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Pancreatic Neoplasms: HELP
Articles by George van Buren
Based on 14 articles published since 2010
(Why 14 articles?)
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Between 2010 and 2020, George Van Buren wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection. 2017

Gilliland, Taylor M / Villafane-Ferriol, Nicole / Shah, Kevin P / Shah, Rohan M / Tran Cao, Hop S / Massarweh, Nader N / Silberfein, Eric J / Choi, Eugene A / Hsu, Cary / McElhany, Amy L / Barakat, Omar / Fisher, William / Van Buren, George. ·The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Taylor.Gilliland@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Nicole.Villafane@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Kevin.Shah@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Rohan.Shah@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Hop.TranCao@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Nader.Massarweh@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. ejs@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Eugene.Choi@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Cary.Hsu@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Amy.McElhany@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Omar.Barakat@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. wfisher@bcm.edu. · The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. George.vanburen@bcm.edu. ·Nutrients · Pubmed #28272344.

ABSTRACT: Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

2 Review Pancreatic cancer disparities in African Americans. 2015

Khawja, Shumaila N / Mohammed, Somala / Silberfein, Eric J / Musher, Benjamin L / Fisher, William E / Van Buren, George. ·From the *Michael E. DeBakey Department of Surgery, †The Elkins Pancreas Center, ‡Dan L. Duncan Cancer Center, and §Department of Medicine, Baylor College of Medicine, Houston, TX. ·Pancreas · Pubmed #25872128.

ABSTRACT: OBJECTIVES: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. The incidence of pancreatic cancer in African Americans is 50% to 90% higher than the incidence in other racial groups. African Americans also have the worst prognosis. This is an evidence-based review of pancreatic cancer in African Americans with particular emphasis on baseline characteristics, treatment, and survival. METHODS: We queried PubMed in search for articles describing racial disparities in pancreatic cancer. Two categories of terms were "anded" together: pancreatic cancer terms and race terms. The last search was performed on November 14, 2013. RESULTS: We summarized the data on pancreatic cancer baseline characteristics, treatment, and survival for African Americans that we obtained from the following databases: (1) Surveillance, Epidemiology, and End Results, 1988-2008; (2) California Cancer Registry 1988-1998; (3) Cancer Survivor Program of Orange County/San Diego Imperial Organization for Cancer Control, 1988-1998; and (4) Harris County, 1998-2010. CONCLUSIONS: Overall, pancreatic cancer survival of African Americans has not significantly improved over the past several decades despite advances in multimodality therapy; African Americans continue to face worse outcomes than whites. Although baseline characteristics, treatment, and biological factors offer some explanation, they do not completely explain the disparities in incidence and survival.

3 Review Pancreatic cancer: advances in treatment. 2014

Mohammed, Somala / Van Buren, George / Fisher, William E. ·Somala Mohammed, George Van Buren II, William E Fisher, The Elkins Pancreas Center, Michael E DeBakey Department of Surgery, and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States. ·World J Gastroenterol · Pubmed #25071330.

ABSTRACT: Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.

4 Clinical Trial Phase II study of induction fixed-dose rate gemcitabine and bevacizumab followed by 30 Gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma. 2013

Van Buren, George / Ramanathan, Ramesh K / Krasinskas, Alyssa M / Smith, Ryan P / Abood, Gerard J / Bahary, Nathan / Lembersky, Barry C / Shuai, Yongli / Potter, Douglas M / Bartlett, David L / Zureikat, Amer H / Zeh, Herbert J / Moser, A James. ·Division of Surgical Oncology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA. ·Ann Surg Oncol · Pubmed #23904005.

ABSTRACT: BACKGROUND: Eighty percent of patients with resected pancreatic ductal carcinoma (PDC) experience treatment failure within 2 years. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with the angiogenesis inhibitor bevacizumab (BEV) and accelerated 30 Gy radiotherapy (RT) would improve outcomes among patients with potentially resectable PDC. METHODS: This phase II trial tested induction FDR GEM (1,500 mg/m(2)) plus BEV (10 mg/kg IV) every 2 weeks for three cycles followed by accelerated RT (30 Gy in 10 fractions) plus BEV directed at gross tumor volume plus a 1-2 cm vascular margin. Subjects underwent laparoscopy and resection after day 85. Therapy was considered effective if the complete pathologic response rate exceeded 10 % and the margin-negative resection rate exceeded 80%. RESULTS: Fifty-nine subjects were enrolled; 29 had potential portal vein involvement. Two grade 4 (3.4%) and 19 grade 3 toxicities (32.8%) occurred. Four subjects manifested radiographic progression, and 10 had undetected carcinomatosis. Forty-three pancreatic resections (73%) were performed, including 19 portal vein resections (44%). Margin-negative outcomes were observed in 38 (88%, 95% confidence interval [CI] 75-96), with one complete pathologic response (2.3%; 95% CI 0.1-12). There were seven (6 grade 3; 1 grade 4) wound complications (13%). Median overall survival for the entire cohort was 16.8 months (95% CI 14.9-21.3) and 19.7 months (95% CI 16.5-28.2) after resection. CONCLUSIONS: Induction therapy with FDR GEM and BEV, followed by accelerated BEV/RT to 30 Gy, was well tolerated. Although both effectiveness criteria were achieved, survival outcomes were equivalent to published regimens.

5 Article Mutant p53 2019

Polireddy, Kishore / Singh, Kanchan / Pruski, Melissa / Jones, Neal C / Manisundaram, Naveen V / Ponnela, Pavani / Ouellette, Michel / Van Buren, George / Younes, Mamoun / Bynon, John S / Dar, Wasim A / Bailey, Jennifer M. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas McGovern Medical School, Houston, TX, 77030, USA. · Division of Immunology and Organ Transplantation, Department of Surgery, The University of Texas McGovern Medical School, Houston, TX, 77030, USA. · Division of Gastroenterology, Department of Internal Medicine, The University of Nebraska Medical Center, Omaha, NE, 68198, USA. · Division of Surgical Oncology, Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA. · Division of Pathology and Laboratory Medicine, The University of Texas McGovern Medical School, Houston, TX, 77030, USA. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas McGovern Medical School, Houston, TX, 77030, USA. Electronic address: Jennifer.M.Bailey@uth.tmc.edu. ·Cancer Lett · Pubmed #30946870.

ABSTRACT: Pancreatic cancer remains a highly lethal malignancy. We have recently shown that simultaneous expression of Kras and mutant Tp53

6 Article Mesothelin and TGF-α predict pancreatic cancer cell sensitivity to EGFR inhibitors and effective combination treatment with trametinib. 2019

Poteet, Ethan / Liu, Dongliang / Liang, Zhengdong / Van Buren, George / Chen, Changyi / Yao, Qizhi. ·Michael E. DeBakey Department of Surgery, Division of Surgical Research, Baylor College of Medicine, Houston, Texas, United States of America. · Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, Texas, United States of America. ·PLoS One · Pubmed #30921351.

ABSTRACT: Clinical trials of EGFR inhibitors in combination with gemcitabine for the treatment of pancreatic ductal adenocarcinoma (PDAC) have generated mixed results partially due to the poorly defined effectiveness of EGFR inhibitors in PDAC. Here, we studied a panel of PDAC cell lines to compare the IC50s of the EGFR inhibitors gefitinib and cetuximab. We found that gefitinib induced biphasic inhibition in over 50% of PDAC cells, with the initial growth inhibition occurring at nanomolar concentrations and a second growth inhibition occurring outside the clinical range. In contrast to gefitinib, cetuximab produced a single phase growth inhibition in a subset of PDAC cells. Using this sensitivity data, we screened for correlations between cell morphology proteins and EGFR ligands to EGFR inhibitor sensitivity, and found that mesothelin and the EGFR ligand TGF-α have a strong correlation to gefitinib and cetuximab sensitivity. Analysis of downstream signaling pathways indicated that plc-γ1 and c-myc were consistently inhibited by EGFR inhibitor treatment in sensitive cell lines. While an inconsistent additive effect was observed with either cetuximab or gefitinib in combination with gemcitabine, the cell pathway data indicated consistent ERK activation, leading us to pursue EGFR inhibitors in combination with trametinib, a MEK1/2 inhibitor. Both cetuximab and gefitinib in combination with trametinib produced an additive effect in all EGFR sensitive cell lines. Our results indicate that mesothelin and TGF-α can predict PDAC sensitivity to EGFR inhibitors and a combination of EGFR inhibitors with trametinib could be a novel effective treatment for PDAC.

7 Article SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma. 2019

Song, Xianzhou / Chen, Hui / Zhang, Chengwei / Yu, Yang / Chen, Zhongyuan / Liang, Han / Van Buren, George / McElhany, Amy L / Fisher, William E / Lonard, David M / O'Malley, Bert W / Wang, Jin. ·Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, 77030, USA. · Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. · Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA; Department of Statistics, Rice University, Houston, TX, 77030, USA. · Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. · Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA. · Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. Electronic address: dlonard@bcm.edu. · Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. Electronic address: berto@bcm.edu. · Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. Electronic address: wangj@bcm.edu. ·Cancer Lett · Pubmed #30423406.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.

8 Article Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy. 2019

Baugh, Katherine A / Tran Cao, Hop S / van Buren, George / Silberfein, Eric J / Hsu, Cary / Chai, Christy / Barakat, Omar / Fisher, William E / Massarweh, Nader N. ·Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX. · Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX. Electronic address: massarwe@bcm.edu. ·Surgery · Pubmed #30243481.

ABSTRACT: BACKGROUND: Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management. METHODS: In this retrospective cohort study of 4,404 patients aged 18-79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004-2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression. RESULTS: Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log-rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89-1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55-0.74). CONCLUSION: The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher-stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease.

9 Article Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. 2018

Fisher, William E / Cruz-Monserrate, Zobeida / McElhany, Amy L / Lesinski, Gregory B / Hart, Phil A / Ghosh, Ria / Van Buren, George / Fishman, Douglas S / Rinaudo, Jo Ann S / Serrano, Jose / Srivastava, Sudhir / Mace, Thomas / Topazian, Mark / Feng, Ziding / Yadav, Dhiraj / Pandol, Stephen J / Hughes, Steven J / Liu, Robert Y / Lu, Emily / Orr, Robert / Whitcomb, David C / Abouhamze, Amer S / Steen, Hanno / Sellers, Zachary M / Troendle, David M / Uc, Aliye / Lowe, Mark E / Conwell, Darwin L / Anonymous3680965. ·Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH. · Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center. · Department of Pediatrics, Baylor College of Medicine, Houston, TX. · Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville. · Division of Digestive Diseases and Nutrition, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. · Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. · Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA. · Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA. · Department of Surgery, University of Florida College of Medicine, Gainesville, FL. · Clinical Research Support Center, The University of Texas MD Anderson Cancer Center, Houston, TX. · Indiana Clinical and Translational Sciences Institute, Specimen Storage Facility, Indianapolis, IN. · Clinical and Translational Sciences, University of Florida, Gainesville, FL. · Departments of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA. · Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Lucile Packard Children's Hospital and Stanford University School of Medicine, Stanford, CA. · Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, TX. · Stead Family Department of Pediatrics, University of Iowa, Stead Family Children's Hospital, Iowa City, IA. · Department of Pediatrics, Washington University School of Medicine, St Louis, MO. ·Pancreas · Pubmed #30325860.

ABSTRACT: High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.

10 Article Venous thrombosis following pancreaticoduodenectomy with venous resection. 2018

Mohammed, Somala / Mendez-Reyes, Jose E / McElhany, Amy / Gonzales-Luna, Daniel / Van Buren, George / Bland, Daniel S / Villafane-Ferriol, Nicole / Pierzynski, Jeanne A / West, Charles A / Silberfein, Eric J / Fisher, William E. ·Baylor College of Medicine, The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Houston, Texas. · Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Baylor College of Medicine, The Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Houston, Texas. Electronic address: wfisher@bcm.edu. ·J Surg Res · Pubmed #29907222.

ABSTRACT: BACKGROUND: Addition of en bloc segmental venous reconstruction (VR) to pancreaticoduodenectomy (PD) for venous involvement of pancreatic tumors increases the complexity of the operation and may increase complications. The long-term mesenteric venous patency rate and oncologic outcome has not been well defined. METHODS: Our prospective database was reviewed to assess 90-day postoperative outcomes for patients who underwent PD or PD + VR (September 2004-June 2016). Two independent observers reviewed CT scans to determine long-term vein patency. In patients with pancreatic ductal adenocarcinoma, the impact of VR on 5-year overall survival was assessed using multivariate Cox proportional hazards regression. Student's t-test was used to evaluate continuous variables and the chi-square test for categorical variables. RESULTS: Three hundred ninety-three patients underwent PD (51 PD + VR). Patients undergoing PD + VR had longer operations (561 ± 119 versus 433 ± 89 min, P < 0.00001) and greater blood loss (768 ± 812 versus 327 ± 423 cc, P < 0.00001). There was no difference in 90-day mortality, overall postoperative complication rates, complication severity grades, reoperation, readmission, or length of stay. 26.7% experienced venous thrombosis. Most thromboses occurred in the first year after surgery, but we also observed late thrombosis in 1 patient after 89-month follow-up. Among 135 patients with pancreatic ductal adenocarcinoma, survival was significantly longer in the PD-alone group (31.3 months [95% confidence interval: 22.9-40.0] versus 17.0 [95% confidence interval: 13.0-19.1], p CONCLUSIONS: PD + VR does not increase short-term morbidity, but venous thrombosis is frequent and can occur long after surgery. Survival is inferior when VR is required especially in the absence of neoadjuvant chemotherapy.

11 Article Value of lymph node positivity in treatment planning for early stage pancreatic cancer. 2017

Tran Cao, Hop S / Zhang, Qianzi / Sada, Yvonne H / Silberfein, Eric J / Hsu, Cary / Van Buren, George / Chai, Christy / Katz, Matthew H G / Fisher, William E / Massarweh, Nader N. ·Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX. Electronic address: hop.trancao@bcm.edu. · Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX. · Department of Medicine, Baylor College of Medicine, Houston, TX; VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX. · Division of Surgical Oncology, U.T. MD Anderson Cancer Center, Houston, TX. · Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX. ·Surgery · Pubmed #28666686.

ABSTRACT: BACKGROUND: Multimodal therapy is recommended for early stage pancreatic cancer, although whether all patients benefit and the optimal timing of chemotherapy remain unclear. METHODS: Retrospective cohort study of patients aged 18-79 years with stage I-II pancreatic ductal adenocarcinoma in the National Cancer Database (2004-2012). Patients were grouped based on treatment strategy as surgery only, adjuvant, and preoperative. Accuracy of nodal staging and rate of nodal downstaging were ascertained using pretreatment clinical and postresection pathologic nodal status data. Association between overall risk of death and treatment strategy was evaluated with multivariable Cox regression. RESULTS: Among 19,031 patients, 31.1% underwent surgery only, 59.6% received adjuvant, and 9.3% preoperative therapy. Based on patients receiving upfront surgery, clinical nodal staging bore sensitivity, specificity, positive predictive value, and negative predictive value of 46.2%, 95.7%, 95.1%, and 49.8%, respectively. Preoperative therapy downstaged 38% of cN1 patients to ypN0; 5-year overall survival for this group was 27.2% vs 12.3% for ypN1 patients (P < .001). Relative to surgery only, adjuvant (HR 0.75, 95% CI [0.71-0.78]) and preoperative therapy (HR 0.66 [0.60-0.73]) were associated with lower risk of death among patients with pN1, but not pN0 (adjuvant-HR 1.01 [0.94-1.09]; preoperative-HR 1.10 [0.99-1.22]), disease. CONCLUSION: Our data provide strong support for preoperative chemotherapy for patients with node-positive pancreatic cancer, one third of whom may be downstaged. Among those with seemingly node-negative disease, half will be understaged with current clinical staging modalities. These results should be considered when planning treatment for patients with early stage pancreatic cancer.

12 Article Whole-genome landscape of pancreatic neuroendocrine tumours. 2017

Scarpa, Aldo / Chang, David K / Nones, Katia / Corbo, Vincenzo / Patch, Ann-Marie / Bailey, Peter / Lawlor, Rita T / Johns, Amber L / Miller, David K / Mafficini, Andrea / Rusev, Borislav / Scardoni, Maria / Antonello, Davide / Barbi, Stefano / Sikora, Katarzyna O / Cingarlini, Sara / Vicentini, Caterina / McKay, Skye / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / McLean, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Wilson, Peter J / Anderson, Matthew J / Fink, J Lynn / Newell, Felicity / Waddell, Nick / Holmes, Oliver / Kazakoff, Stephen H / Leonard, Conrad / Wood, Scott / Xu, Qinying / Nagaraj, Shivashankar Hiriyur / Amato, Eliana / Dalai, Irene / Bersani, Samantha / Cataldo, Ivana / Dei Tos, Angelo P / Capelli, Paola / Davì, Maria Vittoria / Landoni, Luca / Malpaga, Anna / Miotto, Marco / Whitehall, Vicki L J / Leggett, Barbara A / Harris, Janelle L / Harris, Jonathan / Jones, Marc D / Humphris, Jeremy / Chantrill, Lorraine A / Chin, Venessa / Nagrial, Adnan M / Pajic, Marina / Scarlett, Christopher J / Pinho, Andreia / Rooman, Ilse / Toon, Christopher / Wu, Jianmin / Pinese, Mark / Cowley, Mark / Barbour, Andrew / Mawson, Amanda / Humphrey, Emily S / Colvin, Emily K / Chou, Angela / Lovell, Jessica A / Jamieson, Nigel B / Duthie, Fraser / Gingras, Marie-Claude / Fisher, William E / Dagg, Rebecca A / Lau, Loretta M S / Lee, Michael / Pickett, Hilda A / Reddel, Roger R / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Epari, Krishna / Nguyen, Nam Q / Zeps, Nikolajs / Falconi, Massimo / Simbolo, Michele / Butturini, Giovanni / Van Buren, George / Partelli, Stefano / Fassan, Matteo / Anonymous6880896 / Khanna, Kum Kum / Gill, Anthony J / Wheeler, David A / Gibbs, Richard A / Musgrove, Elizabeth A / Bassi, Claudio / Tortora, Giampaolo / Pederzoli, Paolo / Pearson, John V / Waddell, Nicola / Biankin, Andrew V / Grimmond, Sean M. ·ARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. · QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. · Medical Oncology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, General Hospital of Treviso, Department of Medicine, University of Padua, Italy. · Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy. · The University of Queensland, School of Medicine, Brisbane 4006, Australia. · Pathology Queensland, Brisbane 4006, Australia. · Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Brisbane 4006, Australia. · Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. · School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Centre for Cancer Bioinformatics, Peking University Cancer Hospital &Institute, Beijing 100142, China. · Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. · Department of Anatomical Pathology. St Vincent's Hospital, Sydney, New South Wales 2010, Australia. · Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. · Department of Pathology, Queen Elizabeth University Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. · Michael E. DeBakey Department of Surgery and The Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3411, USA. · Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia. · Children's Medical Research Institute, The University of Sydney, Westmead, New South Wales 2145, Australia. · Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. · University of Sydney. Sydney, New South Wales 2006, Australia. · Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. · School of Medicine, Western Sydney University, Penrith, New South Wales 2175, Australia. · Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. · School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia 6009, Australia. · St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. · Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. · University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, 3010, Victoria, Australia. ·Nature · Pubmed #28199314.

ABSTRACT: The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

13 Article Overexpression of Semaphorin-3E enhances pancreatic cancer cell growth and associates with poor patient survival. 2016

Yong, Lin-Kin / Lai, Syeling / Liang, Zhengdong / Poteet, Ethan / Chen, Fengju / van Buren, George / Fisher, William / Mo, Qianxing / Chen, Changyi / Yao, Qizhi. ·Michael E. DeBakey Department of Surgery, Division of Surgical Research, Baylor College of Medicine, Houston, TX, USA. · Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA. · Department of Pathology, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA. · Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA. · Department of Medicine, Baylor College of Medicine, Houston, TX, USA. · Michael E. DeBakey Department of Surgery, Division of General Surgery, Baylor College of Medicine, Houston, TX, USA. · Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA. ·Oncotarget · Pubmed #27911862.

ABSTRACT: Semaphorin-3E (Sema3E) is a member of an axon guidance gene family, and has recently been reported to contribute to tumor progression and metastasis. However, its role in pancreatic cancer is yet unknown and uncharacterized. In this study, we showed that Sema3E is overexpressed in human pancreatic cancer, and that high Sema3E levels are associated with tumor progression and poor survival. Interestingly, we also observed Sema3E expression in the nucleus, even though Sema3E is reported to be a secreted protein. Overexpression of Sema3E in pancreatic cancer cells promoted cell proliferation and migration in vitro, and increased tumor incidence and growth in vivo. Conversely, knockout of Sema3E suppressed cancer cell proliferation and migration in vitro, and reduced tumor incidence and size in vivo. Moreover, Sema3E induced cell proliferation via acting through the MAPK/ERK pathway. Collectively, these results reveal an undiscovered role of Sema3E in promoting pancreatic cancer pathogenesis, suggesting that Sema3E may be a suitable prognostic marker and therapeutic target for pancreatic cancer.

14 Article Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. 2016

Gingras, Marie-Claude / Covington, Kyle R / Chang, David K / Donehower, Lawrence A / Gill, Anthony J / Ittmann, Michael M / Creighton, Chad J / Johns, Amber L / Shinbrot, Eve / Dewal, Ninad / Fisher, William E / Anonymous400856 / Pilarsky, Christian / Grützmann, Robert / Overman, Michael J / Jamieson, Nigel B / Van Buren, George / Drummond, Jennifer / Walker, Kimberly / Hampton, Oliver A / Xi, Liu / Muzny, Donna M / Doddapaneni, Harsha / Lee, Sandra L / Bellair, Michelle / Hu, Jianhong / Han, Yi / Dinh, Huyen H / Dahdouli, Mike / Samra, Jaswinder S / Bailey, Peter / Waddell, Nicola / Pearson, John V / Harliwong, Ivon / Wang, Huamin / Aust, Daniela / Oien, Karin A / Hruban, Ralph H / Hodges, Sally E / McElhany, Amy / Saengboonmee, Charupong / Duthie, Fraser R / Grimmond, Sean M / Biankin, Andrew V / Wheeler, David A / Gibbs, Richard A. ·Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mgingras@bcm.edu. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. · Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Surgery, TU Dresden, 01307 Dresden, Germany. · Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; Academic Unit of Surgery, Institute of Cancer Sciences, Glasgow Royal Infirmary, Level 2, New Lister Building, University of Glasgow, Glasgow G31 2ER, UK. · Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Pathology, TU Dresden, 01307 Dresden, Germany. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Department of Pathology, Southern General Hospital, Greater Glasgow and Clyde NHS, Glasgow G51 4TF, UK. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wheeler@bcm.edu. ·Cell Rep · Pubmed #26804919.

ABSTRACT: The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.