bluuebunny/crossref_metadata_2025 huggingface dataset:
PS02.047: TARGETED SILENCING OF SOX2 BY AN ARTIFICIAL TRANSCRIPTION FACTOR SUPPRESSED THE GROWTH OF ESOPHAGEAL CANCER CELLS
Authors: Yamatsuji Tomoki , Yokota Etsuko , Sera Takashi , Manabe Noriaki , Fukazawa Takuya , Naomoto Yoshio
Published: September 2018

Background

SOX2 is a transcription factor that is fundamental for early development and for the maintenance of stem cells in multiple adult tissues and also plays an important role in squamous cell differentiation. Amplification of chromosome 3q26 is the most common of the genetic alterations found in squamous cell carcinoma (SCC). SOX2 is a candidate oncogene present in this locus and amplification of SOX2 has been reported in lung and esophageal squamous cell SCC. In this study, we have developed a zinc finger-based artificial transcription factor (ATF) to selectively suppress SOX2 expression in cancer cells and termed the system ATF/SOX2.

Methods

We engineered the ATF using six zinc finger arrays designed to target a 19 bp site in the SOX2 distal promoter and a KOX transcriptional repressor domain. A recombinant adenoviral vector Ad-ATF/SOX2 that expresses ATF/SOX2 suppressed SOX2 at the mRNA and protein levels in esophageal SCC cells(TE1 and TE4) expressing SOX2.

Results

Ad-ATF/SOX2 decreased esophageal SCC cells proliferation and colony formation more effectively than the recombinant adenoviral vector Ad-shSOX2, which expresses SOX2 short hairpin RNA (shSOX2). Ad-ATF/SOX2 induced the cell cycle inhibitor CDKN1A more strongly than Ad-shSOX2. Moreover, Ad-ATF/SOX2 effectively inhibited tumor growth in a SCC xenograft mouse model.

Conclusion

In this study, we have shown that the targeted down-regulation of SOX2 using ATF based technologies can be used as an effective tool for the treatment of SCC in esophageal cancers that express SOX2. Our results indicate that ATF/SOX2 would lead to the development of an effective molecular-targeted therapy for esophageal SCC.

Disclosure

All authors have declared no conflicts of interest.
PS02.051: HMGB IS INVOLVED IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PROGRESSION
Authors: Matsubara Daiki , Konishi Hirotaka , Shoda Katsutoshi , Arita Tomohiro , Kosuga Toshiyuki , Shiozaki Atsushi , Kubota Takeshi , Fujiwara Hitoshi , Okamoto Kazuma , Otsuji Eigo
Published: September 2018

Background

High-mobility group box-1 (HMGB1), originally characterized as a non-histone, nuclear DNA-binding protein, acts as a crucial proinflammatory cytokine, mediating a broad range of inflammatory responses as a secretory form. Recently, it has been reported to be involved in the tumorigenesis and progression of various types of malignancies, but it is unclear whether HMGB1 plays an important role in the progression of esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the significance of HMGB1 in ESCC.

Methods

The tissue and plasma samples were obtained from ESCC patients at before or after operative period and healthy volunteers. The ESCC cell lines and normal human cell lines, such as fibroblast (WI-38) or Human umbilical vein endothelial cell (HUVEC), were used in vitro analyses. The expression levels of HMGB1 in tissue samples were measured by quantitative RT-PCR. The protein levels of HMGB1 were measured using the HMGB1 enzyme-linked immunosorbent assay kit in plasma samples, and using immunohistochemical staining or western blotting in tissue samples or cell lines. The functions of HMGB1 on the ESCC cell lines were investigated by proliferation, invasion, or migration assays.

Results

The mRNA and protein expression of HMGB1 in ESCC tissue was significantly higher than that in paired non-cancerous esophageal mucosa tissue. Plasma HMGB1 level was slightly higher, but not significant, in ESCC patients than in healthy volunteers. However, it was significantly higher in ESCC patients with Neoadjuvant chemotherapy (NAC) than in those without NAC. The mRNA and protein expression of HMGB1 were higher in ESCC cell lines than in WI-38 or HUVEC. In ESCC cells with high HMGB1 expression, knockdown of HMGB1 using specific siRNAs inhibited the cell proliferation, migration and invasion.

Conclusion

These findings suggest that HMGB1 plays a crucial role in tumor malignant potential through its overexpression in esophageal squamous cell carcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.053: DUAL-STRANDS OF MIR-150-DUPLEX (MIR-150–5P AND MIR-150–3P) ACTED AS ANTI-TUMOR MIRNAS THROUGH TARGETING SPOCK1 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Osako Yusaku , Seki Naohiko , Idichi Tetsuya , Kita Yoshiaki , Omoto Itaru , Sasaki Ken , Uchikado Yasuto , Natsugoe Shoji
Published: September 2018

Background

MicroRNAs (miRNAs) belong to a group of small non-coding RNA molecules that act as pivotal agents responsible for fine-tuning RNA expression in a sequence-dependent manner. A large number of studies showed that dysregulated miRNAs are deeply involved in the development of cancer cells, as well as their metastasis and drug resistance. Based on our original miRNA expression signatures by RNA-sequencing revealed that both strands of miR-150–5p (the guide strand) and miR-150–3p (the passenger strand) was downregulated in several cancers. The general concept of miRNA biogenesis posits that the passenger strand of miRNA (the minor strand or miRNA*) derived from duplex miRNA is degraded and does not regulate gene expression. Here, we aimed that to investigate functional significance of these miRNAs in esophageal squamous cell carcinoma (ESCC).

Methods

Cancer cell proliferation, migration and invasion abilities were performed by using mature miRNAs or siRNAs. Genome-wide gene expression analyses and in silico analyses were applied to identify miRNA target genes in ESCC cells.

Results

Expression levels of miR-150–5p and miR-150–3p were significantly reduced in ESCC clinical specimens and cell lines. Cancer cell aggressiveness was inhibited by ectopic expression of these miRNAs. A total of 12 genes were identified as oncogenic targets by both miR-150–5p and miR-150–3p in ESCC cells. SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miR-150–5p and miR-150–3p by luciferase reporter assay. Overexpression of SPOCK1 was detected in ESCC specimens and knockdown of SPOCK1 by siRNA significantly inhibited cancer cell migration and invasion abilities.

Conclusion

Both strands of miR-150-duplex (miR-150–5p and miR-150–3p) acted as anti-tumor miRNAs in ESCC. Overexpression of SPOCK1 was enhanced cancer cell aggressiveness. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept in cancer research. We suggest that identification of novel function of passenger strands of miRNAs and the RNA networks they regulate might enhance our understanding of the molecular pathogenesis of ESCC.

Disclosure

All authors have declared no conflicts of interest.
PS02.055: IN ESOPHAGEAL ADENOCARCINOMA (EAC) BARRET LIKE AND CARDIO PYLORIC LIKE SUB TYPES ARE DIFFERENTIATED ACCORDING TO MICRORNA (MIRNA) 221 AND 483–3.P EXPRESSION PROFILES
Authors: Bonora Elena , Isidori Federica , Bozzarelli Isotta , Lugaresi Marialuisa , Malvi Deborah , Räsänen Jari , Kauppi Juha , Sala Claudia , Castellani Gastone , D’Errico Antonietta , Fiocca Roberto , Seri Marco , Krishnadath Kausilia , Mattioli Sandro
Published: September 2018

Background

miRNAs play a key role in cancer development. In esophageal adenocarcinoma (EAC), we analyzed the relationship between miR-221 and 483–3p expression, cancer specific survival, recurrence, their distribution in EAC sub types characterized by the presence/absence of intestinal metaplasia in esophagus (BIM) and stomach (GIM) [BIM + GIM- (Barret's like) and BIM-GIM- (cardio-pyloric like) types].

Methods

RNAs was extracted from 39 formalin-embedded surgical specimens (EAC and normal gastric). miRNA221 and miR-483–3p validation with TaqMan MicroRNA Assay was performed and data were normalized using RNU44. Kruskall-Wallis and Mann-Whitney tests were used to study correlations.

Results

A statistically significant relationship between miRNAs (miR-483–3p P = 0.017; miR-221 P = 0.037) and cancer specific survival and between miR-221 and recurrence (P = 0.043) was detected. miR-221 and miR-483–3p showed a significant decreased expression in the Barret's like group vs Cardio-pyloric-like group (miR-483–3p Kruskall-Wallis test P = 0.009; miR221 Kruskall-Wallis test P = 0.066; miR-483–3p Mann-Whitney test P = 0.002; miR-221 Mann-Whitney test P = 0.047)

Conclusion

In EAC increase of miR-221 and miR-483 is linked with poor survival and recurrence. Their different distribution patterns, support a biological differentiation of Barret's like versus cardio-pyloric like subtypes.

Disclosure

All authors have declared no conflicts of interest.
PS02.057: INDUCTION OF APOPTOSIS IN ESOPHAGEAL ADENOCARCINOMA CELLS BY CURCUMIN
Authors: Thieme René , Michiels Florian , Maurer Luisa , Hoffmeister Albrecht , Eichfeld Uwe , Dietrich Arne , Jansen-Winkeln Boris , Gockel Ines
Published: September 2018

Background

Curcumin naturally occurring in curry powder from Curcuma longa is an anti-inflammatory and anti-proliferative agent. It represses NFκB activation and induces apoptosis in cancer cells. Because, inflammation favours the onset of an intestinal metaplasia in esophageal squamous epithelial cells and esophageal carcinoma cells, a reduction of such processes may contribute to establish a stable disease and/or sensitization for chemotherapeutic approaches.

Methods

Curcumin receptivity was investigated in metaplastic (CP-A), dysplastic (CP-B), adenocarcinoma (OE19, OE33), and esophageal fibroblast (FFE3) cell lines, which were treated with 10 or 25 μM Curcumin for 48h or 72h. Response to Curcumin was measured by proliferation assays as well as by induction of apoptosis and Akt activation by western blot analyses.

Results

The EAC cell lines OE33 and OE19 show a decrease of proliferation with raising curcumin concentration with an IC50 of 9.6 and 14.8 μM, respectively. While the metaplastic and dysplastic cell lines showed a comparable IC50 of 7.7 and 11.6 μM to the EAC cell lines, the FEF3 cell showed a higher IC50 of approx. 20μM. The phosphorylation of Akt was decreased and apoptosis was induced, showing cleaved PARP, when treated with 25μM curcumin after 48h and 72h.

Conclusion

Metaplastic, dysplastic and EAC cells show a higher receptivity to curcumin than esophageal fibroblasts cells. This constrains the NFκB activation and its contribution in the manifestation of the Barrett's esophagus. The usage of curcumin to generate an anti-inflammatory microenvironment will potentially help to develop a stable disease or to reverse the development of the Barrett's esophagus.

Disclosure

All authors have declared no conflicts of interest.
PS02.060: EXPLORATION OF RADIOSENSITIVITY-RELATED LNCRNA IN ESOPHAGEAL CANCER STEM CELL
Authors: Li Jiancheng , Sun Weijie
Published: September 2018

Background

Esophageal cancer stem cells are the most radiation-resistant cells, to study radiosensitivity with esophageal cancer stem cells is a better method, Previously study was only the relevant microRNA research, so we explore radiosensitivity-related LncRNA in esophageal cancer stem cell.

Methods

The Eca109 cells were divided into tumor sphere cells group and adherent cells group by using suspended and adherent culture. Differences in stem cell characteristics of two groups were compared by CD44 positive expression rate, CCK8 cell proliferation and plate cloning formation. Using Arraystar LncRNA microarray analysis the gene expression differences of CD44+ esophageal cancer stem cells and CD44− esophageal cancer cells sorting out by flow separation technology. Bioinformatics analysis and real-time PCR were applied to verified the specific LncRNA related to radiation sensitivity of esophageal cancer stem cells.

Results

1.The result of CCK8 cell proliferation experience showed that the absorbance value of the tumor sphere cells group was significantly higher than and adherent cells group after 24h, 48h and 72h (P < 0.05). The cell clone formation rate of the tumor sphere cells group was higher than adherent cells group (P < 0.05). 2. The plate cloning formation showed that the values of D0, Dq, N and SF2 were significantly higher in the tumor sphere cells group than adherent cells group, and the radiation sensitization ratio was 1.556. 3. Arraystar LncRNA chip analysis showed following the criteria that DEGseq at |log2Ratio| ≥ 1和q < 0.05, 4961 DEGs including 2517 up-regualted genes and 2444 down-regulated genes were identified. 4. We verified the top 10 difference LncRNA genes by realtime PCR. The results showed that MSTRG. 73,085 was down-regulated and its expression level on average was 20.7 times (chip was 49.3 times), CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated and their expression level on average were 2.7, 8.7, 3.7, 5, 7 (chip were 8.2, 5.2, 78.9, 3, 4.7 times).

Conclusion

We verified the different LncRNA genes by arraystar LncRNA chip and realtime PCR, The results showed that MSTRG. 73,085 was down-regulated and CH17–360D5.2, RP11–439E19.10, MSTRG.424, MSTRG.64087, MSTRG.15903 was up-regulated. These LncRNA genes may be related to the radiosensitivity of esophageal cancer stem cells and could be a potential new target for esophageal squamous carcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.068: CORRELATION BETWEEN 18F-FDG PET/CT METABOLIC PARAMETERS AND LYMPH NODE METASTASIS OF ESOPHAGEAL CANCER
Authors: Li Jiancheng , Chen Shaoxing , Wu Haishan , Huan Zhiyu
Published: September 2018

Background

The regional lymph nodes metastasis plays a crucial role in treatment strategies selection. Nowadays, computed tomography (CT) scan and endoscopic ultrasound (EUS) were main examination techniques to assess the regional lymph nodes metastasis. PET/CT metabolic parameters correlated to the lymph node metastasis, but the value of the prediction of lymph node metastasis need to be confirmed in additional studies.

Methods

82 esophageal cancer patients that were pathologically confirmed and received initial treatment in our hospital from October 2011 to September 2016 were retrospectively analyzed. All patients underwent systemic 18F-FDG PET/CT examination within two weeks before operation. The metabolic parameters of primary lesions and postoperative pathological lymph node metastasis of esophageal cancer patients were recorded. The correlation between lymph node metastasis and metabolic parameters of primary lesion of esophageal cancer were analyzed by ROC curve and logistic binary regression.

Results

1. The correlation between metabolic parameters of primary lesion (including SUVmax, SUVmean, MTV, TLG, HF) and lymph node metastasis were analyzed by ROC curve and logistic binary regression. Results showed that the P value obtained from the two methods was less than 0.05, suggesting that there was correlation between metabolic parameters of primary lesion and lymph node metastasis of esophageal cancer. 2. Multivariate analysis showed that only TLG had statistical significance, P = 0.027, suggesting that TLG of primary lesion had a certain diagnostic value for the lymph node metastasis of esophageal cancer. 3. ROC curve analysis showed that, the area under the curve (AUC) was 0.722 when TLG > 24.08, P = 0.001, suggesting that the minimum TLG of lymph node metastasis of esophageal cancer was 24.08. In addition, the thoracic esophageal cancers at the upper and middle segment were statistically significant. When TLG > 23.06, its AUC was 0.755, P = 0.001, suggesting that the minimum TLG was 23.06.

Conclusion

18FDG-PET/CT metabolic parameters (SUVmax, SUVmean, MTV, TLG, HF) is closely related to lymph node metastasis of esophageal cancer. The TLG has a certain diagnostic value for the lymph node metastasis of esophageal cancer.

Disclosure

All authors have declared no conflicts of interest.
PS02.074: ENDOSCOPIC TUMOUR MORPHOLOGY AFFECTS SURVIVAL IN OESOPHAGEAL CANCER
Authors: Habib Wais , Zylstra Janine , Knight William , Bott Rebecca , Mahadeva Ula , Davies Andrew , Gossage James
Published: September 2018

Background

Oesophageal carcinoma can present with a variety of endoscopic morphologies. No previous studies have ascertained whether endoscopic tumour morphology impacts survival. This study describes three distinct endoscopic tumour morphologies; ulcerating, exophytic and stenosing, and analyses their impact on survival.

Methods

This is a retrospective cohort study of 181 patients who underwent diagnostic endoscopy prior to oesophagectomy at St Thomas’ Hospital, London. Univariable and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals for overall survival.

Results

There were 56 ulcerating, 68 exophytic and 57 stenosing lesions. Median survival was 52.7 months for ulcerating lesions, 46.8 months for exophytic lesions and 33.8 months for stenosing lesions (P = 0.01). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on univariable analysis (exophytic HR 0.53; 95%CI 0.21–0.95, ulcerating HR 0.37; 95%CI 0.19–0.73).

Conclusion

This study demonstrates that endoscopic morphology may be an important prognostic factor in oesophageal cancer. Further studies are needed to confirm whether this is an independent prognostic indicator which may help guide future neoadjuvant and surgical treatment strategies.

Disclosure

All authors have declared no conflicts of interest.
PS02.080: CLINICAL SIGNIFICANCE OF THE NUMBER OF PERITUMORAL LYMPHATIC VESSELS AFTER CHEMOTHERAPY IN ESOPHAGEAL CANCER PATIENTS
Authors: Hara Takeo , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuyuki , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro
Published: September 2018

Background

Neoadjuvant chemotherapy (NAC), a standard treatment for locally-advanced esophageal cancer, often achieves significant antitumor effect as clinically or microscopically confirmed. However, how chemotherapy histologically impacts upon normal tissues, in particular lymphatic vessels, adjacent to a tumor remains unclear.

Methods

A total of 137 patients who underwent curative esophagectomy with (NAC group n = 62)/without (nonNAC group n = 75) NAC for thoracic esophageal cancer in our department from 2004 to 2012 were analyzed. The number of lymphatic vessels (NLV) adjacent to primary tumor (within 1000μm from the edge of tumor) in lamina propria mucosae layer was assessed by immunostaining of D2–40 and its association with clinico-pathological parameters was analyzed.

Results

The NLV was significantly lower in the NAC group as compared with the nonNAC group (NAC vs nonNAC; 19.1 ± 9.0 vs 22.8 ± 8.6, P = 0.014). In the nonNAC group, when classified into two (high vs low NLV) groups by using the cutoff value of the median NLV in nonNAC group, NLV did not correlated with any clinico-pathological factors including age, gender, tumor location, pT, pN, pM, ly, v, and overall survival. On the other hand, in the NAC group, high NLV (classified by the same cutoff value as noted above) was significantly associated with good histological response (grade1b-2) (high vs low NLV; 52 vs 26%, P = 0.026) and less development of lymph node recurrence (16 vs 40%, P = 0.029) but not with other parameters including age, gender, tumor location, pT, pN, pM, ly, and v. Notably, the high NLV group showed the more favorable 5-year overall survival compared to the low NLV group (61 vs 49%, P = 0.0041). Multivariate analysis of overall survival further identified low NLV (HR = 3.68, 95%CI 1.54–10.83, P = 0.0005) to be one of independent prognostic factors along with pT(HR = 2.87, 95%CI 1.37–6.35, P = 0.0050) and pN(HR = 4.04, 95%CI 1.53–13.89, P = 0.0034) in the NAC group.

Conclusion

NAC might decrease the number of lymphatic vessels adjacent to primary tumor in resected specimen, and this number was associated with tumor response to NAC and long-term outcome in patients who underwent NAC plus surgery.

Disclosure

All authors have declared no conflicts of interest.
PS02.082: OPTIMAL TIMING FOR ASSESSMENT OF TUMOR RESPONSE TO NCRT WITH MRI IN PATIENTS WITH ESOPHAGEAL CANCER
Authors: Borggreve Alicia , Heethuis S , Goense L , Van Rossum P , Van Lier A L H M W , Hillegersberg Richard , Ruurda Jelle , Lagendijk J , Mook Stella , Meijer G J
Published: September 2018

Background

Accurate identification of esophageal cancer patients with a pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) could enable safe omission of surgery in these patients. Diffusion-weighted (DW-)MRI imaging during the first 2–3 weeks of nCRT has shown promising results in the prediction of pCR to nCRT in esophageal cancer. However, the optimal timing of scanning for pathologic response prediction is unclear. The purpose of this study was to assess the optimal timing of DW-MRI scanning during nCRT to predict pCR.

Methods

Consecutive patients with esophageal cancer undergoing nCRT (carboplatin/paclitaxel combined with 41.4Gy), followed by esophagectomy were eligible for inclusion in this prospective study. Patients underwent 6 sequential MRI scans of which one was performed prior to nCRT, and 5 were performed weekly during nCRT. The relative change in median tumor apparent diffusion coefficient (ADC) of the tumor on DW-MRI was determined at these six time points: ΔADC week(n)(%) = (ADCweek(n)-ADCbaseline)/ADCbaseline*100%. Response to nCRT was determined based on histopathologic evaluation of the resection specimen.

Results

A total of 123 MRI scans of 21 patients with locally advanced esophageal cancer were analyzed. A pCR was found in 23.8% (5/21). Results of the linear mixed model analysis and logistic regression analysis (per week) are depicted in Table 1. The difference in tumor ADC values between pCR and non-pCR patients was most prominent in week 3 of nCRT (after 12–14 fractions, P = 0.04).

Conclusion

The treatment-induced changes on DW-MRI during the first 3 weeks of nCRT appear to be the most promising for prediction of pCR in esophageal cancer patients. This information can be used in future DW-MRI validation studies, and eventually lead to accurate preoperative identification of pCR.

Disclosure

All authors have declared no conflicts of interest.
PS02.090: WHY BARRETT’S ESOPHAGEAL ADENOCARCINOMAS WERE FOUND AS WIDE LESIONS
Authors: Yamasaki Akira , Fujisaki Junko , Yamamoto Yasunori , Ishiyama Akiyoshi , Yoshio Toshiyuki , Tsuchida Tomohiro , Sasaki Yutaka
Published: September 2018

Background

Barrett's esohageal adenocarcinoma(BEA) originated from Long-segment Barrett's esophagus(LSBE) were found to be larger lesions than BEA from Short-segment Barrett's esophagus(SSBE). In Japan, superficial BEA were found and treated by ESD. However, most of superficial BEA in Japan are originated from SSBE. We investigated about the differences between BEA from SSBE and LSBE.

Methods

We examined macroscopic appearance and histology for superficial BEA. And we compared with BEA between SSBE and LSBE.And then we examined imminohistochemical study using p53 for operated specimens of superficial BEA.

Results

The multiple lesions were presented only LSBE cases. Operations were the far more common treatment for LSBE. The ratio of lesions involving more than one-half of the lumen was significantly larger in LSBE cases. The percentage of type 0-IIb was only 3.2%(3/95) for SSBE, whereas 32.6%(15/46) for LSBE (P < 0.05). When we placed each macroscopic type into one of two groups (Elevated and Flat or depressed type), we found that elevated types accounted for 63.2%(60/95) in SSBE cases. In LSBE cases, 50.0%(23/46) were of the flat or depressed type. In SSBE, simple macroscopic types accounted for 69.5%(66/95). Whereas, in LSBE cases, 50.0%(23/46) were of complex macroscopic types (P < 0.05). The lesions with accompanied type 0- IIb accounted for 2.1%(2/95) of SSBE and 21.7%(10/46) of LSBE(P < 0.05). The more common macroscopic type of T1b invasion was type 0- IIa +  IIc. p53 immunohistochemical study was done for an operated specimen. This case was operated for superficial BEA. p53 was strongly positive on adenocarcinoma. However, we could find p53 strongly positive part on other part of the specimens. There were three part of p53 positive are in this operated specimens. These parts were not defined adenocarcinoma by HE stained.

Conclusion

Most superficial BEA originated from SSBE could be distinguished by the elevated lesions. Whereas, in cases of LSBE, flat type lesions including the accompanied type 0- IIb and multiple lesions, operation cases, the ratios of lesions involving a large range and the complex macroscopic types were significantly higher. When we diagnose and treat superficial BEA, it is necessary to consider the differences between SSBE and LSBE, such as macroscopic types.

Disclosure

All authors have declared no conflicts of interest.
PS02.095: THE FIRST SERIES OF ESOPHAGEAL ESD FOR SUPERFICIAL SQUAMOUS CELL CARCINOMA IN THAILAND
Authors: Swangsri Jirawat
Published: September 2018

Background

Esophageal cancer is 11th common in Thailand and incidence of new case is around 2500 cases per year. Because of screening protocol is unavailable then most of patient come to hospital with advanced stage cancer which relate with poor quality of life and survival out come. We are pioneer of early esophageal screening and treatment and begin screening endoscopy since 2015 and first case ESD was success on 30 Sep 2015. Until now our unit accomplished esophageal ESD for 8 cases and report in this case series.

Methods

During 2015 - 2017 esophageal cancer parient visit out patient clinic at Siriraj hospital around 260 cases and 7 cases of superficial esophageal squamous cell carcinoma were detected. Clinical staging was evaluated by magnified power endoscopy to detect IPCL and EUS was underwent. ESD was decided for both therapeutic and diagnostic procedure. All of 7 cases were accomplished ESD in 8 procedure (1 case present of metachronous lesion and performed 2nd ESD).

Results

All of 7 patients were success 8 ESD. Average lesion size is 2.68 cm in diameter. Average operative time is 182.25 min. Pathological report of HGD for 3 cases, m2 for 1 case, Sm1 for 2 cases and Sm2 for 1 case. 1 patient present of metachronous after 1st ESD 11mo and success 2nd ESD. Local recurrent found in 2 case post 1st ESD 11 mo and 14 mo respectively, treatment by APC. Post ESD perforation found in 2 cases, both of them were full recovery by non operative treatment by fully cover SEMS. No major bleeding or severe pulmonary complications were found. No evidence of 30 - day mortality. Longest follow up period is 29 mo. Average recurrent time is 12 mo (3 cases). No evidence of distance or lymphatic metastasis in all patients.

Conclusion

Esophageal ESD was established in Japan more than 20 year ago and just beginning in Thailand from 2015. Our report of initial ESD experiences for superficial esophageal cancer. Even though learning time and more volumn practice is needed, however this procedure found low rate of severe complications and can improve survival benefit as well. This knowledge should be distributed nationwide in near future.

Disclosure

All authors have declared no conflicts of interest.
PS02.096: ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL HIGH-GRADE SQUAMOUS DYSPLASIA: A CASE REPORT
Authors: Ying Khoo Hui , Voon Kelvin , Yee Lim Shyang
Published: September 2018

Background

Endoscopic resection is a novel therapeutic technique for early esophageal cancer and it is indicated in well differentiated superficial M1 or M2 lesion. The selection criteria have been expanded to selected M3 and SM1 lesion with the advancement of endoscopic technology and detailed study of relation between depth of lesion and lymphatic spread.

Methods

We report a case of endoscopic submucosal dissection (ESD) for esophageal high grade dysplasia.

Results

Madam S, a 50-year-old lady with no known medical illness, presented with gradual dysphagia for 1 year. She had no prior history of corrosive ingestion or reflux disease. She was diagnosed with esophageal stricture and underwent esophageal dilatation twice, before she was referred to our center. Clinical examination revealed no abnormality and her BMI was 25. OGDS revealed a 1cm superficial ulcerative lesion at proximal esophagus (25cm from incisor) with abnormal capillary pattern on narrow band imaging. Biopsy revealed high grade intraepithelial neoplasia. PET-CT showed metabolically active esophageal lesion with no distant metastasis. She decided for ESD after given the option of endoscopic treatment versus esophagectomy. ESD was done (Figure 1) and she had an uneventful recovery. Histopathology revealed complete resection of high grade squamous dysplasia.

Conclusion

Endoscopic treatment is less invasive option for early esophageal tumour which spares patients from esophagectomy and the related morbidities. However, it carries the risk of incomplete resection, recurrence and under-staging of the disease. It also requires highly specialized center and has a steep learning curve. Careful patient selection and proper pre-operative counseling are crucial in endoscopic treatment of early esophageal cancer. Long term surveillance is needed for early detection of recurrence.

Disclosure

All authors have declared no conflicts of interest.
PS02.098: LONG-TERM OUTCOMES OF ADDITIONAL THERAPY FOLLOWING ENDOSCOPIC RESECTION FOR T1B-SM ESOPHAGEAL CANCER
Authors: Tanaka Tsuyoshi , Ueno Masaki , Iizuka Toshiro , Hoteya Shu , Haruta Shusuke , Udagawa Harushi
Published: September 2018

Background

Esophagectomy is the standard treatment strategy for superficial esophageal cancer diagnosed as pT1b(sm) following endoscopic resection (EMR/ESD). However, chemoradiotherapy (CRT) is expected to be an alternative treatment option. This study retrospectively compared the long-term outcomes of surgery and CRT as additional treatments for EMR/ESD pT1b esophageal cancer.

Methods

In a retrospective single-center study, the data of 83 consecutive patients who underwent EMR/ESD and were diagnosed with pT1b(sm) from January 2002 to December 2013 were collected, and additional treatment was administered to 59 of these patients (26 surgery and 33 CRT). Long-term outcomes, recurrent patterns, and risk factors for recurrence were analyzed.

Results

Median patient age was 63 (range, 43–79) years, and male/female ratio was 54:5. Tumor characteristics were as follows: location, Ce/Ut/Mt/Lt/Ae/EG = 1/6/32/13/3/4; median size, 25 (range, 5–88) mm; depth, sm1/sm2 = 18/41; vascular invasion (ly, v), + / − = 37/22; and cut end (HM, VM), + or × / − = 17/42. Sex, Charlson comorbidity index, tumor size, macroscopic type, cut end, and resection state were not different between the two groups. Meanwhile, age, tumor location, histological type, tumor depth, and vascular invasion were different between the two groups. The 5-year survival rates (relapse-free survival rate; RFS) were 92.3% (92.3%; RFS) and 80.3% (70.4%; RFS) in the surgery and CRT groups, respectively. The surgery group was significantly superior to the CRT group in terms of RFS (P = 0.042). All tumor recurrence was observed in the CRT group (P = 0.030). Recurrent patterns were as follows: hematogenous metastases (lung, bone, and adrenal gland) in three patients and lymph node metastases (four regional and an extra-regional) in four patients. In multivariate analysis, tumor size (P = 0.048) and lymphatic invasion (P = 0.032) were revealed as significant risk factors for recurrence in the CRT group.

Conclusion

Surgery is recommended as the additional treatment for ESD/EMR-pT1b esophageal cancer for better recurrent-free survival. Although CRT could be an acceptable treatment choice, the indication should be carefully decided, particularly in cases with large tumor size or lymphatic invasion.

Disclosure

All authors have declared no conflicts of interest.
PS02.101: PREOPERATIVE TREATMENT BASED ON THE DCF CHEMOTHERAPY AND SUPPORTIVE THERAPY FOR ESOPHAGEAL CANCER
Authors: Tanabe Shunsuke , Shirakawa Yasuhiro , Maeda Naoaki , Ninomiya Takayuki , Noma Kazuhiro , Fujiwara Toshiyoshi
Published: September 2018

Background

The neoadjuvant chemotherapy using CDDP and 5-FU(CF) is the standard treatment for advanced esophageal cancer, defined as clinical stage II/III in Japan. However, more powerful chemotherapy has been required for the treatment of cases of cStageIII cases. In 2011, the combination treatment of CF and Docetaxel (DCF) was introduced for the treatment of those cases in our institute. DCF therapy increased chemotherapy remarkable cases. But, adverse events occur at high rates, including high myelosuppression. Therefore, it is necessary to ensure support by early intervention of supportive therapy so as not to exacerbate adverse events. We report about treatment outcome in preoperative DCF therapy cases.

Methods

We treated 128 esophageal cancer patients who underwent surgery following preoperative DCF therapy between 2011 and July 2017, and preoperative DCF was administered to 128 patients 2 course completely. The neoadjuvant chemotherapy regimen using DCF is Docetaxel:70mg/m2 (day1) + CDDP:70mg/m2 (day1) + 5-FU:700mg/m2 (day1–5).

Results

In the preoperative DCF group, overall response rate (over PR) was 51.5%. There were 37 cases in 128 cases of pathological tissue effect judgment for Grade 2 and 3. 14 cases of them (14cases/37cases:37.8%) had lymph node metastasis. Therefore it is necessary to control lymph node metastasis by surgery even in a remarkable group. Almost all patients experienced grade 4 adverse events, particularly neutropenia is a high frequency. From the start of chemotherapy, pretreatment of intraoral infection lesion and prevention and treatment of oral mucositis are performed. Considering the degree of myelosuppression during initial chemotherapy, in the second course, we actively administer G-CSF preparation.

Conclusion

A good prognosis can be expected if preoperative DCF therapy is effective. It is necessary to perform intensive and safe preoperative chemotherapy with appropriate supportive therapy intervention.

Disclosure

All authors have declared no conflicts of interest.
PS02.102: RESULTS FROM MULTICENTER, RANDOMIZED PHASE 3 FLOT4-AIO-TRIAL
Authors: Mönig Stefan , Al-Batran Salah
Published: September 2018

Background

The MAGIC trial established perioperative (periop) epirubicin, cisplatin, and 5-FU (ECF) as a standard treatment for patients (pts) with operable esophagogastric cancer, but survival continues to remain poor. FLOT4 (NCT01216644) is a multicenter, randomized, investigator-initiated, phase 3 trial (AIO-trial). It compares the docetaxel-based triplet FLOT with the anthracycline-based triplet ECF/ECX as a periop treatment for pts with resectable gastric or GEJ adenocarcinoma.

Methods

Eligible pts of stage ≥ cT2 and/or cN + were randomized to either 3 preoperative and 3 post-operative 3-week cycles of ECF/ECX (epirubicin 50 mg/m2, cisplatin 60 mg/m², both d1, and 5-FU 200 mg/m² as continuous infusion or capecitabine 1250 mg/m2 orally d1–21) or 4 pre-operative and 4 post-operative 2-week cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m², leucovorin 200 mg/m², and 5-FU 2600 mg/m² as 24-hour infusion, all d1). The primary endpoint was overall survival (OS; 80% power; HR of 0.76; 2-sided log-rank test at 5% type I error).

Results

Between Aug 2010 and Feb 2015, 716 pts (360 ECF/ECX; 356 FLOT) were randomly allocated. Baseline characteristics were similar between arms (overall, male 74%; median age 62; cT3/T4 81%; cN + 80%; GEJ 56%). 91% and 37% of pts with ECF/ECX and 90% and 50% with FLOT completed planned pre-operative and post-operative cycles, respectively. Median follow-up was 43 mon. 369 pts died (203 ECF/ECX; 166 FLOT). FLOT improved OS (mOS, 35 mon with ECX/ECF vs. 50 mon with FLOT; HR 0.77 [0.63 - 0.94]; P = 0.012). 3y OS rate was 48% with ECF/ECX and 57% with FLOT. FLOT also improved PFS (mPFS, 18 mon with ECX/ECF vs. 30 mon with FLOT; HR 0.75 [0.62 - 0.91]; P = 0.004). Periop complications were 50% with ECF/ECX and 51% with FLOT. 30- and 90-day mortality was 3% and 8% with ECF/ECX and 2% and 5% with FLOT. There was more G3/4 nausea and vomiting with ECF/ECX and more G3/4 neutropenia with FLOT.

Conclusion

Periop FLOT improved outcome in patients with resectable gastric and GEJ cancer compared to periop ECF/ECX.

Disclosure

All authors have declared no conflicts of interest.
PS02.110: PREDICTION OF PROGNOSIS BY EVALUATING RELATIVE CHANGE IN FDG-UPTAKE OF THE METASTATIC LYMPH NODES AFTER NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Yoshino Shigefumi , Takeda Shigeru , Kanekiyo Shinsuke , Kitahara Masahiro , Nishiyama Mitsuo , Iida Michihisa , Suzuki Nobuaki , Tokuhisa Yoshihiro , Tomochika Shinobu , Tokumitsu Yukio , Ueno Tomio , Hazama Shoichi , Nagano Hiroaki
Published: September 2018

Background

Prognosis of patients with esophageal squamous cell carcinoma (ESCC) can be significantly improved by neoadjuvant chemotherapy (NAC). The current best clinical method to predict pathologic response of chemotherapy is the maximum standardized uptake value (SUVmax) in 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). However, most of the FDG-PET evaluation has been focused on the primary tumors, but not on other metastatic lesions. The aim of this study was to determine the predictive value of FDG-uptake measured prior and after NAC both in the primary tumors and in the metastatic lymph modes (mLN) in ESCC.

Methods

Forty-five consecutive potentially resectable ESCC patients treated with NAC, which consisted of 2 courses of continuous infusion of 5-FU for days 1–5 and CDDP on day 1, between 2009 and 2016 were evaluated. FDG-uptake was measured at baseline and after chemotherapy in the primary tumors and in the mLN, and all patients underwent esophagectomy with R0 resection. The predictive values of FDG-PET and clinicopathological characteristics were determined with univariate and multivariate analyses.

Results

The median age was 66 years, with 35 males and 9 females. Pretreatment clinical classification of tumor depth was T1 in 9, T2 in 10, T3 in 26, respectively, and that of lymph modes metastases was N0 in 9, N1 in 12, N2 in 18, N3 in 6, respectively. The average SUVmax before and after NAC in the primary tumors was 13.9 and 7.9, respectively, and the average SUVmax reduction was 39.8% after chemotherapy. Pathological response was found to correlate well with the SUVmax reduction in the primary tumors, however, relative change in FDG uptake after chemotherapy was not associated with overall survival (OS). The average SUVmax before and after NAC in the mLN was 6.9 and 3.3, respectively, and the average SUVmax reduction was 46.2% after chemotherapy. Univariate and multivariate analyses revealed that both of the SUVmax and relative change in FDG uptake after chemotherapy in the mLN were well correlated with OS.

Conclusion

Post-NAC SUVmax and relative change in FDG uptake after chemotherapy in the mLN are valuable independent preoperative predictor of prognosis for patients with ESCC who received chemotherapy before surgery.

Disclosure

All authors have declared no conflicts of interest.
PS02.114: CLINICAL SIGNIFICANCE OF PREOPERATIVE CHEMORADIOTHERAPY FOR RESECTABLE ESOPHAGEAL CANCER PATIENTS USING PROPENSITY SCORE
Authors: Fujiwara Yoshinori , Kubota Hisako , Higashida Masaharu , Watanabe Yusaku , Okada Toshimasa , Uraoka Mio , Okamoto Yuko , Mineta Shyumei , Inoue Masatoshi , Fukuda Shuichi , Tsuruta Atsushi , Ueno Tomio
Published: September 2018

Background

Preoperative chemoradiotherapy(CRT) for advanced resectable esophageal cancer patients is controversial in Japan, and it is different from other countries. We examine the clinical significance of it using propensity score(PS).

Methods

142 patients in resectable cStageII/III/IV(TNM 6th edition) esophageal cancer patients were studied. There were 55 preoperative CRT cases (Group A), 87 patients with surgery alone(Group B). The survival was analyzed between the two groups. PS was calculated by Logistic analysis and the background factor was adjusted by the PS matching and IPTW(Inverse probability of treatment weighting) method for the preoperative CRT (Group A) vs surgery alone group (GroupB), Cox model was used to analyzed the prognostic factors.

Results

1, Unmatched situation: In OS(Overall survival), no difference was found between the two groups. In DFS(Disease free survival), the prognosis of group A was better than that of group B (5 years DFS: 52.2% vs 34.55%, P < 0.05). 2, After PS matching: OS, GroupA was tended to be better(P = 0.097). DFS: the prognosis of the Group A was better (5 years DFS: 57.2 vs 28.1%, P < 0.01). With Cox analysis, the presence or absence of preoperative CRT was a significant prognostic factor. 3, After IPTW: Prognosis of group A in both OS and DFS was better (5 years OS: 77.25 vs 41.13%, P < 0.05, 5 years DFS: 76.7 vs 32.14%, P < 0.01). In Cox analysis, preoperative CRT and TNM stages were independent prognostic factors.

Conclusion

1, Preoperative CRT for resectable advanced esophageal cancer is a recommended treatment by analyzing the PS. 2, IPTW and PS matching are different methods for evaluating PS, and since there is a possibility that different results may be occurred when evaluated between two groups by PS, the evaluation of it should be done more carefully.

Disclosure

All authors have declared no conflicts of interest.
PS02.115: PERIOPERATIVE CHEMOTHERAPY VERSUS NEOADJUVANT CHEMORADIATION FOR PATIENTS WITH ADENOCARCINOMA OF THE DISTAL OESOPHAGUS IN AUSTRIA
Authors: Koch Oliver , Tschoner Andreas , Partl Richard , Perathoner Alexander , Gehwolf Philipp , Weitzendorfer Michael , Varga Martin , Kapp Karin , Függer Reinhold , Öfner-Velano Dietmar , Emmanuel Klaus
Published: September 2018

Background

The aim of this study is to compare the outcome of patients with adenocarcinoma of the distal oesophagus (AEG Type I) treated with perioperative chemotherapy or neoadjuvant chemoradiation.

Methods

A retrospective analysis of eligible patients from four Austrian centers was conducted. All patients with AEG type I treated between January 2007 and October 2017 with chemotherapy (EOX-protocol) or chemoradiation (CROSS-protocol, or 5-FU/Cisplatin), followed by oesophagectomy were included in the study. Primary outcomes overall survival, and disease free survival as well as secondary outcomes, achievement of pathological complete response pCR (ypT0N0M0) or downstaging of T- or N-stage were analyzed. Primary outcomes were calculated by the Kaplan-Meier-method.

Results

Data of 117 patients were analyzed, 59 received chemoradiation (50/59 CROSS and 9/59 5-FU/Cisplatin) and 58 patients received perioperative chemotherapy (EOX). Complete data at time of submission were available in 40 patients in the chemoradiation group and in 37 patients in the chemotherapy group. The median follow-up time in the chemoradiation group was 13,0 months (CI 95%: 11,0–15,0) and in the chemotherapy group 45,0 months (CI 95%: 28,8–61,3). Overall survival rate in the EOX group after ½, 1, 3 and 5 years was 92%, 83%, 63% and 34%. So far long term data are not available after chemoradiation, after ½ year overall survival was 84% and after one year 60%. Disease free survival rate in the EOX group after ½, 1, 3 and 5 years was 91%, 81%, 54% and 32%, in the chemoradiation group after ½ and one year 80% and 50%. A significant difference was found in the pathological complete response (pCR) rate, it was achieved in 19% of patients after chemoradiation and in 3% after chemotherapy (P = 0000).

Conclusion

Concerning major response of the primary tumor there are clear advantages for chemoradiation. In regards to systemic tumor control there seems a tendency in favor for chemotherapy.

Disclosure

All authors have declared no conflicts of interest.
PS02.116: FEASIBILITY OF DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL (DCF) VERSUS RADIOTHERAPY WITH DCF (DCF-RT) AS PREOPERATIVE THERAPY FOR LOCALLY ADVANCED ESOPHAGEAL CANCER
Authors: Natsugoe Shoji , Sasaki Ken , Uchikado Yasuto , Okumura Hiroshi , Omoto Itaru , Osako Yusaku , Owaki Tetsuhiro
Published: September 2018

Background

In Japan, preoperative chemotherapy with cisplatin plus 5-fluorouracil (CF) followed by radical surgery has been accepted as the standard therapeutic approach for resectable esophageal squamous cell carcinoma (ESCC) result from a Japan Clinical Oncology Group randomized control trial. Whether preoperative chemoradiotherapy (CRT) followed by radical surgery is effective for Japanese ESCC patients has yet to be established. Some trials have reported usefulness of CF plus docetaxel therapy (DCF) for advanced or metastatic ESCC. Here, we have launched a randomized controlled trial to compare preoperative DCF versus DCF plus radiotherapy (DCF-RT) followed by surgery in locally advanced esophageal cancer.

Methods

Patients with clinical stage II/III (Japanese Classification of Esophageal Cancer, 11th Edition) are randomized to 2 groups. Patients in DCF group receive 2 courses of preoperative DCF (docetaxel, 60 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; 5-FU, 700 mg/m2/day, days 1–5) repeated every 3 weeks. Patients in DCF-RT group receive preoperative chemoradiotherapy (40Gy/20fr) with 2 courses of DCF (docetaxel, 30 mg/m2/day, day 1, 15; cisplatin, 7 mg/m2/day and 5-FU, 350 mg/m2/day, days 1–5, days 8–12, days 15–19, days 22–26). The primary endpoint is overall survival and the secondary endpoints include adverse events, response rate and pathologic complete response rate.

Results

Twenty-seven patients were assigned to the DCF group and 26 patients to the DCF-RT group. Grade 3/4 leukopenia and febrile neutropenia occurred 37% and 19% in the DCF group, 35% and 12% in the DCF-RT group. The clinical response rates were 16.0% and 64.0% in the DCF and DCF-RT group. Twenty patients and 23 patients underwent surgery in the DCF and DCF-RT group, and the R0 resection rate was 80.0% and 91.3%. With regard to the surgical complications, the incidence of anastomotic leakage was significantly higher in the DCF-RT group compared with the DCF group. The histological effects of DCF-RT were significantly higher than those of DCF. Two-year survival rate was 46% in the DCF group and 70% in the DCF-RT group.

Conclusion

The DCF and DCF-RT were found to be feasible as neoadjuvant therapy, and DCF-RT demonstrated higher efficacy than DCF in clinical stage II/III esophageal cancer patients.

Disclosure

All authors have declared no conflicts of interest.