bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Prognostic factors and scoring model for survival in advanced biliary tract cancer.
Authors: Park Hyung Soon , Park Ji Soo , Roh Yun Ho , Moon Jieun , Yoon Dong Sup , Jeung Hei-Cheul 
Published: March 2017

264 Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( < 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P < 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P < 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P< 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection.
Proposal of size-based surgical indication criteria for liver hemangioma based on a nationwide survey in Japan.
Authors: Sakamoto Yoshihiro , Kokudo Norihiro , Watadani Takeyuki , Shibahara Junji , Yamamoto Masakazu , Yamaue Hiroki 
Published: March 2017

265 Background: Although hepatic hemangioma is one of the most frequent benign tumors in the liver, surgical indication for this neoplasm remains unclear. The objective of the present study was to conduct a nation-wide survey on resected cases of liver hemangioma and propose evidence-based surgical indication criteria for this disease (Research project of Japanese Society of Hepato-Biliary-Pancreatic Surgery). Methods: Of a total of 510 patients undergoing surgical resection for liver hemangioma in 118 Japanese centers between 1998 and 2012, abdominal symptoms, coagulopathy, diagnostic accuracy and surgical outcomes were analyzed according to the tumor status. Results: The patients were classified into 4 groups based on the tumor size; Group A) ≤ 5cm (n = 122, 24%), B) 5-10cm (n = 164, 32%), C) 10-15cm (n = 124, 24%), and D) > 15cm (n = 100, 20%) Hemangioma in Group A was most frequently diagnosed as a malignant tumor (43.5%) due to absence of typical imaging findings as cavernous hemangioma and with highest incidence of positive of HBV (15.7%). Diagnostic accuracy was 98.4% in Groups B-D. In Group B, 71% of patients presented no abdominal symptoms or Kasabach-Merritt syndrome. Symptoms associated with hemangioma increased in proportion as the size increased, and the incidence of abdominal distension, tumor rupture, and Kasabach-Merritt syndrome were 55%, 2.0%, and 26%, respectively, in Group D. The incidence of liver failure after hepatectomy was higher in Group D than in Groups A-C (3.0% vs. 0.5%, p = 0.02). There was only one operative death (0.2%) in Group D. Conclusions: In patients with = /< 5cm hemangioma, surgical resection is indicated when malignant tumor can not be ruled out. However, surgical indications for 5-10cm asymptomatic hemangiomas should be limited because preoperative diagnosis of benign disease is trustworthy in this subgroup. Tumor size > 10cm would be candidate for surgery when accompanied with abdominal symptom or coagulopathy, and hepatectomy for tumors > 15cm should be performed in high volume centers by experienced hepatic surgeons to avoid serious morbidity or mortality.
Visceral thromboses (VT) in pancreas adenocarcinoma (PDAC): A systematic review.
Authors: Mier Hicks Angel , Derosa Antonio , Raj Micheal , Do Richard Kinh Gian , Yu Kenneth H. , Lowery Maeve Aine , Varghese Anna M. , O'Reilly Eileen Mary 
Published: March 2017

268 Background: Within the spectrum of gastrointestinal malignancies, primary liver (HCC) and pancreatic ductal adenocarcinoma (PDAC) are frequently associated with visceral thromboses (VT). Thrombus formation in the portal (PVT), mesenteric (MVT), or splenic vein (SVT) system leads to portal hypertension and intestinal ischemia. VT in PDAC may convey a risk of increased distal thrombosis and poses therapeutic uncertainty regarding the role of anticoagulation. An increasing number of reports describe VT associated with PDAC. It is possible that early diagnosis of these events may help reduce morbidity speculatively improve oncologic outcomes. Methods: Perform a systematic review to study occurrences of visceral thromboses (portal, mesenteric and splenic vein thromboses) associated with PDAC and provide a clinical review on this area. Main databased were searched; PubMed, EMBASE, Web of Science, Scopus, and the Cochrane library. Two blinded independent observers extracted and assessed the studies for diagnosis of PVT, MVT, and SVT in PDAC. Studies were restricted to English literature published after 2007 to 2016. Results: Eleven articles were identified. Five case reports and 7 retrospective studies were found with a total of N=127 patients meeting the inclusion criteria. The mean age at diagnosis was 64 years. PVT was found in 35% (N= 46), SVT in 52% (N= 65), MVT in 13 %( N= 15). Mean follow up time was 26 months. Only 3 of the selected articles studied the impact of anticoagulation in visceral thrombosis. All patients with non-visceral thrombosis (e.g. DVT, PE) were therapeutically treated, in contrast, to only rare occurrences with VT received treatment. Conclusions: Visceral thrombosis in PDAC can be a frequent finding at diagnosis or during disease progression. This literature analysis has shown VT to be a poor prognostic indicator for short term survival. Evidence to guide treatment choices are inadequate and current management is based on inferred experience from other non-oncologic populations. Anticoagulation appeared to be a safe modality in visceral thrombosis with most of the large studies recommending a careful assessment for patients with high risk of bleeding.
The clinical impact of PET/CT with 68Ga-DOTATATE in neuroendocrine tumors (NETs): The experience of a private institution in Brazil.
Authors: Tsukamoto Jessica Sayuri , Wassano Noelle Suemi , Barbosa Luiza Damian Ribeiro , Braga Virginia Moreira , Rigo Letícia , Racy Douglas Jorge , Soares De Souzsa Tercia Tarciane , Belotto Marcos , D'Alpino Renata D'Alpino 
Published: March 2017

271 Background: The introduction of PET/CT with 68Ga-DOTATATE (68Ga-PET) determined an exponential increase of the accuracy in diagnosing and following up NETs. However, this exam is not frequently available in developing countries. Methods: We have retrospectively evaluated the efficacy of 68Ga-PET in patients with NETs and its impact on clinical decision at Hospital São José, Brazil. Results: Between February 2014 and July 2016, 28 patients (15 males) with histologically confirmed NETs underwent Ga68-PET at our hospital. Median age was 57 (range 21 - 82). Primary sites were pancreas (n = 10), small bowel (n = 7), lung (n = 3) and others (n = 8). The Ki-67 index was < 2% in 7 patients and > 20% in 6 patients. Five patients had unknown Ki67 index. There was 68Ga uptake in 82% of the patients (21,4% in patients with Ki67 > 20%). Median SUV was 16,3 (range 1,7- 129,8). Only 32% of the patients underwent concomitant Octreoscan. Results were divergent between both imaging methods in 55% of the patients, which resulted in therapeutic change. The main reason to request the exam was to measure the extent of metastatic disease (n = 14). Other reasons were to access response to therapy (n = 8), to evaluate the possibility of treatment with Lutetium (n = 3), to investigate the primary tumor (n = 2), and others (n = 1). Conclusions: Ga68-PET is an important imaging key to guide therapeutic management in NETs, especially among patients with Ki67 < 20%. When available, Ga68-PET is superior to Octreoscan.
Orally administered CCR2 selective inhibitor CCX872-b clinical trial in pancreatic cancer.
Authors: Noel Marcus Smith , Hezel Aram F. , Linehan David , Wang-Gillam Andrea , Eskens Ferry , Sleijfer Stefan , Desar Ingrid , Erdkamp Frans , Wilmink Johanna , Diehl Janet , Potarca Antonia , Zhao Niky , Deng Jun , Lohr Lisa , Miao Shichang , Charo Israel , Singh Rajinder , Schall Thomas J. , Bekker Pirow 
Published: March 2017

276 Background: CCR2 inhibition decreases tumor-associated macrophages and Treg cells, and increases CD8+ and CD4+ T cells in pancreatic tumors. Single oral doses of 150 mg CCX872-B were well tolerated in patients with pancreatic cancer. The first stage results of the multiple dose part of this study are presented. Methods: Patients with locally advanced or metastatic pancreatic cancer, ECOG score ≤ 2 were studied. Patients received FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) q2weeks for up to 24 wks plus 150 mg CCX872-B once or twice daily until disease progression or intolerance to CCX872-B. The primary efficacy endpoint is progression-free survival (PFS) at 24 wks. Tumor control rate (TCR) and the objective response rate (ORR), a secondary endpoint, are presented. Results: Fifty patients were enrolled. Baseline: Mean ± SD age: 60 ± 8.6 years, male 52%; primary tumor location: head 57%, body/tail 41%, local recurrence 2%; metastatic disease 78%, ECOG score 0: 62%, ECOG score 1: 38%. Thirty five of 50 patients completed week 12. Most common reasons for early withdrawal were subject request (5 pts) and adverse events typically associated with FOLFIRINOX (4 pts). In the pre-specified analysis population, i.e., those with ≥ 1 post baseline CT scan, tumor control at wk 12 was achieved in 32 of 41 (78%) patients, with 15 of 41 (37%) partial responders, and 17 of 41 (41%) with stable disease. The ORR was 37% (all partial responders) in the primary analysis population (30% when all enrolled patients were included). Thirteen of 21 patients with available CT scan results at week 24 were progression-free. Mean trough CCX872 plasma level was ~8 μg/mL. CCR2 was covered 88% on average by CCX872-B based on receptor occupancy assays. CCX872-B appeared to be well tolerated and the incidence of ≥ Gr 3 AEs was not increased with CCX872-B plus FOLFIRINOX vs historical data with FOLFIRINOX alone. The complete set of PFS data will be available by the end of 2016. Conclusions: CCX872-B plus FOLFIRINOX resulted in a TCR of 78% and an ORR of 30 to 37% with no safety issues ascribed to CCX872-B use. Clinical trial information: NCT02345408.
Tumor interface stability on CT imaging is an early marker of response to cytotoxic therapy in pancreatic ductal adenocarcinoma.
Authors: Wilke Christopher , Amer Ahmed , Elganainy Dalia , Bhosale Priya , Le Ott , Lee Yeonju , Cloyd Jordan , Wang Huamin , Herman Joseph M. , Taniguchi Cullen M. , Rhim Andrew , Fleming Jason B. , Maitra Anirban , Wolff Robert A. , Varadhachary Gauri R. , Lee Jeffrey Edwin , Katz Matthew H. G. , Tamm Eric P. , Koay Eugene Jon 
Published: March 2017

284 Background: There is currently no reliable biomarker for assessing the response to therapy of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated how changes in the tumor/parenchyma interface associate with response. Methods: We reviewed pre- and post-therapy scans of patients who received chemotherapy and/or chemoradiation for both localized and metastatic PDAC. We classified the interface between the PDAC tumor and surrounding pancreas parenchyma as stable (remains or becomes well-defined) or unstable (becomes poorly defined) using a novel visual scoring system and quantified changes in enhancement at this interface (Philips Intellispace Portal, quantitative European Association for the Study of Liver [qEASL]). Results: Three retrospective datasets were used to develop this method with consensus visual scoring performed by 3 radiologists. The first dataset included 99 patients with localized PDAC who received neoadjuvant chemoradiation. Patients who were classified as having a stable interface had significantly higher probability of achieving a complete or near-complete pathologic response (21% vs 0%, p = 0.01) and additionally demonstrated an improved median disease-free survival (DFS, 20.9 vs 7.9 mos., p < 0.01) and overall survival (OS, 47.7 vs 19.1 mos., p < 0.01). These results were validated in a separate dataset of 94 patients receiving protocol-based chemotherapy and chemoradiation (chemoRT cohort) and a cohort of 86 patients with stage IV disease. In both cohorts, a stable interface was associated with a significant improvement in progression free survival (PFS, Hazard Ratio [HR] 0.44, p = 0.01 for chemoRT and HR 0.70, p = 0.16 for stage IV) and OS (HR 0.42, p < 0.01 for chemoRT and HR 0.59, p = 0.05 for stage IV). Multivariate analyses for each cohort showed interface stability to be independently associated with both DFS/PFS and OS. Measurements obtained using qEASL were concordant with the visual scoring results. Conclusions: The interface stability of PDAC is an early readout of response to therapy. Integration of this imaging feature into clinical trials for localized and metastatic PDAC may aid in the future development of adaptive treatment strategies.
Health-related quality of life (HRQoL) in patients with advanced neuroendocrine tumors (NET) of gastrointestinal origin in the phase 3 RADIANT-4 trial.
Authors: Singh Simron , Strosberg Jonathan R. , Bubuteishvili-Pacaud Lida , Degtyarev Evgeny , Neary Maureen , Hunger Matthias , Eriksson Jennifer , Ricci Jean-Francois , Fazio Nicola , Kulke Matthew H. , Pavel Marianne E. , Yao James C. 
Published: March 2017

285 Background: In the RADIANT-4 trial, everolimus (EVE) plus best supportive care (BSC) improved progression-free survival (PFS) compared to placebo (PBO) plus BSC in 302 patients with advanced progressive nonfunctional NET of gastrointestinal (GI) or lung origin (Yao, Lancet 2015) and in patients of GI origin only (Singh, ASCO-GI 2016). In addition, HRQoL was maintained with no statistically or clinically relevant differences in patients receiving EVE compared to PBO in the full sample (Pavel, ASCO 2016) and in patients with NET of GI origin (Pavel, NANETS 2016). Complementary analyses are presented to assess treatment effect on HRQoL in the subpopulation of patients with NET of GI origin. Methods: HRQoL was measured with FACT-G, a 27-item validated questionnaire with 4 domains: physical (PWB), social/family (SWB), emotional (EWB), and functional wellbeing (FWB). FACT-G was completed at baseline and every 8 weeks until month 12, then every 12 weeks until study drug discontinuation. Linear mixed models (LMM) were fitted to analyze mean FACT-G total (scale: 0 – 108) and subscale scores over time. A responder analysis in terms of cumulative distribution functions (CDF) of patients mean change from baseline across the entire study period was also conducted. Results: The subgroup of patients with NET of GI origin included 211 patients (141 on EVE and 70 on PBO) with NET of ileum, rectum, jejunum, stomach, duodenum, colon, caecum, appendix, or cancer of unknown primary (CUP), generally known as GI origin. In LMM, FACT-G total score at week 8 was 79.9 (95% CI: 77.7, 81.1) for EVE and 79.9 (95% CI: 77.0, 82.8) for PBO, declining to 77.1 (95% CI: 73.9, 80.4) and 78.7 (95% CI: 73.4, 83.9) at week 48. At each time point, differences in mean scores between treatment arms were lower than the minimally important difference (MID) of 7 points. Differences in mean subscale scores between treatment arms also did not exceed the MID (3 points). CDF plots showed no differences in distributions for the FACT-G total score (p = 0.9348). Conclusions: In addition to PFS benefits, HRQoL is maintained in patients with NET of GI origin receiving EVE despite usual toxicities of active cancer treatment. Clinical trial information: NCT01524783.
Prognostic value of CD8+CD45RO+ tumor-infiltrating lymphocytes (TIL) and PD-L1 in cholangiocarcinoma.
Authors: Kim Dae Won , Coppola Domenico , Chang Young , Kim Richard D. 
Published: March 2017

286 Background: Cholangiocarcinoma is a malignancy arising from the epithelial cells of the biliary tract with poor prognosis. TILs and PD-L1 have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Methods: Formalin-fixed paraffin-embedded tumor samples from 41 patients with resected and histologically verified cholangiocarcinoma between 1990 and 2015 were identified and immunohistochemically (IHC) stained with anti-CD8, anti-CD45RO and the anti-PDL1 mouse IgG1 (clone 5H1; Thompson) antibodies. Stained tumor samples were reviewed and enumerated by a GI pathologist. PD-L1 positivity was defined ≥ 5% of tumor cells with a minimum of 100 evaluable tumor cells. The association between expression of PDL1, CD8 or CD45RO and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results: The median age of patients was 64 (41-85) with 53% male. 22%, 41% and 37% were stage I, II and III, respectively. CD8 was positive in 16 (39%), CD8CD45RO (memory CD8 cells) was positive in 5 (12%), and PD-L1 was positive in 19 (46%). With a median follow-up of 21.4 months, tumors with CD8+CD45RO+ TIL has better cancer specific survival (median: unreached vs 41.2mo, HR = 0.27, 95% CI: 0.09-0.83, P = 0.023) and overall survival (median: unreached vs 21.4mo, HR = 0.34, 95%CI: 0.14-0.82, P = 0.016) than CD45RO-. The expression of CD8 alone or PD-L1 in tumor was not associated with prognosis. Multivariate analysis showed that CD8+CD45RO+ TIL (HR = 0.13, 95% CI: 0.02-0.99, P = 0.049) as well as stage, adjuvant treatment and R0 resection (microscopically margin-negative) were independent predictors of OS. Conclusions: Presence of CD8 memory T cells (CD8+CD45RO+) in tumor microenvironment was associated with significant better clinical outcome, and the expression of PD-L1 on cholangiocarcinoma cells may suggest a potential therapeutic target of antiPD-L1 antibody therapy in cholangiocarcinoma.
Association of elevated alpha-1 antitrypsin with advanced clinicopathologic features of hepatocellular carcinoma.
Authors: Abdel-Wahab Reham , Hassan Manal , Wolff Robert A. , Lacin Sahin , Al-Shamsi Humaid Obaid , Raghav Kanwal Pratap Singh , Shalaby Ahmed S , Yao James C. , Kaseb Ahmed Omar 
Published: March 2017

289 Background: Alpha-1 Antitrypsin (A1AT) is a circulating liver derived protease inhibitor. There is an evolving evidence that elevated level of A1AT stimulate tumor cell proliferation, and invasion in different cancers. Despite A1AT well-known involvement in hepatic fibrosis, its role in hepatocellular carcinoma (HCC) pathogenesis is not well characterized. The current study aimed to investigate the association between A1AT and clinicopathologic features and prognosis of patients with HCC. Methods: Between 2001 and 2014, total of 766 HCC patients from MD Anderson Cancer Center were enrolled. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. The normal level of plasma A1AT was defined based on the Mayo clinic reference value (1 – 1.9 mg/ml). Survival analysis included Kaplan Meier statistic and Cox regression analysis. Multivariate Hazard Ratio (HR) and 95% Confidence interval (CI) were estimated to determine the independent effect of A1AT on HCC prognosis. Results: The mean and standard deviation of plasma A1AT level was 2.7 ± 0.98 mg/mL. All patients were categorized into 2 groups: group 1 (N = 156) with normal serum level ( ≤ 1.9) and group 2 (N = 610) with higher values ( > 1.9). Median survival (months), 95% CI were 24.4 (18.02 – 30.7) and 11.6 (9.6 – 13.6) in group 1 and 2 respectively, (P < .0001). Patients in group 2 experienced poor clinical characteristics than group 1. The estimated multivariate HR (95% CI) for A1AT is 1.4 (1.1 – 1.7) after adjustment for age, sex, race, cirrhosis, AFP, TNM staging, and treatment exposure. Conclusions: High plasma level of A1AT is associated with higher α-feto protein, advanced TNM and Barcelona clinic liver cancer (BCLC) staging and poor survival of HCC patients. Recent preliminary studies suggested that changes in glycosylaion of production of A1AT by HCC cells correlates with the microenvironment inflammatory and proteolytic activities, which are probably linked to advanced clinicopathologic features and poorer survival. Future excremental studies are warranted to understand the mechanistic pathways of potential A1AT involvement in HCC initiation and progression.