In addition, the

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D dimer values of day seven reduced from the day of discovery
are significantly different between groups A and B and between
groups A and C. Conclusion This results showed that FPX andDOAC are sufficiently effective for the treatment of VTE in thefield of gynecology compared with other existing anticoagulants.

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Fertility sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary Nobuhisa
Yoshikawa1, Toshiya Teshigawara2, Kimihiro Nishino1, Jun
Sakata1, Fumi Utsumi1, Kaoru Niimi1, Shiro Suzuki1, Hiroaki
Kajiyama1, Fumitaka Kikkawa1 Nagoya University 1, Ogaki Municipal Hospital 2
Objective The purpose of this study was to evaluate the longterm clinical outcome of young women with malignant transformation arising from mature cystic teratoma of the ovary（MTMCT）by comparing radical surgery and fertility sparing surgery（FSS）.Methods All patients treated with radical surgery
or FSS for MT MCT in multiple institutions were registered inthis analysis. Univariate and multivariate analyses were performed to evaluate clinical outcome, including overall survival（OS）and disease free survival（DFS）. Results From 1986 to
2016, 62 patients with MT MCT were treated in our group. The
median follow up period was 38.0（2.0 227.9）months, and the
median age was 54（17 82）years old. Multivariate analysis revealed that only advanced stage was significantly correlatedwith poorer prognosis of patients［hazard ratio（HR）for death：

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rally and delivered healthy babies. 1 patient became pregnant
five years after chemotherapy and peripheral stem cell transplantation. Finally, 1 patient became pregnant via intrauterine
insemination, fifteen years after chemotherapy. Conclusion In
patients with acute hematologic malignancies where rapid intervention is necessary, preserving fertility before treatment isseldom possible. In some patients, a viable pregnancy via natural means or ART is possible despite previous treatment withchemotherapy. We speculate that, for hematologic malignancies,
the appropriate timing for fertility preservation is not limited tothe period before initial treatment.

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A questionnaire study of awareness of the foster care system
and adoption for the young cancer survivor in Japan Kouhei
Sugimoto1, Eriko Shiraishi2, Yodo Sugishita3, Nao Suzuki3 Dokkyo Medical University Saitama Medical Center 1, The Jikei University Hospital 2, St. Marianna University School of Medicine 3
Objective To objective this study was to elucidate the criteria
for the young cancer survivors to be the foster parents and theadopted parents in each child guidance offices and adoption
agencies in Japan. Methods We researched the criteria for the
young cancer survivors to be the foster parents and the adopted
parents in sixty nine each child guidance offices and twenty
three adoption agencies by a questionnaire. Results Five childguidance offices or adoption agencies answered that it is hardfor the young cancer survivors during the period of cancer
treatments to be the foster parents or the adopted parents. No
one answered it hard for the young cancer survivors in follow
up duration after cancer treatments to be the foster parents or
the adopted parents. Almost of all answered that it is possible
after they confirm the health status of cancer survivors. This
trend was same as the young cancer survivors fully healed aftercancer treatments. More than eighty percent answered thatthey will use the consultation service for the health status of thefoster parents or the adopted parents, if The Japan Society for
Fertility Preservation will set up that. Many mentioned individual correspondence was important in free comment. Conclusion
This study showed that child guidance offices or adoption agencies did not eliminate the young cancer survivors, however,they paid attention to the health status of them. These results
enhanced that healthcare providers should advance great partnership with child guidance office or adoption agencies.

The best and safest strategy for fertility preservation forcancer patients in Japan Koichi Kyono1, Tomoko Hashimoto2,
Masae Koizumi1, Mayumi Toya1, Hideki Igarashi1 Kyono ART
Clinic 1, Kyono ART Clinic Takanawa 2, Human Ovarian tissue
Preservation Enterprise 3
Objective To investigate the best and safest strategy of fertility
preservation（FP）for cancer patients in Japan. Methods PubMed
and reference lists were searched for papers of cryopreservation, transplantation, transportation, pregnancy, and birth using
human ovarian tissue（HOT）. Results It is estimated that the
number of new FP patients using HOT is around 400 at most inJapan each year. Ninety three out of 95 children have been bornfrom HOT cryopreservation by slow freezing（SF）worldwide.
In vitrification methods（VF）, residual cryoprotectants（RC）remained in HOT after warming just before transplantation. However, in SF, RC were washed out after thawing. The concentration of cryoprotectants is four times higher and warming time isfour times shorter in VF compared with SF. A transportation
system using a special box at 4 8 degrees Celsius for 24h has
been established. It costs 5 million euros for to establish andmaintain one cryopreservation center for 30 years. Quality control and assessment, including detection of minimal residual disease are important keys to a successful safe birth by transplantation of frozen thawed HOT. Conclusion SF is the safest
proven method at present. A transportation network with a few
cryopreservation centers is an ideal strategy to lighten the burden of patients, medical staff, and the Government. It has the potential to increase the number of patients and local medical staff
who are in geographic areas that lack an oncofertility program
to have ovarian tissue preserved for later use in transplantationor other emerging FP options. Further studies are needed.

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Evaluation of fertility preservation in 25 patients with hematologic malignancies at our hospital Yuta Kasahara, Eriko
Shiraishi, Keiko Kamoshita, Takayuki Haino, Aikou Okamoto
The Jikei University HospitalObjective Hematologic malignancies present an acute challenge
for fertility preservation due to the need for rapid chemotherapeutic intervention. Although more and more patients are referred for fertility preservation, it is unclear whether fertility
preservation and assisted reproductive therapies（ART）are effective once chemotherapy has begun. Methods We retrospectively examined medical records of 25 female patients with hematologic malignancies who visited our hospital between June2014 and August 2017. We analyzed for outcomes of fertility
preservation and ART. Results Of the 25 patients who were referred to our clinic, 14（56%）wished to receive fertility preservation or ART. Of these patients, 6 had not yet received initial
treatment for their malignancy, while 8 had already begun
treatment. Of the patients who thought fertility preservation
therapy before initial treatment, we were able to preserve fertility in 1 patient via embryo freezing. Among patients who had already received chemotherapy, 2 patients became pregnant natu-

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Fertility preservation by ovarian tissue cryopreservation foradolescent and young adult patients in our department Yuta
Fujii, Yu Wakimoto, Ryu Takeyama, Naoharu Morimoto, Kayo
Inoue, Hiroshi Tsubamoto, Akiko Hasegawa, Hiroaki Shibahara
Hyogo College of Medicine
Objective Fertility preservation by ovarian tissue cryopreservation for adolescent and young adult（AYA）patients with cancer
has been performed, and many cases of pregnancy and delivery
after warming and transplantation have been reported. In our
department, the number of ovarian tissue cryopreservation
cases has been increasing after Hyogo oncofertility network（Hyogo OFN）was established. Here we evaluated the current
status of fertility preservation by ovarian tissue cryopreservation. Methods We preserved fertility using ovarian tissue cryopreservation for seven patients between February 2017 and August 2017. We collected data retrospectively from medical records. Results Patient ages ranged from 11 to 42 years and all
patients were nulligravida. Among these patients, 2 had breast
cancer, 2 had leukemia, 1 had Ewing sarcoma, 1 had vulvar sarcoma, and 1 had a mediastinal tumor. 4 of 7 patients were per-!

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6.58, 95% confidence interval（CI）：1.82 24.78, P=0.0048；HR forrecurrence：5.59, 95% CI：1.52 21.83, P=0.01］. Of a total of 13
women with stage I II disease at less than 45 years old, 7 weretreated with FSS, and there was no recurrence except for in one
woman with stage II MT MCT. There was no significant difference in long term oncological outcome between radical surgery
and FSS. Of patients treated with FSS, 2（29%）were successfully
pregnant. Conclusion FSS may be indicated for patients withstage I MT MCT, who hope to preserve fertility, as no relapse
was found after FSS. However, FSS should not be recommended
for patients with stage II disease.

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formed ovarian tissue cryopreservation following chemotherapy. The average value of Anti Müllerian hormone（AMH）was
0.87 ng/ml. One of seven patients was initially cryopreserved
oocytes, then ovarian tissue cryopreservation was performed. In
4 of 7 patients, oocyte pick up without controlled ovarian stimulation was carried out simultaneously from ipsilateral ovary
when removal of one ovary under laparoscopic surgery. The total number of oocytes collected was 10 from 4 patients. However, only one oocyte matured in vitro could be cryopreserved.
Conclusion Fertility preservation will help AYA patients fightcancer by providing hope that they can conceive in the future.
Further accumulation of cases and consideration will be needed
to yield any findings about its usefulness.

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was diagnosed as Ewingʼs sarcoma by histopathologic and genetic tests. In our cancer joint conference, chemotherapy（VAC
IE therapy）was planned and we explained the effects on themother and fetus associated with VAC IE therapy if the pregnancy was continued, leading to the patient and her familychoosing artificial termination of her pregnancy at 18 weeks ofgestation. Moreover, because VAC IE therapy significantly impairs the ovarian function irreversibly, the patient and her family requested to freeze a fertilized embryo prior to the initiationof chemotherapy, and succeeded in freezing one fertilized embryo, after which we immediately initiated the VAC IE therapy
over a total of 12 scheduled courses.

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Two cases of the fertility preservation for ovarian malignant
tumor to reconfirm the importance of the oncofertility network Naoko Kida, Tomoko Tsuzuki, Mio Matsumoto, Takeharu
Kido, Maiko Kobayashi, Yoji Hisamatsu, Hiromi Murata,
Toshiko Ono, Sonoko Okada, Hidetaka Okada Kansai Medical
University
The number of the consultation for the fertility preservation is atendency to increase in our hospital. As the fertility preservation is generally known, the cases which were consulted by
medical doctors, health care providers, and patients themselves
increase. However, the confusion sometimes happens because of
the insufficient correspondence of management. We report 2
cases that reconfirmed the importance of the oncofertility network. The first case is 41 year old woman. She had right ovarian tumor pointed put at reproduction clinic in Osaka city. She
introduced other hospital and diagnosed of the ovarian cancer,
and radical operation was recommended. She refused the radical operation and consulted other hospital in Tokyo. The laparotomy right adnexa resection was performed at the hospital.
The diagnosis was clear cell carcinoma, Stage IA. After that shecame to our hospital for fertility preservation and the adjuvant
chemotherapy. We obtained a fertilized egg with random start
controlled ovarian stimulation before chemotherapy. The second case is 32 year old woman. She had both sides ovarian tumor pointed out at reproduction clinic. She had laparoscopic
surgery in other hospital. The laparoscopic finding was Stage
IIIB. Only the biopsy was performed and the diagnosis wasserous borderline tumor. She wished for fertility preservation in
our hospital. However, we decided the fertility preservation isinappropriate at that time and started chemotherapy and plan
to operation again. We started to setup oncofertility network
and want to contribute patient referral system and provide theappropriate information.

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A case of retroperitoneal Ewing sarcoma in early pregnancy
Masashi Noguchi1, Kiyonori Miura1, Michio Kitajima1, Yuri
Hasegawa1, Daisuke Hamaguchi1, Naoko Murakami1, Naoki
Fuchi1, Nahoko Komatsu1, Kouichi Hiraki2, Akira Fujishita2,
Hideaki Masuzaki1 Nagasaki University Hospital 1, Saiseikai Nagasaki Hospital 2
The patient was a 33 year old female, garvida 1 para 0. As she
was diagnosed to have an 8cm tumor lesion with a solid part in
the right adnexal region in early pregnancy, laparoscopic surgery was conducted at 12 weeks of gestation. The tumor waspresent engulfed in the ureter from the right posterior broad
ligament through Douglasʼ fossa and was suspected of being atumor outside the gynecology region；therefore, she was referred to our hospital at 13 weeks of gestation. At 15 weeks ofgestation, laparoscopic surgery was jointly conducted by the
Surgical Oncology Department and the Urology Department. It! !

Fertility Preservation before treatment of malignant disease
Shiho Takeuchi, Takashi Nakasuji, Nobuyuki Kidera, Yuki
Iwahara, Tomonori Ishikawa, Naoyuki Miyasaka Tokyo Medical
and Dental University
Objective Fertility Preservation for the patients who survive
from malignant disease has become more important, because
the treatment of the malignant disease has progressed and thenumber of malignant disease surviver has increased recently.
Here we report our study of fertility preservation. Methods
This is a retrospective analysis of patient records who underwent ovarian stimulation and oocyte retrieval for the purpose of
to prevent depression of fertility induced from cancer treatment
or any other drug which decrease fertility. The study was done
at our Hospital from June 2015 to September 2017. Results
Twenty four women were evaluated who were before or undergoing treatment for malignant disease；breast cancer, 18；hematologic disease, 4；atypical endometrial hyperplasia, 1；collagen disease, 1. Average age of the patients was 34.2 years（2245）. 23 patient preserved oocytes or embryos in 33 cycles. Peakestradiol levels ranged from 135 to 4,239pg/ml. Average AMH
was 3.17（0.22 11.6）. The average number of the frozen oocytes
and the embryos per cycle was 11（2.5 26）and 1.3（0 6）.Conclusion We found that we could get sufficient number of oocyte orembryo in short period before malignant treatment. Continued
research is needed to investigate the pregnancy rate after treatment of malignant disease.

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Diagnostic value of bioactive factors from blood sample forthe early detection of uterine sarcoma Hideaki Tsuyoshi,
Yoshio Yoshida University of Fukui
Objective The reliable biomarker of uterine sarcoma for the
early diagnosis can enable to achieve early and complete resection, leading to improving the prognosis. The comprehensive
study of bioactive factors based on genome data has been reported the potential biomarker for the early diagnosis of cancer.
The aim of our study is to clarify the role of the bioactive factor
for the early diagnostic biomarker in uterine sarcoma. Methods
To identify the candidates for the early detection of uterine sarcoma, the genome wide expression data from 57 uterine sarcoma, 23 leiomyoma and 23 myometrium were used. Four candidate genes were identified as the uterine sarcoma specific bioactive factors and these concentrations were measured by
ELIZA from blood sample of 41 patients with gynecologic tumors（leiomyoma, ovarian, cervical, endometrial cancer anduterine sarcoma）. Results A comprehensive analysis of genome
data identified four candidate gene, Midkine, Osteopontin, GDF
15 and Granulin. Uterine sarcoma revealed higher concentrations of Midkine（6,732±4,500 pg/ml）than leiomyoma（2,634±1,585 pg/ml）（P＞0.05）.Uterine sarcoma showed significantly
higher concentration of Osteopontin, GDF 15 and Granulin（5058±1,173, 1,152±610.7 and 16,508±2,890 pg/ml）than leiomyoma

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Survival impact of reduction surgery for elderly or obese patients with endometrial cancer Junko Minato, Hitoshi Niikura,
Yusuke Shibuya, Shoko Sakurada, Chiaki Hashimoto, Tomoyuki
Nagai, Michiko Kaiho, Masafumi Toyoshima, Hideki Tokunaga,
Muneaki Shimada, Nobuo Yaegashi Tohoku University HospitalObjective Conservative surgery without systematic lymphadenectomy is a treatment option for patients with endometrial cancer who are elderly or obese. In our institution,conservative surgery has been performed for patients 70 yearsof age or older and those with a body mass index（BMI）＞32 kg/
m2. The aim of this study is to evaluate the survival impact ofconservative surgery for elderly or obese patients with endometrial cancer retrospectively. Methods From 2007 to 2012,
215 patients underwent standard surgery and 183 patients received conservative surgery as initial treatment. The subjects
for analysis were 59 patients undergoing conservative surgery
due to old age（elderly group）and 40 undergoing conservative
surgery due to obesity（obese group）.The clinical and histological characteristics and survival of these patients were analyzed
and compared with those of the standard surgery group. Univariate analysis was performed to determine prognostic factors.
Results A large proportion of elderly group had type2 endometrial cancers, whereas most of obese group had stage I endometrioid carcinoma（G1/G2）.The disease free survival（DFS）
rate were 68.1% in the elderly group, 94.6% in the obese group,and 84.5% in the standard surgery group. The 5 year DFS rate
was significantly shorter in the elderly group than in the standard surgery and obese group（p=0.0018）. In univariate analysis,
advanced stage and type2 histology correlated with poor prognosis in both the elderly group and the obese group. Conclusion
Standard surgery can also be a treatment option in patients whoare elderly and obese when they have advanced stage disease or
type2 histology.

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Introduction of transperitoneal paraaortic lymphadenectomy
for endometrial cancer Eiji Kobayashi1, Mamoru Kakuda2,
Tsuyoshi Takiuchi1, Yuri Matsumoto1, Michiko Kodama1, KaeHashimoto1, Seiji Mabuchi1, Yutaka Ueda1, Kenjiro Sawada1,
Takuji Tomimatsu1, Kiyoshi Yoshino1, Tadashi Kimura1 Osaka
University 1, Sakai City Medical Center 2
Objective Lymphadenectomy is an integral part of staging andtreatment of gynecologic malignancies. The aim of this study isto evaluate the feasibility and perioperative outcome of laparoscopic surgery including paraaortic lymphadenectomy for endometrial cancer in the early learning curve of this procedure.
Methods From December 2015, surgery including laparoscopic
hysterectomy, bilateral salpingo oophorectomy, pelvic and transperitoneal paraaortic laparoscopic lymphadenectomy was performed in 15 patients at our institute as a clinical study. We
evaluated the clinical characteristics, surgical outcomes, surgery related complications, and hospital stays. Results The
study included 15 consecutive patients. Median length of operation was 445 min（range, 345 546）.Median blood loss was 80 ml（range, 20 1,600）. The median number of harvested lymph node
was 63（range, 46 120）
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Germline BRCA1/2 mutations in patients with epithelial ovarian cancer Akiko Abe, Masato Nishimura, Minoru Irahara
Tokushima University
Objective In Japan, the number of BRCA testing is increasing
annually. But, till recently, genetic counselling for epithelial
ovarian cancer（EOC）has not been generalized according to hereditary breast and ovarian cancer（HBOC）. We investigated
the awareness survey and the rate of gBRCA1/2 mutation with
EOC, regardless of their family histories. Methods 105 patientswith EOC who had treated at our hospital were enrolled for 2
years. After genetic counselling, four patients refused gBRCA1/
2 test because of no relatives or depression. For 101 patients,
analyses for gBRCA1/2 test were performed. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced withnext generation sequencing in our laboratory. Results 83 patients（82%）wished for gBRCA1/2 result disclosure, and other18 patients did not wish to know that result because of worrying. Thirteen of the 107 patients（12.8%）；5 patients in gBRCA1
mutation and 8 patients in gBRCA2 mutation. 8 of 13 withgBRCA1/2 mutation were serous carcinoma, three；adenocarcinoma, one；poorly differentiated adenocarcinoma, and one clear
cell carcinoma. Conclusion Almost patients with EOC wanted
to know genetic risk after genetic counselling. The rate ofgBRCA1/2 mutation in tested Japanese EOC patients with an
inherited risk, regardless of a family history, was 12.8%. Thisfinding indicates that the cooperation of genetic counsellingwith other department would be important for patients withovarian cancers.

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rienced conversion from laparoscopy to laparotomy. The overall
complication rate was 53% with 13.3% intraoperative（one transfusion and one organ residue）and 40% postoperative complications（six chylous ascites and one surgical site infection）. All
postoperative chylous ascites resolved conservative treatment.
Median duration postoperative hospital stay was 7 days（range,
7 23）. Conclusion By transperitoneal laparoscopic lymphadenectomy, an adequate number of lymph nodes can be removed in an adequate time. The rate of chylous ascites washigher than expected and will be minimized by standardizationof the procedure.

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（2,226±200.6 165.3±16.56 and 9,065±608.3 pg/ml）（P＜0.01）.
GDF 15 was bioactive factor which uterine sarcoma revealed
significantly higher concentration than all gynecologic tumors（P＜0.01）. Conclusion We demonstrated that the measurementof bioactive factors based on genome data can offer the high diagnostic performance for the early diagnosis of uterine sarcoma.
The combined analysis of bioactive factors might improve thediagnostic accuracy.

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The refractoriness to anti VEGF therapy in ovarian cancer
is mediated via infiltration of GM CSF induced MDSCs
Naoki Horikawa1, Kaoru Abiko2, Noriomi Matsumura3, Junzo
Hamanishi2, Tsukasa Baba2, Ryusuke Murakami2, Ikuo Konishi4,
Masaki Mandai2 Shiga Medical Center for Adults 1, Kyoto University 2, Kindai University 3, Kyoto Medical Center 4
Objective Although bevacizumab has been used to treat ovariancancer, few cases achieve complete response. The mechanism of
resistance to anti VEGF therapy is unknown. Myeloid Derived
Suppressor Cells（MDSCs）are immunosuppressive cells composed of myeloid lineage cells at various stages of differentiationthat expand in the tumor sites. Herein, we elucidated the alteration of immune condition in anti VEGF antibody（a VEGF
abs） resistant tumor. Methods HM 1, mouse ovarian cancer
cell line, exhibited resistance to a VEGF abs（B20 4.1.1）inmouse model. The resistant tumors were collected and analyzed
by immunohistochemistry for Gr 1, CD8 and Pimonidazole as a
hypoxic marker. Membrane based cytokine array of tumor
lysates was performed. Expression of GM CSF in ovarian cancer cells cultured under hypoxic conditions was analyzed. The
impact of GM CSF on MDSC function was analyzed. The combination therapy of anti VEGF antibody and anti GM CSF anti-

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body was performed. Results Increased Gr 1+ MDSC and decreased CD8+ lymphocytes were observed in a VEGF abs resistant tumors. Pimonidazole+ area was increased in a VEGF
abs resistant tumor. MDSCs were preferentially infiltrated into
hypoxic lesions. Protein array exhibited increased GM CSF ina VEGF abs resistant tumors. The expression level of GM CSF
was up regulated in HM 1 cells cultured under hypoxic condition. The migration assay showed hypoxia promoted MDSC recruitment through GM CSF signal. The combination therapy
with anti GM CSF abs significantly inhibited the tumor growthcompared with a VEGF abs only. Tumor infiltrating MDSC
were reduced and CD8+ lymphocytes were increased by combination therapy. Conclusion Anti VEGF therapy induced tumor
hypoxia and up regulated GM CSF expression. Anti GM CSF
abs improve the efficacy of a VEGF abs through blockade of
MDSC influx into tumor.

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Overexpression of cyclase associated protein 2（CAP2）is a
new prognostic indicator in Type II ovarian cancer Masataka
Adachi1, Kouji Banno1, Mayuka Anko1, Takayuki Takahashi1,
Moito Iijima1, Takashi Takeda1, Miho Iida1, Yusuke Kobayashi1,
Eiichiro Tominaga1, Mamoru Tanaka1, Michiie Sakamoto2,
Daisuke Aoki1 Keio University 1, Department of Pathology, Keio
University 2
Objective The cyclase associated protein 2（CAP2）is proteinthat regulates actin dynamics and known as cell cycle regulator
or carcinogenic factor. Although CAP2 expression is associatedwith progression of hepatocellular carcinoma, CAP2 expressionin other malignancies remains unclear. The aim of this study
was to assess the clinicopathological significance of CAP2 expression in ovarian cancer. Methods The subjects were 518 patients with ovarian cancer who underwent surgical resection in
our institute between 2000 and 2016. The study included 336
cases of Type I（low grade serous, well differentiated endometrioid, clear cell and mucinous carcinoma）and 182 of TypeII（high grade serous, poorly differentiated endometrioid andundifferentiated carcinoma）ovarian cancer. CAP2 immunohistochemistry was performed and staining criteria was defined
based on its intensity and area. Each case was classified in overexpression or low expression of CAP2. Correlation analyses of
CAP2 and clinicopathological factors were performed by Chi
square test. The log rank test and univariate and multivariate
Cox regression analysis were performed to assess the prognostic significance of CAP2. This study was approved by our ethical committee. Results CAP2 overexpression was observed in
59（11.4%）cases and significantly related to Type II histology（4.8% of Type I vs 23.6% of Type II, p＜0.001）, decreased progression free survival（PFS）（67.4 vs 157.2 months, p＜0.001）andoverall survival（98.9 vs 166.4 months, p=0.009）compared withlow expression. Amongst Type II ovarian cancer, CAP2 expression was an independent prognostic factor for PFS［HR, 2.077；
95% CI, 1.297 3.324；p=0.002］. Conclusion This study suggeststhat CAP2 is a new prognostic indicator in Type II ovarian cancer.

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The histone methyltransferase, SUV39H2, involved in resistance to anti cancer treatment with γ H2AX production, is apotent therapeutic target in high grade serous ovarian carcinoma Kenbun Sone1, Katsutoshi Oda2, Asako Kukita1, Hidenori
Machino1, Machiko Kojima1, Shinya Oki1, Michihiro Tanikawa1,
Kazunori Nagasaka1, Yoko Matsumoto1, Osamu Hiraike2, Yutaka
Osuga2, Tomoyuki Fujii2 The University of Tokyo Hospital 1, The
University of Tokyo 2
Objective Dysregulation of histone modification, especially the

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process of histone methylation, has been considered as one of
key regulators for human carcinogenesis. Overexpression ofvarious histone methyltransferases has been reported in multiple cancers. However, there are no reports about SUV39H2 inhigh grade serous ovarian carcinomas（HGSC）.The aim of thisstudy is to clarify expression and functions of SUV39H2 in
HGSC. Methods We analyzed 39 clinical HGSC specimens underinformed consent and approval of our ethics committee. We performed quantitative real time PCR（q PCR）to evaluate expression of SUV39H2. The functional analysis of SUV39H2 was examined with in vitro methylation assay, mass spectrometry, invitro kinase assay, and dominant negative experiments. Results
The q PCR revealed that SUV39H2 was overexpressed in clinical HGSC specimens（P=0.006）,compared with normal ovariantissues. In vitro methylation assay and mass spectrometry revealed that SUV39H2 methylated histone H2AX on lysine 134.
In vitro kinase assay indicated that lysine 134 methylation on
histone H2AX enhanced H2AX serine 139 phosphorylation（γ H
2AX）.Introduction of K134 substituted histone H2AX, which is
not methylated by SUV39H 2, increased the sensitivity of cancer
cells to ionizing radiation and chemotherapeutic agents（doxorubicin and cisplatin）. Conclusion SUV39H2 inhibition may reduce γ H2AX production and sensitize the cancer cells to radiotherapy and chemotherapy. Inhibition of SUV39H2, in combination with DNA damaging agents, may be a novel therapeuticstrategy in HGSC

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Safety and efficacy of neoadjuvant chemotherapy with
bevacizumab in advanced stage peritoneal/ovarian cancer
patients Kazunari Fujino1, Soshi Kusunoki1, Takashi Hirayama1,
Takafumi Ujihira2, Tsuyoshi Ota2, Yasuhisa Terao1, Atsuo
Itakura1, Satoru Takeda1 Juntendo University Hospital 1, Juntendo University Urayasu Hospital 2
Objective The aim of this study was to evaluate the outcomes ofneoadjuvant chemotherapy（NAC）with bevacizumab（Bev）at
our institute. Methods Eleven patients with stage IIIC or IV
peritoneal/ovarian cancer who underwent interval debulking
surgery（IDS）after NAC with Bev between December 2014 andDecember 2016 were enrolled retrospectively（TCB group）. As
a control group, we enrolled 13 patients evaluated between December 2012 and December 2014 who underwent IDS and received NAC without Bev（TC group）. Both the TCB and TC
groups received combination chemotherapy consisting of paclitaxel（175 mg/m2）or docetaxel（70 mg/m2）and carboplatin（area under the curve 6 mg/mL/min）administered intravenously every 3 weeks（cycles 3 6）
. Results All patients in bothgroups underwent IDS. There were 7（63.6%）and 8（61.5%）caseswith stage IIIC disease and 4（36.3%）and 5（30.7%）with stage
IV disease in the TCB and TC groups, respectively. The complete resection rate was 81.8% in the TCB group and 69.2% in
the TC group. The rate of achieving either complete or optimalresection was 100% in the TCB group and 69.2% in the TC
group（p=0.043）. Hematoxicity（grade 3 or higher）was observedin 9 patients（81.8%）in the TCB group and 12（92.3%）patientsin the TC group. One patient（9%）experienced abdominal incisional hernia due to a fascial defect in the TCB group. Conclusion IDS after NAC with Bev is safe, with a similar efficacy asthat after NAC without Bev.

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Differential requirement of amino acids on cell survival ofovarian cancer cells Akiko Furusawa1, Jun Inoue2, Hitoshi
Tsuda3, Naoyuki Miyasaka1, Johji Inazawa2 Tokyo Medical and
Dental University 1, Medical Research Institute, Tokyo Medical
and Dental University 2, National Defense Medical College Hospi-

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Serum CA125 level after neoadjuvant chemotherapy is predictive of prognosis and surgical outcomes in advanced epithelial ovarian cancer Tomohiko Matsuhashi1, Hisamori Kato2,
Kazuho Nakanishi1, Takashi Yamada1, Gen Ishikawa1, Seiryu
Kamoi1, Toshiyuki Takeshita1 Nippon Medical School 1, Kanagawa Cancer Center 2
Objective Neoadjuvant chemotherapy（NACT）followed by interval debulking surgery（IDS）has recently been recommended
for selected patients with advanced epithelial ovarian cancer（EOC）because NACT IDS was shown to have fewer complications compared to conventional primary debulking surgery（PDS）, without any significant difference in therapeutic efficacy. Reductions in cancer antigen 125（CA125）levels before
and after primary treatment have been known to predict the
prognosis of advanced EOC patients. However, the correlation
between post NACT CA125 levels and successful IDS remains
controversial. The objective of this study was to evaluate associations between post NACT serum CA125 levels, surgical outcomes, and clinical outcomes in advanced EOC. Methods We
retrospectively analyzed 107 patients with FIGO stage III or IV
ovarian cancer who were treated with NACT IDS between
January 2001 and December 2012. All patients provided verbal
and written informed consent for the use of their anonymized
clinical records for the research. Results Serum CA125 levels after NACT were significantly lower in the complete/optimal IDS
group（n=77）compared to the suboptimal IDS group（n=30,
mean±standard deviation：48.1±27.6 vs. 346.5±295.2 U/mL, p＜0.01）. Patients with low preoperative CA125 levels（＜35 U/mL）had a higher probability of optimal IDS（78.1±41.9% vs. 33.3
±19.2%, p ＜0.01）and longer progression free survival（mean±standard deviation：30.4±14.3 months vs. 21.3±7.3 months, p＜0.05）than patients with high CA125 levels（＞100 U/mL）. Conclusion Patients with low CA125 levels（＜35 U/mL）had ahigher probability of complete/optimal IDS and longer progression free survival compared to patients with high CA125 levels（＞100 U/mL）
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Investigation for characteristics of clear cell carcinoma be-!

tween developing and non developing endometriosis Yu
Horibe, Toshiyuki Kanno, Junna Taguchi, Yuri Itai, Fumika
Tsuchiyama, Nobuko Takahashi, Yoshika Akizawa, Akira
Nakabayashi, Kazunori Hashimoto, Jun Kumakiri, Hideo
Matsui, Shoko Inokuchi Tokyo Womenʼs Medical University
Hospital
Objective Clear cell carcinoma（CCC）is a rare subtype of epithelial ovarian cancer. However, in Japan, 20% of ovarian cancer isCCC. CCC is well known as adverse prognosis clinically because of low chemosensitivity and high rate of recurrence. For
long term investigation, part of CCC has developed from endometriosis. If characteristics of CCC with or without endometriosis are pointed out, it would reflect to finding patientunder high risk developing CCC, estimating prognosis andstrategy for surgery. Methods We investigated 19 patients who
underwent primary surgery due to CCC in our institution from2016 to 2017. Patients were divided into two groups which developed endometriosis or not. Each group assessed by age
weight, height, elevation of CA125 and CA199, maximum size ofovary, surgery completeness, pelvic and para aorta lymphadenectomy, peritoneal washing, FIGO classification, content
and length of chemotherapy, recurrence after six months,
gravidity and parity. Data was examined by Box and whisker
plot and Fisherʼs exact test. Results As a results, we couldnʼtfind any significant difference statistically on pelvic and para
aorta lymphadenectomy, gravidity, parity, elevation of CA125
and CA199 between two groups. In box plot, patient with endometriosis, tumor marker and maximum size of ovary were
wide ranged and weight and height were high value. Conclusion This study couldnʼt point statistical significant differenceout. Whereas we found characteristics from graphical data. To
obtain accurate result, further investigation and increasing parameter would be required.

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ISP-32-4
Clinical impact of routine DNA genotyping on the management of suspected early hydatidiform mole Yoko Aoyagi1,
Kentaro Kai2, Takao Matsuda3, Shimpei Sato1, Kanetoshi
Takebayashi1, Naoko Oyama4, Kaei Nasu1, Hisashi Narahara1
Oita University Hospital 1, Nakatsu Municipal Hospital 2, Nishibeppu National Hospital 3, Oita Red Cross Hospital 4
Objective The widespread use of transvaginal ultrasonography
and the high sensitive human chorionic gonadotropin（hCG）test
makes the pathological differentiation of partial or complete hydatidiform mole（HM）and hydrops abortus difficult. We compared the utility of a combined routine use of DNA genotyping
with that of a conventional diagnostic evaluation in women withsuspected HM. Methods We analyzed the cases of 44 consecutive women with suspected HM who underwent a routine DNA
genotyping in addition to a conventional diagnostic evaluation（combination group, n=29）or a conventional diagnostic evaluation only（conventional group, n=15）. The primary endpoint
was the diagnostic yield for DNA genotyping. The secondary
endpoints were the diagnostic concordance rate in the combination group and the percentage of re evacuation and definite diagnostic yield in both groups. We compared the allelic patternof maternal peripheral blood and chorionic villus by short tandem repeat typing. Approval for the study was obtained fromthe institutional review board. Results The diagnostic yield for
DNA genotyping was 96.6%. The diagnostic concordance rate in
the combination group was 58.6%. The re evacuation rate wassignificantly lower in the combination group than the conventional group（44.8% vs. 86.7%；p=0.008）.The definite diagnostic
yield was obtained in all patients in the combination group, but
in only 73.3% in the conventional group（p=0.01）. Conclusion
Routine DNA genotyping combined with a conventional diagnostic evaluation provided a decreased re evacuation rate and

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tal 3
Objective Amino acids（AAs）play an important role on cellular
metabolism in cancer cells. However, which AAs are indispensable the survival of which cancer cells has not been elucidated.
Here, we examined the indispensable AAs for ovarian cancer（OVC）cells and the relationship between the AAs synthetaseand cancer cell survival. Methods To validate the requirementof each AA on cell survival in 14 OVC cell lines, we examinedthe effect of cultivation in single AA depleted conditioned medium on OVC cells. Results By cultivating for 14 OVC cell lines
in different medium in which a single AA was depleted, we
found that the requirement of AAs was cell type dependent.
Next, we focused on the relationship between the sensitivity toglutamine deprivation and glutamine synthetase（GS）. The expression level of GS protein was found to positively correlatewith the cell survival rate under glutamine depleted condition.
GS overexpression in GS downregulated OVC cells induced decreased sensitivity to glutamine deprivation and induced inhibition of in vivo tumor growth, suggesting that OVC cells with GS
downregulation require extracellular glutamine for cell survival. Furthermore, we showed that expression of GS protein
was negative in 10 of 316 primary OVC tumors（3.2%）. Conclusion Our finding suggest that the therapeutic reduction of extracellular glutamine may be effective against OVCs with GS
downregulation.

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an increased definite diagnostic yield, and will be of benefit to
the clinical management of patients with suspected HM.

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Second curettage as initial treatment for molar pregnancy：
who can skip it ?
Shingo Miyamoto1, Yasushi Sasaki2,
Mitsuyoshi Ichihara3, Makoto Nakabayashi1, Yoshiyuki Okada1,
Yuka Asami1, Kanae Shimada1, Chiaki Iitsuka1, Mamiko Onuki1,
Tetsuya Ishikawa1, Koji Matsumoto1, Akihiko Sekizawa1 Showa
University 1, Showa University Fujigaoka Hospital 2, Showa University Northern Yokohama Hospital 3
Objective The therapeutic role of routine second curettage inpatients after first evacuation of molar pregnancy is still controversial. The aim of the present study was to clarify candidates
who could skip the second curettage as an initial treatment formolar pregnancy. Methods A retrospective cohort study was
conducted on 80 patients of hydatidiform mole（56 of complete,and 25 of partial）, who received routine second curettage at one
week after the first curettage between 2007 and 2016. The levelsof serum hCG and the thickness of uterine cavity measured byultrasound sonography before second curettage were obtained
from medical records. Results There were 16 cases with residual molar tissues and 64 cases with no residual molar tissues,
analyzed respectively. The incidence of persistent gestational
trophoblast neoplasia was significantly higher in residual cases.
The levels of hCG was significantly higher in residual cases（median；9,455mIU/ml［2,359 41,500］vs. 2,228mIU/ml［64 12,400］,
p＜0.0001）. Furthermore, the thickness of uterine cavity was
also significantly greater in cases with residual molar tissues（median；15mm［9 23］vs. 7mm［1 15］, p＜0.0001）. Cut offs
of 10 mm of the thickness and 2,000 mIU/ml of hCG at one week
after first curettage gave a sensitivity of 100% to detect a residual condition. Conclusion Our data suggested that the levels of
hCG and the thickness of uterine cavity before second curettage
were related to residual molar tissues. Therefore, the second curettage might be skipped for those patients with the hCG levelsof less than 2,000 mIU/ml and the thickness of less than 10 mm
at one week after first curettage.

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Limitations of hormonal therapy in adenomyosis patients
Chiho Miyagawa, Takako Tobiume, Yasushi Kotani, Kiko
Yamamoto, Risa Fujishima, Masato Aoki, Yoshie Yo, Kosuke
Murakami, Hisamitsu Takaya, Hidekatsu Nakai, Ayako Suzuki,
Noriomi Matsumura Kindai University HospitalObjective Recently hormone therapy made it possible for adenomyosis patients to keep their uteruses intact. However, there isno consensus about which patients require hysterectomies. The
purpose of this study is to define the limitations of hormone
therapy for, evaluate the efficacy of hormonal treatment for andthe necessity of hysterectomies for adenomyosis patients. Methods From January 2008 to September 2017, a total of 96 patientswith adenomyosis had their uterine sizes measured before receiving treatment. From this data, we performed a retrospective study. We define the hormone therapy as GnRH analogs, dienogest, low dose estrogen progestin and levonorgestrel releasing intrauterine systems that are used by themselves or in combination. Results The average uterine length was 98.22 mm. 28
patients（29%）were treated by hysterectomy. The remaining
68 patients（71%）were first treated with hormone therapy only.
A total of 52 patients（54%）were successful. The remaining sixteen patients（17%）required a hysterectomy. A significant number of patients that had larger sized uterus eventually required
hysterectomies（P=0.01）.An ROC analysis was taken, it founda cut off value for uterine lengths of 86mm for heightened riskof requiring a hysterectomy. For uterine lengths greater than 86!

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mm, the percentage of patients requiring hysterectomies was
58%, compared to 17% for these with uterine lengths less than
86mm. Conclusion About half of cases of adenomyosis patientstreated with hormone therapy were successful. However, patients with uterine lengths more than 86mm had a higher
chance of requiring hysterectomy.

ISP-32-7
The frequencies of peripheral blood regulatory T cells andactivated lymphocytes of the premature ovarian insufficiency
Mutsumi Kobayashi1, Akemi Ushijima1, Masami Ito1, Yosuke
Ono1, Daisuke Matsui2, Kazuhiro Kawamura2, Osamu Yoshino1,
Bunpei Ishizuka2, Shigeru Saito1 Toyama University Hospital 1,
Rose Ladies Clinic 2
Objective Premature ovarian insufficiency（POI）is not rare that
1% of the population are affected. Approximately 50% of patients with POI have some autoantibodies. It is suggesting that
POI is one of the autoimmune diseases. Decreased regulatory T（Treg）cells and activated T cells are observed in autoimmune
diseases. Thus we studied the immune system in POI. Methods
Peripheral blood was collected from patients with POI（POI
group, n=35）and normal menstruation women（control group,
n=8）. Using flow cytometry we analyzed the proportion of
monocytes, CD4/8 ratio, Treg and activation marker；CD69, on
these cells. And in POI group, We analyzed correlation between
autoantibody titer and immune cells. Results CD14+ cells were
low proportion in POI group compared to control group（median
7.0% vs 16.8%, p=0.00167）,and there was no change in the CD4/
8 ratio and Treg between two groups（median 1.53 vs 1.45, p=
0.343, 1.27% vs 1.14% p=0.673）. CD69+ CD4/8 ratio were significantly higher in POI group（0.24 vs 0.096, p=0.032）.There were
negative correlations between the anti thyroglobulin antibody
titer and the proportion of Treg（r= 0.519, p=0.039）and between
the proportion of CD69+CD4+ and Treg（r= 0.497, p=0.00236）.
Conclusion We firstly showed that activated CD4+ T cells wereincreased in POI. And there is a possibility decreasing Treg increase autoantibody titer and activated CD4+ cells. These datasuggest immunological dysfunction may be one of the cause of
POI.

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Validity of assisted reproductive technology after laparoscopic myomectomy Takashi Nakasuji, Tomonori Ishikawa,Tokyo
Nobuyuki Kidera, Yuki Iwahara, Naoyuki Miyasaka
Medical and Dental University
Objective Infertile patients in late reproductive age have a riskof developing uterine myoma. Recently, many uterine myoma
have been treated by laparoscopic surgery instead of laparotomy. In general, 3 to 6 months contraceptive period after laparoscopic myomectomy for healing of uterine wound were recommended. So called surgery assisted reproductive technology hybrid therapy were often performed to use the contraceptive periods effectively. Ovum pick up and embryo freezing is performed during the contraceptive period and frozen thawed embryo transfer is performed after contraceptive periods in the hybrid therapy. In this presentation, we report effectiveness of thehybrid therapy in our hospital. Methods We retrospectively investigated six infertile patients with uterine myoma who underwent the hybrid therapy in our hospital between October 2011
and June 2017. Results The mean age of the patients was 39
years old. The mean maximum diameter of enucleated myoma
was 6.7 cm, and endometrium was deformed due to uterine
myoma in 5 of 6 patients. The average number of cryopreserved
embryos in the pre or postoperative period was 2.3. The average
clinical pregnancy rate per embryo transfer after the contraceptive periods was 50%. Conclusion Though contraceptive period

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Prevention of postpartum depression by the intake of omega
3 polyunsaturated fatty acids（PUFAs） Yoko Nagayasu,
Daisuke Fujita, Atsushi Daimon, Misa Nunode, Saori Ota,
Atsuko Okamoto, Sayaka Taga, Takumi Sano, Yusuke Suzuki,
Masami Hayashi, Yoshito Terai, Masahide Ohmichi Osaka Medical College
Objective Omega 3 PUFAs, including EPA, are known to haveprotective effects on depression. However, there is no consensus
as to whether this applies to postpartum depression as well. The
aim of this study is to examine whether the intake of omega 3
PUFAs prevents postpartum depression. Methods Under theapproval by our ethics committee and informed consent, wemeasured the EPA, EPA/AA and conducted a dietary questionnaire survey on 50 singleton pregnant women. The questionnaire was about how often they eat fish. It was performed at thefirst trimester, second trimester and postpartum. EPDS（Edinburgh Postnatal Depression Scale）was tested postpartum after
one month. Results The frequency of eating fish was correlatedwith EPA in the first trimester（r=0.555, p＜0.001）and postpartum（r=0.522, p＜0.001）. Moreover, it was also correlated with
EPA/AA in the first trimester（r=0.527, p＜0.001）, second trimester（r=0.524, p＜0.001）and postpartum（r=0.528, p＜0.001）.
The levels of EPA and EPA/AA in EPDS＞7 were lower thanthe levels in EPDS＜7（p＜0.05）. Conclusion A lower diet intakeof omega 3 PUFAs during pregnancy correlated to the occurrence of postpartum depression. Sufficient intake of omega 3
PUFAs may provide pregnant women a way to prevent postpartum depression.

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ISP-33-2
Are treatment interventions for early onset gestational diabetes based on the International Association of Diabetes andPregnancy Study Groups criteria effective? Yuko Hagiwara1,
Junko Kasai1, Sayuri Nakanishi1, Etsuko Miyagi2, Shigeru Aoki1
Yokohama City University Medical Center 1, Yokohama City
University Hospital 2
Objective To investigate whether the broad interpretation of
the International Association of Diabetes and Pregnancy Study
Groups（IADPSG）criteria with application to the early pregnancy（adopted as the standard in Japan）is appropriate. Methods We conducted this investigation by comparing diabetes related adverse pregnancy outcomes among women treated for
Gestational diabetes mellitus（GDM）following an early pregnancy diagnosis（early onset GDM, n=528）and those treated for
GDM following a mid pregnancy diagnosis, which is the international standard（Mid term onset GDM, n=147）.Results Gestational weight gain was significantly lower in the early onset
GDM group（7.5 kg）than the mid term onset GDM group（8.4kg）. The frequency of hypertensive disorders of pregnancy
tended to be lower in the early onset GDM group（5.6% vs. 8.8%,
p=0.085）, but infant birth weight did not differ significantly between the groups. No between group difference was observedin macrosomia, large for gestational age（LGA）, small for gestational age（SGA）, low Apgar score, shoulder dystocia, cesarean delivery, NICU admission, hyperbilirubinemia, neonatal hypoglycemia, or respiratory distress syndrome. The frequency of
LGA showed a significant association with pre pregnancy body

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mass index but did not differ according to the timing of therapy
initiation. Conclusion We could not find the effectiveness oftherapeutic interventions initiated after GDM diagnosis in theearly pregnancy based on the IADPSG criteria compared toherapeutic interventions after a mid pregnancy GDM diagnosis.
It was suggested that the IADPSG criteria for diagnosing GDM
at 24 to 28 weeks gestation should not be applied to Japanesewomen in the early pregnancy by a broader interpretation.

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after myomectomy can decrease fertility especially in late reproductive age, the hybrid therapy can preserve embryo without oocyte aging in the contraceptive periods. As clinical pregnancy rate of hybrid therapy for infertile patient with myoma
was as high as general assisted reproductive technology for infertile patients, the hybrid therapy is a strong strategy for infertile patients with myoma.

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Three cases of cesarean scar pregnancy treated with conservative surgery Haruka Ueda, Kosuke Yoshihara, Makoto
Chihara, Tatsuya Ishiguro, Sosuke Adachi, Masanori Isobe,
Akiko Kobayashi, Koji Nishino, Nobumichi Nishikawa,
Masayuki Sekine, Takayuki Enomoto Niigata University Medical and Dental Hospital
Cesarean Scar Pregnancy（CSP）is a rare life threatening typeof ectopic pregnancy in which implantation occurs in the previous cesarean section scar. However, optimal treatment strategy
for CSP is unclear. We report three cases of CSP treated withconservative surgery. Case1 A 29 years old woman with a pasthistory of previous cesarean section was diagnosed with CSP atfive weeks of gestation via ultrasound examination. She complained continual vaginal bleeding and lower abdominal pain
since six weeks and we performed uterine artery embolization（UAE）followed by dilatation and curettage（D＆C）at eightweeks. Case2 A 40 years old woman with a past history of previous cesarean section and adenomyomectomy was suspectedwith hydatidiform mole based on ultrasound findings at six
weeks of gestation. She was referred to our hospital by ambulance due to massive vaginal bleeding, and we performed UAE
followed by D＆C at 10 weeks, and diagnosed no molar change
pathologically. Case3 A 33 years old woman with a past historyof previous cesarean section was diagnosed with CSP at five
weeks of gestation through ultrasound examination. She had abnormal vaginal bleeding appeared at 6 weeks of gestation andwas referred for the management of CSP. When she arrived at
our hospital, massive blood flow but not gestational sac was detected around the scar. We performed only UAE. She was diagnosed with clinical invasive mole due to the elevated hCG level（6 days after UAE）
. UAE combined with D＆C might be an effective uterine conservative treatment for CSP and useful forhistological diagnosis of CSP.

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ISP-33-4!

Non invasive positive pressure ventilation for preeclamptic
women；4 case reports Kohei Hamada, Yoshitsugu Chigusa,
Eiji Kondoh, Yusuke Ueda, Shunsuke Kawahara, Haruta
Mogami, Masaki Mandai Kyoto University HospitalObjective Pleural effusion or pulmonary edema caused by
preeclampsia could be an indication for termination of pregnancy. Taking the mortality and morbidity of neonates into account, however, the decision of early preterm delivery is a clinical dilemma for obstetricians. Although non invasive positive
pressure ventilation（NPPV）has been widely used in patientswith respiratory failure, there has been limited data and evidence regarding NPPV during pregnancy thus far. Therefore
the aim of this study was to evaluate the clinical outcome of
NPPV management for respiratory distress in pregnancy due topreeclampsia. Methods The medical record of cases managedwith NPPV during pregnancy in our institution was reviewed,
and patientsʼ characteristics, background, pregnancy outcome,and complications of NPPV were analyzed retrospectively. Results NPPV was employed in four pregnant women between
2011 and 2016 in our hospital, and all cases were diagnosed withsevere preeclampsia. In three cases, pleural effusion was de-

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tected and the other case was complicated with sleep apnea syndrome. NPPV was initiated at 20, 23, 24, and 30 weeks of gestation, respectively. In all cases NPPV alleviated respiratory distress, and succeeded in delaying the termination of pregnancy
for 17 days on average. Maternal outcome was uneventful andno intubation was required. No complication such as aspiration
caused by NPPV was observed. Conclusion NPPV might contribute to prolongation of pregnancy in patients with poor oxygenation due to preeclampsia.

（1,025±189 vs 913±170 ml/min/kg, p＜0.05）,UVFV/kg（136±
51 vs 103±30 ml/min/kg, p＜0.05）and Distribution（13.4±4.5
vs 11.6±3.6%, p＜0.05）.Ritodrine infusion caused increase in fetal heart rate and the right cardiac output relating to CCO, anddiameter of intrahepatic umbilical vein and mean umbilical vein
flow velocity relating to UVFV. Conclusion Ritodrine infusion
increases fetal cardiac distribution to the placenta in AGA witha gestation of 19 39 weeks.

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ISP-33-5!

Study on the Kinetics of Pregnancy Related Proteins in Primates
Hirofumi Kashiwagi, Shunichiro Izumi, Kanako
Mitsuzuka, Atsuko Togo, Hitoshi Ishimoto, Mikio Mikami Tokai
University
Objective Decidual membrane forms the environment to inhibitthat fetus and placenta were excluded as allografts. There areproteins to suppress the cytotoxic activity of T cells and NK
cells which are called pregnancy related proteins. In this study,
it is important to clarify the role of these proteins to contributeto the acceptance of allografts in the pregnancy. We examined
what proteins and functions were preserved evolutionarily andimportant for maintaining placental function through comparing the difference between human and Common Marmoset（CM）pregnant kinetics. Methods Plasma were collected in eachtrimester and non pregnancy cycle, and analyzed by LC/MS.
We predicted the homology and domain structure of these proteins. Finally, expression in placenta was analyzed by IHC and
RT PCR. Results In our LC/MS study, protease inhibitors thatshowed the most prominent changes were PZP in human and A
2ML1 in CM. These proteins belong to the same A2M family asprotease inhibitors capable of inhibiting multiple proteases. Sequence analysis of BAIT REGION which determines the specificity to the proteases showed that this very limited region hadvery low homology compared to all amino acid sequences which
had high homology. These proteases common to PZP in humanand A2ML1 in CM were predicted to be MMP9 and PE. In IHC,PZP and A2ML1 were accumulated in maternal fetal interface
in placenta. Conclusion PZP in human and A2ML1 in CM
showed prominent changes during pregnancy. These molecules
work for the maintenance of pregnancy through inhibitory action against a common protease.

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ISP-33-6
Change in fetal cardiac output distribution to the placentawith ritodrine tocolysis Ryuichi Shimaoka, Tomomi Shiga,
Tatsuro Furui, Kenichiro Morishige Gifu University
Objective To define the normal range of fetal blood flow distribution to the placenta estimated from the ratio of fetal combined
cardiac output（CCO）and umbilical vein flow volume（UVFV）,
and to investigate the change in the distribution with ritodrine
tocolysis. Methods This was a single center cross sectional
study of 189 singleton and appropriate for gestational age（AGA）pregnancies with a gestation of 19 39 weeks. Fetal CCO
and UVFV were measured and the distribution was calculated
in every pregnancy checkup. Ritodrine group was defined ascases with ritodrine therapy more than 50 μg/min for premature labor（n=43）, and non ritodrine group（n=43）was extractedwith propensity score matching for estimated fetal body weight（EFBW）and gestational age at measurement. Results Fetal
CCO and UVFV increased linearly with gestation（r=0.86, p＜
0.01 and r=0.58, p＜0.01 respectively）,and they were almost unchanged in corrected by EFBW. The normal CCO/kg, UVFV/
kg and distribution were on average 1,009±200 ml/min/kg, 115±36 ml/min/kg and 11.8±4.1% respectively. Ritodrine groupwas significantly higher than non ritodrine group in CCO/kg

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Post surgical maintenance of cardiac function in an ex vivopremature lamb model Yusaku Kumagai, Masatoshi Saito,
Nobuo Yaegashi Tohoku University
Objective Ex vivo uterine environment（EVE）therapy is an experimental neonatal intensive care model which involves surgical cannulation of umbilical vessels to connect parallel membranous oxygenators for fetal gas exchange. The aim of the current
study was to evaluate the impact of the cannulation on fetal circulation and cardiac function using ultrasound measurements.
Methods The study was performed on preterm lambs at gestational age（GA）of 115±3 days. Fetuses received either 8 Fr arterial and 10 Fr venous catheters（n=5, Group A）or 10 Fr arterial 10 Fr venous catheters（n=5, Group B）, which were placed
into umbilical vessels. Fetal circulation（flow direction of DA
and FO）and cardiac function（MV/TV E/A, MPI, Ao Vmax
and PLI）were measured after surgery and in ewes of corresponding GA（n=6, Controls）. Data were assessed by ANOVA
and Tukeyʼs test. Results Blood flow at DA and FO was kept
right to left direction in all groups. Regarding MV E/A andTV E/A, Group A had a significantly higher value than Group
B or Controls. There was no significant difference between
Group B and Controls. For MPI and Ao Vmax, both Group A
and B were significantly different from controls. There was no
significant difference between group A and B. No difference
was observed for PLI among the three groups. Conclusion Fetal
circulation was maintained immediately after surgery in bothcatheter groups. Enlargement of catheter diameter contributed
to improvement in cardiac function as a result of decreasing inafterload. However, further improvement is necessary to fill thegap between natural and EVE animals.

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ISP-34-2
What is useful ultrasound screening for congenital heart disease in the first trimester? Mayumi Tokunaka, Ryu Matsuoka,
Hiroko Takita, Tatsuya Arakaki, Tomohiro Oba, Masamitsu
Nakamura, Akihiko Sekizawa Showa University HospitalObjective To evaluate the methods of ultrasound screening for
fetal congenital heart disease（CHD）in the first trimester. Methods A prospective cohort study was conducted at a single university hospital in the period from January 2012 to February
2017. Patients who had first trimester screening and diagnosed
as CHD ant and postnatally were enrolled. All cases were undergoing ultrasound screening by four chamber views（4CV）using B mode at 11 to 13+6 weeks gestation（1stTS）and by 4CV
and outflow tracts views using B and color Dopplar mode at 18
to 20 weeks gestation（2ndTS）.The accuracy of detection in thisscreening protocol for CHD was investigated. Results There
were 5,015 cases which were singleton pregnancy and undertaken 1stTS. Overall, CHD were detected 45 cases. In 15 cases,
the findings suspected for CHD were observed at 1stTS. In
these cases, 9 cases were terminated, 5 cases were intrauterine
death, and one case was confirmed as CHD after delivery. There
were 17 cases which were not suspected at 1stTS and diagnosed
as CHD at 2ndTS. In those cases, 12 cases had possibilities to detect CHD at 1stTS if we assessed not only by 4CV using B mode,
but by 4CV and outflow tracts views using color Dopplar. Addi-

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tionally, 13 cases were diagnosed postnatally as CHD, and mostof those had ventricular septal defect. Conclusion It could bepossible to detect CHD in the first trimester with a higher detection rate if both 4CV and outflow tract views were assessed.

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ISP-34-4
Elastography for predicting time to delivery at third trimester Yoshie Yo, Masao Shimaoka, Ayako Suzuki, Hanako Sato,
Kiko Yamamoto, Risa Fujishima, Shiro Takamatsu, Akiko
Kanto, Yasushi Kotani, Hidekatsu Nakai, Isao Tsuji, Noriomi
Matsumura Kindai University HospitalObjective The Bishop score has been widely used to evaluate
how much the pregnant woman is ready for vaginal delivery.
Although ripening of the uterine cervix is a major component of
the Bishop score, it is subjectively determined, and therefore,
not reproducible among different obstetricians. Elastography is
an ultrasound based modality to evaluate stiffness of tissues.
The aim of the study was to test whether elastography could
evaluate cervical stiffness and predict delivery at third trimester. Methods A total of 43 women who experienced spontaneousvaginal delivery of singleton babies at our hospital were analyzed with written consent of the individuals under the approval of the institutional ethics committee. We assessed cervical ripening of pregnant women every week after 36 weeks ofgestation using both digital examination and ultrasonography.
The stiffness of internal ostium of uterus was classified into
three；hard, middle, and soft. Results The average Bishop scoreof women who delivered within 7 days was higher than women
who delivered over 7 days after the examinations（3.5 vs. 2.6, p＜0.001）. The average cervical length was also different between them（24 mm vs. 29mm, p=0.011）. The soft internal!

ISP-34-5
Timing of birth for women with a twin pregnancy in the past
three years Aya Yoshida, Atsushi Kasamatsu, Chikako Soejima,
Shuhei Nishibata, Yuki Yasuhara, Takuya Yokoe, Yumi Kuroda,
Naoko Kobayashi, Mio Matsumoto, Tomomi Okano, Susumu
Sawaragi, Hidetaka Okada Kansai Medical University
Objective The optimal gestational duration for twin pregnancy
is unknown. The aim of this study was to evaluate the incidenceof serious complications for both maternal women and infants ofa twin pregnancy. Methods From 2014 through 2016, we retrospectively reviewed medical records of 130 women with a twin
pregnancy（monochorionic diamniotic twins 47cases, Dichorionic diamniotic twins 83 cases）delivered at 36 weeks or after
gestation at our institution. We examined maternal serious complications（severe pregnancy induced hypertension, eclampsia,
abruptio placentae, HELLP syndrome, cerebrovascular disease）,
delivery outcomes, infantsʼ complications（respiratory distress,
nasal continuous positive air way pressure or intubation, needfor neonatal intensive care（NICU））, and outcomes. The chisquare test or Fisherʼs exact test was used for categorical variables. Results The success rate of cesarean delivery was 82%（41/50）in the planned cesarean delivery, and that of vaginal
delivery was 79%（63/80）in the planned vaginal delivery. And
that of the cesarean delivery of the second twin after vaginal
birth of the first was 4 cases. The rate of maternal serious complications in women at 36, 37, 38 and 39 weeksʼ gestation, was
1.5%, 13.9%, 2.4% and 16.7%, respectively. There were significant
differences in the respiratory distress and NICU between infants born at 36 weeks and 37 weeks or after（22% and 5%, 33%
and 13%, respectively）. Conclusion Delivery of twins at 37
weeks or after gestation decreases infantsʼ complications without maternal complications increases, as compared with 36
weeksʼ gestation.

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ISP-34-6
Outcomes of placental abruption in 75 patients Kazuma
Onishi, Hiroyuki Tsuda, Masatoshi Esaki, Akiko Kimura, Keiko
Sakata, Kazuya Fuma, Yoshiaki Maseki, Atsuko Tezuka,
Tomoko Ando, Kimio Mizuno Japanese Red Cross Nagoya Daiichi HospitalObjective In pregnancies complicated with placental abruption（PA）, a negative correlation was revealed between the onset
to delivery time and neonatal and maternal outcomes. We investigated the differences in neonatal and maternal outcomes
between patients with and without maternal transfer from otherclinics. Methods We retrospectively reviewed patients with PA
from January 2009 to September 2017. We investigated 75 patients with PA excluding 7 intrauterine fetal deaths, 2 vaginal
deliveries, and 1 chronic PA. We examined the correlation between the onset to delivery time and neonatal and maternal
outcomes. We also compared these outcomes between transferred and non transferred patients. Results The average umbilical artery pH of neonates delivered ＜45 minutes from onset
was significantly higher than those delivered 45 minutes fromonset（7.211 vs. 7.027；p=0.02）. The average onset to delivery
time of patients transferred from other clinics was significantly
longer than non transferred patients（284 vs. 135 minutes；p＜0.0001）. No significant differences were noted in the umbilicalartery pH or DIC score between transferred patients and non

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Analysis of fetal gross movements in light for date infants bya fetal movement acceleration measurement recorder
Masayoshi Morita, Eiji Ryo, Youhei Nagaya, Michiharu Seto,
Hideo Kamata, Yasuhiro Matsumoto, Masahiro Shiba, Yukifumi
Sasamori, Koichiro Kido, Takuya Ayabe Teikyo University HospitalObjective The purpose of this study was to investigate the fetal
gross movements（FGM）of fetal growth restriction（FGR）using fetal movement acceleration measurement recorder（FMAM recorder）.Methods（Subject）Study group：A total of
17 pregnant women who delivered light for date（LFD）single
infant. Control group：A total of 60 pregnant women who delivered appropriate for date（AFD）single infant at term.（Recording）The pregnant women themselves recorded FGM by FMAM
recorder weekly from 28 weeks to term.（Assessment）The records which could be obtained more than 4 hours per night
were assessed by a newly developed software. The following
numbers were calculated.（1）The ratio of 10 second epoch with
FGM to total epoch on the number basis per night.（2）The numbers of FGM per hours.（3）（a）The average number（per hours）
of non FGM periods which were more than 5 min, 10 min, 15min, and 20 min, and（b）the average duration and（c）the longest duration of non FGM periods through night.（Statisticalanalysis）Linear regression analysis was conducted with the
FGM numbers as response variable and explanatory variables（LFD or AFD, gestational weeks, maternal height, and bodymass index）. Results Study group vs Control group：（1）13.57
vs 14.73%（p=0.0118）（. 2）58.64 vs 66.63 times/h（p=0.0017）（. 3）（a）5min 2.34 vs 1.85 times/h（p=0.0002）, 10min 0.69 vs 0.51
times/h（p=0.0025）, 15min 0.32 vs 0.23 times/h（p=0.0085）, 20
min 0.17 vs 0.12 times/h（p=0.0020）.（b）9.34 vs 8.73 min（p=0.0072）,（c）25.3min vs 19.05 min（p＜0.0001）.Conclusion FGR
fetuses decreased FGM and increased non FGM periods.

ostium was correlated with deliveries within 7 days（p=0.027）,
whereas the hard internal ostium was correlated with deliveries
later than 7 days（p=0.0038.）. A multivariate analysis indicatedelastography was an independent predictor of delivery within 7
days. Conclusion Elastography may be useful to predict time todelivery.

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transferred patients. Conclusion PA is an important cause ofperinatal mortality and morbidity, so prompt delivery should be
performed after a diagnosis. However, diagnosing PA exactly isdifficult, and its severity varies. We detected no significant differences in neonatal and maternal outcomes between transferred and non transferred patients. In Aichi Prefecture, aunique maternal transfer system using the iPhone was established, and most patients can transfer from clinics to our hospital smoothly and promptly. This system may have affected theresults of our study.

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ISP-34-7
Hyperfibrinolysis with Consumptive Coagulopathy in Amniotic Fluid Embolism Tomoaki Oda, Naoaki Tamura, Yukiko
Kohmura, Naomi Furuta, Toshiyuki Uchida, Kazunao Suzuki,
HamaHiroaki Itoh, Kazuhiro Sugihara, Naohiro Kanayama
matsu University School of Medicine
Objective Amniotic fluid embolism（AFE）induces an abrupt
and severe disseminated intravascular coagulation（DIC）. Although consumptive coagulopathy has been considered as thecause of DIC, the details are still unknown. Considering the roleof fibrinolysis, fibrin is degraded mainly by plasmin along withneutrophil elastase（NE）. Our objective is to investigate hyperfibrinolysis at the onset of AFE. Methods We have collectedmany blood specimens suspected as AFE from all over Japan.
We investigated plasma from patients of AFE and atonic bleeding collected within 2 hours from the onset without blood transfusion since the year 2009 up to 2017. Diagnosis of AFE wasbased on the Japanese criteria, which also required fibrinogenvalue below 2.0 g/l at the onset. Plasmin α2 plasmin inhibitor
complex（PIC）, fibrin degradation product by elastase（EXDP）,
fibrin degradation product（FDP）, D dimer, and NE were compared. The data was described as median with minimum tomaximum. Chi square and Mann Whitney U test were used forstatistical analysis. Results The number of the patients were 13
in both the two groups. There was no difference in blood loss at
plasma collection. The number of AFE patients with fibrinogen
below 1.0 g/l were significantly more than that of atonic bleeding patients（n=7 vs. 0）. PIC（μg/ml）（42.7［0.3 143］vs. 4.9［1.033.9］）, FDP（μg/ml）（667［304 1,111］vs. 80［27 119］）, and D dimer（μg/ml）（117［45.7 687］vs. 16.6［3.99 57.0］）were significantly higher in the AFE group. EXDP and NE had no significant differences. Conclusion AFE patients had hyperfibrinolysis due to excessive plasmin along with consumptive coagulopathy at the onset.

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ISP-35-1
Identification of risk factors in patients with positive lymph
node after radical hysterectomy for early stage cervical cancer Soyi Lim1, Yoon-Jin Cho1, Kwang-Beom Lee1, Jong-Min Lee2
Gachon University Gil Medical Center, Korea 1, Kyung Hee University Hospital at Gangdong, Kyung Hee University College ofMedicine, Korea 2
Objective To identify risk factors in patients with lymph nodemetastasis after radical hysterectomy for early stage cervicalcancer. Methods The medical records of patients with earlystage cervical cancer with lymph node metastasis after radical
hysterectomy and lymph node dissection conducted fromMarch 2006 to December 2015 at the Gil Medical Center wereretrospectively analyzed. Patients that received chemotherapy,
radiation therapy or concurrent chemoradiotherapy before surgery and patients with neuroendocrine or sarcoma histology
were excluded. Histological tumor type, tumor size, lymph vascular space invasion, parametrial involvement, number of positive nodes, and involvements of common iliac nodes andparaaortic lymph nodes were assessed and correlations with tu-!

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mor recurrence were sought. Results We analyzed 523 patientswith FIGO stage IB to IIA cervical carcinoma that underwent
radical hysterectomy with lymph node dissection. Pathologicalanalyses of surgical specimens showed positive lymph nodes in
127 patients（24.3%）. When the above mentioned variables were
subjected to Cox proportional regression analysis, parametrial
infiltration and metastatic lymph nodes（ 5）were found to besignificantly correlated with disease specific survival. Using
these two factors, node positive patients were divided into lowrisk（n=57）, intermediate risk（n=47）, and high risk（n=23）
groups. Disease specific survival for the high risk group was
significantly poorer than for the intermediate and low risk
groups. Conclusion The prognosis of node positive patients after radical hysterectomy was found to be different according toclinicopathologic risk factors. Current adjuvant therapy strategies after surgery may not be sufficient for patient with positive
nodes. New strategies that improve survival should be considered for such patients.

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ISP-35-2
Sentinel lymph node mapping using indocyanine green in cervical cancer Sahori Kakuda, Eiji Kobayashi, Tsuyoshi Takiuchi,
Yuri Matsumoto, Michiko Kodama, Kae Kashimoto, Seiji
Mabuchi, Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu,
Kiyoshi Yoshino, Tadashi Kimura Osaka University
Objective Sentinel lymph node（SLN）biopsy technique is gradually applied for gynecologic malignancies although its reliability
is unclear. Near infrared（NIR）imaging appears to be a beneficial new technique for SLN biopsy. The objective of this study
was to evaluate the detection rate, sensitivity, and negative predictive value（NPV）of laparoscopic NIR fluorescence imaging
for early stage cervical cancer. Methods From January 2013 toAugust 2017, 36 early stage（FIGO2008, stage1A 2B）cervicalcancer patients undergoing SLN biopsy were retrospectively
analyzed. All patients had undergone laparoscopic radical hysterectomy with pelvic lymphadenectomy after SLN biopsy. Results The overall and bilateral detection rate was 100%（36/of
36）and 86.1%（31/36）. Positive SLNs were found in 11.1%（4/36）.
The sensitivity and negative predictive value for SLN were100% respectively. The average SLN count was 3.7（0 9）. Allprocedures were successfully completed without conversion to
open laparotomy, and no intraoperative or postoperative complications occurred. Conclusion Laparoscopic SLN mapping withICG for cervical cancer patients revealed high detection rate,sensitivity and NPV. Prospective studies are needed to determine if SLN mapping can replace lymphadenectomy in this setting.

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ISP-35-3
Extraperitoneal Radical Trachelectomy With Pelvic Lymphadenectomy：A Novel Fertility Preserving Option for
Early Stage Cervical Cancer Patients Kazunobu Yagi, Seiji
Mabuchi, Tsuyoshi Takiuchi, Yuri Matsumoto, Michiko
Kodama, Eiji Kobayashi, Kae Hashimoto, Yutaka Ueda, Kenjiro
Sawada, Takuji Tomimatsu, Kiyoshi Yoshino, Tadashi Kimura
Osaka University
Objective Radical trachelectomy combined with pelvic lymphadenectomy has been used to treat early stage cervical cancer patients who wish to preserve their fertility. Although vaginal, abdominal, laparoscopic, and robotic approaches have beenused during this procedure, all of these approaches cause peritoneal damage, which could result in periadnexal adhesion. The
aim of the present study was to introduce and discuss a novel
fertility preserving option, extraperitoneal radical trachelectomy with pelvic lymphadenectomy. Methods To minimize
peritoneal damage, we developed a new surgical approach for

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ISP-35-4
Identifying a candidate population for ovarian conservation
in young women with clinical stage IB IIB cervical cancer
Imari Deura1, Muneaki Shimada2, Koji Matsuo3, Satoshi
Yamaguchi4, Hiroyuki Kanao5, Toru Nakanishi6, Toshiaki Saito7,
Shoji Kamiura8, Takashi Iwata9, Nao Suzuki1, Mikio Mikami10,
Toru Sugiyama11 St. Marianna University School of Medicine 1,
Tohoku University Hospital 2, University of Southern California,
USA 3, Hyogo Cancer Center 4, Cancer Institute Hospital 5, Tohoku
Medical and Pharmaceutical University 6, Kyushu Cancer Center 7, Osaka International Cancer Institute 8, Keio University 9, Tokai University 10, Iwate Medical University 11
Objective To identify risk factors associated with ovarian metastasis and to characterize a population with minimum risk ofovarian metastasis in young women with stage IB IIB cervicalcancer. Methods This was a nation wide multicenter retrospective study in Japan examining consecutive cases of surgicallytreated women with clinical stage IB IIB cervical cancer who
had oophorectomy at radical hysterectomy（n=5,697）. Multivariable analysis was performed to identify independent risk factors
for ovarian metastasis. Results Ovarian metastasis was seen in70（1.2%）cases. In the entire cohort, adenocarcinoma, lympho
vascular space invasion, uterine corpus tumor invasion, and pelvic/para aortic nodal metastases remained independent risk
factors for ovarian metastasis（all, adjusted P＜0.05）.In a sensitivity analysis of 3,165 women aged＜50 years（ovarian metastasis, 1.0%）, adenocarcinoma, parametrial tumor involvement,
uterine corpus tumor involvement, and pelvic/para aortic nodal
metastases remained independent risk factors for ovarian metastasis（all, adjusted P＜0.05）.In the absence of these five risk
factors（representing 46.1% of women aged＜50 years）, the incidence of ovarian metastasis was 0.14%. With the presence ofadenocarcinoma alone（representing 18.9% of women aged＜50years）, the incidence of ovarian metastasis was 0.17% and was
not associated with increased risk of ovarian metastasis compared to the subgroup without any risk factors（P=0.87）.Conclusion Nearly two thirds of women aged＜50 years with clinicalstage IB IIB cervical cancer had no risk factor for ovarian metastasis or had adenocarcinoma alone：these subgroups had
ovarian metastasis rates of around 0.1% and may be a candidate
population for ovarian conservation at surgical treatment.

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ISP-35-5
Salvage hysterectomy after concurrent chemoradiotherapy

for advanced cervical cancer Natsuko Kamiya, Yuichi Imai,
Tatsuya Matsunaga, Yukihide Ota, Yukio Suzuki, Naho
Ruiz Yokota, Mikiko Sato, Etsuko Miyagi Yokohama City University HospitalObjective Chemotherapy, salvage hysterectomy, and follow up
are options for patients with residual tumor after concurrent
chemoradiotherapy（CCRT）for locally advanced cervical cancer. We have conducted hysterectomy on such patients since2009. Here, we retrospectively evaluated selection of patients,and effectiveness and safety of the salvage hysterectomy. Methods We conducted hysterectomy on 26 patients suspected tohave residual tumor after CCRT as primary treatment of advanced cervical cancer between January 2009 and March 2017.
We retrospectively assessed the preoperative examinations,presence of residual tumor in resected uterus, adverse eventsand local tumor control rate. Results The median age was 49.5
（29 75）years. The histo pathological diagnosis before CCRT
was squamous cell carcinoma（SCC）in 6 cases and non SCC in
20 cases. Nineteen patients had pathological residual tumor in
resected uterus（group A）and seven had no tumor（group B）.
The sensitivity and specificity of preoperative MRI for detecting residual tumor were 90.5% and 71.4%, and those of pathological examination were 77.8% and 42.9%, respectively. Using bothmeasures, the sensitivity and specificity were 73.7% and 100%,
respectively. Moreover, tumor markers were higher in group A.
The local recurrence rate was 23.1% and the complication rate
was 38.5%. Conclusion Combination of imaging and pathologicalexamination after CCRT may be useful for evaluation of residual tumor. Tumor markers also may be helpful for it. Salvage
hysterectomy could be an effective strategy for advanced cervical cancer, but the indication should be assessed carefully because of surgical complications and it will be shown based on
the further prospective study.

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ISP-35-6
Efficacy of neoadjuvant chemotherapy plus radical hysterectomy for stage IB2, IIA2 and IIB cervical cancer Takahito
Ashihara, Masahiro Sumitomo, Naoki Horikawa, Hirofumi
Nonogaki Shiga Medical Center for Adults
Objective In Japan Society of Gynecologic Oncology guidelines
2017 for the treatment of uterine cervical cancer, the efficacy of
NAC for stage IB2, IIA2 and IIB cervical cancer is restrictively
recognized. Nevertheless, NAC therapy has disadvantages tumor progress before surgery if tumor has not responded, and intraoperative blood transfusion increase due to chemotherapy induced anemia. The aim of this single institution study was toevaluate the disadvantage of NAC plus radical hysterectomy.
Methods We performed a retrospective analysis of patients withstage IB2, IIA2, IIB cervical cancer started therapy at our hospital from January 1, 2009 to January 1, 2016. They were received
either neoadjuvant chemotherapy（NAC）plus radical hysterectomy（NAC group）or radical hysterectomy alone（RH group）or
concurrent chemoradiation therapy（CCRT group）. Results A
total of 56 patients were enrolled, 17 of whom were underwent
NAC plus radical hysterectomy. Twelve patients（70.6%）had
more than 30% decrease in tumor size and 16 patients（94.1%）
had underwent planned radical hysterectomy after NAC. The
NAC group did not show unacceptable toxicity and increase significant intraoperative blood transfusion. On the other hand, although tumor size in NAC group was significantly larger thanin RH group and patients with stage IIB in NAC group and
CCRT group were significantly more than in RH group, there
was no significant difference in overall survival（OS）and disease free survival（DFS）among these three groups. Conclusion
This study confirmed that NAC plus radical hysterectomy is acceptable treatment option for stage IB2, IIA2 and IIB cervicalcancer.

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radical trachelectomy combined with pelvic lymphadenectomy.
All surgical procedures associated with radical trachelectomy
and pelvic lymphadenectomy were performed via an extraperitoneal approach. During this procedure, the uterine arteries, inferior hypogastric nerve, and pelvic splanchnic nerve were preserved. Results Extraperitoneal nerve sparing radical trachelectomy with pelvic lymphadenectomy was performed in 3
Japanese women with FIGO stage IA2 and IB1 cervical cancers.
In all patients, complete resection of the disease was achieved
without causing any intraoperative complications. Although aninfected lymphocele developed in a patient that was managed
conservatively, no severe postoperative complications werenoted. No adjuvant treatments were given, and the patients are
currently free of disease. Conclusion This is the first reportabout extraperitoneal radical trachelectomy in patients withearly stage cervical cancer. Extraperitoneal radical trachelectomy combined with pelvic lymphadenectomy can be safely
performed. Because peritoneal damages, which can cause periadnexal adhesion, could be avoided, we consider that this surgical approach may be an ideal treatment option for women withearly stage cervical cancer who wish to preserve their fertility.

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ISP-35-9Comparison of laparoscopic and open radical hysterectomies
in the surgical treatment of stage IB1 cervical cancer in a single institute in Japan Tsuyoshi Takiuchi, Eiji Kobayashi, Yuri
Matsumoto, Michiko Kodama, Kae Hashimoto, Seiji Mabuchi,
Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu, Kiyoshi
Yoshino, Tadashi Kimura Osaka University
Objective In many countries, the two common ways of surgical
technique of stage IB1 cervical cancer are the laparoscopy andthe laparotomy. Our aim is to compare the intra and postoperative results of laparoscopic radical hysterectomy（LRH）and abdominal radical hysterectomy（ARH）in a single institute in Japan. Methods Twelve LRH and 11 ARH were performed fromJanuary 2015 until December 2016 because of stage IB1 cervicalcancer. Results were analyzed retrospectively. The surgical outcomes include operating time, blood loss, pelvic lymph node
yield, hospitalization days, and intraoperative and postoperativecomplications. Follow up results were also analyzed for all patients. Results Both groups have similar patient and tumor characteristics. Median follow up time was 17 months（range 8 30
months）. There was no significant difference between the twogroups in pelvic lymph node yield, intra and postoperativecomplications and length of hospitalization. The operating time
was significantly shorter in the ARH group. The treatment with
LRH was generally superior to ARH with respect to blood loss.
No conversion of laparotomy occurred in the LRH group. On follow up of patients, there was one relapse reported in bothgroups, respectively. Conclusion Results of LRH are comparable
and not worse than ARH. LRH may pose a safe and feasible alternative to ARH and have a priority because of the general advantages of laparoscopic surgery in the surgical treatment ofstage IB1 cervical cancer in Japan.

Radical hysterectomy after radiotherapy for recurrent or
persistent cervical cancer Seiji Mabuchi, Tsuyoshi Takiuchi,
Yuri Matsumoto, Michiko Kodama, Eiji Kobayashi, KaeHashimoto, Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu,
Kiyoshi Yoshino, Tadashi Kimura Osaka University
Objective To evaluate the safety and efficacy of radical hysterectomy after radiotherapy（RH AR）for recurrent or persistentcervical cancer. Methods The present retrospective study included patients who underwent RH AR for recurrent or persistent cervical cancer between May 1, 2010 and September 30,
2016. Patient characteristics, intraoperative and postoperative
adverse events, and surgical outcomes were investigated to
identify patients at increased risk of recurrence or severe surgical adverse events. Results There were 31 patients scheduled
for treatment with RH AR；one hysterectomy procedure wasaborted. No intraoperative adverse events or treatment related
deaths occurred, and 8（27%）patients experienced severe postoperative adverse events. After a median 34 months of follow
up, 13（43%）patients had developed recurrent disease, predominantly at distant sites. The estimated 3 year overall survival
rate was 53.8%. Positive surgical margins, nodal metastasis,parametrial invasion, and no adjuvant treatment after RH AR
were found to be predictors of increased risk of recurrence. No
predictors of severe surgical adverse events were identified.
Conclusion RH AR was a safe, curative treatment for patientswith recurrent or persistent cervical cancer. However, considering the significant risk of surgical adverse events, RH AR
should only be performed for a select group of patients.

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ISP-35-8
A retrospective study of uterine arterial neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage IB2 to IIB uterine cervicalcancer Takashi Suzuki, Hiroshi Adachi, Hiroharu Kobayashi,
Misa Kobayashi, Hiroko Konno, Shuhei Terada, Naoko Inaoka,
Ayumi Yasuda, Keiichiro Kato, Kentaro Iga, Satoru Nakayama,
Takeshi Murakoshi Seirei Hamamatsu General HospitalObjective To evaluate the effectiveness and adverse events ofuterine arterial neoadjuvant chemotherapy（UAI NAC）plus
radical hysterectomy（RH）compared to RH alone in the stage
IB2 to IIB patients. Methods Patients diagnosed cervical cancer
and treated with both UAI NAC and RH in our facility fromJanuary 2009 through August 2016 with informed consent wereenrolled. Indications of UAI NAC in our facility are；RH could
not be scheduled within 8 weeks since first visit, staging between IB2 and IIB, histopathologies with squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. RH
would be appropriate if the tumor size is reduced. Intraarterial
cisplatin（60 mg/m2）on day 1 followed by intravenous paclitaxel（80 mg/m2）on days 2, 9 and 16 of a 28 day cycle, maximum of 3
courses. We assessed overall survival（OS）with the log rank
test, estimating hazard ratio（HR）with a Cox proportional hazards model. Furthermore, surgical time and blood loss were assessed with Mann Whitney U test. Results Total of 22 cases of
UAI NAC plus RH and 28 cases of RH alone with stage IB2 to
IIB were enrolled. Median ages were 47.5 and 44.5（p=0.463）
years, respectively. p value of OS were 0.882, HR 1.138（95% CI
0.21 6.3）. Surgical time（p=0.123）and blood loss（p=0.984）were
not statistically significant. Conclusion UAI NAC plus RH
might be another option for those who had to wait for RH morethan 8 weeks in stage IB2 to IIB cervical cancer patients.

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ISP-36-1
The efficacy of national HPV vaccination program against
cervical cancer in Japanese young women Risa Kudo1,
Masayuki Sekine1, Manako Yamaguchi1, Sosuke Adachi1, Asami
Yagi2, Yutaka Ueda2, Sharon Hanley3, Etsuko Miyagi4, Takayuki
Enomoto1 Niigata University 1, Osaka University 2, Department of
Womenʼs Health Medicine, Hokkaido University 3, Yokohama
City University 4
Objective To investigate the effectiveness of national HPV vaccination program against cervical cancer for Japanese young
women. Methods We recruited 20 22 years old females who attended the public cervical cancer screening program from April
2014 to March 2017 in Niigata, Japan. HPV testing was performed using HCII（Qiagen）and TM HPV kit（MEBGEN）andquestionnaire about HPV vaccination was conducted. A Chi
square test was used in this statistical analysis. Additionally, we
counted prevalence ratios（PR）and vaccine effectiveness（VE）,
their 95% confidence intervals. Results HPV testing was performed to a total of 2,197 registrants and 2005 women were eligible for this study. A total of 1,546（77.1%）participants were vaccinated, and 459（22.9%）were unvaccinated. High risk HPV infection rate was 12.0% in vaccinated group and 15.3% in unvaccinated group, respectively（p=0.08）. The prevalence of vaccine
types 16 and 18 was significantly lower in vaccinated group（0.2%）than in unvaccinated group（2.2%；p＜0.001）. Similarly,
the prevalence of HPV 31, 33 and 45 which are cross protectedby HPV bivalent and quadrivalent vaccination was significantly
lower in vaccinated group（0.8%）than in unvaccinated group（1.7%；p=0.11）. PR and VE against HPV 16/18 was 0.09（95%CI
0.03 to 0.32）and 91%（95% CI 68% to 98%）
. Conclusion Our study
demonstrates evidence of high effectiveness of national HPV
vaccination program in Japanese young women.

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ISP-36-2!

Correlation among HPV derived transcriptomes, HPV types
and CIN grades Satoshi Baba1, Ayumi Taguchi1, Akira Kawata1,

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ISP-36-3
Phase I/IIa study of photodynamic therapy using talaporfin
sodium and diode laser（L PDT）for Cervical Intraepithelial
Neoplasia
Masaru Sakamoto1, Kiyohiko Miyake1, Hiroshi
Tanabe1, Yasuko Koyamatsu1, Kenji Umayahara1, Tadao
Tanaka1, Aikou Okamoto2 Sasaki Foundation Kyoundo Hospital 1,
The Jikei University Hospital 2
Objective PDT using Photofrin（P PDT）is considered to be atreatment modality with higher fertility sparing capacity thancone resection as uterine preservation therapy for CIN3. However, P PDT has a high efficacy, and despite the low obstetricrisk such as premature birth, side effects of photosensitivity arestrong and the hospitalization period is long, so it has notreached standard treatment. Therefore, in order to investigate
the safety and effectiveness of the next generation L PDT using
semiconductor laser and Laserphyrin with less half life in blood,
we started Phase I/IIa study of L PDT after registration to
UMIN. Methods After approval of the ethical committee, phaseI study of L PDT was performed on nine cases of CIN2 3 withIC. In order to investigate the optimal dose of laser irradiation, 3cases were performed for each step of 50, 75 and 100 J/cm2. Results Phase I study was performed in 9 cases in total. Intra tumor accumulation of Laserphyrin was confirmed by Fluorescence microscopy. Dose Limiting Toxicity was not observed,
suggesting safety. The main side effects were lower abdominal
pain of G1 2 and fever of G1 2. Photosensitivity was G1 in only
one case. Histological disappearance of CIN2 3 was observed inall 9 cases. Recommended Dose for CIN3 was considered to be
100 J/cm2. Conclusion In L PDT, photosensitivity was hardly
seen unlike P PDT, temporary lower abdominal pain and fever
were observed, suggesting safety. All nine cases showed CR after L PDT, suggesting efficacy. We have started phase II study
in order to further investigate safety and effectiveness of L
PDT.

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ISP-36-4
Posttreatment human papillomavirus testing for residual orrecurrent high grade cervical intraepithelial neoplasia：apooled analysis Mamiko Onuki, Koji Matsumoto Showa University
Objective We conducted a pooled analysis of published studies
to compare the performance of human papillomavirus（HPV）
testing and cytology in detecting residual or recurrent diseases
after treatment for cervical intraepithelial neoplasia grade 2 or3（CIN 2/3）. Methods Source articles presenting data on posttreatment HPV testing were identifiedfrom the National Library of Medicine（PubMed）database. We included 5,319 cases
from 33articles published between 1996 and 2013. Results The
pooled sensitivity of high risk HPV testing（0.92；95% confidence interval［CI］, 0.90 to 0.94）for detecting posttreatment CIN
2 or worse（CIN 2+）was much higher than that of cytology（0.76；95% CI, 0.71 to 0.80）.Co testing of HPV testing and cytology maximized the sensitivity（0.93；95% CI, 0.87 to 0.96）, whileHPV genotyping（detection of the samegenotype between preand posttreatments）did not improve the sensitivity（0.89；95%
CI, 0.82 to 0.94）compared with high risk HPV testing alone. The
specificity of high risk HPV testing（0.83；95% CI, 0.82 to0.84）was similar to that of cytology（0.85；95% CI, 0.84 to0.87）and HPV genotyping（0.83；95% CI, 0.81 to 0.85）, while cotesting had reduced specificity（0.76；95% CI, 0.75 to 0.78）.For
women with positive surgical margins, high risk HPV testing
provided remarkable risk discrimination between test positives
and test negatives（absolute risk of residual CIN 2+ 74.4%［95%CI, 64.0 to 82.6］vs. 0.8%［95% CI, 0.15 to 4.6］；pp＜0.001）. Conclusion Our findings recommend the addition of high risk HPV
testing, either aloneor in conjunction with cytology, to posttreatment surveillance strategies.

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ISP-36-5
Conservative management for cervical intraepithelial neoplasia during pregnancy Misato Ogino, Yasuhiko Ebina, Mizuki
Uenaka, Kaho Suzuki, Senn Wakahashi, Yoshiya Miyahara,
Hideto Yamada Kobe University
Objective To assess the safety and efficacy of conservative management for intraepithelial neoplasia（CIN）during pregnancy.
Methods In this prospective study, 60 pregnant women who
were diagnosed as having abnormal cervical cytology underwent colposcopy between 2010 and 2016. A punch biopsy was
performed in cases with abnormal colposcopy findings. Conservative management was performed in women without invasivecancer. All women underwent cervical cytology every 4 months
during pregnancy, and cervical cytology as well as colposcopy 2
months postpartum. Rates of persistence, progression and regression of CIN were assessed. Whether the delivery mode affected the regression of CIN was also assessed. Results The ageof women was median 30（range 20 39）years old. A punch biopsy was performed in 48（80%）of the 60 women, and demonstrated CIN1（n=7）, CIN2（n=8）and CIN3（n=25）. Postpartum
regression, persistence and progression of lesions were observed in 12（30.0%）, 25（62.5%）, and 3（7.5%）of the 40 womenwith CIN, respectively. No progression to invasive cancer wasobserved. Women who had CIN3 lesion showed high persistence/progression rates（80.0% versus 46.7%, p=0.041）when
compared with women who had CIN1/2. The regression rate in
women who delivered vaginally was not different（32.0% versus
33.3%, p=0.93）from that in women who underwent cesarean section. Conclusion Conservative management for CIN during
pregnancy was found to be relevant for pregnant women with
CIN. The delivery mode did not affect the regression of CIN.

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Satoko Eguchi1, Kensuke Tomio1, Katsuyuki Adachi1, Takashi
Iwata2, Akira Mitsuhashi3, Katsutoshi Oda1, Kei Kawana4,
Yutaka Osuga1, Tomoyuki Fujii1 The University of Tokyo 1, Keio
University Hospital 2, Chiba University Hospital 3, Nihon University Hospital 4
Objective High risk HPV（HR HPV）infection is a main causeof cervical cancer. Expression patterns of HPV derived transcriptomes change with epithelial differentiation and/or CIN
progression. Previous reports suggested that E7 modulates CIN
progression, and that E1ˆE4 is expressed along with epithelial
differentiation. We herein investigated characteristics of HPV
derived transcriptomes in CIN lesions according to HPV types
and CIN grades. Methods After obtaining IRB approvals of ourinstitutions, 174 CIN subjects were prospectively enrolled. HPV
subtypes were confirmed by the PGMY PCR based genotyping
assay. Expressions of HPV E7 and E1ˆE4 were analyzed by realtime PCR, especially focusing on four major HR HPV types（HPV16, 18, 52 and 58）. Results HPV subtypes comprised：
HPV16 in 37 patients（Infection rate of 174 CIN patients in thistrial=21.3%）；HPV18 in 7（4.0%）；HPV52 in 43（24.7%）；and
HPV58 in 38（21.8%）, respectively. In HPV16 or in total analysis,
detection rate of E7 was increased along with the CIN progression（Cochran Armitage test, p=0.0257 and p=0.0015, respectively）. Detection rate of E1ˆE4 was also increased along with
the CIN progression in HPV58 or in total analysis（Cochran Armitage test, p=0.0111 and p=0.0031, respectively）, whereas HPV
18 positive samples did not express E1ˆE4 mRNA regardless of
CIN grades. Conclusion HPV derived transcriptomes may reflect the degree of CIN in HPV type dependent manner.

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Decision making with fathers should influence the acceptance of HPV vaccine for their daughters Mariko Shindo,
Sahori Kakuda, Kiyoshi Yoshino, Tadashi Kimura Osaka University
Objective In Japan, HPV vaccination rate has remained low
since the suspension of the governmental recommendation in
2013. A previous survey showed that mothers decided not tovaccinate their daughters under the present condition without
talking with fathers. The objective of the present study was toassess fatherʼs role in HPV vaccination of their daughters for improvement of HPV immunization coverage in Japan. Methods
We conducted an internet survey with Japanese fathers of 18
22 year old girls who could have HPV vaccination under thegovernmental recommendation（n=2,472）. We assessed fatherʼs
attitude toward HPV vaccine and investigated how they wereinvolved in decision making of their daughtersʼ inoculation. Results A total of 1177 fathers knew their daughterʼs HPV vaccination status（48%）, and among them, 1012 fathers were involvedin family council（41%）. Fatherʼs participation in decision making was associated with increased odds of vaccination of theirdaughters（odds ratio：3.9, 95%CI：2.35 6.46）.When fathers had
positive attitude to HPV vaccine, the relationship between fatherʼs participation in decision making and their daughterʼs inoculation was enhanced（odds ratio：10.51, 95%CI：5.16 21.62）.
Conclusion In order to facilitate HPV vaccination, especially after resumption of the governmental recommendation, we should
inform not only motherʼs but should focus on furtherʼs education.
The health providers need to fill the knowledge gap between
husband and wife, and promote a positive fatherʼs participationin decision making.

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ISP-36-7
Human papilloma virus（HPV）vaccination in Japan：An estrangement between self reported information and municipal
personal record of HPV vaccination in Japanese young
women Manako Yamaguchi1, Masayuki Sekine1, Risa Kudo1,
Sosuke Adachi1, Asami Yagi2, Yutaka Ueda2, Sharon Hanley3,
Etsuko Miyagi4, Takayuki Enomoto1 Niigata University 1, Osaka
University 2, Hokkaido University 3, Yokohama City University 4
Objective The national routine vaccination program against
uterine cervical cancer began from April 2013 in Japan and approximately 1,700 municipalities has managed the immunization
records. However, all of the published clinical studies about theefficacy of in HPV vaccination based on self reported vaccination information in Japan. The precent study was aimed to examine the accuracy of self reported information. Methods We
recruited 20 to 22 year old young women, target generation of
HPV vaccination with public aid, when they had uterine cervical cancer screening in Niigata city. The period of recruitment
was from April 2014 to March 2017. We examined past medical
history of HPV vaccination from questionnaires（self reported
information）and compared those with the municipal immunization records in Niigata city. Results Of 1,230 eligible registrants,
the vaccination rate by self reported information and municipal
records was 75.0%（922/1,230）and 77.2%（949/1,230）, respectively. The accuracy rate of self reported information was asfollows：positive predictive value was 87.7%；negative predictive value was 54.5%；sensitivity was 85.2%；and specificity
was 59.8%. A Kappa statistic was 0.44（95% confidence interval
0.37 0.50）. Approximately 11.4%（140/1,230）of all registrants
have not recollected that they had received vaccination at adolescence and they comprised 45%（140/308）of unvaccinatedgroup in self reported information. Conclusion Our study demonstrates that there was an unignorable estrangement between
self reported vaccination status and municipal personal records

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in HPV vaccination with public aid in Japan. About 10% of
women of 20 to 22 year old have ambiguous memory whether
they received HPV vaccination at adolescence.

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Management of cervical high grade squamous intraepithelial
lesions（HSIL）during pregnancy Yusuke Matsuura1, Satoshi
Aramaki2, Hiroshi Mori2, Chiho Koi3, Taeko Ueda3, Tomoko
Kurita3, Seiji Kagami3, Toshinori Kawagoe3, Toru Hachisuga3
Nursing of Human Broad Development, University of Occupational and Environmental Health 1, Hospital of the University ofOccupational and Environmental Health 2, University of Occupational and Environmental Health 3
Objective Early uterine cervical neoplasms and invasive cancers have been increasing gradually in young women. The
women with cervical neoplasia are often diagnosed in early gestation. We studied the management of women diagnosed with
HSIL during pregnancy. Methods During the five years from2010 to 2014, 1,326 pregnant women came to our University Hospital, and the routine Papanicolaou test with cotton swab was
performed in 89%（625 of 705）.Thirty five（5.6%）showed abnormal cytologic results. HSILs were seen in 28 patients（17 moderate dysplasia and 11 severe dysplasia）, and were compared to 92
non pregnant women with moderate dysplasia below the age of
50 around the same period. Results Underestimation by cervicalPap test in pregnancy occurred in 18% and overestimation in
28%. Underestimation of cytology were encountered in 25%（7 of28）pregnant women with HSIL, and were detected in 45%（41of 92）non pregnant women with moderate dysplasia by brush.
Moderate dysplasia had disappeared in 3 of 17 cases, progression was noted in 7 patients. Conization was performed in 6 patients, and radical abdominal hysterectomy was performed in
one patient. Persistent disease was noted in 9 of 11 patients withsevere dysplasia. Regression, persistence and progression weredetected in 35%, 35%, and 30%, respectively, and conization was
performed in 37 of 92 non pregnant patients with moderate dysplasia. Conclusion The incidence of abnormal Pap test is thesame in pregnant and nonpregnant women. Moderate dysplasia
during pregnancy should be followed carefully as non pregnant
women after delivery.

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Physiciansʼ skill may be a prognostic factor of cervical intraepithelial neoplasia after CO2 laser vaporization Koichiro
Kawano, Jongmyung Park, Hiroki Nasu, Ken Matsukuma,
Atsumu Terada, Shin Nishio, Naotake Tsuda, Kimio Ushijima
Kurume University
Objective To confirm whether physiciansʼ skill may affect therecurrence rate of cervical intraepithelial neoplasia（CIN）2/3
after CO2 laser vaporization. Methods Women who underwent
vaporization in diagnosis of CIN2/3 among 2001 and 2014 andfollowed longer than 1 year were enrolled in this study. Recurrence was defined as histologically confirmed CIN2/3 within 2
year of vaporization. We examined the recurrence rate of top 15
operators. Factors related to physicians were discriminated by
the years of experience and the number of vaporizations. Recurrence risk factors were analyzed by logistic regression analysis.
Recurrence rate by physician was analyzed according to therisk factor and the number of vaporization. Results In total, 381
patients were enrolled. Mean age was 32.9±6.7 years old. Median number of vaporization by each physician was 18（range：
14 56）. Recurrence rate of CIN was 13.6%. Recurrence rate ineach physician was 0 to 37.5%, which was statistically significant difference（p＜0.001）. Years of experience of physicians did
not correlate with recurrence. Three quadrant disease（TD）
was identified as a risk factor of recurrence（p＜0.001）. Recur-

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Interim results of a cohort study assessing efficacy of cervical cytology and HPV testing as modalities for population
based cervical cancer screening Tohru Morisada1, Kumiko
Saika2, Eiko Saitou3, Kanako Kono2, Masaru Nakamura1, Takashi
Iwata1, Kyoko Tanaka1, Hiroshi Saito2, Mamoru Tanaka1,
Daisuke Aoki1 Keio University 1, Center for Public Health Sciences, National Cancer Center 2, IUHW Mita Hospital 3
Objective Introduction of HPV testing in cervical cancer screening has been studied from the viewpoint that HPV testing is amore sensitive modality. This study was launched as a cohort
study evaluating the HPV testing and verification project conducted in the Ministry of Health, Labor and Welfareʼs cancer
screening promotion project. The morbidity rate of cervical intraepithelial lesion grade 3 or worse（CIN3+）and benefits andharms of introduction of HPV testing into cervical cancer
screening will be examined. We aimed to provide the results offirst round screening and the compliance rates for a detailed examination and subsequent screening. Methods The project was
conducted in population based cervical cancer screening program in local governments. Subjects were tested using cytology
alone（control group）or cytology and HPV testing（intervention
group）.The results of first round screening and the compliance
rates for a detailed examination and subsequent screening were
examined. Results This study included 25,078 women in 39 local
governments. For participants in the initial registration, thecompliance rate for a detailed examination in cases referred for
immediate check up was 89.3%, whereas in newly appearing
cases in the intervention group who were referred for cytology
after 12 months, the compliance rate was only 53.0% and thecompliance rate for subsequent screening was 48.1%. Conclusion The results of this study show the importance of establishing a system that adjusts the interval of consultation based on
individual screening results and encouraging participants tohave continuous screening when considering introduction of the
HPV testing into population based cervical cancer screening.

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dard procedures, trained human resources to examine HPV test
and managed bar code registration for screening. The target
factory was with 1,000 female workers, average age of 24 years
old and about 20% married. In June 2017, the implementer teamcomposed of 2 doctors, 3 nurses, and 2 secretaries conducted thescreening at Phnom Penh Special Economic Zone. All samples
were double checked by two laboratories. Results Forty four female factory workers, rage of age are 20 years old to 44 years
old（median 29 years old）ever married or with partners wereapplied for the screening and 31 was screened. Four cases are
HPV positive, but no one came for secondary check till September 2017. The first cervical cancer screening among Cambodian
factory workers showed HPV positive rate of 12%. The registered female workers were about 20% of targeted people. Conclusion Challenges are to promote cervical cancer screening
and to connect first screening and secondary check.

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Comparative Study of the effect of cervical cancer screening
by Liquid Based Cytology and High Risk Human Papillomavirus detection in Inner Mongolia Xianzhi Duan1, Yanbo Song2,
Shaoming Wang3, Dan Dong1, Yongdong Zhang4 Tongren Hospital of Beijing, China 1, Yizhuang Hospital of Beijing, China 2, Cancer Hospital of Chinese Academy of Medical Sciences, China 3,
Population and Family Planning Bureau of Zhungeer of Inner
Mongolia, Mongolia 4
Objective To investigate the effect of cervical cancer screening
by liquid based cytology and high risk human papillomavirus（HPV）detection in Inner Mongolia, and to provide scientific
data for the selection of primary screening technologies of cervical cancer in Inner Mongolia. Methods From 2012 to 2014, 30,118
women aged 20〜70 were screened by the Thinprep liquid
based cytology（TCT）and the Cervista HPV detective method
for cervical cancer in Inner Mongolia. Those with abnormal cytological results or HPV infection were referred to colposcopy
examination, and biopsy was taken for pathological confirmation. Results The rate of positive cytology result and HPV infection was 5.54% and 23.18%, respectively. A9 group was the mostcommon HPV types with a positive rate of 7.77%. The predominated HPV types were the same for the Han nationality andMongolian. Both the total HPV infection rate and A9 group HPV
infection rate were positively associated with the grade of cytological abnormity. The positivity of A9 HPV type was increasedby the pathological grades. The consistence（84.71%）between
TCT and Cervista for the detection of high grade cervical intraepithelial neoplasia（CIN2+）was high. The two methods
worked as supplementary for each other. Twenty six cases
were detected by the HPV test while missed by the TCT, and 19
cases with negative HPV results were found by TCT. The combination of the two methods increased the detective rate of CIN
2+ from 84.71% to 98.47%（P＜0.05）. Conclusion The consistenceof TCT and Cervista for the detection of CIN2+ was good. TCT
and Cervista can be used as effective methods for cervical cancer screening in various areas with different health resources,
and their combination can increase the accuracy.

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ISP-37-1
Introduction of HPV test for cervical cancer screening in
Cambodia as low resource setting Maryan Chhit1, Kanal Koun2,
Chansoeung Sann2, Kyna Uy1, Yoshiko Nishigaya3, Sari Nakao4,
Yasuyo Matsumoto5, Yutaka Ueda6, Kouji Banno7, Ruriko
Nishino8, Noriko Fujita9, Tadashi Kimura6 Khmer Soviet Friendship Hospital, Cambodia 1, Cambodian Society of Gynecology and
Obstetrics, Cambodia 2, Kyorin University 3, University ofTsukuba 4, Omori Ladiesʼ Clinic 5, Osaka University 6, Keio University 7, All Japan Labour and Welfare Foundation 8, National Center for Global Health and Medicine 9
Objective In Cambodia, female factory workers are valuablegroup to support their family and Cambodian economy, but are
difficult to consult the doctors because of their sift working andluck of knowledge. We conducted the first cervical cancer
screening in the factory to find out the feasible method withquality in low resource setting. Methods In January 2017, SCGO
project started preparation by advise of JSOG and decided touse hybrid capture HPV detection for the screening because of
its simple procedure and cost benefit. Also we made the stan-!

ISP-37-3
Cervical Cancer in Women with Squamous Cell Carcinoma
Cytology Chumnan Kietpeerakool, Kaniknun Noonlamtong,
Amornrat Temtanakitpaisan, Pilaiwan Kleebkaow, Apiwat
Aue-Aungkul,
BunditChumworathayi,
Sanguanchoke
Luanratanakorn Khon Kaen University, Thailand
Objective To determine rate of cervical cancer among womenwith squamous cell carcinoma（SCCA）cytology and associatedrisk factors. Results were pooled with previously reported findings. Methods We reviewed data regarding women with SCCA

May 11 Fri.
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rence rate in TD and non TD was 24.6% and 8.8%, respectively.
In non TD, recurrence tended to decrease with the number ofvaporization, but not in TD. However, recurrence did not decrease with the number of vaporization in 3 physicians who had
more than 14% of recurrence rate in non TD. Conclusion Recurrence rate of CIN2/3 after vaporization differs depending on
physician. Physicians who had more than 14% of recurrence willneed re education.

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cytology undergoing colposcopy at Khon Kaen University Hospital between October 2008 and March 2016. We also performed
a meta analysis incorporating this study and previous studies
retrieved in order to provide the pooled rate of cervical cancer
among women with SCCA cytology. A random effects model
was applied for meta analysis. Results Data of 69 patients werereviewed. After colposcopy, 64 patients underwent cervical conization and/or hysterectomy and the five remaining patients
underwent colposcopically directed biopsy only. Thirty six patients（52.2%；95% CI, 40.1% to 64.3%）had invasive lesions, allof which were cervical cancer. There were no significant associations between the patientsʼ age, level of education, menopausal status, parity status, infection with human immunodeficiency virus, or symptoms presented during the cervical smear
and the rate of invasive cervical cancer. After combining thedata from this study with data from six other eligible studies,
which were retrieved from a search of standard bibliographic
databases, the pooled rate of cervical cancer among women with
SCCA cytology was 56%（95% CI, 36% to 77%）
. Conclusion Approximately half of women with SCCA cytology in this study
harbored cervical cancer. No significant factors predicting underlying cervical cancer were noted. By means of meta analysis, the pooled rate of cervical cancer among women with SCCA
cytology was found to be 56%.

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Hiroshi Watanabe, Yukihiko Nakayama, Mariko Hashiguchi,
Yoshifumi Nakao, Masatoshi Yokoyama Saga University
Objective Bevacizumab（Bev）, a monoclonal antibody that targets vascular endothelial growth factor（VEGF）, is indicated foradvanced cervical cancer or recurrence of cervical cancer.
Some serious adverse events, including gastrointestinal perforation, vesicovaginal/rectovaginal fistulas, and arteriovenous
thrombosis were reported. In particular, adverse gastrointestinal tract events can deteriorate activities of daily living（ADL）.
Therefore, we must be careful when we use Bev. We examined
adverse gastrointestinal tract events in cases using Bev for cervical cancer in our department. Methods A retrospective review of patients who received chemotherapy including Bev was
performed. Results Between December 2016 and March 2017,
nine patients received chemotherapy include Bev. All patients
received cisplatin（50mg/m2）and paclitaxel（135mg/m2 infusedover 24 hour）and Bev（15mg/kg）.Serious adverse events（morethan G3 in CTCAE）included one gastrointestinal perforation,
two vesicovaginal/rectovaginal fistulas, one paralytic ileus, andone arteriovenous thrombosis. In all cases, radiotherapy was administered before Bev therapy. Gastrointestinal perforation or
fistula cases were irradiated by 30 55.8Gy extrapelvic irradiation and 24 30Gy Intracavitary irradiation. The ileus case resulted from hysterectomy as first therapy, and concurrent
chemoradiotherapy as adjuvant therapy, although the patientwas not irradiated to the para aortic lymph nodes region. Conclusion In our study, radiation dose, hysterectomy, and the siteof the active lesion may be associated with the onset of adverse
gastrointestinal tract events. However, we could not determine
clear tendencies due to the limited number of cases. Further
studies are needed in order to provide safer Bev therapy.

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ISP-37-4
A study of the effectiveness and safety of Bevacizumab combination therapy for advanced or recurrent cervical cancer
Satomi Kameda, Masafumi Toyoshima, Yoshiko Oyama, Asami
Toki, Tomoyuki Nagai, Michiko Kaiho, Hideki Tokunaga,
Muneaki Shimada, Hitoshi Niikura, Nobuo Yaegashi Tohoku
University HospitalObjective Bevacizumab（Bev）, an angiogenesis inhibitor, hasbeen used for the treatment of advanced or recurrent cervicalcancer, but there are only few reports in Japan. In order to investigate the efficacy and safety of Bev combination therapy,
we retrospectively studied the experiences in our hospital.
Methods This study was approved by our institute. We examined the clinical data of the patients who underwent Bev combined therapy during May 2016 and July 2017 in our hospital.
Results The subjects were 10 cases and median age was 58.3
years. The number of stage I/II/III/IV were 3/1/1/5, respectively. Initial and recurrence treatment was 4 and 6, respectively. Administration regimen was TP Bev（5）and TC Bev（5）, and 3 patients were changed to Bev single maintenancetherapy because of side effects. The median number of administrations was 8.2. The response rates were 25%（CR：0, PR：1,
SD：2, PD：1）in initial treatment group and 83%（CR：2, PR：
3, SD：0, PD：1）in recurrence treatment group, respectively.
The common side effects were neutropenia, hypertension, nose
bleeding and thrombocytopenia. However, there were no serious side effects such as gastrointestinal perforation and fistulas.
There were 4 patients who have a risk factor such as hypertension history（1）, DVT history（1）and brain metastasis（2）, butthese patients could continue Bev combination therapy without
serious side effects. Conclusion The response rate of Bev combination therapy for advanced or recurrent cervical cancer patients was 60%, indicating very high effectiveness. Side effects
were acceptable even in cases with a risk factor, and treatment
continuation was possible in many cases.

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ISP-37-5
Examination of adverse gastrointestinal tract events in cases
using Bevacizumab for cervical cancer in our department
Satoshi Nishiyama, Takako Hikari, Asako Fukuda, Satoko
Tsuda, Makiko Kurihara, Maiko Kato, Misako Hideshima,

ISP-37-6
Clinical outcomes of bevacizumab in five recurrent patientswith uterine cervical cancer after concurrent chemoradio
therapy Takashi Ushiwaka, Yayoi Higuchi, Yusuke Ujihara,
Ruriko Yamada, Nagamasa Maeda Kochi Medical School
Background Bevacizumab（Bev）has been approved to the recurrent uterine cervical cancer. We accessed the clinical outcome of Bev in 5 patients with recurrent cervical cancer performed CCRT. Cases Mean age was 58 years old. FIGO stage of
2 cases was 3B and 3 were 4B. Histological type of 4 cases was
squamous cell carcinoma and 1 was adenosquamous cell carcinoma. All patients were received CCRT for primary therapy. 4
patients had lymph nodes recurrence and 1 had lung metastasis.
4 patients was received other chemotherapy before Bev becauseof previous recurrence after CCRT. Conventional chemotherapy
was performed with Bev；TC, weekly TC, DC, and CPT 11.
Mean cycle of Bev administration was 4.6. Clinical outcome was
2 CR, 2 PR, and 1 PD after Bev. Adverse effects were 3 hypertensions, 3 proteinurias, 1 intestinal perforation, 1 recto vaginal
fistula, and 1 ileus. Administration of Bev was discontinued in 2
patients with intestinal perforation and recto vaginal fistula.
Discussion Though the chemotherapy with Bev for recurrent
cervical cancer may be effective, but there are severe adverse
effects. According to our investigation, after CCRT, 2 patientswith intestinal perforation and recto vaginal fistula started Bev
earlier than other patients without severe complications. Conclusion When applying Bev for recurrent cervical cancer, wehave to obtain sufficient informed consent for possibility of severe adverse effects. We conclude that it is necessary to establish the application criteria to predict and prevent severe adverse effects such as intestinal perforation and recto vaginal fistula by Bev.

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Treatment outcome of the definitive high dose ratebrachytherapy combined with external beam pelvic radiotherapy for patients with uterine cervical cancer Hiroshi
Matsushima1, Taisuke Mori1, Morio Sawada1, Haruo Kuroboshi1,
Hiroshi Tatsumi1, Shiori Umemura1, Kaori Yoriki1, Tetsuya
Kokabu1, Jo Kitawaki1 Kyoto Prefectural University of Medicine 1, Department of Radiology, Kyoto Prefectural University of
Medicine 2
Objective The objective is to assess the efficacy and toleranceof high dose rate brachytherapy（HDR BT）combined with external beam pelvic radiotherapy（EBRT）for patients with cervical cancer. Methods A total of 35 patients with uterine cervicalcancer, treated with the definitive HDR BT with or without cisplatin（40 mg/m2, q 1 week）from April 2009 to August 2015,
were retrospectively analyzed. Toxicities were evaluated according to Common Terminology Criteria for Adverse Events
version 4.0 and the responses by the treatment were examinedaccording to RECIST criteria. The primary and the secondary
endpoints were 2 year OS and 2 year PFS, respectively. Results The median age was 61 year old（range 35 89）.Median follow up period was 33.7 months（range 4.0 100.6）.Of the 35 patients, one patient was classified as stage I（FIGO 2009）, 15 wereas stage II（42.8%）, 12 were as stage III（34.2%）, 7 were as stage
IV（20%）. Twenty five patients（71.4%）had pelvic lymph nodes
metastasis. The complete response（CR）rate was 72.7%. The 2
year OS rate was 79%, 2 year PFS rate was 50.8%. Local control
rate was 87.2%. The mild（grade 1/2）late complications was observed in 14 patients（40%）, and the severe（grade 3）complication was seen in 2 patients（5.7%）. Vesico vaginal fistula andrectovaginal fistula were observed in the 2 patients. No grade 4complication was observed. Conclusion HDR BT combinedwith ERBT will be considered as a treatment option for patientswith locally advanced uterine cancer.

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Two cases of uterine cervical adenocarcinoma with successful systemic chemotherapy Hiroshi Kaneda, Shun Masaoka,
Saki Ito, Sachi Sukegawa, Shihori Nishizawa, Norikazu Ueki,
Yoshiko Murase, Satomi Tanaka, Shotaro Yata, Yuka
Yamamoto, Toshitaka Tanaka, Naoki Mitsuhashi Juntendo University Shizuoka Hospital
Cervical adenocarcinoma is less frequent than cervicalsquamous cell carcinoma, progress is faster and chemotherapy
is more difficult to be successful, so early treatment is importantand surgical therapy is primarily chosen. We report two cases
in which systemic chemotherapy was successful against cervical adenocarcinoma. Case 1 72 year old woman with liver andpulmonary metastasis, diagnosed as FIGO I V B, was performed
6 courses of systemic chemotherapy of DC therapy（docetaxel
and carboplatin）. CA125 was under normal value in addition
pulmonary and liver metastasis were disappeared, but ovarian
tumor was found about 1 year later and therefore surgery were
performed as total hysterectomy and bilateral salpingo
oophorectomy. Pathlogical diagnosis of ovary was carcinosarcoma and there was no cancer lesion in the uterine cervix. Case
2 82 year old woman diagnosed as FIGO I I B performed six
courses of systemic chemotherapy of DC therapy because of elderly. After chemotherapy total hysterectomy was performed because loss of measurable lesion was obtained. Systemic chemotherapy and concurrent chemoradiotherapy are main methodsof treatment other than surgery for cervical cancer, and platinum drug is mainly selected for chemotherapy. Cervical adenocarcinoma is considered to have lower response rate of chemotherapy than squamous cell carcinoma, but I would like to report on two cases that have been effective with systemic chemotherapy for future treatment method.

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ISP-37-10
Limitation of postoperative adjuvant chemotherapy（paclitaxel and carboplatin）for treatment of cervical cancer stage
I/II patients at high risk of recurrence Yuki Okuma,
Takehiro Nakao, Erina Hashimoto, Remi Hasegawa, Akiko
Kasuga, Hiromitsu Azuma, Chuyu Hayashi, Atsushi Komatsu,
Yasuji Miyagawa, Shinichi Takada, Fumihisa Chishima, Kei
Kawana Nihon University
Objective Postoperative adjuvant therapy is recommended for
cervical cancer patients at high risk and intermediate risk ofrecurrence. While concurrent chemo radiotherapy（CCRT）is
recommended for the adjuvant therapy, some clinical trials of
adjuvant chemotherapy for cervical cancer had been conducted.
We here examined the clinical efficacy of adjuvant TC（paclitaxel and carboplatin）for patients at risk of recurrence. Methods Under approval of Ethical committee in our hospital, 21 cervical cancer patients（FIGO IB=10, IIA=3, IIB=8）who received
postoperative adjuvant therapy chemotherapy（TC：paclitaxel）were investigated（fol［175mg/m2］and carboplatin［AUC=6.0］
low up time：6 50m, median=19m）. We defined lymph nodemetastasis（LN）, parametrium invasion（Pmm）, and bulky tumor（＞4cm：Bulky）as high risk and vascular lymphatic infiltration（VLI）as intermediate risk of recurrence. Progression freesurvival（PFS）and overall survival（OS）were analyzed by
Kaplan Meier plot and cox hazard proportional model. Results
17 and 4 patients had high risk and intermediate risk factors ofrecurrence, respectively. 3ys OS of all patients was 60.5% and 2
ys PFS was 52.2%, which seemed to be worse than those in general. Cox hazard model did not detect any independent clinico
pathological factor for recurrence. Among nine recurrent patients, six（67%）had recurrence of vaginal stump and all had
VLI. Conclusion The prognosis of our patients received adjuvant TC seemed to be clearly worse when compared with gen-

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Radiation therapy for para aortic lymph node metastasis diagnosed by various imaging modalities and prognosis for advanced uterine cervical cancer Kaho Suzuki, Yasuhiko Ebina,
Yoshiya Miyahara, Senn Wakahashi, Hideto Yamada Kobe University
Objective Various imaging modalities are used to define radiation field before primary therapy in Japan. If we detected metastasis to para aortic lymph node（PAN）in patients with advanced uterine cervical cancer, adequate treatment leads to prevent a recurrence. This study aimed to evaluate the association
between para aortic metastasis lymph node metastasis diagnosed by various imaging modalities and prognosis. Methods
We conducted a retrospective study for women who were diagnosed as having stage IB IVA cervical cancer between January2010 and December 2016. A total of 46 patients were enrolled.
All patients underwent various imaging modalities prior to radiation therapy（CCRT or RT）. Patients were divided into twogroups according to diagnostic imaging. The patients in group
A had positive pelvic lymph node（PLN）and negative PAN. The
patients in group B had positive PLN and positive PAN. The
survival and recurrence rate of each group were assessed. Results The median age of all patients was 64 years（range 24 89）.
The median follow up time for all patients was 18 months（range 2 84）. Significant differences of prognosis（PFS, OS）
were observed between Group A and B（p＜0.05）. Significant
differences in rates of recurrence were observed between
Group A and B（p＜0.05）. Conclusion For patients who had positive PLN and positive PAN, adjuvant chemotherapy might beconsidered because of the high rate of recurrence.

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eral data of patients received adjuvant CCRT. Since the multivariate analysis did not identify any pathological factor, adjuvant TC might be the most responsible factor resulting in poor
prognosis. Our data suggested that adjuvant chemotherapy using TC is not recommended for cervical cancer.

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ISP-38-1
A case of acute abdominal pain caused by the infarcted parasitic leiomyoma Yoojung Lee, Jin Woo Shin, Chan Mi Lim,Da hoe Jung Gachon University of Medicine and Science, Korea
Introduction Parasitic leiomyomas are rare gynecologic conditions of the incidence ranged from 0.12 to 0.95%. Most case presented as pelvic mass on image such as ultrasonography and CT
scan without clinically significant symptoms. The authors report a case of infarcted parasitic leiomyoma after laparoscopic
myomectomy, which presented as acute abdominal pain. Case A
37 year old woman underwent laparoscopic myomectomy withpower morcellation for removing leiomyoma through trocar site
at 12 years ago, came to clinic with acute right lower abdominal
pain for 2 days. CT scan revealed multiple intra abdominal
mass. Total of five leiomyomas were removed（up to 6.2cm）with
one of which were seeded on right lower part of omentum justthe site of patientʼs tender point and histopathological examination confirmed the infarcted leiomyoma. After removing the infarcted leiomyoma, the abdominal pain was subsided and the patient recovered without complication. Conclusion When awomen, who had a history of laparoscopic myomectomy, complaint acute abdominal pain, infarcted parasitic leiomyoma
should be considered.

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ISP-38-2!

The value of serum LDH, CRP and D dimer levels for differentiation among degenerated leiomyoma, variant type leiomyoma
andleiomyosarcoma
Kaori Kiuchi1, Kiyoshi
Hasegawa1, Ayano Suzuki1, Mariko Watanabe1, Nobuaki
Kousaka1, Takanori Sakamoto1, Yoshiko Nishigaya2, Yoichi
Kobayashi2, Ichio Fukasawa1 Dokkyo Medical University 1, Kyorin University 2
Objective The differential diagnosis of degenerated leiomyoma（dLM）or variant type leiomyoma（vLM；cellular LM or LM
with bizarre nuclei）from leiomyosarcoma（LMS）using MRI
findings is sometimes difficult. Therefore, in this study, weevaluated the value of serum LDH, CRP and D dimer levels fordifferentiation among these diseases. Methods Thirteen patientswith dLM, six with vLM and five with LMS（three with FIGO
stage Ib and two with IIIb）who underwent surgery after 2010
were recruited. The serum LDH, CRP and D dimer levels werecompared among these patients groups. Patients with apparent
infectious diseases or thromboembolism were excluded. Results
The serum LDH level was elevated in 1/13 patients with dLM
and in 4/5 with LMS. The serum CRP level was elevated in 1/6
patients with vLM and 5/5 with LMS. The serum D dimer level
was elevated in 1/13 patients with dLM, 1/6 with vLM, and 5/5
with LMS. The serum levels of these three parameters in patients with LMS were significantly higher. Elevated serum levels of all three parameters indicated a diagnosis of LMS, with asensitivity of 80%, specificity of 100%, positive predictive value（PPV）of 100% and accuracy of 95%. On the other hand, normal
serum levels of all three parameters were indicative of not having LMS, with a sensitivity of 79%, specificity of 100%, PPV of
100% and accuracy of 83%. Conclusion The serum levels of
LDH, CRP and D dimer may provide a diagnostic method supplementary to MRI findings for differentiation among dLM,vLM and LMS.

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Preoperative prediction of uterine sarcoma using tumor to
subcutaneous fat signal intensity ratio by T2 weighted imaging（TFSIR）and apparent diffusion coefficient（ADC）on
magnetic resonance imaging（MRI） Yasuko Oka, Masanori
Tamori Komatsu Municipal HospitalObjective Preoperative diagnosis of uterine sarcoma is difficult.
The author focused on TFSIR and ADC, and previously presented. The purpose of this study is to improve the reliability
through further investigations of previous and additional cases.
Methods MRI was performed in 6 cases（7 tumors）of uterine
sarcoma in the last 3 years（sarcoma group）, and 31 cases of leiomyoma in 2015（myoma group）. The author calculated TFSIR
and ADC, and determined threshold value for each. Finally, apreoperative prediction method using these parameters wasconsidered through the application to the 40 tumors in 2016.
This protocol has been approved by the local institutional review board of ethics. Results The sarcoma group had significantly higher TFSIR and lower ADC than the leiomyoma group（p＜0.01）. The minimum cutoff value of TFSIR to diagnose sarcoma is 0.515（sensitivity 100%, specificity 94%）
, and the maximum cutoff value of ADC is 1.280（sensitivity 86%, specificity
87%）. All tumors with both positive TFSIR and ADC were sarcoma（High suspicion group）. All tumors with negative TFSIR
were leiomyoma（low suspicion group）. Tumors with positive
TFSIR and negative ADC included both（Intermediate group）.
Among 40 uterine in 2016, 2 belonged to the High suspiciongroup（all sarcoma）, 3 belonged to the Intermediate group（allleiomyoma）and the other 35 tumors belonged to the Low suspicion group（all leiomyoma）.Conclusion Preoperative predictionof uterine sarcoma is possible using both TFSIR and ADC on
MRI.

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Coincidental detection of diffuse large B cell lymphoma inthe inner inguinal lymph node of a woman undergoing pelvic
lymph node dissection for uterine endometrial cancer
Kazuaki Ohashi1, Takako Shimada1, Ayumi Harada1, Daisuke
Hamaguchi1, Michio Kitajima1, Atsushi Yoshida1, Masanori
Kaneuchi2, Kiyonori Miura1, Hideaki Masuzaki1 Nagasaki University Hospital 1, Otaru General Hospital 2
Simultaneous occurrence of non Hodgkins lymphoma（NHL）and
solid carcinoma such as colon, lung, breast cancers have been reported. However, synchronous non Hodgkins lymphoma（NHL）and endometrial carcinoma is relatively rare. We reporta case of coincidental detection of diffuse large B cell lymphoma（DLBCL）in the inner inguinal lymph node of a woman
undergoing pelvic lymph node dissection for uterine endometrial cancer. The patient was 69 year old woman and she
was aware of increase of the vaginal discharge. She did not haveany other symptoms, including genital bleeding, fever, weight
loss, or night sweats. She was diagnosed as uterine endometrial
carcinoma FIGO clinical stage1A. Laparoscopic hysterectomy,
bilateral salpingo oophorectomy, pelvic lymph node dissection
was performed. The final pathologic examination revealed endometrioid adenocarcinoma grade1 and DLBCL was detected in
the inner inguinal lymph node. PET/CT could not detect anyother lesions of the malignant lymphoma. We diagnosed her asuterine endometrial carcinoma FIGO surgical stage1A, and themalignant lymphoma as Ann Arbor clinical stage1. Therefore,
the postoperative chemotherapy or radiotherapy for the endometrial carcinoma was unnecessary, six cycles of R CHOP（rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone）
for the malignant lymphoma was performed. The patient
remains complete remission 8 months after surgery.

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A rare case of a primary uterine perivascular epithelioid celltumor（PEComa）treated with robotic hysterectomy and adjuvant
chemotherapy
Mizuki Isayama, Manabu Sakurai,
Nobutaka Tasaka, Azusa Akiyama, Ayumi Shikama, Sari
Nakao, Hiroyuki Ochi, Takeo Minaguchi, Toyomi Satoh University of Tsukuba
Perivascular epithelioid cell tumors（PEComas）are rare neoplasms that express both myogenic and melanocytic markers.
Uterine PEComas are usually clinically benign and can often be
cured with surgery. However, there have been reported cases ofaggressive clinical behavior. Standard treatment for such aggressive PEComas is still unestablished. We report a case of a
30 year old Caucasian nulligravida with a high risk uterine PEComa. The patient was transferred after presenting to an outside hospital with lower abdominal pain. A diagnosis of PEComa
was established from endometrial biopsy results. PET/CT
showed no evidence of metastasis, and the tumor was localized
within the uterus. Surgical management consisted of a robotic
assisted laparoscopic hysterectomy, bilateral salpingo
oophorectomy, and pelvic sentinel lymph node mapping with bilateral external iliac lymphadenectomy. The specimen was composed of a solid component measuring 4×3.5×3cm and a cystic
component measuring 9×7×5cm. Immunohistochemistry revealed HMB45 and SMA positivity. The tumor was classified ashigh risk based on the WHO classification system based on its
size, presence of necrosis, and high mitotic activity. The patient
has now finished two cycles of adjuvant chemotherapy with
Adriamycin（A）and Ifosfamide（I）（A 60mg/m2 day 1, I 2g/m2
day1 3, every 21 days）. The patient has tolerated the chemotherapy well. The prospective treatment course is to continue
with Adriamycin and Ifosfamide. Due to the rarity of uterine
PEComas, the effectiveness of adjuvant therapy is still unknown. However, our case reveals that a combination of Anthracycline and Ifosfamide could be considered as effective adjuvant
treatment.

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Multimodality therapy for the patients with advanced or recurrent uterine leiomyosarcoma Mizuho Kuroshima, Yasuhiko
Ebina, Kaho Suzuki, Senn Wakahashi, Yoshiya Miyahara,
Hideto Yamada Kobe University

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Use experience of eribulin for recurrent uterine carcinosarcoma Masato Nishimura, Ayuka Mineda, Takako Kawakita,
Akiko Abe, Minoru Irahara Tokushima University
Objective Eribulin is a new medicine approved for sarcoma,
however the effect is unclear for uterine carcinosarcoma. Second line therapy of carcinosarcoma has not been established forpatient with resistance to paclitaxel and carboplatin（TC）. We
performed this study to clarify the safety and efficacy of
eribulin for carcinosarcoma. Methods 1.4mg/m2 of eribulin was
administered at day1 and 8 in 5 minutes. The treatment was repeated every 3 weeks. The dose was reduced to 1.1mg/m2 after
grade 3/4 neutropenia occurred. Results Treatment was administered in 4 patients（12courses）.Grade3/4 leukopenia was seenin 2 patient（3 courses）,neutropenic fever was seen in 1 patient.
Duodenal hemorrhage was seen in 1 patient. Response was
evaluated in all cases by RECIST. 1 PR, 1 SD, and 2 PD wereconfirmed. One case of PR was recurrent at 2 para aortic
lymphnodes after one year of surgery. The lymphnode enlarged
from 52 to 64mm and 22 to 50mm after 3 courses of TC.
Lymphnode was reduced to 42mm and 36mm after CCRT. CA
125 declined from 208 to 96 U/mL after CCRT. We administerederibulin after CCRT. The tumor still shrank to 27mm and 20mm
after two courses of eribulin. CA125 elevated to 132U/ml duringobservation after CCRT, but reduced to 32U/mL after two
courses of eribulin. In another case of SD, three recurrent tumors in the abdomen showed same size after 2 courses of
eribulin but enlarged during waiting of surgery. Conclusion
There is possibility that eribulin is effective for carcinosarcoma.
Further investigation is needed.

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Uterine sarcoma：20 year Our hospital Experience of 21
Cases Takanori Shimizu, Souta Tanaka, Sara Takahashi, Shohei
Tanabe, Yoko Yoshida, Izumi Sato, Kaori Suenaga, Akiko Kasai,
Goichiro Kasai, Takeshi Aida, Junko Kouno Hachinohe City HospitalObjective Uterine sarcoma（US）is a rare tumor, comprising
about 4 9% of all uterine malignancies. The aim of this study
was to investigate the clinical feature of US in our hospital.
Methods This study included 21 patients with histologically diagnosed uterine leiomyosarcoma（LMS）：17 patients and endometrial stromal sarcoma（ESS）：5 patients in our hospital!

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A case of leiomyosarcoma arising from subserosal leiomyoma Maiko Yamaguchi, Soshi Kusunoki, Rie Seyama, Aya
Takayama, Ayako Masuda, Takashi Hirayama, Kazunari
Fujino, Yasuhisa Terao, Atsuo Itakura, Satoru Takeda Juntendo
University Hospital
Uterine leiomyosarcoma（LMS）is a rare tumor. It has not been
established if LMSs arise de novo or from pre existing leiomyomas. We report a case of LMS arising from subserosal leiomyoma. A 47 year old nullipara was diagnosed with a uterine
tumor measuring 30 cm in diameter by pelvic MRI. The serum
CA 125 level was 369 ng/ml and the WBC count and LDH level. PET CT revealed
were elevated（13,000×109/l and 565 IU/l）abnormal uptake（SUVmax=25.29）into the abdominal tumor.
At laparotomy, the huge tumor with solid and cystic components was shown to arise from subserosal leiomyoma, and invaded the great omentum and small intestine. Abdominal hysterectomy, bilateral salpingo oophorectomy, omentectomy, andsmall intestine resection were performed. Macroscopic findings
showed that the LMS was attached to the subserosal leiomyoma
without continuity between the tumor and the uterus. Our case
supports the hypothesis that LMS can arise from pre existing
leiomyoma.

We report five cases（recurrent 3, advanced 2）of advanced orrecurrent uterine leiomyosarcoma（LMS）treated with multimodality therapy including novel therapeutic agents. The medianage of the patients was 50 years（range, 39 to 65 years）. All patients were given chemotherapy；gemcitabine/docetaxel（GD）（n=5）, doxorubicin（n=3）, ifosfamid（n=2）, pazopanib（n=3）, trabectedin（n=1）, and eribulin（n=1）.Three patients underwent
surgical resection of recurrent tumor, and three patients weretreated with radiation therapy. Maximal efficacy of GD therapy,
pazopanib, trabectedin, and eribulin were partial response, stable disease（SD）, SD, and PD, respectively. GD therapy maintained stable disease for a long term；17 courses（n=1）and 24
courses（n=1）. SD for 10 months was obtained by pazopanib in
one case. However, administration of pazopanib was impossible
because of nausea in one case. SD for 5 months was found using
trabectedin. After a median follow up of 63.5 months, three patients had died of disease（29, 30, and 59 months）, and two patients live with disease（68 and 80 months）. In the three casesthat long term survival was obtained, multiple course of surgery or radiation for the recurrent site were performed. By using multimodality therapy long term survival could be obtained
for the patients with advanced or recurrent LMS.

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from 1997 to 2017. The medical records were reviewed retrospectively. Results The median age was 50 years（range, 40 79）.
The numbers of FIGO stages 1, 2, 3, 4 were 13, 3, 1, 4, respectively. Thirteen patients（61%）have recurrence of the disease.
The most common recurrence site were lung and pelvis（each of
7 cases）. Chemotherapy was administered to 8 recurrent patients. Best supportive care was carried out to 2 recurrent patients. Hormone therapy was given to 2 recurrent patients.
Chemoradiation was given to 1 recurrent patient. Response rateof chemotherapy was 2 partial responses, 2 stable diseases and 4
progressive diseases. The median overall survival was 30
months（range, 4 223）
. The 5 year overall survival rate of the
21 patients was 66%. There is no difference with LMS and ESS
in 5 year overall survival rate（53% vs 46%, p=0.453）. Conclusion It was indicated that US cases had high recurrent rate,even stage 1（54%）. Therapy of first recurrence was mainly chemotherapy in our hospital and the response rate of chemotherapy was only 25%, poor effect. New therapy such as moleculartargeted drugs is expected for the better prognosis.

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Development of a rapid preoperative diagnosis method to assess lymph node metastasis in uterine cancer Emiko Yoshida1,
Yasuhisa Terao1, Yosuke Ito1, Tsuyoshi Ota2, Michio Nojima2,
Daiki Ogishima3, Hiroshi Kaneda4, Soshi Kusunoki1, Kazunari
Fujino1, Takashi Hirayama1, Atsuo Itakura1, Satoru Takeda1 Juntendo University 1, Juntendo University Urayasu Hospital 2, Juntendo University Nerima Hospital 3, Juntendo University Shizuoka Hospital 4
Objective Lymphadenectomy in endometrial carcinoma shouldbe performed based on individualized considerations. In a previous study, we identified expression levels of SEMA3D and anovel isoform of TACC2 as promising biomarkers to evaluate
lymphatic metastasis based on gene expression patterns in the
primary lesion. Since cancer progress with time, diagnosis has
to be completed just before performing lymphadenectomy during a single operation. A major difficulty for its clinical application is a requirement in speed of diagnosis. Here, we attemptedto accelerate gene quantitative analysis for our biomarkers.
Methods RT SmartAmp is a method to detect nucleic acids in
one step, which consists of a reverse transcription and an isothermal amplification of DNA. We chose it for RNA quantification in the required period of time. As a first step, we desgined aset of primers for SmartAmp across the exon exon junction of
the novel TACC2 isoform. We measured the speed of amplification and target specificity based on cDNA. As a second step, we
assessed the reaction based on RNA as the template in one step
containing reverse transcription step. Results We succeeded todevelop a promising candidate of primer set to detect the novel
TACC2 isoform by using SmartAmp. This candidate can detect
quantitatively within 30 minutes. Conclusion Our findings pave
the way for support clinical decisions that minimize irrelevant
lymphadenectomy. We are going to develop primer sets for theother candidate and control genes, with the aim to establish asystem to quantify RNA abundance enabling assessment oflymph node metastasis.

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still controversial because there is patients occurred localizedpara aortic lymph node metastasis through ovarian vessels. The
purpose of this study was to clarify the real frequency of localized para aortic lymph node metastasis without pelvic lymph
node metastasis. Methods We analyzed pelvic lymph nodes ofthe patients who had metastasis only in para aortic basin by ultrastaging method of serial section per 100μm and immunohistochemical staining（AE1/AE3）. Results Between Apr 2009 to
Nov 2016, 217 patients with endometrial cancer received pelvic
and para aortic lymphadenectomy. 32（14.7%）were defined positive lymph node by conventional pathological method. 20（9.2%）
patients had metastasis in both pelvic and para aortic basin, 8（3.7%）had metastasis in only pelvic basin, and 4（1.8%）had metastasis in only para aortic basin. After the further analysis ofultrastaging, pelvic lymph node metastases could be identified
in 3 of 4 patients. 2 had micrometastasis, and one had isolated tumor cells. Conclusion It was suggested that the real frequencyof localized para aortic lymph node was less than reported before. If we examine intrapelvic lymph node by SLN mappingwith cervical injection, it would be possible to reduce missing
para aortic metastatic lymph node.

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The real frequency of localized para aortic lymph node metastasis in endometrial cancer Asami Toki, Hitoshi Niikura,
Satoshi Okamoto, Tomoyuki Nagai, Yusuke Shibuya, Shoko
Sakurada, Chiaki Hashimoto, Michiko Kaiho, Hideki Tokunaga,
Masafumi Toyoshima, Muneaki Shimada, Nobuo Yaegashi Tohoku University HospitalObjective Sentinel lymph node（SLN）mapping for endometrial
cancer has become commonly, but the tracer injection site is

ISP-39-3
Is tumor size really an independent predictor of lymph nodemetastasis in endometrioid endometrial cancer? Kento
Ohnishi1, Koji Yamazawa1, Yuri Ogata1, Hiroki Akaba1, Tomoko
Gota1, Asami Uenoyama1, Hajime Oishi1, Hirotaka Nishi2, Miyuki
Sadatsuki1, Tetsu Yano1 Center Hospital of the National Center
for Global Health and Medicine 1, Tokyo Medical University Hospital 2
Objective To evaluate tumor size as a predictor of lymph nodemetastasis in endometrioid endometrial cancer patients. Methods One hundred eleven patients with endometrioid endometrial cancer who underwent primary surgery including
lymphadenectomy from January 2000 to December 2016 werereviewed. Pathological characteristics including tumor size, tumor grade, depth of myometrial invasion, adnexal involvement,
cervical involvement, peritoneal cytology, lymphovascularspace invasion, and lymph node metastasis were abstracted
from the medical records. Univariate and multivariate analyses
were performed to evaluate the correlation between the pathological characteristics and lymph node metastasis. Two sets ofmultiple logistic regression models were analyzed. Tumor size
was included in each model as a dichotomous form（less than 2
cm versus 2cm and greater）and a continuous form. SPSS software was used. P ＜0.05 was considered statistically significant.
Results Thirteen patients had lymph node metastasis. The distributions of tumor size in patients with or without lymph nodemetastasis were not significantly different（Mann Whitney, P=0.075）. On univariate analyses, lymph node metastasis was not
significantly associated with tumor size of greater than 2cm［P=0.22, odds ratio（OR）3.73, 95% confidence interval（CI）,0.46
30.2］and continuous tumor size（P =0.14, OR 1.15, 95% CI 0.95
1.375）. On multivariate analysis, only depth of myometrial invasion greater than 50% was a significant predictor of lymph node
. Conclusion Unmetastasis（P =0.01, OR 5.02, 95% CI 1.43 17.6）
like depth of myometrial invasion, tumor size may not be an independent predictor of lymph node metastasis in endometrioid
endometrial cancer.

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Administration of cabergoline contributes to preserving fertility in young hyperprolactinemic patients with endometrial
cancer treated with medroxyprogesterone acetate Munekage
Yamaguchi1, Erdenebaatar Chimeddulam1, Fumitaka Saito1,
Ritsuo Honda1, Hironori Tashiro2, Takashi Ohba1, Hidetaka

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Shiomi1, Eiji Kobayashi1, Mamoru Kakuda2, Tsuyoshi Takiuchi1,
Michiko Kodama1, Kae Hashimoto1, Seiji Mabuchi1, Yutaka
Ueda1, Kenjiro Sawada1, Takuji Tomimatsu1, Kiyoshi Yoshino1,
Tadashi Kimura1 Osaka University 1, Sakai City Medical Center 2
Objective Laparoscopic surgery for early stage endometrial
cancer is becoming more common in our country. The primaryobjective was to confirm non inferiority of laparoscopy compared with laparotomy for recurrence and survival rate after
surgical treatment of endometrial cancer. Methods From March2010 to December 2016, 273 patients who were preoperatively
diagnosed as low risk endometrial cancer were surgicallytreated in our institution. Low risk cancer was defined preoperatively as G1 or G2 endometrioid histology and myometrial invasion ＜50% based on magnetic resonance imaging（MRI）. The
surgical procedure was determined by intraoperative frozen
section. Medical records were retrospectively reviewed forpathological diagnosis, site of recurrence and survival rate. Results A total of 131（48%）patients were treated by laparoscopy
and 142（52%）by laparotomy. The median follow up period was
17 months for laparoscopy patients and 51 months for laparotomy patients. There was no significant difference in distributionof BMI, pathological diagnosis and FIGO stage between the twogroups. In laparoscopic group, there were 4 recurrences and no
death. All 4 recurrent patients were pathological stage I. In laparotomy group, there were 10 recurrences and 4 deaths. Amongten, three were pathological stage III. There was no statisticaldifference for overall survival and progression free survival between the two groups. Conclusion Our findings showed that forendometrial cancer, laparoscopy has provided similar recurrent
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A retrospective study of endometrial cancer in elderly
women aged 80 or older Souta Tanaka, Sara Takahashi, Shohei
Tanabe, Takanori Shimizu, Yoko Yoshida, Izumi Sato, Kaori
Suenaga, Akiko Kasai, Goichiro Kasai, Takeshi Aida, Junko
Kouno Hachinohe City HospitalObjective The aim of this study is to investigate endometrial
cancer（EC）
in elderly women aged 80 or older. Methods We analyzed 32 EC cases aged 80 or older retrospectively in their clinical features, methods of treatment, and prognoses, in our hospital from 2007 to 2016. Results Median age of patients was 83
years（range 80 92）. The numbers of FIGO stages 1, 2, 3, 4 were24, 1, 4, 3, respectively. The details of histological types were endometrioid adenocarcinoma（22 cases, G1；13, G2；4, G3；5）,
clear cell adenocarcinoma（4）, serous adenocarcinoma（2）,poorly differentiated adenocarcinoma（2）, mucinous adenocarcinoma（1）, and squamous cell carcinoma（1）. All of 5 patients（PS3 4）had best supportive care（BSC）. Eighteen of 27 patients（PS0 2）underwent surgery（hysterectomy）and their 5 year survival rate was significantly higher than that of the other 9 patients who had radiation therapy or BSC（55.3% vs 16.7%, p=0.0185）. There was no severe postoperative complication. In 17
cases which operation was performed, the 5 year survival rateof 11 EC（endometrioid）patients was significantly higher thanthat of 6 EC（serous, clear）（80% vs 0%, p=0.0006）.Conclusion In
elderly women aged 80 or older（PS 0 2）,our data showed thatthe feasibility of surgery could be enough to do and the prognosis of type1 EC cases having surgery was good, in contrast, thatof type2 was very poor. It is suggested that surgical therapy
should be considered first in type1 EC cases and postoperative
therapy was required to reconsider in type2.

Para aortic lymphadenectomy at primary surgery is critical
for treatment of endometrial cancer Osamu Kobayashi,
Takehiro Nakao, Akiko Kasuga, Yuki Okuma, Remi Hasegawa,
Erina Hashimoto, Kaori Shinya, Chuyu Hayashi, Atsushi
Komatsu, Shinichi Takada, Fumihisa Chishima, Kei Kawana Nihon University Itabashi HospitalObjective Para aortic lymph nodes（PAN）are primary regional
lymph node of the endometrial cancer and then should be removed by para aortic lymphadenectomy（PALA）. However,
PALA can be omitted in some cases with early stage and welldifferentiated adenocarcinoma. We here examined whether
omission of PALA is acceptable for curative surgery by using
our cases. Methods This retrospective study was approved by
the Ethic committee of our institute. Subjects of this study were
68 cases with endometrial cancer which underwent primary
surgery in our hospital from 2013 to 2016. The operation was abdominal simple/semi radical hysterectomy, bilateral salpingo
oophorectomy and pelvic lymphadenectomy（TAH/AEH+BSO+PLA：omission of PALA）for all cases. Clinico pathologicalfeatures（histology, FIGO stage, clinical outcome, recurrent site,etc.）were investigated and analyzed. In our hospital chemotherapy（conventional TC：paclitaxel and carboplatin）was done as
an adjuvant therapy for cases with high risk factors of recurrence. Results Among 68 cases, eight cases（8/68［11%］,FIGO
stage IA IV, G1=4, G2/3/others=4）had recurrence and twocases died. Notably, metastases to the PAN occurred in fivecases among the recurrent cases（5/8［63%］）.All of four caseswith post operative high risk factors of recurrence developed
PAN metastases. Conclusion In our hospital, PALA had notbeen done for endometrial cancer cases until 2017. High risk
group cases could not be prevented from PAN metastasis eventhough adjuvant chemotherapy alone had been done. This indicated PALA is effective and should be done for prevention fromrecurrence for high risk group.

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Prognostic comparison between laparotomy and laparoscopic surgery for early stage endometrial cancer Mayu

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Katabuchi1 Kumamoto University 1, School of Health Sciences,
Kumamoto University 2
Objective The prevalence of hyperprolactinemia is high inwomen with reproductive disorders. An association between hyperprolactinemia and endometrial cancer（EC）has been reported. The aim of this study was to confirm the effect of cabergoline on young hyperprolactinemic patients treated with medroxyprogesterone acetate（MPA）for the preservation of fertility which includes the high risk of disease relapse and progression during the observational period. Methods A retrospective
observational study was conducted to identify patients withatypical endometrial hyperplasia（AEH）or early stage endometrial cancer（EC）aged 40 years or younger who weretreated with oral MPA in our hospital between 1998 and 2016.
Results Thirty four patients were identified and divided into
two groups of 17 patients each, including a non administrationof cabergoline group（NC）and an administration of cabergoline
group（AC）.The ratio of pathological diagnoses of EC in the NC
group was significantly lower than that in the AC group（29.4%
vs. 70.6%, P=0.016）.The mean serum prolactin levels showed asignificant decrease after the administration of cabergoline in
the AC group（25.2±24.0 vs. 5.2±4.2 ng/ml, P=0.003）, and thisdecreased level was also significantly lower than that in the NC
group（5.2±4.2 vs. 12.0±5.0 ng/ml, P＜0.001）. Kaplan Meieranalysis conducted over 150 months revealed that the estimatedmean period until hysterectomy in the NC group was significantly shorter than that in the AC group（83.5 vs. 140.8 months,
P=0.007）. Conclusion The administration of cabergoline may
contribute to preserving fertility in young hyperprolactinemic
patients with EC who were treated with MPA.

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A risk factor of treatment failure of conservative management of atypical endometrial hyperplasia and endometrial
carcinoma Masafumi Yasunaga, Keisuke Kodama, Shinichiro
Yamaguchi, Hiroshi Yagi, Tatsuhiro Ohgami, Ichiro Onoyama,
Eisuke Kaneki, Kaoru Okugawa, Hideaki Yahata, Kenzo Sonoda,
Tsunehisa Kaku, Kiyoko Kato Kyushu University HospitalObjective Hormonal therapy for atypical endometrial hyperplasia（AEH）and well differentiated endometrial cancer（EC）is
one of treatment option for young patients desiring for childbearing. However, this treatment has not been optimal withhigh treatment failure rates. This study is to clarify clinicopathologic risk factors of treatment failure of conservative management of AEH and EC. Methods The institutional database
was searched to identify all AEH and EC patients treated withmedroxyprogesterone acetate（MPA）from 1999 to 2015. Clinicalinformation was obtained from electronic medical records. Relationships between clinicopathologic variables and treatment
failure were calculated using the Wilcoxon rank sum test or
Fisher exact test. All statistical analyses were performed using
the JMP software. A 2 sided P value（＜0.05）was considered significant. Results Between 1999 to 2015, 20 patients were identified for analysis. Thirteen patients had EC, 5 had AEH and 2 had
atypical polypoid adenomyoma. The median patient age was
30.5 years（range, 17 to 42 years）. The median Body Mass Index（BMI）was 22.9（range, 17.6 to 43.4）. Sixteen had a complete response（CR）, 2 stable disease and 1 progression of disease. Sevenof 16 CR patients relapsed. Hysterectomy has been performed
for seven patients who relapsed or had a stable disease. The
other 3 patients has been added next cycle of hormonal therapy.
There was no significant relationship between BMI and treatment failure（p=0.28 by Wilcoxon test）. Conclusion Now, we aregoing to evaluate relationships between endometrial cancer
stem cell markers such as ALDH1 or CD99 and treatment failure by immunohistochemical method.

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ISP-39-9
Diagnostic effectiveness of Sentinel Lymph Node Mapping：Comparison with MRI, PET/CT in early cervical and endometrial cancer Jeong-Yeol Park, Geon-Woo Lee, Dae-Yeon
Kim, Dae-Shik Suh, Jong-Hyeok Kim, Yong-Man Kim,
Young-Tak Kim, Joo-Hyun Nam University of Ulsan College ofMedicine, Asan Medical Center, Korea
Objective To substantiate of the usefulness of sentinel lymph
node mapping（SLNM）with indocyanine green（ICG）compare
to preoperative imaging tools like magnetic resonance imaging（MRI）, positron emission tomography/computed tomography（PET/CT）in early cervical and endometrial cancer. Materials
and Methods We reviewed 203 patients with early stage cervical and endometrial cancer who underwent laparoscopic or robotic surgery with SLNM between August 1, 2015 and April 30,
2017. All patients underwent preoperative MRI and/or PET/CT
and lymphadenectomy was performed during surgery. The diagnostic exactness of MRI, PET/CT, and SLNM was evaluatedusing McNemar test and logistic regression using generalized
estimating equation. Results All patients had SLNM of at least
one hemipelvis. Lymph nodes metastasis on permanent biopsy
were found in 33 patients, and SLNM found metastasis in 31 patients. There was no significant difference in sensitivity（45.5%
vs. 45.5%, p＞0.99）, specificity（91.0% vs. 92.8%, p＞0.99）, accuracy（83.5% vs. 85.0%, p＞0.99）,positive predictive value（PPV）（50.0% vs. 55.6%, p＞0.99）,and negative predictive value（NPV）（89.4% vs. 89.6%, p＞0.99）of MRI and PET/CT. SLNM values
were more accurate results shows at sensitivity（93.9%）, specificity（99.4%）, accuracy（98.5%）, PPV（96.9%）, NPV（98.8%）andstatistical significance was shown at all values（p＜0.05）. In

SLBM in hemipelvis, sensitivity, specificity, accuracy, PPV, andNPV were also more accurate than MRI and PET/CT. Conclusion SLNM using ICG is the compatible and best way to evaluate lymph node status before conventional lymphadenectomy inearly stage cervical and endometrial cancer.

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Efficacy and Safety of En bloc Total Parietal Peritonectomy
for Primary or Recurrent Ovarian Cancer with Peritoneal
Carcinomatosis Aeran Seol, Hee Seung Kim, Jae-Weon Kim
Seoul National University College of Medicine, Korea
Background To evaluate the efficacy and safety of en bloc total
parietal peritonectomy for primary advanced stage or platinum sensitive recurrent ovarian cancer with peritoneal carcinomatosis. Methods Two gynecologic oncologists enrolled patients prospectively in the same criteria as follows：patientswith primary advanced stage（IIIB to IVB）or platinum sensitive recurrent ovarian cancer：those expected to receive optimal debulking surgery（residual tumor 1 cm）in preoperative
studies：those who received en bloc total parietal peritonectomy for treating peritoneal carcinomatosis. Results Among 73
patients, 3（4.7%）, 34（51.5%）, 8（12.5%）and 20 patients（31.3%）
showed IIIB, IIIC, IVA and IVB disease, respectively. The median value of operation time was 465 minutes（range, 100 1080
minutes）,and 61 patients（83.6%）received transfusion（the median value, 6；range, 1 22）. Upper abdominal surgery such as
splenectomy were performed in all patients, and 58（79.5%）and
23 patients（31.5%）underwent large and small bowel resection
and anastomosis, and 4 patients（5.5%）received prophylactic
ileostomy. After the surgery, 54（84.4%）and 10 patients（15.6%）
showed gross free and minimal residual disease（ 1 cm）. Disease recurrence was observed in 20（31.3%）and 6 patients（66.7%）with primary and recurrent ovarian cancer, respectively. Median values of overall survival were 48 months in patients with primary ovarian cancer and 32 months in those withrecurrent disease. Conclusion En bloc total parietal peritonectomy is feasible with acceptable morbidity in primary or recurrent ovarian cancer, and contributes to cytoreduction for treating peritoneal carcinomatosis.

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Reporting of Double Cancer Survivor：10 years survival
from Synchronous Ovarian and Colorectal Tumour Post Surgery Post Chemotherapy Eugene Leong Weng Kong1, April
Roslaini2, Christina Ng3 Taylors University School of Medicine,
Malaysia 1, University of Malaya, Malaysia 2, Sunway Medical
Centre, Malaysia 3
Objective This is just a simple report from a reporter（ELWK）ofsurvival from synchronous ovarian cancer and colorectal cancer
in a patient operated by the primary and second author and chemotherapy by the third author whilst in the University of Malaya in 2006.（This was presented as a poster in the OGSM 2016
in Malaysia for local review）. Patient is still well as of 2017
every year Chinese New Year she calls me ＆ sends me a cakeas she did in 2017. Methodology Madam XX has given permission for anoynomised report. She was operated in 2006 in the
University of Malaya by ELWK, Consultant GynaeOncologist
and Consultant Colorectal Surgeon（Dr. April Roslaini, now Professor）. She was initially diagnosed pre operatively as having
ovarian cancer but on table a colorectal cancer was discovered
as well with histopathological confirmation of both separate tumours. She was subsequently referred for chemotherapy to Dr.
Christina Ng（now in Sunway Medical Centre/Hospital Pantai,
Bangsar）. Every year the patient sends a Chinese New Yearcake to ELWK. ELWK last saw her as a patient in 2013. Being apensioner, she is on follow up in a government hospital. Results

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ISP-40-3
Preoperative neutrophil/lymphocyte ratio and CA125 may be
predictive factors for recurrence in stage I ovarian clear cell
carcinoma
Yuji Takei, Shizuo Machida, Akiyo Taneichi,
Suzuyo Takahashi, Yoshifumi Takahashi, Takahiro Yoshiba,
Hiroyuki Morisawa, Chikako Yoshida, Ayumi Iwashita, Yasushi
Saga, Hiroyuki Fujiwara, Shigeki Matsubara Jichi Medical University
Objective Ovarian clear cell carcinoma（OCCC）is resistant tochemotherapy and even if stage I, its prognosis differs depending on the substage. If prognostic factors other than FIGO staging were found, it may lead to the development of new therapeutic strategies. Therefore, we examined the recurrence predictive factors for stage I OCCC. Methods Patients with stage I
OCCC who had undergone staging lymphadenectomy from 1988
to 2014 were selected. We retrospectively evaluated the association between recurrence and the following parameters：age,
substage, tumor diameter, implementation of postoperative chemotherapy, preoperative white blood cell（WBC）, platelet, neutrophil/lymphocyte ratio（NLR）, and CA125. ROC curve analyses were used to determine the cut off values of WBC, Plt, NLR,
and CA125. Log rank test was used to compare the recurrence
free survival of each group. A Cox proportional hazards model
was applied for multivariate analysis. Results We identified 77
eligible cases. The median tumor size was 13 cm. Fifty sevenpatients received postoperative chemotherapy. The cut off values for WBC, Plt, NLR, and CA125 were 7,350/μl, 28.1×104/μl,
2.79, and 167 U/ml, respectively. Twenty patients had recurrences. The significant recurrence predictive factors were stageIC（vs IA, p=0.014）, NLR：＞=2.79（vs ＜2.79, p=0.012）, and CA
125：＞=167（vs ＜167, p=0.004）. The hazard ratios of the above
three factors by multivariate analysis were 9.92［95% CI：1.28
76.96］, 5.71［95% CI：1.57 20.77］, and 3.65［95% CI：1.34 9.94］,
respectively. Conclusion Substage, preoperative NLR, and preoperative CA125 may be associated with recurrence in stage I
OCCC. NLR and CA125 may be independent predictive factors
for recurrence after adjusting for substage.

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ISP-40-4
Risk Factors for Venous Thromboembolism in Women with
Ovarian Cancer Tetsuya Kawaguchi, Yasuhiko Ebina, Kaho
Suzuki, Senn Wakahashi, Yoshiya Miyahara, Hideto Yamada
Kobe University
Objective We clarify the incidence of venous thromboembolism（VTE）before treatment in women with ovarian cancer andidentify risk factors for VTE. Methods In this prospective study,
110 women underwent venous ultrasonography before cancer
treatment and D dimer levels were measured. We investigatedfactors predicting deep venous thrombosis by logistic regression. Results VTE was detected in 25 women（22.7%）by venous
ultrasonography. A total of 21 women（84.4%）with VTE wereasymptomatic. D dimer levels in women with VTE（median,
10.9；range, ＜0.5 98.2μg/mL）were significantly higher thanthose in women without VTE（2.0；＜0.5 60.8μg/mL；P＜0.01）
.

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When 10.9μg/mL was used as a cutoff value for D dimer levels
to predict VTE, specificity, sensitivity, and positive and negative predictive values were 92.9%, 52.0%, 68.4%, and 86.8%, respectively. The multivariate analysis demonstrated that D dimer level（odds ratio［OR］, 19.7；95% confidence interval［CI］,
5.89 76.76）and clear cell histology（OR, 7.1；95% CI, 2.12 25.67）
were independent factors predicting VTE. Conclusion Asymptomatic VTE frequently occurred before treatment in patientswith ovarian cancer. Because the use of D dimer as a triage factor was limited, routine venous ultrasound was preferable.

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Incidence and timing of venous thromboembolism in patientswith ovarian cancer undergoing primary treatment Mizuki
Uenaka, Yasuhiko Ebina, Kaho Suzuki, Senn Wakahashi,
Yoshiya Miyahara, Hideto Yamada Kobe University
Objective To determine the incidence and timing of venous
thromboembolism（VTE）in patients with ovarian cancer undergoing primary treatment. Methods We conducted a retrospective cohort study for women who were diagnosed as having suspected malignant ovarian tumor and underwent primary treatment between June 2010 and December 2016. The timing andnumber of VTE were assessed. Deep venous thrombosis（DVT）
was based on the results of venous ultrasonography. Women
with DVT underwent enhanced CT of the lung to find pulmonary thromboembolism. The timing of VTE were categorized asfollows：at diagnosis, during neoadjuvant chemotherapy（NAC）, after interval debulking surgery（IDS）, after primarydebulking surgery（PDS）, and during adjuvant chemotherapy.
Results In 97 women with ovarian cancer and 13 with borderline ovarian tumor, 35（31.8%）women developed VTE. Twenty
eight women had VTE at diagnosis, and 7 patients developed
VTE during NAC or after PDS. The incidence of VTE at diagnosis was higher than that during primary treatment（25.5% vs
6.4%；p＜0.001）. 4 patients developed VTE after PDS, three patients experienced VTE during NAC. Conclusion VTE frequently occurred at diagnosis of ovarian cancer. The incidenceof VTE during NAC did not differ from that after PDS.

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ISP-40-6
Clinical characteristics of patients with ovarian cancer developing VTE Kohei Yamaguchi1, Yoko Matsumoto1, Tomoko
Kashiyama1, Satoko Eguchi1, Michihiro Tanikawa1, Kenbun
Sone1, Katsutoshi Oda2, Yutaka Osuga2, Tomoyuki Fujii2 The
University of Tokyo Hospital 1, The University of Tokyo 2
Objective Ovarian cancer has a higher incidence of venous
thromboembolism（VTE）than other cancers. The aim of ourstudy was to identify the predisposing factors for VTE in ovarian cancer. Methods VTE events were identified from hospitalrecords for patients with ovarian cancer who were diagnosed
and treated between 2012 and 2017 under informed consent andapproval of our ethical committee. Pathological results, clinicalstage, the timing of occurrence of VTE and anticoagulant wereanalyzed. Results Of 235 ovarian cancer patients, overall incidence of VTE was 36 cases（15.3%）. Pulmonary embolism was
detected in 21 cases. Diagnosis of VTE was made during pretreatment period in 22 cases, after surgery in 4 cases and duringchemotherapy in 8 cases. Risk factors of the occurrence of VTE
were advanced stage（Stage III IV）（p＜0.05）, and clear cell subtype was not an obvious risk factor（p=0.22）by univariate analysis. We treated VTE with unfractionated heparin for about 10
days followed by oral anticoagulant such as edoxaban（n=16）,
warfarin potassium（n=16）,rivaroxaban（n=2）as maintenancetherapy. No progression of VTE was observed during follow up,
but we experienced incidence of bleeding that required suspended administration in 2 cases of edoxaban. Conclusion The!

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The patient herself（recognizing her voice and diction）called
ELWK to send another Chinese New Year cake on the eveningof 2. 2. 2016 and in 2017 as has been the patientʼs wishes every
year for the past few years without fail. Her voice is hale andhearty and she reported that her follow up at her government
facility so far reveals no further abnormality with no complaints
or any disability despite her age（70 years plus）. Conclusion It is
possible to survive from synchronous ovarian and colorectal
cancer in Malaysia with expert surgery and chemotherapy withinvolvement of the relevant specialities to good effect. This isjust a report on survival basis documenting as such.

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incidence of VTE was high in ovarian cancer with advanced
stage. Over 60% cases, VTE was found during pre treatment.
Advanced clinical stage should be incorporated to protocols of
VTE prophylaxis in patients with ovarian cancer. After diagnosis, prompt management for VTE with anticoagulant would beneeded.

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ISP-40-7
Efficacy and safety of bevacizumab for advance and recurrent Müllerian carcinoma Hiroaki Matsubara, Takeshi
Fukuda, Masahiro Shimomura, Yuta Inoue, Mari Kasai,
Yasunori Hashiguchi, Tomoyuki Ichimura, Tomoyo Yasui,
Toshiyuki Sumi Osaka City University
Objective The aim of this study was to evaluate the efficacy andsafety of bevacizumab in patients with Müllerian carcinoma.
Methods We reviewed 46 patients with Müllerian carcinoma
treated at our hospital from April 2014 to March 2017 and evaluated efficacy based on RECIST and safety based on CTCAE. Results 27 patients were treated primarily with advanced disease
and 19 patients were treated with recurrent disease. The patients with primary treatment consisted of 18 serous carcinomas（66.7%）, 4 clear cell carcinomas（14.8%）,2 endometrioid carcinomas（7.4%）, 1 mucinous carcinoma（3.7%）and 2 other types（7.4%）in histological types. The combined chemotherapy regimen for primarily treatment was all TC（paclitaxel, carboplatin）. The response to primarily treatment were 19 CRs（70.4%）, 6 PRs（22.2%）, 1 SD（3.7%）and 1 PD（3.7%）.The patientswith recurrent treatment consisted of 9 serous carcinomas（47.4%）, 4 clear cell carcinomas（21.0%）, 1 endometrioid carcinoma（5.3%）, 2 mucinous carcinomas（10.5%）and 3 other types（15.8%）in histological types. The combined chemotherapy regimens for recurrent treatment were 13 TCs, 2 DCs（docetaxel,
carboplatin）,2 pegylated liposomal doxorubicins, 1 gemcitabine
and 1 irinotecan+cisplatin. The response to recurrent treatment
were 11 CRs（57.9%）, 4 PRs（21.1%）, 3 SDs（15.8%）and 1 PD
（5.3%）. The adverse effects specific to bevacizumab were fivegrade 2 hypertension（10.9%）, four grade 1 proteinuria（8.7%）,
one grade 2 proteinuria（7.2%）, four grade 3 proteinuria（8.7%）and three grade 4 ileal perforation（6.5%）. Conclusion
Bevacizumab is an effective drug when administered with careful observation.

ISP-40-8
Retrospective analysis of stage II〜IV epithelial ovarian cancer patients treated with systematic pelvic and para aortic
lymphadenectomy followed by chemotherapy Koutarou
Sueoka, Natsuko Shimizu, Kengo Nakashima, Takuya Kajimura,Toshiaki Taketani, Norihiro Sugino Yamaguchi University
Objective To clarify the benefit of systematic lymphadenectomy（SLNE）in advanced epithelial ovarian cancer. Methods
From January, 2007 to December, 2015, 37 cases who were diagnosed stage II〜IV epithelial ovarian or peritoneal cancer andtreated including pelvic and para aortic lymphadenectomy followed by chemotherapy in our hospital were enrolled. We routinely perform SLNE for patients achieved complete and optimal surgery at PDS or IDS. Results The patients were diagnosed as stage II in 6 cases, III in 25 cases, IV in 6 cases, and histological subtype was serous carcinoma in 27 cases. SLNE wasperformed at PDS in 18 cases, IDS in 19 cases and in 20 cases
lymph node（LN）were involved microscopically. 27 cases had
resulted in complete surgery, 10 cases in optimal surgery. In
this population, 5Y PFS was 48.1% and 5Y OS was 79.1%, respectively. Moreover, in patients with microscopic LN metastasis, 5Y PFS was 46.0% and 5Y OS was 76.3%, respectively,
which were not significantly different from patients without
nodal metastasis and same result was observed in only complete

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surgery group. We observed 18 patients had recurrence and thesites were distributed to LN in 8 cases, dissemination in 12
cases, distant organ in 2 cases. Especially in 20 patients with LN
metastasis, 7 patients had recurrence and 5 of 7 had involved LN
at recurrence but 13 with LN metastasis had not recurrence
anywhere. Conclusion Systematic lymphadenectomy might reduce the frequency of the lymph node recurrence in stage II〜
IV epithelial ovarian cancer but could not contribute to improve
the prognosis.

ISP-40-9!

Drug induced aortitis in a patient with ovarian cancer
treated with bevacizumab combination therapy Soshi
Kusunoki, Kengo Hiranuma, Takashi Hirayama, Kazunari
Fujino, Tsuyoshi Ota, Yasuhisa Terao, Atsuo Itakura, Satoru
Takeda Juntendo University
Drug induced vasculitis is an extremely rare complication ofchemotherapy. Few reports have investigated drug induced
large vessel vasculitis. We report a case of a 47 year old woman
with ovarian cancer who developed aortitis during bevacizumab combination chemotherapy. Contract enhanced CT
showed concentric thickening of the descending aorta. The
cause of aortitis was considered to be treatment with granulocyte colony stimulating factor or bevacizumab. Aortitis should
be considered in patients receiving bevacizumab combination
therapy who develop persistent fever and upper abdominal
pain. Contrast enhanced CT is useful for detecting drug induced aortitis.

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ISP-40-10
Identification of Potential Biomarkers of recurrent advanced
ovarian cancer during bevacizumab maintenance therapy aspart of first line treatment Ryosuke Saito, Nozomu Yanaihara,
So Hirose, Takafumi Kuroda, Kazuaki Takahashi, Motoaki Saito,
Hirokuni Takano, Seiji Isonishi, Aikou Okamoto, Suguru
Odajima, Junya Tabata The Jikei University School of Medicine
Objective Although the use of bevacizumab（BEV）in first line
treatment for ovarian cancer has been found to extend progression free survival, its effect in improving overall survival is limited. The search for validated biomarkers to predict disease recurrence is important for the selection of appropriate patients.
We investigated blood biomarkers and clinicopathological attributes to identify predictors of recurrence during BEV maintenance therapy. Methods The study included 48 stage III or IV
ovarian cancer patients who underwent debulking surgery withcombination chemotherapy of paclitaxel, carboplatin, and BEV
between 2013 and 2016. We compared histotype, postoperative
residual tumor, lymph node metastasis status, and several blood
parameters（CRP, WBC, hemoglobin, platelet, neutrophil tolymphocyte ratio, and CA125）
between 12 patients who recurred
during BEV maintenance therapy and 36 who did not. Results
The median age was 52.5 years in the recurrence group and 53
years in the recurrence free group. There was a significant correlation between presence or absence of residual tumor and disease recurrence（p=0.009）. There was no significant correlation
with either histotype or presence or absence of lymph node metastasis. Blood CRP and hemoglobin levels before administrationof first line chemotherapy differed significantly between thetwo groups（CRP：p=0.048；hemoglobin：p=0.001）. Conclusion
Pre chemotherapy CRP levels could be a potential predictor ofrecurrence during BEV maintenance. Further investigation ofnovel biomarkers associated with disease recurrence is required.

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Prognostic value of preoperative lymphocyte monocyte ratio

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Differences in correlation of Progression Free Survival andOverall Survival by clinical variables in epithelial ovariancancer Hyea Park, Youjean Chang, E Sun Paik, Jihye Kim,
Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae,
Chel Hun Choi Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
Objective To investigate significance of progression free survival（PFS）as optimal surrogate endpoint for overall survival（OS）,and the differences in correlation of PFS and OS by different clinical variables in epithelial ovarian cancer（EOC）patients.
Methods The clinical records of 1,134 EOC patients treated at
Samsung Medical Center between 2002 and 2015 were retrospectively reviewed. Correlation analyses with all pair wisecomparison were performed to assess the association of PFS and
OS for each clinical variable. After multivariate analysis for
PFS and OS, scatter plot with hazard ratio（HR）（with 95% CI）of
PFS and OS were drawn for clinical variables. Results For entire cohort, there is a significant linear correlation between PFS
and OS（p value＜0.0001）, and the degree of correlation is high（Spearman correlation coefficient=0.8243）. In Z test using
Fisherʼs transformation, patients with early stage（I, II）（0.9059,
p＜0.001）, lower grade（0.9019, p＜0.001）, and non serous histology（0.8853, p＜0.001）showed higher correlation coefficient. In
patients with no residual disease（0.8661, p＜0.001）, no pelvic
lymph node metastasis（0.8275, p＜0.001）, no paraaortic lymph
node metastasis（0.8267, p＜0.001）,higher correlation coefficient
was shown. In scatter plot for HR of PFS and OS, presence of residual disease, high grade, neo adjuvant chemotherapy, lymph
node metastasis were not located within estimated regression
area implicating low correlation coefficient. Conclusion The
treatment effect on OS is largely predictable according to thaton PFS in EOC, especially for patients with early stage, low

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grade, non serous, no residual disease, without lymph node metastasis.

ISP-41-3!

Pathological findings and prognosis of ovarian epithelial
borderline
malignanttumorsYoshiko Oyama, Hideki
Tokunaga, Satomi Kameda, Shoko Sakurada, Yusuke Shibuya,
Chiaki Hashimoto, Tomoyuki Nagai, Michiko Kaiho, Masafumi
Toyoshima, Muneaki Shimada, Hitoshi Niikura, Nobuo Yaegashi
Tohoku University
Objective The WHO histological classification of ovarian tumors was revised in 2014. The definition of micro invasion waschanged from within 10 mm2 to 5mm in diameter. The recommended treatments for ovarian tumors are different whether or
not there is storomal invasion so that pathological diagnosis
plays an important role. In Japan, mucinous and serous tumors
are majority of borderline malignancies. Methods There were
85 cases of mucinous and 40 cases of serous tumors between
2005 and 2014 in our institute. In the mucinous tumors,（a）6, b）7 cases showedcases had expansile invasion within 10mm2（
expansile invasion exceeding 10mm2 and（c）5 cases had infiltrative invasion. Results Case in（a）group were not changed its
malignancy according to new criteria that determine invasive .
Among the cases of（b）and（c）, one case and three cases did notmatch the new criteria for invasive cartinoma, respectively.
Three cases of serous tumors with tumors with invasion of theprevious criteria over 10mm2 showed obvious invasion exceeding 5 mm in daimeter. There was no recurrence in the fourcases of mucinous carcinoma those might be borderline malignancies. Three cases of them received chemotherapy after surgery. Conclusion Cases around the boundary between the borderline malignancy and carcinoma have good prognosis, adaptation of chemotherapy should be carefully examined.

ISP-41-4
Primary Fallopian Tube Cancer：Clinicopathological Features of Tumor occupying Lesions Shoko Sakurada1, Yoh
Watanabe2, Hideki Tokunaga1, Hidekazu Yamada3, Kazuhiro
Takehara4, Nobuo Yaegashi1 Tohoku University 1, Tohoku Medical and Pharmaceutical University 2, Miyagi Cancer Center 3,
Shikoku Cancer Center 4
Objective Recent studies reported the fimbriae of the fallopian
tube as a significant origin of ovarian high grade serous adenocarcinoma. However, primary epithelial ovarian cancer occurs
at a frequency almost 50 times higher than that of PFTC. Furthermore, no previous study of PFTC has reported clinicopathological differences among the types of tumor occupying lesions in the fallopian tube. Therefore, this study aimed to clarify
the clinicopathological differences of tumor occupying lesions
in patients with PFTC. Methods A multicenter clinical survey
was conducted at three institutions. Using macroscopic and microscopic findings, PFTCs were classified according to the occurrence of fallopian tube lesions as follows：only ampulla occupying type（Type A）, only fimbriae occupying type（TypeF）, both ampulla and fimbriae occupying but ampulla dominant type（Type AD）or fimbriae dominant type（Type FD）,
and undeterminable type（Type UD）. The clinicopathologic
characteristics and P53 immunohistochemical features of eachtype were compared. Results Forty patients with PFTC wereenrolled in this study. The median age was 58 years. Thirty four
（85.0%）patients had serous carcinoma. FIGO stage III（50.0%）was most frequently observed. The median survival duration was 6.5 years. P53 overexpression was confirmed in 22（55.0%）tumors. Nine, 9, 9 8, and 5, cases of A, F, AD, FD, and UD
were reported, respectively. However, no significant differencesin clinicopathologic factors, including P53 overexpression and

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in elderly patients with advanced epithelial ovarian cancer
Hyun Joo Lee, Byung Su Kwon, Seo Yoon Hwang, Sul Lee,
Hye Kyung Noh, Dong Soo Suh, Ki Hyung Kim Pusan National
University Hospital, Korea
Objective To investigate the prognostic significance of preoperative lymphocyte monocyte ratio（LMR）in elderly patientswith advanced epithelial ovarian cancer（EOC）receiving primary cytoreductive surgery and adjuvant platinum based chemotherapy. Methods A total of 42 elderly patients（ 65years）diagnosed with EOC who are receiving primary cytoreductive surgery and adjuvant platinum based chemotherapy
from 2009 to 2012 was included. LMR was calculated from complete blood cell count sampled before operation. Receiver operating characteristic（ROC）curves were used to calculate optimal cut off values for LMR. Prognostic significance with respect to overall survival（OS）and progression free survival（PFS）were determined using log rank test and Cox regression
analysis. Results The optimized LMR cut off value determined
by ROC curve analysis was 3.63 for PFS and OS. The high LMRgroup（LMR 3.63）was found to be significantly more associated with optimal debulking（P=0.045）and platinum response（P=0.018）than the low LMR group. In addition, Kaplan Meieranalysis revealed the LMR high group was significantly moreassociated with high PFS and OS rates（P=0.023, P=0.033, respectively）, and univariate analysis revealed that a high LMR,
histology type, and optimal debulking and platinum responses
were significantly associated with prolonged PFS and OS. However, subsequent COX multivariate analysis showed only optimal debulking and platinum response were independent prognostic factors of PFS or OS. Conclusions This study suggeststhat LMR might be associated with treatment and survival outcomes in elderly patients with EOC receiving standard oncology treatment.

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long term prognosis, were observed among the types of tumor
occupying lesions. Conclusion The present study found no significant correlation of tumor occupying lesions in the fallopian
tube with PFTC carcinogenesis.

ISP-41-5

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Treatment free interval（TFI）is useful not only for choiceof second line agents but for prognostic factor in ovarianhigh grade serous carcinoma cases stage III/IV Remi
Hasegawa, Chuyu Hayashi, Yuki Okuma, Erina Hashimoto,
Osamu Kobayashi, Kaori Shinya, Akiko Kasuga, Takehiro
Nakao, Atsushi Komatsu, Shinichi Takada, Fumihisa Chishima,
Kei Kawana Nihon University
Objective Since most of high grade serous carcinoma（HGS）progress to advanced stage III/IV, HGS often acquire platinum resistance during first line chemotherapy. Stratification by treatment free interval（TFI）is useful for choice of second line
agents and platinum partially sensitive cases（TFI：6m＜＜12m）are considered to receive first line agents again. We here examine whether TFI guided second line agents was best choice
for recurrent HGS cases. Methods Under approval by Ethicalcommittee in our hospital, twenty two HGS cases with FIGO
stage III/IV treated in our hospital were investigated retrospectively（follow up time 13 62m, median=41m）. Surgically debulked cases had undergone conventional paclitaxel（175mg/
2（plus bevacizumab［n=4］）. Rem ）and carboplatin（AUC=6.0）
current cases with TFI＞6m received TC again. The progression free survival（PFS）, overall survival（OS）were analyzed
by Kaplan Meier plot and cox proportional hazard model. Results 3ys OS and PFS of all ovarian HGS cases with stage III/IV
was 79% and 23%, respectively. Median PFS of our cases was 12
m. Among 16 recurrent cases, median OS of platinum partiallysensitive and resistant cases was 44m vs. 40m, respectively.
Cox hazard model revealed that TFI was independent prognostic factor with statistical significance（p=0.05）. Lymphadenectomy（LA）
was not a prognostic factor for stage III/IV HGS. Conclusion TFI was not only a useful marker to choose second line
agents but an independent prognostic marker for recurrent
HGS cases. Our data confirmed that platinum partially sensitive
cases receive TC again at the recurrent treatment. More effective second line agents must be needed for treatment of HGS
cases at least with TFI of shorter than 6m.

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ISP-41-6
Oligoclonality following chemotherapy in high grade serous
ovarian cancer Hisamitsu Takaya, Hidekatsu Nakai, Takako
Tobiume, Ayako Suzuki, Kosuke Murakami, Shiro Takamatsu,
Masao Shimaoka, Yoshie Yo, Masato Aoki, Risa Fujishima,
Hanako Sato, Noriomi Matsumura Kindai University
Objective High grade serous ovarian cancer（HGSOC）was genetically characterized TP53 mutation resulted in intratumor
heterogeneity due to dysregulation of apoptosis and DNA repair
process. Intratumor heterogeneity give rise to tumor progression and recurrence and chemo resistance, but few studies havebeen reported about quantification of intratumor heterogeneity
throughout cancer treatment in HGSOC. The aim of this study isto reveal relation between clonal diversity of HGSOC and clinical course. Methods A whole genome single nucleotide polymorphism array was applied to generate the genome wide segmentation data which included log2 ratio（L2R）and B allele frequency（BAF）. Two dimensional plots of L2R and BAF wereclassified with percentage of aberrant cells at the part of loss ofheterozygosity and we could estimate the clonal composition by
the number of plots line. We analyzed the clonal composition oftumor in 34 tumor samples from 20 HGSOC cases at the time ofprimary surgery（biopsy or maximum cytoreductive surgery）,

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after neoadjuvant chemotherapy（NAC；in 4 cases）, and recurrence（in 10 cases）. Results Higher number of clonal composition（＞2）had a tendency of poor progression free survivals（pvalue=0.0821）. The number of clonal composition of the 4 NAC
cases was as follows；（pre NAC, post NAC, at recurrence）=（3,1, 3）（, 3, 1, 2）（, 2, 1, 2）,and（2, 1, N/A；no recurrence）, indicating oligoclonality following chemotherapy. Conclusion HGSOC
would consist of chemo sensitive and chemo resistant clones
and intratumor heterogeneity of HGSOC would relate with recurrence.

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ISP-41-7
Difference in prognosis and prognostic factors of patientswith epithelial ovarian cancer according to age Masahiro
Shimomura, Takeshi Fukuda, Yuta Inoue, Hiroaki Matsubara,
Mari Kasai, Yasunori Hashiguchi, Tomoyuki Ichimura, Tomoyo
Yasui, Toshiyuki Sumi Osaka City University
Objective The aim of this study was to compare the prognosis ofpatients with epithelial ovarian cancer between old patients（＞
65 years old）and young patients（＜65 years old）,moreover toinvestigate the difference of prognostic factors between thesepatients. Methods 114 patients with epithelial ovarian cancer
who were treated in our hospital between January 2008 and December 2011 were enrolled in this study. We divided these patients in two groups, the one included old patients（＞65 yearsold）and the other included young patients（＜65 years old）.We
compared the characteristics and prognosis retrospectively andmultivariate analysis was performed to investigate the prognostic factors of these groups. Results There were no statisticallysignificant differences in performance status, clinical stage,
lymph nodes status, serum albumin level, hemoglobin level, CA
125 level, the completion rate of the standard treatment and thesize of postoperative residual disease between two groups. However, there was a statistically significant differences only in distribution of histological types（P=0.006）. As for the prognosis,
there were no statistically significant differences in overall survival and disease free survival between two groups. The multivariate analysis revealed that clinical stage and the completion
rate of the standard treatment were independent prognostic factors of young patients（P＜0.001）and performance status was independent prognostic factors of elderly patients（P=0.019）. Conclusion There was difference in prognostic factors between two
groups although they had equivalent prognosis. We might needdifferent strategy according to patients age to improve theprognosis of the patients with ovarian cancer further.

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Hyperfibrinogenemia shortens progression free survival inwomen with ovarian cancer Yuka Murata, Yasuhiko Ebina,
Kaho Suzuki, Senn Wakahashi, Yoshiya Miyahara, Hideto
Yamada Kobe University
Objective To determine clinical factors which are associatedwith progression free survival（PFS）in women with ovariancancer. Methods A retrospective cohort study enrolled 81
women who were diagnosed as having ovarian cancer between
June 2010 and December 2015. The median age was 59（range
21 91）years. This study evaluated whether laboratory findings
and clinicopathological factors were associated with PFS. The
laboratory findings included elevated levels of D dimer（＞1.0μg/ml）,hyperfibrinogenemia（＞400 mg/dl）and thrombocytosis（＞40×104/μl）. The clinicopathological factors included theage, presence of venous thromboembolism, FIGO stage, histology, tumor diameter, presence of ascites and CA 125 levels.
Kaplan Meier method and Cox proportional hazards regression
model were used. Results In univariate analyses, advanced
stage（p＜0.001）, presence of ascites（p＜0.05）, hyperfibrinogene-

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Diagnostic utility of peritoneal effusion cell block and immunocytochemistry for advanced stage ovarian/peritoneal
cancer prior to neoadjuvant chemotherapy Yasuhiko Ebina,
Kaho Suzuki, Senn Wakahashi, Yoshiya Miyahara, Hideto
Yamada Kobe University
Objective To assess if peritoneal effusion cell block（CB）and
immunocytochemistry could be useful in recognition of ovarian/peritoneal cancer cells prior to neoadjuvant chemotherapy（NAC）. Methods We conducted a prospective study for women
who were diagnosed as having suspected stage III IV ovarian/
peritoneal cancer（ovarian cancer n=26, peritoneal cancer n=5）between September 2010 and May 2017. A total of 31 peritoneal effusion cytology and concurrently prepared CB obtained
from paracentesis were reviewed. The median age was 66（range 38 88）years. The correlation between the cytology/CB
result and final histological diagnosis was assessed. Results Of
the 31 peritoneal effusion specimen, 21 malignancies were detected by cytology；however, CB increased the number of detected malignancies to 25 for an increased diagnostic yield of
19%. Twenty three（92%）showing morphologic features consistent with ovarian/peritoneal cancer were PAX8+/WT 1+. The
remaining 2 adenocarcinoma cases with CK20+/CDX2+/
PAX8 /WT 1 represented metastasis from stomach and pancreas. Six patients who had benign results of CB underwent exploratory laparotomy and were diagnosed as primary ovarian/
peritoneal cancer. Twenty six patients received NAC and 17
patients underwent interval debulking surgery（IDS）afterward.
Residual tumor measuring ＜0.5 cm was achieved in 94% of thepatients. The incidence of serous carcinoma（76%）in the patients having malignant CB result was significantly higher thanthat in the patients with benign CB result（17%, p=0.018）. Conclusion Peritoneal effusion CB and immunocytochemistry isuseful for the patients before NAC to confirm primary ovarian/
peritoneal cancer. In case of benign CB results, non serous histological types should be considered.

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Effect of red ginseng on genotoxicity and health related quality of life after adjuvant chemotherapy in patients with epithelial ovarian cancer：a randomized, double blind, placebo
controlled trial Soo Jin Park, Hee Seung Kim, Jae-Weon Kim
Seoul National University College of Medicine, Korea
Objective We evaluated the effect of red ginseng on toxicity,
health related quality of life（HRQL）and survival after adjuvant
chemotherapy in patients with epithelial ovarian cancer（EOC）.
Methods A total of 30 patients with EOC were randomly assigned to placebo（n=15）and red ginseng groups（n=15）after
cytoreductive surgery and adjuvant chemotherapy. All patients
took placebo or red ginseng（3,000 mg/day）for three months.
Then, we compared toxicity using laboratory markers, adverse
events and genotoxicity between the two groups at week 0（before consumption）and week 12（after consumption）.For genotoxicity, we evaluated binucleated cells（BN）index and micronuclei（MN）yield. Moreover, HRQL was investigated using questionnaire of the EORTC QLQ C30, BFI, BPI, HADS and MOS

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SS. Results Red ginseng reduced MN yield in comparison withplacebo despite no difference of BN index. Although red ginseng
increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse
events between placebo and red ginseng groups. In terms of
HRQL, red ginseng was associated with improved emotional
functioning and decreased symptoms of fatigue, nausea andvomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there wasno effect of red ginseng on prognosis of EOC. Conclusion Red
ginseng may be safe and effective to reduce genotoxicity andimprove HRQL despite no benefit of survival in patients with
EOC who received chemotherapy.

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Practice patterns of debulking surgery for advanced stage
ovarian cancer：analysis from national and society sponsored surveys Soyeon Kweon, Hee Seung Kim, Jae-Weon Kim
Seoul National University College of Medicine, Korea
Background To investigate practice patterns of debulking surgery, and identify surgical trends for advanced stage ovariancancer（AOC）. Methods After searching for 878 studies on debulking surgery for AOC till 2016, we extracted 19 questions
with similar query and answer formats in eight survey studies.
Among them, five（26.3%）,one（5.3%）,and 13（68.4%）questions
were classified into general, training, and procedure information. Results In general information, there was a higher preference for optimal debulking surgery defined as no visible tumor（44%）compared with residual tumors＜1 cm（38%）or ＜2 cm（2%）, and omental disease involving the spleen or pancreas became more important as an intraoperative finding precluding
optimal debulking surgery（35%）since 2010. The preference forneoadjuvant chemotherapy was the highest at use for 1 10%（36%）of AOC patients, which was preferred in Europe over theUnited States. In training information, there was a lack of additional training outside of gynecological fellowships（30%）. In
procedure information, conventional gynecological surgery was
mainly performed by gynecological oncologists, whereas morethan 50% of upper abdominal or urological surgeries were conducted by other surgeons or their cooperation. European clinicians showed a higher response rate of diaphragmatic stripping（88% vs. 60%）or resection（69% vs. 24%）than those from theUnited States. Conclusion No visible tumor as the criterion for
optimal debulking surgery has become important in AOC,
which requires aggressive surgery based on additional training
programs. A high preference for neoadjuvant chemotherapy is
associated with high preference of aggressive surgery.

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The clinical significance of tertiary lymphoid structures（TLS）and tumor infiltrating B cells in ovarian cancer
Masayo Ukita, Junzo Hamanishi, Ryusuke Murakami, Kaoru
Abiko, Tsukasa Baba, Masaki Mandai Kyoto University
Objective Tertiary lymphoid structure（TLS）are transient ectopic lymphoid organizations which develop under chronic inflammation. CXCL13 was shown to play a major role in TLS neogenesis. Recently TLS were detected in various type of cancers,
however there are few reports about TLS in ovarian cancer. We
investigated clinical significance of TLS in ovarian cancer.
Methods 32 patients who were diagnosed with ovarian cancer（HGSC）and treated surgically in our hospital were selectedfrom microarray data（KOV 75；GSE39204/55512）. We evaluated TLS and tumor infiltrating lymphocyte（TIL）subsets（CD8+ T cell, CD20+ B cell, CD38+ plasma cell）and correlation
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mia（p＜0.05）and thrombocytosis（p＜0.001）were associatedwith shorten PFS. Cox regression model demonstrated advanced stage（stage III or IV）（hazard ratio 27.8, 95% confidence
interval 3.6 201.1, p＜0.05）and hyperfibrinogenemia（2.6, 1.0 6.3,
p＜0.05）were independent prognostic factors for shorten PFS.
Conclusion Hyperfibrinogenemia shortens progression freesurvival in women with ovarian cancer independently of advanced stage. These results have important implications for clinicians.

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nohistochemical staining. We analyzed the correlation between
gene expression of CXCL13 and survival time of the patients（pts）by using KOV 75 and the cancer genome atlas（TCGA）
data set. Results Immunohistochemical staining revealed that
TLS were detected in 72%（23 pts）of ovarian cancer patients,
and the numbers of tumor infiltrating CD8+T cells, CD20+B
cells and CD38+ plasma cells were significantly higher in caseswith TLS（p＜0.05）. The numbers of tumor infiltrating CD20+B
cells and CD38+plasma cells were significantly higher in
CXCL13 high tumor than in CXCL13 low tumor（p＜0.05）. And
also in microarray analyses of both KOV 75 and TCGA, high
CXCL13 gene expression was significantly correlated with bothfavorable progression free survival and overall survival（p＜0.05,
each）. Conclusion CXCL13 contributes to better prognosis in
HGSCs by inducing tumor infiltrating B cells and plasma cells.
Induction of CXCL13 might be a new therapeutic target for
HGSC.

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Management of a ruptured perivascular epithelioid cell tumor during and after pregnancy：a case report Kenta
Nitahara1, Megumi Sasaki1, Hiroaki Hiraga1, Saori Ichikawa1,
Keita Tsuji1, Yuji Yoshida1, Shinji Fukunaga2 Japanese Red
Cross Ishinomaki Hospital 1, Shin-Yurigaoka General Hospital 2
Perivascular epithelioid cell tumors（PEComas）are a rare groupof tumors with the distinctive feature of epithelioid cell proliferation. Their clinical behaviors are unclear；however, theyshow an anatomical predilection for the gynecological tract. We
report a case of a ruptured PEComa at 34 weeks of pregnancy
that was found incidental to intra abdominal bleeding. A 30
year old woman, gravida 2, abortus 1, presented with sudden
onset left lower quadrant pain at 34 weeks of pregnancy. Computed tomography and sonography revealed abundant hemorrhagic ascites. An emergent exploratory laparotomy showedthat the source of the bleeding was rupture of a hematoma liketumor on the left round ligament of the uterus. The hemorrhage
was controlled by excising the tumor. A pathological diagnosis
of PEComa was confirmed following the observation of epithelioid perivascular cell proliferation, and positive immunostaining for both melanocytic（Melan A, HMB45）and smooth muscle
markers（SMA, desmin, caldesmon）.The pregnancy continued
and ended with an uncomplicated full term vaginal delivery.
Because PEComas have a borderline malignant nature and apossible recurrent mass was detected by postoperative magnetic resonance imaging, we performed an additional surgicalresection of the left round ligament. Though no palpable mass
was found, pathological findings showed vascular invasion and apossible residual lesion. We are continuing postoperative outpatient follow up without adjuvant chemotherapy. Because of the
scarcity of such cases, universally established management
methods for PEComas are lacking, particularly during pregnancy. We consider that primary surgical resection and additional chemotherapy in case of recurrence are a good choice oftreatment.

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A case of a postmenopausal woman with a spontaneously ruptured seromucinous borderline tumor of the ovary：A reviewof theliterature
Mamiko Ohta, Noriyoshi Oki, Naoko
Koriyama, Moyu Narita, Yukiko Mizuno, Ritsuko Yasuda,
Mieko Inagaki, Homare Murakoshi, Juzo Okada, Satoru
Motoyama, Shigeki Yoshida Chibune General Hospital
Ovarian seromucinous borderline tumor（SMBT）has been
newly categorized according to the WHO classification of tumors of the female reproductive organs revised in 2014. This
type of tumor is rare and comprises 7.8% of all of ovarian bor-derline tumors. Here, we present the first documented case of aspontaneously ruptured SMBT of the ovary in a postmenopausal
woman. Case A 56 year old nulliparous woman presented tothe emergency department with an acute abdomen. MRI
showed a 10 cm left ovarian cyst with thick walls that exhibited
hypointensity on T1WI and hyperintensity on T2WI, with retention of ascites and no solid component, which suggests a ruptured endometrial cyst. Through laparoscopy, a ruptured left
ovarian cyst and retention of brown ascites were observed. We
therefore performed a left salpingo oophorectomy, and because
postoperative pathological examination revealed SMBT of theleft ovary, the patient additionally underwent total abdominal
hysterectomy, right salpingo oophorectomy, omentectomy, appendectomy, and biopsies of brown nodules on the peritoneum.
Pathological examination confirmed SMBT of the left ovary
with no metastases, and the brown nodules on the peritoneum inthe pelvis were found to be noninvasive epithelial implants. The
patient was diagnosed with stage IIB disease, did not receive additional chemotherapy, and has been recurrence free for 11
months since surgery. Conclusion Because of the rarity of endometrial cyst ruptures in postmenopausal women, an awareness of the possibility of ovarian borderline or malignant tumors, including SMBT, is necessary when a ruptured endometrial cyst is suspected in postmenopausal women.

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Advanced ovarian cancer developing in a cyst of the canal of
Nuck Kazue Togashi, Noriaki Ohyama, Hirokazu Sato Japanese
Red Cross Akita Hospital
Ovarian cancer metastasizing to rare regions is sometimes challenging to diagnose. A cyst of the canal of Nuck is a rare cause
of inguinal swelling in adult women. A 45 year old woman presented with swelling in her right groin. The mass lesion measured 4×3 cm. Ultrasonography, magnetic resonance imaging
suggested that it is a cyst of the canal of Nuck, and also suggested a left ovarian incidental tumor measured 7×4 cm. Pathological diagnosis during surgery revealed it to be an unusual
metastatic cyst in the canal of Nuck. TAH+BSO+OMT, extraction of the right inguinal mass lesion, and closure of the deep inguinal ring were performed. In women presenting with swellingof the groin, a cyst of the canal of Nuck might be a suggestion ofovarian cancer.

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A case of neuroendocrine carcinoma developing from thebroad ligament of the uterus Yui Itonaga, Masakazu Nishida,
Harunobu Matsumoto, Kaei Nasu, Hisashi Narahara Oita University Hospital
Neuroendocrine carcinoma（NEC）, also called small cell carcinoma or large cell carcinoma, is a rare and aggressive tumor
that develops mainly in the lung and intestine. More rarely,
NEC develops in gynecologic organs, with poor prognoses. We
experienced a case of NEC in the broad ligament of the uterus.
The patient was a 74 year old woman with symptoms of abdominal distension and constipation. Ultrasound sonography detected an abdominal tumor larger than 10 cm. She was then admitted to our hospital. She underwent surgery under the diagnosis of ovarian cancer, but the bilateral ovaries and uterus werenormal in appearance, and a tumor was developing instead fromthe broad ligament of the uterus. The patient then received ahysterectomy, salpingo oophorectomies, and lymphadenectomy,
and the peritoneal membrane was stripped around the pelvic
space. Despite our suggestion, she never accepted the adjuvant
treatment. She discontinued her periodic follow up with us andwas followed in another hospital. Generally, the prognosis of
NEC is poor, and there is no established treatment for a tumor

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in a gynecologic lesion. However, we anticipate that the accumulation of experience treating such cases will eventually leadto a standard treatment for NEC.

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Primary
retroperitoneal
Müllerianadenocarcinoma（PRMA）：A Case Report and Review of the Literatures
Chia-Yi Lee, Wen-Chun Chang National Taiwan University Hospital, Taiwan
Müllerian adenocarcinoma rarely originates from retroperitoneal space. Different differentiated cell types had been reported.
Laparotomic tumor excision with avoidance of intra operative
rupture is an ideal surgical treatment. However, the recommended adjuvant treatment remains elusive due to limited casenumber and treatment experience.

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A case of Serous Tubal Intraepithelial Carcinoma detected byabnormal cervical cytology Masahiro Sumitomo, Takahito
Ashihara, Naoki Horikawa, Hirofumi Nonogaki Shiga Medical
Center for Adults
Introduction Serous Tubal Intraepithelial Carcinoma（STIC）isvery rare findings in women without genetic risk factor forovarian and breast cancer. In this presentation, we describe acase of STIC without genetic risk factor diagnosed by abnormal
cervical cytology. Case Forty eight years old Japanese woman,
Gravida 3 Para2, was referred to our hospital for further examination of abnormal cervical cytology. She had no familial historyof ovarian and breast cancer. A cytological finding was adenocarcinoma, but no abnormal findings were detected in corn biopsy and endometrial curettage specimen. One year later, cervical cytology was detected adenocarcinoma once again, therefore
she wished to be performed hysterectomy, and salpingectomy
as well for reducing ovarian cancer risk. Histological findings inremoved fallopian tube revealed serous intraepithelial carcinoma in distal fimbriated end. P53 staining was positive in immunohistological study. Adenocarcinoma cells derived form cervical cytology were remarkably similar to tubal intraepithelial
carcinoma cells. Discussion We sometimes experience tubal
cancer case diagnosed by abnormal cervical cytology, but inthis case just epithelial lesion in distal end of fallopian tube wasdiagnosed by abnormal cervical cytology. This clinical course isthought to be extremely rare. Furthermore, this STIC lesion isconsidered to remain intraepithelial（not invaded into stroma）
for more than one year period because her adenocarcinoma
cells were detected 1 year before hysterectomy. Result We experienced a rare case of STIC diagnosed by cervical cytology.
From this case, it is suggested STIC remains intraepithelial fora long time.

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Alpha fetoprotein producing ovarian malignant tumor in a
postmenopausal woman Shozo Yoshida, Akira Onogi Osaka Gyoumeikan Hospital
Most of the AFP producing ovarian tumors are germ cell tumors and occur in young women. We report a case of AFP producing ovarian malignant tumor in postmenopausal woman. A!

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Malignant ovarian tumors diagnosed after laparoscopic surgery at a general gynecological unit Yoko Hasumi, TakahiroHino, Yu Takahashi, Masakazu Sato, Nao Itaoka, Chiharu
Ueshima, Maki Nakata, Minako Koizumi Mitsui Memorial HospitalObjective To assess characteristics of malignant ovarian tumors

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Incidence and clinical outcomes of ovarian clear cell carcinoma in surgically resected endometrioma Jinju Lee, Jigeun
Yoo, Keun-Ho Lee Seoul St. Maryʼs Hospital, The Catholic University of Korea, Korea
Background We reviewed clinical features and survival outcomes of ovarian clear cell carcinoma patients who were initially diagnosed and surgically treated as benign ovarian endometrioma. Methods This study retrospectively reviewed
medical records of patients who were surgically diagnosed withovarian endometrial cyst from July 2008 to June 2014 in Seoul
St. Maryʼs hospital. We also reviewed records of clear cell carcinoma patients who underwent surgery at the same period oftime. We compared clinical characteristics, stage of cancer at
the time of diagnosis, and survival data of each group. Results
Eight out of 529 patients（1.51%）who were treated surgically for
benign endometrioma were diagnosed with clear cell carcinoma
on pathologic examination. Six patients were diagnosed withmalignancy on frozen section during the operation, followed bystaging surgery including total hysterectomy, bilateral lymphadnexectomy and omentectomy. Two patients were diagnosed on final pathologic report after unilateral or bilateralsalpingo oophorectomy, and did not take restaging surgery. All
8 patients had stage I disease, and showed no recurrence. The
median follow up period was for 58.5 months. We also identified
24 patients who were primarily diagnosed with ovarian clear
cell carcinoma and underwent surgical treatment during thesame period of time. The median follow up period was for 46
months. Among them, 11（45.8%）patients had surgically or pathologically proven endometriosis simultaneously, and they
showed comparable recurrence rate and overall survival withthe suspected endometrioma group. Thirteen patients, whowere not associated with endometriosis showed more advanced
stage at the time of diagnosis, higher rates of recurrence anddeath, while mean tumor size was smaller（14.45 cm vs. 11.09 cm,
p=0.05）. Conclusion We measured 1.51% of patients who were
surgically treated for endometrial cyst were finally diagnosed
with clear cell carcinoma on the pathological review. They werediagnosed with relatively lower stages of cancer and showed
better survival outcomes. We were also able to confirm that endometriosis in those with clear cell cancer is associated with
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53 year old nulliparous woman who had been postmenopausal
for 3 years visited to our hospital with the chief complains of abdominal fullness and appetite loss. Magnetic resonance imagingof the abdomen and pelvis demonstrated a huge multilocular
cystic mass with enhanced irregular solid component, measuring at least 30cm in diameter. Serum level of AFP was markedly
elevated to 77,657.2 ng/ml, CA125 was 122.8 U/ml and CA19 9
was 305.9 U/ml. These results suggested the mass seemed to bea malignant ovarian germ cell tumor. The patient underwent
surgical resection including a total hysterectomy, bilateralsalpingo oophorectomy and omentectomy. The mass was rightovary and weighed about 10kg. Postoperative histological examination revealed the tumor consisted of both germ cell andepithelial tumor components. Germ cell tumor component wasyolk sac tumor and epithelial one was endometrioid adenocarcinoma with the background of endometriotic cyst. Immunohistochemical staining showed that yolk sac component was positive
for AFP and SALL4 and endometrioid adenocarcinoma component was positive for CK7 and p53. After the surgery, the patient underwent six courses of adjuvant chemotherapy with docetaxel and carboplatin. Serum AFP level gradually decreased
to below normal level 74 days after surgery. She is currently doing well without any sign of recurrence, 15 months postoperatively.

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diagnosed after laparoscopic surgery at a gynecology unit.
Methods A retrospective study of malignant ovarian tumor patients who underwent laparoscopic surgery at a single institution from January 2015 to August 2017 was performed. Results
We identified 6 patients. One patient had ovarian cancer andfive patients had low potential malignancies. The median age
was 55（31 74）years old, The median size of the tumor was 4.5（3 10）cm. One patient underwent cytectomy and five patients
underwent salpingooophrectomy, of which four patients underwent follow up hysterectomy and omentectomy. All cases had
stage 1 disease. Compared to the 13 malingant ovarian tumor patients who underwent laparotomy during the same period, thelaparoscopic surgery group had tendency of smaller tumors
with smaller solid parts in the tumor, and poor contrast enhancement of blood supply in the tumor upon preoperative ultrasound and MRI evaluations. Conclusion Altough the incidence is low, there are malignant ovarian tumor cases which are
difficult to predict preoperatively. Especially in elderly paitents,
it is important to be aware of this possibility and to provide sufficient information for patients upon treatment.

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of vulvar cancer. Methods From 2009 to 2015, 21 women withvulvar cancer underwent VEIL H, this inguinal procedure were
performed with four working ports placed in the hypogastricarea. Results All patients underwent the bilateral VEIL H, andsix of which underwent additional laparoscopic pelvic procedure following VEIL H via the initially working ports. Themean（range）operative time of VEIL H was 89.5 minutes（70127 minutes）, with the retrieval of 16.5（12 22）superficial nodes
and 8.9（6 13）deep nodes. The estimated median blood loss was
21.7 ml（5 120ml）and the drain volume was 103.6 ml（60 220ml）on average. The median hospital stay was 8.3 days（3 14days）.The great saphenous vein（GSV）was spared in 39 limbs.
No major intraoperative complications occurred except the hypercarbia and rupture of GSV. The postoperative complications
included hypesthesia of groin, infection of skin edges surrounding the working port, lymphocele, mild moderate lymphedema
and local erythema. With a median follow up of 69 months（4197 months）, isolated skin bridge metastasis within the rightgroin was identified via biopsy in one patient with ipsilateral lesion（4cm）postoperatively. Surgical resection had been attempted. Conclusion This preliminary series indicates that
VEIL H could be an alternative to the open approach for thetreatment of genitourinary malignancies. However, a larger series with more cases and longer follow up are necessary toevaluate the full therapeutic efficacy of this novel technique.

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Endometrioid adenocarcinoma arising from deep infiltrating
endometriosis involving the bladder：A case report and review of the literature Yosuke Tarumi, Taisuke Mori, Fumitake
Ito, Takuya Sugahara, Hiroyuki Okimura, Eiko Maeda, Hisashi
Kataoka, Osamu Takaoka, Yukiko Tanaka, Akemi Koshiba,
Izumi Kusuki, Jo Kitawaki Kyoto Prefectural University of
Medicine
Introduction Endometriosis is a common disease, but deep infiltrating endometriosis（DIE）, especially DIE involving the bladder, is rare. Malignant transformation of endometriosis is wellestablished pathology, but only 8 cases of malignant transformation of DIE involving the bladder have been reported. We reporta very rare case of endometrioid adenocarcinoma arising from
DIE involving the bladder. Case Our patient was a 45 year old
woman who presented with frequent urination and miction pain
during her menstrual period. Transvaginal ultrasonography and
MRI revealed a lesion in the posterior wall of the bladder. Preoperative cystoscopy findings revealed focal lesions of endometriosis, and a blueberry spot on the mucous membrane of the bladder. We preoperatively diagnosed DIE involving the bladderand performed laparoscopic total hysterectomy and partial bladder resection. Histopathological examination revealed the coexistence of endometriosis and endometrioid adenocarcinoma
involving the bladder wall, and the continuum between the benign focus and malignant glands in sections of deep infiltrating
endometriosis involving the bladder. Postoperative CT findings
showed no other malignant lesions. We regarded this case asperitoneal carcinoma because the lesions were adjacent to theperitoneal serosa, and administered 6 cycles of adjuvant chemotherapy. There was no evidence of recurrence or metastasis after 30 months of follow up. Conclusion The treatment for malignant transformation involving the bladder is poorly defined.
Further case studies are needed to confirm the optimal treatment and the likely prognosis of this malignancy.

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Video endoscopic inguinal lymphadenectomy via the hypogastric subcutaneous approach（VEIL H）：A preliminary series
report Yifeng Wang, Gaowen Chen, Zengying Cui, Youhong
Zheng, Xiaoxuan Li, Ying Wang, Ying Zhu Southern Medical
University, China
Objective To summarize our experiences and preliminary results of video endoscopic inguinal lymphadenectomy via a hypogastric subcutaneous approach（VEIL H）in the management

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Repurposing itraconazole as an anticancer agent：rapid clinical response of metastatic vaginal melanoma Roze Nakata,
Kayo Inoue, Yu Kato, Shinichiro Saeki, Hidetake Kamei,
Tomoko Ueda, Hiroshi Tsubamoto, Hiroaki Shibahara The Hospital of Hyogo College of Medicine
Background Itraconazole, a common anti fungal agent, has anticancer activity. We have reported preclinical and clinical studies in various types of cancer. We show the rapid clinical response in a patient with metastatic vaginal melanoma. Case 64
year old woman presented vaginal bleeding and left inguinal
pain with lymphnode swelling. Vaginal examination showed thefragile hemorrhagic vaginal tumor of ping pong ball size with
intact cervix. Metastatic vaginal cancer was diagnosed, and informed consent of a window of opportunity trial of itraconazole（UMIN000018388）was obtained. She was administered 400ml
itraconazole per day. Pathological diagnosis was malignant
melanoma, having 20% expression of PD L1 without VRAF mutation. PET/CT scan showed metastases to pelvic and left inguinal lymphnodes and her right foot. Brain MRI revealed 2 metastases. After 10 day intake of itraconazole, her left inguinal
lymphnodes shrunk and, her pain or tender was diminished. Administration of itraconazole continued until she completed
stereotactic radiosurgery of brain metastases, then she received
nivolumab. After 28 day administration of itraconazole, 18 FDG
uptake in any lesion decreased. mRNA isolated from obtained
tissue by biopsy before and 10 day after itraconazole administration was subjected to cDNA microarray analysis. Transcriptof 4 genes coding statherin, EEF1A2, transthyretin, and N cadherin was down regulated to the level of ＜1/100. Conclusion
Two clinical trials of plitidepsin targeting EEF1A2 had modest
activity in patients with melanoma. Expression of transthyretin
and N cadherin were reported to be associated with progression of melanoma. Itraconazole could be an alternative drugwith safe and low cost for malignant melanoma.

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Anaplastic lymphoma kinase negative uterine inflammatory
myofibroblastic tumor containing the ETV6 NTRK3 fusion
gene：the first case report Akimasa Takahashi, Mao Uemura,

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Trousseauʼs syndrome associated with gynecologic malignancies. Clinicopathologic features of 11 cases Kazuya Onuma,
Takanori Fukuda, Remi Watanabe, Yutaka Kohata, Tomoyuki
Ichida, Yuri Aihara, Ayumi Kumagai, Yuina Kubo, Yoshie
Uzawa, Kenji Hishikawa, Takeshi Kusaka, Hiromi Inoue Shonan
Kamakura General HospitalObjective Trousseauʼs syndrome（TS）is known to be typicallyassociated with pancreatic, gastric, or pulmonary carcinoma,
but rarely documented in association with gynecologic malignancies. Methods Our oncology database was searched for casesof gynecologic malignant neoplasms with the document of TS,
infarction, or embolism for a 5.5 year period. For the cases
meeting the diagnosis of TS, medical records were retrieved toobtain the data including age, BMI, clinical manifestation, D Dimer（DD）,stage, outcome and the size and histologic type of tumor. Results Eleven cases with available data were subjected tothis study. The patient age ranged from 35 to 75（median 63）,
and BMI from 16.3 to 29.5（mean 21.3）. The events of TS were
pulmonary embolism（5）, cerebral infarction（5）, and multiple
organ infarction（1）. TS was the initial presentation, leading todiscovery of malignant neoplasms in 6 cases. All but one patientwith endometrial carcinoma had ovarian carcinoma, and mostly
in advanced stage. The mean size of ovarian tumor was 11 cm.
Clear cell carcinoma（CCCA）was the most common histologic
type, comprising 6 of 10 cases, and followed by mucinous tumor
in 2 cases. The mean of DD was 21.0 μg/ml. With prompt diagnosis and management, TS did not affect the prognosis in most patients. Conclusion TS was mainly associated with ovarian carcinomas and CCCA was the most common histologic type. Thromboembolic events of TS were frequently the initial presentation
prior to the diagnosis of malignancy. We should be aware of occurrence of TS in patients with ovarian carcinoma.

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Vulvar apocrine adenocarcinoma responded to weekly paclitaxel and biweekly bevacizumab. A case report Shinichiro

Saeki, Tomoko Ueda, Roze Nakata, Michie Matsuoka, Riya
Sakane, Kayo Inoue, Hiroshi Tsubamoto, Hiroaki Shibahara The
Hospital of Hyogo College of Medicine
Apocrine adenocarcinoma（AA）of the skin sweat gland is a raredisease. Among previous reports of about 50 AA cases, vulvar
AA counted for only 9 cases. Case A 63 year old woman wasreferred to our institution with a complaint of her left vulvar
mass and the lymphedema of the left leg with slight pain. Biopsy of her enlarged inguinal lymphnode showed adenocarcinoma. PET/CT scan revealed 18 FDG uptake in the left vulvar
and in the pelvic, para aortic, and the left supraclavicularlymph nodes. Local resection of vulvar tumor was conducted,
and metastatic AA was diagnosed with positive androgen receptor and GCDFP 15. The first regimen of 175mg/m2 of paclitaxel（PTX）and AUC5 of carboplatin was conducted according
to the previous report of head AA. After the first cycle, her leg
swelling was improved with 3kg weight loss. However, her leg
began to swell again after 2 cycles. After 3 cycles, the lymphedema extended to her lower abdomen with redness, warmth,and pain. Her serum creatinine and CEA elevated. She had theleft hydronephrosis and ureter stent was placed. The second
regimen with PTX and bevacizumab（Bev）was conducted according to TNBC. Combination of weekly administration of PTX（80 mg/m2）and biweekly administration of bevacizumab（10mg/kg）was reported to have synergistic effect in platinum resistant ovarian cancer. After she received the second regimen（wPTX/Bev）, her symptom was improved and PET/CT scanrevealed loss of 18 FDG uptake in any lymphnodes. Conclusion
wPTX/Bev could be a promising candidate for the treatment of
AA.

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Three different clinical courses and the conservative management of uterine arteriovenous malformation（AVM）diagnosed by color Doppler ultrasonography Madoka Tsuzuki,
Tomohiko Ishida, Hiroaki Naitou, Ritsuko Ishii, Mariko
Tomosaka, Emi Saga, Kazuya Abe, Sumiko Hasegawa,
Hirohumi Ohashi, Shinichiro Takubo Itabashi Chuo Medical
CenterUterine arteriovenous malformation（AVM）used to be a rare
and life threatening disease, with a massive genital hemorrhageof unknown origin. Nowadays, the ultrasonography（US）guides
us to diagnose AVM more easily and in earlier stage of the disease, bringing more opportunities of conservative management.
Three cases of acquired AVM with successful conservative
treatment are shown, in which the accurate diagnosis was established by two dimensional（2D）and three dimensional（3D）color Doppler US, and in which various clinical courses were observed. Case 1 Primipara 33 years old, a month after the preceding artificial abortion. Case 2 Primipara 26 years old, and Case 3
Primipara 39 years old, both 2 weeks and 1 week after the spontaneous miscarriage emission and both post IVF ET. The 2D
color Doppler showed clearly that both arterial and venous vessels are combined in a complex. The 3D color Doppler made it
more visible, proved that it rather has the nidus than the fistula.
All were considered to go under the uterine conservative management. In Case 1, gonadotropin releasing hormone agonist（GnRHa）was given and abnormal vessels all regressed to an undetectable level after few months. In Case 2, uterine artery embolization（UAE）was introduced, and prompt regression wasobserved. In Case 3, UAE was also performed, then continuous
GnRHa was given due to poor response to UAE. Quick diagnosis
of AVM in early stage of the disease using ultrasonography provides more opportunities of uterine conservative management,
which definitely fulfills the wish of patients.

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Jun Kitazawa, Yoshihiko Hayashi Nagahama City Hospital
An inflammatory myofibroblastic tumor（IMT）is currently regarded as a neoplasm of low malignant potential, and it is themost commonly found tumor in the lung or orbit. However, theuterus is a distinctly rare site of occurrence. About 50% of patients have anaplastic lymphoma kinase（ALK ）gene rearrangement, and recent studies have described novel fusions involving
the ROS1 , PDGFR β , and ETV6 genes in a subset of ALK
negative patients. We describe the case of a uterine IMT in a
44 year old woman presenting with anemia. Her ultrasonogramand magnetic resonance imaging scan showed a myxoid degenerative myoma like mass measuring 70 mm in maximum diameter on the left side wall of the uterine body. Hysterectomy was
performed as definitive treatment. Microscopic examination revealed spindle cell proliferation with numerous lymphocytes
and plasma cells. Immunohistochemically, the spindle cells were
negative for ALK 1 , desmin, and smooth muscle actin. The pathologic diagnosis was IMT arising from the uterus. Her tumor
showed ETV6 NTRK3 translocation, as demonstrated by fluorescence in situ hybridization, not ALK , ROS1 , or PDGFR βtranslocation. She underwent computed tomography（CT）of herlung and abdomen at 31 months postoperatively, and the CT
scans showed no disease recurrence. This is the first report ofthe presence of the ETV6 NTRK3 fusion oncogene in an ALK
negative IMT of a patientʼs uterus. Its association with theETV6 NTRK3 fusion gene provides some clues to better understand this neoplasm and to eventually develop specific therapies.

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A case of lymphangiomyomatosis with suspected primary
peritoneal cancer and struggling to control ascites Ken
Matsukuma, Koichiro Kawano, Sayo Kubo, Jongmyung Park,
Hiroki Nasu, Atsumu Terada, Shin Nishio, Naotake Tsuda, Kan
Komai, Kimio Ushijima Kurume University Hospital
Lymphangiomyomatosis（LAM）is a rare disease with a incidence of 1.9 to 4.5 cases per million, and it occurs exclusively inwomen of reproductive ages. LAM cells showing smooth muscle
cell like morphology proliferate in the lungs, axial lymphatics
including the mediastinum, retroperitoneum. Approximately
15% of patients have been diagnosed based on the presence ofchylothrax, chylous ascites, and lymphangioleiomyomas of theretroperitoneum and pelvis. A 44 year old woman was referredwith a suspicious of primary peritoneal cancer due to the findings of pleural effusion, ascites, pelvic lymph node swelling, andperitoneal irregularity. Exploratory laparoscopy revealed chylous ascites and pelvic lymphadenopathy without peritoneal dissemination. Right slpingo oophorectomy, left salpingectomy,
omentectomy, and pelvic lymphadenectomy was performed.
Pathological diagnosis showed no adnexal tumor but paraganglioma in pelvic lymph nodes. Postoperatively, we could not control the chylous ascites by fasting, diuretics, somatostatin analogue, and cell free and concentrated ascites reinfusion therapy.
Therefore, laparotomy was performed. Because we failed to
identify lymphatic efflux sites using indocyanin green, thelymph duct above the excised lymph node was ligated. Histological findings of lymph node showed that cells with homogeneous circular nuclei in the eosinophilic cytoplasm formed vesicular nests. Immunohistochemistry was positive for alphasmooth muscle actin, HMB45, and Melan A. Computed tomography revealed the vesicular lesion in her both lungs. These findings were diagnosed as LAM and we started to administrate sirolimus. Her symptoms dramatically improved after the initiation of sirolimus. Although there was no change in pulmonary
lesions, ascites markedly decreased without a sign of relapse for6 months.

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A case of amelanotic malignant melanoma arising from vagina
Takashi Hirayama, Soshi Kusunoki, Kazunari Fujino,
Yasuhisa Terao, Atsuo Itakura Juntendo University Hospital
Malignant melanoma（MM）arising from vagina is an extremelyrare and highly malignant disease. It constitutes less than 0.3%
of all melanomas and less than 3% of all malignant vaginal tumors. In the MM, it contains 15 20% of amelanotic MM showing
only a few or no melanin component in the tumors on the pathological findings. Therefore it is often difficult to diagnose and to
determine the surgical margin preoperatively. We describe a
66 year old female patient with an MM arising from vagina,
which was almost composed of an amelanotic lesion. She visited
a local hospital due to abnormal genital bleeding. Since endocervical cytology showed AGC and endocervical biopsy showed
MM, she was referred to our hospital suspected MM from uterine cervix. We found the black spots suspected MM at the vagina, around the external urethral orifice, uterine cervix andvulva preoperatively. There is no metastasis on the PET CT.
Therefore, we performed the anterior pelvic exenteration, pelvic lymphadenectomy and transverse rectus myocutaneous flap
to resect completely including urinary organs suspected unexpected spread of tumors. As a result of pathological findings, theMM originated from vagina spread widely at vulva, urethral orifice and uterine cervix, and almost the MM lesions wereamelanotic. Since the tumor thickness was 50 μm and the surgical margin and lymph nodes metastasis were negative, we confirmed that complete resection was achieved. In case of MM

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arising from genital tract, we should consider the possibility ofamelanotic lesion and determine the surgical procedure carefully to perform complete resection.

ISP-44-9
Isolated fallopian tube torsion diagnosed and treated with laparoscopic surgery Yuji Takahashi, Fumitake Ito, Osamu
Takaoka, Hiroshi Tatsumi, Izumi Kusuki, Jo Kitawaki Kyoto
Prefectural University of Medicine
Among diseases causing acute lower abdominal pain in women,
isolated fallopian tube torsion is very rare with an annual prevalence of 1 in 1.5 million. Because it has fewer findings on imaging compared to adnexal torsion, the correct diagnosis canrarely be made before an operation. We present a case of isolated fallopian tube torsion that was suspected preoperatively
by its clinical course and findings on computed tomography. A
24 year old woman repeatedly experienced acute colicky painin the right lower back. Transvaginal ultrasonography and magnetic resonance imaging showed a right pelvic cystic lesion
with intact ovaries；these findings led us to schedule a laparoscopic examination. However, the patient presented to the emergency room with acute severe right back pain. The preoperative diagnosis considering the computed tomography findings
and clinical course was consistent with fallopian tube torsion.
An earlier diagnosis may have help to preserve the fallopian
tube and future fertility.

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Primary peritoneal malignant mesothelioma with massive ascites：a case report Yayoi Higuchi, Takashi Ushiwaka, Yusuke
Ujihara, Ruriko Yamada, Kayo Taniguchi, Nagamasa Maeda Kochi Medical School
Background Primary peritoneal malignant mesothelioma（PPMM）is a very rare tumor. This disease accounts for about
10 15% in all types of mesothelioma. It is difficult to differential
diagnosis from peritoneal cancer. We demonstrate in this papera case of PPMM that is very rare and also difficult to differential
diagnose from peritoneal cancer. Case Eighty four years old
woman complained lower abdominal pain and abdominal distension. Massive ascites was pointed out and consulted to our clinic.
According to CT examination, massive ascites and peritoneal
thickening were observed. PET CT revealed high FDG accumulation in the omentum and peritoneum. Though the abdominal puncture was performed twice, but cyto diagnosis for ascites was negative. Thus, exploratory laparotomy was performed for its diagnosis. Intra operative findings revealed about
4,000ml of thin yellow ascites and diffuse white nodular lesions
spreading in omentum and peritoneum. According to the pathological and immunohistological findings, the tumor was diagnosed for epithelial type PPMM, especially decidual type that is
a subtype. General condition was getting worth after laparotomy because of massive ascites. Medical staff and her family decided not to perform chemotherapy because of rapid decline of
the general condition. The patient was deceased on the 27th day
after admission. Conclusion Because PPMM is originated fromthe peritoneum, differential diagnosis with peritoneal cancer
may be extremely difficult. When cyto diagnosis for ascites cannot be identified regardless of massive ascites and wide
spreaded peritoneal lesions, PPMM should be considered.

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Epidemiology of prolonged pregnancy in Mongolia：Incidence and risk factors Saruulsaikhan Erdenebat, Amgalanbaatar
Dorjkhuu, Enebish Sundui, Enkhtsetseg Jamsranjav Mongolian
National University of Medical Sciences, Mongolia
Aim Prolonged pregnancy is associated with an increased fre-

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drill（L＆D）using DRCBRAVADO were given to each BSL
group, consisting of 5 8 persons of the fifth year medical students. We analyzed self assessment score sheets recorded before and after L＆D. The sheet included multiple items scored0 5 points separately. Results Twenty five groups, total of 170
students were enrolled. Prior learning score were quite low but
their need for an efficient method to learn cardiotocogram wasvery high（2.9±0.066（mean±SE）,4.9±0.020）. Scores were increased significantly（p＜0.01）after the L＆D in overall confidence to assess cardiotocogram, understanding of the learning
points and interpretability of them（1.4±0.047 vs 4.0±0.049, 1.7±0.052 vs 4.3±0.046, 1.3±0.042 vs 3.8±0.051）.There revealed apositive correlation between understanding and interpretability（R=0.60, P＜0.001）but little relation between interpretability and feel useful or feel applicable（R=0.36, 0.37, NS）.Conclusion Introduction and practice of DRCBRAVADO as an educational tool seemed to be useful to enhance the motivation forlearning but not to be sure about long term effect on assessment skills because they had limited opportunity for clinical application.

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JICA projects to disseminate cardiotocography in Mongolia
Kazutomo Ohashi1, Masayuki Endo2 Osaka University, Divisionof Health Sciences 1, Osaka University 2
Objective We conducted two JICA projects to disseminate CTG
in Mongolia, and present our views on international cooperation
among Japanese obstetricians. Methods We introduce two JICA
projects in Mongolia：1）Midwifery training course（2013 2016）
and 2）Feasibility survey for introducing cardiotocography（2016）. In Project 1, 20 pairs of midwives and obstetricians participated in training in Japan. Project 2 was a JICA partnershipwith private sector activities in developing countries and we examined the effect of introducing a CTG central monitoring system in one tertiary hospital from May to September 2016 withthree visits to Mongolia. On the second visit in August, we organized a CTG seminar for medical staff and medical engineers（ME）. Clinical data were divided into two stages：stage 1（before the second visit）and stage 2（after the second visit）. Results
The ex participants in Project 1 supported the operation of Project 2. The numbers of deliveries were 483 and 307 in stages 1
and 2, respectively. The numbers（%）of vacuum extractions,neonatal resuscitations and neonatal deaths were 9（1.86%）vs.
15（4.89%）, 14（2.90%）vs. 3（0.98%）,and 6（1.25%）vs. 3（0.96%）,
respectively. Additionally, the use of a central monitoring system led to reduce working hours and improvement of the working environment. Conclusion Project 2 was planned according
to requests of participants in Project 1. When developing overseas support projects, it is important to sufficiently grasp theneeds of medical professionals working at the site. Multidisciplinary cooperation was essential for the projectʼs success.

Imprisoned and Pregnant：Evaluating the Use of Correctional Restraints Mallory Fox, Kelly Best University of Florida
College of Medicine, USA
Background The use of physical restraints in pregnant incarcerated patients is commonplace in many health care institutions. The American College of Obstetricians and Gynecologists（ACOG）among other organizations have adopted position statements opposing the use of physical restraints. My project aimed
to assess the baseline knowledge of the correctional guard staff
implementing restraints, and to educate guard staff in efforts ofaligning practices in accordance with ACOG. Methods An educational seminar was presented to a voluntary group of correctional guards involved in the care of UF Health obstetric patients. The lecture covered associated health risks and current
practice recommendations. An anonymous pre and post IRB approved survey was administered. The rate of correct answers
by question was described across time periods using counts andpercentages, and analyzed using Fisherʼs exact tests and Wilcoxonʼs Signed Rank Test using SAS Ⓡ Version 9.4 for Windows.
Results Fifteen correctional guard staff participated and completed the pre and post survey. There was no significant relationship between time period（pre/post）and correct responses（p=0.2148 1.0）
. Additionally, there was no significant change inoverall score between time periods（p=0.1052）. Conclusion The
current study showed that several guard staff are not familiar
the current guidelines set forth by ACOG and the Florida State
Statute. While there was not a statistically significant differencein pre and post survey answers, the need for education remains
evident. Efforts should be made to limit the use of physical restraints to improve quality of care and patient safety.

ISP-45-3

ISP-45-5

An effective introduction and practice of DRCBRAVADO
as an educational tool of Cardiotocogram for medical students in bed side learning Mariko Watanabe, Susumu
Miyashita, Shoko Ochiai, Ayano Suzuki, Chiyori Sakamoto, Emi
Motegi, Kazumi Tada, Ichio Fukasawa Dokkyo Medical University
Objective ALSO（Advanced Life Support in Obstetrics）,multidisciplinary simulation training course, employs DRCBRAVADO , initial letters for systematic review of cardiotocogramas an educational tool. We investigated the effect on the introduction and practice of DRCBRAVADO for bed side learning（BSL）of medical students. Methods An inclusive lecture andDeterminants of Utilization of Antenatal Care Services
among Women in Kungyangone Township, Myanmar
San San Myint University of Medicine 1, Myanmar
This study was to detect the determinants of utilization of antenatal care services in Kungyangone Township, Myanmar. Thiscross sectional analytic study was done using both quantitativeand qualitative methods from January 2014 to January 2015. 284
women（83 from urban and 201 from rural area）rearing under
one year old child were interviewed with a structured questionnaire. For qualitative approach, six focus group discussions andnine in depth interviews were conducted. Qualitative and qualitative data were analyzed using SPSS version 16 and manually.

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quency of perinatal mortality, maternal complications, labordysfunction and postpartum hemorrhage. The purpose of ourstudy was to investigate the incidence and some risk factors forprolonged pregnancy in Ulaanbaatar, Mongolia. Methods We
retrospectively analyzed 13,444 cases with prolonged pregnancy
in the period of 2014 2016. The information was obtained fromthe patientsʼ histories in four maternity hospitals in Ulaanbaatar, Mongolia. Results In the period of 2014 2016, there were
123,218 deliveries in Ulaanbaatar. Of these 13,444（10.9%）wereprolonged pregnancies. Among the prolonged gestation, 67%
were multiparous women and 33% in primiparous women. The
risk of prolonged pregnancy is higher in the age group under 20
and over 36 years old mothers. There was a significant difference between gender of a fetus（P＜0.000001）. The overall riskof pregnancy loss（stillbirth and infant mortality）significantly
increased as compared with term births（0.6% vs. 0.2% P＜
0.000001）. Also, Neonatal mortality rates fell significantly increased with advancing gestation to reach at 41 weeks of gestation. Conclusion Our data showed that prolonged pregnancy is
associated with an excess of stillbirth, a gender of the fetus andmaternal age.

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There were 64.1% of mothers took proper antenatal care. In urban areas, 56.6% took proper antenatal care whereas 67.2% took
proper antenatal care in rural areas. In multivariable model,
educational level of husband, neonatal complication in previous
pregnancies, mode of transportation, waiting time at antenatal
clinic were significantly associated with antenatal care utilization. The respondents mentioned that availability of transportation to antenatal clinic, the condition of being apparently
healthy pregnant women, migration to different places andopening hours of the antenatal clinic are main factors influencing the proper antenatal care. The majority of women in thequalitative study supported antenatal care. A few mentioned
the benefits of antenatal care such as birth plan, preparednessfor emergency situation and timely referral of high risk cases. A
few respondents had awareness of early antenatal visit, antenatal care timing and minimal antenatal care frequency. To conclude, these results would be valuable to raise awareness ofproper antenatal care in the community to ensure good maternal and fetal outcome thereby reducing maternal and perinatal
morbidity and mortality.

ISP-45-6
Transvaginal And Colour Doppler Ultrasound In Pregnant
Women With Previous Caesarean Scar With Placental Praevia Mar Ma Wynn University of Medicine 1, Myanmar
This study was a hospital based prospective descriptive study,
done in Central Womenʼs Hospital, Yangon from October 2013 to
September 2014, to determine placenta accreta in pregnant
women with previous caesarean scar with placenta praevia by
Transvaginal colour Doppler ultrasound and to assess the accuracy of detection of placenta accreta by Doppler ultrasound.
Fifty patients with caesarean section scar with placenta praevia
were recruited for transvaginal colour Doppler ultrasound.
Among them, 39（78%）patients had one previous caesarean section, 10（20%）patients had two previous caesarean section and
one patient had three previous scars. Presence of placenta accreta were detected by transvaginal colour Doppler ultrasoundand were confirmed at caesarean section. Morbid adhesion ofplacenta praevia were diagnosed by ultrasound in 8 patients.
Among them, 4 patients really had morbid adhesion and the rest
had no occurrence of morbid adhesion at caesarean section.
Positive predictive value of TVCDS in detection of placenta
praevia is 50% and negative predictive value was 100%. Correctly diagnosed morbid adhesion（accuracy of percentage
agreement）was 92%. Four cases of placenta accreta had to undergo hysterectomy for life saving. One maternal death was occurred due to uncontrolled PPH with morbid adhesion with Rh
negative blood group. Women in this study are high risk for placenta accreta. Antenatal imaging techniques should be considered where part of the placenta lies under previous scar. If thereis imaging evidence of morbid adhesion, delivery should beplanned in setting with adequate resources.

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Fear of childbirth and associated factors among pregnant
women in Siriraj Hospital Matus Phunyammalee, Dittakarn
Boriboonhirunsarn Siriraj Hospital, Thailand
Objective To determine prevalence of childbirth fear among uncomplicated pregnant women in Siriraj Hospital and possible associated factors. Methods A total of 315 uncomplicated, singleton pregnant women were enrolled during early third trimester.
All participants were interviewed regarding baseline demographic, social, economic, family, and obstetric characteristics.
Fear of childbirth（FOC）was evaluated by Thai version of Wijma Delivery Expectancy/Experience Questionnaire Version A（WDEQ A）.Prevalence of low, moderate, high and severe fear!

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of childbirth were estimated according to WDEQ A scores（＜37, 38 65, 66 84, and ＞85 respectively）. WDEQ A scores andlevel of FOC were compared between various characteristics todetermine possible associated factors. Results Mean age was
29.1 years, mean GA was 34.6 weeks, 50.2% were nulliparous,
22.6% had prior abortion, 22.6% were housewives, 33.8% graduated bachelor degree or higher, 56.7% were in extended family,
28.9% had inadequate family income. Of them, 63.6% wereplanned pregnancy. Majority（96.1%）had ever been told about
delivery experience and 76.7% had ever witnessed delivery.
Mean WDEQ A scores was 51.9+14.4. Prevalence of low, moderate, high, and severe FOC were 18.4%, 64.9%, 16.1%, and 0.7%, respectively. Mean FOC score was significant higher in womenwith unplanned compared to planned pregnancy（54.2 vs. 50.6, p=0.033）.Significant higher prevalence of high/severe FOC wasobserved in women who had inadequate family income（23.9%
vs. 13.8%, p=0.033）, without family support（31.3% vs. 15%, p=
0.02）, never been told about delivery experience（41.7% vs.
15.7%, p=0.034）and never witness delivery（26.8% vs. 13.7%, p=0.01）. Conclusion Prevalence of high and severe FOC were
16.1% and 0.7%, respectively. High/severe FOC was related to
low financial and family support and less understandings on delivery process.

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Evidence of exposure to chemicals and heavy metals during
pregnancy in Japanese women Ryo Maekawa1, Yumiko
Mihara1, Yuichiro Shirafuta1, Masahiro Shinagawa1, Lifa Lee1,
Isao Tamura1, Hiromi Asada1, Toshiaki Taketani1, Hiroshi
Tamura1, Tsunehisa Makino2, Norihiro Sugino1 Yamaguchi University 1, Yurin Koseikai Fujioyama Hospital 2
Objective Prenatal exposure to environmental chemicals suchas phthalates, PFCs, pesticides, bisphenol A, nicotine, PBDEs,
and heavy metals is a growing concern because such exposures
have been shown to be associated with various diseases. The
levels of chemicals and heavy metals in maternal blood, cord
blood, maternal urine and amniotic fluid in Japanese pregnant
women were investigated. Methods One hundred and forty five
women, including 14 fetal growth restriction cases, were included in this study. The levels of phthalates（DEHP and
MEHP）, PFCs（PFOS, PFHxS, PFOA and PFNA）, pesticides（DMP, DMTP, DEP, DETP, 3 PBA and S 421）
, bisphenol A,
nicotine（NIC, NNIC, COT, NCOT and HCOT）, PBDEs andheavy metals were measured. The relationship between fetal
growth and the levels of chemicals and heavy metals were also
investigated. Results Phthalates, PFCs, pesticides, PBDEs andheavy metals were detected in high frequency, whereas nicotine
and bisphenol A were almost negative. The levels of phthalates,
PFCs and several heavy metals in the maternal blood, cord
blood and amniotic fluid indicated that these contaminants weretransferred to the fetus. High PFNA levels in the maternal bloodand cord blood were significantly and negatively associatedwith fetal growth. Conclusion The present study showed thelevels of chemicals and heavy metals in the maternal blood, cord
blood and amniotic fluid in pregnant women in Japan. Pregnant
women in Japan and their fetuses are exposed to a variety ofchemicals and heavy metals.

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ISP-45-9
Impact of maternal inadequate gestational weight gain on
neonatal birth weight in Japanese women Satoru Ikenoue, Kei
Miyakoshi, Yu Sato, Yohei Akiba, Toshimitsu Otani, Marie
Fukutake, Yoshifumi Kasuga, Daigo Ochiai, Tadashi
Matsumoto, Mamoru Tanaka, Daisuke Aoki Keio University
Objective Japanese pregnant women are characterized as low
rate of overweight and high rate of inadequate gestational

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Fluctuation of Oral Microbiome during pregnancy in Maternity Log Study Riu Yamashita1, Daisuke Ochi2, Takafumi
Yamauchi2, Yoshiki Tsunemoto2, Yuki Harada3, Maiko Wagata5,
Osamu Tanabe3, Nobuo Yaegashi4, Masao Nagasaki3, Junichi
Sugawara5 Tohoku University Tohoku Medical Megabank Organization 1, NTT DOCOMO, INC./Tohoku University 2, Tohoku
University 3, Department of Biobank, Tohoku University Hospital 4, Department of Community Medical Supports, Tohoku University Tohoku Medical Megabank Organization 5
Objective Oral microbiome changes during pregnancy, and thechanges are possibly associated not only with oral health but
also with pregnancy related diseases such as preterm birth.
However, there is still only limited knowledge on the changes.
Here we focused on the fluctuation of oral microbiome in Maternity Log Study , a prospective cohort study recruiting pregnant women, for the investigation of the relationships between
pregnancy related diseases, environmental factors, and multilayer omics data. Methods We have collected dental plaque（bytooth brushing）and saliva at two time points during pregnancy
from 302 participants. After DNA purification, we performed
amplicon sequencing of the V4 region of the 16S rRNA gene. We
have obtained 138 data sets of both first and second samplings
with more than 5,000 sequence reads. Microbiome annotation
was performed by our original pipeline to associate the reads
with bacteria species. Results We compared oral microbiomes
between first and second samplings. Although the number ofidentified bacteria did not significantly change between the two
samplings（p=0.45）, the relative abundances of some bacteria
showed significant change. While Corynebacterium durum andCardiobacterium horminis decreased, Campilobacter gracillis
increased during pregnancy（p＜0.05）. Interestingly, both Porphynomonas gingivalis （p=0.05）and Tannerella forsythia （p=0.07）,members of Red Complex often observed in the periodontal disease, increased. These data are consistent with theclinical observations that the risk of periodontal disease increases during pregnancy. Conclusion The relative abundanceof several bacteria including those related to the periodontal disease changes during pregnancy. Our microbiome data should
contribute to further investigation of oral health during pregnancy.

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Expression of progesterone induced blocking factor（PIBF）inwomen with severe fetal growth restriction Tomohiro Oba,Akihiro Kawashima, Keiko Miyagami, Keiko Koide, Ryu
Matsuoka, Kazuhisa Shimodaira, Akihiko Sekizawa Showa University
Objective Progesterone induced blocking factor（PIBF）was reportedly associated with trophoblast invasion, and a failure oftrophoblast invasion could lead to fetal growth restriction. However, the molecular mechanisms have not be elucidated. The objective of this study is to explore PIBF expression in the placenta and the blood of patients with fetal growth restriction（FGR）. Methods A case control study of pregnant women wereconducted and approved by the ethical committee. Cases weresevere FGR patients whose birth weight were ＜3% tile（n=6）.
Birth weight ＞10% tile was defined as control（n=10）. The maternal blood samples were collected at 22 34 weeks of gestation
to quentify serum PIBF and progesterone levels using ELISA.
The postpartum placenta samples were also collected for immunohistochemical staining to detect PIBF expression in the placenta. Results Birth weight（g）（cases vs controls）were 1,074±484（ 3.0±0.4SD）vs 3,021±317（0.3±0.7SD）（p＜0.05）, gestational weeks of blood sampling were 29±3.5 vs 31.5±3.4, Thelevel of serum PIBF in Cases is higher than that of Controls（225±100 ng/ml vs 73±33 ng/ml p＜0.05）. On the other hand, thelevel of progesterone expressed similarly in both groups. In immunohistochemical study, PIBF increased in syncytiotrophoblast parts of the placenta of FGR cases. Conclusion In severe FGR, PIBF expressed higher in their placenta and also intheir circulation without the change of progesterone. PIBF expression might be an intrauterine environmental factor associated with a part of placentation in fetal growth restriction.

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ISP-46-2
Systolic and diastolic time interval ratios of the ductus venosus flow velocity waveform in fetal growth restriction
Natsuko Yokoi1, Masami Hayashi1, Aki Takase1, Yasushi
Kurihara2, Kayoko Nakagawa3, Hiroko Katayama1, Akihiro
Hamuro1, Takuya Misugi1, Akemi Nakano1, Daisuke Tachibana1,
Masayasu Koyama1 Osaka City University 1, Kashiwara Municipal Hospital 2, Izumiotsu Municipal Hospital 3
Objective The objective of this study is to investigate the sequential changes of time intervals of the ductus venosus（DV）
flow velocity waveform（FVW）in fetuses with growth restriction（FGR）. Methods This is a retrospective longitudinal observational study on 26 FGR cases, and the study population was divided into two groups：Group 1 with abnormal umbilical artery（UA）Doppler, which is defined as elevated UA pulsatility index（PI）more than 95 percentile of the normal reference range, andGroup 2 with normal UA Doppler. Time intervals of systolic（S）
and diastolic（D）components of DV FVW were measured andthe ratios（S/D）were calculated and converted to z scores forstatistical analysis. The measurements performed within 7 days
before delivery and those performed one week before the last
examination were compared. Results Thirteen cases in Group 1
and 11 cases in Group 2 were included in this study. The mediangestational age of delivery and birth weights were 28w2d（range, 27w1d 32w3d）and 626g（range, 350 1,026）in Group 1
and 38w2d（range, 36w3d 40w3d）and 1,972g（range, 1,503 2,360）
in Group 2. Comparing the difference between the last measured values and those of one week before the last examination,in Group 1, S/D decreased significantly（p=0.028, median 1.85
SD to 2.12SD）,while in Group 2, the S/D showed no significant
change（p=0.722, median 0.15SD to 0.34SD）. Conclusion S/Dof DV FVW decreased in FGR with abnormal UA Doppler inthe last week of pregnancy. Our findings suggest that S/D of

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weight gain（GWG）, compared to those in other developed countries. To date, the impact of GWG in Japanese women on neonatal outcomes has not been fully understood. The aim of thisstudy was to investigate the association between GWG and neonatal birth weight（BW）in Japanese women. Methods We retrospectively analyzed uncomplicated Japanese singleton pregnancies who delivered at term gestation from 2011 to 2016 in our
hospital. The association between GWG and BW was analyzed
by multiple linear regression. Potential confounding factors included maternal age, parity, pregravid BMI and neonatal sex.
The association between inadequate GWG, determined by theInstitute of Medicine recommendations, and small for gestational age（SGA：birth weight ＜10th percentile）was also examined by logistic regression. Results A total of 2,246 mother neonate dyads were analyzed. Maternal GWG was 9.81±3.85 kg（mean±SD）,and 1,519（67%）had inadequate GWG. After adjustment for confounding factors, GWG significantly correlated withBW（β=0.189, p＜0.001）, and inadequate GWG increased the riskof SGA（adjusted odds ratio（aOR）=2.31［95%CI：1.50 3.53］）.
This association was significant in underweight（aOR=2.97［1.13 7.75］）and normal weight mothers（aOR=2.16［1.32 3.53］）,
not in overweight mothers. Conclusion Our study demonstrated
that maternal GWG was associated with BW in Japanese womenwith singleton pregnancies. Inadequate GWG was related to increased risk of SGA in underweight and normal weight mothers.

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Biomarkers for predicting delivery before 34 weeks of gestation in fetal growth restriction Akihiro Kawashima, TomohiroOba, Akihiko Sekizawa Showa University
Objective The molecular mechanisms involved in placental implantation are associated with the proliferative and invasive capacity of trophoblast cells. Current pieces of evidence suggest a
conjunction between the placental implantation and tumor progression. This study aims to develop a model of prediction of
SGA who deliver before 34 weeks of gestation based on serum
protein related with tumor progression. Methods Severe FGR is
defined by estimated weight below the third percentile. We collected blood samples from women with severe FGR（n=24）andnormal growth fetus（n=31）before 34 weeks of gestation after
obtaining the written consent. The serum proteins were assayedusing Bio Plex Pro Human Cancer Biomarker Panel including
23 proteins. Logistic regression analysis was used to develop a
prediction model. Results In the women with severe FGR, 15
cases were delivered before 34 weeks of gestation, and the median of the delivery week was 32 weeks of gestation（range：26
33 weeks）. In severe FGR group, the serum levels of sCD40L,
Endoglin, Leptin, IGFBP1, sVEGFR1 were increased, and PLGF
was decreased. At the estimated detection rate of 100%, thespecificity by a combination of the six proteins was 77.8% for severe FGA requiring delivery before 34 weeks of gestation in severe FGR group and 44.4% for total cases of this study. Conclusion In pregnancies with severe FGR, the women requiring before 34 weeks of gestation could be identified. This study yields
the groundwork for future investigations to analyze the molecular biomarkers for management of FGR.

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Superb microvascular imaging of the fetus, placenta, and umbilical cord Kenta Yamamoto, Mohamed Aboellail, Masato
Mashima, Nobuhiro Mori, Kenji Kanenishi, Toshiyuki Hata Kagawa University
Objective Superb microvascular imaging（SMI）is a new Doppler technology that uses a unique algorithm to minimize motion artifacts by eliminating tissue motion（clutter）,and can depict low velocity blood flow in small vessels due to significantly
reducing motion artifacts. We present our experience of using
SMI to assess fetal organ vasculature, placental vascularity, andumbilical cord. Methods Fetal organ vasculature, placental vascularity, and umbilical cord were assessed using the SMI with ahigh resolution probe in 7 normal and three fetal growth restriction（FGR）pregnancies at 11 33 weeks of gestation. Results
Fetal intra cranial, pulmonary, splenic, renal, and intercostal
vessels were clearly depicted. In the first trimester placenta,
the primary and secondary stem villous vessels, and spiral artery jet flow were noted. In the second and third trimester placentas, the primary, secondary, and tertiary stem villous vessels,
and whole spiral artery jet flow were clearly depicted using
SMI, compared with conventional two dimensional color/power
Doppler sonography. In the thick heterogeneous placenta withsevere FGR, SMI demonstrated very sparse villous trees in theplacenta, and each stem villous vessels became straight. Especially, primary stem villous vessels were thick and long（Baobab tree like appearance）. Velamentous cord insertion was
clearly identified using SMI at 11weeks and 3 days of gestation.
Conclusion SMI provides a more comprehensive, detailed viewof fetal organ vasculatures, placental vascularity, and umbilicalcord, and might facilitate precise diagnosis of normal and abnormal pregnancies.

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Fetal echocardiographic evaluation of dilated cardiomyopathy during mouse pregnancy Takao Owa1, Takekazu Miyoshi2,
Yoko Kawanishi3, Aiko Okada3, Etsuko Kajimoto3, Hiroko
Tanaka3, Aiko Kakigano3, Kazuya Mimura3, Masayuki Endo3,
Takuji Tomimatsu3, Tadashi Kimura3 National Cerebral andCardiovascular Center, Department of Regenerative Medicine 1,
National Cerebral and Cardiovascular Center Department of
Perinatology and Gynecology 2, Osaka University 3
Objective The knock in mouse having a deletion mutation δK
210 in the cardiac troponin T gene develop enlarged hearts withleft ventricular（LV）systolic dysfunction and premature sudden
cardiac sudden death. However, the fetal cardiac function of thisdilated cardiomyopathy（DCM）model mouse remains unknown.
Our objective is to evaluate the fetal cardiac function of thismodel by successive echocardiography, compared with histology and gene expression analysis. Methods We studied mouse
fetuses（embryonic day 16.5 and 18.5）by using a high frequency
ultrasound and evaluate cardiac function and hemodynamics.
Cardiothoracic area ration, LV area, and % fractional shortening
were examined. At embryonic day 18.5, fetal hearts were sampled. Results Echocardiography demonstrated the increase ofleft ventricular end diastolic dimension and progressive reduction of left ventricular ejection fraction from embryonic day 16.5
to 18.5 in mutant fetuses. In histology, the ventricle of mutant fetuses showed enlargement and thinning. The gene expression of
atrial natriuretic peptide were increased in mutant heart, however those of α myosin heavy chain（MHC）and β MHC were
not altered significantly. Conclusion Fetal cardiac dysfunctionof this DCM model mouse is aggravated in prenatal period.

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Relationship between maturation of the autonomic nervous
system in fetal growth restricted mice and onset of cerebral
hemorrhage at ischemia reperfusion load Takahiro Minato1,
Takuya Ito2, Sayaka Ooshio1, Yoshitaka Kimura1, Nobuo
Yaegashi1 Tohoku University Hospital 1, Jichi Medical University 2
Objective Fetal growth restriction（FGR）is a risk factor exacerbating a poor neurological prognosis at birth. A disease exacerbating a poor neurological prognosis is cerebral hemorrhage including intraventricular hemorrhage. It is believed to be causedby an inability to autoregulate cerebral blood flow and bloodpressure due to autonomic nerve immaturity. Methods Hereautonomic nerve immaturity in mouse FGR fetuses was evaluated and the relationship with cerebral hemorrhage incidence
when applying hypoxic load to resemble the brain condition at
the time of delivery was examined. Furthermore, FGR incidence
on cerebral nerve development and differentiation was examined at the gene expression level. FGR model fetuses were prepared by ligating uterine arteries to reduce placental blood flow.
To compare autonomic nerve development in FGR mice withthat in control mice, fetal short term variability（STV）was
measured from electrocardiograms. Results In the FGR group, asignificant decrease in the STV was observed and immatureautonomic nerves were confirmed. Among genes related tonerve development and differentiation, Ntrk and Neuregulin 1,
which are necessary for neural differentiation and plasticity,were expressed at reduced levels in FGR fetuses. And the cerebral hemorrhage rate significantly increased in the FGR group.
Conclusion FGR delays autonomic nerve development, whichbecomes a risk factor for cerebral hemorrhage onset at birth.
This study demonstrated that cerebral hemorrhage risk may beevaluated before delivery for FGR management by evaluating
autonomic nerve immaturity. Further, this study suggests thatchoosing an appropriate delivery timing and delivery method

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contributes to neurological prognosis improvement.

be a possible marker in utero and ex utero to evaluate fetal/neonatal circulatory compromise before 31 weeksʼ gestation.

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Clinical significance of umbilical venous NT proBNP andtroponin T in the cases with at risk for fetal circulatory compromise before 36 weeksʼ gestation Takaaki Shinagawa,Toshiyuki Yoshizato, Takashi Horinouchi, Yutaka Kozuma,
Kimio Ushijima Kurume University HospitalObjective To evaluate the clinical significance of umbilical venous N terminal pro brain natriuretic peptide（NT proBNP）
andtroponin T, biomarkers for cardiac failure, in the cases with atrisk for fetal/neonatal circulatory compromise before 36 weeksʼ
gestation. Methods Subjects with NT proBNP and troponin T
were 327 and 55 cases of preterm delivery at 26 35 weeksʼ gestation in our hospital between 2009 2017 and 2016 2017, respectively. Umbilical venous NT proBNP and troponin T levels
were measured at birth. At risk groups were 137 cases with
NT proBNP and 26 cases with troponin T having maternal andfetal complications including severe form of pregnancy induced
hypertension, oligohydramnios, fetal growth restriction and umbilical arterial pH＜7.2. Control groups were 190 cases with NT
proBNP and 29 cases with troponin T not having the above
mentioned complications. The gestational age was divided into
early（26 30 weeks）and late（31 35 weeks）groups. NT proBNP
and troponin T levels were compared between at risk and control groups in the early and late gestational ages. The statisticalanalysis was made using Mann Whitney test and the significance was set at P＜0.05. Results In the early gestational age,
NT proBNP levels of at risk group（median：6,085.3, range：
571.7 160,271.0 pg/mL）were higher than control group（2,066.1,
28.9 32,001.0 pg/mL）but no difference was found in the troponin
T level. In the late gestational age, neither NT proBNP nor troponin T levels showed any differences between the groups. Conclusion Umbilical venous NT proBNP but not troponin T may

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17 alpha hydroxyprogesterone caproate combined maintenance tocolysis could prolong gestational period in case of
preterm labor with mild intra amniotic inflammation Satoshi
Yoneda, Noriko Yoneda, Mika Ito, Yosuke Ono, Arihiro
Shiozaki, Shigeru Saito University of Toyama
Objective Although progesterone therapy is effective for thosewith asymptomatic short cervical cases and for those with a history of preterm birth, it is unclear whether 17 alpha hydroxyprogesterone caproate（17 OHPC）combined maintenancetocolysis is effective in cases of preterm labor（PTL）cases with
intact membranes. Methods One hundred and six PTL patients
who administered appropriate antibiotic therapy using PCR detection system were selected, and they were divided into groupT（tocolysis only：n=54）and group P（tocolysis and 17 OHPC：
n=52）, respectively. The severity of amniotic inflammation atadmission was classified into sub group A（no inflammation）,
B（mild）and C（severe）by amniotic IL 8 level. The obstetricaland neonatal prognosis was examined statistically. Results 1）
Prolonged gestational days（group T vs. group P）was 66（43119）vs. 64（40 91）in sub group A（n=22）,50（8 104）vs. 75（13 126）in sub group B（n=66）and 26（8 67）vs. 22（8 88）in
sub group C, respectively, and there was significant differencein sub group B（p=0.016）. 2）The rate of neonatal total morbidity
and NICU admission were similar. 3）The amount administered
Rit（mg/day）in sub group B was 95（0 150）in group P, which
was significantly lower than that［115（55 150）
］in group T（p＜0.01）. Conclusion We firstly showed that 17 OHPC combined
maintenance tocolysis can prolong gestation period in PTL
cases with mild intra amniotic inflammation. 17 OHPC did not
prolong gestation period in no intra amniotic inflammation
cases and severe inflammation cases.

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ISP-47-2
Neurological outcome in preterm infants with maternal Tocolytic
management
Emi Kino1, Masanao Ohashi2, Hiroshi
Sameshima1, Ichiro Yasuhi3, Sachie Suga3, Masato Kamitomo4,
Toru Funakoshi5 University of Miyazaki Hospital 1, Miyazaki
Medical Association Hospital 2, Nagasaki Medical Center 3,
Kagoshima City Hospital 4, Hyogo Prefectural Kobe Childrenʼs
Hospital 5
Objective To investigate the effects of tocolytic agents on infantsʼ neurodevelopment of preterm infants. Methods This is aretrospective cohort study of birth between 28 and 36 weeks ofgestation at 4 perinatal tertiary centers in Japan. 1,083 cases of
2 year survivors were categorized into four groups；no tocolytics, magnesium sulfate（Mg）,β stimulant（β）and the combination of Mg and β（Combined）group. The diagnosis of cerebral
palsy（CP）or mental retardation（MR）at 2 year old was confirmed by pediatric neurologists in each of the 4 institutions. Results Mg group consists of 218 cases with 2（1.8%）of CP and 1（0.9%）of MR. No tocolytics group of 418 with 10（2.4%）of CP
and 16（3.8%）of MR. A multivariate analysis of the data, including tocolytics, gestational age, sex, fetal growth restriction, antenatal steroids, low pH（＜7.1）,pathological chorioamnionitis andfacilities, showed that the Mg administration during pregnancy
had significantly lower rate of mortality and brain damage（CPor MR）with odds ratio（OR）0.43 and 95% confidence interval（CI）0.24 0.74. A stratified subgroup analysis of infants born between 28 and 33 weeks of gestation showed that the incidence of
normal development infants in Mg group is significantly highest
among four groups with multiple comparison. Conclusion This
study found that administration of magnesium sulfate for the

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Low socioeconomic status is a risk factor for small for gestational age birth in Japan Ken Yamaguchi, Kaoru Kawasaki,
Sachi Yamamura, Eri Ogura, Yu Matsuzaka, Masahito
Takakura, Mari Ujita, Yumi Takao, Kenji Takakura, Ikuo
Konishi Kyoto Medical Center
Objective Small for gestational age（SGA）birth increases theneonatal risk for chronic diseases including heart disease anddiabetes in the future. Socioeconomic status（SES）has been related to SGA birth in developing countries. The aim of thisstudy is to evaluate the effect of socioeconomic inequalities
among Japanese pregnant women and lifestyle related factors
before pregnancy on the prognosis of pregnancy and birth outcomes. Methods From January 2007 to December 2011, Japanese
singleton pregnant women（n=2,686）were enrolled into thisstudy. We used the pregnant childbirth hospitalization support
policy system as an indicator of low SES, and investigatedwhether SES status affects adverse delivery and birth outcomes
including preterm birth, emergency cesarean section, still birth,and SGA. Results The proportion of low SES pregnant womenwas 12.1%. There were significantly more SGA infants in the
low SES group, and the crude odds ratio was 1.64（95% CI=1.14
2.36, p=0.008）. The odds ratio for SGA in low SES adjusted bymaternal age, pre pregnancy body mass index, pre pregnancy
smoking behavior, and gestational body weight gain was 1.57
（95% CI=1.03 2.39, p=0.035）. However, low SES did not influence preterm birth, emergency cesarean section, and stillbirth.
Conclusion Low SES among Japanese pregnant women is associated with SGA birth. These findings suggest that improvement of socioeconomic disparities are important for the prevention of chronic diseases in the future.

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management of preterm labor had the ability to improve the infant mortality rate and brain damage between 28 and 36 weeks
of gestation at birth. Antepartum exposure to magnesium sulfate is one of the preferred options for infant neuroprotection.

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Changes of leukocyte migration during pregnancy Ai
Takamizu, Jun Takeda, Shintaro Makino, Atsuo Itakura, Satoru
Takeda Juntendo University
Objective Preterm birth is a worldwide problem. Its prediction
has been needed for appropriate intervention；however there
are no tests that can positively predict when pregnant women
will deliver. We focus on the leukocyte infiltration to the uterus
or the placenta which is important in parturient mechanism. We
hypothesized that more leukocytes migrated as gestation progressed. Using the principle of leukocyte invasion of the uterus
at each delivery, we determined whether the Leukocyte Migration Assay（LMA）could predict the timing of delivery by using
Modified Boyden chemotaxis chambers. Methods Leukocytes（100,000）were obtained from pregnant women sequentially at
1st, 2nd, 3rd trimester, labor and postpartum day 3, and placed
into the upper chamber. Chemotactic factor isolated from termlabor fetal membranes were placed in the lower chamber. Migrated leukocytes number and its subtypes were assessed byflow cytometry using antibodies. Results Migrated leukocytes
count of the 2nd trimester was significantly higher than those of
the 1st（p=0.03）. Unexpectedly, leukocytes in the 2nd trimester
significantly more migrated than those of the 3rd trimester（P=0.002）.No differences were found between the 3rd trimester andthe time of labor in this study. More than 80% of the migrated
leukocytes were granulocytes, and what is more, 95% of those
are CD11b positive. The ratio of leukocyte population was remained same throughout the gestation. Conclusion The leukocytes specifically changed their property during pregnancy.
CD11b positive leukocytes migrated toward the chemoattractants not gradually through the gestation but higher in the 2ndtrimester and labor.

ISP-47-4
Longitudinal Lifestyle Monitoring for Prediction of Preterm
Birth in Maternity Log Study Daisuke Ochi1, Takafumi
Yamauchi1, Yoshiki Tsunemoto2, Maiko Wagata6, Riu
Yamashita4, Yuki Harada3, Osamu Tanabe3, Nobuo Yaegashi5,
Masao Nagasaki3, Junichi Sugawara6 NTT DOCOMO, INC./Tohoku University Tohoku Medical Megabank Organization 1,
NTT DOCOMO, INC. 2, Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization 3, Department of Biobank, Tohoku University Tohoku Medical
Megabank Organization 4, Tohoku University Hospital 5, Department of Community Medical Supports, Tohoku University Tohoku Medical Megabank Organization 6
Objective Pregnancy related disorders, including preterm birth（PTB）, are caused by a complex interaction of genetic and environmental factors such as lifestyle and living environment. We
have designed a prospective cohort study named Maternity
Log Study to investigate unrevealed mechanisms of those disorders from both genetic and environmental aspects. Methods 302
participants were recruited by written informed consent. We
collected daily lifelogs of physiological data（body weight, bloodpressure, pulse rate, physical activity, body temperature, andhours of sleep）and symptoms（morning sickness, abdominal
pain, uterine contraction, and bowel movement）as well as bloodand urine samples at several points throughout pregnancy. We
analyzed the association between the course of lifelogs and PTB.
Results Several lifelog features showed differences between aspontaneous PTB（SPTB）group（n=14）and a control group（n=130）. Especially, daily caloric expenditure of the SPTB
group measured by a wearable activity monitor was significantly lower than controls after 20 weeks of gestation（1,577±
180 vs 1,915±291 kcal, p＜0.0003）. Interestingly, morning bodytemperatures of the control group decreased gradually according to the gestational age（36.55 36.35˚C from 16 to 30 weeks ofgestation）, while those of the SPTB group did not as much（36.62
36.53˚C during the same period as the control）. A SPTB prediction model using lifelogs before 26 weeks of gestation demonstrated sensitivity higher than 0.95 and specificity higher than
0.90. Conclusion Combinations of daily lifelogs could be predictive markers for SPTB. Further combinations with genome,transcriptome, and metabolome data may improve our prediction model and reveal underlying mechanisms of SPTB.

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ISP-47-5
The effect of antepartum MgSO4 therapy on pathological chorioamnionitis and infants outcome Masanao Ohashi1, Hiroshi
Sameshima2, Emi Kino2, Ichiro Yasuhi3, Sachie Suga3, Masato
Kamitomo4, Toru Funakoshi5 Miyazaki Medical Association Hospital 1, University of Miyazaki Hospital 2, Nagasaki Medical Center 3, Kagoshima City Hospital 4, Hyogo Prefectural Kobe Children Hospital 5
Objective Infants neurological outcome is associated with bothpreterm birth and pathological chorioamnionitis（pCAM）. The
risk of poor neurological outcome in the setting of preterm birth
can be decreased by antenatal maternal administration of magnesium sulfate（Mg）.We examined the effects of Mg on neonatal
outcomes in the setting of preterm birth complicated by pCAM.
Methods We conducted an analysis of data from multicenter
retrospective cohort study. Using singleton non anomalous
pregnancies born between 28 and 36 weeks of gestation, we
compared the effect of pCAM by the administration of Mg ornot. Primary outcome was poor neonatal outcome which consists of neonatal death, cerebral palsy by the age of 2 years andneurodevelopmental delay including mental retardation. Results Of the 1,143 infants included in this study, 1083 infants
were included in this analysis. 160（14.8%）were diagnosed with
pCAM. Neonates exposed to Mg in the absence of pCAM had asignificant reduction in poor outcome at 2 years of age compared to neonates non exposed to Mg in the presence of pCAM
（adjusted OR 0.40, 95% CI：0.18 0.90）. In the setting of pCAM,
there was a tendency of reduction in poor outcome at age 2
years with magnesium therapy, but not significantly different.
Conclusion Mg does not demonstrate a significant protective effect in the setting of pCAM, but showed the ability of improvement in neonatal outcome. We need to collect more data to clarify the effectiveness of Mg on neonatal outcome with pCAM.

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Accuracy of maternal clinical signs for prediction of histological chorioamnionitis in preterm labor Yohei Maki, Hiroshi
Sameshima University of Miyazaki
Objective To evaluate the accuracy of clinical signs for histological chorioamnionitis. Methods This was a retrospective cohort study. We reviewed the medical records of pregnant
women with preterm delivery between 22 and 33 weeks of gestation and obtained clinical data and histopathological placental
findings at our hospital and their neonatal outcome including
neonatal death, death within 1 year, neuroimaging abnormalities, and composite outcome, defined as 1 or more of them between January 2007 and May 2017. Results were compared between CAM group and non CAM group. Results Infants in the
CAM group had significantly earlier gestational age（26.93±1
weeks vs 25.4±2.9weeks, p＜.01）,lower birth weight（1,053±423
g vs 860±388g, p＜.01）, higher incidence of neuroimaging ab-

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ISP-48-1
Case report of spontaneous septostomy of the dividing membrane accompanied with cord entanglement in a monochorionic diamniotic twin：Importance of identification of dividing
membrane
Tomoki Kotera, Takashi Shibata, Hisato
Tokuda, Noriaki Iiduka, Satoshi Nakago Takatsuki General Hospital
We experienced a case of the spontaneous septostomy of the dividing membranes（SSDM）in monochorionic diamniotic twin
（MD twin）.One fetus with the loss of end diastolic velocity ofumbilical artery caused by the cord entanglement was saved bya cesarean section. This case was 37 year old, G1P0. At ten
weeks of pregnancy, she had a diagnosis of MD twin by the ultrasonography because the dividing membrane was recognized
in a yolk sac. At 15 weeks of pregnancy, the consecutive dividing membrane from the anterior wall to posterior wall was became invisible. However, the part of the membrane was found in
the amniotic cavity and we did not think of possibility of the
SSDM. At 27 weeks of pregnancy, the prolong deceleration andthe loss of end diastolic velocity of umbilical artery was suddenly found in one fetus. Cesarean section was promptly performed. At the operation, dividing membrane in the amniotic
cavity was not found. However, the residual membrane was
identified also found between placental attachments of the twoumbilical cords, suggested SSDM. This case was accompaniedwith nine times cord entanglements and two cord knots. Apgar
scores at the five minutes of both newborn infants were eight.
The pH of umbilical artery was 7.329 and 7.400, respectively.
When the consecutive dividing membrane in the amniotic cavity became invisible during pregnancy course of MD twin, we
should think of recognize the possibility that of SSDM occurs.
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ISP-48-2
The outcome of fetoscopic laser photocoagulation using theSolomon technique versus selective coagulation for twin twintransfusion syndrome Seiji Kanazawa, Noriyuki Nakamura,Rika Sugibayashi, Katsusuke Ozawa, Seiji Wada, Haruhiko Sago
National Center for Child Health and Development
Objective We compared the outcomes in monochorionic twins
who underwent fetoscopic laser photocoagulation（FLP）for
twin twin transfusion syndrome（TTTS）using selective coagulation of placental anastomoses（standard technique）and equatorial dichorionization of the anastomoses（Solomon technique）.
Methods The outcomes were retrospectively analyzed in TTTS
cases who underwent FLP in our institution from 2010 2016 andwere followed to delivery. We adopted the Solomon technique
for selective coagulation in August 2014 and compared outcomes before and after that point. Results Among 286 cases, 198

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underwent the standard technique（group 1）,and 88 underwent
the Solomon technique（group 2）.Gestational age（GA）at FLP,
operation time, laser coagulation time, and laser coagulation total energy were not markedly different between the groups.
Four cases of recurrent TTTS（2.0%）and 3 cases of twin anemia polycythemia sequence（TAPS）（1.5%）occurred postoperatively in group 1；there were no such cases in group 2. There
were no significant differences between the groups in the double survival rate（74.7% vs. 79.5%；P=0.381）or at least one survival rate（95.5% vs. 97.7%；P=0.358）. Placental abruption was
significantly more frequent in group 2 than in group 1（2.5% vs.
11.3%, OR 4.9, P=0.005）,as was premature rupture of membrane（PROM）（OR 3.1, P＜0.001）, but GA at delivery（32.8±4.4 vs. 32.8
±4.0 weeks；P=0.899）was not significantly different between
the groups. Conclusion The Solomon technique decreased recurrent TTTS and TAPS following FLP but increased the occurrence of placental abruption and PROM. There were no significant differences in the GA at delivery or twin survival rates.

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Meckel Gruber syndrome involving both fetuses in a DD twin
pregnancy, a case report Shoko Ochiai, Susumu Miyashita,
Chiyori Sakamoto, Emi Motegi, Tatsuya Kuno, Kazumi Tada,
Hiroshi Watanabe, Ichio Fukasawa Dokkyo Medical University
Hospital
Case A 29 year old woman, 2 gravida, 0 para, was referred because of brain ventriculomegary in both of twin fetuses on 13
weeks. DD chorionicity had been confirmed at eight weeks. She
had been healthy and no remarkable familial history. Serial ultrasound scans revealed deformed cranium, encephalocele anddysplastic enlarged kidney in both fetuses, which were compatible with Meckel Gruber syndrome（MGS）involving both ofthem. The couple decided termination of pregnancy after serial
genetic counseling. The fetuses were stillborn on 21 weeks andwe confirmed occipital encephalocele, bilateral dysplastic kidney and polydactyly in both. After the investigation of causative
genes revealed a compound heterozygosity of deletions in exon
34 and 35 of CC2D2A in both of the fetuses, which were inherited from the parents. The fetuses were proven to be monozygotic by another investigation using multiple genetic markers.
She got singleton pregnant spontaneously one year later. Excessive large low echoic area in the fetal brain was noted in nine
weeks. After the serial scan deformed cranium and occipital encephalocele were confirmed on 11 weeks. Termination was decided again and encephalocele was confirmed in the aborted fetus, in which the mutations of CC2D2A were under the investigation. Discussion We had a case of MGS in monozygotic dichorionic twin fetuses. Investigation for causative genes and the zygosity was significant for the genetic counseling in this case. We
could recognize abnormal findings in fetal brain at first trimester scan, which provided an essential information to support theparents for making a decision.

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ISP-48-4
What should we know about Turner syndrome before pregnant? 2 cases with different outcomes Tomohiro Arai1,
Kouki Samejima1, Sumiko Era1, Yoshihisa Ono1, Yasushi Takai2,
Masahiro Saitoh1, Kazunori Baba1, Hiroyuki Seki1, Sachie Seto3,
Ryugo Okagaki3, Yoshimasa Kamei3, Osamu Ishihara3 Center for
Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama Medical University 1, Saitama Medical Center, Saitama Medical University 2, Saitama Medical University Hospital 3
Background Although primary ovarian insufficiency is a classic feature of Turner syndrome（TS）, more TS women haveused assisted reproductive technology（ART）with donated oocytes（OD）to become pregnant recently. Whereas, as well as!

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normalities（18% vs 35.4%, p＜.05）and poorer composite outcome（21.2% vs 42.9%, p＜.01）. Pregnant women in the CAM group
had significantly higher body temperature（36.9±0.42˚C vs 37.1
±0.58˚C, p＜.01）, higher incidence of fever（＞38˚C）（0% vs
11.1%, p＜.05）, higher white blood cell（WBC）counts（10,295±2,549/μL vs 13,493±3,996/μL, p＜.001）, higher incidence of
leukocytosis（WBC＞15,000/μL）（2.3% vs 35.1%, p＜.001）, andhigher C reactive protein level（0.97±1.07mg/dL vs 3.22±2.66
mg/dL, p＜.001）. The cut off value of CRP 1.24mg/dL had thehighest accuracy of 70.8% while fever and WBC＞15,000/μL had
accuracy of 40.5% and 55.1%, respectively. The accuracy of any
one sign of fever, leukocytosis and/or CRP＞1.24mg/dL was
75.2%. Conclusion Any one sign of fever, leukocytosis and/or
high CRP level can be useful for prediction of histological chorioamnionitis.

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Marfan syndrome and vascular Ehlers Danlos syndrome, TS
demonstrate a high rate of aortic dissection（DA）which is increased by 100 fold compared with the general female population. Aortic size index（ASI, diameter of the ascending aorta normalized to body surface area）may serve to predict risk for DA,
but is not well known in obstetrics and reproductive area. We
report two cases of TS women which followed different courses.
Case 1 A 36 year old TS woman became pregnant after ART
with OD in Taiwan. At 14 weeks, she presented with chest pain.
Transthoracic echocardiography（TTE）suggested dilated aorta（ASI 2.37 cm/m2）. Although enhanced CT showed no significant findings, she decided to have an artificial abortion. Case 2
A 37 year old TS woman became pregnant after ART with OD
in United States. Although she presented with back pain from 8
weeks, repetitive TTEs did not suggest aortic dilation（ASI
1.61 1.83 cm/m2）. She is now in 35 weeks with an uneventful
course. Conclusion Although TS women need to be aware ofsignificant risk of aortic dissection, favorable obstetric outcomesare achievable with careful cardiovascular assessment and multidisciplinary antenatal monitoring. ASI may be a marker whichshould be evaluated before ART with OD for TS women.

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Case Report：The outcomes of fetal bradycardia Ryoko Ono,
Masahiro Nakao, Takuya Kawamura, Ryo Suzuki, Ikuno
Kawabata, Atsushi Yoshida, Shinji Katsuragi Sakakibara Heart
Institute
Background Fetal bradycardia can be detected during the fetal
heart monitoring or routine prenatal ultrasound examination.
Sustained bradycardia is often associated with structural heartdisease. These cases have reported a worse outcome comparedto fetuses with isolated bradycardia. They require a risk assessment and careful management during pregnancy. Case Presentation We present three retrospective case reports in which fetal bradycardia with structural heart disease was diagnosed byechocardiography. Two of the three cases showed sinus bradycardia with a fetal heart rate（FHR）of 90 100 beats per minute（bpm）. The remaining one showed 2：1 atrioventricular blockwith a ventricular rate is 60 bpm. The common findings of them
are complex cardiac malformations and interruption of the inferior vena cava with azygos continuation. All cases had a diagnosis of left isomerism at the CT scan after birth. During pregnancy, we performed a frequent evaluation of the fetuses by ultrasonography and determined the time of delivery. None ofthem showed severe fetal hydrops. All cases resulted in fullterm delivery. The elective cesarean section was performed in
the case of the atrioventricular block due to poor tracing of the
FHR monitoring. In the other two cases, FHR tracing allowed toassess fetal well being during labor resulting in normal vaginal
delivery. Conclusion In cases of fetal bradycardia with structural heart disease, there are often some ultrasound findings ofleft isomerism. The magnitude of bradycardia affects the fetal
prognosis and time and mode of delivery.

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ISP-48-6Prenatal diagnosis of hypospadias in a tertiary care center：a retrospective analysis of 10 years Takashi Kaji, Atsuko
Hichijo, Naoto Yonetani, Minoru Irahara Tokushima University
Hospital
Objective Hypospadias is a common congenital anomaly with aprevalence rate of approximately 1 per 500 live male births,
wherein the urethral meatus is located on the ventral side of thepenis. In the present study, we determined the efficacy of ultrasonography in establishing a prenatal diagnosis of hypospadias
in our tertiary care center. Methods We retrospectively studied
29 consecutive patients born at our center who were diagnosed

with hypospadias after birth between January 2008 and August
2017. Results Of the 29 cases, 14（48%）, 9（31%）, and 7（24%）werecomplicated with fetal growth restriction（FGR）, anomalies
other than hypospadias, and hypertensive disorders of pregnancy（HDP）, respectively. In all fetuses except one, the external genitalia were assessed using an axial view of the perineum
using two dimensional ultrasonography to determine the sex of
the fetuses. Only 10 of the 29（35%）cases were prenatally detected using the image of the ventrally curved penis between
the scrotums. Three（10%）cases were diagnosed prenatally byvisualizing the urethral meatus on the ventral side on the sagittal view of the penis during fetal micturition. Conclusion Prenatal detection of hypospadias remains uncommon；furthermore,prenatal diagnosis is rare in our tertiary care center. The commonly used axial view of the fetal perineum appears inadequate
for detecting hypospadias. However, a sagittal view of the penis
may improve the efficacy of prenatal detection of hypospadias,
particularly in high risk pregnancies involving FGR, anomalies,
and HDP.

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Novel technique to assess fetal fractional shortening by twodimensional tracking Sumito Nagasaki, Masahiko Nakata,
Mayumi Takano, Kento Usui, Junya Sakuma, Mineto Morita
Toho University Omori Medical Center
Objective To assess the usefulness of novel 2D tracking technique to measure fetal cardiac fractional shortening automatically（Auto FS）in normal singleton pregnancies. Methods Two
dimensional tracking system to pursue wall motion of fetal
heart, Auto FS, was constructed. In this study, temporalchanges of Auto FS throughout gestation was studied in normal
singleton pregnancies. At first, cardiac motion of the four chamber view was recorded in B mode and then the Auto FS was
calculated. The Region of interest（ROI）was set at a two thirdof the wall from apex, in to in of the ventricular wall or septum,
and tracking was performed. The values measured between theventricular septum and at left side are defined as L Auto FS.
That at right side is R Auto FS. We also obtained the value between each ventricular septum, which was defined as Combined Auto FS. Results This study was carried out from May to
September 2017. The data was obtained from 95 of singleton fetuses. L Auto FS decreased significantly with gestational
weeks, and R Auto FS showed the same tendency（Spearman
correlation analysis：p= 0.30 and p= 0.55 respectively）. Combined Auto FS showed the same decline as gestational age（p=0.62）. Conclusion Two dimensional and automatically calculation of fractional shortening was succeeded. This novel technique can assess fetal heart contractility by being combinedwith both longitudinal and short axial dimensions. All L R
and Combined Auto FS showed a trend towards a negative correlation with gestational weeks. Further examination would beneeded for clinical usage.

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ISP-48-8
A case with BASM（biliary atresia splenic malformation）syndrome diagnosed with agenesis of inferior vena cava without
visceral heterotaxy in utero Kunio So, Takaaki Shinagawa,
Masato Yokomine, Toshiyuki Yoshizato, Kimio Ushijima Kurume University Hospital
Introduction Agenesis of inferior vena cava（IVC）is often associated with visceral heterotaxy syndrome. We present a casewith prenatal diagnosis of agenesis of IVC without visceral heterotaxy and BASM（biliary atresia splenic malformation）syndrome was confirmed for additional postnatal findings of biliaryatresia and splenic abnormality. Case A 30 year old pregnant
woman was referred to our department because of agenesis of

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ISP-48-9Prenatal genetic diagnosis for neonatal alloimmune thrombocytepenia for women with the history of neonatal alloimmune
thrombocytopenia Akari Shirakuni1, Masashi Deguchi1, Maho
Miyaji1, Yutoku Shi1, Akiko Uchida1, Sanae Ichihashi1, Masashi
Nishimoto1, Tokuro Shirakawa1, Kenji Tanimura1, Mayumi
Morizane1, Ichiro Morioka2, Hideto Yamada1 Kobe University
Hospital 1, Department of Pediatrics, Kobe University Hospital 2
Objective Neonatal alloimmune thrombocytopenia（NAIT）isblood related disease caused by maternal antibodies against alloantigens on fetal platelets. NAIT can be a cause of perinatal intra cranial hemorrhage（ICH）and death or severe sequelae.
We experienced two cases of prenatal genetic diagnosis andperinatal management of women with history of NAIT. Case1 A
Russian woman with human platelet antigens（HPA）1a antibody married again and get pregnant with another Japanese.
Her first child suffered ICH and thrombocytopenia due to HPA
1a antibody. Genetic test of HPA 1 of parents was HPA 1b/b
（patient）and HPA 1a/a（spouse）. Fetal genotype was presumed
as HPA 1a/b and suspected risk for NAIT. C section was chosen to minimize the ICH risk. Newborn suffered thrombocytopenia but not ICH. Case2 A Japanese woman with HLA A2
antibody conceive the second or third pregnancy. Her first childsuffered thrombocytopenia and diagnosed as NAIT by HLA A2
antibody. Serological test shows positive HLA A2 antibody,then amniocentesises were performed to determine HLA typeof fetuses. The third fetus carried HLA A2 but not second.
Vaginal delivery was chosen for second, and C section for third.
Both newborn did not suffer thrombocytopenia. Conclusion
Perinatal genetic diagnosis of the NAIT risk for women withhistory of NAIT by HPA antibody might be effective to decrease ICH by caesarian delivery, prepare antigen negative donor platelets for the neonates and avoid unnecessary cord blood
sampling or caesarian delivery. On the other hand, HLA antibody is still controversial to cause NAIT, prenatal genetic diagnosis is not recommended for NAIT due to HLA antibody.

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ISP-48-10
Chromosomal abnormalities：ultrasonographic soft signs infirst and second trimester―an evidence based review Coralia
Stefanescu, Eduart Balasa Euromaterna Hospital, Romania
Down syndrome（trisomy 21）is the most common karyotipic abnormality in live borns. Other sonographically detectable aneuploidies include trisomy 13, trisomy 18, monosomy X, and triploidy. The scan detects 2 types of markers. Markers for major fe-!

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tal structural abnormalities comprise the first type, the others
often include mild or moderate non specific, sometimes transient, modifications（ soft markers , soft signs ）.Unfortunately,
studies evaluating the significance of these soft signs vary
widely and show contradictory results. In this paper, theauthors review the most used soft markers and discuss ultrasound techniques and measurement criteria for their detection.
We also evaluated the clinical significance to aneuploidy risk assessment and evidence based strategies for the management ofaffected pregnancies and correct counselling of the parents.

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ISP-49-1
Intracranial pathologies during pregnancy Yuri Niwa,
Tomomi Kotani, Teruyuki Mizutani, Asuka Tachi, Masataka
Nomoto, Yukako Iitani, Mayo Miura, Yoshinori Moriyama,
Takafumi Ushida, Kenji Imai, Tomoko Nakano, Fumitaka
Kikkawa Nagoya University
Intracranial pathologies during pregnancy are uncommon, but
special considerations are required for the management. To reveal their clinical course and perinatal outcome, we retrospectively investigated cases of intracranial pathologies during
pregnancy treated at one tertiary hospital between January 1,
2007 and December 31, 2016. Among 4,426 deliveries in this period, 27 patients with intracranial tumors including 5 post operative cases, 23 patients with cerebrovascular diseases including 9 post operative cases and 3 patients with previous historyof cerebral hemorrhage or cerebral infarction were detected.
Seventeen cases（63.0%）in tumor cases were pituitary tumor,and seven cases（30.4%）in cerebrovascular cases wereMoyamoya disease. Preterm birth rate in the tumor group was
higher than that in the cerebrovascular group（22.2 vs. 8.7%, p=
0.26）. More patients in tumor cases discontinued pregnancy for
deterioration of intracranial pathologies. Four patients（17.4%）in
cerebrovascular group developed bleeding or infarction during
pregnancy, but had normal courses. Ten cases（28.5%）among
patients without intervention at preconception required intervention during pregnancy, but none（0.0%）required among patients with intervention at preconception（28.6 vs. 0.0%, p=0.002）. In conclusion, perinatal prognosis of pregnant womenwith intracranial pathologies might be improved by intervention at preconception, although further study is needed.

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ISP-49-2
Five cases of intracranial diseases in pregnant women Chie
Koide, Satoshi Urabe, Takako Sadakane, Norifumi Tanaka, Eiji
Hirata, Yoshiki Kudo Hiroshima University Hospital
Introduction The awareness of saving the lives of pregnant
women has been increasing. When pregnant women develop
cranial neurological diseases such as stroke, rapid diagnosis andtreatment at high level facilities with appropriate provisions forneurosurgery are required. We reviewed 5 cases of intracranial
disease occurring in pregnant women. Methods Between January 2010 and August 2017, 5 of the 2,785 pregnant women admitted to our hospital developed fatal intracranial diseases. We reviewed the diagnosis, treatment, and influence of pregnancy onthese diseases. Results The 5 cases of intracranial diseases inpregnant women included one case each of subarachnoid hemorrhage, basal nucleus bleeding, multiple bleeding lesions due toacute lymphocytic leukemia, anaplastic astrocytoma, andglioblastoma. As symptoms, headache was observed in 3 cases,
paralysis in 3 cases, convulsions in 1 case, and declining consciousness level in 2 cases. In all the cases, diagnosis was performed using computed tomography or magnetic resonance imaging. In 4 cases, cesarean section was performed under generalanesthesia at from 24 to 40 weeks of gestation because thewomen required treatment for the underlying cranial disease. In!

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IVC on a routine screening at 32 weeksʼ gestation. The ultrasonographic examination revealed situs solitus with normal intracardiac structure. IVC was not detected. A dilated vein running along with the descending aorta was connected with thesuperior vena cava, indicating a dilated azygos vein. Spleen wasobserved on the left adjacent to stomach. Agenesis of IVC withazygos connection but no visceral heterotaxy was diagnosed. At
37+2 weeksʼ gestation, a 2,910g male neonate was delivered with
1/5 min Apgar scores of 9/10 points, respectively, and was discharged on day 7 after birth. On day 42, he was consulted with apediatrician because of umbilical hernia and referred to our hospital for further examinations of jaundice and whitish tool. The
laparotomy on day 60 showed that the gallbladder and extrahepatic biliary tracts were hypoplastic and biliary atresia type III
C1 ν was diagnosed. The abnormal contour of spleen was foundon MRI. Conclusion BASM syndrome should be considered incases with agenesis of IVC without visceral heterotaxy and theextensive examinations for the presence/abnormalities of gallbladder, biliary tract and spleen should be made before and after birth.

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the case with subarachnoid hemorrhage, pregnancy was maintained. Only 1 patient completely recovered, 2 underwent rehabilitation, 1 was receiving treatment for the primary cranial disease, and 1 died because of the primary cranial disease. Discussion An intracranial disease during pregnancy can be life
threatening. Therefore, rapid diagnosis, and adequate andtimely treatment of these diseases is essential. Cooperation between the several medical departments involved is needed for
effective treatment in such cases.

rolled to the study. Two had mild disease condition and underwent normal vaginal delivery. Four were symptomatic and obstetric analgesia plus operative vaginal delivery was chosen. All
patientʼs parturition took place smoothly and no adverse event
occurred during the labor. No neonatal complication was noted.
Conclusion In conclusion, MG affected pregnancy can safely
undergo spontaneous or operative vaginal delivery dependingon the severity. Obstetric analgesia is a good option for circumventing the effects of maternal fatigue on delivery.

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ISP-49-5

Impact of maternal schizophrenia on protein expression of
fetal immune system Yoshinori Moriyama, Tomomi Kotani,
Masataka Nomoto, Mayo Miura, Yukako Iitani, Asuka Tachi,
Yumiko Ito, Takafumi Ushida, Kenji Imai, Tomoko Nakano,
Fumitaka Kikkawa Nagoya University
Objective There is accumulating evidence showing involvement of intrauterine environment（IUE）in fetal life in the onsetof various diseases. It is known that children born to motherswith schizophrenia（SCZ）have an elevated risk of SCZ, but the
influence of IUE has not been investigated well. Here, we performed proteomic analysis of cord blood to evaluate the influence of maternal SCZ on the next generation via IUE. Methods
Six pregnant women with SCZ and as many pregnant controls
were included. Cord blood was sampled at delivery, and centrifuged for serum isolation. Proteome of the serum was measured
by LC MS/MS, and then analyzed by gene ontology（GO）andpathway enrichment analysis. Maternal blood samples during
the third trimester for 5 case control pairs were put into thesame analysis. Results In cord blood, 348 proteins were detected, 81 of which showed more than 2 fold differential expression in one or more case control pairs. In GO enrichment analysis, complement activation，classical pathway had the largest. Pathway enrichment analysis resignificance（P=1.1×10!41）
vealed Complement And Coagulation Cascades The most significant（P=5.9×10!27）. As for maternal blood, 83 proteins withover 2 fold change was identified, and the same GO term andpathway were listed as the most significant. Conclusion In thechildren of mothers with SCZ, complement pathway had already activated during their fetal period, similarly to theirmothers, suggesting they could be programmed for some diseases by maternal SCZ. Reduction of this effect via improved
IUE could contribute to prevention of diseases later in their life.

Case Report：Nonimmune Fetal Hydrops Following Maternal Suicide Attempt Kristen Elmezzi1, Scott Petersen1, Barton
Staat1,2, Kimberly Hickey1 Walter Reed National Military Medical Center, USA 1, Uniformed Services University of the Health
Sciences, USA 2
Background Hydrops is the abnormal accumulation of fluid in
fetal cavities and soft tissues in two or more locations. Etiologies
include infectious processes, fetal anomalies and hematologic
abnormalities. Diagnostic criteria include abnormal fluid collections such as abdominal ascites, pleural or pericardial effusions
and skin edema measuring ＞5 mm. Additional sonographic
findings may include placental thickening and polyhydramnios.
Case A 24 years old gravida 3 para 1,011 attempted suicide byingestion of Acetaminophen/Aspirin/Caffeine/Benadryl tabletsat 21 weeks gestation. Her prenatal course was complicated bylimited obstetrical care. While hospitalized, her acetaminophen
levels, salicylate levels and hepatic enzymes were mildly elevated. She received N acetylcysteine and bicarbonate with normalization of all levels. Fetal anatomic survey was obtained at
the time of admission without apparent abnormality. After discharge from the hospital, the patient reported absence of fetal
movement during her obstetrics visit. Hydrops was seen on alimited ultrasound at this office evaluation visit and the patient
was subsequently transferred to a tertiary care facility for further evaluation. Unfortunately, after weekly monitoring, the patient was diagnosed with a fetal demise at 29+2 weeks and underwent an uncomplicated induction of labor. Conclusion
Nonimmune fetal hydrops results from various etiologies. Thiscase is unique due to the timing of the diagnosis and the possible relation to ingestion of the medication. Evaluation for infection, fetal anomalies and genetic syndromes were negative.
PUBS performed at 25+6 weeks revealed normal fetal liver enzymes and a low albumin. Catastrophic liver damage remains apossible etiology.

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ISP-49-4
Maternal myasthenia gravis：Management of labor and delivery Kotoi Tsurane, Yoshie Oka, Mayuko Saito, Sakiko Oshiro,
Atsushi Fusegi, Shinji Baba, Izumi Honda, Tsutomu Ida,
Kazunori Koike, Yoshimi Taniguchi, Akira Kohyama Tokyo
Metropolitan Tama Medical Center
Objective In Myasthenia gravis（MG）affected pregnancy, it is
crucial to ease the second stage of labor, because maternal voluntary muscle weakness can be exacerbated during expulsive
efforts or postpartum period. Although obstetric analgesia is agood option for circumventing the effects of maternal fatigue ondelivery, the appropriate management is not well understood.
The aim of this study is to assess the impacts and outcomes oflabor and delivery, and to establish a protocol in management ofmaternal MG. Methods In this prospective study, we developed
an algorism to manage the delivery depending on the severity ofthe disease：For mild to moderate（asymptomatic）disease conditions, spontaneous vaginal delivery is chosen and vacuum delivery is performed when needed. For those who have moderate（symptomatic）to severe disease condition, obstetric analgesia
plus immediate vacuum delivery once achieving a position enabling suction is conducted. Results Total of six patients were en-

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ISP-49-6
Postnatal depression associated with pregnancy induced byassisted reproductive technology Haruhiko Udagawa, Hiroaki
Aoki, Miki Muto, Keiko Yabuzaki, Akihiro Hasegawa, Tomona
Matsuoka, Michihiro Yamamura, Yuki Ito, Kazuhiro Kajiwara,
Satoshi Sohda, Osamu Samura, Aikou Okamoto The Jikei University School of Medicine
Objective Although the number of pregnancies resulting fromassisted reproductive technology is increasing annually, therisks associated with these treatments are not fully understood.
In this study, we investigated whether infertility treatment constitutes a risk factor for postnatal depression. Methods 827
women who gave birth at our hospital between January and December 2015 were evaluated for postpartum depressive tendencies 1 month after delivery using the Edinburgh Postnatal Depression Scale（EPDS）. We excluded women with a known psychiatric disorder and those whose babies had been admitted to
the neonatal intensive care unit. Patients were stratified into
EPDS high scoring（＞9 points）and low scoring groups（＜8points）and retrospectively analyzed for the use of infertility

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Clinical study of pregnant women with psychotic disorders
Sara Takahashi, Souta Tanaka, Shohei Tanabe, Takanori
Shimizu, Yoko Yoshida, Izumi Sato, Kaori Suenaga, Akiko
Kasai, Goichiro Kasai, Takeshi Aida, Junko Kouno Hachinohe
City HospitalObjective In recent years the number of pregnant women withpsychotic disorders is increasing. To consider how to manage
pregnant women with psychotic disorders, we investigated theclinical outcomes of pregnant women with depression, manic
depression and schizophrenia. Methods Out of 4,759 deliveries
at our hospital from April 2014 to September 2017, there were
52 cases（1.1%）of depression, 12 cases（0.25%）of manic depression and 11 cases（0.23%）of schizophrenia. Pregnant womenwith depression, manic depression and schizophrenia were divided into groups who needed medication therapy during pregnancy（n=36）and groups who did not need medication therapy（n=39）. We analyzed retrospectively whether they needed support of social workers or not. Results 5 cases（6.7%）were preterm birth. 16 cases（21.3%）underwent cesarean section not due
to their mental disorders. 8 cases（10.6%）were threatened premature birth. Ratios of preterm birth, cesarean sections andthreatened premature birth did not have a significant difference
between the ratios of women without psychotic disorders in our
hospital. 25 cases of 36（69.4%）pregnant women who needed
medication therapy during pregnancy required support of social
workers. On the other hand, 15 cases of 39（38.4%）pregnant
women who did not need medication therapy required. Conclusion This study suggests that women with psychotic disorders
who need medication during pregnancy are likely to have needof support of social workers. Consistent management by bothobstetrician and psychiatrist might be required for women withpsychotic disorders, and social workers would be essential tosupport mothers after pregnancy.

ISP-49-8
The Effect of the Edinburgh Postnatal Depression Scale atPostpartum Checkup Asuka Tachi, Tomomi Kotani, Teruyuki
Mizutani, Yuri Niwa, Yukako Iitani, Masataka Nomoto, YumikoIto, Masanori Moriyama, Takafumi Ushida, Kenji Imai, Tomoko
Nakano, Fumitaka Kikkawa Nagoya University
Objective We have provided a postpartum checkup under the
protocol including the Edinburgh Postnatal Depression Scale（EPDS）.We tested whether EPDS is useful for finding a risk of
postpartum depression（PPD）and need for postpartum support.
Methods We collected the data from 44 women delivered in
May August 2017. Based on the EPDS scores, they were divided
into 2 groups, Group A（n=33, EPDS score＜9）and Group B（n=11, EPDS score＞8 defines depressive symptoms）. We analyzed the risk factors of PPD and need for postpartum support.

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Results Group B showed higher mean score（3.05±2.74 vs 13.4
±5.31）. Despite no significant differences between 2 groups inmost risk factors；age at delivery, cesarean section rate andpresence or absence of past mental illness, there were significantly more first births（P=0.013）and infertility treatment（P＜0.01）. Public health nurse, midwife, obstetrician, psychologist,
and/or psychiatrist were selected as postpartum support depending on patient situation. All cases in Group B received some
support. Four needed psychiatrist and public health nurse support. Three of them had a history of mental illness showed nodeterioration, but supports continued：two person support
seems appropriate. Another patient developed PPD state. It was
not contradictory from the onset frequency of PPD. In Group A,
4 needed support, and only one ended support at first time.
EPDS cannot sufficiently extract patients who require support.
Conclusion While the screening effect of EPDS for PPD was
confirmed, it was not sufficient as mental examination tool. This
study suggests that overall examination of perinatal mental
health is needed.

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ISP-50-1
Obstetric and neonatal complications in pregnancies achievedby oocyte donation in our institution Naoko Takahashi,
Tatsuya Miyake, Hitomi Nakamura, Aiko Kakigano, Tsuyoshi
Takiuchi, Shinya Matsuzaki, Kazuya Mimura, Keiichi
Kumasawa, Takuji Tomimatsu, Masayuki Endo, Tadashi
Kimura Osaka University
Objective To assess the risk of adverse obstetrics and perinatal
outcomes in pregnancies achieved by oocyte donation（OD）.
Methods Obstetrics and neonatal outcomes were retrospectively compared between 3 groups, the oocyte donation pregnancies group（n=18）,extremely advanced maternal aged pregnancies（over 45 years old）achieved by in vitro fertilization withautologous oocytes（IVF）group（n=9）, and spontaneous conception（n=16）. All deliveries were performed in our hospital fromJanuary 2008 to August 2017. Results The oocyte recipientswere aged 42 55 years（mean±SE；49.2±0.86 years）.Multiple
gestations were 2 cases（11.1%）, and both of them were twins.
Antenatal complications included hypertensive disorders ofpregnancy（n=7）, gestational diabetes（n=4）, preterm delivery（n=5）, postpartum hemorrhage（n=12, included 3 postpartum
hysterectomy）,and low birth weight（＜2,500g）（n=5）. Thirteen（72.2%）deliveries were performed by Caesarean section. The
gestational age at delivery for singletons was 36.8±0.96 weeks（range 29 41 weeks）,with birth weight 2,644.4±195.5 g. Neonatal complications occurred in 4 babies included light for date（n=2）, tetralogy of Fallot（n=1）, respiratory distress syndrome（n=1）. Compared with IVF and spontaneous conception groups,
the risk of hypertensive disorders of pregnancy and preterm delivery is higher. Moreover, compared with spontaneous conception group, oocyte donation and IVF groups are at higher risk of
having Caesarean section and postpartum hemorrhage. Conclusion Pregnancies by oocyte donation have increased risk of arange of obstetrics and neonatal complications.

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ISP-50-2
Analysis on the perinatal outcome of pregnant patients complicated with inflammatory bowel disease Kunihiko Yoshida1,
Masayuki Yamaguchi1, Tomoyuki Sekizuka1, Ryo Tamura1,
Mina Itsukaichi1, Taro Nonaka1, Kazufumi Haino1, Koichi
Takakuwa2, Takayuki Enomoto1 Niigata University Medical and
Dental Hospital 1, Center for Perinatal, Maternal and Neonatal
Medicine, Niigata University Medical and Dental Hospital 2
Objective Inflammatory bowel disease（IBD）is divided into ulcerative colitis（UC）and Crohnʼs disease（CD）,and IBD is appeared more commonly in younger generation and there are

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treatment, age, previous miscarriage, and previous deliveries.
Results Responses to the EPDS questionnaire were received
from 573 women. There were 77 women（13.4%）in the highscoring group and 496 women（86.6%）in the low scoring group.
A significantly higher proportion of infertility treatment utilization was found in the high scoring group（32/77（41.6%）vs 148/
496（29.8%）；p=0.0393）. Multiparity was associated with lower
risk for postnatal depression（23/77（29.9%）vs 229/496（46.2%）；
p=0.0073）. No significant difference was found among women
who became pregnant after the age of 35（p=0.7579）or whom
had a previous miscarriage（p=0.5146）. Conclusion Women who
had utilized infertility treatment to induce pregnancy accounted for a significantly higher proportion of participants
with a high EPDS score, suggesting that use of infertility treatment may be a risk factor for postnatal depression.

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some occasions to manage pregnant women complicated with
IBD. Patients with IBD have inflammatory and autoimmune
background. The purpose is to investigate the perinatal outcome in pregnant patients complicated with IBD. Methods
Twenty nine pregnancies of 25 patients with IBD（21 cases；
UC, 4 cases；CD）who delivered during 2006 and 2016 in our
hospital were enrolled in this study. The perinatal outcomes
were analyzed retrospectively, using medical records. As control, the pregnancy outcome was analyzed in 509 pregnancy
cases with no complications including IBD. Results The developing rates of p PROM, preterm delivery, or HPD were not significantly different between two groups. The body weight gain
during pregnancy in patient group of IBD was significantly
more than that in control group（11.6±4.0kg vs 10.2±3.7kg, p=
0.023）.The body weight, Apgar score and pH of umbilical arteryof neonates were not significantly different between the twogroups. However, the admission rate of NICU in patient groupwas significantly higher compared with control group（24.1% vs
11.4%, p=0.041）. The causes for admission in patient group weremassive aspiration syndrome, neonatal distress, neonatal bradycardia, or suspection of GBS infection, etc. Conclusion Although
the perinatal outcome of pregnant patients with IBD is not almost different from that of control population, it was consideredthat the careful observation to the neonate was important.

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ISP-50-3
Live birth after intravenous treatment for uterine arteriovenous malformation, a case report Kazumi Tada, Susumu
Miyashita, Tatsuya Kuno, Ichio Fukasawa Dokkyo Medical University
Introduction Uterine arteriovenous malformation（U AVM）isa rare complication with massive hemorrhage after uterine curettage or postpartum period, which can leads to life threatening condition. We report a case of live birth after the interventional radiological（IVR）treatment for U AVM. Case A 39
year old woman, gravida 6, para 2, was referred because of massive uterine bleeding after three weeks of curretage for incomplete abortion. Pathological vessels and blood flow were noted in
the low uterine segment by ultrasonography and MRI, which
was compatible with U AVM. Uterine bleeding was decreased
spontaneously at that time, but massive hemorrhage appeared
again eight months after and urgent IVR was indicated. Feeding
vessels from the left uterine artery were suspected and selected
embolus was carried out. She got pregnant spontaneously after
the IVR treatment and gave birth 20 months afterward. The intrapartum hemorrhage was 1,302g. She discharged without
pathological bleeding. Although abnormal bleeding did not appeared after the delivery, continuous bleeding was observed after a complete abortion after 27 months. We carried out pelvic
angiography 29 months after, and performed the right uterine
artery embolus. The patient got inserted an intrauterine contraceptive device with luteinizing hormone and under the follow
up. Discussion We reported a case of live birth after the IVR
treatment for U AVM. The massive hemorrhage from the U
AVM could lead a life threatening condition, and aggressive
IVR was rationalized

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Mild paroxysmal nocturnal hemoglobinuria in pregnancy,that was difficult to distinguish from hemolysis, elevatedliver enzymes, and low platelet count syndrome：A case report Youhei Tsunoda, Ikuno Kawabata, Eika Harigane, Yukiyo
Harigane, Hiroki Shimmura, Manabu Shimada, Masahiko Kato,
Yuri Shouda, Takehiko Fukami, Takashi Matsushima, Koichi
Yoneyama, Toshiyuki Takeshita Nippon Medical School
Paroxysmal nocturnal hemoglobinuria（PNH）is a rare type ofhemolytic anemia, involving bone marrow failure and thrombosis. We present a case of PNH complicated pregnancy thatproved difficult to distinguish from hemolysis, elevated liver enzymes, and low platelet count（HELLP）syndrome. The patient
was a 36 year old nullipara with pregnancy initiated by assisted reproductive technology. At the gestational age of 35
weeks and 0 days, she developed severe proteinuria, fetal
growth restriction, and thrombopenia. The findings at initial examination were Hb 10.0 g/dL, Plt 83,000, AST 64 U/L, LDH 1,201
IU/L, antithrombin III 98.3% and haptoglobin was less than 10
mg/dL. Hemoglobinuria or schizocytes were not found. As clinical findings suggested partial HELLP syndrome, we performed
an emergency cesarean section. After the delivery, her platelet
count normalized, but her AST and LDH levels remained high.
We made a closer examination of LDH. We suspected hematological disease because LDH1 and LDH2 levels were abnormal.
We finally diagnosed her with PNH because sugar water test
was positive, haptoglobin level was low, and high sensitivity
flow cytometry showed low levels of CD55 and CD59 on erythrocyte surfaces. As the patientʼs condition appeared mild, wemonitored her without treatment. If there are no specific findings for HELLP syndrome, the possibility of PNH complicatedpregnancy should be considered. PNH complicated pregnancy
involves the high risk of thrombosis, and the risk of death forboth the mother and fetus. It is important to establish a diagnosis of PNH for treatment during the next pregnancy.

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Uterine prolapse during pregnancy：two case reports Yuta
Momono, Tetsuro Hoshiai, Kaou Tanoue, Kosuke Tanaka,
Takahiro Minato, Michiyo Kurakata, Hidekazu Nishigori,
Masatoshi Saito, Nobuo Yaegashi Tohoku University Hospital
Introduction Uterine prolapse that develops during pregnancy
is rare, and it is regarded as one case in 10,000 to 15,000 deliveries. There is no definite view on labor management. We report
two cases in which uterine prolapse develops during pregnancy
and has a different outcome. Case 1 A 37 year old woman,gravida 5, para 0. She developed uterine prolapse at 37 weeks
and 2 days of gestation. On the next day, uterine prolapse worsened and became POP Q stage III, which caused symptoms ofurination difficulty and abdominal distension. However, theuterine vagina became highly congested and the cervix varied.
We concluded that it was impossible to deliver vaginally, andcaesarean section was performed. Case 2 A 39 year old woman,gravida 0. She developed uterine prolapse at 35 weeks of gestation. Based on the experience of the above cases, we decided tocarry out planned delivery. At the 38 weeks 0 day of gestation,using the metroillintel, and induction of labor was started byoxytocin. Although descending of the fetal head was smooth, expansion and retraction of the uterine cervix was poor and it required manual opening of the cervical canal. The baby was bornon natural birth. Cervical laceration was found at 8 oʼclock direction and sutured. Conclusion There are many reports that cesarean section was performed as in case 1, in patients with uterine prolapse who developed during pregnancy. However, it issuggested that natural delivery may be performed if planned labor is carried out as in case 2.

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Shakuyakukanzoto could be an effective treatment for apregnant women with lumbar disk herniation and crampy
pain Miyuki Terata, Yuka Okada, Hanae Kawamura, Gen Haba,
Yuri Sasaki, Tomonobu Kanasugi, Chizuko Isurugi, Rie Oyama,
Akihiko Kikuchi, Toru Sugiyama Iwate Medical University
Introduction Shakuyakukanzoto（SKT）, which is composed ofKanzo（Glycyrrhizaeradix）and Syakuyaku（Paeoniae radix）
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Predicting Data based Induction Interval of Labor Induction
with Titrated Oral Misoprostol Solution Shi-Yann Cheng,
Fung-Chang Sung, Cheng-Li Lin China Medical University of
Taiwan, Taiwan
Objective Determine the dominant factors which affect the induction interval in labor induction with titrated oral misoprostol
solution. Methods Women between 36 to 42 weeks of gestation
under labor induction with titrated oral misoprostol solution
were collected from March 2004 to August 2011. Women received basal unit of 20 ml misoprostol solution（1 μg/ml）every
one hour for 4 doses, and then were titrated against individual
uterine response. The recorded induction to vaginal delivery
interval（IVDI）was the primary dependent variable. Nine independent variables including maternal age, maternal bodyheight, maternal body weight, parity, gestational age at induction, birth weight of newborn, Bishop score, cervical length andcervical Os were also recorded. There were one hundred fiftynine women in our database, 6 of them who underwent emergency cesarean delivery and 22 of them with poor response tomisoprostol were excluded. Multivariable regression analysis
was used to estimate the IVDI associated with all related factors. Results There were 55 nullipara women（42.0%）and 76 multipara women（58.0%）in our study. There were 3 factors significantly related to IVDI：Cx length, Cx Os, and maternal parity.
The regression equation was acquired such as Y＝（4.44±15.8）＋（3.20±1.24）×A−（1.22±0.44）×B−（2.81±0.85）×C【Y：IVDI（hrs）；A：cervical length（cm）；B：cervical os（cm）；
C：para, where value＝0 for nullipara or value＝1 for multipara】Conclusion The Bishop score, Cx length, Cx Os, and maternal parity are the dominant variables to evaluate labor induction and predict IVDI.

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Comparison of maternal and perinatal morbidity in term
breech presentation between elective and emergency cesarean
sectionBenjamas Kitnithee, Sanitra Anuwutnavin,
Pharuhas Chanprapaph, Suanya Heamar, Pimnara Rongdech
Siriraj Hospital, Mahidol University, Thailand
Objective To compare maternal and neonatal adverse outcomes
between planned and emergency cesarean section for singleton
term breech presentation. Methods In a retrospective cohort
chart review, data were received from women with a singleton
breech presentation who underwent elective or emergency cesarean section at term between 2007 and 2015 at Siriraj Hospital,

Bangkok, Thailand. The medical records of all women and theirnewborns were statistically analyzed. Results During the 9year period, complete data were collected for 2,203 pregnant
women. Of the 1,332（60.5%）women underwent emergency cesarean delivery, 871（39.5%）women were delivered by planned
cesarean section. The significant predisposing factors（all P＜
0.001）associated with emergency operation included maternal
age ＜35 years, gestational age ＜38 weeks, multiparity, no previous uterine surgery, and being non private case. There wasno maternal or perinatal death in either group. Maternal morbidity in both groups was comparable except for the longer hospital stay in the emergency group（P=0.047）. A 1 minute Apgar
score（P=0.037）was significantly lower in the emergency group.
However, the Apgar score at 5th minute（P=0.825）and admission
to neonatal units（P=1.00）were similar between the groups. Certain emergency indications, such as cord prolapse and placenta
previa, were related to the adverse outcomes while cesarean delivery in advanced cervical dilatation（＞6 cm）or low fetal station（＞0）did not have any excesses of maternal and neonatal
complications. Conclusion In singleton term breech presentation, emergency cesarean delivery in tertiary care setting was
not associated with an increase in serious maternal and neonatal
morbidity compared with planned cesarean section.

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Uterine tonic contraction after initiation of oxytocin infusion
for induction or augmentation of labor Takahiro Yamashita,
Shinichiro Otera, Yoko Gekka, Tomoko Shinohara, Taiki
Samejima, Nobuko Akamata, Shinichiro Yabe, Yukiko Kawana,
Yoshiharu Takeda, Tomoko Adachi, Takashi Okai, Masao
Nakabayashi Aiiku HospitalObjective We report 39 cases of uterine tonic contraction within
30 minutes after administration of oxytocin infusion. Methods
Medical records, including fetal cardiotocograms and partograms were investigated retrospectively. Cases of uterine
tonic contraction occurring within 30 minutes after initiation ofoxytocin infusion with two mIU/min were picked up. Characterof tonic contraction, existence of fetal deceleration, treatment,
prognosis of the newborns, etc. were analyzed. Results The
number of deliveries after 22 weeks of gestation from November
2016 to September 2017 were 2,641, of which 1,256 cases wereadministered intravenous oxytocin and/or prostaglandin F2α（PG）infusion. 1,122 cases were administered oxytocin alone, 55
cases；PG alone, and 79 cases；both oxytocin and PG in a sequential order. Uterine tonic contraction was observed in 39
cases, all of which were after oxytocin infusion, 35 of whichwere accompanied deceleration of the fetal heart rate. The average and median interval between oxytocin initiation and tonic
contraction was 5.0±6.3 and two minutes, respectively. The average and median interval between oxytocin initiation and fetal
deceleration was 8.7±7.5 and 8 minutes, respectively. The bottom and duration of the deceleration were 72±13 bpm, 6.7±2.4
minutes, respectively. 27 cases were administered oxytocin
again with one mIU/min and no cases observed tonic contraction. Vacuum delivery was performed in two cases after fetal deceleration. In all the 39 cases, the newbornsʼ conditions were
good. Conclusion Close observation is recommended for about
15 minutes after the initiation of oxytocin.

ISP-51-4
Can we stop Oxytocin after entering the active phase of labor
for fetal growth restriction（FGR）babies；pros. or cons?
Sayuri Iwai, Kazuya Mimura, Tatsuya Miyake, Aiko Kakigano,
Shinya Matsuzaki, Keiichi Kumasawa, Masayuki Endo, Tadashi
Kimura Osaka University
Objective To investigate whether discontinuation of oxytocin

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is a kind of Japanese Kampo Medicine. A major effect of SKT is
to improve symptoms of muscle cramps. We herein report
apregnant woman with lumbar disk herniation, to whom SKT
was quite effective torelieve severe pain. Case A 33 year old
pregnant woman, Gravida 1, Para 0, was referred to ourhospitalat 24 weeks of gestation. MRI at 14 weeks at another hospital
showed lumbardisk herniation. Her pain gradually worsened,and she became unable to walk by herself at 24 weeks. We
started SKT without any other medication at 25 weeks ofgestation. The pain score drastically dropped from 6/10 to 1 2/10 immediately aftertaking SKT for the first time, and we could finally cease SKT at 29 weeks of gestationwith no recurring pain.
Conclusion SKT has two important effects, that is, to keepbalance and amendment of Ketsu（blood）and Sui（body fluid）,and
therefore it canmitigate the cramp in body and smooth muscles.
Based on our experience, SKT maybe quite effective for treating a pregnant woman with a crampy pain caused by lumbardisk herniation. It might be considered as one of the possible first
medication and analternative to other treatment such as
NSAIDs and a nerve block during pregnancy.

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infusion increases the duration of the active phase of labor or reduces maternal and neonatal complications undergoing labor induction for fetal growth restriction. Methods This is a retrospective study involving 136 women with singleton pregnancy
who underwent labor induction due to FGR at our institution,from January 2010 to August 2017. Two groups were compared：continuation of oxytocin（control）until delivery versus
once discontinuation of oxytocin（DC）at the beginning of active
phase of labor, which was determined as 4cm dilatation with active labor. At beginning, there was no abnormal FHR monitoring. Primary outcome was duration of the active phase. Secondary outcomes were total duration of labor, uterine hyperstimulation and FHR abnormalities rates, mode of delivery, and neonatal outcomes. Results Duration of the active phase was 6 minlonger in the DC group, and the length of second stage was 22
min longer in the DC group；however, these were not statistically significant. The rate of FHR abnormalities was higher inthe DC group, but it did not reach statistical significance（41.8%
in control vs 57.3% in DC, P=0.08）. Uterine hyperstimulation
was significantly higher in the control group（18.9% vs 4.9%；P=0.01）. Total C/S rate was 14.8% in the control group, whereas
24.5% in DC group（P=0.15）.Conclusion Discontinuation of oxytocin infusion at the beginning of active phase of labor for FGR
elongated labor period. However, we can perform DC at the onset of active phase safely without increase uterine hyperstimulation and CS rate under strict monitoring.

ISP-51-5
Risk factors for nonreassuring fetal status before labor in
the presence of premature rupture of membranes Urara Idei,
Norikazu Watanabe, Mika Fukase, Akiko Sugiyama, Seiji
Tsutsumi, Satoru Nagase Yamagata University HospitalObjective This retrospective study examined risk factors for
nonreassuring fetal status（NRFS）before labor in the presenceof premature rupture of membranes（PROM）.Methods We recorded continuous fetal cardiotocography（CTG）from PROM toinitiation of labor. Patients with at least one level three or more
deceleration, as defined by the Japan Society of Obstetrics andGynecology, were considered NRFS. We compared the following
factors in NRFS patients and others：age, gestational weeks, duration from PROM to initiation of labor, maternal or fetal complications, labor induction, mode of delivery, and recording duration of CTG. Results Among 54 women, preterm delivery occurred in six（11.1%）. The median duration from PROM to initiation of labor was 14 hours, 10 minutes. The median CTG recording time was seven hours, one minute. There were 21（39%）patients with NRFS from PROM to initiation of labor. The longer
the duration, the more NRFS appeared during this time period（odds ratio 1.05；95% confidence interval 1.00 1.10；p=0.032）.
Induced delivery with NRFS during this period was only performed in one case with placental abruption. Conclusion The
longer the duration from PROM to initiation of labor, the more
NRFS appeared during this time period. A patient with NRFS
who required induced delivery did not show an increase with
time.

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A Potential Contribution of Bradykinin Receptor B1 Agonist
to the Mechanism of Development of Myometrial InterstitialEdema
Yi Shen, Naoaki Tamura, Tomoaki Oda, Kazuhiro
Sugihara, Hiroaki Itoh, Naohiro Kanayama Hamamatsu University School of Medicine
Objective Myometrial interstitial edema is one of the most common histopathological diagnoses of uterine atony and its treatment options are limited. kinins are important mediators of mostkinds of inflammation that are released during injury, infection

and immune system activation. The effects of kinins are mediated by 2 type of receptors（B1 and B2 receptor）and inductionof vascular hyperpermeability and edema. The objective of thisstudy was to assess whether bradykinin receptor B1 agonist is
involved in myometrial interstitial edema. Methods Tissues
were collected by abdominal hysterectomy after the onset of
postpartum hemorrhage. 10% buffered formalin fixed specimens were embedded in paraffin, and cut into 3 μm thick sections. We selected the cases with myometrial interstitial edema.
Control group is from normal pregnant women after receiving
written informed consent. Primary antibodies of B1 and B2 receptor were used for immunohistochemistry staining. ImageJ
was used for quantitative microscopy analysis for the IHC staining. Results Immunohistochemistry of B1R but not B2R showeda much stronger staining and an increased count of B1R positive cells within the myometrial interstitial edema comparedwith controls. Significant differences were observed in the
B1R+ area ratio/total cells in tissue sections using the unpairedt test（P＜0.05）.Conclusion Uterine atony is estimated to be responsible for 75 80% of postpartum hemorrhage, however, theetiology remains to be clarified. These data demonstrate thatbradykinin receptor B1 agonist can promote myometrial interstitial edema and may open new avenues for postpartum hemorrhage treatment in future.

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Pregnancy outcomes subsequent to uterine arterial embolization for severe post partum hemorrhage Hitomi Imafuku,
Mayumi Morizane, Tokuro Shirakawa, Kenji Tanimura,
Masashi Deguchi, Hideto Yamada Kobe University HospitalObjective To assess pregnancy outcomes subsequent to uterine
arterial embolization（UAE）for severe post partum hemorrhage（PPH）. Methods Eighteen pregnancies after UAE from January
2003 to December 2016 in the single center were studied. Results During the study period, 88 women underwent UAE for
sever PPH（blood loss ＞2,000ml）and 16 subsequently required
hysterectomy due to uncontrolled hemorrhage（14/16）or infection（2/16）. Sixteen women conceived subsequently to UAE including 2 women who conceived twice. Five of 18 pregnancies
required infertility treatment. The median interval from UAE
to the subsequent pregnancy was 25 months（13 77 months）.
The outcomes of 18 pregnancies were two miscarriages, two artificial abortions, one ectopic pregnancy, one invasive mole and
12 live births（7 cesarean and 5 vaginal delivery）including 2 preterm deliveries. Although pregnancy induced hypertension andfetal growth restriction occurred in one case, each growth of theother babies was appropriate for gestational age. One had placenta previa and 2 had placenta accreta. In one case of artificial
abortion, cesarean section was performed at 20 weeks becauseof massive bleeding during the termination of a fetus with multiple malformation. The median blood loss at delivery of 13
cases including the case terminated at 20weeks was 1991ml（395 8,500ml）. There were 6 cases（2 cesarean and 4 vaginal delivery）of severe PPH in 18 pregnancies. Two were used Bakri
tamponade, 4 underwent UAE and 3 subsequently required hysterectomy. Conclusion There was a high incidence of severe
complications after UAE in subsequent pregnancies.

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Promotion of a new technique for cesarean section at fulldilatation Kotaro Shimura, Aiko Kakigano, Tatsuya Miyake,
Tsuyoshi Takiuchi, Shinya Matsuzaki, Kazuya Mimura, Keiichi
Kumasawa, Masayuki Endo, Takuji Tomimatsu, Tadashi
Kimura Osaka University
Objective Incidence of cesarean sections（CS）has increased and
we often encounter CS at full dilatation. Deeply impacted head

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Non Invasive Monitoring of the Cardiac Effects of Continuous Intravenous Oxytocin Infusion during Cesarean Delivery
Kayo Tanaka, Hiroaki Tanaka, Michiko Kubo, Masafumi Nii,
Junko Watanabe, Kuniaki Toriyabe, Kazuhiro Osato, Yuki
Kamimoto, Tomoaki Ikeda Mie University
Objective The effects of continuous intravenous oxytocin infusion on cardiac output（CO）and stroke volume（SV）have notbeen investigated. Therefore, we evaluated whether a continuous intravenous infusion of oxytocin had a major impact on CO
and SV. Methods Ten pregnant women were recruited. Non invasive monitor（EV1000/VolumeView）was used to measure CO,
SV, heart rate（HR）, and mean aortic pressure（mAP）during
a 5 minute infusion of oxytocin during Caesarian sections. Data
were analyzed using unpaired t tests and the generalized linear
model for repeated measures. Results The mean increase in CO
was 123%（relative to baseline）after 60 seconds, which was a
few seconds after the delivery of the baby. CO remained above
baseline. We observed a minor increase in SV between baseline
and the start of the intervention. SV increased approximately
8% after injection of oxytocin. There was an overall increase inHR, reaching a maximum 80 seconds after the intervention. Initially, there was a slight increase in mAP, which then slowly
decreased remained under baseline. Conclusion Continuous intravenous infusion of oxytocin does not have a major effect on
CO or SV, similar to its lack of a major effect on HR and bloodpressure.

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ISP-52-2
Evaluation of circulatory dynamics during cesarean section
using electrical cardiometry Atsuko Hichijo, Takashi Kaji,Naoto Yonetani, Minoru Irahara Tokushima University
Objective Changes in the circulatory dynamics of pregnant
women are significant. Cardiac output increases during pregnancy and especially changes due to uterine contraction andpain during delivery. In previous studies, we confirmed that cardiac output in vaginal delivery（VD）markedly increased during
delivery, and high cardiac output status persisted for 2 hours
thereafter using electrical cardiometry. On the other hand, thecirculatory dynamics in caesarean section（CS）is predicted tobe completely different from VD due to anesthesia etc. How-ever, there is no report that continuously evaluated the variation. Therefore, we evaluate hemodynamics around delivery at
CS by noninvasive continuous cardiac monitoring using electrical cardiometry. Methods We examined the transition of strokevolume, heart rate, and cardiac output from before operation to
2 hours after baby birth using electrical cardiometry in15
healthy pregnant women who underwent CS. Atonic bleedingcases and hypertensive disorders of pregnancy cases were excluded. Analysis was evaluated for normality and comparedwith VD 15 cases by t test. Results In CS, stroke volume andcardiac output were found to increase significantly in 15 minutes after birth（P＜0.001）. Also in CS, the cardiac output in minutes was reduced to its original condition within 120 minutes after birth. These fluctuations were less compared with VD. Conclusion The circulatory dynamics in CS was different from in
VD. By electrical cardiometry, fine evaluation of circulatory dynamics was also possible in CS.

ISP-52-3
Outcome of twin delivery：A single center experience
Masami Hayashi, Hiroko Katayama, Ryo Uemura, Aki Takase,Natsuko Yokoi, Akihiro Hamuro, Takuya Misugi, Akemi
Nakano, Daisuke Tachibana, Masayasu Koyama Osaka City University
Objective The aim of this study is to evaluate neonatal outcomeof twin pregnancy by comparison between groups who planned
to vaginal delivery and cesarean delivery. Methods We reviewed that all twin pregnancies delivered after 34 weeks ofgestation during January 2014 and September 2017. The caseswith obstetrical and fetal complications were excluded. Results
The study population included 88 women with twin pregnancies. Forty women were selected vaginal delivery（Group A）and
48 women were selected cesarean delivery（Group B）. In group
A, 30 twin pregnancies（75%）delivered vaginally. Average gestational age was 36w6d in group A, and 36w4d in group B. Average Apgar scores of the first baby, and second baby（at 5 min）
were 9.0 and 8.9 in group A respectively. Average Apgar scoresof the first and second baby are 8.9 and 8.9 in group B. There isno significant difference between these groups. The number ofneonates with transient tachypnea were similar between thegroups（19% vs. 17%）.There is no significant difference between
MD and DD for failure of vaginal delivery in group A. In group
B, emergent cesarean section was performed in 48% pregnancies because of labor onset and rupture of membranes. Conclusion The success rate of vaginal delivery is 75 percent regardless of chorionicity. There was no significant difference between
groups who hope to vaginal delivery and cesarean delivery inneonatal outcome. We consider that vaginal delivery of twin
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ISP-52-4
A study of factors associated with increased lactic acid levels
in umbilical arterial blood Ryuhei Kurashina, Yoshimitsu
Kuwabara, Mirei Yonezawa, Nozomi Ohuchi, Tomoko Ichikawa,
Rintaro Sawa, Shigeo Akira, Toshiyuki Takeshita Nippon Medical School HospitalObjective This study aimed to identify risk factors associatedwith increased umbilical arterial blood lactic acid levels that reflect fetal acidosis. Methods We retrospectively studied the
medical records of 459 patients with singleton vaginal deliveries
at our hospital between August 2015 and March 2017. We analyzed the correlations between umbilical arterial blood gas andclinical parameters. Spearmans rank correlation coefficient, theMann Whitney U test, the t test, χ2 test, and logistic regression
were used for statistical analysis. Results Umbilical arterial
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into the pelvis makes the procedure technically difficult and CS
at full dilatation is associated with major maternal and fetal
morbidity. Instead of a conventional method of pushing headthrough vagina, we introduced a new technique called reverse
breech extraction technique from 2016, which has been reported
to have less maternal complications. We evaluated maternal andneonatal morbidity of this new technique. Methods We retrospectively analyzed CS cases performed at full dilatation. We
compared maternal and neonatal outcomes between cases delivered by pushing head through vagina（push group）and thosedelivered by reverse breech technique（pull group）.Results We
reviewed 601 CS reports and 298 emergent CS cases were included. Full dilatation was noted in 49 cases（16.4%）. There is atrend that maternal complications including mean operative
time and blood loss were lower in the pull group compared withthe push group. Rate of another maternal complications including postpartum hemorrhage, blood transfusion, extension of theuterine incision and puerperal endometritis, or neonatal outcomes including birth asphyxia and NICU admission rate were
not different significantly. Conclusion Reverse breech extraction technique might be safer and smoother than pushing technique for delivery of a deeply impacted head at emergent CS.
Reverse breech extraction technique can minimize maternal
complications.

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acid levels, and 1 and 5 minute Apgar scores, pH, base excess,and HCO3! also showed negative correlations. The duration of
the first and second stages of labor were positively correlatedwith lactic acid levels. Lactic acid levels were significantly
higher in groups in which the duration of the second stage of labor was 30 59 minutes, 60 119 minutes, or ＞120 minutes, compared to the group with a duration of 0 29 minutes. Univariate
analysis showed that parity, duration of the first and second
stages of labor, use of oxytocin, and vacuum extraction were significant risk factors associated with increased lactic acid levels.
Multivariate analysis showed that prolonged first and second
stages of labor were independent risk factors associated with increased lactic acid levels. Conclusion Prolonged first and second stages of labor are associated with increased lactic acid levels in umbilical arterial blood and may affect fetal acidosis.

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ISP-52-5
The Origin of Inflammation in the Pathophysiology of Postpartum Acute Myometritis involved in Amniotic Fluid Embolism Divyanu Jain, Tomoaki Oda, Naoaki Tamura, Hiroaki Itoh,
Kazuhiro Sugihara, Naohiro Kanayama Hamamatsu University
School of Medicine
Objective There is massive infiltration of inflammatory cells including neutrophils and macrophages alongwith C5a receptor
expression and mast cell degranulation, that is Postpartum
Acute Myometritis（PAM）, in the uterine myometrium after
hysterectomy in Amniotic Fluid Embolism（AFE）. However,uterine cervix is usually ripened during vaginal delivery with
infiltration of inflammatory cells. Our aim is to investigate theorigin and distribution of these inflammatory and immune cells
related to anaphylactoid reaction in the uterine tissue affectedwith PAM in AFE. Methods Under the AFE registry programin Japan, these cases are registered and investigated in our institution. We investigate every uterine tissue at body, isthmus
and cervix with（vaginal delivery）and without（scheduled cesarean delivery）cervical maturation. We performed immunohistochemistry for inflammatory, immune cell markers Neutrophil
elastase, CD68, Mast cell tryptase, IL 8, MCP 1 and C5a receptor and observed their expression at these uterine sites. Results
We investigated uterine tissues from two and three patientswith and without cervical maturation respectively. Mast cell degranulation was observed in body, isthmus and cervix in bothgroups which is not seen in normal cervical maturation. Neutrophil elastase, CD68 and IL 8 were increased in body comparedwith isthmus or cervix in two cases without cervical maturationgroup indicating more inflammatory reaction in body. Conclusion There is a possibility that sudden activation of mast cells inall sites of uterine tissue may play an important role in PAM
pathophysiology alongwith inflammatory changes in the body,which is independent of the cervical ripening and cervical inflammatory cells.

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ISP-52-6
A case of unscarred uterine rupture：A rare and difficult diagnosis Shihori Nishizawa, Satomi Tanaka, Shun Masaoka,
Asako Kumagai, Sachi Sukekawa, Yoshiko Murase, Shotaro
Yata, Hiroshi Kaneda, Yuka Yamamoto, Toshitaka Tanaka,
Naoki Mitsuhashi Juntendo University Shizuoka Hospital
Introduction Unscarred uterine rupture is rare and it is often
difficult to diagnose. We report a case of unscarred uterine rupture that we could not diagnose before surgery. Case A 31
year old first gravid woman delivered a boy with 2,962g andApgar score 8/9 by forceps at 40 weeks 5days gestation with induction of labor. After parturition, she became emergency
transportation to our hospital due to the increase of vaginal hematoma and the hemorrhagic shock. On her arrival, her blood!

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pressure was 76/54 mmHg, heart rate was 140/min, Shock Index（SI）was 1.8. We suspected unscarred uterine rupture as oneof the differential diagnosis, but ultrasonography showed no disruption of the uterine muscle layer. The vaginal examination
showed vaginal hematoma and vaginal laceration. While applying transfusion to her, we performed a vaginal laceration suture
under general anesthesia. Hematoma around uterus continuingfrom vaginal hematoma was confirmed by contrast CT examination after surgery, but there was no obvious abnormality in theuterus. The next day, because genital bleeding was persistingand hemostasis was difficult, transcatheter arterial embolization
was performed. On the fourth day, since rebreeding occurred,
we performed a total hysterectomy and found incomplete horizontal uterine rupture in lower urine segment. Discussion It
seemed difficult to diagnose using images in case of incompletehorizontal unscarred uterine rupture. Even if diagnosis with images is difficult, it is necessary to consider uterine rupture as
differential diagnosis of postpartum hemorrhage.

ISP-52-7
What kind of risk factors can foresee the postpartum hemorrhage after vaginal delivery in uncomplicated pregnancy?
Kazuhiro Nishioka1, Naoto Furukawa2, Seigo Imanaka1, Ayumi
Tsuji1, Taketoshi Noguchi1, Hirotaka Kajihara1, Kiyoshige Horie1
Yamato Takada Municipal Hospital 1, Nara Prefecture Western
Medical Center 2
Objective Postpartum hemorrhage（PPH）is the leading causeof maternal morbidity after a vaginal delivery. As most coagulation factors increase during normal pregnancy, the prothrombintime（PT）and the activated partial thromboplastin time may
be decreased, but the association between PPH and the coagulation profile is unclear. The present study aimed to identify risk
factors for PPH in uncomplicated pregnancies. Methods Our retrospective cohort study included 396 pregnant women withoutcomplications from two institutions between Jan 1, 2015 and Dec
31, 2016. The logistic regression model was used to evaluate univariate and independent multivariate associations of the clinicalparameters with PPH（blood loss＞800 ml）. Results The incidence of PPH＞800ml was 11.6%（46/396）. Univariate analysis
using the logistic regression model revealed that PT/INR at 36
37 weeks of gestation, birth weight＞3,000g, episiotomy or laceration multipara, and age（＞30）were significantly associatedwith PPH. Multivariate analysis revealed that independent risk
factors for PPH were PT/INR, episiotomy or laceration, andbirth weight（p=0.0103, 0.0042, and 0.0106, respectively）. Basedon receiver operating characteristic analysis, the cut off valueof PT/INR level to predict PPH＞800ml was 1.03. Conclusion
The findings of the present study indicated that risk factors for
PPH＞800ml were PT/INR at 36 37 weeks of gestation, episiotomy or laceration, and birth weight＞3,000 g. The PT/INR value
at 36 37gestational weeks＞1.03 is an independent predictor ofsevere PPH.

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Clinical outcome of linear salpingotomy for a different lesionof tubal pregnancy
Toshimichi Oki1, Chie Oki2, Natsuko
Uchida2, Sayuri Hiwatashi2, Yukiko Nakajo2, Hideki Yamasaki3,
Ichiro Iwamoto4, Hiroaki Kobayashi4 Kagoshima University
School of Health Sciences 1, Kagoshima University Medical and
Dental Hospital 2, Kagoshima Medical Association Hospital 3,
Kagoshima University 4
Objective Recently, a few report has described about linear
salpingotomy. We tried to preserve an impaired tube of tubal
pregnancy after salpingotomy with fully informed consent. In
this study, we retrospectively investigated clinical outcomes ofliner salpingotomy in an individual site of tubal pregnancy.

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ISP-53-2
Impact of parity on the transition of fetal presentation transition
duringpregnancy
Shogo Yamaguchi1, Takeshi
Nagamatsu2, Rieko Shitara1, Hitomi Furuya1, Aki Hara3,
Takahiro Seyama1, Toshio Nakayama1, Takayuki Iriyama1,
Yutaka Osuga2, Tomoyuki Fujii2 The University of Tokyo Hospital 1, The University of Tokyo 2, Saitama Cancer Center 3
Objective Prediction of the final fetal presentation is important
for the planning of delivery. This study aimed to clarify thecharacteristics of fetal presentation during pregnancy distinctively in primiparous and multiparous women. Methods This
study was conducted under the approval of ethics committee of
our facility. Perinatal records of 1,923 women｛1,173 primiparous
women（P）and 750 multiparous women（M）｝who deliveredat our hospital from 2015 to 2016 were retrospectively reviewed.
The data on fetal presentation was confirmed by ultrasonography at prenatal visits between 30 and 34 weeks of gestation（WG）. Correlation among non cephalic delivery, Fetal presentation during this period and parity was statistically analyzed. Results The frequency of non cephalic presentation from 30 to 34
WG was not significantly distinct between P and M（13.3% vs
14.0%, p=0.60）. However, P showed significantly higher non cephalic rate than M at delivery at term（4.52% vs 2.67%, p＜0.05）.
The ratio of non cephalic delivery was significantly higher inwomen without any findings of cephalic presentation from 30 to
34 WG, compared with those showing cephalic presentation atleast one time during the same period in both P and M（P：
0.60% vs 47.1%, p＜0.05, M：1.08% vs 31.8%, p＜0.05）. Conclusion The information on fetal presentation during the period
from 30 to 34 WG is useful for the prediction of the final presentation. Transition to cephalic presentation is estimated to occur
more frequently in M than in P.

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ISP-53-3
A case review of methotrexate therapy in ectopic pregnancy
Yoshihide Inayama, Koji Yamanoi, Jumpei Ogura, Tsutomu
Ohara, Mie Sakai, Haruka Suzuki, Koh Suginami Toyooka HospitalObjective Methotrexate（MTX）treatment for ectopic pregnancy
is common and effective. In some cases, however, it fails andsubsequent surgeries are required. The aim of this study is to
discuss pit falls in MTX treatment. Methods In our hospital,
MTX treatment is performed for un ruptured ectopic pregnancies whose hemodynamic status is stable and initial serum hCGlevels are less than 10,000 mIU/ml. Before MTX treatment we
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locations. We analyzed the clinical records of ectopic pregnancies who were initially treated with MTX in our hospital from
April 2016 to September 2017. Results During the period, six patients were treated with MTX；five were tubal pregnancies
and one was interstitial pregnancy. The median age at diagnosis
was 29 and one patient received assisted reproductive therapy.
MTX treatment succeeded in five patients but failed in one patient. The serum hCG level of this patient at diagnosis, on MTX
treatment day 3 and day 9 were 2,596, 4,132, 3,468 mIU/mL, respectively. Additional MTX injection was administrated on day
9, but tubal rupture occurred and an emergent laparoscopic surgery was performed on treatment day 12. Two patients who
were successfully treated with MTX got pregnant within ayear. Conclusion MTX treatment may fail even in patients withrelatively low serum hCG levels at diagnosis. It is important toobserve symptoms, vital signs, and serum hCG levels carefully
during MTX treatment. Surgery should be considered immediately when rupture is suspected.

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Two cases of uterine rupture occurred during second trimester Ryo Uemura, Takuya Misugi, Masami Hayashi, Megumi
Fudaba, Aki Takase, Natsuko Yokoi, Hiroko Katayama, Akihiro
Hamuro, Akemi Nakano, Daisuke Tachibana, Masayasu Koyama
Osaka City University
Uterine rupture is rare for a pregnant woman without uterine
operation or caesarean section. We report the two cases of uterine rupture occurred during second trimester. A 40 year old
gravidity 2, parity 1 patient without caesarean section was admitted to previous hospital due to threated abortion at 17weeks
of gestation. Sudden abdominal pain was occurred and transferred to our hospital at 18weeks of gestation. Moderate abdominal pain limited uterus was recognized, but the next day, pain
became severe and shock index increased to 2.0. Contrast enhanced CT showed intraabdominal hemorrhage and we underwent exploratory laparotomy. In the operation, we recognizedmassive hemorrhagic ascites, uterine rupture at fundus uteri
and placenta accrete, and performed supra cervical hysterectomy. A 40 year old gravidity 6, parity 4 patient without caesarean section was diagnosed complete abortion at anotherclinic at 8weeks gestation. Chorion membrane was not confirmed, but gestational sac was not detected in uterus by ultrasound, and clinical follow was over. After 6 weeks later, sudden
abdominal pain was occurred and intraabdominal hemorrhage
and fetus in uterus was recognized and transferred to our hospital. We diagnosed 13 weeks gestation by ultrasound and suspected interstitial portion of the right fallopian tubal pregnancy
by MRI, so we underwent exploratory laparotomy. In the operation, we recognized massive hemorrhagic ascites and uterine
rupture at interstitial portion of right fallopian tube, and performed total hysterectomy. Uterine rupture can occur even patient without uterine operation or caesarean section. When abdominal pain limited uterus was recognized, it is important tosuspect uterine rupture.

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ISP-53-5
Obstetric Outcome of Subsequent Pregnancy following Uterine Artery Embolization for postpartum hemorrhage Mariko
Jitsumori, Shinya Matsuzaki, Tatsuya Miyake, Aiko Kakigano,Tsuyoshi Takiuchi, Kazuya Mimura, Keiichi Kumasawa,
Masayuki Endo, Takuji Tomimatsu, Tadashi Kimura Osaka University
Objective Uterine artery embolization（UAE）is used to treat
uncontrollable postpartum hemorrhage. The obstetric outcomeof subsequent pregnancy following UAE has been shown in alimited number of studies, with some reports showing a higher

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Methods Subjects were as follows, 10 cases of fimbrial pregnancy（F group）,16 of isthmic pregnancy（I group）,and 107 of
ampullar pregnancy（A group）who underwent laparoscopic
salpingotomy. Between three groups, findings of fallopian tubes,
blood loss during surgery, and success rate of laparoscopic
salpingotomy were compared. Results Intraoperative blood loss
was greater in I group than F and A groups. Rupture rate ofserous membrane：F group 0%（0/10）, I group 18.8%（3/16）,
A group 1.9%（2/107）. Rupture rate of muscle layer；complete：0%（0/10）,37.5%（6/16）,1.9%（2/107）, incomplete：0%（0/10）,43.8%（7/16）, 0%（0/107）,respectively. The success rateof fallopian tube preservation was 90.0%（9/10）, 50.0%（8/16）,
93.5%（100/107）, recovery rate of tubal patency after the surgery was 100%（9/9）,75.0%（6/8）,96.0%（96/100）respectively.
Conclusion Isthmic pregnancy have negative impact to preserve an impaired tube by salpingotomy, because isthmus pregnancy often complicated with severe damage of tubal wall. However, an addition of end to end anastomosis to salpingotomy ofisthmic pregnancy is a useful alternative.

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rate of placenta accreta. However, there has been no case control study；therefore, we conducted a case control study of subsequent pregnancy following UAE in our hospital. Methods In a
retrospective analysis, data from deliveries in our hospital, between January 2012 and June 2017, was reviewed. The deliveries were divided into previous UAE（study group）and non UAE（control group）groups. Placenta accreta was defined as confirmed by pathological examination. Results Data from 2,845 patients were included in the study. Fifteen patients were included in the study group, and 2,830 patients were included in
the control group. Although our control group could contain significant bias of preterm birth rate as a referral hospital, there
are no differences were observed between the study and control
groups in the frequency of preterm delivery［2/15（13.3%）vs447/2,830（15.7%）；P=1.00］. However, placenta accreta was significantly more common in the study group than in the control
group［5/15（33.3%）vs 27/2,830（0.95%）；P=0.001］.Conclusion
Our study suggested that previous UAE was a significant risk
factor of placenta accreta.

ronmental factors that regulate CD59 expression in the isolated
EVT. Methods The first trimester chorionic samples were obtained from artificial abortions and were subjected to the organ
cultures to isolate the primary EVTs（isolated EVTs）. Possible
effect of hypoxic culture or co culture with platelets on CD59
expression in the isolated EVTs was assessed with q PCR and/or flow cytometry. In addition, possible effects of treatment withvarious cytokines that are abundantly released from activatedplatelets（i.e., IL 1β, CCL5, TGF β1, VEGF and PDGF）on their
CD59 expression were examined with q PCR. Results CD59 expression in the isolated EVTs was down regulated under the
hypoxic condition and up regulated by co culture with platelets. Among the various cytokines examined, only TGF β1 could
alter（up regulate）CD59 expression in the isolated EVTs. Conclusion High CD59 expression on eEVT could be at least in part
explained by the surrounding microenvironment such as highoxygen concentration in the maternal spiral artery and TGF β1
released from the platelets that are activated following thedeposition on eEVT.

ISP-53-6

ISP-54-2

Epidemiology of ectopic pregnancy：incidence, risk factors
and outcomes in Mongolia Tsevelmaa Baldan1, Munkhtsetseg
Davaatseren2, Enkhtsetseg Jamsranjav2 Marie Stopes International Mongolia, Mongolia 1, Mongolian National University of
Medical Sciences, Mongolia 2
Objective We aimed to identify potential risk factors and toevaluate the contribution of the risk factors associated to EP.
Methods This case control study was conducted from 1998 to2016 in the four Hospitals in UB, Mongolia. In case group there
were a total of 121 women diagnosed with EP, while in the control group I；130 women who had normal pregnancy and in thecontrol group II；129 women who had induced abortion. The basic recorded information and the laboratory method was determination of anti chlamydia trachomatis IgG titer. The association between EP and the factors studied was analysed by Multivariate multinomial logistic regression and adjusted relativerisk ratios（aRRR）. Results EP group had higher IgG antibody titres than group I and group II. Then fitted as a trend variable,using log base 2（IgG titre）the association was highly significant（aRRR=1.1 95%CI：1.0 1.3 and aRRR=1.2 95%CI：1.1 1.4；
P=0.0019）. A history reproductive tract infection（RTI）was associated with increased risk of EP, even after adjustment foranti chlamydial IgG titre with aRRR between 2.2（95%CI：0.96
7.0）and 4.2（95%CI：1.5 11.7）compared to ANC and IA controls.
Also, cigarette smoking was a strong risk factor for EP with
aRRR of 2.8（95%CI：1.3 6.2）and 4.4（95%CI：1.8 11.0）.Conclusion In this UB city population, history of infection with Chlamydia trachomatis was independent, dose related risk factor for
EP.

Serum autotaxin level as a biomarker for placental function
Yumiko Nishimori1, Takeshi Nagamatsu1, Tatsuya Fujii2,
Nobuko Mimura1, Takayuki Iriyama1, Yutaka Osuga1, Tomoyuki
Fujii1 The University of Tokyo 1, Kanto Rosai Hospital 2
Objective Autotaxin（ATX）is a major enzyme that produces lysophosphatidic acid, a phospholipid mediator. ATX is known toincrease in malignant tumors, arteriosclerosis, pulmonary fibrosis. Placental production is a major source of serum ATX during
pregnancy. This study aimed to examine the association of serum ATX concentration with the placental weight and fetal
growth. Methods This study was conducted under approval of
our facility ethics committee. We collected serum samples from148 women with singleton pregnancy, including 116 women of
uncomplicated pregnancy and 32 women complicated withpreeclampsia（PE）and/or fetal growth restriction（FGR）. The
correlation of the serum ATX levels in the second and the third
trimesters with placental weight, birth weight and BPR（birthweight to placental weight ratio）was evaluated. Serum ATX
concentration in the second and the third trimester was determined by ELISA. Results The serum ATX levels increased
along with the progression of gestation, reaching its peak atterm pregnancy, and rapidly returned to pre pregnancy level at
postpartum period. In uncomplicated pregnant women, a significant negative correlation（R=0.72 P＜0.001）was detected between BPR and the serum ATX level in the second trimester,
but not in the third trimester. This negative correlation in thesecond trimester was canceled in the pregnancies with PE and/or FGR. Conclusion Our findings imply that placental ATX in
normal pregnancy could be involved in the mechanism to adjust
fetal growth to appropriate status. It is possible that dysregulation of ATX production is associated with the pathoetiology ofPE and FGR.

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ISP-54-1
CD59 expression on human extravillous trophoblast may beregulated by surrounding microenvironment Masashi Ueda1,
Akihito Horie1, Yukiyasu Sato2, Hirohiko Tani1, Asuka
Okunomiya1, Yusuke Sagae1, Masaki Mandai1 Kyoto University 1,
Japanese Red Cross Otsu Hospital 2
Objective In human placenta, although endovascular extravillous trophoblast（eEVT）makes direct contact with maternal
complement components, eEVT is not eliminated by their activation. Previously, we found that expression of CD59, one ofmembrane bound complement regulators, is higher on eEVT
than on interstitial EVT invading the maternal decidua in vivo.
In addition, we demonstrated that CD59 provides some protection against complement dependent cytotoxicity to trophoblastic cell line in vitro. In this study, we investigate possible envi-

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ISP-54-3
Transport mechanism of nicotine in BeWo cells Takako
Sadakane, Iemasa Koh, Yoshiki Kudo Hiroshima University
Objective Maternal nicotine exposure via smoking has been associated with birth complications, such as spontaneous abortionand fetal growth restriction. To understand the adverse effects
of maternal smoking during pregnancy, it may be important toclarify the mechanism underlying the transplacental transfer of
nicotine. In this study, we investigated the mechanism of nicotine uptake using BeWo cells as a model of the human placental
trophoblast. Methods BeWo cells were cultured for 4 days andwere used for the uptake study. BeWo cells were incubated

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ISP-54-4
Accumulation of prostaglandin E2 in amniotic fluid and expression of PGE synthases and transporters during human labor Nanase Takahashi, Shintaro Makino, Atsuo Itakura, Satoru
Takeda Juntendo University HospitalObjective Metabolites of arachidonic acid（AA）, especially
prostaglandin E2（PGE2）, are known to induce labor. PGE2 production from AA is catalyzed by cyclooxygenases（COX）1, 2,
and PGE synthases（cPGES and mPGES 1, 2）. PGE2 is transported to the extracellular space by the transporters such as
SLCO2A1. However, the detailed mechanism of PGE2 production
and transportation during human labor is largely unknown.
Methods This study includes pregnant women at term who
were classified into the following groups：women who delivered at term in labor（TLB）and at term not in labor（TNL）. All
patients provided written, informed consent before the collection of subjects, which were approved by the Ethics Committee.
Results We revealed that the concentrations of PGE2 in amniotic
fluid of subjects at TLB are much higher than those of TNL by
LC MS. By RT qPCR, we found significantly higher expressions of cPGES both in TLB villus tissue and fetal membranethan TNL. The same results were also shown by western blotting analysis. Immunohistochemistry revealed that expressionsof COX 2, cPGES, and SLCO2A1 were observed in syncytialtrophoblast, chorion trophoblast, and amnion epithelium. Finally,
we performed human membrane transwell model analysis
which showed significantly higher PGE2 production in TLB
membranes both in fetal and maternal sides than those of TNL.
Conclusion In summary, we showed that PGE2 in amniotic fluid
is possibly produced mainly by COX 2 and cPGES in syncytialtrophoblast, choriodecidua and amnion epithelium during laborand may induce uterine contraction directly or indirectly. Ourstudies are the first to reveal the unknown function of cPGES inlabor.

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ISP-54-5!

Expression of TrkB isoforms in FGR and non FGR Akane
Kondo1, Daichi Nakaoku1, Mikio Yamasaki1, Yumiko Goto2,
Kazumi Takahashi2, Mikio Morine1, Kenji Hinokio1, Kazuhisa
Maeda1 Shikoku Medical Center for Children and Adults 1, Tokai
University 2
Objective Brain derived neurotrophic factor（BDNF）and its receptor Tropomyosin related kinase B（TrkB）are expressed inplacenta. TrkB has a basic function of inducing invasion and cell
survival. However, their function in the placenta is not clear yet.
Trophoblasts remodel blood vessels by replacing the vascularendothelium infiltrating the decidua after the epithelial mesenchymal transition（EMT）.Cytotrophoblast（CT）becomes Extravillous Cytotrophoblast（EVT）and Syncytiotrophoblast（STB）. TrkB is expressed on these cells and may involve the re-!

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modeling of the vessels by EMT, which is essential for fetal
growth. Methods We analysed expression of TrkB and BDNF, aligand of TrkB in the group of 27 cases of FGR and 31 normal
pregnancy. Since there is a possibility of the defect of TrkB isoforms in FGR samples of human, we analyzed all isoforms in
FGR to reveal the correlation between BDNF signal deficientisoforms and FGR. The expression of isoforms were confirmed
by using RT PCR with primers of corresponding TrkB exons.
Results 12 out of 14 FGR placenta showed multiple defect of exons. Within FGR group, 35 41w groups showed more defects
than earlier gestation, 28 34w. This was similar tendency compared to non FGR Groups. Compared to FGR and non FGR,
more sample showed expression of less lesion within non FGRGroup. Conclusion Expression of binding site of BDNF and intracellular domains were lower in FGR 35 41w Group. This alteratioon was shown in all gestation non FGR group. From thisresults, placantal TrkB showed insufficient downstream signalling in late gestational period.

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ISP-54-6!

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Effects of TNF α and IGF I on proliferation and angiogenesis of BeWo cells Kei Tanaka, Miho Matsushima, Tomoko
Izawa, Shinji Tanigaki, Seishi Furukawa, Yoichi Kobayashi,
Mitsutoshi Iwashita Kyorin University
Objective Circulating levels of TNF α and IGF I are elevatedin obesity and obesity is considered as chronic inflammation.
Placental hypertrophy and macrosomia are often observed in
pregnancy with obesity. However, it is not elucidated yet
whether TNF α and IGF I are involved in pathogenesis of placental hypertrophy. We investigated the effects of TNF α and
IGF I on proliferation and angiogenesis of trophoblast cells byusing BeWo cells. Methods After incubating BeWo under the, wepresence of TNF α（10×105 pg/ml）and IGF I（102ng/mL）
assessed cell number and proliferation by WST 1 assay and
BrdU uptake assay, respectively. Apoptosis was evaluated by
TUNEL assay and caspase 3, 8 activity assay. We also measured
the concentrations of VEGF, PlGF, and FGF in the conditioned
media by ELISA. Results Under the presence of IGF I（102 ng/
mL）, cell number and BrdU uptake of BeWo was dose dependently enhanced by TNF α（10×102 pg/ml）,while no such
effects were detected without IGF I. The number of TUNEL
positive cells were decreased and caspase activities were suppressed by 102 pg/ml of TNF α. IGF I（102 ng/mL）also decreased the number of TUNEL positive cells and suppressedcaspase activities. The concentrations of PlGF and VEGF weresignificantly higher in the presence of 10×102 pg/ml of TNF α,
while TNF α showed no signifiant effects on FGF. Addition of
IGF I（10×103 ng/mL）dose dependently suppressed PlGF secretion and enhanced VEGF secretion. Conclusion TNF α and
IGF I stimulate proliferation synergistically and regulate apoptosis and angiogenesis by independent mechanisms, which suggests that TNF α and IGF I are responsible for placental hypertrophy in pregnancy with obesity.

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ISP-54-7
The study for the effect of different diameter in bilateral umbilical arteries on the formation of umbilical twist Masamitsu
Nakamura, Tomohiro Oba, Tatsuya Arakaki, Mayumi
Tokunaka, Minako Goto, Ryu Matsuoka, Akihiko Sekizawa
Showa University
Objective To clarify the effect of the difference of diameters inbilateral umbilical arteries on formation mechanism of umbilicaltwist. Methods Cross sectional cohort study was performed.
The subjects measured the umbilical arteries diameter from 19
to 22 weeks after determining gestational age at 9 10 weeks
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with［3H］nicotine, and the amounts taken up by the cells were
measured by liquid scintillation counting. Results［3H］Nicotine
uptake was time and temperature dependent and showed saturation kinetics with a Michaelis constant Km of 300.6 μM in the
BeWo cells. In addition, the Eadie Hofstee plots were linear,suggesting that a single transport system was involved in nicotine uptake in BeWo cells.［3H］Nicotine uptake in the BeWo
cells showed clear pH dependence and was high at high pH. The
uptake of［3H］nicotine was potently inhibited by organic cations
such as clonidine, diphenhydramine, and pyrilamine, but was
not affected by substrates and/or inhibitors of known organic
cation transporters, such as carnitine, 1 methyl 4 phenylpyridinium, or tetraethylammonium. Conclusion These results suggest that a specific transport system is involved in the uptake ofnicotine in BeWo cells.

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rection of umbilical twist was diagnosed by ultrasound, and thedegree of umbilical twist was assessed using antenatal coilingindex（ACI）at free loop of the umbilical cord. The cases with fetal anomaly and single umbilical artery were excluded in thisstudy. Results One hundred nine cases were included in thepresent study. The median（range）gestational age measured diameter of umbilical vessels was 20（19 22）weeks. The frequencies of cases with left umbilical twist were significantly higher
than those of right twist［left 81.7%（89 cases）vs 18.3%（20）］.
The diameters of left and right umbilical arteries（mean±SD）
were 1.7±0.4 and 1.9±0.4（p=0.024）. Cases with right umbilicalartery thicker than left were 63.3%（69）, with right umbilical artery thinner than left were 24.8%（27）, and with right equaled
left were 11.3%（13）. The frequency of cases with left twisted
umbilical cord which had right umbilical artery thicker thanleft were 92.8%（64/89）significantly more than 48.1%（13/27）with right artery thinner than left（p＜0.01）. Conclusion It
is revealed that the frequency of left umbilical twist was morethan 70%. The difference of diameter in right and left umbilicalartery might be related to the direction of umbilical twist.

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ISP-55-1

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ISP-55-2
Association between birth weight and subsequent risk for hypertensive disorders of pregnancy Maiko Wagata1, Yasuhiro
Kurosawa2, Hirotaka Hamada2, Michiyo Kurakata2, Tetsuro
Hoshiai2, Hidekazu Nishigori2, Masatoshi Saito2, Hirohito
Metoki3, Nobuo Yaegashi2, Junichi Sugawara2 Tohoku University Tohoku Medical Megabank Organization 1, Tohoku University 2, Tohoku Medical and Pharmaceutical University 3
Objective To clarify the association between womanʼs own birthweight and her subsequent risk for hypertensive disorders ofpregnancy（HDP）in each subtype and assess the risk for HDP

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Soluble endoglin inhibited autophagy enhances LPS inducing
inflammasome production in peripheral blood of pregnant
women Akitoshi Nakashima, Tae Kusabiraki, Aiko Aoki, Azusa
Sameshima, Tomoko Shima, Osamu Yoshino, Shigeru Saito University of Toyama
Objective Autophagy plays an important role for inflammasome
removal, resulting in control of inflammation. We have reported
that soluble endoglin（sENG）, mRNA of which are elevated inearly onset of PE, inhibited autophagy in trophoblasts. It is,meanwhile, still unknown the mechanism how systemic inflammation could be induced in preeclampsia. This study examined
whether sENG enhanced inflammasome derived IL 1β by LPS
in peripheral blood mononuclear cells（PBMCs）of pregnant
cases. Methods Informed consent was obtained from all participants（n=23）. The secreted IL 1β levels were measured in
PBMCs in the presence of sENG with LPS by ELISA. Results
The concentration of IL 1β was significantly higher in PBMCs
with LPS than that without LPS（180 ±168, 1.3 ±0.9 pg/ml）.
The IL 1β levels were no difference in PBMCs between pregnant and non pregnant women, or between under normoxic andhypoxic conditions. To firstly investigate the effect for IL 1β
production by autophagy inhibition, 3MA, a PI3K inhibitor, wastreated in PBMCs with LPS. The IL 1β levels were increased
5.7 fold in the presence of 3MA（p=0.002）. In addition, the LPS
mediated IL 1β expression levels were also significantly higher
in PBMCs with 100, 500, or 1,000 ng/ml sENG, compared withthat with LPS alone（p=0.008, 0.0002 or＜0.0001）. Conclusion We
firstly showed that autophagy inhibition by 3 MA or sENG enhanced IL 1β production by LPS in PBMCs. Soluble endoglin
mediated autophagy inhibition might be involved in not only
anti angiogenesis, but also dysregulation of inflammasome, resulting in onset of preeclampsia.

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among women born small and overweight in adulthood. Methods In this study, 4,770 singleton pregnant women were included. We analyzed the association between womenʼs birthweight and HDP by multivariate logistic regression analysis adjusting for age, pre pregnancy body mass index（BMI）and family history of hypertension in each subtype. We also constructed
a composite variable that combined birth weight（＜2,500, 2,500
3,500, ＞3,500g）and pre pregnancy BMI（＜18.5, 18.5 22, 22 25,＞25kg/m2）, providing 12 categories and performed multivariate logistic regression analysis. Results In total, 497 women
were affected by HDP（10.4%）. The prevalence of HDP was
17.65%, 14.41%, 10.41%, 9.95%, 11.11%, and 4.88% in birth weight＜2,000g, 2,000 2,500g, 2,500 3,000g, 3,000 3,500g, 3,500 4,000g,
and ＞4,000g group, respectively（p for trend=0.07）. In birthweight＜2,500g group, the adjusted odds ratio（OR）for HDP was
1.73（95% confidence interval：1.16 2.57）in whole HDP, 1.75
（0.96 3.17）for gestational hypertension, 3.42（1.76 6.65）for
preeclampsia, compared with 2,500 3,500g group. In the combination of birth weight and pre pregnancy BMI, birth weight＜
2,500g and pre pregnancy BMI＞25kg/m2 group had the highest
adjusted OR：6.60（1.84 23.60）for gestational hypertension, and21.18（7.19 62.41）for preeclampsia. Conclusion A significant association exists between birth weight and subsequent HDP,
whereas this association differs by HDP subtypes. Women born
small and overweight in adulthood have particularly high risk
for HDP and weight control is important.

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ISP-55-3
A role of Sonic hedgehog pathway in preeclamptic placenta
Hiroshi Takai, Eiji Kondoh, Haruta Mogami, Yosuke
Kawamura, Shingo Io, Mai Sato, Yoshitsugu Chigusa, Masaki
Mandai Kyoto University
Objective We previously reported that Sonic hedgehog（Shh）
pathway was involved in preeclamptic placentas. Insulin likegrowth factor 1 receptor（IGF1R）is known to be a key role in fetal growth and placental function. The aim of this study is toelucidate the association between Shh pathway and IGF1R inplacenta. Methods The study protocol was approved by the Ethics Committee. Twenty placental samples were collected fromnormal and preeclamptic singleton pregnancies（n=10, respectively）.The expressions of Patched homolog 1（PTCH1）, a Shh
receptor, and IGF1R were examined by qPCR. Clinical data including placental weight and fetal birth weight were collectedfrom medical records to investigate their association with
PTCH1 or IGF1R expression. Primary cytotrophoblasts（CTBs）
were treated with or without cyclopamine, a Shh pathway inhibitor or si Gli2, one of the transcriptional factors in Shh pathway. CTBs were treated with or without recombinant Shh（rShh）. Results PTCH1 and IGF1R expressions were significantly down regulated in preeclamptic placentas（both P＜
0.001）. PTCH1 expressions were correlated with IGF1R expressions（R=0.4821, P=0.0313）.PTCH1 expressions were highly correlated with fetal birth weight（R=0.7807, P＜0.001）and placental weight（R=0.5839, P=0.0069）.PTCH1 and IGF1R expressions
in CTBs were significantly down regulated by cyclopamine（n=6, P=0.010, P=0.032）and si Gli2（n=6, P=0.001, P=0.017）. The
protein expressions of IGF1R in CTBs treated with rShh was increased and not increased treated with rShh and Cyclopaminecompared with control. Conclusion Shh pathway may contribute to the regulation of IGF1R expression in the placenta.

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ISP-55-4
Correlation between intracranial imaging by MRI and development at age of 3 in the children born from mothers with hypertensive disorders of pregnancy or spontaneous preterm
birth Tae Kusabiraki, Noriko Yoneda, Satoshi Yoneda, Mutsumi

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ISP-55-5
A novel of biomarker profiles in experimental aged maternalmouse with hypertensive disorders of pregnancy Kiichiro
Furuya, Keiichi Kumasawa, Hitomi Nakamura, Tadashi Kimura
Osaka University
Objective Advanced maternal age（AMA）has increased and related to feto maternal mortality and morbidity. One major complication of AMA is hypertensive disorders of pregnancy（HDP）. We established a mouse model that mimics the phenotypes of human AMA. Methods Aged pregnant Jcl：ICR mice
were used as AMA model mice and analyzed their phenotypes.
We also examined their blood pressure and some biomarkers
that are associated with the pathogenesis of HDP；soluble fms
like tyrosine kinase 1（sFlt 1）and placental growth factor（PlGF）, the key factors of HDP. Results The significant findingsof our investigation are；1）The AMA model mice manifested
the same phenotypes of human AMA including maternal obesity, declining fertility, small gestational age（SGA）, and higher
percentage of intrauterine fetal death（IUFD）, 2）The AMA
mouse model represented increasing blood pressure at late gestation（108.2±7.7 vs 92.7±5.7 mmHg, P＜0.01）and normalizationof it after delivery similar to human HDP patients, and 3）While
HDP and placental dysfunction are complicated, AMA mice andhuman HDP AMA patients manifested a low serum level ofsFlt 1 in late gestational period（mice；16,800.0±10,709.5 vs26,611.9±8,702.0 pg/mL, P＜0.01, human；8,507.6±3,298.7 vs
14,816.9±5,413.5 pg/mL, P＜0.05）. Conclusion AMA model miceresembled human AMA. AMA model mice was complicatedwith HDP；however, the serum sFlt 1 level displayed a low
level in late gestational period. Our findings provide the evidence that the serum sFlt 1 level does not necessarily reflect
the conventional pathogenesis of HDP in aged human andmurine pregnancies, and may contribute to the future management of HDP in AMA.

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ISP-55-6
Risk Factors for Bleeding Complications after Cesarean Sec-tion among Preeclampsia Cases Followed by Postoperative
Prophylactic Anticoagulation Naoya Tsujimoto, Hironobu
Hyodo, Satoshi Nitta, Saho Fujino, Miho Saito, NorihikoNakazato, Etsuko Saito, Midori Funakura, Sorahiro Sunagawa,
Koji Kugu Tokyo Metropolitan Bokutoh HospitalObjective Preeclampsia is reported to increase bleeding complications with prophylactic anticoagulation. The objective of thisstudy was to identify risk factors for bleeding complications
among cases of preeclampsia with prophylactic anticoagulants
after cesarean section. Methods Sixty eight cesarean cases ofpreeclampsia（including superimposed preeclampsia）with postoperative prophylactic anticoagulation were reviewed retrospectively at a tertiary perinatal center between 2012 and 2017.
Bleeding complications were defined as subcutaneous hematoma, subfascial hematoma, and intraperitoneal hematoma detected by ultrasonography or computed tomography. Age, bodymass index, preoperative 24 hour urine protein, 24 hour urine
volume, and other clinical and laboratory data were studied
about the association with bleeding complications by univariate
and multivariate analysis. Results Among a total of sixty eightcases, bleeding complications were recorded in nine cases；subcutaneous hematoma in four, subfascial hematoma in four, andintraperitoneal hematoma in one. Univariate analysis showedthat preoperative platelet count and preoperative 24 hour urine
protein were associated with bleeding complications. Multivariate logistic regression analysis revealed that a preoperative decreased platelet count was an independent risk factor for bleeding complications（OR, 0.852；95% CI, 0.73 0.99；P =0.04）.Conclusion A preoperative platelet count was significantly related
to bleeding complications in cases of preeclampsia after cesarean section followed by postoperative prophylactic anticoagulation even the count was not abnormally low.

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ISP-56-1
Examination of the influence of infectious stress in postnatal
period on sexual behavior of male rats in adulthood Mayila
Yiliyasi, Toshiya Matsuzaki, Rie Yanagihara, Kiyohito Yano,
Takeshi Iwasa, Minoru Irahara Tokushima University
Objective We examined the influence of infectious stress exposure in early postnatal period on sexual behavior of male rats.
Methods SD male rats were divided into 3 groups：control
group（n=17）, PND10LPS group（n=31）and PND25LPS group（n=16）. Lipopolysaccharide（LPS）（100 μg/kg）was injected to
PND10LPS and PND25LPS groups on the 10th and 25th days ofage, respectively. Sexual behavior was observed for 30 minutes
in 10 to 12 weeks. We checked hypothalamic mRNA expression
levels of sexual behavior related factors and serum testosterone（T）concentration. Thereafter, the testes were removed at 14
weeks, and a silicone tube containing T was placed in the backof the neck and sexual behavior was observed. Results The sexual behavior of the PND10LPS group was significantly less thanthe control group. PND10LPS and PND25LPS groups showedsignificant lower serum T and mRNA expression of progesterone receptor B（PRB）and GnRH than in control group. After
supplementation of T, sexual behavior of the PND10LPS andPND25LPS groups still was significantly less than that of thecontrol group. Conclusion That attenuation of sexual behavior
in adult male rats which were exposed to infectious stress inneonatal period could not be recovered by testosterone supplementation and might be brought by lower expression of PRB in
hypothalamus.

ISP-56-2
The influence of early life psychological stress on sexual
maturation and on sexual activity in female rats Kiyohito
Yano, Toshiya Matsuzaki, Rie Yanagihara, Mayila Yiliyasi,

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ISP

Kobayashi, Kaori Fukuta, Arihiro Shiozaki, Shigeru Saito University of Toyama
Objective We evaluated the correlation between intracranial
imaging by MRI（Kidokoro score：KS）and development at ageof 3 in the children born from mothers with hypertensive disorders of pregnancy（Child HDP）or spontaneous preterm birth（Child PTB）
. Methods Eighteen cases of Child HDP and 41
cases of Child PTB managed in our hospital from 2006 to 2015
were selected. They were all evaluated intracranial abnormality
by MRI before discharge from NICU and development at age 3
by Bayley III. Poor development was defined as cerebral palsy,
mental retardation, and low score of Bayley III. KS which canaccurately evaluate intracranial lesions was used in this study.
Results 1）The rate of KS was 12.2%（Normal）, 41.5%（Mild）,
31.7%（Moderate）and 14.6%（Severe）in Child PTB, while thatwas 50.0%, 14.6%, 11.1% and 0% in Child HDP. 2）In Child PTB,
delivery weeks of gestation tended to correlate according to severity of KS（28.9 of Normal, 28.2 of Mild, 27.3 of Moderate and25.9 of Severe, p=0.082）, and the frequency（%）of poor development also tended to correlate（0, 11.8, 7.7 and 50.0, p=0.058）, but
not in Child HDP. 3）There was a significant difference between
development and KS in Child PTB（7.0±0.8 of good development vs 13.7±1.8 of poor, p＜0.01）, but not in Child HDP. Conclusion The interesting relationship was observed between intracranial imaging by MRI and long term prognosis at age of 3
in children born from PTB mothers, while there was no correlation in HDP cases. In HDP cases, neurodevelopment might berecognized as functional damage rather than organic damage.

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Takeshi Iwasa, Minoru Irahara Tokushima University
Objective The influence of early life psychological stress induced by maternal separation（MS）on the sexual maturationand the sexual activity was examined in female rats. Methods
Female rats were divided into control（C）and maternal separation（MS）groups, respectively（n=24 per group）.Pups in MS
groups were placed in isolated cages during 240min/day frompostnatal day（PND）2 to PND11. Onset of vaginal opening（VO）
in rats were monitored from PND29 to PND40. Thereafter, estrous cycle were monitored from PND62 to PND72. We collected the ovaries at 11 week age and observed sexual behaviors at 12 and 14 week ages. We injected progesterone（1mg）in
the ratʼs back at 48 and 24 hours before the sexual behavior test,
and estradiol（10μg）4 hours before the test. Female rats were
put in a cage with male rats and monitored for 30 minutes. Results Body weight at PND 14 was significantly lower in MS
group than in C group, respectively（p＜0.05）. VO and numberof estrous did not differ between the groups. Parameters of sexual behavior at 12 week did not differ between C group and MS
group；Number of darts（C：41.3±12.2times, MS：36.5±10.1）,
Number of ear wiggles（C：20.2±6.0, MS：23.3±8.2）, Lordosis
quotient（LQ）（C：56.8±10.2%, MS：52.4±10.6）, Lordosis rating（LR）（C：0.86±0.21, MS：0.77±0.18）. The sexual behavior at
14 week also did not differ between the groups. Conclusion Psychological stress in early life did not influence on sexual maturation and sexual activity in female rats.

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ISP-56-3
Nine cases of Turner syndrome with differences in menstrual
abnormality and physical findings Makiho Ishibashi1,
Takafumi Watanabe1, Miki Ohara1, Toshifumi Takahashi2,
Hiromi Komiya1, Hideki Mizunuma2, Keiya Fujimori1 Fukushima
Medical University 1, Fukushima Medical Center of Children and
Women 2The structural abnormality of the X chromosome is characterized by phenotypes such as short stature and amenorrhea, depending on the site of the abnormalities. We here report the diagnostic indications and phenotypes of nine cases of Turner syndrome observed in our department. Regarding the diagnostic indications, two patients were diagnosed at school age due toshort stature. One patient was diagnosed in her late teens due tolack of secondary sex characteristics. Six patients were over theage of 20 years at the time of their respective diagnoses, whichwere made because of infertility and primary amenorrhea. In
patients with short stature and external malformations such as
underdevelopment of the external genitalia, and in case of infertility and no response to ovulation induction, the period until the
execution of until chromosome analysis was short. On the other
hand, the period until diagnosis tended to be longer in the six
patients, who did not have desire of pregnancy, and weretreated for secondary amenorrhea. Regarding menstruation abnormality and karyotype, primary amenorrhea was found in fivecases, and their karyotype were monosomy, disomy and ring
chromosome（with mosaicism）, or the breakpoint of X autosomal chromosome was Xq21.1. Secondary amenorrhea was observed in three cases, and the breakpoint of the X autosomal
chromosome and deletion were regions of Xq22 qter. One patient with first degree secondary amenorrhea had unbalanced
X autosomal translocation, and her phenotype and menstrual
disorder were mild because of the inactivation of the derivative
X chromosome and the small deletion such as Xq28 qter.

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Tsukuda1, Yuki Mori1, Toyomi Satoh1 University of Tsukuba 1,
Ibaraki Prefectural Central Hospital 2
For the patients with vaginal agenesis, vaginoplasty is an essential treatment. Vaginoplasty includes both nonsurgical and surgical treatments. The nonsurgical method is safe and easy to
perform；therefore it is considered as a firstline treatment. In
our hospital, vaginal dilation using uterine cervical dilators
named Hegar dilators is performed on patients with Mayer
Rokitansky Kuster Hauser syndrome, and on patients undergoing vaginoplasty to prevent vaginal stenosis after the procedure.
This study reports five patients successfully treated with thismethod. Out of four patients with MRKH syndrome, two lacked
a vagina completely, and two had a shallow vagina. Gynecologists initiated dilation with an adequately sized cervical dilator,
which made a 3 cm deep cavity in the external genital area. After the examination, they instructed patients on how to use thedilator, and patients continued self dilation daily at home. Patients visited the hospital every month for further instructions.
The size of the dilator was gradually increased, until the vaginalcavity extended to 6 cm in depth with a No.30 dilator. The duration needed to achieve the end point was between 5 and 20
months. One patient had a congenital vaginal aplasia with a normal uterus. Following surgical vaginoplasty, she underwent avaginal dilation to prevent vaginal stenosis. After other types ofvaginal dilators failed at vaginal dilation, Hegar dilator proved
effective. All patients were successfully treated without complications. However, a large scale study is required to confirm theefficacy of this method.

ISP-56-5
The retrospective analysis of 53 patients of primary amenorrhea Yuri Miyahara1, Yasuhiko Kamada1, Hirofumi Matsuoka1,
Shiho Fujita1, Kotaro Kubo1, Ai Sakamoto1, Sayoko Kotani1,
Hisashi Masuyama1, Mikiya Nakatsuka2 Okayama University 1,
Faculty of Health Sciences, Okayama University 2
Objective Primary amenorrhea is defined as the absence ofmenstruation at the age of 18 years. It may be caused due tovarious conditions. This study aimed to identify those conditions
and assess their diagnosis and management. Methods A retrospective study was conducted between January 2004 to July
2017, during which 53 cases were analyzed. In this analysis, we
also included patients with delayed menarche. Results The median age of patients at their first visit was 19 years［15 35（median, range）］,which is greater than that in the existing reports.
The chief complaint of 48 patients was amenorrhea. Out of the
53 cases, 27 had uterine amenorrhea（Mayer Rokitansky
Kuster Hauser syndrome）, 13 had hypothalamic and pituitarydisease, 6 had ovary related amenorrhea, 4 had outflow tract
disorders, 2 had polycystic ovarian disease, 2 had symptomatic
amenorrhea, and 1 had gonadal dysgenesis. There is some overlapping. 24 patients were analyzed based on chromosomal tests,
and 3 abnormalities were detected. 19 patients received hormone replacement therapy, and 21 patients underwent surgicaland nonsurgical techniques for vaginal reconstruction. Conclusion Some patients with primary amenorrhea, depending on
their disorders, face difficulty in conception. Sometimes, their
sex differs from their perceived gender. Therefore, careful
physical examination and systematic evaluation are imperative
for a proper diagnosis. Additionally, we should pay proper attention to the provision of physical and/or mental support to suchpatients.

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ISP-56-4

ISP-57-1

Five patients with vaginal agenesis treated using non surgicalvaginoplasty using uterine cervical dilators Akiko Kawasaki1,
Hiroko Ijiri1, Hiroyuki Yoshikawa2, Iku Gamada1, Yoko

The role of endometrial and uterine vascular status measurement in predicting pregnancy outcome in frozen thawed embryo transfer cycles Byung Kyoo Park, Moo Sung Jo, Jong-Kil

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ISP-57-2
Endometrial Receptivity Array：Retrospective Review ofReproductive Outcomes Among Patients with Personalized
Embryo Transfer（pET）Justin Tan1, Arohumam Kan1, Samer
Tannus3, Gary Nakhuda1,2 University of British Columbia, Canada 1, Olive Fertility Centre, Canada 2, McGill University HealthCare Centre, Canada 3
Human implantation is an intricate process that requires synchronous dialogue between a healthy embryo and a receptive
endometrium. In the context of in vitro fertilization（IVF）, aneuploid embryos which lack developmental competence likely account for the most common cause of implantation failure；however, even euploid, morphologically normal blastocysts fail to
implant in about 1/3 of transfers. Endometrial receptivity represents another potential cause of implantation failure andthrough advances in proteomic analysis, an endometrial receptivity array（ERA）has been developed to accurately and reproducibly identify endometrial receptivity status. The clinicalbenefit of such an assay, however, is still undergoing further investigation. In this retrospective review, we investigatedwhether the contribution of the endometrial factor could be
identified with the ERA test, particularly in patients with a history of euploid blastocyst implantation failure. Among 88 patients who underwent ERA testing at a private clinic in Vancouver, Canada, between October 2014 January 2017, 81（92.1%）had
a history of implantation failure, 48 underwent euploid embryotransfer with CCS, and 19（40%）were determined to have an unreceptive endometrium on initial ERA biopsy. After personalized embryo transfer（pET）, we found that implantation and ongoing pregnancy rates were improved（73.7% vs. 54.2% and63.2% vs. 41.7%, respectively）compared to patients without
pET, although differences were not statistically significant ow-!

ing to small sample size. Hence, larger prospective studies are
required to validate our findings. Nevertheless, our experiencedemonstrates that pET among patients with a non receptive endometrium yields improved reproductive outcomes. Hence,
there is likely clinical benefit to identifying the personal window of implantation（WOI）with ERA.

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ISP-57-3
Retrospective study on the clinical efficacy of single embryotransfer（SET）for IVF adverse cases；a single IVF center
Kaori Shinya, Chuyu Hayashi, Erina Kato, Remi Hasegawa,Yuki Okuma, Erina Hashimoto, Akiko Kasuga, Atsushi
Komatsu, Yasuji Miyagawa, Shinichi Takada, Fumihisa
Chishima, Kei Kawana Nihon University
Objective Single embryo transfer（SET）is recommended to
avoid multiple pregnancy following IVF ET. Double embryotransfer（DET）has been also acceptable only for repeated IVF
failures or elder cases. Indication of SET could extend to suchadverse cases because of recent technical innovation. We here
examined whether SET including frozen embryo transfer is effective for the cases. Methods Under the informed consents, 212
cycles of SET during 2013 2017 in our hospital were investigated. Clinical pregnancy and live birth rates were comparedwith the nationwide IVF ET data（2014）reported by JSOG using Fisherʼs exact test. Cumulative pregnancy rates after SET
were also investigated focusing on over 40 years old cases. Results Clinical pregnancy rates following SET were 20.2%, 22.4%
and 10.2% for all, 35 39, and 40 45 years old cases, respectively,
which were worse than JSOG data. In turn, live birth rates following SET were 16%, 15.8% and 7.1% for all, 35 39, and 40 45
years old cases, respectively, which were equivalent to JSOG
data. The cumulative pregnancy rates at third and fifth SET
were 51% and 79%, respectively. As for over 40 years old cases,
the rates at third and fifth SET were 35% and 74%, respectively.
There was no difference in the rate at fifth SET between all andover 40 years old cases. Conclusion Live birth rate following
SET was equivalent to that of JSOG data regardless of age. The
cumulative pregnancy rates caught up at fifth IVF even thoughover 40 years old cases. These data suggested that SET might
be effective for IVF adverse cases.

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ISP-57-4
Cases that needed GnRH agonist in artificial FET cycle Yuri
Yamamoto1, Akira Kuwahara1, Ayaka Tachibana1, Kenji
Hinokio2, Minoru Irahara1 Tokushima University 1, Shikoku
Medical Center for Children and Adults 2
Objective Recently, it has reported that GnRH agonist does not
influence clinical pregnancy rate, but there were sometimes
cancellation cycles due to premature ovulation. Therefore we
extracted the cases which had spontaneous ovulation during
HRT FET cycle and examine the case considered that additionof GnRH agonist was appropriate. Methods Between January
2016 and December 2016, data from HRT FET cycles involving
164 cycles, 115 cases were analyzed. Estradiol patch gradually
was increased and on day 14, endometrial thickness was measured. After that, Chlormadinone Acetate was started, and FET
was performed 6 days after progestin initiation. If follicle
growth or premature ovulation were detected by ultrasoundscan, serum hormone levels were analyzed. Serum P level over1.5ng/ml, the cycle were cancelled. We compared follicle
growth group（group A, n=5）and ovulation group（group B, n=4）and non follicle group（group C, n=106）about age, basic
FSH level, the oocyte collection number. Results Mean age andbasal FSH level were significantly higher in group A（41.4±2.1
years, 14.7±12.4IU/ml）and group B（40.5±2.6 years, 17.9±6.0
IU/ml）than group C（36.5±4.3 years, 6.3±2.5U/ml）.Oocyte col-

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ISP

Joo, Kyu Sup Lee, Byung Su Kwon, Yoon Hwa Kim, Sul Lee,
Ka Yeong Yun, Dong Soo Suh, Ki Hyung Kim, Hyun Joo Lee,
Sieun Han Pusan National University Hospital, Korea
Objective An appropriate endometrial condition and vascularsupply are usually known as essential for implantation of embryo. This study was performed to assess the role of endometrial and uterine vascularity status measurement in predicting pregnancy outcome during frozen thawed embryotransfer（FET）cycles. Methods After endometrial preparation,
vitrified blastocysts were thawed and assisted hatching by zonadissection was performed. On the day of embryo transfer（ET）,
endometrial thickness（EMT）,resistance index（RI）and pulsatility index（PI）of sub endometrial artery（SEA）and uterine
artery（UA）were obtained by transvaginal sonography（TVS）.
All women were divided into pregnant or not groups, and thesevariables were compared between 2 groups. Results Patientsʼ
general demographic characteristics werenʼt different statistically between pregnant and nonpregnant groups. The overall
implantation rate, clinical pregnancy rate, and ongoing pregnancy rate were 31.1%, 41.4% and 28.6%, respectively. 29 Patients who conceived had average EMT, RI of SEA, PI of SEA,
RI of UA, and PI of UA values of 9.15mm, 0.91, 2.42, 0.95, and 3.37,
respectively. 41 Patients who didnʼt conceive had average EMT,RI of SEA, PI of SEA, RI of UA, and PI of UA values of 9.31mm,
1.01, 2.56, 0.94, and 3.00, respectively. In two groups, all variables
were not statistically different（p＞0.05）. Conclusion Measurement of endometrial thickness and blood flow index of uterus
and endometrium by transvaginal sonography during frozen
thawed embryo transfer（FET）cycles canʼt seem to predict the
pregnancy outcome. But endometrial receptivity is thought tobe still important factor in successful implantation of FET cycle
and many studies agree that high degrees of endometrial perfusion shown by Doppler sonogram suggests more receptive endometrium.

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lection number were 10.2±5.1 in group A, 7.5±7.1 in group B,
13.3±7.8 in group C. FSH＞15IU/ml was only two cases ingroup C. Conclusion It was revealed that premature ovulation
tended to be easy to happen during HRT FET without GnRH
agonist in advanced age, the ovarian failure such as FSH＞15
IU/ml and desirable for use GnRH agonist.

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ISP-57-5
Impact of ovarian stimulation protocols on perinatal outcomes in fresh single embryo transfers：Analysis of 36,469
singleton deliveries in Japanese Assisted Reproductive Technology Registry between 2007 and 2013 Seungchik Jwa1, Akira
Nakashima5, Akira Kuwahara2, Kazuki Saito3, Minoru Irahara2,
Osamu Ishihara1, Hidekazu Saito4 Saitama Medical University 1,
Tokushima University 2, Tokyo Medical and Dental University 3,
National Center for Child Health and Development 4, Sora noMori Clinic 5
Objective To investigate whether ovarian stimulation protocols
affect perinatal outcomes in fresh embryo transfer（ET）cycles.
Methods A retrospective cohort study was conducted using
Japanese assisted reproductive technology（ART）registry between 2007 and 2013. A total of 36,469 singleton deliveries bornafter fresh single ET were included. Ovarian stimulation protocols include natural（n=3,942）, clomiphene citrate（CC）（n=4,594）,CC+gonadotropin（n=5,218）, Gonadotropin releasing hormone（GnRH）agonist（n=15,651）and GnRH antagonist（n=7,064）.
Main outcomes were still birth, Cesarean section（CS）,preterm
delivery（PTD）,low birth weight（LBW）, very low birth weight（VLBW）, small for gestational age（SGA）and large for gestational age（LGA）. Odds ratios（ORs）and 95% confidence intervals（CIs）were calculated using a generalized estimating equation adjusting for correlations within institutions and confounders of year, maternal age and infertility diagnosis. Results
Compared with natural cycle, ovarian stimulation cycles wereassociated with significant increased risk for PTD, LBW and
SGA（p＜0.01）. Especially, ovarian stimulations using CC+gonadotropin demonstrated highest increased risks for LBW and
SGA（adjusted OR［95% CI］：1.68［1.48 to 1.92］for LBW（p＜0.001）, and 1.82［1.57 to 2.11］for SGA（p＜0.001））,and further
associated with significant increased risk for stillbirth（2.52［1.30
to 4.91］, p＜0.006）,CS（1.13［1.02 to 1.24］, p＜0.017）and VLBW
（2.65［1.51 to 4.6］,p＜0.001）.Ovarian stimulation using CC without gonadotropin demonstrated similar significant associations
except stillbirth. Conclusion Ovarian stimulation was associated with adverse perinatal outcomes of PTD, LBW and SGA.
Ovarian stimulations using CC may have adverse effect on perinatal outcomes in fresh ET.

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ISP-57-6!

A long term cohort study on 3,509 babies born through assisted reproductive technology（ART）for 6 years of age
Kensuke Akitsu, Tomoya Hasegawa, Akina Yamanaka, Keiko
Ueno, Naoaki Kuji, Hirotaka Nishi Tokyo Medical University
Hospital
Objective There are still few clear studies that investigate
long term prognosis of children born from ART. Therefore, thisstudy aimed to investigate that the difference between thegrowth and development of singleton children conceived after
different infertility treatments and those conceived naturally at
6 years of age. Methods A total of 4,095 mothers who conceived
through ART at 26 clinics in Japan, participated in the study between October 1, 2008 and November 30, 2009, and informed
consent was obtained from all patients before entering thestudy. Each baby was born after frozen embryo transfer（FET,
n=1,223）, fresh embryo transfer（FrET, n=1,005）, or natural conception（NC, n=1,281）. The data on their growth and develop-!

ment（Weight, height, KIDS scale）at 18 months and 6 years ofage were obtained using a questionnaire. Results Finally, 1,582（45.1%）participants undertook the follow up survey. The birthweight of singleton children conceived via FET, FrET, and NC
was 3,071, 3,017, and 2,998 g；that at 6 years of age was 20.3, 20.4,
and 19.7 kg, respectively. The birth height of singleton children
conceived via FET, FrET, and NC was 49.1, 49.0, and 48.5 cm；
that at 6 years of age was 114.8, 115.3, and 114.2 cm, respectively.
On the other hand, there was no significant difference in the
KIDS score between each treatment group at 6 years of age（p＜0.05）. Conclusion At 6 years of age, the weight and height ofchildren conceived through ART are higher than those of children conceived naturally.

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ISP-57-7!

Hysteroscopy performed at mid luteal period of previous cycle of ART treatment did not improve the uterine receptivity
for embryo but might cause the over invasive examination
Kyoko Nishimura1, Jun Kawagoe1, Koki Matsuo1, Isao Takehara1,
Jun Matsukawa1, Hideki Igarashi2, Satoru Nagase1 Yamagata
University 1, Kyono ART Clinic 2
Objective Though several methods are reported that may improve the uterine receptivity for embryo and the success ratioof artificial reproductive technologies（ART）,their usefulness isstill controversial. Since hysteroscopy was one of those reported
methods, we evaluated if the hysteroscopic examination is practically useful or not. Methods Between May, 2016, and April,2017, we performed 180 cycles（129 in vitro fertilization（IVF）cycles and 51 frozen embryo transfer（FET）cycles）of
hysteroscopy at the mid luteal period of the previous cycle of
ART treatment and compared their outcome of ART with theimmediate treatment cycles which did not undergo hysteroscopy. We also examined the adverse outcome of hysteroscopy. Patient allocation depended on the choice of each patients after the information was provided. Statistical analysis
was performed by Studentʼs t test. Approval of the ethics committee was obtained. Results Among the hysteroscopy group for
IVF, 73 cycles（56.6%）could undergo fresh embryo transfer（ET）, but 56 cycles could not（26 performed all embryo freezing；21 did not acquire embryos；9 canceled IVF）
. Within thehysteroscopy group for FET, 42 cycles（82.4%）could undergoET, but 9 canceled ET. Endometrial polyp was found in 2 cycles（1.1%）. One cycle developed the pelvic inflammatory disease.
There were no statistical differences in age of patients, treatment number, pregnancy ratio, and miscarriage ratio between
hysteroscopy group and immediate treatment group. Conclusion Hysteroscopy does not improve pregnancy rates. Moreover, almost half of cycles canʼt undergo ET after hysteroscopy
cycle. Therefore, routine hysteroscopy has less reasonability forrecommendation.

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ISP-57-8
Treatment outcome of In Vitro Fertilization―Embryo transfer in patients who have treated abnormal thyroid function
Chiaki Heshiki, Keiko Mekaru, Maho Miyagi, Kozue Akamine,
Yoichi Aoki University of the Ryukyus
Objective It is known that an abnormal thyroid function increases the risk of infertility and miscarriage, although it remains unclear whether a treated abnormal thyroid function affects the treatment outcomes of IVF ET. We therefore evaluated the treatment outcomes of IVF ET in patients with an abnormal thyroid function. Methods We retrospectively analyzed
the first IVF ET cycle of 209 women from 2009 to 2015. Three
analyses were conducted：（1）treated abnormal thyroid function vs. normal thyroid function；（2）TSH level of ＜2.5 μU/mL
vs. that of ＞2.5 μU/mL；and（3）hypothyroidism with autoim-

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The comparison between mechanical and laser assisted hatching in Frozen thawed blastocyst transfer cycles：A retrospective study of clinical outcomes Moosung Jo, Hyunjoo Lee,
Kayeong Yun, Hyunnyung Jo, Seungchul Kim, Sul Lee,
Hyekyung Noh, Seoyoon Hwang, Lee Youngjoo, Lee Sieun,
Jong-Kil Joo, Kyusup Lee Pusan National University Hospital of
Korea, Korea
Objective We widely had used either mechanical assisted hatching（MAH, partial zona dissection）or laser assisted hatching（LAH）in frozen thawed embryo transfer program. Therefore
we decided conduct a retrospective study, aiming to compare
clinical outcomes after MAH or LAH in women of frozen
thawed blastocyst transfer undergoing ART. Methods A total of
206 AH cycles（101 MAH and 105 LAH）were performed fromthe January 1, 2014 until the December 31, 2016 at infertility
center, Pusan National University Hospital in Busan, Korea. All
AHs were included by autologus single or double frozen
thawed blastocysts transfer. Results The implantation rates per
ET cycle was 55.1% in MAH group and 49.5% in LAH group（p=0.40）. The clinical pregnancy rates per ET cycle was 42.6% in
MAH group and 43.8% in LAH group（p=0.86）, and the ongoing
pregnancy rates was 37.6% in MAH group and 33.3% in LAH
group（p=0.52）. In our all clinical outcomes, the implantation
rates, clinical pregnancy rates, ongoing pregnancy rates were
not showed differences between MAH and LAH groups. Conclusion No significant differences were noted in implantation, clinical and ongoing pregnancies between the two test group, laser
and mechanical techniques. Although not significant, both implantation and ongoing pregnancy rates were higher in MAH
group, but clinical pregnancy rates were higher in LAH group.

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The efficacy of in vitro Fertilization（IVF）in treating vaginismus causing infertility：a retrospective analysis of 13 cases
Ying-Wen Wang, Kuo-Chung Lan Kaohsiung Chang Gung Memorial Hospital, Taiwan
Objective The purpose of this study was to retrospectively review the cases of severe vaginismus causing infertility and theoutcome after receiving IVF treatment at Kaohsiung Chang
Gung Memorial Hospital. We analyzed the demographic features, average oocyte pick up number, embryo quality, pregnant outcome and way of delivery among these patients. Methods We reported a case series of women suffering from severevaginismus and infertility. In this retrospective study, 13 patients with vaginismus treated with IVF between 1998 and 2017at our hospital were analyzed. Results The mean duration of infertility before their seeking intervention was 5.3 years at the
average age of 34.5. The average oocyte pick up number was!

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6.5. 11 out of the 13 patients became pregnant after IVF treatment with pregnancy rate 54.2% per cycle. Most of these womenchoose cesarean section when delivery. Conclusion Cognitive
behavioral therapy seems to be the mainstay treatment for vaginismus based on current literature review. However, if a women
visited Obstetrics/Gynecology doctor directly for infertility,
IVF is also a solution for women with severe vaginismus causing infertility based on the satisfactory outcome.

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munity positive vs. negative. Results In analysis（1）, there wereno significant differences in clinical pregnancy rate, miscarriage
rate, and birth weight between women treated for abnormal
thyroid function（n=34）and those with a normal thyroid function（n=175）. No woman in the treated abnormal thyroid functiongroup had perinatal complications. In analysis（2）, there were no
significant differences in the clinical pregnancy rate, miscarriage rate, and birth weight between women with hypothyroidism with TSH levels of ＜2.5 μU/mL（n=22）and ＞2.5 μU/mL（n=7）. In analysis（3）, there were no significant differences in
the clinical pregnancy rate, miscarriage rate, and birth weightof women with hypothyroidism who were either thyroid autoimmunity positive（n=10）or negative（n=19）. Conclusion If treated,abnormal thyroid function will not compromise the IVF ET
treatment outcomes or perinatal outcomes, regardless of TSH
threshold or thyroid autoimmunity.

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Shall we Pause PGS? Shizuko Takahashi1, Pasquale Patrizio2
The University of Tokyo 1, Yale University, USA 2
Objective Japan, just began preimplantation genetic screening（PGS）this year since there seems to be increasing evidence andis performed in the US and Europe. In the US, approximately
22 33% of all cycles utilize PGS. Marketed for several decades,
PGS advocates are pressuring and criticizing those restricting
PGS as unethical. However, while PGS is increasingly performed worldwide, some institutions in the US are beginning to
put PGS on pause. We explore the ethics of performing tests
without sufficient evidence. Methods A review of the previous
publications on PGS, focusing on controversies. Comparing publications from the US and from Europe. Results Two major factors contribute to this pause ：the ongoing absence of a convincing randomized control trials using appropriate populations
and outcome measures, and human failure to presume that technology can accurately predict an embryoʼs intrinsic nature toerr and self repair during its development. For patients to discard or transfer what has been diagnosed abnormal of a developing embryo can mean embryo loss or burden the pregnancy.
For providers, distress of ethically providing a test that has limited evidence, and explaining what abnormal truly means without inflicting a patient is challenging. Conclusion Countries andinstitutions should always consider sufficient evidence prior toincorporating testing, even if it has been marketed over decades
and seem less controversial with technological advancements.
Despite demands from patients and pressures from society, institutions and countries should boldly put a testing on pause.
Results from the pilot study will help to reveal the truth.

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A comparative retrospective study between controlled hyper
stimulation and mild stimulation protocol for women with
low AMH value Rena Toriumi, Takashi Nagashima, Yukiko
Matsuzawa, Yoichi Kobayashi, Mitsutoshi Iwashita Kyorin University HospitalObjective Despite small number of oocytes in oocyte retrieval
and low clinical pregnancy rates, there is no consensus aboutovarian stimulation protocol for women with low Anti Müllerian hormone（AMH）value, which has been studied about thepotential clinical utility for assessment of follicle reservation.
The purpose of this study was to assess clinical outcomes andclarify appropriate stimulation protocol for women with low
AMH value. Methods In cases of oocyte retrieval in our hospital,
we assessed 78 cycles, 34 from younger than 40 years and 44 cycles from older than 40 years, with low AMH value. The cycles
were also divided two groups；controlled hyper stimulationgroup and mild stimulation group. We compared total numberof obtained oocytes and clinical pregnancy rates of these groups
depending on the age. Results In the cycles from younger than
40 years, the total number of obtained oocytes and clinical pregnancy rates were not differences between controlled hyper
stimulation group and mild stimulation group. Meanwhile, inthe cycles from older than 40 years, there were also no differences between controlled hyper stimulation group and mild
stimulation group in the total number of obtained oocytes and

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clinical pregnancy rates. Conclusion From our results, it is indicated that there was no change about the total number of obtained oocytes and pregnancy rates between controlled hyper
stimulation and mild stimulation in case of low AMH value.

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The interval between oocyte retrievals was not correlatedwith the number of eggs retrieved Takeshi Fukunaga, Isao
Takehara, Jun Kawagoe, Kyoko Nishimura, Jun Matsukawa,
Michi Nishi, Koki Matsuo, Hideki Igarashi, Satoru Nagase Yamagata University
Objective In assisted reproductive technology（ART）,patients
often undergo repeated oocyte retrievals because of the failureof their treatment. People have thought that the extension of interval between oocyte retrievals may increases the number of
retrieved oocytes compared to shorter period. However, the appropriate interval between oocyte retrievals is unclear. Therefore, we examined whether the interval between oocyte retrievals should be increased to improve ovary function. Methods We
used the ART database of our Hospital（May 1989 to September2016）and evaluated 392 cycles in 157 patients who underwent
two or more consecutive ovarian hyperstimulation using thelong protocols of GnRH agonist. Intervals of more than 6 months
were excluded to avoid the effects of ovarian aging. We measured the correlation between the interval period of oocyte retrievals and 1）the changes of oocyte number of second or third
oocyte retrievals from the one of the first treatment, 2）the volume of injected gonadotropin, or 3）the success of pregnancy.
We used Spearmanʼs rank order correlation and Mann Whitney
U tests for statistical analysis. Approval of the ethics committee
was obtained. Results There were no significant relationships
between the interval of oocyte retrievals and the number of retrieved oocytes（correlation coefficient： 0.04, p=0.52）, the total
volume of injected gonadotropins（p=0.83）, or pregnancy outcomes（p=0.08）. Conclusion The interval between oocyte retrievals may not affect the number of retrieved oocytes. Extending the interval of oocyte retrieval to wait for recovery of ovary
function may not be required.

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ISP-58-6

successful live births and the cost of social egg freezing should
be provided to patients to aid in the decision making process ofthe patients.

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Successful delivery in a 44 year old woman using vitrified
human oocytes taken from the woman at 41 years of age
Miyako Funabiki1, Sagiri Taguchi1, Masako Karita1, Yoshihiro
Tada1, Terumi Hayashi1, Yuri Iwaki1, Takashi Matsubara1,
Takeharu Ohta2, Kazunori Maeda1, Yoshitaka Nakamura1 Oak
Clinic 1, Oak Clinic GINZA 2
Successful pregnancies and deliveries are rare in women over
40 years of age. To date, no case report has been published about
a successful delivery in a woman over 40 years of age using vitrified oocytes obtained through social egg freezing from awoman over 40 years of age. Here we report a case of a successful live birth from a 44 year old woman using vitrified oocytes
taken from the woman at 41 years of age. In addition, the technique using vitrified oocytes was used for social reasons. The
44 year old patient delivered a 2,534 g female infant by Caesarean section in the 37th week of pregnancy. The Apgar scores forthe female infant were 9 at 1 min and 9 at 5 min. The female infant exhibited no anomalies and is developing normally under
the close surveillance of pediatricians. In addition, the 44 year
old patient provided written informed consent. And, the clinicalstudy was approved by Institutional Review Board（IRB）at ourclinic. However, the concept of social egg freezing has medical,
ethical and social problems. Furthermore, the rate of live births
differs among clinics or hospitals due to variations in the vitrification and warming techniques used. Therefore, informationfrom individual clinics or hospitals about the risks, the rates of

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Effect of resveratrol supplementation during embryo transfer on IVF outcomes in infertile women：a cross sectional
study Asako Ochiai1, Keiji Kuroda1, Yuko Ikemoto1, Rie Ozaki1,
Keisuke Murakami1, Makoto Jinushi1, Koji Nakagawa2, Rikikazu
Sugiyama2, Mari Kitade1, Atsuo Itakura1 Juntendo University
Hospital 1, Sugiyama Ladies Clinic 2
Objective Resveratrol is a polyphenolic compound and naturalactivator of sirtuin（SIRT）1. Based on animal experiments, resveratrol has been mooted as a potentially therapeutic and preventive agent for cell senescence including ovarian aging. Clinical trials have not been performed to evaluate the impact of resveratrol on implantation and pregnancy outcome in humans. Recently, we showed that resveratrol inhibits decidualization ofhuman endometrial stromal cells in vitro. This study was performed to clarify the impact of resveratrol supplementation on
in vitro fertilization（IVF）outcomes in embryo transfer（ET）cycles. Methods This single center, cross sectional retrospective
study（2012 to 2014）was designed to compare the outcomes of
ET in women with taking resveratrol supplementation（200 mg/d）during luteal phase or not. Out of 7,520 ET cycles, we excluded 1,097 cycles with poor prognostic factors：44 years old
and over and ET with morphologically poor quality embryos（Veeck classification, grade 4 and 5）. We compared the resveratrol（RES）group（205 cycles in 101 women）and control（nonRES）group（6,218 cycles in 3,831 women）.Odds ratios（OR）and
95% confidence intervals（CI）were calculated by multivariate
logistic regression after controlling potential confounders：patient age and transferred embryo grade. Results Statisticalanalysis showed significantly lower implantation rate（OR=0.72；95% CI 0.49 1.06）, lower clinical pregnancy rate（OR=0.54；95%CI 0.34 0.85）and higher miscarriage rate（OR=2.6；
95%CI 1.06 6.34）in the RES group compared to the non RES
group. Conclusion In line with the adverse effect of resveratrol
on decidualization of primary endometrial cultures, supplementation during luteal phase appears detrimental for IVF outcomes, although additional studies are warranted.

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A Study on the usefulness of hysteroscopy for ET repeated
failure cases in ART Yusuke Fukuda, Yukiko Katagiri Toho
University Omori Medical Center
Objective Chronic endometritis is one of reason for implantation
failure. We studied on the usefulness of hysteroscopy for ET repeated failure cases in ART. Methods We investigated 18 casesof ET repeated failure which were conducted from January 2016
to March 2017. Olympus HYF TYPEV was used as hysteroscopy. They were treated by internal use of antibiotic for
two weeks and more after hysteroscopy. Dividing them into
pregnancy and non pregnancy groups who got and didnʼt get
pregnant after hysteroscopy, respectively, hysteroscopy findings were compared and treatment cycle until pregnancy aswell as pregnancy rate were calculated for pregnancy group.
Square test and t test were used. Results Of 18 cases in total, 6
and 12 cases were pregnancy group and non pregnancy group,
respectively. The average number of ET failure were 4.3（2 11）.
Age of pregnancy group（median value：35.0）was significantly
younger than that of non pregnancy group（median value：
39.0）. Conclusion Hysteroscopy is useful for ET repeated failurecases in ART with relatively less age factor. In consideration of
the fact that pregnancy has been achieved in pregnancy groupduring the first treatment cycle after hysteroscopy, it is be-

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lieved that other cause should be sought for cases with hysteroscopy findings that pregnancy has not been achieved evenafter treatment. It is believed to be necessary to review whether
hysteroscopy should be positively introduced before startingART.

The regulation of endoplasmic reticulum stress improved thedevelopment of aged oocytes Isao Takehara1, Hideki Igarashi2,
Jun Matsukawa1, Satoko Suzuki1, Koki Matsuo1, Jun Kawagoe1,
Satoru Nagase1 Yamagata University 1, Kyono ART Clinic 2
Objective In assisted reproductive technology, the number oftreatment cycles required for aged women is increasing. Advanced maternal age results in the deterioration of oocyte quality, but the exact cause is unknown. We focused on the endoplasmic reticulum stress（ERS）reported in various aging relateddiseases and examined the relationship of ERS with the qualityof aged oocytes and whether the control of ERS improved oocyte quality. Methods We used 5 week old B6C3F1 female
mice and 10 week old ICR male mice. We defined oocytes released from the oviduct at 13 h and 19 h after hCG induction as
fresh and aged, respectively. We compared（A）embryo
development and（B）GRP78 expression（a chaperone proteinincreased by ERS）in fresh and aged oocytes and embryos. Furthermore, using aged oocytes treated with salubrinal（to control
the effects of ERS on the PERK pathway）, we compared（C）embryo development,（D）the expression of GRP78 and p eIF2a（phosphorylated via the PERK pathway）, and（E）the rate ofdead cells in blastocysts with untreated aged oocytes. Results（A）The development of aged embryos was significantly poorer.
（B）GRP78 expression was higher in aged oocytes.（C）Salubrinal treated aged embryos showed improved development.（D）In salubrinal treated aged oocytes, lower GRP78 and higher p
eIF2a expression were observed.（E）In salubrinal treated aged
blastocysts, fewer dead cells were found. Conclusion Aged oocytes were more influenced by ERS than fresh oocytes were. Salubrinal improved the development of aged embryos. The regulation of ERS can be a breakthrough treatment for the aged oocytes.

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ISP-59-2
Novel antigens involved in ovarian autoimmunity in POI（primary ovarian insufficiency）, and their localization and function in the human ovary Satoko Osuka, Akira Iwase, Yukiyo
Kasahara, Sayako Yoshita, Ayako Muraoka, Shotaro Hayashi,
Natsuki Nakanishi, Takashi Nagai, Tomohiko Murase, Maki
Goto, Fumitaka Kikkawa Nagoya University
Objective Previous studies indicated an association between
POI and autoimmunity. We analyzed the sera of POI patientswith thyroid autoimmunity（TA）, in order to identify the antigens involved in ovarian autoimmunity（OA）and analyze their
biological functions. Methods IP products of patients（POI patients with/without TA, and control patients）sera and proteinfrom the granulosa cell line（HGrC1）were analyzed using mass
spectrometry to identify the antigens involved in OA. We confirmed the expression of the identified antigens in the ovary
samples. HGrC1 were used for evaluating the functions of theseantigens. The recombinant antigens were produced using HEK
293T. Results POTE E/F were identified as the candidate antigens using mass spectrometry. POTE（prostate, ovary, testis
and placenta）genes expressions in ovaries has been reported
but the functions werenʼt well established. Immunohistochemistry of the human ovary revealed POTE E/F staining in granulosa cells and oocytes, moreover, the intensity were changed indifferent stages of follicle development. TSH treatment in HGrC
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ISP-59-1

tivity than control subject. POTEF siRNA transfection in HGrC
1 downregulated POTEF gene expression, meanwhile, proliferation activity was increased. Recombinant human POTEF protein were produced from whole length cDNA. Conclusion Proteomic analysis identified POTE proteins as candidate antigens
involved in OA. POTE expression levels were changed in different stages of follicle development, and may affect the proliferation activity of HGrC1. In future, revealing the functions of
POTE proteins may help in elucidating POI pathogenesis, furthermore, quantification of the antibody using recombinant protein could be a marker for detecting pre POI patients.

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The effects of chronic testosterone administration on bodyweight, food intake, and fat weight were changed age dependently Takeshi Iwasa, Toshiya Matsuzaki, Rie Yanagihara,
Mayila Yiliyasi, Kiyohito Yano, Minoru Irahara Tokushima University
Objective To examine whether androgens effects on bodyweight（BW）, food intake（FI）and body composition might bechanged age dependently, the effects of chronic testosterone（T）administration were evaluated in rats of different ages.
Methods Young（10 weeks of age）and middle aged（12 monthsof age）rats were randomly assigned to either the T administered or the non administered group. Silastic tube filled withcrystalline T and empty tube was implanted in T administeredgroup and non administered group, respectively. BW and cumulative FI were assessed every week, and the rats were sacrificed
by decapitation at 4 weeks after the implantation. The weights
of visceral and subcutaneous fat were assessed, and blood andbrain were harvested. Serum leptin and hypothalamic NPY
mRNA levels were measured to evaluate leptin resistance. Results Although chronic T administration increased BW gain, FI,and feed efficiency in both young and middle aged rats, it increased visceral fat weight only in middle aged rats. Therefore,
it is possible that T promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of T increased theserum leptin level, it did not alter hypothalamic neuropeptide Y
mRNA level in middle aged rats. On the contrary, such T induced changes were not observed in young rats. Thus, T might
induce hypothalamic leptin resistance, which could lead to fat
accumulation in older individuals. Conclusion T might disrupt
the mechanisms that protect against adiposity and hyperphagia
and represent a risk factor for excessive body weight and obesity, especially in older females.

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Impact of vitamin D supplementation on preconception immune tolerance in infertile women Yuko Ikemoto1, Keiji
Kuroda1, Koji Nakagawa2, Asako Ochiai1, Rie Ozaki1, Keisuke
Murakami1, Makoto Jinushi1, Rikikazu Sugiyama2, Satoru
Takeda1 Juntendo University Hospital 1, Sugiyama Clinic 2
Objective Successful pregnancy is favor of T helper（Th）2 cells（Th2）, and Th1 is related to embryonic rejection. Vitamin D（VD）is an important immune modulator via inhibition of proliferation of Th1 and promotion of Th2. VD deficiency is associated with reproductive failure and pregnancy complications.
The aim of this study is to investigate the clinical efficacy of VD
in infertile woman for preconception care in maternal immune
tolerance. Methods Serum 25 hydroxyvitamin D3（25（OH）VD）,
Th1（CD4+/IFN γ+）and Th2（CD4+/IL 4+）levels were measured in 276 infertile women from 2014 to 2016. We categorized
VD deficiency（25（OH）VD＜20ng/ml）,insufficiency（21 30ng/ml）and sufficiency（＞30ng/ml）, and compared T helper cellamong 3 groups. We additionally examined detailed immu-

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nological test pre and post VD supplementation（1,000IU/d）in
8 patients with VD deficiency. This study was approved by the
Local Ethics Committee. Results Our data shows 87.3% of infertile women were lacking 25（OH）VD levels. In immunological
profiles, the number of patients with aberrant high Th1/Th2 ratio（＞10.3）in sufficient group was significantly smaller thanother 2 groups（p=0.046）. After supplementation, 25（OH）VD
were increased in all patients（p=0.008）, levels of Th1 were significantly decreased（p=0.016）, leading to reduction of Th1/Th
2 ratios（p=0.023）. There were no complications or adverse effects. Conclusion Most of infertile women were lack of VD
status. Preconception VD supplementation with VD deficiency
may sufficiently optimize maternal immune rejection to embryo
via Th1/Th2 ratio, leading to prevention against proinflammatory obstetrical complications during pregnancy.

ISP-59-5
Effect of metformin on androgen receptor expression in endometrial epithelial/stromal cell lines Miki Ohara1, Akiko
Yamaguchi1, Fumiko Saito1, Satoshi Suzuki1, Ryota Suganuma1,
Toshifumi Takahashi2, Hideki Mizunuma2, Hiromi Komiya1,
Keiya Fujimori1 Fukushima Medical University 1, Fukushima
Medical Center for Children and Women 2
Objective There are few studies focusing on the effect of metformin on the endometrium in patients with polycystic ovary
syndrome（PCOS）.Our previous study showed that expressionof endometrial androgen receptor（AR）decreased and HOXA10
increased with administration of metformin to PCOS patients. In
this study, to examine whether the metformin effects on PCOS
endometrium may be direct or not, we utilized endometrial epithelial/stromal cell lines. Methods After culturing the Ishikawa
cells and Human Endometrial Stromal cells（HESCs）from each
respective subculture for 24 hours, we added testosterone（Tgroup）,or both testosterone and metformin（T+M group）to theculture medium. For control, we also cultured cells without testosterone and metformin（C group）.Protein was extracted fromthe cells after culturing for 48 hours from addition of the preparations. We analyzed the AR expression levels using Western
blotting. Results In the T group, the expression levels of AR inboth cell lines increased as compared to the C group. The levelsof AR in the T+M group were lower than those in the T group.
Conclusion Addition of testosterone increased AR expression inboth Ishikawa cells and HESCs, while addition of metformin to
testosterone reduced AR expression. Based on these findings,
metformin may reduce AR expression by acting directly on theendometrium in the presence of testosterone.

ISP-59-6!

The Effectiveness of a New Comprehensive Numerical Multi
Scoring System for Endometriosis Masao Ichikawa, Shigeo
Akira, Hanako Kaseki, Kenichiro Watanabe, Shuichi Ono,
Toshiyuki Takeshita Nippon Medical School HospitalObjective To evaluate the diagnostic effectiveness of a new Numerical Multi Scoring System for Endometriosis（NMS E）.
Methods In this prospective observational research, we included 94 women diagnosed with endometriosis at our hospital.
The NMS E combines internal examination and transvaginal ultrasonography to evaluate the adnexa, adhesions, pain, and theuterus. The E score then gives an idea of the overall severity ofendometriosis（out of 40 points；10 per item in the NMS E）.
The diagnostic accuracy of each evaluated item of the NMS E
was verified by comparison with intraoperative findings, andthe usefulness of the E score was evaluated by comparison withthe revised American Society for Reproductive Medicine（rASRM）score. Results The average overall E score and r
ASRM score were 17.7±5.8 and 69.0±32.6, respectively. A posi-

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tive correlation（r=0.662）
was observed between the E score andthe r ASRM score. The accuracies of adnexal, adhesional, anduterine evaluation by transvaginal ultrasonography were 91.8%,
83.0%, and 90.6%, respectively. Compared with the lesion freegroup, the pain score was significantly higher in the group withendometriotic lesions in the pouch of Douglas（4.34±2.7 vs. 1.84
±2.06 p=3.0E 04）, right uterosacral ligament（4.26±2.63 vs. 2.29
±1.97 p=1.0E 04）, and left uterosacral ligament（3.88±2.56 vs.
2.27±2.56 p=2.4E 03）. Conclusion The NMS E accurately diagnosed the overall status and severity of endometriosis, andwould be useful as an index for medical and surgical strategy.

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ISP-59-7
Efficacy of individualized dose of FSH in ovarian stimulation
for unexplained sterility Toshiya Matsuzaki, Rie Yanagihara,
Kiyohito Yano, Takeshi Iwasa, Minoru Irahara Tokushima University
Objective The ovarian stimulation to unexplained infertility frequently induces multiple pregnancy. In this study, we evaluatedindividualized initial dose of FSH by BMI in patients of unexplained infertility. Methods Twenty one patients who were diagnosised unexplained infertility or luteal insufficiency weretreated with self injection of recombinant FSH in a low dose. Patients with BMI＜20 injected 50IU, while patients with BMI＞20
injected 62.5IU. They started self injection on cycle day 3〜6.
We measured follicle size using transvaginal ultrasonography. If
no follicle developed, dose of FSH was increased by 12.5IU pertime（up to 4 times）.When follicle diameter reached 18mm, hCG
5,000IU was injected. Results The ovulation rate was 100%. The
number of growing follicle was 1.29±0.63（mean±SD）. The
monofollicular development was seen in 85.7%（BMI＜20）and
78.6%（BMI＞20）. Number of follicle were 1〜3 and there wereno cycle with follicle number over 3. No pregnancy achieved.
Conclusion The method of individualizing initial dose of FSH by
BMI got high rate of ovulation and monofollicular development.
This method seemed safe while no pregnancy happens. We needto clarify whether monofollicular deveropment cycles using
FSH are useful as treatment of unexplained sterility.

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Comparison of Anti Müllerian Hormone levels between
pregnant women with natural conception and sterile womenin assisted reproductive technology Kento Usui, Yukiko
Katagiri, Yusuke Fukuda, Akiko So, Mamoru Kitamura, Azusa
Moriyama, Ayumu Ito, Yuko Hayashi, Yuko Tamaki, Takehiko
Tsuchiya, Mineto Morita Toho University Omori Medical Center
Objective Anti Müllerian Hormone（AMH）is a well established marker of the ovarian reserve. Ovarian reserve is one of
the important factors in assisted reproductive technology（ART）especially for controlled ovarian hyperstimulation. However, it has not been clear the relation between AMH concentration and fertility. We assessed the AMH levels in pregnant
women conceived naturally, and compared to sterile women inART. Methods The pregnant women in 6 to 14 gestational
weeks, who conceived naturally, were recruited for this study.
Their AMH levels were assessed by AMH Gen II ELISA kit andwere compared to the AMH levels of infertile women treated by
ART in our center. Results A total of 320 pregnant women（1944 years old）and 496 infertile women（25 50 year old）were assessed. The cases with polycystic ovarian syndrome, passed history of operation on ovaries, and the FSH level is ＜14 mIU/ml,
were excluded. The AMH levels were decreased according as
their age in the both groups. However, there were not significant the levels between pregnant women and infertile women.
Conclusion It has been suggested that AMH is not a marker to

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ISP-59-9

non endometriosis patients at all. Inhibition of RAS system by
MAS1 may characterize microenvironment of the eutopic endometrium in the endometriosis patients.

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Dominant expression of angiotensin 1 7 receptor（MAS1）inthe eutopic endometrium in the endometriosis patients
Takahiro Nakajima, Fumihisa Chishima, Takehiro Nakao,
Chuyu Hayashi, Akiko Kasuga, Kaori Shinya, Takuo Nakayama,
Hiromitsu Azuma, Go Ichikawa, Atsushi Komatsu, Tatsuo
Yamamoto, Kei Kawana Nihon University Itabashi HospitalObjective Tissue renin angiotensin system（RAS）plays important roles in the tissue remodeling. We have demonstrated AT1
and AT2, receptors of angiotensin II, are expressed and both
pathways balance RAS system in endometriosis by their opposing effects to each other. MAS1, a specific receptor of angiotensin1 7, also oppose AT1 pathway relating tissue remodeling. Here we examined whether MAS1 has any effect on pathogenesis of endometriosis. Methods Under informed consents,
ovarian endometriotic tissues and eutopic endometrial tissues（endo Em）were obtained from 32 patients with endometrial
cyst. As control, normal endometrial tissues（cont Em）were obtained from patients undergoing hysterectomy for benign diseases. Immunohistochemical staining were performed for MAS
1, AT1 and AT2. The mRNA levels of the MAS1, AT1 and AT2
were examined by quantitative RT PCR. Results Immunohistochemistry revealed that MAS1 was immune positive at the apical side of glandular epithelium in endometriotic lesions. RT
qPCR revealed that MAS1 mRNA level in ovarian endometriosis was significantly higher than that cont Em whereas not different from those in endo Em. In the endometrium at proliferative phase, MAS1 mRNA level in endometriosis cases was significantly higher than that in controls. MAS1/AT1 mRNA ratio
in the endometrium at proliferative phase was increased predominantly in endometriosis cases when compared with controls. Conclusion MAS1 was expressed not only in the ovarian
endometriosis but in the eutopic endometrium. The expressionof MAS1 in the eutopic endometrium was not observed in the

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ISP-60-2!

Clonal expansion and diversification of cancer associatedmutations in endometriosis and normal endometrium
Kazuaki Suda1, Kosuke Yoshihara1, Tatsuya Ishiguro1, Ryo
Tamura1, Kaoru Yamawaki1, Yutaro Mori1, Hiroaki Kase2,
Takayuki Enomoto1 Niigata University 1, Nagaoka Chuo General
hospital 2
Objective Endometriosis is characterized by ectopic endometrial like epithelium and stroma. The aim of this study is
to clarify molecular characteristics of endometriosis leading todevelopment of better treatments. Methods After ethical committee approval and written informed consents, we performed
whole exome and target gene sequencing for 107 ovarian endometriotic epithelium samples from 54 endometriosis patientsand 82 normal uterine endometrial epithelium samples from 32
non endometriosis patients. All samples were isolated from frozen sections by laser microdissection. We also performed target gene sequencing for 109 single endometrial glands obtained
from three patients. Results In both endometriotic and uterine
endometrial epithelium samples, numerous somatic mutations
were identified within genes, including KRAS and PIK3CA , frequently mutated in endometriosis associated ovarian and endometrial cancers. Analysis of mutant allele frequency（MAF）in
endometriotic epithelium revealed a unique mutational landscape, wherein KRAS was frequently mutated, with a higher
MAF accompanied by arm level copy number alterations, leading to clonal expansion of cells carrying these changes. MAF
distributions in normal uterine endometrium were lower than inendometriotic epithelium. To show that each endometrial gland
was clonal in origin, we sequenced single endometrial glands
and found that each gland carried a clonal state of distinct mutations, proving how heterogeneous genomic architecture of endometrial epithelium is. Conclusion We clarified that endometriosis and normal endometrium samples had already harbored cancer associated mutations which were considered as
driver mutations in endometriosis associated ovarian and endometrial cancers. Combined with retrograde menstruation,
overlapping in somatic mutations between endometriosis anduterine endometrium might be the molecular evidence that endometriosis derives from uterine endometrium.

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ISP-60-3!

Treatment with a selective estrogen receptor modulator, SR
16234 results in regression of endometriosis like lesions in amurine model Khine Yinmon, Fuminori Taniguchi, Kei Nagira,Yukihiro Azuma, Takashi Uegaki, Tasuku Harada Tottori University
Objective SR 16234（SR）（Nobelpharma Co.,）is a newly developed selective estrogen receptor modulator（SERM）,which has
an estrogen receptor（ER）α pure antagonist and ER β partial
agonist activity. We investigated the efficacy of SR 16234 on endometriosis like lesions in the murine model of endometriosis.
Methods A mouse endometriosis model was established bytransplanting autologous endometrial tissue. Ovariectomized,
estradiol replaced, 6 week old BALB/c mice with surgically induced endometriosis（n=30）were injected with lipopolysaccharide（LPS）with or without SR（1mg/kg/day）treatment or vehicle, over a period of 4 weeks. Upon treatment completion, theendometriosis like lesions that developed in the abdominal cavity of mice were counted, measured, and collected. Gene expression of inflammatory cytokines in the lesions was assessed byreal time RT PCR. Immunohistochemical analysis was used to

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Individualized initial dose in low dose FSH therapy for WHO
group 2 patients Rie Yanagihara, Toshiya Matsuzaki, Takeshi
Iwasa, Kiyohito Yano, Minoru Irahara Tokushima University
Objective Incidences of multiple pregnancy by ovulation induction has been a ploblem to be solved for the long time. FSH
treatment in a low dose step up method can reduce the frequency of multiple pregnancy, but the rate is still higher thannatural pregnancy. In this study, we evaluated our protocol oflow dose FSH therapy with individualized initial dose by BMI.
Methods Twenty nine patients who were diagnosised WHOgroup 2 ovarian insuficiency were treated with self injection ofrecombinant FSH in a low dose step up protocol. Patients with
BMI＜20 and BMI＞20 were injected 50IU and 62.5IU as initialdose. If no follicle is developed, dose of FSH was increased by
12.5IU per time（up to 4 times）. When follicle diameter reached
18mm, hCG 5,000IU was injected. We evaluated ovulation rate
and monofollicular development and compared with reported
best results of which the ovulation rate was over 90% and monofollicular development was over 70%. Results The ovulation
rate was 100%（BMI＜20）and 90.9%（BMI＞20）. The monofollicular development was seen in 80%（BMI＜20）and 77.3%（BMI＞20）. The average of number of growing follicle was 1.07±0.47（mean±SD）and there were no cycle with follicle number over
2. The pregnancy rate was 60%（3/5 BMI＜20）and 18.2%（4/22
BMI＞20）. No multiple pregnancy achieved. Conclusion The
method of individualizing initial dose of FSH by BMI got highrates of ovulation and monofollicular development. This method
could reduce multiple pregnancy in ovulation induction.

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evaluate the effect of SR on cell proliferation, angiogenic activity, and inflammation. Results Treatment with SR significantly
reduced the total number, weight and surface area of lesions per
mouse. In addition, SR downregulated LPS enhanced Vegf, Il 6,
Ptgs 2 and Ccl 2 mRNA expression in endometriosis like lesions. Immunohistochemical analysis demonstrated a decreasein percentage of positive cells of Ki 67, and intensity and rate of
positive cells of CD3, F4/80, and PECAM by SR treatment. Conclusion SR 16234 had a regressive effect on the development ofmurine endometriosis like lesions. It may be used as a novel
agent for the treatment of endometriosis.

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ISP-60-4
Role of Focal Adhesion Kinase（FAK）in development of endometriosis
Takashi Nagai, Akira Iwase, Chiharu Ishida,
Shotaro Hayashi, Ayako Muraoka, Tomohiko Murase, Satoko
Osuka, Maki Goto, Fumitaka Kikkawa Nagoya University
Objective The effect of cell adhesion itself on endometriosis has
been hardly explored. Integrins, the cell adhesion molecules,
have been demonstrated to regulate cell survival, proliferationand invasion via focal adhesion kinase（FAK）in many types ofcells including endometriosis. Monocyte chemoattractant protein 1（MCP 1）is one of the highly upregulated chemokines inendometriotic tissues. The purpose of this study is to investigate the role of FAK in endometriosis and to test the effect of
FAK inhibitor on a surgically induced endometriosis mousemodel. Methods FAK, MCP 1, CD68 and TGF β1 expression
was assessed by immunohistochemistry in endometriotic cyst.
We assayed the concentrations of MCP 1 in the culture media ofendometrial stromal cells with or without endometriosis（eESC
and ESC, respectively）and endometriotic cyst derived stromalcells（CSC）. TGF β1 was measured by co culture with CSCs
and macrophages. In a mouse of endometriosis, FAK inhibitor
treatment was evaluated for lesion of ectopic endometrium. Results IHC showed that FAK, MCP 1 were enhanced on endometriotic cysts compared to endometrium. The MCP 1 concentration of CSC was higher than that of ESC, and secretion of
MCP 1 was inhibited by FAK Inhibitor. In a mouse model,
FAK inhibitor treatment significantly reduced number of lesion per mouse. Conclusion In conclusions, increased secretionof MCP 1 from endometriotic stromal cells was mediated via
FAK which was stimulated by integrin extracellular matrix adhesion. These results suggest that inflammatory response andcell adhesion is interrelated and implicated in the development
endometriosis.

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ISP-60-5
Peritoneal NK cell suppression for cytotoxicity and chemotaxis in women with endometriosis Shimpei Yamamoto,Takashi Ushiwaka, Chiaki Izumiya, Tamami Tsuzuki, Kayo
Taniguchi, Nagamasa Maeda Kochi University
Objective In women with endometriosis, immunologic suppression by natural killer（NK）cells and macrophages in peritoneal
fluid（PF）is considered to be associated with the pathogenesisof endometriosis. In this paper, we investigate the immunologic
behavior of peritoneal NK cells from women with endometriosis
by time lapse imaging system. Methods PF samples obtained atlaparoscopic surgery from women with endometriosis werecompared to without endometriosis. We investigated the immunocompetent PF cell movement and behavior by time lapse
imaging under microscope incubator. The cell movement speed
was calculated as a chemotaxis index. This study was approvedby IRB at own affiliation. Results During the menstrual period,
we can observe retrograde endometrial cells in PF. Interestingly, immunocompetent cells from women without endometriosis were cytotoxic to retrograde endometrial cells. In particular,!

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peritoneal NK cells are most cytotoxic and retrograde endometrial cells were damaged and collapsed by surrounding NK
cells and finally disappeared. On the contrary, in women withendometriosis, retrograde endometrial cells were hardly damaged and they remained after menstrual period. The cell movement speed of NK cells from women with endometriosis was
significantly decreased compared to control. On the other hand,the cell movement speeds of both macrophages and lymphocytes were not significantly difference between with and without endometriosis. Conclusion In women with endometriosis,
peritoneal NK cell has not only decreased cytotoxity but also
has decreased chemotaxis assessed by cell movement speed.
This immunologic suppression of NK cells in women with endometriosis may be associated with the pathogenesis of endometriosis.

ISP-61-1
Healthcare for young gynecologic malignant tumor patientsat our hospital Kanako Yoshida, Yuri Kadota, Kana Kasai,
Takako Kawakita, Takeshi Kato, Minoru Irahara Tokushima
University
Objective 30 to 40% of gynecologic malignant tumor patientsare women under the age of 50. Most of the patients are undergoing surgery including bilateral oophorectomy, chemotherapy
or radiation therapy, resulting in ovarian dysfunction. Total
health care after cancer treatment is important, even for gynecological cancer being relatively good prognosis. Methods We
examined ovarian deficiency symptoms, dyslipidemia, bone mineral density and treatment method of 13 patients with ovariandysfunction after cancer treatment at our hospital. Results Diagnosis were 4 cervical cancers（2 squamous cell carcinomas
and 2 adenocarcinomas）,5 endometrial cancers（5 endometrioid
adenocarcinomas）and 4 ovarian cancers（3 endometrioid adenocarcinomas, 1 mucinous tomor of borderline malignancy）. The
average age at treatment was 40（31 47）years old. For ovarian
deficiency symptoms, hot flash was the most common in 8 cases,
followed by complaints of symptoms such as malaise, insomnia,
anxiety. Dyslipidemia was found in 7 cases, bone mineral density was normal in 7 cases, osteopenia in 3 cases, osteoporosis in
2 cases. For cervical cancer and ovarian cancer, Hormone Replacement Therapy（HRT）was started from the early stage oftreatment. In contrast, HRT was performed carefully in endometrial cancer, and treatment was done with Kampo and vitamin D as necessary at the early stage of cancer treatment. In 5
of 7 patients in which HRT was initiated, improvement in ovarian deficiency symptom was observed. Conclusion Managementof young gynecologic malignant tumor patients requires not
only the presence or absence of recurrence, but also management with attention to the total health care including HRT.

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Intraoperative Surgical Apgar Score predicts 30 day morbidity in elderly gynecological patients Kazumi Kurata, Yoko
Chino, Akiko Shinagawa, Tetsuji Kurokawa, Yoshio Yoshida
University of Fukui
Objective The aim of this study was to determine whether apreoperative health status index and intraoperative data could
predict perioperative morbidity and mortality in women over
the age of 65 years undergoing surgery for gynecologic disorders. Methods The medical records of 70 female patients who
were＞65 years of age and who underwent surgery under general anesthesia in our university hospital from January 2014 toDecember 2015 were retrospectively reviewed. Preoperative
data were extracted from a database and included comorbidities, American Society of Anesthesiologists physiological statusclassification, the Charlson Comorbidity Index, the Subjective

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for POP. Methods From July 2012 to May 2016, for the case of
grade III Pelvic Organ Prolapse, we checked the emergence ofvaginal vault of posterior wall at the end of operation for thevaginal front wall. If not there, we did not perform the restoration of vaginal posterior wall. Results In 209 cases of grade III
and IV of POP, 192 cases were able to be followed up for over
one year. Of the 192 cases, 14 of the 147 cases where restorationof only the vaginal front wall were performed had vaginal vault
of posterior wall after operation. All gradually begins enlarging
from 6 months post operation and some have become beyond
the hymen ring in 1 2 years. On the other hand, none of the 26
cases observed during the same period where restoration ofvaginal front and posterior wall were performed together havevaginal vault of posterior wall. Conclusion The restoration of
pubocervical fascia and rectovaginal fascia together is necessary in the case of grade III or higher of POP, because existenceof damage of not only pubocervical fascia but also rectovaginal
fascia should be considered.

ISP-61-3

ISP-61-5

The comparison of lower urinary tract symptoms after various surgeries for pelvic organ prolapse Kaori Hoshino1, Mai
Myouga1, Kazuaki Yoshimura1, Toru Hachisuga2 Wakamatsu
Hospital of the University of Occupational and Environmental
Health 1, University of Occupational and Environmental Health 2
Objective Most of the patients of pelvic organ prolapse（POP）
have some lower urinary tract symptoms（LUTS）and gynecologists should consider the changes of LUTS. There are few reports that analyze the changes of LUTS between different typesof POP surgeries. In this study, we analyzed pre and post operative LUTS in various POP surgeries. Methods Seventy two patients who underwent POP surgeries in our hospital fromMarch 2016 to March 2017 were enrolled in this study. The
types of surgeries were transvaginal mesh（TVM, n=33）,laparoscopic sacrocolpopexy（LSC, n=18）, laparoscopic uterosecral
ligament suspension（L USLS, n=12）, and transvaginal nonmesh surgery（n=9）. Voided volume（VV）, average and maximum flow rate（Qave and Qmax）,and post void residual urine（PVR）were measured by uroflowmetry and ultrasound before
and 1, 3, 6 months after the surgeries. Core urinary tract symptoms score（CLSS）and quality of life（QOL）score was simultaneously obtained. Results There was no significant difference
between the groups in the backgrounds. VV and Qave of LSCgroup were significantly higher than those of TVM group until
3 month after the surgeries. PVR of TVM group was greaterthan LSC group at 1 month after the surgeries and reduced at
3 month. Regarding stress urinary incontinence（SUI）,CLSS of
LSC was significantly worse than that of TVM. L USLS wasnʼt
any significant difference compared with the other surgeries.
QOL score significantly improved after all surgeries. Conclusion TVM tended to cause voiding difficulty, however, it recovered after 6months. On the other hand, LSC caused more possibility of SUI. QOL improved after all POP surgeries.

Four cases of Pelvic Organ Prolapse（POP）complicated withuterine cancer or precancerous lesion Ayuko Otoshi1, Hiromi
Kashihara1, Mai Temukai1, Yuri Kamino1, Yoshimi Tokugawa1,
Chikako Tsukahara1, Takeshi Hisamatsu1, Takashi Miyatake1,
Koji Hisamoto1, Masahiko Tsujimoto2, Yukihiro Nishio1 Osaka
Police Hospital 1, Department of Pathology, Osaka Police Hospital 2
Recently, with the aging of the population, patients with POP
are increasing, and it seems that cases complicated with uterine
malignancy will increase in the future. Before the POP surgeries, we check the cervical cytology and endometrial thickness.
With these examinations, we decide the type of surgery. We present four cases of POP patients with co existing uterine malignancy or precancerous lesion who underwent surgery. Case 1 isan 84 year old woman with uterine prolapse. Her cervical cytology was HSIL, the colposcopy biopsy showed CIN1, therefore total vaginal hysterectomy and all vaginal excision were performed. The diagnosis was cervical squamous cell carcinoma
stage IA. Case 2 is an 82 year old woman with uterine prolapse.
She had endometrial thickening, biopsy and MRI were performed and the diagnosis was uterine corpus clear cell adenocarcinoma stage IA. Total abdominal hysterectomy（TAH）,bilateral salpingo oophorectomy（BSO）,omentum resection, USL
fixation were performed. Case 3 is a 77 year old woman withuterine prolapse. Her cervical cytology was SCC. The colposcopy biopsy showed CIS, however PET CT showed abnormal uptake in the cervices. Semi radical hysterectomy, BSO
and USL fixation were performed. Case 4 was a 69 year old
woman with cystocele. Endometrial cancer was suspected by biopsy. TAH, BSO and USL fixation were performed. From the reflection that we should predict the carcinoma before the surgery of case 1, in other cases, procedure of the surgeries weremainly for the carcinoma, for the POP only USL fixation was
performed. Therefore there is a possibility of cystocele recurrence in the future.

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ISP-61-4
The restoration of vaginal front and posterior wall together
is necessary with Native Tissue Repair in the case of grade
III and IV of Pelvic Organ Prolapse Tetsuya Oishi, Hiroki
Kato, Takashi Shibata, Hisato Tokuda, Fumikazu Kotsuji Takatsuki General HospitalObjective In announcement until the last time, we reported usefulness of Native Tissue Repair of vaginal front wall using
Pubocervical Fascia Pulling Up Method and of vaginal posterior wall using Rectvaginal Fascia Pulling Up Method for Pelvic Organ Prolapse（POP）. Here we introduce the results thatexamined the need of the restoration of vaginal posterior wall

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ISP-61-6
Repair of the Stage 3 POP That a Ring Pessary Made Giant
Rectovaginal Fistulas and the Rectal Mucosa Covered the
Posterior Vaginal Wall Beyond the Fistula：Operative Technique
Hiroki Kato, Tetsuya Oishi, Takashi Shibata, Hisato
Tokuda, Satoshi Nakago, Fumikazu Kotsuji Takatsuki General
Hospital
We experienced a repair of the stage 3 POP that a ring pessary
made giant rectovaginal fistulas and the rectal mucosa covered
the posterior vaginal wall beyond the fistula. We thought thatMay 11 Fri.
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Global Assessment 2011 revision, the subjectsʼ risk of falling,
body mass index, and age. The intraoperative factors investigated included the type of surgery and the Surgical Apgar
Score（SAS）. Major postoperative complications were defined as＞Grade 3 based on the Clavien Dindo classification version 2.0.
Results Of the 70 elderly gynecological patients, 6（8.6 percent）developed serious Grade 3 or worse complications within
30 days of surgery. The only factor that significantly affected
postoperative complications was the SAS, an index of the patientʼs intraoperative condition. The optimum cut off SAS forthe occurrence of complications was determined by the receiver
operating characteristic curve to be＞6 points. A score＞6
points predicted the development of postoperative complications with 66.7 percent sensitivity and 85.9 percent specificity.
Conclusion In this study, the SAS predicted the development ofserious complications in elderly gynecological patients within
30 days of surgery more accurately than did other comorbidities, preoperative assessments, and type of surgery.

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broad separation of the rectal wall from its neighboring tissues
and the order of a surgical procedure were the vital for the success of the operation. For accurate separation of the rectal wall,
the perineal skin was transversely cut and the edge of the posterior vaginal wall was grasped and stretched. This made the precise separation of the rectal wall possible. When the separationof the rectal wall reached to the fistula, the rectal mucosa overlying the vaginal mucosa was removed. Then, the rectal wallabove the fistula was removed from the vaginal wall. Followings
are the operative order；1）the separation of the pubocervicalfascia from the anterior vaginal mucosa, 2）repair of the rectal
fistula, 3）hysterectomy, 4）reconstruction of the pubocervicalfascia, and 5）repair of the anterior and posterior vaginal mucosa. We thought about this surgical order due to the followings.
Firstly, when we perform hysterectomy and anterior colporrhaphy before syringeal repair, the position of the fistula moves
to deep in the vaginal canal. This makes repair of the fistula difficult. Secondarily, if syringeal restoration is preceded, vaginal
traction during the POP repair may produce a stress to the sutured rectal wall. Tertiary, the hysterectomy prior to repairing
the fistula makes the separation of the rectum from the vagina
difficult.

ISP-61-7
Effects of drospirenone on adhesion molecule expression andmonocyte adherence in human endothelial cells Fumitake Ito,
Osamu Takaoka, Yukiko Tanaka, Akemi Koshiba, Hiroshi
Tatsumi, Taisuke Mori, Jo Kitawaki Kyoto Prefectural University of Medicine
Objective A major concern in hormone replacement therapy is
the associated increased risk of cardiovascular diseases. A progestogen without the unfavorable effects on cardiovascular disease should be explored. Monocyte adhesion to endothelial cells
is an important initial event in atherosclerosis. In this study, theeffects of the alternative progestogen drospirenone（DRSP）on
monocyte adhesion in human umbilical venous endothelial cells（HUVECs）were examined. Methods In HUVECs treated withestrogens and progestogens, including DRSP and medroxyprogesterone acetate（MPA）, the expression of the adhesion molecules E selectin, P selectin, ICAM 1, and VCAM 1 were examined by real time PCR and using an enzyme linked immunosorbent assay. A flow chamber system was used to investigate
the effects of DRSP on U937 monocytoid cell adherence to HUVEC monolayers. All experimental data were compared using
one way Analysis of Variance. Results Upregulation of adhesion molecule mRNA or protein was not seen in HUVECs
treated with DRSP alone or with 17β estradiol+DRSP. DRSP
alone, 17β estradiol+DRSP or ethinylestradiol+DRSP did not increase the number of adherent monocytoid cells to HUVECs in
the flow chamber system. However, MPA significantly en. Conclusion
hanced the monocytoid cell adherence（P ＜0.05）
DRSP did not increase the expression of adhesion molecules ormonocytoid cell adherence to endothelial cells, indicating thatDRSP could reduce the risk of atherogenesis caused by MPA.
These results suggest that DRSP may be an alternative to MPA
in hormone replacement therapy.

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ISP-61-8
Levonorgestrel intrauterine system for previous delivery
scar defect related postmenstrual bleeding management
Ying-Yi Chen1, Yu-Che Ou1,2 Kaohsiung Chang Gung Memorial
Hospital and Chang Gung University College of Medicine, Taiwan 1, Chang Gung Memorial Hospital at Chiayi and Chang Gung
University College of Medicine, Taiwan 2
Objective Abnormal uterine bleeding associated with previous
cesarean delivery scar defect（PCDS）have become a serious

problem with the increasing cesarean section rate. The mostcommon bleeding pattern is postmenstrual bleeding. The aim of
the present study is to evaluate the efficacy of levonorgestrel（LNG）intrauterine system（IUS）for postmenstrual bleeding
treatment. Methods This was an observational study performed
between May 2007 and February 2017. For patients who experienced postmenstrual bleeding after receiving cesarean section,
we performed transvaginal ultrasound and hysteroscopy forevaluation. Treatment options including surgical intervention
and LNG IUS insertion were provided once the PCDS related
postmenstrual bleeding was impressed. Total 22 patients chose
LNG IUS were enrolled. The basic background history and thegynecological symptoms of the patients were recorded. Written
informed consent was obtained from the participants. Results
The mean number of previous cesarean sections was 1.91±0.61.
The mean age of the study population was 43.1±4.7 years. 91.3%
participants reported clinical improvement. The mean time toimprovement was 7.4±7.9 months. The duration of postmenstrual bleeding significantly shortened after LNG IUS use（10.41±5.98 days and 1.09±3.21 days, p＜0.001）.Four patients（18.2%）
became amenorrhea after 12 months. No headache, pelvic pain,
or increased vaginal discharge was complained by the participants during the observation periods. Conclusion LNG IUS isan effective treatment for PCDS related postmenstrual bleeding.
We recommend LNG IUS usage for patients in perimenopause
status, young patient who desire for childbearing in the futureor anyone who asks for conservative treatment instead of surgery.

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ISP-62-1
Clinical features of Thoracic endometriosis：a series of 25
cases from a single facility Shinya Fukuda, Tetsuya Hirata,
Kazuaki Neriishi, Akari Nakazawa, Miyuki Harada, Yasushi
Hirota, Kaori Koga, Osamu Hiraike, Yutaka Osuga, Tomoyuki
Fujii The University of Tokyo HospitalObjective Thoracic endometriosis（TE）is one of the extra genital endometriosis characterized by the presence of endometrial
tissue in thoracic cavity. To clarify the clinical features of TE,
we retrospectively studied 25 cases with TE in our hospital.
Methods Twenty five cases of TE were diagnosed from 2000 to2016 in our hospital. The clinical features and management（age,symptom, laterality, prior operation, hormonal therapy and thefrequency of relapse）were analyzed retrospectively by reviewing the records of our hospital. This study was approved by theInstitutional Review Board of our hospital. Results Eighteen
cases had catamenial pneumothorax（CP）and seven cases had
catamenial hemoptysis（CH）. The age of patient was significantly higher in CP compared to CH（36.8 vs 29.6 years old, P＜0.05）and 16 cases（88.9%）of CP were right sided, but CH cases
showed no significant tendency in laterality. Nine cases（50%）in
CP relapsed and one（14%）in CH. As for CP, the recurrence rate
was 66.7%（2/3）in the patients without operation and 46.6%（7/15）even after operation. Hormonal therapy was performed in 16
cases with CP（89.9%）. And four cases（4/16, 25%）relapsed in
the patients with hormone therapy, whereas seven cases（7/16,
43.8%）relapsed in the patients without hormone therapy. Conclusion Considering the difference between CP and CH, wemight hypothesize that pathogenesis of CP and CH can be distinctly categorized. Improvement of management strategy in
CP is required because the recurrence rate of CP symptoms after treatment is high.

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ISP-62-2
Alteration of coagulation status in the patients with endometriotic cysts Kanoko Shoji, Fumihisa Chishima, Takahiro
Nakajima, Takehiro Nakao, Erina Kato, Hiromitsu Azuma,

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Okimura, Hisashi Kataoka, Osamu Takaoka, Fumitake Ito,
Izumi Kusuki, Jo Kitawaki Kyoto Prefectural University of
Medicine
Objective In management of patients with endometriosis, preventing the recurrence of lesions and symptoms after primaryconservative surgery is important to avoid additional surgeries
and preserve fertility. The purpose of this retrospective study
was to evaluate whether endocrine therapy immediately after
post surgical recurrence of ovarian endometrioma suppresses
aggravation of the disease and reduce the necessity of secondline surgeries. Methods We enrolled 146 patients treated for endometrioma at our hospital between 2009 and 2015. After laparoscopic cystectomy using the stripping technique, opening of
cul de sac obliterations, and complete resection of deep infiltrating endometriosis lesions, the patients received no treatment（n=83）, an oral contraceptive（OC, n=32）,or dienogest（n=27）depending on their medical background, and were followed
up every 3 months. Those that developed recurrence of endometrioma immediately received dienogest, OC, or gonadotropin releasing hormone agonist. Results Of the 16 cases with endometrioma recurrence（12 in the non treatment group, 3 in the
OC group, and 1 in the dienogest group）, complete or partial
resolution was achieved in 10 of the 11 cases treated with dienogest and one case with gonadotropin releasing hormone agonist.
However, there was no improvement in the 3 patients who received OC, and 1 of whom underwent secondary surgery. Conclusion Dienogest therapy at the early stage of post surgical endometrioma recurrence appears to be a viable option to reduce
the necessity of repeated surgery. It may also aid with conserving the ovarian reserve and maintain fertility in patients withendometriosis.

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Laparoscopic cystectomy of endometrioma（LC）followed byoral contraceptives（OC）until conception is desired；will thissustain later fecundability? Arisa Takeuchi, Kaori Koga, Erina
Satake, Tomoko Makabe, Mariko Miyashita, Gentaro Izumi,
Masashi Takamura, Miyuki Harada, Tetsuya Hirata, Osamu
Hiraike, Yutaka Osuga, Tomoyuki Fujii The University of Tokyo
Objective Laparoscopy enhances fecundability in patients withendometriosis；however, the effect declines as the post operative time goes by, and this decline discourages patients with endometrioma who do not wish immediate childbearing from undergoing laparoscopy. Post operative use of oral contraceptives（OC）reduces recurrence of endometrioma after laparoscopic
cystectomy（LC）；however, its effect on later fecundability is
unknown. To test our hypothesis：LC followed by OC sustains
later fecundability, we conducted the following study. Methods
Under IRB approval, 107 patients who underwent LC between
2009 and 2012, and have wished conception, and were followed
up for at least 24 months after LC, were retrospectively analyzed. According to the point of arising a wish for pregnancy,
patients were divided into two groups：right after LC（GroupA, n=83）, and right after the discontinuation of post operative
OC（Group B, n=24）. The cumulative pregnancy rate and thetime to pregnancy were compared between groups. Results The
cumulative pregnancy rate in Group B（54.2%）was equivalent
to that in Group A（56.6%）. Similarly, the time to pregnancy inGroup B（12.8±7.3 months, mean±SEM）was comparable withthat in Group A（11.7±9.3）. Conclusion The pregnancy rate andthe time to pregnancy were comparable between two groups,
which suggests that the fecundability did not decline after LC
followed by post operative OC. This finding encourages patients with endometrioma who do not wish immediate childbearing to undergo LC followed by OC.

Validity of management against the endometriotic cyst：aretrospective study Takeharu Kido, Tomoko Tsuzuki, Naoko
Kida, Maiko Kobayashi, Yoji Hisamatsu, Hiromi Murata,
Tomomi Mizokami, Masato Kita, Hidetaka Okada Kansai Medical University
Objective Endometriosis causes dysmenorrhea, infertile andmalignancy in reproductive women. The aim of this study was
to investigate the factors that indicate clinical management
against the endometriotic cyst. Methods We researched retrospective records of 104 patients（mean age：36）with the endometriotic cyst between June 2014 and December 2016. A surgery group was 41 patients and a non surgery group was 63 patients. In the surgery group, 24 patients received medication before surgery and 21 patients received medication after surgery.
Results Maximum diameter of the endometriotic cyst was significantly larger in the surgery group than in the non surgery
group（74.2±44.8mm vs 45.6±18.9mm, p＜0.05）. Age was also
higher（38.8±8.1years old vs 33.2±5.9 years old, p＜0.05）. Therewas no differences between the presence of subjective andmaximum diameter of the endometriotic cyst（57.1±36.8mm vs
57.7±28.5mm, p=0.6）. No significant association was observed
between the presence of subjective and medication before surgery（p=0.91）. Medication after surgery was also no differences（p=0.54）. Conclusion The results of present study showed surgical indication is affected by tumor size and age because of malignancy risk. Management of endometriosis treatment isneeded to select medication before and after surgery whether
desiring to bear children.

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Dienogest therapy at the early stages of recurrence of endometrioma following primary surgery suppresses the aggravation of the disease Akemi Koshiba, Taisuke Mori, Hiroyuki

Long term dienogest administration in patient with symptomatic adenomyosis Kazuaki Neriishi, Tetsuya Hirata, Shinya
Fukuda, Gentaro Izumi, Akari Nakazawa, Miyuki Harada,

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Chuyu Hayashi, Go Ichikawa, Atsushi Komatsu, Yasuji
Miyakawa, Shinichi Takada, Kei Kawana Nihon University Itabashi HospitalObjective Occurrence of cardiovascular morbidity；myocardial
infarction, and angina has been reported in the patients with endometriosis. Slight alteration in coagulation and fibrinolysis parameters have been noted in patients with endometriosis supports a potential hypercoagulable status in the patients with endometriosis. It has not been obtained confirmative views association of hypercoagulation in the patients with endometriosis,
although some researchers suggests that active phase of the disease is associated with blood hypercoagulability. This study
aimed at evaluating some variables of coagulation status and inflammatory markers in patients with endometriosis. Methods Ina case control study, 39 patients with endometriosis and 17 patients without endometriosis were evaluated. Informed consent
were obtained from all patients. The routine preoperative included complete blood count parameters, C reactive protein,platelet（Plt）, Plateletcrit（PCT）,mean platelet volume（MPV）,
platelet distribution width（PDW）, PT, PT ratio, APTT, APTT
ratio. Results In patients with endometriosis, White blood cellcounts, values of MPV, and PT were significantly higher whencompared to control group（p＜0.05, p＜0.0001, and p＜0.05, subsequently）. Conclusion Alteration of the local coagulation system, in addition to inflammation may have an important role in
the pathogenesis of endometriosis.

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Yasushi Hirota, Kaori Koga, Osamu Hiraike, Yutaka Osuga,
Tomoyuki Fujii The University of Tokyo HospitalObjective Adenomyosis is a common gynecological disorderthat causes dysmenorrhea, hypermenorrhea, and metrorrhagia.
Previously, we reported that 24 weeks of dienogest treatment ishighly effective for pain in symptomatic adenomyosis. In thisretrospective cohort study, we investigated the course of longterm dienogest treatment in patients with symptomatic adenomyosis. Methods The study protocol was approved by the Institutional Review Board of our hospital. This was a retrospective
cohort study. The outcomes of a total of 18 cases were investigated using the medical records. Dienogest was continuously
administered at a dose of 1mg twice daily. The main study variables were the visual analog scale score of adenomyosis associated pain, blood test（levels of hemoglobin（Hb）, CA125, and E2）
and the size of uterus. MRI was performed at baseline in allcases, which were categorized according to previously reported
criteria based on the MRI exam（Kishi et al.）.Results Twelve of
18 patients（66.7%）received dienogest until menopause or fora period of ＞80 months. Four cases（22.2%）discontinued dienogest treatment because of severe metrorrhagia. A comparison
between cases with long term use and those who discontinued
treatment because of severe metrorrhagia showed a significant
difference in hemoglobin level at baseline, pain score for dysmenorrhea at baseline, and the frequency of type 2 adenomyosis.
Moreover, long term dienogest use showed that serum estradiol
level did not decrease. Conclusion Our report suggests that dienogest is tolerable for long term use and may be an alternative
treatment option in some patients to avoid hysterectomy.

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Unusual hyper inflammatory degeneration of adenomyosis
after cesarean section Atsushi Fusegi, Yoshie Oka, Yuno
Ariyama, Osamu Yasui, Minako Matsuda, Momoko Ozawa,
Kotoi Tsurane, Tsutomu Ida, Kazunori Koike, Yoshimi
Taniguchi, Akira Kohyama Tokyo Metropolitan Tama Medical
CenterAlthough pregnancy rates in patients with adenomyosis haverisen due to the progress of infertility treatment, the adverse
pregnancy outcomes associated with adenomyosis are unclear.
We report a case in which unusual degeneration of adenomyosis
occurred after a cesarean section（CS）and caused hyper inflammation. A 40 year old（gravida 1, para 0）Japanese woman who
was 27 weeks pregnant was transferred to our hospital due topremature threatened delivery. Ultrasound disclosed a 6 cm
thickness of the uterine anterior wall. We diagnosed adenomyosis during pregnancy based on magnetic resonance imaging. We tried to maintain the pregnancy using tocolytic agents.
At 31 weeks the patient had hypertension and the babyʼs
growth was restricted. At 33 weeks and 3 days we conducted a
CS due to non reassuring fetal status. A 1,334 g infant was delivered. Postsurgically, the patientʼs hyper inflammatory status
and tendency to bleed continued. Uterine enlargement and a hematoma around the CS wound were found on computed tomography. Antibiotics were ineffective in reducing the inflammation. We performed a hysterectomy and removed the hematoma on postoperative day 5. Thereafter the patientʼs inflammatory status improved quickly. On histological examination decidual change in the adenomyosis with invasion of inflammatory
cells was detected in a wide area of the uterus, part of which
had become necrotic. Our case demonstrated an unusual degeneration of the adenomyosis occurring after delivery and causing
hyper inflammation. Hysterectomy was a fast and effective
treatment method. This case showed that degeneration of adenomyosis should be included in the differential diagnosis ofpost CS hyper inflammation.

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Analysis of clinical problems in medical treatment for adenomyosis
Minako Koizumi, Takahiro Hino, Yu Takahashi,
Masakazu Sato, Nao Itaoka, Chiharu Ueshima, Maki Nakata,
Yoko Hasumi Mitsui Memorial HospitalObjective Although medical treatment for adenomyosis has notbeen established, Dienogest and levonorgestrel releasing intrauterine system（LNG IUS）are often chosen for symptoms including pain and abnormal uterine bleeding. We aimed to clarify
the clinical problems of both treatments. Methods A retrospective study was designed covering 38 patients who were treatedwith Dienogest（Group A：18 cases）or LNG IUS（Group B：21
cases）between January 2015 and August 2017. We investigatedthe clinical backgrounds and the reasons of discontinuation.
Only one patient received both treatments. Results Patientsʼ age
in group A and B was 43.8±4.9 and 42.7±6.8, respectively. The
observation period was 11.9±7.2 months in group A and 11.6±
10.1 months in group B. The number of patients who weretreated previously was as follows；13 cases（72.2%）in group
A（GnRHa：10 cases, LEP：3 cases）, and 9 cases（45%）in group
B（GnRHa：3 cases, Dienogest：6 cases）. Three patients ingroup A（16.7%）and six patients in group B（30%）discontinued
the medication due to the following reasons；we observed 3
cases with severe atypical bleeding in group A, including one
case in which transfusion and hysterectomy was required. We
also observed 4 cases with atypical bleeding in group B, including 3 cases in which hysterectomy was required and one case inwhich transfusion was required. Furthermore, we ceased LNG
IUS treatment because of general fatigue in 2 cases. Conclusion
We experienced several cases of severe atypical bleeding during medical treatment for adenomyosis. It is necessary to consider and inform the benefits and limitations.

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Cystic adenomyoma uteri confused with LEGH in Diagnosis
Yoko Tsuzuki, Shinichiro Wada, Masae Yamamoto, Kanako
Takimoto, Kaoru Minowa, Risa Tsunematsu, Kazuaki Imai,
Hajime Ota, Ayako Nakajima, Takuma Matsuda, Yoshiyuki
Fukushi, Takafumi Fujino Teine Keijinkai Hospital
Cystic lesions of uterus are rarely seen, in approximately 0.035%
of all uterine tumors. A cystic adenomyoma is one of them and abenign neoplasm composed of endometrial type glands andstroma with well formed smooth muscle bundles. We report acase of multiple cystic uterine adenomyoma confused with
Lobular endocervical glandular hyperplasia（LEGH）in diagnosis
before operation with a review of the literature. A 36 year old
woman（gravida 4, para 1）presented to our hospital complainingof abdominal distension without dysmenorrhea. MRI revealed
multiple cystic lesions, approximately 8cm in diameter, were located at corpus uteri to upper side of cervix uteri. Those cysts
showed a high intensity on T2 weighted image and a low intensity on T1. Diffusion weighted image and apparent diffusion coefficient map did not show malignant findings. The result ofuterine cervical biopsy was cervical squamous intraepithelial
neoplasia 3（CIN3）. We preoperatively diagnosed it as LEGH
and CIN 3. As she did not desire fertility preservation, we performed total laparoscopic hysterectomy and bilateral salpingectomy. The pathological diagnosis was adenomyoma of corpus
uteri and CIN 3. She discharged uneventfully on the postoperative third day in good condition.

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The size of endometrial polyps as predictors of spontaneous
vanishing prior to surgical procedures：a retrospective
analysis of hysteroscopic endometrial polypectomy Eriko
Yano, Wataru Isono, Yasunori Komatsu, Michiko Honda, Hiroko

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Analysis of the effect of microwave endometrial ablation fordysmenorrhea
Yoshinobu Hamada1, Teppei Ichikawa1,
Yasumasa Koroku1, Kanami Saito1, Naoki Yoshikawa1, Yoko
Saito1, Taichi Irie1, Kayo Suzuki1, Makoto Iizuka1, Kouhei
Sugimoto2, Shuichi Sakamoto1, Satoshi Takakura1 Dokkyo Medical University Saitama Medical Center 1, Reproduction Center
Dokkyo Medical University Saitama Medical Center 2
Objective Microwave endometrial ablation（MEA）alleviates thesymptons of menorrhagia. The efficacy of MEA for dysmenorrhea is controversial. We performed the retrospective analysis
to evaluate the efficacy of MEA for dysmenorrhea. Methods
Twelve patients who were treated with MEA for menorrhagia
between April 2012 and June 2017 and could be checked thecondition of menorrhagia and dysmenorrhea 3 6 months after
MEA according to medical records were investigated. We compared age, preoperative hemoglobin, uterine length, times of ablation, vertical diameter, anteroposterior diameter and transverse diameter of uterine body between the patients with alleviation of dysmenorea and the patients with no alleviation.
Mann Whitney U test was used. Results Menorrhagia was improved in all patients. In 9 patients dysmenorrhea was alleviated, diffuse adenomyosis was present in 6 patients and uterine
myoma was present in 3 patient. The rate of improvement ofdysmenorrhea was 75%（9/12）. Between 9 patient with alleviation of dysmenorrhea and 3 women without alleviation, no significant difference was observed in age（45.1±2.4 vs 41.0±2.6）,preoperative hemoglobin（9.3±1.9 g/dl vs 9.8±1.9 g/dl）,uterine
length（8.4±1.4 cm vs 8.8±1.3 cm）,times of sounding（6.4±2.8
vs 8.0±1.7）,anteroposterior diameter（61.4±20.7 mm vs 74.9±
20.7 mm）,transverse diameter（66.0±12.3 mm vs 70.2±5.0 mm）.
The vertical diameter of patients with alleviation of dysmenorrhea was shorter than that of patients without alleviation, significantly（56.4±8.5 mm vs 79.7±17.3 mm, p＜0.01）. Conclusion
In case of menorrhagia with short vertical diameter of uterine
body, the short term efficacy of MEA for dysmenorrhea may be

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Two cases of combined medical and surgical management of
rudimentary uterine horn pregnancy Daisuke Suzuki1,
Toshifumi Takahashi1, Satoshi Suzuki2, Manabu Kojima2, Shu
Soeda2, Hideki Mizunuma1, Keiya Fujimori2 Fukushima Medical
Center for Children and Women 1, Fukushima Medical University 2
Background A pregnancy within a noncommunicating rudimentary uterine horn pregnancy（NCRHP）is a rare entity, witha frequency of 0.24% to 0.6% of all ectopic pregnancies. We report two cases of noncommunicating rudimentary horn pregnancy that were medically terminated, with the patients subsequently undergoing uterine horn and fallopian tube resection.
Case report Case 1. The patient was a 19 year old nullipara.
She was considered to have a missed abortion, and had 2 gestational sacs（GSs）without heartbeats at 8 weeksʼ gestation. Because the gestational sacs remained intact during curettage, she
was diagnosed with NCRHP. Her serum level of human chorionic gonadotropin （ hCG ） was 40,199 mIU / ml. Aftermethotrexate injections into the GSs, 2 courses of systemic
methotrexate were administered. Laparoscopic surgery was
performed on day 106 after the initial methotrexate treatment.
The left rudimentary horn and fallopian tube were successfully
excised, with minimal bleeding. Case 2. The patient was a 30
year old nullipara. She was diagnosed with a left unicornuate
uterus with right noncommunicating rudimentary uterine hornby hysterosalpingography and magnetic resonance imaging. As
1 GS with heartbeat was observed in the right rudimentaryuterine horn at 6 weeksʼ gestation, she was diagnosed with
NCRHP. Her serum level of hCG was 104,619 mIU/ml. A single
methotrexate injection into the GS was administered. Laparoscopic surgery was performed on day 50 after the initial
methotrexate treatment. The right rudimentary horn and fallopian tube were successfully excised with minimal bleeding.
Conclusion Combined methotrexate treatment and laparoscopic
surgery for patients with NCRHP is safe and effective.

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Less invasive and easier vaginoplasty using laparoscopy andatelocollagen sponge Yoshiya Miyahara, Mizuki Uenaka,
Satoshi Nagamata, Kaho Suzuki, Senn Wakahashi, Yasuhiko
Ebina, Hideto Yamada Kobe University
Objective The purpose of this study was to validate the therapeutic efficacy of the innovative surgical approach using laparoscopy and atelocollagen sponge, and the commercialized
mould on the achievement of a satisfactory neovagina in patients with vaginal agenesis. Methods The current study involved six patients diagnosed as having Mayer Rokitansky
Kuster Hauser syndrome. At first, the exploration of the pelvic
and abdominal organs was performed carefully by laparoscopy.
Then, after creating a vaginal tunnel, the commercialized mould
wrapped with atelocollagen sponge was placed within the neovagina. The mould was started to insert into the neovagina at 7days after operation. Since this mould was easier to manage
compared with the previous methods using colon, it was lessstressful for the patients and doctors to master the procedure after operation. Results Median operation time was 116 minutes
and median blood loss was 75 ml. Median hospital stay was 22days. The median length of the neovagina at discharge was 8 cm
with two fingers in width in all patients. No remarkable postoperative complications were noted. At two months after surgery,the neovagina was confirmed to be completely epithelialized in
all patients, assessed by Schiller test. Conclusion This innovative surgical procedure using laparoscopy and the mould

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Tsuchiya, Reiko Matsuyama, Akira Tsuchiya, Akihisa
Fujimoto, Osamu Nishii Teikyo University Hospital, Mizonokuchi
Objective It is sometimes observed that endometrial polyps become unclear or even vanish by the time of operation when they
were previously visible at the time of diagnostic hysteroscopy
in the office setting. The objective of our study is to elucidate
the clinical factors that influence the vanishing of endometrial
polyps. Methods The medical records of 300 cases of hysteroscopic endometrial polypectomy from January 2015 to December 2017 in our hospital were retrospectively reviewed following the approval of our institutionʼs review board. We definedcases of interest as vanished polyp, in which the target polypwas not detected clearly by transvaginal ultrasound just before
operation. As factors that contribute to vanished polyp, we extracted the following 10 characteristics： advanced age（＞=
40 years）, small polyp size（=＜10 mm）, large body mass index（＞=22）, multiparity, presence of multiple polyps, infertility, dysmenorrhea, abnormal bleeding, and hormonal
drug use. Statistical multivariate analysis was performed. Results From the 300 cases, we extracted data of 184 cases, inwhich the size of polyps from both before and after hospitalization were available. Ten cases of vanished polyp were identified. In a multivariate analysis of the 10 factors, only small
polyp size showed a significant difference（odds ratio=6.8, P＜0.05）. Conclusion Our study revealed the possibility that endometrial polyps smaller than 10 mm may spontaneously vanish
without surgical assistance, regardless of the number of the polyps or symptoms present. This insight may contribute to reducing the unnecessary scheduling of surgery.

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wrapped with atelocollagen sponge may be a more useful andeasier approach for the treatment of vaginal agenesis.

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The efficacy of laparoscopic omentectomy in patients withgynecological cancer Risa Yoshimoto, Hatsuo Isogai, Takuji
Ueno, Takuma Yamada, Takehiko Takeda, Kaname Uno, Sho
Tano, Mayu Ukai, Teppei Suzuki, Toko Harata, Yasuyuki
Kishigami, Hidenori Oguchi TOYOTA Memorial HospitalObjective Omentectomy should be performed in patients withovarian cancer and borderline ovarian tumor. But laparotomy
with omentectomy often requires extending abdominal incision.
The purpose of this study was to evaluate the efficacy of laparoscopic omentectomy（LOM）.Methods This was a single centerprospective cohort study. Patients with gynecologic cancer between January 2016 and March 2017 were eligible for this study.
We analyzed the operative time, omental weight, the amount ofblood loss, and complications. Results Twenty four patientswere enrolled for this study. The mean age was 51.3 years, andthe mean BMI was 22.2 kg/m2. The prevalence of ovarian cancer, borderline ovarian tumor, cervical cancer, ovarian and cervical cancer, peritoneal cancer, and ovarian and endometrial
cancer were 12, 5, 2, 2, 2, and 1, respectively. Laparoscopic surgery was performed in 8 patients and the other 16 patients underwent both laparotomy and LOM. All patients were performed laparoscopic subtotal omentectomy, and visualizationand magnification of small lesions such as hepatic and splenic
flexure were better than laparotomy. The mean operative timeof LOM was 41.5 minutes, the omental weight was 189.5g, andthe estimated blood loss during LOM was small amount. All surgery could be accomplished without extending the incision to
the upper abdomen, and no patient experienced intraoperativeand postoperative complications. The mean hospital stay was 7.6
days. One patient of serous borderline tumor had peritoneal implant. Conclusion LOM is comparatively safe and an effective
treatment for the patients with ovarian cancer and borderline
ovarian tumor.

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Two cases of surgically treated genital chronic graft versus
host disease in females Yasuhiko Kamada1, Yuri Miyahara1,
Hirofumi Matsuoka1, Shiho Fujita1, Kotaro Kubo1, Toru
Hasegawa1, Ai Sakamoto1, Sayoko Kotani1, Mikiya Nakatsuka2,
Hisashi Masuyama1 Okayama University Hospital 1, Okayama
University 2
Allogenic hematopoietic stem cell transplantation（HSCT）is a
crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after HSCT, and such cases
may require hormone replacement therapy（HRT）. Genital
chronic graft versus host disease（GVHD）is another complication post HSCT. It starts with vulvar discomfort and dysuria
due to erosions, fissures, and ulcers, subsequently progressing todyspareunia and difficulty with penetration due to vaginal
stenosis and obstruction. Surgical interventions are occasionallynecessary in women with genital chronic GVHD to enable continuation of HRT and facilitate sexual intercourse. We report on
two women who underwent surgery for vaginal obstruction due
to genital chronic GVHD. Case 1 A 22 year old Japanese
woman was referred to us for treatment of hematocolpos. She
had received HSCT for acute myelogenous leukemia at the ageof 19 years. Her labia minora were fused in the midline. Magnetic resonance imaging（MRI）revealed that the lower two
thirds of the vagina were closed. She underwent vaginoplasty
using an artificial dermis（an atelocollagen sponge）. She could
have sexual intercourse 4 months after surgery. Case 2 A 24
year old Japanese woman was referred to us for hematometra

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and hematocolpos. She had received HSCT for acute lymphoblastic leukemia at the age of 18 years. Her vulvar synechia
was firm. MRI revealed that the lower one third of the vagina
was closed. She underwent vulvar adhesiolysis and removal ofvaginal blood. Laparoscopically assisted vaginal reconstruction
by Granjonʼs method was performed three months later. We believe that her condition has resolved.

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A retrospective review of re laparoscopy cases due to postoperative bleeding after laparoscopic surgery：Sequential
monitoring of intra abdominal drainage volume and vital
sign trend for prompt diagnosis and intervention Keisuke
Murakami1, Rie Ozaki1, Ayako Masuda1, Shinichiro Ikuma1,
Makoto Jinushi1, Keiji Kuroda1, Jun Kumakiri2, Mari Kitade1 Juntendo University Hospital 1, Tokyo Womenʼs Medical University
Hospital 2
Objective Postoperative bleeding is rare, but one of a serious
complication. Prompt diagnosis and intervention are crucial. In
this study, we aimed to identify signature of re laparoscopy
cases and then clarify value of monitoring drainage volume andvital sign trend for prompt diagnosis and intervention. Methods
Among 5,438 cases who underwent laparoscopic surgery for gynecologic benign pathologies at our institution between 2009
and 2016, twelve cases（0.2%）required re laparoscopy for postoperative bleeding. Initial surgical findings and postoperativedrainage volume and vital sign trends were reviewed. Relatively large drainage volume cases（total drainage volume atpostoperative 12 hours ＞300ml）who did not necessitate re laparoscopy were included for comparison（n=107, 2009 2016）.
Results Initial surgery of re laparoscopy cases were uterine
surgery（n=8, myomectomy；7, hysterectomy；1）, adnexal surgery（n=3）,uterus and adnexal combined surgery（n=1）. Bleeding sites were uterus（n=6）, adnexa（n=4）,trocar wound（n=1）,
mesentery suspected to be injured by first trocar approach（n=1）. Ten cases were successfully controlled hemorrhage by re laparoscopy, however, two cases in shock vital required further
intervention（laparotomy or arterial embolization）. Continuous
excessive drainage was observed in re laparoscopy cases,
whereas excessive drainage was transient in cases without relaparoscopy. Vital sign monitoring could not distinguish bothgroups in early stage. Conclusion Re laparoscopy is useful approach for postoperative bleeding. In cases with continuous excessive drainage, intervention should be undergone immediately before going into hemorrhagic shock.

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Two cases of perineal plastic operation for patients of persistent cloaca Mayu Nagata1, Kana Hiasa1, Keiko Kawamura1,
Teruhiko Kawamura1, Natsuko Yokota1, Katsuko Egashira1,
Kiyoko Kato1 Kyushu University 1, University of Occupational
and Environmental Health 2
Objectives Persistent cloaca is rare congenital anorectal malformation. Usually, multiple surgical procedures are required during the childhood for the correction of complicated problems.
We herein report two cases of perineal plastic surgery during
the long term follow of persistent cloaca. Case1 A 27 year old
woman had undergone proctoplasty and vaginal plastic surgery
as an infant. After menarche, vaginal dilation was performed byprosthesis. Before her marriage, she elected to receive dilatationof vaginal and perineal plastic surgery. First, we designed bilateral gluteal fold flaps, 8×3 cm, along with preserved perforating
branch of the perineal artery. We then rotated the flaps 120˚ andcovered around the vaginal introitus. The postoperative course
was normal. Case2 A 23 year old woman had undergone urethral and a vaginal plastic surgeries many times in childhood.

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ISP-63-9Tumorectomy for gynecological cancer recurrence：case series Sen Wakahashi, Yasuhiko Ebina, Kaho Suzuki, Yoshiya
Miyahara, Hideto Yamada Kobe University HospitalObjective We report single institution clinical outcomes ofwomen treated with tumorectomy for gynecological cancer recurrence. Methods From 2004 to 2016, 20 patients were treatedwith tumorectomy and retrospectively analyzed. Primary cancer diagnoses were 9 ovarian, 4 endometrial, 4 cervical, 1 tubal,
and 2 uterine sarcomas. The median age of the patients was 65
years（range, 38 to 83 years）. The complete resection rate andsurvival were analyzed. Progression free survival（PFS）was
determined using Kaplan Meier analysis. Results Median follow up was 17（range, 2 55）months. Recurrence locations were40% pelvic cavity, 15% lung, Liver, 15% paraaortic node, and 5%
inguinal node. We achieved in 75% a complete resection, and
55% of patient underwent treatment with after resected chemotherapy. In univariate analysis, age, cancer type（cervix, endometrial or ovary）were not associated with PFS. Whereas chemotherapy free interval（defined as the time from the date oflast chemotherapy to that of tumolectomy for recurrence）and
received or not after resected chemotherapy tended to be asso. Conciated with prognosis（P ＜0.01, and P =0.06, respectively）
clusion The tumorectomy is effective local treatment modality
in patients with gynecological cancer recurrence. Distant progression remains the primary mode of failure in this patient
population. In carefully selected patients, a combination of systemic treatment and tumorectomy may offer long term PFS.

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Women with Acute Abdomen and its Laparoscopic Management ― Senerio in Developing country
Jyoti Chaube1,
Mahendra Bhusari1, Sanjay Chaube1, Manish Jain2, Rajkumar
Verma2 St. Judeʼs Hospital, India 1, M L B Medical College, Jhansi,
India 2Gynecological emergency are majority four diseases ectopic
gestation, torsions of adnexa, rupture of ovarian tumour andovarian bleeding. Diagnostic modalities are inconclusive sometime or not available. laparotomy was the main option for thetreatment. Laparoscopy was used to confirm the findings of theimaging modalities and as therepeutic option in patients of gynecological emergency. Laparoscopic management was performed in 98 cases during a period of five years. In majority ofcases ectopic gestation was the cause. In 8 patients twisted
adnexa was there. Except two all were managed with laparoscopic method. Laparoscopy is a good modality to tackle the patients of acute abdomen of gynecological causes.

ISP-64-1
Subserosal Leiomyoma Complicated with Peritoneal Cysts
Difficult to Differentiate from Brenner tumor of the Ovary
Masafumi Katakura1, Takehiko Tsuchiya1, Tomoko Taniguchi1,
Junya Sakuma1, Masaru Nagashima1, Youhei Takano2, Yoshihiro
Yoshida2, Youichi Matsue2, Toshimitsu Maemura1, Masahiko
Nakata1, Yukiko Katagiri1, Mineto Morita1 Toho University
Omori Medical Center 1, Tokyo Rosai Hospital 2

It is difficult to discriminate between pedunculated subserosal
leiomyoma and solid ovarian tumor occasionally. Because ofpedunculated subserosal leiomyoma frequently grew in the direction of the adnexal lesion. We reported that a case of pedunculated subserosal leiomyoma complicated peritoneal cyst difficult to differentiate from Brenner tumor of the ovary. A 53
year old woman, G2P2. The menstrual cycle is irregular. The
patient was found to have the pelvic mass, but she did not seek
medical treatment. Her chief complaint was low back pain. The
pain was getting worse and worse as the day went on. She wasreferred to our hospital for further evaluation by her local physician for a huge pelvic mass by ultrasonography test. Magnetic
resonance imaging（MRI）test showed that 22 cm pelvic mass
at right adnexal area within complex solid and cystic mass. Her
serum tumor markers were within normal limits. These findings suggested that subserosal myoma, ovarian mutinous tumor
or Brenner tumor. After GnRH agonist for 2 months, the operation was undergone. Total abdominal hysterectomy and bilateral salpingo oophorectomy was undergone. Total specimen
weight was 2,390 g. The postoperative course was uneventful.
Pathological examination revealed that pelvic mass was Leiomyoma. Bilateral adnexa had no structural disorder. Peritoneal
cysts might have been adhesive caused by pedunculated subserosal leiomyoma. Leiomyoma caused inflammation. It is difficult
to differentiate a mass at the adnexal lesion complicated withsolid and cystic tumor. Therefore it is necessary to determine
the management of these findings carefully.

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A case of Leiomyomatosis peritonealis desseminata（LPD）
Kana Kasai, Takeshi Kato, Yuri Kadota, Kanako Yoshida,
Minoru Irahara Tokushima University
Leiomyomatosis peritonealis disseminate（LPD）is a rare disorder characterized by peritoneal dissemination of benign smoothmuscle nodule. Most cases occur in individuals of reproductive
age and often associated with pregnancy or oral contraceptive
use. Treatment is tumorectomy, but there is no consensus on
postoperative treatment. This disease is considered to be an estrogen dependent disease, and there are also papers that recommend GnRH agonist therapy. A 36 year old woman of gravida 2para 2 was introduced to our clinic for lower abdominal pain.
She had no history of abdominal surgery or hormone therapy.
MRI revealed large myoma uteri, and simple total hysterectomy
was performed. There were multiple myoma, and many nodular
tumors were disseminated on the greater omentum, mesentery
and Douglasʼ pouch. Both ovaries were normal. We suspected amalignant tumor, submitted a tumor of the peritoneum to therapid examination, but it was the result with leiomyoma. Simple
hysterectomy was performed and disseminated lesions werealso extracted within a possible range. Since every tissues wereleiomyoma in postoperative histopathology, this case was confirmed as LPD. In postoperative CT, disseminated masses of 1
cm in size were found in the peritoneum and Douglasʼ pouch,but no hematogenous metastasis was observed. Although we
recommended GnRH agonist therapy, patients did not wish andfollow up observation, but slghtly increase in tumor mass is recognized.

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ISP-64-3
Effect of uterine artery embolization using by microspheres：review of 129 cases Gen Ishikawa1, Yasunori Taki2,
Kimisato Asano3 Nippon Medical School 1, Chofu Keijinkai
Clinic 2, Artemis Womenʼs Hospital 3
Introduction After the year 2014, when use of microspheres foruterine artery embolization（UAE）came to be covered by insurance, number of procedure of UAE has been increased gradu-

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After menarche, vaginal dilation was performed by prosthesis.
She received vaginal and perineal plastic surgery similar tocase1, with a gluteal fold flap designed at the left side of body.
After operation, the wound was ravaged and antibiotics was administered, due to the infection of the wounded area. The subsequent postoperative course was normal. Conclusion The case of
infant persistent cloaca aims to achieve bowel control and urinary control. It is important to consider the prospect of a patientʼs marriage or their sexual function.

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ally in Japan. Methods Between April and August 2016, the hospital records of our facility who underwent UAE were retrospectively reviewed. Results During study period, 129 cases received UAE, and their median age was 44 years（range 35 53）.
All cases were received UAE in complete. Forty eight cases
were undertaken UAE by using only microsphere, in other 81
cases, they were given gelatin sponge additionally. In 48 cases
who were undertaken UAE by using only microsphere, their
median age was 44.5 years and 75% of them were nulliparous.
The median dose of microsphere was 4.5 vials（range 1.6 13.0）,
fluoroscopy time was 14.3 minutes（range 7.7 27.0）and exposure
dose was 483.3 mGy（range 193.0 1384.4）.Between preoperative
period and 1 year follow up, uterine volume was evaluated by
MRI. The percent reduction in uterine volume was 44.2%（range
13.9 82.4）. In those 48 cases, 28 cases were evaluated serum estradiol in 3 points（preoperative, 1 month and 1 year follow
up）. As those results, percent change of serum estradiol showed
69.9% at one month after and 77.8% at one year after. Conclusion
We showed clinical features and outcome of uterine fibroids
cases who underwent UAE by using microspheres in the manner of single institutional retrospective study. In all cases, there
was no major adverse event, and they received beneficial outcomes.

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ISP-64-4
Treatment outcomes of uterine artery embolization with microspheres for symptomatic fibroids：a single center experience Kyoso Ishida, Kenjiro Sawada, Aasa Shimizu, Masaki
Kobayashi, Eriko Yokoi, Akihiko Yoshimura, Erika Nakatsuka,
Michiko Kodama, Kae Hashimoto, Seiji Mabuchi, Tadashi
Kimura Osaka University
Objective Uterine artery embolization（UAE）
with microspheres（Embosphere）for uterine fibroids has been covered by insurance since January 2014 in Japan. We analyzed the efficacies of
UAE with microspheres for symptomatic uterine fibroids. Methods From January 2014 to August 2017, 34 premenopausal
women underwent UAE with microspheres at our hospital.
They were routinely followed up at 1, 3, 6, and 12 months after
the procedure, checked whether they had any UAE related
complications or not and evaluated the uterine fibroids related
symptoms. Pelvic magnetic resonance imaging（MRI）was performed before and at 3 and 12 months after the UAE and thechanges in volume of the uterine fibroids were calculated. Results Median age was 45 years（range 38 51 years）,and medianfollow up period was 12.7 months（range 1 39 months）.The volumes of uterine fibroids on MRI decreased by 31.4% at 3 monthfollow up and 44.2% at 12 month follow up compared to baseline volumes. During the follow up period, only one patient（2.9%）required hysterectomy because of enlarging fibroids after UAE. Conclusion Almost all the patients after UAE with microspheres had the symptomatic fibroids decreased and showed
improvement in fibroids related symptoms. UAE is one of thegood minimally invasive methods of treating for fibroids.

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ISP-64-5
Introduction and Experience to Uterine Artery Embolization
Yousuke Sakai, Hiroe Ito, Michirou Yushima, Naoaki Kuji,
Fumitoshi Terauchi, Hirotaka Nishi Tokyo Medical University
Hospital
The effective treatment options for uterine fibroids are expanding by patientʼs age and medical history, In 2014, Uterine Artery
Embolization（UAE）gained medical insurance and was introduced in our institution. This review will focus on the outcomeof treatment and satisfaction from UAE. Seven patients weretreated with UAE after acquiring informed consent from July
2016 to August 2017. Inclusion criteria；the average age of 43

years, symptomatic fibroids with no desire for surgery, patientsseeking symptomatic relief and no desire for children. The
mean fluoroscopic time was 38.8 minuts, mean exposure dose
was 815.5 mGy and the mean decrease in fibroid size was 57.6%.
Clinical improvement of symptoms in the most patient wasnoted post UAE. The degree of satisfaction was analyzed
through a set of questionnaire, and all patients gave a fair satisfactory review. The hormone level was within normal range andthe effect of UAE on ovaries was avoided. UAE is regarded as astandard treatment in United States and Western Europe, but it
is a relatively new in Japan. Publication of UAE as the substitute treatment of surgery to the new 2017 guidelines for Obstetrics and Gynecology, and its adaptation of medical health insurance could expand its usage in future. Most patients were satisfied with the procedure, no complications were noted and mostpatientʼs had an adequate reduction in the size of fibroids. UAE
is considered as a new treatment option for uterine fibroids regarding complicated surgical cases and preservation of uterus.

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