bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-conflict reconstruction: Negotiating school leadership practice for inclusive education of conflict-affected children in Kenya
Authors: Wanjiru Jenestar
Published: January 2019

Provision of education during/after violent conflicts remains a global dilemma with many conflict-affected children excluded from/within education. Likewise, school leadership is increasingly seen as a key element in developing inclusive schools across communities. This single intrinsic case study with aspects of ethnography was conducted in one post-conflict community school in Kenya, where 71% of the pupil population comprised conflict-affected children following the 2007–2008 post-election violence. The aim was to explore and understand how the headteacher and teachers perceived and developed teacher participation in school leadership practice, in order to respond to learning and development needs of conflict-affected children, and promote inclusive practices in post-conflict schooling. Thematic analysis of interviews, observations, and textual displays indicated that by diagnosing the state of local affairs, that is, violence-disrupted livelihoods, school demographics, and systemic demands, the headteacher encouraged active participation of teachers in school leadership practices. Although overall accountability remained locked in hierarchical structures, teacher leadership emerged in arrangements like “office-referenced” individual leadership and collaborating groups (e.g., task groups and “team leadership”). With school leadership practice often attributed to headteachers in Kenya, this study contributes to debates on the construction of teacher leadership and offers insights into the experiences of school leaders in combating exclusionary practices after societal violence.
The International comparison of Systems of care and patient outcomes In minor Stroke and Tia (InSIST) study: A community-based cohort study
Authors: Levi Christopher R , Lasserson Daniel , Quain Debbie , Valderas Jose , Dewey Helen M , Alan Barber P , Spratt Neil , Cadilhac Dominique A , Feigin Valery , Zareie Hossein , Garcia Esperon Carlos , Davey Andrew , Najib Nashwa , Magin Parker
Published: January 2019

Rationale

Rapid response by health-care systems for transient ischemic attack and minor stroke (TIA/mS) is recommended to maximize the impact of secondary prevention strategies. The applicability of this evidence to Australian non-hospital-based TIA/mS management is uncertain.

Aims

Within an Australian community setting we seek to document processes of care, establish determinants of access to care, establish attack rates and determinants of recurrent vascular events and other clinical outcomes, establish the performance of ABC2-risk stratification, and compare the processes of care and outcomes to those in the UK and New Zealand for TIA/mS.

Sample size estimates

Recruiting practices containing approximately 51 full-time-equivalent general practitioners to recruit 100 TIA/mS per year over a four-year study period will provide sufficient power for each of our outcomes.

Methods and design

An inception cohort study of patients with possible TIA/mS recruited from 16 general practices in the Newcastle-Hunter Valley-Manning Valley region of Australia. Potential TIA/mS will be ascertained by multiple overlapping methods at general practices, after-hours collaborative, and hospital in-patient and outpatient services. Participants’ index and subsequent clinical events will be adjudicated as TIA/mS or mimics by an expert panel.

Study outcomes

Process outcomes—whether the patient was referred for secondary care; time from event to first patient presentation to a health professional; time from event to specialist acute-access clinic appointment; time from event to brain and vascular imaging and relevant prescriptions. Clinical outcomes—recurrent stroke and major vascular events; and health-related quality of life.

Discussion

Community management of TIA/mS will be informed by this study.
Clinically relevant drug interactions with multikinase inhibitors: a review
Authors: Hussaarts Koen G. A. M. , Veerman G. D. Marijn , Jansman Frank G. A. , van Gelder Teun , Mathijssen Ron H. J. , van Leeuwen Roelof W. F.
Published: January 2019

Multikinase inhibitors (MKIs), including the tyrosine kinase inhibitors (TKIs), have rapidly become an established factor in daily (hemato)-oncology practice. Although the oral route of administration offers improved flexibility and convenience for the patient, challenges arise in the use of MKIs. As MKIs are prescribed extensively, patients are at increased risk for (severe) drug–drug interactions (DDIs). As a result of these DDIs, plasma pharmacokinetics of MKIs may vary significantly, thereby leading to high interpatient variability and subsequent risk for increased toxicity or a diminished therapeutic outcome. Most clinically relevant DDIs with MKIs concern altered absorption and metabolism. The absorption of MKIs may be decreased by concomitant use of gastric acid-suppressive agents (e.g. proton pump inhibitors) as many kinase inhibitors show pH-dependent solubility. In addition, DDIs concerning drug (uptake and efflux) transporters may be of significant clinical relevance during MKI therapy. Furthermore, since many MKIs are substrates for cytochrome P450 isoenzymes (CYPs), induction or inhibition with strong CYP inhibitors or inducers may lead to significant alterations in MKI exposure. In conclusion, DDIs are of major concern during MKI therapy and need to be monitored closely in clinical practice. Based on the current knowledge and available literature, practical recommendations for management of these DDIs in clinical practice are presented in this review.
Multiple Stent Delivery System “Multi-LOC”: Focal self-expanding nitinol stenting of complex femoropopliteal lesions—A monocenter feasibility pilot study
Authors: Sigl Martin , Jung Johannes , Kölble Heinz , Amendt Klaus
Published: January 2019

Aims

The Multiple Stent Delivery System (VascuFlex® Multi-LOC) is a novel stent delivery system with six short stents (13 mm long each) mounted on one wire-guided catheter, designed for the treatment of femoropopliteal arteries. The aim of the present study is to evaluate the safety and the feasibility of the VascuFlex® “Multi-LOC” stent delivery system, which enables spot stenting without changing the delivery system.

Methods and results

After proof of concept in a porcine model and after European Conformity marking, first clinical experiences were gathered in 20 patients with severe intermittent claudication or critical limb ischemia. First-in-human data are presented. The study included 20 limbs that underwent femoropopliteal revascularization for claudication (n = 14) or critical limb ischemia (n = 6). “Multi-LOC” provisional spot stenting resulted in acute technical success in all lesions with resolution of flow-limiting dissection and elastic recoil after balloon dilatation of the femoropopliteal artery. There were no device-related complications. Follow-up examinations after 30 to 40 days revealed no major adverse events, and six months’ results were encouraging.

Conclusions

First clinical use of the novel Multiple Stent Delivery System (Multi-LOC) after balloon dilatation of the femoropopliteal artery was safe and feasible in this early study.
Current Strategies in Prevention of Postoperative Infections in Spine Surgery
Authors: Atesok Kivanc , Papavassiliou Efstathios , Heffernan Michael J. , Tunmire Danny , Sitnikov Irina , Tanaka Nobuhiro , Rajaram Sakthivel , Pittman Jason , Gokaslan Ziya L. , Vaccaro Alexander , Theiss Steven
Published: January 2019

Study Design:

Narrative review.

Objectives:

Postoperative surgical site infections (SSIs) are among the most common acute complications in spine surgery and have a devastating impact on outcomes. They can lead to increased morbidity and mortality as well as greater economic burden. Hence, preventive strategies to reduce the rate of SSIs after spine surgery have become vitally important. The purpose of this article was to summarize and critically analyze the available evidence related to current strategies in the prevention of SSIs after spine surgery.

Methods:

A literature search utilizing Medline database was performed. Relevant studies from all the evidence levels have been included. Recommendations to decrease the risk of SSIs have been provided based on the results from studies with the highest level of evidence.

Results:

SSI prevention occurs at each phase of care including the preoperative, intraoperative, and postoperative periods. Meticulous patient selection, tight glycemic control in diabetics, smoking cessation, and screening/eradication of Staphylococcus aureus are some of the main preoperative patient-related preventive strategies. Currently used intraoperative measures include alcohol-based skin preparation, topical vancomycin powder, and betadine irrigation of the surgical site before closure. Postoperative infection prophylaxis can be performed by administration of silver-impregnated or vacuum dressings, extended intravenous antibiotics, and supplemental oxygen therapy.

Conclusions:

Although preventive strategies are already in use alone or in combination, further high-level research is required to prove their efficacy in reducing the rate of SSIs in spine surgery before evidence-based standard infection prophylaxis guidelines can be built.
Establishing Clinically Significant Outcomes After Meniscal Allograft Transplantation
Authors: Liu Joseph N. , Gowd Anirudh K. , Redondo Michael L. , Christian David R. , Cabarcas Brandon C. , Yanke Adam B. , Cole Brian J.
Published: January 2019

Background:

Traditionally, the primary outcome in meniscal allograft transplantation (MAT) has been long-term survivorship; however, short-term clinically significant outcomes are necessary to fully evaluate patient improvement after surgery.

Purpose:

To (1) establish the minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) with respect to patient-reported outcome measures (PROMs) and (2) evaluate preoperative and intraoperative variables correlated with achieving these threshold values.

Study Design:

Cohort study (diagnosis); Level of evidence, 2.

Methods:

A prospectively maintained institutional registry was queried for all MATs performed between 1999 and 2017. The following PROM scores were collected: International Knee Documentation Committee (IKDC) score, Lysholm score, and Knee injury and Osteoarthritis Outcome Score (KOOS). Patients who completed preoperative and postoperative PROMs within a 1-month window were included to calculate the distribution-based MCID at this interval. An anchor question regarding satisfaction with surgery was asked at the same time point and was employed to determine the PASS using nonparametric receiver operating characteristic curve/area under the curve analysis. Multivariate regression analysis was performed to correlate patient demographics, medical history, and concomitant procedures to propensity in achieving the MCID and PASS.

Results:

A total of 98 patients who underwent MAT met the inclusion/exclusion criteria, of whom 10 underwent concomitant ligamentous procedures, 65 underwent concomitant cartilage procedures, and 7 underwent concomitant realignment procedures. The mean patient age was 29.4 ± 9.0 years, and the mean body mass index (BMI) was 26.8 ± 5.2 kg/m2. The distribution-based MCID and PASS were determined for the Lysholm score (12.3 and 66.5) and IKDC (9.9 and 36.0) as well as the KOOS Pain (9.9 and N/A ), Symptoms (9.7 and 73.0), Activities of Daily Living (9.5 and N/A), Sport (13.3 and N/A), and Quality of Life (14.6 and 53.0) subscales, respectively. A preoperative Short Form Physical Component Summary (SF PCS) score greater than 32.0 was predictive of postoperative satisfaction. Patients with work-related claims had a reduced likelihood of achieving the MCID for the IKDC and the PASS for the KOOS Symptoms. An increased BMI was also associated with failing to achieve the PASS for the KOOS Quality of Life (QOL).

Conclusion:

This study established the MCID and PASS for the Lysholm score, IKDC, and KOOS in patients undergoing MAT. Workers’ compensation and higher BMI were associated with failing to achieve clinically significant values. Lower preoperative Lysholm, IKDC, and KOOS scores were predictive of achieving the MCID, while higher preoperative SF PCS scores were associated with achieving satisfaction after MAT.
The Long Road to Economic Independence of German Women, 1973 to 2011
Authors: Haupt Andreas
Published: January 2019

Over the past few decades, women’s educational attainment and subsequent labor market participation have increased substantially in Germany. In comparison with these well-studied trends, little is known about changes in women’s contributions to couples’ joint income that may be associated with them. To address this question, the author provides a visualization of changes in the distribution of women’s income contributions in Germany from 1973 to 2011.
Puzzling in Teams: A Multipurpose Group Activity for Teamwork, Communication, Problem Solving, and Creativity
Authors: Crowne Kerri Anne
Published: January 2019

Completing a jigsaw puzzle can be a fun activity, but it can also be a learning experience. Here an exercise is presented that involves student teams completing a simple puzzle while at least one of the members is blindfolded. The blindfolded member is the only member allowed to touch the puzzle pieces, and the other team members have to communicate how to put the puzzle together to the blindfolded member. The activity has often been used to introduce a broad spectrum of management topics on the first day of class. It may also be used to highlight specific topics such as teamwork, communication, problem solving, and creativity. The activity requires little set-up and preparation for the instructor and students participating. Debriefing questions are included.
Effect of weft yarn twist level on mechanical and sensorial comfort of 100% woven cotton fabrics
Authors: Atalie Desalegn , Ferede Addisu , Rotich Gideon Kipchirchir
Published: January 2019

Fabric sensory properties are complex concepts which include dimensional changes at small forces such as tensile, shear, compression and bending, surface properties (friction and roughness) plus surface coolness or warmness. The aim of this study was to investigating the effect of weft yarn twist level on sensorial comfort of 100% woven cotton fabrics. Five cotton fabrics were woven with incremental weft yarn twist levels and their tensile and shear strength, pure bending, compression, surface friction and roughness were evaluated using Kawabata Evaluation System and compared. The other sample parameters such as count, thread density and fabric structure were kept constant. Fabric water permeability and its wicking ability were also evaluated. The results showed that as the twist level increased, the fabric tensile, shear and bending properties also increased. This was observed in both the warp and weft direction. At higher level of twist, lower surface friction, less compressibility, less slipperiness (0.264 warp and 0.199 weft direction), rougher surface (0.026 warp and 0.020 weft) and less even surface (2.643 warp and 1.998) were observed. The wicking ability also reduced with the increase in twist level while there was an improvement in water permeability.
An integrated deep learning solution for petrophysics, pore pressure, and geomechanics property prediction
Authors: Naeini Ehsan Zabihi , Green Sam , Russell-Hughes Iestyn , Rauch-Davies Marianne
Published: January 2019

In unconventional plays, wells are drilled at an unprecedented rate. This, together with technical challenges in terms of complex stratigraphy, multiple play types, variable rock properties, and various elements of pore pressure, geomechanics, fracturing, and diagenesis, calls for more sophisticated, faster, consistent, and wider ranging analytical tools. Given the scale of the work — i.e., the number of wells — performing classical workflows for petrophysics, pore pressure, and geomechanics prediction can be impractical (if not impossible) due to turnaround considerations. Also such workflows might not use any preexisting regional studies efficiently. In principle, a machine learning approach can mitigate these shortcomings. We show that a supervised deep neural network approach can be an alternative innovative tool for petrophysical, pore pressure, and geomechanics analysis enabling the use of all the previously interpreted data to devise solutions that simultaneously integrate wide-ranging wellbore and wireline logs. Beyond that, a similar approach is taken to predict a certain number of attributes solely from seismically derived properties, which allows one to compute volumetric models. The application of such an algorithm is shown on a Permian case study in which the automatic neural-network-based algorithms achieve reasonable accuracy in a fraction of the time.
Associations between childhood maltreatment and inflammatory markers
Authors: Palmos Alish B. , Watson Stuart , Hughes Tom , Finkelmeyer Andreas , McAllister-Williams R. Hamish , Ferrier Nicol , Anderson Ian M. , Nair Rajesh , Young Allan H. , Strawbridge Rebecca , Cleare Anthony J. , Chung Raymond , Frissa Souci , Goodwin Laura , Hotopf Matthew , Hatch Stephani L. , Wang Hong , Collier David A. , Thuret Sandrine , Breen Gerome , Powell Timothy R.
Published: January 2019

Background

Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.

Aims

To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.

Method

We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.

Results

Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.

Conclusions

Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.

Declaration of interest

D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
Robotic versus laparoscopic gastrectomy for gastric adenocarcinoma: Propensity matched analysis of the National Cancer Database.
Authors: Ryan Sean , Murphy Amy , Tameron Ashley , Hussain Lala , Teng Annabelle , Dunki-Jacobs Erik M. , Lee David Y
Published: January 2019

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Background: The use of robotic technology in gastrointestinal surgical oncology is on the rise. We compared the outcomes of laparoscopic (LG) and robotic gastrectomies (RG) performed for gastric adenocarcinoma (GA) in the National Cancer Database (NCDB). Methods: The NCDB database was queried for patients ≥ 18 years old with stage I-III GA who underwent LG or RG. Propensity matching was performed between the two groups with regards to clinical staging, adjuvant treatment, demographics, and the extent of surgery. Results: A cohort of 1893 (1262-LG, 631-RG) patients was identified in a 2:1 propensity matching. Demographics and co-morbidities were similar between the groups. The clinical staging and the extent of the surgery were well matched. The rate of negative margin as well 30 and 90-day mortality was similar between the two cohorts. Outcomes with respect to readmission and length of stay were also similar (Table 1). Long-term survival was not significantly different between the two cohorts, with a median survival of 49 months for LG cohort and 56.1 months in the RG cohort (p=0.405). Also, lymph node (LN) positivity was similar between the two groups (40.1 % 42.8%, p= 0.278) However, the average number of LN sampled was significantly higher in the RA group compared to the LA group (19.6 vs 17.4, p<0.001). Similarly, the percentage of surgeries in which ≥ 15 LNs were sampled was also greater in the RG group compared to the LG group (63.9% vs 57.6%, p=0.010). Conclusions: Greater number of patients in the RG group achieved NCCN guideline of harvesting ≥ 15 lymph nodes for more accurate staging. RG may allow a greater harvest of lymph nodes without increasing short term adverse outcomes compared to LG. Long term outcomes in this well matched cohort appears comparable for both approaches.
Radiation dose to the thoracic vertebral bodies and impact on hematologic toxicity in patients receiving concurrent chemoradiation for esophageal cancer.
Authors: Fabian Denise , DiCostanzo Dominic J. , Barney Christian , Aljabban Jihad , Wuthrick Evan John , Williams Terence Marques , Bazan Jose G.
Published: January 2019

105

Background: Concurrent chemotherapy and radiation (CRT) for the treatment of esophageal cancer (EC) is associated with acute hematologic toxicity (HT). There are few data evaluating the relationship between radiation dose (RT) to the thoracic vertebral bodies (TVB) and the development of HT in EC patients receiving CRT. We hypothesized that increasing RT to the TVB contributes to the development of HT in EC patients receiving CRT. Methods: We identified cases of EC treated with curative intent CRT from 2007-2016. We retrospectively contoured the thoracic vertebral bodies (TVB). The TVB-mean dose and the TVB V5-V50 were calculated from the dose volume histogram. HT was graded according to the Common Terminology Criteria for Adverse Events, v4 based on leukocyte, neutrophil, and platelet nadirs during CRT. Grade≥3 HT (HT3+) was the primary endpoint. Logistic regression was used to test associations between HT3+ and dosimetric/clinical parameters. Results: We included 137 cases: 115 males (84%); median age 61 years (Interquartile range [IQR], 55-67); predominantly stage III (54%). Most patients received concurrent carboplatin/paclitaxel (N = 83). Median RT dose was 50.4 (IQR = 50.4-50.4) Gy, and the majority underwent surgery (60.6%). The rate of HT3+ was 39.4% (N = 54) at a median of 28 (IQR = 21-32) days after CRT start. On univariate analysis, a 5% increase in TVB-V40 was associated with increased odds of HT3+ (OR = 1.13, 95% CI 1.04-1.23, p = 0.0004). TVB-mean and TVB V30-V50, age (OR = 1.04, p = 0.03), males (OR = 0.38, p = 0.04), and carboplatin/paclitaxel vs. other regimen (OR = 2.66, p = 0.01) were significantly associated with HT3+, while BMI was not (OR = 1.00, p = 0.94). On multivariate analysis, TVB-V40 (OR = 1.20, p = 0.0004), carboplatin/paclitaxel (OR = 4.84, p = 0.0007), and age (OR = 1.04, p = 0.03) were independently associated with HT3+ while male gender (OR = 0.48, p = 0.16) was not. The results were similar for TVB-mean and TVB V30-V50. Conclusions: We found that increasing TVB dose was associated with HT3+ in EC patients treated with CRT. This suggests that efforts to spare RT to the TVB may reduce rates of HT3+ and prospective evaluation of these results is needed.
Prognostic impact of splenic hilar lymph node metastasis in proximal gastric carcinoma: A retrospective analysis of 665 patients treated with D2 total gastrectomy.
Authors: Jeong Oh , Park Young-Kyu , Ryu Seong Yeob
Published: January 2019

11

Background: Standard D2 lymph node (LN) dissection for proximal gastric carcinoma includes removing splenic hilar LNs. However, patients with splenic hilar LN metastasis often show a poor prognosis even after curative surgery. This study aimed to investigate the prognostic impact of splenic hilar LN metastasis in proximal gastric carcinoma. Methods: We reviewed prospectively constructed data of 665 patients who underwent total gastrectomy with D2 LN dissection for proximal gastric carcinoma. Clinicopathological features and survivals were compared between patients with and without splenic hilar LN metastasis. The prognostic value of splenic hilar LN metastasis was examined using a multivariate Cox prognostic model. Results: Of 665 patients, 63 (9.5%) with stage III or IV disease had splenic hilar LN metastasis. Splenic hilar LN metastasis was associated with a larger tumor size, B4 gross type, undifferentiated histology, and lymphovascular invasion. The 5-year survival of patients with splenic hilar LN metastasis was significantly worse at each tumor stage (stage III = 45% vs. 66%, p = 0.044, stage IV = 12% vs. 32%, p = 0.017). The 5-year survival of patients with splenic hilar LN metastasis did not significantly differ from that of the distant metastasis group (26% vs. 31%, p = 0.484). Multivariate analysis revealed that splenic hilar LN metastasis is an independent poor prognostic factor when adjusting for tumor node metastasis stage and other prognostic factors. Conclusions: Patients with splenic hilar LN metastasis show a poor prognosis after surgery. More intensive adjuvant treatment and postoperative surveillance will be required for patients with splenic hilar LN metastasis.
Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).
Authors: Matsuyama Jin , Kurokawa Yukinori , Nishikawa Kazuhiro , Kimura Yutaka , Takeno Atsushi , Kawada Junji , Kawabata Ryohei , Makari Youichi , Tamura Shigeyuki , Doki Yuichiro , Sakai Daisuke , Shimokawa Toshio , Satoh Taroh
Published: January 2019

119

Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.
Retrospective observational study of salvage line ramucirumab monotherapy (RAM) for patients (pts) with unresectable advanced gastric cancer (AGC) which was refractory to fluoropyrimidine and taxanes.
Authors: Fukuda Naoki , Kawai Sadayuki , Omae Katsuhiro , Mitani Seiichiro , Wakatsuki Takeru , Kato Ken , Kadowaki Shigenori , Takahari Daisuke , Boku Narikazu , Muro Kei , Machida Nozomu
Published: January 2019

129

Background: RAM showed a survival benefit over best supportive care in second-line treatment after failure of fluoropyrimidine-containing chemotherapy for pts with advanced gastric or gastro-esophageal junction adenocarcinoma (AGC). In clinical practice, RAM is used for some pts who have disease refractory to fluoropyrimidine and taxanes in salvage line setting. Methods: We retrospectively evaluated efficacy and safety of RAM in salvage lines between June 2015 and April 2017 for AGC at four Japanese institutions. All pts received 2 or more prior regimens containing fluoropyrimidine and taxanes, but not ramucirumab. We also explored prognostic factors for progression free survival (PFS) and overall survival (OS). Results: Fifty-one pts were collected. Pts' characteristics were as follows; median age: 67 (range 39-84) years; ECOG performance status ≤ 1: 43 (84%) pts; HER2 positive: 17 (33%) pts; number of metastatic sites ≥ 2: 29 (57%); number of prior therapies 2/3/4/5: 7(14%)/25(49%)/12(24%)/7(14%) pts. Median PFS and OS were 1.9 (95% confidence interval [CI]: 1.6-2.2) and 5.1 (95% CI: 4.1-6.8) months, respectively. Twelve-week PFS rate was 25.5%. Objective response rate in 43 pts who had measurable disease was 2%. Disease control rate was 35%. Grade 3 adverse events (AEs) occurred in 7 (13%) pts such as anemia in 2 (4%), fatigue in 1 (2%), hypertension in 2 (4%), proteinuria in 2 (4%), intestinal bleeding in 1 (2%), and others in 2 (4%) pts. No grade 4 AEs and treatment related deaths were observed. Although multivariate analyses suggested that absence of primary tumor and neutrophil lymphocyte ratio < 2.5 at baseline were associated with better PFS, while statistically significant prognostic factors for OS were not identified in this study. Conclusions: Salvage line RAM showed acceptable toxicities and comparable efficacy with those reported in previous studies of second-line setting. It is suggested that RAM could be considered for salvage line treatment after fluoropyrimidine and taxanes containing regimens.
Survival outcomes for de novo versus relapsed stage IV gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Chan Bryan Anthony , Sim Hao-Wen , Natori Akina , Moignard Stephanie , Yokom Daniel , Lim Charles Henry , Jiang Di Maria , Chen Eric Xueyu , Knox Jennifer J. , Liu Geoffrey , Darling Gail Elizabeth , Swallow Carol Jane , Brar Savtaj Singh , Brierley James D. , Ringash Jolie , Wong Rebecca , Kim John , Hafezi-Bakhtiari Sara , Elimova Elena , Jang Raymond Woo-Jun
Published: January 2019

148

Background: In gastric/GEJ cancer, 40% of patients (pts) are metastatic at diagnosis ( de novo stage IV) and up to 70% with locoregional disease recur (relapsed stage IV). We compared survival outcomes between de novo vs relapsed stage IV. Methods: A retrospective observational study of stage IV gastric/GEJ pts was conducted (2012-2015). Overall survival (OS) was from date of stage IV diagnosis. PFS1 defined the period from stage IV diagnosis to first progression. PFS2 was from first to second progression. For relapsed stage IV pts, disease-free interval (DFI) was the period from initial diagnosis to metastatic relapse. Cox proportional hazards models compared OS, PFS1 and PFS2 between de novo vs relapsed stage IV pts, stratified by DFI [ < 6, 6-12 and > 12 months (mo)] and controlled for baseline patient characteristics. Results: Of 198 pts, 62% were male and median age was 64 years (26-93), with 64% gastric and 36% GEJ adenocarcinomas. Primary therapy for locoregional pts included surgery (75%), perioperative chemotherapy (42%) and radiotherapy (42%). De novo and relapsed stage IV pts represented 68% and 32% of the cohort respectively. Median follow-up was 13 mo. Controlled for age, performance status and Charlson comorbidity index, there were no significant differences in OS (median OS 12.5 ( de novo) vs 12.2 mo (relapsed); HR 1.22, 95% CI 0.83-1.77, p = 0.31), PFS1 (6.8 vs 7.4 mo; HR 1.00, 95% CI 0.65-1.56, p = 0.98) or PFS2 (3.8 vs 3.0 mo; HR 1.03, 95% CI 0.44-2.41, p = 0.95). Median OS for relapsed stage IV patients were different by DFI groups (log-rank p = 0.02): 22.9 mo (for DFI > 12mo; n = 31), 11.2 mo (DFI 6-12; n = 19) and 7.5 mo (DFI < 6; n = 14). Additionally, OS was significantly better if the DFI was greater than 12 mo, compared with de novo stage IV (HR 0.50, 95% CI 0.28-0.88, p = 0.02). Conclusions: There was no observed difference in the natural history of de novo vs relapsed stage IV gastric/GEJ pts. DFI was strongly prognostic with median OS (from date of relapse) approaching 2 years for relapsed pts with DFI > 12 mo. In addition to implications for treatment strategy, tumor biology within subgroups should be examined to identify novel biomarkers and potential therapeutic targets.
Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.
Authors: Shirasu Hiromichi , Tsushima Takahiro , Furuta Mitsuhiro , Kawahira Masahiro , Kawakami Takeshi , Yoshida Yukio , Kawai Sadayuki , Hamauchi Satoshi , Todaka Akiko , Machida Nozomu , Yokota Tomoya , Yamazaki Kentaro , Fukutomi Akira , Onozawa Yusuke , Yasui Hirofumi
Published: January 2019

156

Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI < 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI > 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p < 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites > 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.
Efficacy and safety of ramucirumab containing chemotherapy in patients with pretreated metastatic gastric neuroendocrine carcinoma.
Authors: Mishima Saori , Kawazoe Akihito , Matsumoto Hiroshi , Kuboki Yasutoshi , Bando Hideaki , Kojima Takashi , Doi Toshihiko , Ohtsu Atsushi , Yoshino Takayuki , Nonte Elizabeth M , Chintharlapalli Sudhakar , Nasir Aejaz , Kuwata Takeshi , Shitara Kohei
Published: January 2019

157

Background: Gastric neuroendocrine carcinoma (G-NEC) is associated with poor prognosis. Most patients (pts) present with advanced disease and have short survival. Ramucirumab (RAM), a monoclonal antibody for VEGFR-2, has been effective for advanced gastric adenocarcinoma (AC). However, little is known about efficacy of RAM containing chemotherapy in G-NEC. Methods: We retrospectively analyzed and compared the efficacy and safety of RAM containing chemotherapy in pretreated G-NEC and AC pts in our hospital (March 2015- January 2017). G-NEC was defined by NEC features, regardless of the proportion, based on histology and neuroendocrine markers (synaptophysin, chromogranin A or CD56). VEGFR-2 expression in tumor vessels was evaluated in archival primary G-NEC tissues by immunohistochemistry using the same anti-VEGFR2 primary antibody and scoring scheme (vascular VEGFR2 H-score) as in REGARD trial (Fuchs CS, et al. BJC. 2016). Results: Seventeen G-NEC and 173 AC pts were analyzed. Therapy for G-NEC included RAM + paclitaxel (n = 13), RAM + irinotecan (n = 2), and RAM monotherapy (n = 2). The overall response rate was significantly better in pts with G-NEC than AC (59 vs. 22%, p = 0.001). Progression-free survival was significantly longer in pts with G-NEC than AC (median 6.8 vs. 3.2 months, HR 0.38 [95%CI 0.22-0.66]; p < 0.001). Overall survival was significantly longer in pts with G-NEC than AC (median 16.2 vs. 9.6 months, HR 0.4 [95%CI 0.19-0.86]; p = 0.014). No severe or unexpected adverse event occurred. Median vascular VEGFR2 H-score, based on available G-NEC tissues from 12 pts, was 220 (range 150-260) which was markedly higher than that reported on AC tissues from REGARD trial as historical control (median 35, range 0-240). Conclusions: Compared to AC patients, RAM containing chemotherapy showed a promising activity without severe or unexpected safety profile in G-NEC patients. This may in part be explained by higher vascular VEGFR-2 expression in G-NEC tissues. These data, though preliminary, support further clinical evaluation of RAM and biomarker investigation in this subset of gastric cancer.
Evaluation of the outcome of adjuvant treatment for gastric cancer in Brazil and Peru: A retrospective study in two cancer centers in Latin America.
Authors: Nunez Jose Eduardo , Felismino Tiago , Enriquez Daniel , Montenegro Paola Catherine , Coimbra Felipe , Costa Wilson L. , Begnami Maria D. , Taxa Luis , Casavilca Sandro , Fogaroli Ricardo , Alves Ana Caroline , Mello Celso Lopes
Published: January 2019

160

Background: Gastric cancer (GC) is one of the most frequent malignancies in developing countries. In Peru, it is the fourth most incident cancer, and the sixth one in Brazil. Mortality is still high. The chance of relapse of patients with non-metastatic disease undergoing surgery is more than 50%. It is suspected that Latin American patients present worse evolution compared to those treated in Asia or in developed countries, therefore it is fundamental to study factors related to the prognosis and evolution of patients with GC in our continent. We aimed to evaluate the outcome of adjuvant treatment for GC in patients from two countries with different racial miscegenation and eating habits, and correlate this with clinicopathological features. Methods: We retrospectively analyzed 187 patients with GC who underwent curative surgery and received CRT at AC Camargo Cancer Center (ACCCC) in Brazil and Instituto Nacional de Enfermedades Neoplasicas (INEN) in Peru. CRT was defined as MacDonald protocol. Primary endpoint was overall survival (OS). Cox regression model was performed in order to calculate hazard ratio (HR) and 95% confidence intervals (95%CI). Results: Median follow up time was 51 and 20 months in Brazil and Peru, respectively. Median age of our cohort was 54 years-old. Male sex was predominant in both countries (Brazil: 54.7%; Peru: 56.9%). Diffuse subtype also was predominant (Brazil: 58.3%; Peru: 55.1%). Median OS was 103.9 and 45.2 months in Brazil and Peru respectively (p < 0.001). In the multiple analysis, we found that pathological stage (I/II vs. III; HR = 4.1, 95%CI 1.4-11.7; p = 0.009) was independent prognostic factor adjusted by country of treatment, histological subtype, localization, age and gender. Conclusions: Survival differences exist between Brazil and Peru. We observed that patients from Peru had more advanced pathological stage after surgery. This difference suggests a possible prognostic factor in OS. Ethnic/genetic factors, eating habits and other clinicopathological or molecular factors may also explain different prognosis. Future studies are warranted to determine these prognostic factors in Latin American gastric cancer patients.
Safety, effectiveness, and rapid adaptation of robotic gastrectomy for advanced gastric cancer.
Authors: Chen Lin , Li Jiyang , Xi Hongqing , Gao Yunhe , Cui Jianxin , Qiao Zhi , Zhang Kecheng , Xie Tianyu , Liang Wenquan , Wei Bo
Published: January 2019

161

Background: As robotic surgery techniques advances, robotic gastrectomy has emerged as an alternative modality for advanced gastric cancer (AGC). However, there is a lack of supporting evidence regarding the safety, effectiveness and surgeon acceptance of robotic gastrectomy for AGC patients. Methods: An ambispective cohort study was conducted. We compared surgical and oncological outcomes between robotic and traditional laparoscopic gastrectomy for AGC patients. The Cumulative Sum (CUSUM) method was developed and used to analyze the learning curves of robotic gastrectomy for AGC by two surgeons who had different surgical experience. Results: From August 2011 to June 2017, a total of 134 AGC patients were performed robotic gastrectomy by surgeon A (n = 42) and surgeon B (n = 147). And there were 238 AGC patients received traditional laparoscopic gastrectomy which performed by the same two surgeons over the same period. There were no significant differences between the two operation methods regarding the clinicopathologic characteristics and long-term outcomes (p=0.737). However, robotic gastrectomy group had less operative blood loss (229 ml vs. 240 ml, p=0.031) and less Clavien-Dindo Grade II to IV complications (p=0.006) than laparoscopic group. Clinicopathologic characteristics, short-term and long-term outcomes of the patients treated by surgeon A and surgeon B are similarity. CUSUM analysis showed that operative time reached a stable state after around 12 cases in surgeon A who had more open gastrectomy experience than laparoscopic gastrectomy experience, and 21 cases in surgeon B who had more laparoscopic gastrectomy experience than open gastrectomy experience. The stable operation time was 242 min for surgeon A and 236 min for surgeon B. The number of lymph node dissections was 38 for surgeon A and 28 for surgeon B during their capacity-increasing phase. Conclusions: Robotic gastrectomy achieved superior short-term outcomes and comparable long-term outcomes compared with traditional laparoscopic gastrectomy for AGC patients. Surgeons with sufficient experience in either open or laparoscopic gastrectomy can rapidly overcome the learning curve and performed gastrectomy for AGC patients safely.
Regional variation in the costs of treating curative gastric cancer.
Authors: Jeong Yunni , Mahar Alyson L. , Zagorski Brandon , Coburn Natalie
Published: January 2019

165

Background: Gastric cancer is a highly morbid and fatal disease. While the clinical challenge with gastric cancer is widely described, little is known about the economic burden of the disease. Many guidelines outline the curative treatment for gastric cancer and in a universal healthcare system, equal access and uniform healthcare delivery is predicted. Yet, regional variation in practice exists and may result in increased healthcare costs. We therefore aimed to investigate of the costs of treating curative gastric cancer, explore regional variation in costs, and to identify the factors which drive these costs. Methods: We conducted a patient-level cost analysis of curative-intent stage I-III gastric cancer diagnosed between 2005 and 2008 from the perspective of a universal healthcare system, using a 26-month time horizon. Clinical and stage data were abstracted from a provincial chart review. Costs associated with physician billings, same day surgery, hospitalization, drug benefits, emergency department visits, continuing care, and long-term care were derived using administrative healthcare databases and compared among healthcare regions. Costs were inflated to 2017 United States dollars (USD). We used a linear regression model to identify factors predictive of these treatment costs. Results: A total of 722 patients with Stage I-III gastric cancer were identified. Mean costs per region ranged from $55,650 to $92,852 (USD) across 14 health regions. The lowest contributing cost sector was long-term care and the highest contributing proportion of costs was from hospital admissions. A laparoscopic surgical approach was predictive of lower costs while age over 70 years and death at one year from diagnosis was predictive of higher costs. Conclusions: Regional variation exists in the treatment costs for patients with curative gastric cancer despite guidelines directing appropriate care and healthcare delivery in a universal healthcare system. Governmental intervention to ensure quality care delivery is necessary for improved and sustainable curative gastric cancer care across regions.
Short-term and long-term outcomes of laparoscopic pylorus-preserving gastrectomy.
Authors: Onoyama Haruna , Cho Haruhiko , Oohinata, Ryouki
Published: January 2019

181

Background: Distal gastrectomy is still a standard surgical procedure for early gastric cancer locating in the middle third of the stomach. Laparoscopic pylorus-preserving gastrectomy (LPPG) is promising method which can achieve both minimally invasive and function-preserving outcomes; however, the advantage of PPG against laparoscopic distal gastrectomy (LDG) has not been clarified. Methods: This study examined the clinical outcomes of 71 patients who underwent LPPG for cT1 N0 GC located in the middle part of the stomach and 168 patients who underwent LDG with BillrothI reconstruction for cT1 N0 GC located in the middle or lower part of the stomach between September 2006 and December 2014. Surgical outcomes of LPPG were retrospectively compared with those of LDG. Results: The pathological T- and N-stage of the two groups were similar. There was no significant difference in the mean number of resected lymph nodes (37 in LPPG and 33 in LDG). Operation time was longer in LPPG than LDG (248min:LPPG, 228min:LDG) and blood loss were higher in LPPG than LDG (72ml:LPPG, 54ml:LDG). Postoperative hospital stay was longer in LPPG than LDG (13days:LPPG, 11days:LDG). There was no difference in the surgical complications (12.7%:LPPG, 9.5%:LDG) and no mortality occurred(no in-hospital deaths). Only one case of LDG was died of postoperative recurrence. The mean weight loss rate in 3 years after gastrectomy was lower in LPPG than in LDG (7.7% and 10.4%, respectively). Conclusions: LPPG is an acceptable and favorable operative method with possible prevention of weight loss for clinically diagnosed early stage GC.