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David C Whitcomb

Pranav Murthy, Aatur D Singhi, Mark A Ross, Patricia Loughran, Pedram Paragomi, Georgios I Papachristou, David C Whitcomb, Amer H Zureikat, Michael T Lotze, Herbert J Zeh Iii, Brian A Boone
Background: Neutrophil extracellular traps (NETs) are generated when activated neutrophils, driven by PAD4, release their DNA, histones, HMGB1, and other intracellular granule components. NETs play a role in acute pancreatitis, worsening pancreatic inflammation, and promoting pancreatic duct obstruction. The autophagy inhibitor chloroquine (CQ) inhibits NET formation; therefore, we investigated the impact of CQ mediated NET inhibition in murine models of pancreatitis and human correlative studies. Methods: L-arginine and choline deficient ethionine supplemented (CDE) diet models of acute pancreatitis were studied in wild type and PAD4-/- mice, incapable of forming NETs...
2019: Frontiers in Immunology
Mohannad Dugum, Amir Gougol, Pedram Paragomi, Xiaotian Gao, Bassem Matta, Cemal Yazici, Gong Tang, Phil Greer, Ioannis Pothoulakis, Stephen J D O'Keefe, David C Whitcomb, Dhiraj Yadav, Georgios I Papachristou
Background: The effect of diet on risk of acute pancreatitis (AP) has been suggested by prior studies, but the association of dietary habits with severity of AP has not been previously evaluated. Objective: The objective of the study was to assess differences in reported dietary habits in patients with severe AP compared with those with mild or moderate AP. Methods: A prospectively maintained cohort of patients with AP was utilized. A brief questionnaire on dietary habits was implemented...
December 2018: Current developments in nutrition
Ekaterina Orlova, Andrew Yeh, Min Shi, Brian Firek, Sarangarajan Ranganathan, David C Whitcomb, David N Finegold, Robert E Ferrell, M Michael Barmada, Mary L Marazita, David A Hinds, John R Shaffer, Michael J Morowitz
Appendicitis affects 9% of Americans and is the most common diagnosis requiring hospitalization of both children and adults. We performed a genome-wide association study of self-reported appendectomy with 18,773 affected adults and 114,907 unaffected adults of European American ancestry. A significant association with appendectomy was observed at 4q25 near the gene PITX2 (rs2129979, p value = 8.82 × 10-14 ) and was replicated in an independent sample of Caucasians (59 affected, 607 unaffected; p value = 0...
November 3, 2018: Human Genetics
Phil A Hart, Dana K Andersen, Kieren J Mather, Alicia C Castonguay, Mandeep Bajaj, Melena D Bellin, David Bradley, Noemy Contreras, Aida Habtezion, Murray Korc, Yogish Kudva, Maxim S Petrov, David C Whitcomb, Dhiraj Yadav, Ying Yuan, Jo Ann S Rinaudo, Sudhir Srivastava, Jose Serrano, Mark O Goodarzi
Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap...
November 2018: Pancreas
Dhiraj Yadav, Walter G Park, Evan L Fogel, Liang Li, Suresh T Chari, Ziding Feng, William E Fisher, Christopher E Forsmark, Christie Y Jeon, Aida Habtezion, Phil A Hart, Steven J Hughes, Mohamed O Othman, Jo Ann S Rinaudo, Stephen J Pandol, Temel Tirkes, Jose Serrano, Sudhir Srivastava, Stephen K Van Den Eeden, David C Whitcomb, Mark Topazian, Darwin L Conwell
Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP...
November 2018: Pancreas
William E Fisher, Zobeida Cruz-Monserrate, Amy L McElhany, Gregory B Lesinski, Phil A Hart, Ria Ghosh, George Van Buren, Douglas S Fishman, Jo Ann S Rinaudo, Jose Serrano, Sudhir Srivastava, Thomas Mace, Mark Topazian, Ziding Feng, Dhiraj Yadav, Stephen J Pandol, Steven J Hughes, Robert Y Liu, Emily Lu, Robert Orr, David C Whitcomb, Amer S Abouhamze, Hanno Steen, Zachary M Sellers, David M Troendle, Aliye Uc, Mark E Lowe, Darwin L Conwell
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...
November 2018: Pancreas
Mark E Lowe, Marc T Goodman, Gregory A Coté, Marshall J Glesby, Mark Haupt, Nicholas J Schork, Vikesh K Singh, Dana K Andersen, Stephen J Pandol, Aliye Uc, David C Whitcomb
Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes, and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018, in Pittsburgh, Pennsylvania, to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes, and research methods...
November 2018: Pancreas
Jens Brøndum Frøkjær, Fatih Akisik, Ammad Farooq, Burcu Akpinar, Anil Dasyam, Asbjørn Mohr Drewes, Ingfrid S Haldorsen, Giovanni Morana, John P Neoptolemos, Søren Schou Olesen, Maria Chiara Petrone, Andrea Sheel, Tooru Shimosoegawa, David C Whitcomb
The paper presents the international guidelines for imaging evaluation of chronic pancreatitis. The following consensus was obtained: Computed tomography (CT) is often the most appropriate initial imaging modality for evaluation of patients with suspected chronic pancreatitis (CP) depicting most changes in pancreatic morphology. CT is also indicated to exclude other potential intraabdominal pathologies presenting with symptoms similar to CP. However, CT cannot exclude a diagnosis of CP nor can it be used to exclusively diagnose early or mild disease...
October 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Jorge D Machicado, Amir Gougol, Pedram Paragomi, Stephen J OʼKeefe, Kenneth Lee, Adam Slivka, David C Whitcomb, Dhiraj Yadav, Georgios I Papachristou
OBJECTIVES: Clinical trials on tube feedings (TFs) have not been sufficiently powered to change practice patterns in acute pancreatitis (AP). We aimed to describe the use, duration, and resource utilization of TF in AP patients at an expert US center. METHODS: Of 423 AP patients prospectively enrolled at the University of Pittsburgh Medical Center from 2004 to 2014, 139 (33%) received TF. Data on TF were assessed in 100 (72%) of 139 patients with complete data available...
October 2018: Pancreas
Wei Zhan, Celeste A Shelton, Phil J Greer, Randall E Brand, David C Whitcomb
Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways...
September 2018: Pancreas
Julia B Greer, Phil Greer, Bimaljit S Sandhu, Samer Alkaade, C Mel Wilcox, Michelle A Anderson, Stuart Sherman, Timothy B Gardner, Michele D Lewis, Nalini M Guda, Thiruvengadam Muniraj, Darwin Conwell, Gregory A Cote, Christopher E Forsmark, Peter A Banks, Gong Tang, Kim Stello, Andres Gelrud, Randall E Brand, Adam Slivka, David C Whitcomb, Dhiraj Yadav
BACKGROUND: Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. METHODS: We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-α; and C-reactive protein (CRP)...
August 13, 2018: Nutrition in Clinical Practice
Celeste A Shelton, Chandraprakash Umapathy, Kimberly Stello, Dhiraj Yadav, David C Whitcomb
OBJECTIVES: Hereditary pancreatitis (HP), an autosomal dominant disease typically caused by mutations in PRSS1, has a broad range of clinical characteristics and high cumulative risk of pancreatic cancer. We describe survival and pancreatic cancer risk in the largest HP cohort in the US. METHODS: HP probands and family members prospectively recruited from 1995 to 2013 completed medical and family history questionnaires, and provided blood for DNA testing. Overall survival (until 12/31/2015) was determined from the Social Security Death Index (SSDI), National Death Index (NDI), and family members...
July 18, 2018: American Journal of Gastroenterology
David T Chao, Nilesh H Shah, Herbert J Zeh, Aatur D Singhi, Nathan Bahary, Kevin M McGrath, Kenneth E Fasanella, Amer H Zureikat, David C Whitcomb, Randall E Brand
Background: Adolescent obesity is a national epidemic that recently has been shown to increase risk for pancreatic adenocarcinoma (PC) and is associated with an earlier age of PC onset. We hypothesized that PC patients who are overweight or obese at age 18 would have an earlier age of PC onset. Methods: Retrospective review of 531 patients in our PC registry was completed. Self-reported weight at age 18 and maximum lifetime weight were used to calculate body mass index (BMI) at age 18 (BMI-18) and maximum lifetime BMI...
2018: Gastroenterology Research and Practice
Nalini M Guda, Venkata Muddana, David C Whitcomb, Philippe Levy, Pramod Garg, Gregory Cote, Aliye Uc, Shyam Varadarajulu, Santhi S Vege, Suresh T Chari, Chris E Forsmark, Dhiraj Yadav, D Nageshwar Reddy, Scott Tenner, Colin D Johnson, Fatih Akisik, Ashok K Saluja, Markus M Lerch, J Shawn Mallery, Martin L Freeman
Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research...
July 2018: Pancreas
Gregory A Coté, Dhiraj Yadav, Judah A Abberbock, David C Whitcomb, Stuart Sherman, Bimaljit S Sandhu, Michelle A Anderson, Michele D Lewis, Samer Alkaade, Vikesh K Singh, John Baillie, Peter A Banks, Darwin Conwell, Nalini M Guda, Thiruvengadam Muniraj, Gong Tang, Randall Brand, Andres Gelrud, Stephen T Amann, Christopher E Forsmark, C Mel Wilcox, Adam Slivka, Timothy B Gardner
OBJECTIVES: The impact of recurrent acute pancreatitis (RAP) on quality of life (QOL) is unknown. We hypothesized that RAP would reduce QOL even in the absence of chronic pancreatitis (CP). METHODS: Data were pooled from three prospective, cross-sectional studies conducted across 27 U.S. centers (the North American Pancreatitis Studies); these included subjects with chronic pancreatitis (n = 1086), RAP alone (n = 508), and non-disease controls (n = 1025)...
June 2018: American Journal of Gastroenterology
Anna Evans Phillips, Jessica LaRusch, Phil Greer, Judah Abberbock, Samer Alkaade, Stephen T Amann, Michelle A Anderson, John Baillie, Peter A Banks, Randall E Brand, Darwin Conwell, Gregory A Coté, Christopher E Forsmark, Timothy B Gardner, Andres Gelrud, Nalini Guda, Michele Lewis, Mary E Money, Thiruvengadam Muniraj, Bimaljit S Sandhu, Stuart Sherman, Vikesh K Singh, Adam Slivka, Gong Tang, C Mel Wilcox, David C Whitcomb, Dhiraj Yadav
BACKGROUND: Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. METHODS: We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA...
May 19, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
David C Whitcomb, Tooru Shimosegawa, Suresh T Chari, Christopher E Forsmark, Luca Frulloni, Pramod Garg, Peter Hegyi, Yoshiki Hirooka, Atsushi Irisawa, Takuya Ishikawa, Shuiji Isaji, Markus M Lerch, Philippe Levy, Atsushi Masamune, Charles M Wilcox, John Windsor, Dhiraj Yadav, Andrea Sheel, John P Neoptolemos
BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of Early CP is not possible using imaging criteria alone. If this were possible and early treatment instituted, the later, irreversible features and complications of CP could possibly be prevented. METHOD: An international working group supported by four major pancreas societies (IAP, APA, JPS, and EPC) and a PancreasFest working group sought to develop a consensus definition and diagnostic criteria for Early CP...
May 21, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Niloofar Y Jalaly, David C Whitcomb, Vikesh K Singh
No abstract text is available yet for this article.
April 2018: American Journal of Gastroenterology
Harkirat Singh, Amir Gougol, Rawad Mounzer, Dhiraj Yadav, Efstratios Koutroumpakis, Adam Slivka, David C Whitcomb, Georgios I Papachristou
OBJECTIVES: In our experience, a subset of mild acute pancreatitis (AP) patients, as defined by the Revised Atlanta Classification, has longer than expected hospitalization. Our aims are to report the prevalence of patients with mild AP who have a prolonged length of stay (LOS), evaluate the etiology, thoroughly phenotype, and finally compare this subset to those with expected LOS. METHODS: Patients admitted with AP from 2003 to 2015 were prospectively enrolled into this cohort study...
December 7, 2017: Clinical and Translational Gastroenterology
Shrinivas Bishu, Efstratios Koutroumpakis, Rawad Mounzer, Kimberly Stello, Nijole Pollock, Anna Evans, David C Whitcomb, Georgios I Papachristou
OBJECTIVES: Inflammation in the setting of acute pancreatitis (AP) is partially driven by pathogen recognition receptors that recognize damage-associated molecular patterns. Interleukin (IL)-8 is a chemotactic factor produced by pathogen recognition receptor-expressing cells. A single-nucleotide polymorphism in IL8 promoter region (-251 A/T) has been implicated in inflammatory diseases. We examined whether this IL8 polymorphism confers susceptibility to AP. METHODS: Patients with AP (n = 357) were prospectively recruited...
January 2018: Pancreas
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