bluuebunny/crossref_metadata_2025_split huggingface dataset:
The usefulness of condom method EUS for esophageal mass evaluation.
Authors: Moon Jeong Seop , Seol Sang Yong , Song Pil Hun , Sung Hyun , Lee Jeonghun , Kim Jae J , Yoon Won Jae , Ryu Soo Hyung , Kim You Sun 
Published: February 2017

23 Background: The endoscopic ultrasonography (EUS) is positioned as the method of choice to evaluate the origin and depth of invasion for the esophageal mass. To overcome the disadvantages as aspiration resulting from water filling EUS and balloon rupture resulting from balloon EUS, we used condom method EUS for esophageal mass evaluation. Methods: We investigated retrospectively twenty six patients examined condom method EUS using high frequency ultrasound probes after diagnosed esophageal mass lesion including submucosal tumor by standard endoscopy between January 2007 and April 2015 at Seoul Paik Hospital, Seoul, Korea. We checked the originating layer, invasion depth and echogenicity of the mass and events complicated by procedure. Results: The condom method EUS provided high quality images without aeration and well-defined five layers of esophagus through 360 degrees. In all segments of esophagus; upper (n = 5), middle (n = 10), lower esophagus(n = 11), showed high resolution images without difference. Diagnosis were squamous cell cancer (n = 4), leiomyoma (n = 5), squamous intraepithelial neoplasia (n = 2), acanthosis (n = 2), inflammatory fibrinoid polyp (n = 1) and extrinsic compression (n = 1). Tumors were originated from mucosa (n = 5), muscularis mucosa (n = 10), submucosa (n = 3), mucosa invading into submucosa (n = 4), muscle propria (n = 3). One was diagnosed as outer compression. In esophageal cancer patients, by confirming the location and invasion of the tumor, we could make a decision the next step such as follow up, endoscopic removal or surgery. No complications had occurred in all cases, aspiration or balloon rupture. Conclusions: The condom method EUS is already known as a safe image diagnostic tool of high resolution. Simply to apply inexpensive latex condom filled with water can provide good EUS visual field and images of the esophageal mass lesions along the whole esophagus without aspiration risk.
A molecular biomarker targeted approach to adjuvant therapy for resected pancreatic adenocarcinoma: Results of a phase II prospective trial.
Authors: Postlewait Lauren McLendon , Ethun Cecilia G. , Kooby David A. , Sarmiento Juan , Staley Charles A. , Brutcher Edith , Adsay Volkan , El-Rayes Bassel F. , Maithel Shishir Kumar 
Published: February 2017

230 Background: Standard adjuvant treatment for resected pancreatic adenocarcinoma is gemcitabine (Gem) (CONKO-001 trial: Gem vs placebo DFS 13.4 vs 6.7 mo; p<0.001; OS 22.8 vs 20.2 mo; p=0.01). Adding cisplatin (Cis) to Gem has shown increased response rates in the metastatic setting. This benefit may be inhibited by high expression of excision repair cross-complementing gene–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis chemotherapy, stratifying results by tumor ERCC1 expression. Methods: Patients with resected pancreatic adenocarcinoma at a single institution were enrolled from 2010-2013. Initially, patients received Gem (1000 mg/m2) / Cis (50 mg/m2) Day 1/8/15, Q28d for 6 cycles. After enrolling 5 pts, this was modified to Day 1/15 due to toxicity. Two dose reductions were permitted. Intent to treat analyses were conducted. Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low and high expression groups. Primary outcomes were RFS and OS stratified by ERCC1 expression. Results: Of 22 pts, 16 (73%) had Stage IIB disease, 5 (23%) Stage IIA, and 1 (4%) Stage IA. Thirteen (59%) completed all 6 cycles of therapy, of whom 9 required dose reduction. Of the remaining 9 pts, 4 completed >68% of intended therapy. Grade 3 and 4 toxicity occurred in 13 pts (59%); neutropenia was most common (n=9;41%). Median follow-up was 37.5 mo. Median RFS was 16.7 mo, and OS was 35.5 mo. ERCC1 tumor expression data were available for 20 pts: 15 low (75%) and 5 high (25%). Low compared to high ERCC1 was not associated with improved RFS (12.4 vs 16.7 mo; p=0.68) or OS (Median not reached vs 21.6 mo; p=0.22). Conclusions: Adjuvant gemcitabine/cisplatin is tolerated by patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in the majority of patients. Further prospective trials evaluating Gem/Cis as an adjuvant regimen and ERCC-1 as a biomarker in resected pancreatic adenocarcinoma are warranted. Clinical trial information: NCT01188109.
Stereotactic body radiation therapy for pancreatic cancer: Assessing motion with and without abdominal compression.
Authors: Stumpf Priscilla K. , Jones Bernard , Jain Supriya K. , Amini Arya , Thornton Dale A. , Dzingle Wayne , Schefter Tracey E. 
Published: February 2017

234 Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for locally advanced pancreatic cancer. This ablative therapy requires highly accurate delivery due to nearby organs at risk. To minimize tumor motion, our institution applies abdominal compression during computed tomography (CT) simulation. The purpose of this study is to evaluate the effect of compression in the context of pancreatic SBRT. Methods: In the last 6 months, 32 patients who completed SBRT to the pancreas at our institution were selected for analysis. In each patient, two 4DCT images were acquired, one with and one without abdominal compression. Abdominal compression was achieved with an indexed compression belt with a customized degree of inflation. Each patient had fiducial markers implanted in or near the pancreatic tumor prior to simulation. These fiducials were contoured on both planning CT scans for each gated phase. Motion was assessed by fiducial position changes throughout each gated phase. Results: In the anterior to posterior, transverse, and superior to inferior dimension, compression decreased motion in 19 of 32 cases (59%), 21 of 32 cases (66%), and 28 of 32 cases (88%) respectively. In the anterior to posterior (AP) dimension compression decreased motion by a mean of 0.43mm ± 1.7mm with a range of -2.1-6.5mm (p = 0.16). The mean decrease in motion with compression in the transverse dimension was 0.93mm ± 1.9mm with a range of -1.6-8.6mm (p = 0.01). In the superior to inferior dimension, compression decreased motion by a mean of 2.72mm ± 2.8mm with a range of -1.2-11.5mm (p < 0.001). Displacement of tissue due to compression led to increased patient AP separation at the level of T12 by a mean of 9.1±5.8mm (p < 0.001). Conclusions: Abdominal compression significantly reduced tumor motion in the superior to inferior and transverse directions for patients undergoing SBRT to the pancreas. This decrease in motion allows for significant reductions in the size of the volume necessary to treat the tumor. Given our findings, we would recommend using abdominal compression over free-breathing for pancreatic SBRT.
Genomically adjusted radiation dose to predict for survival with adjuvant radiation in resectable pancreatic cancer.
Authors: Strom Tobin Joel Crill , Hoffe Sarah E. , Frakes Jessica M. , Fulp William J. , Coppola Domenico , Springett Gregory M. , Malafa Mokenge Peter , Harris Cynthia L. , Eschrich Steven A. , Shridhar Ravi , Torres-Roca Javier 
Published: February 2017

240 Background: The median survival of patients with resectable pancreatic cancer remains low at approximately 2 years. A major limitation of treating patients with postoperative radiation therapy (RT) is the close proximity of the small bowel, which confines the RT dose. We hypothesized that a subset of patients might exist who would benefit from an escalated RT dose based on their underlying tumor radiosensitivity. Methods: Genomically-profiled patients with pancreatic cancer were identified from an IRB-approved prospective observational protocol. Patients treated with upfront surgery and postoperative RT were included. Briefly, the radiosensitivity index (RSI) is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells. The RSI was combined with the delivered RT dose to derive a genomically adjusted RT dose (GAD). The GAD patient subsets were split at the middle GAD value and rounded up to the nearest integer (27). Our primary endpoint was to assess whether the GAD would predict for survival. Results: Forty patients underwent surgery and postoperative RT with GAD and clinical outcome data available. The median RT dose was 50.4 Gy (range 45-54) and the median follow-up among surviving patients was 68 months (range 42-141). Eighteen patients with a GAD > 27 had a median survival of 32.1 months, while 22 patients with a GAD < 27 had a median survival of 17.9 months (p = 0.48). On Cox multivariate analysis, both high-risk pancreatic cancer patients (positive margins, positive lymph nodes or a postoperative CA 19-9 > 90) and patients with a GAD < 27 had significantly decreased survival (Hazard ratio [HR] 5.0 [95%CI 1.8,13.6], p = 0.002 and HR 2.6 [1.1-6.0], p = 0.03, respectively). Among patients with a GAD < 27, 3 of 22 (14%) would have exceeded a GAD of 27 with an escalated RT dose of 54 Gy, and 8 of 22 (36%) patients would have exceeded a GAD of 27 with an escalated dose of 56 Gy to the pancreatic bed. Conclusions: GAD is predictive of survival among patients with resectable pancreatic cancer when combined with known prognostic factors. The GAD provides a tool to determine who might benefit from dose-escalated RT based on the underlying tumor radiosensitivity.
A new immunohistochemistry prognostic score (IPS) for recurrence and survival in pancreatic neuroendocrine tumors (PanNET).
Authors: Viudez Antonio , Carvalho Filipe LF , Maleki Zahra , Zahurak Marianna , Laheru Daniel A. , Stark Alejandro , Azad Nilofer Saba , Wolfgang Christopher Lee , Baylin Stephen , Herman James Gordon , De Jesus-Acosta Ana 
Published: February 2017

241 Background: We aimed to evaluate the expression and prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in resected pancreatic neuroendocrine tumors (PanNET). Methods: Ninety-two patients with resected primary PanNET and follow-up > 24 months were included in this study. Nuclear staining for MGMT and PHLDA-3 were scored as 0, 1-5%, 6-50% and ≥ 51%; cytoplasmic NDRG-1 staining was scored based on intensity and pattern from 0 to 2. We then grouped IHC scores for MGMT (absent versus any expression); for NDRG-1 (0 versus 1 versus 2) and for PHLDA-3 ( < 50% versus ≥ 51%). Finally, we developed an immunohistochemistry prognostic score (IPS) based on MGMT, NDRG-1 and PHLDA-3 IHC expression to predict disease free survival (DFS) and overall survival (OS). The discriminatory ability of multivariate models combining the IPS and important clinical variables was assessed with Harrel’s c-index (HCI) and a modification of Harrell’s c-index (mHCI). Results: DFS was significantly worse in patients without any expression of MGMT compared with those with any grade of expression (HR: 2.21; 95%CI: 0.97-5.02; p = 0.013), in patients with moderate or high score for NDRG-1 (p = 0.005), and in those with high-expression for PHLDA-3 (HR: 1.94; 95%CI: 1.05,3.6; p = 0.036). A significant difference in OS was observed based on NDRG-1 score (p = 0.013). In multivariate analyses, ki-67 (HR: 2.45; 95% CI: 1.20-5.01; p = 0.01) and IPS (HR: 2.68; 95% CI: 1.60,4.49; p = 0.00018) were independent prognostic factors for DFS, while age (HR: 7.67; 95% CI: 2.14,27.45; p = 0.0017) and IPS (HR: 2.67; 95% CI: 1.11, 6.41; p = 0.03) were independent prognostic factors for OS. HCI for the multivariate DFS and OS models were 0.796 and 0.788, respectively. Conclusions: Our IPS is a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET. Prospective studies are warranted to validate our findings and determine its role for patients’ selection to neo/adjuvant treatments
Impact and mechanistic role of MicroRNA-1291 on pancreatic tumorigenesis.
Authors: Tu Mei-Juan , Pan Yu-Zhuo , Qiu Jing-Xin , Kim Edward Jae-hoon , Yu Aiming 
Published: February 2017

243 Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Better understanding of pancreatic cancer biology and identification of new targets are highly warranted. MicroRNAs (miRs or miRNAs) play a critical role in the control of tumor progression via crosstalk with cancer signaling pathways. Our recent studies showed that miR-1291 improved chemosensitivity through targeting of efflux transporter ABCC1. This current study investigated the mechanistic role of miR-1291 in the suppression of pancreatic tumorigenesis. Methods: PANC-1 and AsPC-1 cell lines were stably transfected with miR-1291. Cell cycle status and apoptosis of stable miR-1291-expressing cells were tested against control cells using flow cytometry. Cells were injected subcutaneously into nude mice and tumorigenesis was measured in vivo. Proteomic studies were performed by two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis. Computationally predicted miR-1291 targets were assessed by luciferase reporter assay and Western blot. Primary PDAC and control samples were tested for miR-1291 and target gene expression levels. Results: Our data showed that stable miR-1291-expressing PANC-1 and AsPC-1 cells both showed a significantly lower rate of proliferation than the control cells, which was associated with a cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 suppressed the tumorigenesis of PANC-1 cells in mouse models in vivo. Proteomic studies revealed the protein level of several cancer-related genes were downregulated by miR-1291, including a pancreatic tumor promoting protein AGR2 which was reduced ~10-fold. Through computational and experimental studies we further identified that FOXA2, a transcription factor governing AGR2 expression, was a direct target of miR-1291. In addition, we found a significant down-regulation of miR-1291 in a set of PDAC patient tumor samples overexpressing AGR2. Conclusions: These results indicate that miR-1291 suppresses pancreatic tumorigenesis via targeting of FOXA2-AGR regulatory pathway providing new insight supporting development of miR-1291-based therapy for PDAC.
Overall survival and clinical characteristics of BRCA germline/somatic cholangiocarcinoma (CCA).
Authors: Golan Talia , Raitses-Gurevich Maria , Kelley Robin Kate , Bocobo Andrea Grace , Borgida Ayelet , Shroff Rachna T. , Holter Spring , Gallinger Steven , Lowery Maeve Aine , Abou-Alfa Ghassan K. , Ahn Daniel H. , Jain Apurva , Bekaii-Saab Tanios S. , Friedman Eitan , Javle Milind M. 
Published: February 2017

244 Background: Biliary tract cancers (BTC) exhibit a diverse and high frequency of actionable mutations detectable using next generation sequencing (NGS). The Breast Cancer Linkage Consortium reported that BRCA2 mutation carriers are at increased risk for BTC with estimated relative risk of 4.97, (95% CI = 1. 50-16.52). The purpose of this study was to evaluate the clinical characteristics of germline/somatic BRCA1/2mutations in CCA patients. Methods: Multi-center retrospective analysis of patients with germline/somatic BRCA1/2- associated CCA diagnosed between January 2000 and December 2013. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures and systemic chemotherapy or radiation were extracted from patient records. Results: Overall, we identified 18 cases including 5 carriers of germline BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic mutations (7 BRCA1; 6 BRCA2) using a NGS panel testing tumor for 'actionable' mutations. One patient presented with two different somatic mutations in the BRCA2gene. Mean age at diagnosis was 60 years (range 36-75), male: females (61.2% vs 38.8%, respectively). Stage at diagnosis: I (n = 4), II (n = 3), III (n = 3) and IV (n = 8). Six patients had extrahepatic CAA; twelve patients had intrahepatic CCA. Prior therapy in 13 patients included platinum-based therapy with one patient receiving prior olaparib. Median overall survival for patients with stage I/II is 34.7 months (95% CI, 7.06-62.9) and for stages III/IV is 25 months (95% CI, 12.02-35.84). Conclusions: BRCA associated CCA may have an enhanced therapeutic sensitivity to DNA damaging agents. This needs confirmation in a larger cohort of patients.
Genomic landscape of pancreatic adenocarcinoma: Does age matter?
Authors: Ben-Aharon Irit , Elkabets Moshe , Pelossof Raphael , Yu Kenneth H. , Allen Peter J. , Iacobuzio-Donahue Christine A , Leach Steven D. , Lowery Maeve Aine , Goodman Karyn A. , O'Reilly Eileen Mary 
Published: February 2017

250 Background: State-of the art genomic analyses of pancreatic adenocarcinoma (PDAC) has yielded insights into signaling pathways underlying carcinogenesis. PDAC is characterized by substantial genomic heterogeneity. We aimed to determine if early-onset PDAC ( ≤ 55 yrs) displays a distinctive molecular landscape from average-age onset PDAC ( ≥ 70 yrs). Methods: Three distinct datasets of PDAC in age groups ≤ 55 and ≥ 70 years old were analyzed. In the first, patients undergoing treatment at MSKCC were consented for MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) next generation sequencing. The second cohort analyzed was The Cancer Genome Atlas (TCGA) dataset for differences in somatic mutations, gene expression and protein expression. The third dataset was the Australian cohort of PDAC (Waddell et al, Nature, 2015). Clinical data were correlated with genomic analyses. Results: One hundred and eighty-three samples were analyzed, yielding N = 56 patients (pts) aged ≤ 55 years and N = 127 pts aged ≥ 70 years. Several genes known to be associated with carcinogenesis differed in mutation frequency across age groups: SMAD4, MYC and PIK3CA displayed higher mutation rates in younger patients (p < 0.05, table below). Comprehensive analysis by cellular pathways indicated that the PI3Kpathway is further altered in the younger population. Protein expression had different patterns in younger versus older patients. Smoking was more prevalent in the early-onset group in all three cohorts (59% vs. 47%). Survival outcomes revealed no differences between the age groups. Conclusions: This exploratory analysis suggests that there may be somatic gene alterations within the population of early onset PDAC patients that involve unique cellular pathways compared with average onset PDAC. Former studies imply these cellular pathways may play a role in smoking-related PDAC carcinogenesis. Larger genomic datasets are warranted for future analysis to support this observation. [Table: see text]
A pooled analysis of long pentraxin for patients with advanced pancreatic cancer.
Authors: Sasaki Mitsuhito , Kondo Shunsuke , Hosoi Hiroko , Koga Futa , Sakamoto Yasunari , Morizane Chigusa , Ueno Hideki , Okusaka Takuji 
Published: February 2017

251 Background: Pancreatic carcinoma is one of the most lethal cancers and is the fourth leading cause of cancer-related death in Japan. Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis, affecting immune surveillance and response to therapy. We previously reported that pentraxin family members, especially long pentraxin (PTX3), are promising biomarkers for the prognosis of pancreatic carcinoma patients. The objective of the present study was to determine whether PTX3 levels could be a prognostic factor for patients with unresectable or recurrent pancreatic carcinoma. Methods: We analyzed data from two clinical trials (UMIN000002323 and UMIN000009474) using the Kaplan-Meier method and Cox proportional hazards model. We included data from patients who were chemo-naïve pancreatic invasive ductal carcinoma patients, had a 0–2 performance status score, and had adequate organ function. PTX3 levels and other laboratory and clinical data were assessed before initial treatment. Results: Overall, 181 patients with unresectable or recurrent pancreatic carcinoma were evaluated for the baseline plasma PTX3 level (median, mean, and range PTX3: 3.54 ng/mL, 4.34 ng/mL, and 0.9–17.7 ng/mL, respectively). In this study population, the median overall survival was 327 days (95% confidence interval, 281–372 days). The median overall survival was significantly shorter at high PTX3 levels( > 4.34ng/mL) than at low PTX3 levels ( < 4.34ng/mL)(223days vs 409 days; log rank test, P < 0.0001). In a multivariate analysis, the PTX3, C-reaction protein (CRP), and cancer antigen (CA) 19-9 levels, and performance status were independent predictors of survival. High PTX3 levels were associated with high CA19-9 and high CRP levels. Conclusions: We confirmed that a high PTX3 level may be a useful prognostic marker for advanced pancreatic carcinoma. However, the mechanism of tumor inflammation and the exact nature of the role of PTX3 expression remain unclear, calling for investigation of the mechanisms underlying PTX3 activity in carcinoma cells and in the tumor environment. Clinical trial information: UMIN000002323 and UMIN000009474.
Sensitivity and specificity of signs and symptoms to determine the risk of death associated with gastric cancer patients.
Authors: Rojas Uribe Gustavo A. , Martinez Jose , Londono Paula 
Published: February 2017

26 Background: Risaralda (Colombia) has an irregular pattern in the risk of death for gastric cancer; for these reasons, the survival analysis was made with the information of gastric cancer patients treated in Oncólogos del Occidente clinic during 2014. Methods: A cross-sectional study was done with oncologic patients in order to evaluate the replicability of a binary list of signs and symptoms of gastric cancer, also its corresponding principal component factors for the proper identification of their dimensions. A sum of the set of signs and symptoms was done. This total sum of signs and symptoms was used to identify the sensitivity and specificity of each of cut-off related to the patient’s death condition. This evaluation was established by the ROC (Receiver Operating Characteristic) methodology, which is a graphic representation of the sensitivity in front of the specificity for a classifying binary system that may vary the threshold of rejection. The analysis was done in Stata. Results: There were 173 patients, of whom 69.9% were males; the group with the highest incidence was the 60-69 years old group (32%); These patients referred 5 signs and symptoms that conformed the list from which every single item behaved as a binary variable. Cronbach’s alpha was 0.62 and the analysis of principal components factors defined only one dimension. The ROC curve established a sensitivity of 65% and a specificity of 72% for the determination of the risk of death with a score equal or higher to 4 in the sum of the list of signs and symptoms. Adding the gender, the sensitivity increased to 66%. In the ≥ 80 years old group the sensitivity was 70.9%, meanwhile the group of ≥ 40 years old the sensitivity was 93%. Conclusions: The list of signs and symptoms could be a diagnostic technology relevant for unspecific clinical but has an important high frequency in Colombia for gastric cancer patients. The sensitivity was very variable according to the age range, being more sensible and specific for the patients of the ≥ 40 years old group.