bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of the extent of gastric resection on advanced gastric cancer treated with systemic chemotherapy.
Authors: Sasaki Yusuke , Watanabe Yutaka , Ohkita Ichiro , Hirota Jojo , Konno Jun
Published: March 2017

194

Background: In previous clinical trials of adjuvant chemotherapy for gastric cancer, severe toxicity and discontinuation of chemotherapy was more common in patients receiving total gastrectomy (TG) than in those with distal gastrectomy (DG). However, data on the significance of the extent of gastric resection for stage IV gastric cancer treated with systemic chemotherapy are not available. Methods: This is a retrospective review of patients who were received chemotherapy with S-1 and cisplatin for stage IV gastric cancer at our institution between June 2009 and August 2015. The patients were classified into three groups according to the extent of gastrectomy (TG, DG and no gastric resection (NG)) before chemotherapy. Patient characteristics, survival and toxicities of chemotherapy were compared between three groups. Results: Among the 83 patients, 24 underwent TG, 19 DG, and 40 NG. Patient characteristics were well balanced between three groups. There was no significant difference in the requirement for dose reduction between TG, DG and NG patients (29% vs 11% vs 20%, respectively, p= 0.32). However, the rate of discontinuation because of toxicity was significantly higher in TG than in DG or NG patients (46% vs 16% vs 25%, respectively, p= 0.04). The main reasons of discontinuation were anorexia (43%), myelosuppression (23%), nausea (18%) and diarrhea (16%). The median progression-free survival was 8.9, 6.1 and 5.3 months ( p= 0.25), and the median overall survival was 16.0, 16.0 and 9.8 months ( p= 0.40) in the patients with TG, DG and NG, respectively. Conclusions: There was a high frequency of discontinuation of systemic chemotherapy in the advanced gastric cancer patients who underwent TG, but it was not associated with prognosis.
Recurrence patterns in esophageal cancer patients undergoing curative trimodality therapy.
Authors: Chan Edwin , Vanderwater Catherine , Woo Rachel , Cho Charles , Wong Jason , Xu Wei , Zhang Qihuang , Liu Geoffrey , Zhang Beibei , Cheung Agnes , Lee Alex , Chacko Pravin Philip , Fadhel Ehab , Kassam Zahra
Published: March 2017

195

Background: To document pattern of recurrence and its relationship to the radiation treatment volume in esophageal cancer patients treated with trimodality therapy. Methods: Patients with adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus, T1-4N0-3 (AJCC 7thEd.) treated with chemoradiation (CRT) and esophageal resection between June 2010 and November 2015 participated in a prospective cohort study. Patients were planned using 4DCT and IMRT or VMAT. GTV and CTV were contoured on 4D exhale, inhale phases and voluntary exhale helical CT. CTV margins were 3-4cm superiorly and inferiorly, and 1cm circumferentially. CTVs were combined to form the ITV. PTV margin was 0.5cm. Site of first disease recurrence was classified as in-field (within 90% isodose), marginal (between 50-90%), or out-of-field (outside 50%). Results: Fifty-eight patients participated. Median age was 66 years (range: 40–78); 52 males: 6 females. 49 had adenocarcinoma, 7 SCC, and 2 mixed histology. 52 (90%) had clinically node positive disease. 31 received concurrent radiation 45-50Gy/25fr with Cisplatin/5FU and 27 received 41.4Gy/23fr with Carboplatin/Paclitaxel (CROSS protocol). 15 (27%) achieved a pathological complete response (pCR). Median follow up was 1.6 years (range: 0.2-4.8), 2-year overall survival 71%, disease-free survival 59%, median survival 4.4 years and median time to relapse 2.3 years. 17 patients (29%) had disease recurrence of which, at initial diagnosis, all were clinically node positive and 3 had pCR after CRT. Five developed locoregional recurrence (2 anastomatic, 3 locoregional nodes), 4 both locoregional and distant, and 8 distant recurrence alone. Of 9 patients with locoregional recurrence, 1 had in-field, 6 out-of-field and 2 had disease traversing in and out-of-field areas. 4 of 17 (24%) were treated with curative intent (1 surgery, 3 CRT) and all were alive at the latest follow up (time from first recurrence: 6 to 49 months). Conclusions: Survival and recurrence outcomes in this small cohort are similar to those reported in the literature. Only a small proportion of patients experienced in-field relapse. Of those who relapsed, 24% received curative salvage therapy.
Retrospective study of ramucirumab in patients with advanced gastric cancer.
Authors: Sakai Daisuke , Kudo Toshihiro , Kato Aya , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Takiguchi Shuji , Mori Masaki , Doki Yuichiro , Satoh Taroh
Published: March 2017

199

Background: Ramucirumab is a human, monoclonal antibody that specifically blocks activation of vascular endothelial growth factor (VEGF) Receptor. Ramucirumab with paclitaxel have shown the efficacy, and is recommended as second line chemotherapy in the gastric cancer treatment guideline in Japan. June 2015, ramucirumab was approved in Japan. Methods: We retrospectively investigated the efficacy and safety of ramucirumab in the patients with advanced gastric cancer in our institution from July 2015 to September 2016. Results: 50 patients were eligible. 11 patients were administered as ramucirumab monotherapy, and 39 patients were in combination with paclitaxel. 22 patients were administered as 2nd line treatment and 24 patients as third or more lines. Progression free survival and overall survival of all assessable patients was 2.4 months (95% CI: 1.8 - 4.6) and 6.0 months (95% CI: 4.6 - 9.2), respectively. PFS in subgroup of 2nd line and combined with paclitaxel (n = 20) was 7.0 months. Response rate in patients who had mesuarable lesion was 22.8 %. Major grade 3/4 adverse events were Leukopenia (59.1%), Neutropenia (68.2 %), febrile neutropenia (9.1%), and GI perforation (2.0 %). Conclusions: Ramucirumab seemed to be effective and safe in clinical setting against advanced gastric cancer.
A retrospective analysis of eye disorders induced by chemotherapy including S-1 for gastrointestinal cancer.
Authors: Yagisawa Masataka , Nakamura Michio , Matsuda Chika , Murai Taichi , Itaya Kazufumi , Sone Takayuki , Koike Yuta , Endo Ayana , Tsukuda Yoko , Ono Yuji , Nagasaka Atsushi , Nishikawa Shuji
Published: March 2017

20

Background: Eye disorders (EDs) are common adverse events in patients received S-1 chemotherapy. Although there are some retrospective reports about EDs induced by S-1 mono therapy (mono) as adjuvant chemotherapy (Adj) in gastric cancer (GC), there are few reports about S-1 induced EDs in other gastrointestinal cancer (GIC). So we conducted this retrospective cohort study to investigate the incidence of S-1 induced EDs in GIC and the association with several clinicopathological factors, such as primary site, treatment setting, regimen, and duration. Methods: All the patients received S-1 chemotherapy for GIC in our institution from January 2008 to May 2016 were identified through medical records review extracted by our hospital data warehouse. We analyzed the incidence of S-1 induced EDs by reviewing all the medical records and the association between ED incidence and several clinicopathological factors using a chi-square test or a Fisher's exact test and logistic regression. Results: Two hundred eighty three GIC patients were analyzed on this study. Patients characteristics were as follows; male/female 170/113, GC/colorectal cancer (CRC)/pancreatic cancer (PC)/biliary cancer (BC) 119/67/57/32, non-Adj/Adj 263/20, S-1 mono/S-1 combination therapy (combo) 130/153. The overall incidence rate with EDs such as epiphora, gum, photophobia, nephelopsia was 15.2% (n = 43). The median time to onset of EDs was 109 days (range 5-1100). The each of ED incidence was 16.5% (n = 28) and 13.3% (n = 15) in male and female (p = 0.503), 14.8% (n = 39) and 20.0% (n = 4) in non-Adj and Adj setting (p = 0.520), 13.8% (n = 18) and 16.3% (n = 25) in S-1 mono and combo (p = 0.619), respectively. The incidence of EDs in GC, CRC, PC, and BC were 15.1% (n = 18), 17.9% (n = 12), 17.5% (n = 10), and 9.4% (n = 3) (p = 0.635), respectively. Conclusions: We found that the incidence of EDs induced by S-1 chemotherapy for GIC was relatively high regardless of cancer site, treatment regimen, setting and duration. Further accumulation of data as prospective cohort study is necessary to confirm the incidence of S-1 induced EDs. Clinical trial information: UMIN000024160.
Evaluation of hepatectomy, radiofrequency ablation, and transarterial chemoembolization for the local treatment of liver metastases in gastric cancer patients.
Authors: Chen Lin , Li Jiyang , Cui Jianxin , Xi Hongqing , Cai Aizhen , Zhang Kecheng , Gao Yunhe , Wei Bo
Published: March 2017

200

Background: The optimal local treatment for liver metastases remains controversial. Except for hepatectomy, radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are both effective and low risk treatment modality with more expanded indications in patients with liver metastases. Thus, the aim of this study is to evaluate the efficacy of different methods for the local treatment of GCLM. Methods: From January 2006 to December 2015, 97 consecutive patients were eligible and included in a prospective database. They all received multidisciplinary treatments based on curative gastrectomy and local treatments (hepatectomy, RFA and TACE) for liver metastases. The 97 patients enrolled in a cohort study were divided into two groups, Group A (37 patients, curative hepatectomy with or without other local treatments) and Group B (60 patients, palliative RFA and/or TACE).The primary endpoints were overall survival (OS) and 5-year survival rate. Results: Baseline characteristics in the two groups were comparable. Correlation analysis found that interval time of metachronous, neutrophil to lymphocyte ratio and body mass index were not significantly linear associated with survival, with ρ = 0.051, ρ = 0.014 and ρ = 0.056, respectively. The overall survival time between the two groups were 94.1 months and 57.2 months, with 1-year, 3-year and 5-year survival rate 83.3%, 50.0% and 30.6% in Group A, respectively; and 83.7%, 28.6% and 18.4% in Group B, respectively (P = 0.049). Furthermore, subgroup analyses proved that among these three local treatments, hepatectomy was the most effective method (P = 0.014), with significantly difference from RFA (P = 0.001). Nevertheless, combination with RFA and/or TACE did not improve patients’ benefits (P = 0.062). And TACE has a similar (P = 0.227) efficacy with RFA, but significantly less costs. Conclusions: Hepatectomy is the optimal local treatment for liver metastases when the surgical R0 resection was intended. And it is not necessary to combine with other local treatments. As palliative local treatment, TACE is an acceptable method with relatively high cost-effective.
A proposal for a novel and simple TNM staging for gastric cancer.
Authors: Son Taeil , Sun Jiyu , Kim Hyoung-Il , Kim Jong Won , Cheong Jae-Ho , Choi Seung Ho , Noh Sung Hoon , Woo Yanghee , Fong Yuman , Park Sohee , Hyung Woo Jin
Published: March 2017

21

Background: Current TNM staging system for gastric cancer has controversies regarding N classification. We aimed to develop a simple and novel TNM staging system for gastric cancer by re-grouping N classification. Methods: We retrospectively reviewed 14260 patients treated for gastric cancer. To develop simple combinations of TNM staging with similar weighted value between T and N classification, N classification was restructured with different cutoffs. The optimal cutoffs for the number of metastatic lymph node which maximize the x2 statistic of log-rank test for survival differences among patients were selected. C-statistic was used to compare the discriminating performance of the proposed N classification with the current N classification in the TNM staging system. We performed validation with 2 external datasets from a hospital in Korea (n = 1500) and SEER (n = 11324). Results: We identified the new cutoffs of N classification as 1~4, 5~10, 11~24, and 25 or more for N1, N2, N3a, and N3b, respectively. We found survival of the new N3b classification was similar to M1, regardless of T classification. Thus, we stratified these groups of N3b and M1 disease as stage IV, simultaneously. Our new TNM staging had similar weighted value between T and N classification resulting in simple combinations. (Table) Survival curves of subgroups in the new TNM staging had higher x2 value than current staging system (x2: 8239 vs. 7023, respectively) and homogeneity among subgroups in the same stage increased. However, C-statistics (0.801, 95%CI: 0.795, 0.807) of new model showed similar discrimination power than that (0.797, 95%CI: 0.791, 0.803) in 7th TNM staging system. C-statistics were also similar in other hospital in Korea (0.805 vs. 0.802, respectively) and SEER database (0.709 vs. 0.706, respectively). Conclusions: This novel staging system by recalculating cut-offs of N classification provides exceptionally simple and practical way to stratify substages in TNM staging for gastric cancer. [Table: see text]
Comparison of cisplatin induced nephrotoxicity with short hydration or conventional hydration in gastric cancer: A retrospective study.
Authors: Aoyama Takeshi , Kato Hiroki , Hagino Akane , Furutani Ryota , Ito Kazuyuki , Yoshioka Hidenori , Nakamura Masashi , Tunoda Takashi , Kawakami Kazuyoshi , Suzuki Kenichi , Ichimura Takashi , Yamaguchi Kensei , Hama Toshihiro
Published: March 2017

211

Background: Cisplatin is administered in combination with massive and long term hydration to avoid renal toxicity. Although a short hydration protocol for cisplatin has been recently developed in lung cancer, which in gastric cancer has not been well clarified. We modified our XPT (capecitabine / cisplatin / trastuzumab) regimen, adopting short hydration method. This study was conducted to compare the preventive effect for renal toxicity of XPT therapy between the short hydration regimen and the conventional regimen. Methods: Medical records of patients with gastric cancer who received XPT therapy containing cisplatin at a dose of ≥ 80 mg/m2 were reviewed for 3 cycles of the observational period. Patients received either the short hydration regimen or the conventional regimen; short hydration regimen consisted of 2200 - 2500 mL of hydration over a period of 6.2 hours with furosemide and magnesium supplementation on day 1 and 1050 mL of hydration over 4 hours on day2 and 3, and the conventional regimen consisted of 3200 - 3500 mL of hydration over 24 hours on day 1 and 1550 ml of hydration over 6 hours on day2 and 3. Renal toxicity was then compared between the two groups. Results: Out of the total 31 patients, 6 received the short hydration regimen and 25 received conventional regimen. An elevated serum creatinine level ≥ grade 1 was significantly less frequent in the group receiving the short hydration regimen (0%, 0/6) than in the group receiving the conventional regimen (48.0%, 12/25) ( P < 0.05). The completion rate for the planned treatment in the short hydration group (100.0%, 6/6) was higher than that in the conventional hydration group (84.0%, 21/25). Conclusions: Based on the results of this study, short hydration may be a feasible regimen for XPT therapy in gastric cancer.
Development of follow up recommendations for completely resected gastroenteropancreatic neuroendocrine tumours (GEP-NETS): Practice Survey of Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) in conjunction with North American Neuroendocrine Tumour Society (NANETS).
Authors: Singh Simron , Chan David Lok Hang , Moody Lesley , Carsley Sarah , Metz David C. , Strosberg Jonathan R. , Segelov Eva
Published: March 2017

224

Background: Published guidelines for follow up after R0 resection of GEP-NETS are complex and emphasize closer surveillance in the first 3 years, as per other GI malignancies. NETS have a different pattern and timescale of recurrence, hence require more practical and tailored follow up. Aim: To examine real world follow up practices compared to published guidelines for follow up of patients with GEP-NETs. Methods: A detailed electronic cross-sectional survey was developed and distributed to members of the CommNETS Collaboration (Australia, NZ, Canada) and NANETs. Questions addressed demographics, knowledge and use of current guidelines and follow up practices relating to various prognostic factors. Descriptive statistics were obtained for all responses, stratified by country, patient volume and specialty. Results: There were 163 respondents: Australia: 59; NZ: 25; Canada: 46; US: 33. 50% were Medical Oncologists; 23% Surgeons; 13% Nuclear Medicine; 14% other. 38% of respondents were “very familiar” with NCCN NET guidelines; 33% with ENETS, 17% with ESMO, however only 15%, 27% and 10% found them “very useful”, respectively. 63% reported not using guidelines at their institution. Ranking of prognostic factors (top 5, decreasing order): grade, Ki67/mitotic count, T stage, N stage and site of origin. Follow up in 1st 2 years was most commonly every 6 months (62%); in years 3-5 every 12 months (59%) and > 5 years, 12 months (41%). Follow up patterns did not differ significantly by patient volume. The commonest investigations were CT scans (66%) and CgA (86%). When poor prognostic factors were introduced, increased visits and tests were recommended. Conclusions: This large international survey yields detailed information, highlighting variation in current follow up practices not well addressed by current guidelines. This forms a strong basis for the upcoming CommNETS/NANETS consensus meeting, which aims to produce user friendly, practical guidelines tailored to the expected pattern of recurrence in patients with NETs.
Correlation of phase 2 trials (Ph2t) results with outcomes of phase 3 trials (Ph3t) of investigational agents (IA) in locally advanced and metastatic pancreas cancer (LAMPC).
Authors: Tang Monica , Chen Julia , Goldstein David , Links Matthew , Lord Sally , Marschner Ian , Simes John , Lee Chee Khoon
Published: March 2017

227

Background: There has been minimal improvement in treatment outcomes in LAMPC. We examined results of Ph2t and Ph3t to better understand potential reasons in order to improve future trial design. Methods: We conducted a systematic review of published Ph2t and Ph3t (1978-2015) of first-line treatment for LAMPC. Data for baseline characteristics and best objective response rate (ORR) were compared. Where possible, we compared outcomes for IA tested in Ph2t with corresponding Ph3t. Results: We identified 149 Ph2t with 180 treatment arms comprising 7499 participants. Ph2t were predominantly single-arm (83%) or multi-arms with different IA doses or combinations (5%). Only 12% were randomized studies with concurrent control. The median sample size was 42 (range 8-133). The pooled ORR was 13.8% (95% CI 13.0%-14.6%) but there was substantial heterogeneity (range 0-60%, Pheterogeneity < .001; I2= 75.9%). Although 56% of Ph2t concluded that IA should be considered for Ph3t, only 11% actually proceeded to Ph3t testing. Factors associated with Ph3t testing included absence of randomized design with concurrent control (12.2% vs 5.6%), higher proportion of performance status 0 patients (24.4% vs 21.7%), higher proportion of locally advanced disease only (23.4% vs 15.4%), and higher median ORR (22.0% vs 15.4%). Of 26% Ph2t that investigated novel biological IA, 92% had a potential predictive biomarker but only 1 trial was enriched for the biomarker. Only 8% of Ph2t with novel biological IA proceeded to Ph3t. ORR of IA tested in Ph2t correlated moderate poorly with ORR (r2 = 0.21) and 6 month progression-free survival rate (r2 = 0.26) in corresponding Ph3t. Only 3 IA in Ph3t demonstrated clinically meaningful improvements. Conclusions: Despite multiple Ph2t conducted over 4 decades, only 11% progressed to Ph3t, with 3 IA ultimately improving clinical outcomes. Ph2t results do not inform Phase 3 testing of IA. Potential reasons include patient heterogeneity, overly optimistic interpretation of Ph2t results, lack of concurrent control in Ph2t and ineffective agents. These issues should be addressed in order to improve success of future Ph3t in LAMPC.
Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis.
Authors: Udompap Prowpanga , Mannalithara Ajitha , Kim Donghee , Kim W. Ray
Published: March 2017

230

Background: Sustained virological response (SVR) has been associated with decreased morbidity and mortality from hepatitis C virus (HCV) infection. Data are sparse, however, about the long-term benefits of direct-acting antiviral agents (DAAs) in terms of risk reduction for hepatocellular carcinoma (HCC). We estimate the impact of SVR on the HCC incidence in the DAA era when SVR is achieved nearly universally even in patients with advanced fibrosis and cirrhosis. Methods: We constructed a Markovian model of 50-year-old patients with compensated HCV cirrhosis (n=1,000) to model the incidence of HCC over 20-years of follow-up. We compared 2 cohorts: 1) SVR following DAA therapy and 2) no SVR (natural history). In the latter, HCC would develop at an annual rate of 4.2% and patients would die as a result of end stage liver disease (ESLD) according to their MELD (=6 at baseline). In the former, MELD score would not increase, the HCC risk would decrease and, in some patients, cirrhosis would regress. Results: The table summarizes the 20-year outcome in the two cohorts. In the cohort without SVR, HCC would occur in 33% and 63% would die of ESLD. In the SVR cohort, the proportion of HCC would increase to 37% as the number of subjects at HCC risk would increase, as a result of a dramatic reduction in deaths from ESLD. In the univariate sensitivity analyses, the cumulative HCC incidence was mainly influenced by the rate at which the risk of HCC is decreased after SVR, followed by the change in cirrhosis regression rate. Conclusions: Although HCC risk would decrease after SVR in a given individual patient with cirrhosis, on the population level, highly effective DAA therapy may lead to a paradoxical increase in the burden of HCC. These data underscore the important of (1) HCC surveillance in patients with cirrhosis even after SVR and (2) DAA intervention before cirrhosis develops. [Table: see text]
Weak correlation of overall survival and time to progression in advanced hepatocellular carcinoma.
Authors: Huang Liping , De Sanctis Yoriko , Shan Minghua , Bruix Jordi , Llovet Josep , Cheng Ann-Lii , Meinhardt Gerold , Nakajima Keiko
Published: March 2017

233

Background: Time to progression (TTP) is a potential surrogate endpoint in oncology clinical trials. The correlation of TTP and overall survival (OS) in advanced hepatocellular carcinoma (HCC) has been studied by meta-analyses (Terashima et al, Hepatol Res 2016;46:650); however, these analyses may be biased by trial selection and heterogeneity. We assessed the correlation between TTP and OS using simulated trials based on patient level data from 2 large sorafenib trials in patients (pts) with unresectable HCC (uHCC). Methods: To assess the correlation between OS and TTP, a bootstrap approach was applied to simulate 10,000 trials based on data from the randomized, phase III sorafenib trials in uHCC pts (SHARP [n = 602] and Asia-Pacific [AP; n = 226]). Individual data correlation between OS and TTP was conducted for 828 pts included in SHARP and AP. Pearson correlation was calculated between estimated median OS (mOS) and estimated median TTP (mTTP) for sorafenib and placebo (PLA) arms separately. Pearson correlation of log rank test statistics and hazard ratios were calculated to compare sorafenib and PLA for OS and TTP. Results: Simulated mOS and mTTP trial data were similar to that reported in SHARP and AP (Table). In SHARP, the correlation between mOS and mTTP was 0.270 for sorafenib and 0.218 for PLA, and in AP, 0.333 for sorafenib and 0.251 for PLA. The correlation of log rank test statistics comparing sorafenib and PLA was 0.387 in SHARP and 0.540 in AP. Conclusions: The simulated mOS/mTTP data was representative of pt population data in SHARP and AP. Our analysis showed a weak correlation between OS and TTP. This finding challenges TTP as a surrogate endpoint in HCC and should be considered when interpreting TTP results for the evaluation of treatment effect in uHCC. These data reinforce that the pattern of progression is potentially more relevant to OS than tumor progression as suggested by Reig et al ( Hepatol 2013;58:2023). Clinical trial information: NCT00105443; NCT00492752. [Table: see text]
Research on predictive value of five current staging systems in advanced hepatocellular carcinoma patients who received loco-regional therapies.
Authors: Chen Zhan-Hong , Wei Li , Hong Ying-Fen , Lin Jin-Xiang , Li Xing , Wu Xiang-yuan
Published: March 2017

237

Background: Many HCC patients are diagnosed at advanced stage and loco-regional therapies improve their prognosis. Transarterial chemotherapy with or without concomitant embolization(TACE) and percutaneous ethanol injection(PEJ) are two common loco-regional therapies.Overall survival(OS) of these patients varies differently. It is very important to identify who benefits most from loco-regional therapies. We research on five current staging systems’ predictive value. Methods: Our research analyzed 220 advanced HCC patients. They received TACE or PEJ and did not receive radical surgery, chemotherapy or target therapy. At first diagnosis all patients were classified according to CLIP (Cancer of the Liver Italian Program), Advanced Liver Cancer Prognostic System (ALCPS), Japan Integrated Scoring (JIS) system, Barcelona Clinic Liver Cancer Classification (BCLC) and model for end-stage liver diseases (MELD) score. 6 month OS, 1-year OS, 2-year OS and OS were the end points. Results: The median survival is 23.8 months. When predicting 6 month OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.847, 0.724, 0.710, 0.521 and 0.509,respectively;When predicting 1-year OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.872, 0.689, 0.693, 0.503 and 0.552,respectively; When predicting 2-year OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.855, 0.683, 0.669, 0.503 and 0.553,respectively;AUC of CLIP is significantly higher than other four staging systems in predicting 6 month OS, 1-year OS, 2-year OS(P < 0.05), while AUC difference between ALCPS and JIS does not have statistical significance in predicting 6 month OS, 1-year OS, 2-year OS(P > 0.05). When predicting OS, likelihood ratio test shows χ2 of CLIP, ALCPS, and JIS is 90.2,13.1 and 16.5 respectively. AIC of CLIP, ALCPS and JIS is 1338, 1415 and 1411 respectively. CLIP has the highest χ2 value and the lowest AIC value. As for discriminatory ability, homogeneity and monotonicity, CLIP performs best. Conclusions: The best staging system in predicting 6 month OS, 1-year OS, 2-year OS and OS for advanced HCC patients who received loco-reginal therapies is CLIP.
Early obesity and risk of cholangiocarcinoma in the United States.
Authors: Shalaby Akram , Javle Milind M. , Shroff Rachna T. , Abousamra Ahmed OS , Abdel-Wahab Reham , Rallapalli Vijayashri , Li Donghui , Hassan Manal
Published: March 2017

239

Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( > 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC.
Application of ALBI and PALBI score as prognostic variables in hepatocellular carcinoma patients treated with transarterial-chemoembolization.
Authors: Aravind Preetha , Thillai Kiruthikah , Suddle Abid , Heaton Nigel , Karani John , Kane Pauline , Peddu Praveen , Lewis Dylan , Sarker Debashis , Ross Paul J.
Published: March 2017

241

Background: Albumin-Bilirubin Score(ALBI) is simple prognostic tool to stratify HCC patients on liver function. It is proposed as more accurate predicting score of hepatic dysfunction compared with Child-Pugh (CP) grading. Platelet-Albumin-Bilirubin Score (PALBI) incorporating platelet count may offer further prognostic sensitivity. We sought to correlate ALBI, PALBI and CP grade with overall survival in HCC patients who underwent transarterial-chemoembolization (TACE). Methods: 431 HCC patients who received TACE between 2006 and 2012 at a Liver Centre, UK was included. Serum albumin, bilirubin and platelet were used to calculate ALBI and PALBI scores. Patients were classified into three groups using previously described formulas. Survival outcomes (Median OS) were measured using Kaplan-Meier method. Results: Median age of study population was 62 years. Patients classified by ALBI score, Group 1 was 208 patients (48%), 2 was 196 (45.4%) and 3 was 27 (6.3%). Median OS for Group 1 was 26.1 months (m) (95% CI 19.5-32.6), 2 was 18.6m (95% CI 14.9-21.5) and 3 was 11.7m (95% CI 6.1-17.3) (p < 0.001). PALBI Group 1 was 179 (41.5%), 2 was 150 (34.8%) and 3 was102 (23.7%). PALBI group 1 had median OS 25.5m (95% CI 17.9-33.1), 2 had 22.3m (95% CI 18.3-26.3), 3 had 10m (95% CI 5.9-14.3) (p < 0.001). Majority were class CP-A. (A = 365, B = 63, C = 2). CP-A patients were re-stratified on ALBI and PALBI status. ALBI Group 1 (N = 204) OS 26.0m (95% CI 19.5-32.6), 2 (N = 151) OS 19.1m (95% CI 14.7-23.5), 3 (N = 7) OS 7.6m (95% CI2.27-12.9) (p = 0.04). Survival of CP-A patients by PALBI was significantly different - Group1 (N = 175) OS 28.8m (95%CI 20.79-36.74), 2 (N = 140) OS 22.6m (95%CI 18.89-26.25) and 3 (N = 50) OS 8.9m (95%CI 6.25-11.5) (p < 0.001). Conclusions: Significant comparable survival difference was seen in ALBI and PALBI groups. CP-A patients with group 3 ALBI or PALBI had significantly poorer survival than groups 1 and 2 suggesting increased sensitivity determining hepatic dysfunction compared with CP status. Our results suggest ALBI and PALBI scores likely more accurate stratifying method for mild liver disease and guide treatment. Further prospective studies using both scores are warranted.
Health insurance and pancreatic cancer.
Authors: Schlegel Cameron , Du Liping , Shyr Yu , Whiteside Martin , Parikh Alexander A.
Published: March 2017

247

Background: Health insurance disparities affect the treatment and outcomes of many cancers and include differences in screening, surgical therapy and receipt of adjuvant therapy. The purpose of this study is to better identify the effect of health insurance on surgical therapy and overall survival (OS) in pancreatic adenocarcinoma (PDAC). Methods: 4564 patients diagnosed with PDAC between 2004 and 2013 from the Tennessee Cancer Registry were stratified into 5 groups: Private, Medicare, Military, Medicaid, and uninsured. Univariate analysis and multivariable (MV) logistic regression models were used to test the association of insurance with receipt of surgical therapy, adjuvant therapy, OS and cost. Results: Uninsured and Medicaid patients were more often black and presented with later stage disease. In patients with stage 1 and 2 disease, R0 resection rates, lymph node positivity and overall cost were similar across insurance groups. By MV analysis, Medicare and Military insurance patients were more likely to be resected (OR 2.52 and 3.30 respectively) with a trend for private insurance (OR 2.19) compared to the uninsured and Medicaid. There was no difference in the use of adjuvant chemotherapy (ACT). By Cox-proportional hazards regression, OS in resected patients amongst different insurance groups and race were similar (Table). Factors associated with decreased OS survival included increasing age, stage, lymph node status, and grade while the use of ACT, but not chemoradiation (ACRT), was associated with improved OS. Conclusions: Uninsured and Medicaid patients with PDAC present with later stage disease and are less likely to undergo resection. The use of adjuvant chemotherapy, OS and cost, however, are similar among insurance types. These results are in contrast to other cancers, suggesting that disparities in health insurance may play a smaller role in more aggressive cancers without effective screening. [Table: see text]
Role of HSF1 expression for tumor microenvironment in intrahepatic cholangiocarcinoma.
Authors: Saito Yu , Morine Yuji , Takasu Chie , Iwahashi Shuichi , Higashijima Jun , Ikemoto Tetsuya , Imura Satoru , Shimada Mitsuo
Published: March 2017

249

Background: Heat shock factor 1 (HSF1) is a master regulator of heat shock response. HSF1 is recently identified to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 in intrahepatic cholangiocarcinoma (IHCC) remain unknown. The aim of this study was to investigate the relationship between HSF1 expression and clinicopathological factors in IHCC patients after hepatic resection, and its possible mechanism for malignant behavior. Methods: Forty-nine patients with IHCC who undergo hepatic resection were enrolled in this study. HSF1 expressions in tumor tissue were determined by immunohistochemistry. Patients were divided into two groups, the HSF1 high and low expression group. Clinicopathological factors including prognosis were compared between the high group (n = 20) and low expression groups (n = 29) in tumor tissues. Furthermore, the correlation between HSF1 with Fbxw7 or Ki-67 expressions was also examined. Results: HSF1 expression in tumor tissues was significantly higher than that in normal tissues. HSF1 expression was not significantly correlated with any clinicopathological characteristics, including age, sex, tumor markers, maximum tumor size, tumor number, and tumor staging curability . The overall survival rate in the HSF1 high expression group was significantly worse than that in the HSF1 low expression group ( p= 0.018). On multivariate analysis, HSF1 high expression was detected as the independent prognostic factor. There was a significant inverse correlation between HSF1 and Fbxw7 expression ( p= 0.008). Ki67 labeling index was significantly higher in the high than in the low HSF1 expression group ( p= 0.030). Conclusions: HSF1 high expression in tumor tissues may be prognostic biomarker in IHCC. Targeting the Fbxw7/HSF1 axis might be a critical therapeutic strategy in IHCC.
Quantitative CT imaging features for hepatocellular carcinoma (HCC) with b-catenin (CTNNB1) gene mutation.
Authors: Khalaf Ahmed M. , Fuentes David T. , Ahmed Kareem , Abdel-Wahab Reham , Hassan Manal , Kaseb Ahmed Omar , Hazle John D. , Elsayes Khaled M.
Published: March 2017

253

Background: To determine whether CT imaging features can provide quantitative biomarkers to differentiate HCC with pathologic B-catenin gene mutation and those without mutation. Methods: Quantitative imaging features were extracted from a database of manually labeled liver with enhancing and non-enhancing tumor tissue,which were established using multiphasic CT images from 17 patients. CT studies were done before each patient underwent surgical removal of the HCC, which were subjected to pathologic analysis to evaluate B-catenin mutation.The mean period between the CT studies and the pathologic analyses was 18 days. According to the pathology results, the patients were divided into two groups: HCC with CTNNB1 mutation and HCC without. Image feature extraction included image gradients, co-occurrence matrix, and pixel neighborhood statistics of the first, second, and third moments. Pairwise analyses of the imaging features were performed on the mutated and non-mutated HCC images and the background liver tissue of both groups. Independent samples t-test and Mann Whitney U test were performed to quantitatively compare between the means of the imaging features extracted from the tumor tissues of both groups and those extracted from the background liver tissue of both groups. Results: Imaging feature analysis of the pairwise difference between the mutated and non-mutated HCC scans for multiple pixel-neighborhood image features are statistically significant.The top stratifying image features include the skewness (p = 0.02), energy (p = .03), and entropy (p = .03) during the venous and arterial phase. Conclusions: This preliminary study demonstrates the feasibility of quantitative imaging feature extraction from CE-CT imaging to differentiate between HCC with proven B-catenin gene mutation and those without mutation. Non-invasive methods of identifying HCC with B-catenin mutations may be clinically beneficial since B-catenin is an important potential target in novel cancer therapies, and identifying B-catenin mutations may also help provide information regarding prognosis.Verifying the quantitative features in larger patient populations is needed to confirm the results of this study.
Tumor stage and primary treatment selection among a large cohort patients with hepatocellular carcinoma.
Authors: You Xue-Mei , Zhong Jian-Hong , Peng Ning-Fu , Ma Liang , Li Le-Qun
Published: March 2017

256

Background: This study reviewed the distribution of each tumor stage and each type of primary treatment modality among patients with primary hepatocellular carcinoma (HCC) treated at a tertiary tumor hospital between January 2003 and October 2013. Methods: Baseline data of patients with primary HCC treated between January 2003 and October 2013 were retrospectively collected. Tumor stage was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system and Hong Kong Clinic Liver Cancer (HKLC) staging system. Results: A total of 6241 patients with primary HCC were included in the analysis. In accordance with the BCLC, 28.9% of patients were in stage 0/A, 16.2% in stage B, 53.6% in stage C, and 1.3% in stage D. According to the HKLC stage system, 8.4% patients were in stage I, 1.5% in stage IIa, 29.0% in stage IIb, 10.0% in stage IIIa, 33.6% in stage IIIb, 3.4% in stage IVa, 2.5% in stage IVb, 0.2% in stage Va, and 11.4% in stage Vb. Treatment modalities applied to this patient group were as follows: 33.3% of patients underwent hepatic resection, 36.7% underwent transarterial chemoembolization (TACE), 2.2% underwent radiotherapy, 0.9% underwent local ablated therapy, 8.8% underwent systemic chemotherapy, 4.2% underwent traditional herbal medicine therapy, 0.1% underwent targeted drug therapy, and 13.8% received no treatment. Hepatic resection was the most frequent therapy for patients with BCLC 0/A/B disease, and TACE was the first-line therapy for patients with BCLC C disease. In the HKLC stage, the main treatments for HKLC I to IIIb disease is hepatic resection and TACE. Systemic chemotherapy was the first-line therapy for patients with HKLC IVa/IVb disease. Most HKLC Va/Vb patients received traditional Chinese medicine (TCM) treatment. Conclusions: Prevalence of stage BCLC B and C disease was high among our HCC patients. In HKLC stage, HKLC I to IIIb disease was high among our HCC patients. Hepatic resection and TACE are first-line therapies.
Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection.
Authors: Xiang Xiao , Zhong Jian-Hong , Ke Yang , You Xue-Mei , Peng Ning-Fu , Ma Liang , Li Le-Qun
Published: March 2017

257

Background: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n = 155) or ADV (n = 46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free and overall survival, as well as antiviral medication costs. Results: Despite significant improvement in HBV-DNA and ALT level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2 and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, 56.4%) than in the ADV group (0%, 3.3%, 14.5%; P < 0.001). Overall survival at 1, 2, 3 years after resection was similar for the LAM group (84.5%, 69.3%, 64.6%) and the ADV group (84.1%, 77.8%, 63.4%; P = 0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, 43.9%) and the ADV group (81.1%, 66.1%, 53.0%; P = 0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, €5.6 per person per day) than in the ADV group (€2.2, €2.4, €3.1 per person per day; all P < 0.05). Conclusions: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.
Impact of preoperative sarcopenia and accelerated muscle loss on survival after resection of pancreatic cancer.
Authors: Lee Kyungjin , Choi Moon Hyung , Yoon Seung Bae , Lee In Seok , Lim Chul-Hyun , Kim Jin Soo , Cho Yu Kyung , Park Jae Myung , Lee Bo-In , Cho Young-Seok , Choi Myung-Gyu
Published: March 2017

258

Background: Sarcopenia and accelerated muscle loss leading to cachexia is commonly observed in patients with pancreatic cancer. This study aimed to assess the influence of sarcopenia and accelerated skeletal muscle on survival in pancreatic cancer patients who underwent surgery. Methods: We analyzed the data of patients who were diagnosed with pancreatic adenocarcinoma who underwent surgery from 2008 to 2015. Skeletal muscle areas and changes were analyzed from two sets of computed tomography images at L3 vertebral levels obtained before and after resection of cancer. Sarcopenia was determined by the sex-specific cut-offs by an international consensus on the definition of cancer cachexia. Results: Among 175 patients, 83(47.4%) had preoperative sarcopenia and median survival were significantly shorter than patients without sarcopenia (423 vs. 694 days, p = 0.001). In addition, 50 (28.6%) patients with accelerated muscle loss after surgery ( > 15%/90 days) showed poorer survival compared with the patients without accelerated muscle loss (423 vs. 637 days, p = 0.017). Sarcopenia (hazard ratio [HR], 1.96: 95% confidence interval [CI], 1.24-3.10) and accelerated muscle loss (HR, 1.73: 95% CI, 1.10-2.72) were identified as independent predictors of survival on multivariate analyses. Combining these two factors, patients who had both preoperative sarcopenia and accelerated muscle loss showed the poorest survival after surgery compared with the other groups (p < 0.001). Conclusions: Preoperative sarcopenia and accelerated muscle loss identified by CT scans have negative impact on survival after resection of pancreatic cancer. Early detection and intensive nutritional support were essential for cachexic patients with pancreatic cancer.
Laparoscopic function-preserving gastrectomy based on sentinel node concept for early gastric cancer patients.
Authors: Takeuchi Hiroya , Goto Osamu , Shimada Ayako , Fukuda Kazumasa , Nakamura Rieko , Suda Koichi , Wada Norihito , Kawakubo Hirofumi , Yahagi Naohisa , Kitagawa Yuko
Published: March 2017

26

Background: Recent meta-analyses have shown acceptable SN detection rates and accuracy of determination of lymph node status. SN mapping may play a key role to obtain individual metastatic information and allows modification of the surgical procedures such as function-preserving gastrectomy for early gastric cancer. Methods: A dual-tracer method that employs radioactive colloids and blue dyes is currently considered the most reliable method for the stable detection of SNs in patients with early gastric cancer. The new technologies such as indocyanine green infrared or fluorescence imaging are also useful for accurate SN mapping in gastric cancer. Results: SN mapping has been performed for 489 patients with clinically T1N0M0 gastric cancer in our institute since 1999. Sensitivity to predict the lymph node metastasis was 90%, and overall accuracy of nodal status based on SN concept was 99 % (484 of 489). Sentinel lymphatic basin dissection is strongly recommended to cover the false-negative results of SN mapping in clinical practices. Based on these results, laparoscopic minimized gastrectomy such as partial resection, proximal gastrectomy, segmental gastrectomy and pylorus-preserving gastrectomy with individualized selective and modified lymphadenectomy for early gastric cancer with negative SN has been performed in our institution. The recent appearance of a new technique, referred to as non-exposed endoscopic wall-inversion surgery (NEWS) is a technique of full thickness resection using endoscopy and laparoscopic surgery without transluminal access mainly designed to treat gastric cancer with partial resection. The combination of NEWS with SN biopsy is expected to become a promising, ideal minimally invasive, function-preserving surgery for cN0 early gastric cancer. We initiated a new multicenter prospective trial to evaluate function-preserving gastrectomy with SN mapping in terms of long-term survival and patients’ QOL. Conclusions: Our results suggested that SN concept for cN0 early gastric cancer could be validated, and function-preserving surgery based on the SN concept which might retain the patients’ quality of life should be established as the next surgical challenge.