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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2017; 23(39): 7059-7076
Published online Oct 21, 2017. doi: 10.3748/wjg.v23.i39.7059
Less common etiologies of exocrine pancreatic insufficiency
Vikesh K Singh, Mark E Haupt, David E Geller, Jerry A Hall, Pedro M Quintana Diez
Vikesh K Singh, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Mark E Haupt, Medical Affairs, AbbVie Inc., North Chicago, IL 60064, United States
David E Geller, Cystic Fibrosis Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
Jerry A Hall, CREON® Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
Pedro M Quintana Diez, CREON® Development, AbbVie Inc., North Chicago, IL 60064, United States
Author contributions: Singh VK, Haupt ME, Geller DE, Hall JA and Quintana Diez PM designed the “search terms” of the literature review, analyzed the data, and summarized the findings; all authors critically reviewed and revised the manuscript, and approved the final version of the article, including the authorship list.
Conflict-of-interest statement: Singh VK is a consultant for Ariel, Kowa, Novo Nordisk, and AbbVie; he has been an advisory board participant for Akcea and Nordmark; Geller DE and Hall JA are employees of AbbVie and may own AbbVie stock and/or options; Haupt ME and Quintana Diez PM are former employees of AbbVie and may own AbbVie stock and/or options.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vikesh K Singh, MD, MSc, Associate Professor of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, 1830 E Monument Street, Room 436, Baltimore, MD 21287, United States. vsingh1@jhmi.edu
Telephone: +1-410-6146708 Fax: +1-410-6147631
Received: September 7, 2016
Peer-review started: September 10, 2016
First decision: October 10, 2016
Revised: May 27, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: October 21, 2017
Processing time: 408 Days and 9.5 Hours
Abstract

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Keywords: Celiac disease; Inflammatory bowel disease; Exocrine pancreatic insufficiency; Malabsorption; Epidemiology; Pancreas; Pancreatic cancer; Secretion/absorption; Surgery

Core tip: Exocrine pancreatic insufficiency (EPI) results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Pancreatic enzyme replacement therapy (PERT) may prevent serious nutritional complications when such patients have symptomatic EPI. However, EPI may be more prevalent in patients with non-pancreatic diseases, diabetes, and pancreatic cancer than has generally been appreciated. Scant published evidence on EPI in these less common etiologies precludes firm recommendations on management. Robust clinical studies are urgently needed to understand the relationships between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.