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Kang J, Wang J, Su J, Wang W, Lu Y, Tang Z, Zou L, Yin A, Li J, Ren H, Zhou Q, Wan H, An P. Pancreatic Enzyme Replacement Therapy Improves Exclusive Enteral Nutrition Related Diarrhea in Crohn's Disease: A Prospective Randomized Trial. United European Gastroenterol J 2025. [PMID: 40243170 DOI: 10.1002/ueg2.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 02/21/2025] [Accepted: 03/03/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND & AIMS Previous results showed that combined treatment of biologics and exclusive enteral nutrition (EEN) brought moderate-to-severe Crohn's disease patients significant improvements in clinical and endoscopic outcomes. Despite its essential role and favorable safety profile, EEN in the treatment of adult Crohn's disease is frequently underestimated because of lower compliance and several side effects, including EEN-related diarrhea (EEND). METHODS In this prospective, single-center randomized clinical trial, 147 eligible patients with actively moderate-to-severe Crohn's disease treated with biologics and concomitant 16-week EEN were included. Sixty-one patients without EEND were enrolled in the ND group (without EEN-related diarrhea), and other patients with EEND who received pancreatic enzyme replacement therapy (PERT) (43 patients) or not (43 patients) were recruited in PERT and NPERT groups, respectively. The clinical outcomes, biologic outcomes, and endoscopic outcomes were evaluated. Quality of life (QoL) and psychological status were also assessed at baseline and endpoints (week 16). RESULTS Bowel movements (daily frequency decreased by 5.3 times) and stool consistency (reduced watery and loose stool) were greatly improved in PERT group at week 16. At week 16, patients in the ND and PERT groups achieved similar clinical responses (93% in ND group and 94.7% in PERT group, p = 0.731) and clinical remission (86.0% in ND group and 86.8% in PERT group, p = 0.90) while patients in the NPERT group had significantly lower proportions of these clinical outcomes (67.9% clinical response and 57.1% clinical remission). No significant difference was observed in endoscopic outcomes between each group (p = 0.904). QoL and mental status including anxiety and depression in PERT group had great improvement compared with the NPERT group. CONCLUSIONS Our prospective results provided invaluable evidence that PERT supplementation efficiently improved EEND in Crohn's disease patients with combined treatment of biologics and 16-week EEN, which had a promising effect in active Crohn's disease induction. TRIAL REGISTRATION ChiCTR2200058343.
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Affiliation(s)
- Jian Kang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jing Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Juan Su
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Wei Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Yueyue Lu
- Department of Gastroenterology, First Hospital of Yangtze University, Jingzhou, China
| | - Zhishun Tang
- School of Sports Medicine, Wuhan Sports University, Wuhan, China
| | - Liping Zou
- The Clinical Skill Center, Teaching Office of the First School of Clinical Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Anning Yin
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Haixia Ren
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qian Zhou
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Huipeng Wan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ping An
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
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Fang LH, Zhang JQ, Huang JK, Tang XD. Inflammatory bowel disease increases the risk of pancreatitis: a two-sample bidirectional Mendelian randomization analysis. BMC Gastroenterol 2025; 25:13. [PMID: 39799299 PMCID: PMC11725204 DOI: 10.1186/s12876-024-03571-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 12/17/2024] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Previous studies have suggested an association between inflammatory bowel disease (IBD), and pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). We aimed to examine the potential causal relationship between IBD and pancreatitis using the Mendelian randomization (MR) method. METHODS We obtained data from genome-wide association studies (GWASs) in European individuals for IBD and its main subtypes, Crohn's disease (CD) and ulcerative colitis (UC) (31,665 IBD cases, 13,768 UC cases, 17,897 CD cases and 33,977 controls). Four independent summary statistics of pancreatitis from the the European Bioinformatics Institute (EMBL-EBI, 10,630 AP cases and 844,679 controls, 1,424 CP cases and 476,104 controls) and FinnGen Consortium (8,446 AP cases, 4,820 CP cases and 437,418 controls) were used for bidirectional MR analyses and sensitivity analysis. Finally, further meta-analysis was conducted on the MR results. RESULTS Generally, IBD is associated with an increased risk of pancreatitis (IBD-AP, OR = 1.050, 95% CI 1.020-1.080, P = 7.20 × 10-5; IBD-CP, OR = 1.050, 95% CI 1.010-1.090, P = 0.019). In addition, UC increased the risk of pancreatitis (UC-AP, OR = 1.050, 95% CI 1.020-1.070, P = 9.10 × 10-5; UC-CP, OR = 1.090, 95% CI 1.040-1.140, P = 1.44 × 10-4) and CD increased the risk of acute pancreatitis (OR = 1.040, 95% CI 1.020-1.060, P = 9.61 × 10-5). However, no causal association was found between CD and the risk of chronic pancreatitis (P > 0.05). The reverse MR results showed that AP may be associated with a reduced risk of IBD and CD (AP-IBD, OR = 0.880, 95% CI 0.810-0.960, P = 0.003; AP-CD, OR = 0.830, 95% CI 0.730-0.940, P = 0.003). However, there is no causal relationship between AP and the risk of UC, and there is no causal relationship between CP and the risk of IBD and its subtypes(P > 0.05). CONCLUSION In conclusion, based on MR analysis and meta-analysis, our results showed a positive causal effect of IBD on pancreatitis, and subgroup analyses showed that UC and CD may promote the development of acute pancreatitis, whereas UC may promote the development of chronic pancreatitis. Reverse MR analysis suggests that AP may have a potential protective effect on IBD and CD.
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Affiliation(s)
- Li-Hui Fang
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Jia-Qi Zhang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Jin-Ke Huang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Xu-Dong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
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Gordon H, Burisch J, Ellul P, Karmiris K, Katsanos K, Allocca M, Bamias G, Barreiro-de Acosta M, Braithwaite T, Greuter T, Harwood C, Juillerat P, Lobaton T, Müller-Ladner U, Noor N, Pellino G, Savarino E, Schramm C, Soriano A, Michael Stein J, Uzzan M, van Rheenen PF, Vavricka SR, Vecchi M, Zuily S, Kucharzik T. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2024; 18:1-37. [PMID: 37351850 DOI: 10.1093/ecco-jcc/jjad108] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Indexed: 06/24/2023]
Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, London, Centre for Immunobiology, Blizard Institute, Faculty of Medicine, Barts & The London Medical School, Queen Mary University of London, UK
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre Hospital, University of Copenhagen, Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Giorgos Bamias
- GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Manuel Barreiro-de Acosta
- University Hospital Santiago De Compostela CHUS, Department of Gastroenterology - IBD Unit, Santiago De Compostela, Spain
| | - Tasanee Braithwaite
- School of Immunology and Microbiology, King's College London, The Medical Eye Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, GZO - Zurich Regional Health Center, Wetzikon, Division of Gastroenterology and Hepatology, University Hospital Lausanne - CHUV, Lausanne, Switzerland; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Catherine Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
| | - Nurulamin Noor
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Christoph Schramm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alessandra Soriano
- Gastroenterology Division and IBD Center, Internal Medicine Department, Azienda Unità Sanitaria Locale - IRCCS, 42122 Reggio Emilia, Italy
| | - Jürgen Michael Stein
- Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/Main, Germany
| | - Mathieu Uzzan
- Department of Gastroenterology, Hôpital Henri Mondor, APHP, Créteil, France
| | - Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stephane Zuily
- Vascular Medicine Division and French Referral Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Münster, Lüneburg, Germany
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George J, Gnanamoorthy K, Suthakaran PK, Baliga KV. Hyperlipasemia Sans Pancreatitis: A Case Series. Cureus 2023; 15:e47781. [PMID: 38021537 PMCID: PMC10679796 DOI: 10.7759/cureus.47781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2023] [Indexed: 12/01/2023] Open
Abstract
Acute pancreatitis results in inflammation and autodigestion of pancreatic acinar cells leading to the elevation of pancreatic enzymes, namely, amylase and lipase. Serum lipase levels have long been considered a hallmark of acute pancreatitis. However, pancreatitis is not always the cause of elevated serum lipase levels. This series presents four patients who had elevated serum lipase levels without any demonstrable damage to the pancreas on imaging. On further evaluation, one of the patients was found to have acute on chronic kidney disease (CKD) whose lipase levels settled later. A patient presenting with an episode of acute gastroenteritis, later diagnosed to have Crohn's disease, also had hyperlipasemia, which improved after a course of initial antibiotics. Non-gastrointestinal causes, such as lupus nephritis and organophosphate (OP) poisoning, also had elevated lipase levels on presentation, in which the hyperlipasemia settled with supportive treatments. It is important to remember other causes of elevated lipase levels in patients with a normal pancreas on imaging studies.
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Affiliation(s)
- Jisa George
- Internal Medicine, Employees State Insurance Corporation (ESIC) Medical College & Post-Graduate Institute of Medical Sciences and Research (PGIMSR), Chennai, IND
| | | | - Prasanna Karthik Suthakaran
- Internal Medicine, Saveetha Medical College Hospital, Saveetha Institute of Medical And Technical Sciences (SIMATS), Kanchipuram, IND
| | - Krishna Venkatesh Baliga
- Nephrology, Employees State Insurance Corporation (ESIC) Medical College & Post-Graduate Institute of Medical Sciences and Research (PGIMSR), Chennai, IND
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Conti Bellocchi MC, Crinò SF, De Marchi G, De Pretis N, Ofosu A, Caldart F, Ciccocioppo R, Frulloni L. A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty? Biomedicines 2023; 11:biomedicines11051393. [PMID: 37239064 DOI: 10.3390/biomedicines11051393] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
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Affiliation(s)
| | - Stefano Francesco Crinò
- Diagnostic and Interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Nicolò De Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
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Mathew A, Fernandes D, Andreyev HJN. What is the significance of a faecal elastase-1 level between 200 and 500μg/g? Frontline Gastroenterol 2023; 14:371-376. [PMID: 37581180 PMCID: PMC10423608 DOI: 10.1136/flgastro-2022-102271] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 01/26/2023] [Indexed: 08/16/2023] Open
Abstract
Background Pancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear. Methods This retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g. Results Of these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence. Conclusion Clinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.
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Affiliation(s)
| | - Darren Fernandes
- Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln, UK
- School of Health and Social Care, Community and Health Research Unit, University of Lincoln, Lincoln, UK
| | - H Jervoise N Andreyev
- Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln, UK
- The Biomedical Research Centre, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
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Whitcomb DC, Duggan SN, Martindale R, Lowe M, Stallings VA, Conwell D, Barkin JA, Papachristou GI, Husain SZ, Forsmark CE, Kaul V. AGA-PancreasFest Joint Symposium on Exocrine Pancreatic Insufficiency. GASTRO HEP ADVANCES 2022; 2:395-411. [PMID: 39132652 PMCID: PMC11307793 DOI: 10.1016/j.gastha.2022.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/03/2022] [Indexed: 08/13/2024]
Abstract
Exocrine pancreatic insufficiency (EPI) is a clinically defined syndrome based on the physician's assessment of a patient's maldigestion. However, current clinical definitions are inadequate in determining (1) the threshold of reduced pancreatic digestive enzyme secretion that determines "pancreatic insufficiency" in an individual patient; (2) the role of pancreatic function tests; (3) effects of differing metabolic needs, nutrition intake, and intestinal function/adaptation (4) when pancreatic enzyme replacement therapy is needed; and (5) how to monitor and titrate multiple therapies. Experts and key opinion leaders were invited to PancreasFest 2021 to discuss and help clarify mechanistic issues critical to defining EPI and to address misconceptions and barriers limiting advancements in patient care. Clinically EPI is defined as inadequate delivery of pancreatic digestive enzymes to meals to meet nutritional needs and is reversed with appropriate treatment. A new mechanistic definition of EPI was proposed that includes the disorders essence and character: (1) EPI is a disorder caused by failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of a series of individual snacks and meals over time to meet nutritional and metabolic needs, given (a) the specific macronutritional and micronutritional needs; (b) nutrient intake; (c) exocrine pancreatic function; and (d) intestinal anatomy, function, diseases, and adaptative capacity. (2) EPI is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, by gastrointestinal symptoms of nutrient maldigestion and by improvement or correction of nutritional state with lifestyle changes, disease treatment, optimized diet, dietary supplements, and/or administration of adequate pancreatic enzyme replacement therapy. EPI is complex and individualized and multidisciplinary approaches are needed to optimize therapy. Better pancreas function tests and biomarkers are needed to diagnose EPI and guide treatment.
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Affiliation(s)
- David C. Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sinead N. Duggan
- Department of Surgery, School of Medicine, Trinity College Dublin, Tallaght University Hospital, Dublin, Republic of Ireland
| | - Robert Martindale
- Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Mark Lowe
- Department of Pediatric Science, Washington University School of Medicine, St. Louis, Missouri
| | - Virginia A. Stallings
- Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Darwin Conwell
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky
| | - Jodie A. Barkin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida
| | - Georgios I. Papachristou
- Division of Gastroenterology, Department of Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sohail Z. Husain
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford School of Medicine and Stanford Medicine Children's Health, Stanford, California
| | - Christopher E. Forsmark
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida
| | - Vivek Kaul
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York
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Hedström A, Steiner C, Valente R, Haas SL, Löhr JM, Vujasinovic M. Pancreatic exocrine insufficiency and Crohn's disease. MINERVA GASTROENTERO 2020; 66:17-22. [PMID: 31760738 DOI: 10.23736/s1121-421x.19.02636-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND According to the European evidence-based consensus, published by European Crohn's and Colitis Organization (ECCO), diseases of the pancreas are included as extra-intestinal manifestations in IBD in the forms of acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP), pancreatic duct abnormalities and pancreatic exocrine insufficiency (PEI). Presence of pancreatic autoantibodies directed against the exocrine of the pancreas has been reported in about one-third of CD. However, association between CD and PEI is not fully elucidated. METHODS Patients with a diagnosis of CD were recruited at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Fecal elastase-1 (FE-1) measurements were performed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS There were 20 patients included in the study, 13 (65%) males and 7 (35%) females, mean age 48.3±1.4 years (range 29-67 years). Mean duration of CD was 15.7±2.1 years (range 1-40 years). There were 11 (55%) patients without history of bowel surgery and 9 (45%) patients after ileocecal resection. FE-1 test was normal in all patients, among them 15 (75%) patients with the values of FE-1>500. CONCLUSIONS Fecal elastase-1 level was normal in all patients with CD strongly indicated absence of PEI in this group of patients.
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Affiliation(s)
- Aleksandra Hedström
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Corinna Steiner
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Roberto Valente
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Stephan L Haas
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - J-Matthias Löhr
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden -
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Akhmedov VA, Gaus OV. [Pancreatic diseases and inflammatory bowel diseases: a random or regular combination?]. TERAPEVT ARKH 2020; 92:76-81. [PMID: 32598667 DOI: 10.26442/00403660.2020.01.000463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
Pathology of the pancreas in inflammatory bowel disease (IBD) is more common than in the general population and includes a wide range of manifestations from asymptomatic to severe disorders. Acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency, increased pancreatic enzymes and structural duct anomalies are often associated with IBD. They can be either a manifestation of IBD itself or develop independently.
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The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease. J Clin Med 2019; 8:jcm8070916. [PMID: 31247968 PMCID: PMC6679036 DOI: 10.3390/jcm8070916] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 06/18/2019] [Accepted: 06/21/2019] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn's disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.
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Malluta ÉF, Maluf-Filho F, Leite AZDA, Ortiz-Agostinho CL, Nishitokukado I, Andrade AR, Lordello MLL, dos Santos FM, Sipahi AM. Pancreatic endosonographic findings and clinical correlation in Crohn's disease. Clinics (Sao Paulo) 2019; 74:e853. [PMID: 31166473 PMCID: PMC6542499 DOI: 10.6061/clinics/2019/e853] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Accepted: 01/17/2019] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES We aimed to evaluate the incidence of pancreatic alterations in Crohn's disease using endoscopic ultrasound (EUS) and to correlate the number of alterations with current clinical data. METHODS Patients diagnosed with Crohn's disease (n=51) were examined using EUS, and 11 variables were analyzed. A control group consisted of patients with no history of pancreatic disease or Crohn's disease. Patients presenting with three or more alterations underwent magnetic resonance imaging (MRI). Pancreatic function was determined using a fecal elastase assay. RESULTS Two of the 51 patients (3.9%) presented with four EUS alterations, 3 (5.9%) presented with three, 11 (21.5%) presented with two, and 13 (25.5%) presented with one; in the control group, only 16% presented with one EUS alteration (p<0.001). Parenchymal abnormalities accounted for 39 of the EUS findings, and ductal abnormalities accounted for 11. Pancreatic lesions were not detected by MRI. Low fecal elastase levels were observed in 4 patients, none of whom presented with significant pancreatic alterations after undergoing EUS. Ileal involvement was predictive of the number of EUS alterations. CONCLUSION A higher incidence of pancreatic abnormalities was found in patients with Crohn's disease than in individuals in the control group. The majority of these abnormalities are related to parenchymal alterations. In this group of patients, future studies should be conducted to determine whether such morphological abnormalities could evolve to induce exocrine or endocrine pancreatic insufficiency and, if so, identify the risk factors and determine which patients should undergo EUS.
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Affiliation(s)
- Éverson Fernando Malluta
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Fauze Maluf-Filho
- Departamento de Gastroenterologia, Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, SP, BR
| | - André Zonetti de Arruda Leite
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Carmen Lucia Ortiz-Agostinho
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Iêda Nishitokukado
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Adriana Ribas Andrade
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Maria Laura Lacava Lordello
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Fabiana Maria dos Santos
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Aytan Miranda Sipahi
- Laboratorio de Gastroenterologia Clinica e Experimental, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
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Fousekis FS, Theopistos VI, Katsanos KH, Christodoulou DK. Pancreatic Involvement in Inflammatory Bowel Disease: A Review. J Clin Med Res 2018; 10:743-751. [PMID: 30214645 PMCID: PMC6135003 DOI: 10.14740/jocmr3561w] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multisystemic disease, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases in Crohn’s disease and ulcerative colitis is more frequent compared to the general population. Pancreatic manifestations in IBD include a wide heterogenic group of disorders and abnormalities of the pancreas and range from mild self-limited diseases to severe disorders. Acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, pancreatic autoantibodies, exocrine pancreatic insufficiency and asymptomatic imaging and laboratory abnormalities are included in related-IBD pancreatic manifestations. Involvement of the pancreas in IBD may be the result of IBD itself or of medications used.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
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Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23:7059-7076. [PMID: 29093615 PMCID: PMC5656454 DOI: 10.3748/wjg.v23.i39.7059] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 05/27/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- 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
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14
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Chen YL, Hsu CW, Cheng CC, Yiang GT, Lin CS, Lin CL, Sung FC, Liang JA. Increased subsequent risk of inflammatory bowel disease association in patients with chronic pancreatitis: a nationwide population-based cohort study. Curr Med Res Opin 2017; 33:1077-1082. [PMID: 28277863 DOI: 10.1080/03007995.2017.1300143] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study. METHODS Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts. RESULTS When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn's disease (adjusted hazard ratio [aHR] = 12.9, 95% confidence interval [CI] = 5.15-32.5) and ulcerative colitis (aHR = 2.80, 95% CI = 1.00-7.86). CONCLUSIONS This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.
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Affiliation(s)
- Yu-Long Chen
- a Department of Emergency Medicine , Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Taipei , Taiwan
- e Department of Emergency Medicine, School of Medicine , Tzu Chi University , Taipei , Taiwan
| | - Chin-Wang Hsu
- b Department of Emergency Medicine, School of Medicine, College of Medicine , Taipei Medical University , Taipei , Taiwan
- c Department of Emergency and Critical Medicine , Wan Fang Hospital, Taipei Medical University , Taipei , Taiwan
| | - Cheng-Chung Cheng
- d Division of Cardiology, Department of Medicine , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan
| | - Giou-Teng Yiang
- a Department of Emergency Medicine , Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Taipei , Taiwan
- e Department of Emergency Medicine, School of Medicine , Tzu Chi University , Taipei , Taiwan
| | - Chin-Sheng Lin
- d Division of Cardiology, Department of Medicine , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan
| | - Cheng-Li Lin
- f Management Office for Health Data, China Medical University Hospital , Taichung , Taiwan
- g College of Medicine , China Medical University , Taichung , Taiwan
| | - Fung-Chang Sung
- h Department of Health Services Administration , China Medical University , Taichung , Taiwan
- i Faculty of Public Health , Mahidol University , Bangkok , Thailand
| | - Ji-An Liang
- j Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine , China Medical University , Taichung , Taiwan
- k Department of Radiation Oncology , China Medical University Hospital , Taichung , Taiwan
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15
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Abstract
Autoimmune pancreatitis (AIP) occurring in association with inflammatory bowel disease (IBD) is rather rare and carries a worse prognosis and greater disease severity compared with IBD alone. Although it is an infrequently documented association, progress over the last 20 years has led to better understanding of the association between AIP and IBD. IBD has a stronger association with type 2 than with type 1 AIP. Clinical and histologic features of AIP-IBD more often reveal features of type 2 AIP. Imaging is not helpful in facilitating the diagnosis of AIP and IBD. Similarly, attempts to identify a serological marker have not yielded better result. A proposed lymphocyte homing mechanism provides some insight into the mechanism of pathogenesis. This review represents an update of our current knowledge of the association between AIP and IBD.
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Fernández-Bañares F, Accarino A, Balboa A, Domènech E, Esteve M, Garcia-Planella E, Guardiola J, Molero X, Rodríguez-Luna A, Ruiz-Cerulla A, Santos J, Vaquero E. Diarrea crónica: definición, clasificación y diagnóstico. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:535-59. [DOI: 10.1016/j.gastrohep.2015.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 09/21/2015] [Accepted: 09/30/2015] [Indexed: 12/16/2022]
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Antonini F, Pezzilli R, Angelelli L, Macarri G. Pancreatic disorders in inflammatory bowel disease. World J Gastrointest Pathophysiol 2016; 7:276-282. [PMID: 27574565 PMCID: PMC4981767 DOI: 10.4291/wjgp.v7.i3.276] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 07/08/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD.
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18
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Ramos LR, Sachar DB, DiMaio CJ, Colombel JF, Torres J. Inflammatory Bowel Disease and Pancreatitis: A Review. J Crohns Colitis 2016; 10:95-104. [PMID: 26351384 DOI: 10.1093/ecco-jcc/jjv153] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 08/19/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Pancreatic abnormalities are common in inflammatory bowel disease (IBD) patients and represent a heterogeneous group of conditions that include acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis and asymptomatic abnormalities. We sought to review the available evidence concerning the aetiology, clinical presentation, diagnosis and treatment of pancreatic conditions in IBD patients. METHODS A PubMed/Medline query was conducted addressing pancreatic disorders in IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Relevant manuscripts about pancreatic disorders in patients with IBD were selected and reviewed. RESULTS Thiopurines and gallstones are the most frequent causes of acute pancreatitis in IBD patients. Thiopurine-induced acute pancreatitis is usually uncomplicated and self-limited. Some evidence suggests that chronic pancreatitis may be more common in IBD. Most cases are idiopathic, affecting young males and patients with ulcerative colitis. Autoimmune pancreatitis is a relatively newly recognized disease and is increasingly diagnosed in IBD, particularly for type 2 autoimmune pancreatitis in ulcerative colitis patients. Asymptomatic exocrine insufficiency, pancreatic duct abnormalities and hyperamylasaemia have been identified in up to 18% of IBD patients, although their clinical significance and relationship with IBD remain undefined. CONCLUSIONS The wide spectrum of pancreatic manifestations in IBD is growing and may represent a challenge to the clinician. A collaborative approach with a pancreas specialist may be the most productive route to determine aetiology, guide additional diagnostic workup, illuminate the aetiology and define the treatment and follow-up of these patients.
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Affiliation(s)
- Lídia Roque Ramos
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - David B Sachar
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Christopher J DiMaio
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Jean-Frédéric Colombel
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Joana Torres
- Ichan School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
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19
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Kuwata G, Kamisawa T, Koizumi K, Tabata T, Hara S, Kuruma S, Fujiwara T, Chiba K, Egashira H, Fujiwara J, Arakawa T, Momma K, Horiguchi S. Ulcerative colitis and immunoglobulin G4. Gut Liver 2013; 8:29-34. [PMID: 24516698 PMCID: PMC3916684 DOI: 10.5009/gnl.2014.8.1.29] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 02/20/2013] [Accepted: 04/03/2013] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). Conclusions UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.
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Affiliation(s)
- Go Kuwata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Koichi Koizumi
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Taku Tabata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Seiichi Hara
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Sawako Kuruma
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takashi Fujiwara
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kazuro Chiba
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Hideto Egashira
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Junko Fujiwara
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takeo Arakawa
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kumiko Momma
- Department of Endoscopy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
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Investigative MRI cholangiopancreatography for primary sclerosing cholangitis-type lesions in children with IBD. J Pediatr Gastroenterol Nutr 2012; 55:308-13. [PMID: 22569526 DOI: 10.1097/mpg.0b013e31825bb3dc] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. METHODS Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. RESULTS Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. CONCLUSIONS The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.
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Nakamura K, Ito T, Kotoh K, Ihara E, Ogino H, Iwasa T, Tanaka Y, Iboshi Y, Takayanagi R. Hepatopancreatobiliary manifestations of inflammatory bowel disease. Clin J Gastroenterol 2012; 5:1-8. [PMID: 26181867 DOI: 10.1007/s12328-011-0282-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2011] [Accepted: 12/13/2011] [Indexed: 12/23/2022]
Abstract
Inflammatory bowel disease (IBD) is frequently associated with extraintestinal manifestations such as hepatopancreatobiliary manifestations (HPBMs), which include primary sclerosing cholangitis (PSC), pancreatitis, and cholelithiasis. PSC is correlated with IBD, particularly ulcerative colitis (UC); 70-80% of PSC patients in Western countries and 20-30% in Japan have comorbid UC. Therefore, patients diagnosed with PSC should be screened for UC by total colonoscopy. While symptoms of PSC-associated UC are usually milder than PSC-negative UC, these patients have a higher risk of colorectal cancer, particularly in the proximal colon. Therefore, regular colonoscopy surveillance is required regardless of UC symptoms. Administration of 5-aminosalicylic acid or ursodeoxycholic acid may prevent colorectal cancer and cholangiocarcinoma. While PSC is diagnosed by diffuse multifocal strictures on cholangiography, it must be carefully differentiated from immunoglobulin G4 (IgG4)-associated cholangitis, which shows a similar cholangiogram but requires different treatment. When PSC is suspected despite a normal cholangiogram, the patient may have small-duct PSC, which requires a liver biopsy. IBD patients have a high incidence of acute and chronic pancreatitis. Most cases are induced by cholelithiasis or medication, although some patients may have autoimmune pancreatitis (AIP), most commonly type 2 without elevation of serum IgG4. AIP should be accurately identified based on characteristic image findings, because AIP responds well to corticosteroids. Crohn's disease is frequently associated with gallstones, and several risk factors are indicated. HPBMs may influence the management of IBD, therefore, accurate diagnosis and an appropriate therapeutic strategy are important, as treatment depends upon the type of HPBM.
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Affiliation(s)
- Kazuhiko Nakamura
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Tetsuhide Ito
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kazuhiro Kotoh
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Haruei Ogino
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tsutomu Iwasa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshimasa Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoichiro Iboshi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ryoichi Takayanagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Idiopathic pancreatitis preceding the diagnosis of inflammatory bowel disease is more frequent in pediatric patients. J Pediatr Gastroenterol Nutr 2011; 52:714-7. [PMID: 21478760 DOI: 10.1097/mpg.0b013e3182065cad] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVES Acute pancreatitis (AP) can be a rare extraintestinal manifestation of inflammatory bowel disease (IBD). There are only a few reports of AP presenting before the diagnosis of IBD. We aimed to characterize the demographic, clinical, and laboratory data of patients with IBD in whom AP preceded disease onset and compare the presentation of AP between children and adults. PATIENTS AND METHODS Pediatric and adult patients presenting with AP as the first symptom of IBD were retrospectively identified (10 years, 7 university hospitals). Demographic and clinical data, IBD type, disease extension, and laboratory data were extracted from the charts. Imaging methods, number of AP episodes, and lag time between onset of first pancreatitis episode and onset of IBD were recorded. RESULTS AP preceding the diagnosis of IBD was found in 10 in 460 pediatric patients with IBD (2.17%), compared with only 2 in 3500 adults (0.06%). Eight children had colonic disease (4 Crohn disease, 4 ulcerative colitis [3 pancolitis]). Mean amylase level was 1419 and range 100 to 1370. Three children (30%) had mildly elevated transaminases. Median time between onset of first episode of AP in relation to onset of IBD was 24 (range 1-156) weeks. AP most commonly presented with abdominal pain. CONCLUSIONS IBD presenting as AP was more frequent among the pediatric population with IBD in comparison to adults. It was more common in patients with colitis than in those with ileal disease, suggesting that patients with idiopathic AP should be observed carefully for a possible diagnosis of IBD.
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Narula N, Vasudev M, Marshall JK. IgG₄-related sclerosing disease: a novel mimic of inflammatory bowel disease. Dig Dis Sci 2010; 55:3047-51. [PMID: 20521111 DOI: 10.1007/s10620-010-1287-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2010] [Accepted: 05/13/2010] [Indexed: 02/06/2023]
Abstract
High levels of IgG₄-positive plasma cells are commonly seen in autoimmune pancreatitis. It has recently become evident that autoimmune pancreatitis is one component of a larger multi-system disease. IgG₄-positive plasma cells have been identified in many extrapancreatic tissues, including the colon, biliary tract, liver, and lungs, and thus the term "IgG₄-related sclerosing disease" has been proposed. Awareness of IgG₄-related sclerosing disease is important, as it has been shown to mimic other conditions like malignancy. This review discusses IgG₄-related colitis and its potential for mimicking inflammatory bowel disease.
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Affiliation(s)
- Neeraj Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada
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Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis 2010; 16:1598-619. [PMID: 20198712 DOI: 10.1002/ibd.21219] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated.
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Keller J, Beglinger C, Holst JJ, Andresen V, Layer P. Mechanisms of gastric emptying disturbances in chronic and acute inflammation of the distal gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 2009; 297:G861-8. [PMID: 20501434 DOI: 10.1152/ajpgi.00145.2009] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
It is unclear why patients with inflammation of the distal bowel complain of symptoms referable to the upper gastrointestinal tract, specifically to gastric emptying (GE) disturbances. Thus we aimed to determine occurrence and putative pathomechanisms of gastric motor disorders in such patients. Thirteen healthy subjects (CON), 13 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 7 with diverticulitis (DIV) underwent a standardized (13)C-octanoic acid gastric emptying breath test. Plasma glucose, CCK, peptide YY, and glucagon-like peptide-1 (GLP-1) were measured periodically and correlated with GE parameters. Results were given in means +/- SD. Compared with CON, GE half time (T) was prolonged by 50% in CD (115 +/- 55 vs. 182 +/- 95 min, P = 0.037). Six CD, 2 DIV, and 2 UC patients had pathological T (>200 min). Postprandial plasma glucose was increased in all patients but was highest in DIV and correlated with T (r = 0.90, P = 0.006). In CD, mean postprandial CCK levels were increased threefold compared with CON (6.5 +/- 6.7 vs. 2.1 +/- 0.6 pmol/l, P = 0.027) and were correlated with T (r = 0.60, P = 0.041). Compared with CON, GLP-1 levels were increased in UC (25.1 +/- 5.2 vs. 33.5 +/- 13.0 pmol/l, P = 0.046) but markedly decreased in DIV (9.6 +/- 5.2 pmol/l, P < 0.0001). We concluded that a subset of patients with CD, UC, or DIV has delayed GE. GE disturbances are most pronounced in CD and might partly be caused by excessive CCK release. In DIV there might be a pathophysiological link between decreased GLP-1 release, postprandial hyperglycemia, and delayed GE. These explorative data encourage further studies in larger patient groups.
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Keller J, Aghdassi AA, Lerch MM, Mayerle JV, Layer P. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders. Best Pract Res Clin Gastroenterol 2009; 23:425-39. [PMID: 19505669 DOI: 10.1016/j.bpg.2009.02.013] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders.
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Affiliation(s)
- Jutta Keller
- Department of Medicine, Israelitisches Krankenhaus, Hamburg, Germany
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Kathrani A, Steiner JM, Suchodolski J, Eastwood J, Syme H, Garden OA, Allenspach K. Elevated canine pancreatic lipase immunoreactivity concentration in dogs with inflammatory bowel disease is associated with a negative outcome. J Small Anim Pract 2009; 50:126-32. [DOI: 10.1111/j.1748-5827.2008.00693.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Garrido Gómez E, Lopez San Román A, Bermejo San José F. Idiopathic pancreatitis in inflammatory bowel disease. J Crohns Colitis 2008; 2:237-40. [PMID: 21172217 DOI: 10.1016/j.crohns.2008.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2008] [Accepted: 03/18/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The incidence of pancreatitis is increased in inflammatory bowel disease. However, pancreatitis as an extraintestinal manifestation of the intestinal disease is exceedingly rare. We have retrospectively analyzed the prevalence of pancreatitis in a combined hospital cohort, and specifically studied cases in which no other cause than the intestinal disease itself could be found. METHODS The prevalence of pancreatitis in 1057 inflammatory bowel disease patients from two hospitals in the Community of Madrid, Spain, was determined by means of database examination. RESULTS The prevalence of pancreatitis was 2.74% (29 cases); only in four patients (0.38%) it was considered idiopathic and thus a possible extraintestinal manifestation. Underlying chronic pancreatitis was identified in three of these four patients. CONCLUSIONS In inflammatory bowel disease patients, pancreatitis is more often due to a nonrelated cause, and cases that can be adscribed to extraintestinal manifestation of the intestinal disease are comparatively rare.
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Affiliation(s)
- Elena Garrido Gómez
- Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, Madrid, Spain
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Maconi G, Dominici R, Molteni M, Ardizzone S, Bosani M, Ferrara E, Gallus S, Panteghini M, Bianchi Porro G. Prevalence of pancreatic insufficiency in inflammatory bowel diseases. Assessment by fecal elastase-1. Dig Dis Sci 2008; 53:262-70. [PMID: 17530399 DOI: 10.1007/s10620-007-9852-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2005] [Accepted: 03/01/2006] [Indexed: 02/06/2023]
Abstract
Pancreatic insufficiency (PI) may be an extraintestinal manifestation of inflammatory bowel diseases (IBD). We report the results of a cross-sectional study that was carried out to investigate both the prevalence of PI in IBD patients and its clinical course over a 6-month follow-up period. In total, 100 Crohn's disease (CD) patients, 100 ulcerative colitis (UC) patients, and 100 controls were screened for PI by the fecal elastase-1 (FE-1) test. The decision limits employed were: < or =200 microg/g stool for PI and < or =100 microg/g for severe PI. Patients with abnormal FE-1 values were re-tested after 6 months. Odds ratios (OR) for PI were estimated by unconditional logistic regression analysis. PI was found in 22 UC and 14 CD patients. The OR for the FE-1 test < or =200 microg/g was 10.5 [95% confidence interval (CI): 2.5-44.8] for IBD patients compared to the controls. The risk of PI was related to three or more bowel movements per day (OR = 25.0), the passage of loose stools (OR = 7.7), and previous surgery (OR = 3.7). At the 6-month follow-up, FE-1 values became normal in 24 patients and showed persistently low concentrations in 12. These patients had a larger number of bowel movements per day (OR = 5.4), previous surgery (OR = 5.7), and a longer duration of the disease (OR = 4.2). PI is frequently found in IBD patients, particularly in those with loose stools, a larger number of bowel movements/day and previous surgery. PI is reversible in most patients, and persistent PI is not associated with clinically active disease.
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Affiliation(s)
- Giovanni Maconi
- Department of Clinical Sciences, L Sacco University Hospital, Via GB Grassi, 74, Milan, Italy.
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Rothfuss KS, Stange EF, Herrlinger KR. Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol 2006; 12:4819-31. [PMID: 16937463 PMCID: PMC4087615 DOI: 10.3748/wjg.v12.i30.4819] [Citation(s) in RCA: 215] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.
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Affiliation(s)
- Katja S Rothfuss
- Robert-Bosch-Hospital, Department of Gastroenterology, Hepatology and Endocrinology, Auerbachstrasse 110, D-70376 Stuttgart, Germany.
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Barthet M, Lesavre N, Desplats S, Panuel M, Gasmi M, Bernard JP, Dagorn JC, Grimaud JC. Frequency and characteristics of pancreatitis in patients with inflammatory bowel disease. Pancreatology 2006; 6:464-71. [PMID: 16847384 DOI: 10.1159/000094564] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2005] [Accepted: 04/28/2006] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Clinical symptoms of inflammatory bowel disease (IBD)-associated pancreatitis are found in approximately 2% of patients, but the frequency of the disease could be much higher since IBD-associated pancreatitis could be mainly a silent disease. The aim of this study was to describe the radiological and biological features of IBD-associated pancreatitis and assess its frequency by comparing data from IBD patients with or without a history of pancreatitis. METHODS 79 patients were prospectively enrolled (median age 36 years). Symptoms of pancreatitis had been previously recorded in 30 of them (group P; the other 49 patients (group C) had no history of pancreatitis. Pancreatic ductal changes were investigated by pancreato-MRI. Exocrine function was assessed by the fecal elastase test and by assaying serum amylase, lipase, C-reactive protein, PAP, IgG4 and pancreatic autoantibodies. RESULTS Increased levels of amylase and lipase occurred in 11% of IBD patients, that frequency being significantly higher in group P (23%) than in group C (4%) (p = 0.01). Low fecal elastase reflecting impaired exocrine function was observed in 30% of patients and again significantly more in group P (50%) than in group C (17%) (p = 0.04). The frequency of elevated values varied from 12% for amylase and lipase to 18% for PAP, 20% for pancreatic autoantibodies and 45% for CRP, without a difference between groups P and C. Silent exocrinopathy was observed in both groups, pancreatic autoantibodies and pancreatic duct alterations being found in 20 and 11% of patients, respectively. CONCLUSION Finding pancreatic insufficiency in about 30% of the included patients and in 50% of those with a previous history of pancreatitis suggests that IBD might be associated with chronic pancreatic alteration. Episodes of mild acute pancreatitis observed in some patients are not always due to adverse effects of treatments and can be acute manifestations of the chronic disease.
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Affiliation(s)
- Marc Barthet
- Department of Gastroenterology and Hepatology, Hôpital Nord, Chemin des Bourrely, Marseille, France.
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Toda N, Akahane M, Kiryu S, Matsubara Y, Yamaji Y, Okamoto M, Minagawa N, Ohgi K, Komatsu Y, Yahagi N, Yoshida H, Kawabe T, Ohtomo K, Omata M. Pancreas duct abnormalities in patients with ulcerative colitis: a magnetic resonance pancreatography study. Inflamm Bowel Dis 2005; 11:903-8. [PMID: 16189420 DOI: 10.1097/01.mib.0000183419.17563.17] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The presumed etiology and prevalence of pancreatic abnormalities in patients with ulcerative colitis (UC) have been controversial. We conducted a controlled (cross-sectional) study of patients with UC compared with non-UC controls to determine the prevalence of pancreatic duct abnormalities in patients with UC and to determine if these are specific to UC using magnetic resonance cholangiopancreatography. METHODS Magnetic resonance cholangiopancreatography was performed on 79 unselected patients with UC and 45 non-UC controls, without a history of pancreatitis attack, between February 2000 and May 2003. RESULTS Among patients with UC, the prevalence of pancreatic duct abnormalities was 16.4% (95% confidence interval, 8.3%-24.6%): coexisting dilatation and narrowing of the main pancreatic duct were found in 5; diffuse narrowing of pancreatic ducts in 5; and dilatation of pancreatic ductal branches in 3. These abnormalities were compatible with chronic pancreatitis. Among the controls, no pancreatic duct abnormality was found. CONCLUSIONS Changes in the pancreatic duct were found in approximately one-sixth of patients with UC, none of whom had a history of overt pancreatitis. These pancreatic duct abnormalities are likely to be specific to patients with UC.
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MESH Headings
- Adolescent
- Adult
- Aged
- Case-Control Studies
- Cholangiopancreatography, Magnetic Resonance
- Colitis, Ulcerative/complications
- Colitis, Ulcerative/diagnostic imaging
- Constriction, Pathologic/complications
- Constriction, Pathologic/diagnostic imaging
- Constriction, Pathologic/epidemiology
- Cross-Sectional Studies
- Dilatation, Pathologic/complications
- Dilatation, Pathologic/diagnostic imaging
- Dilatation, Pathologic/epidemiology
- Female
- Humans
- Male
- Middle Aged
- Pancreatic Ducts/diagnostic imaging
- Pancreatitis, Chronic/complications
- Pancreatitis, Chronic/diagnostic imaging
- Pancreatitis, Chronic/epidemiology
- Prevalence
- Radiography
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Affiliation(s)
- Nobuo Toda
- Division of Gastroenterology, Department of Internal Medicine, University of Tokyo, Japan.
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Sahel J, Barthet M, Gasmi M. Autoimmune pancreatitis: increasing evidence for a clinical entity with various patterns. Eur J Gastroenterol Hepatol 2004; 16:1265-8. [PMID: 15618830 DOI: 10.1097/00042737-200412000-00005] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Autoimmune pancreatitis is a clinical entity with many different clinical and biological characteristics that make diagnosis difficult. Sensitive and specific pancreatic antibodies are still lacking to assess the diagnosis as is the availability of interpretable pathological specimens. However, suggestive features consist mainly of radiological findings and clinical anomalies, particularly if there are associated autoimmune-related diseases. The immunological pathway is probably of cell-mediated origin, although various autoantibodies, insensitive and non-specific, may exist. Finally, many studies are needed to define more efficient diagnostic criteria and to discover the true prevalence of autoimmune pancreatitis.
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Affiliation(s)
- José Sahel
- Department of Gastroenterology, Sainte Marguerite Hospital, and bDepartment of Gastroenterology, Hospital Nord, Marseille, France.
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Winter TA, O'keefe SJD, Callanan M, Marks T. Impaired gastric acid and pancreatic enzyme secretion in patients with Crohn's disease may be a consequenece of a poor nutritional state. Inflamm Bowel Dis 2004; 10:618-25. [PMID: 15472524 DOI: 10.1097/00054725-200409000-00018] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Impaired pancreatic function has been reported in Crohn's disease, the cause of which is uncertain. This study investigated the effect of malnutrition, and subsequent re-feeding, on digestive function and protein synthesis in Crohn's disease patients. METHODS Gastric acid and pancreatic secretion studies were performed on malnourished Crohn's patients before, and after a period of intensive nutritional support. Whole body, as well as pancreatic enzyme protein synthesis was investigated by [14C]leucine isotope incorporation studies. Results were evaluated in comparison to normal healthy volunteers. RESULTS The mean body mass index (BMI) of the Crohn's patients was 14.14 kg/m2. The Crohn's patients had reduction in the secretion of gastric acid (7.36 versus 25.53 mEq/h; P < 0.01), and the pancreatic enzymes, amylase (759.6 versus 2305 U/h; P < 0.01), lipase (33.01 versus 118.6 U/h; P < 0.01) and trypsin (97.43 versus 341.4 U/h; P < 0.01). Resting energy expenditure (REE), expressed in relation to body mass, was greater in the malnourished Crohn's disease patients (38.25 versus 25.36 kcal/kg/d; P = 0.01). Total body protein synthesis was reduced (2.82 versus 4.39 g protein/kg/d; P < 0.05), with significant impairment in the synthesis of pancreatic enzymes, and reduction of zymogen stores. Following re-feeding, the BMI of the Crohn's patients improved to 16.80 +/- 0.66 kg/m2. Pancreatic enzyme synthesis improved, with significant increase in pancreatic enzyme stores and secretion, to levels similar to control values. Gastric acid secretion also improved, although still lower than the control value. CONCLUSION Malnutrition may play a significant role in the impairment of gastric acid and pancreatic secretion in Crohn's disease patients.
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Affiliation(s)
- T A Winter
- Gastrointestinal Clinic, Department of Medicine, University of Cape Town, Groote Schuur hospital, Observatory, Cape Town, 7925, South Africa.
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Jouffret C, Garçon S, Fikri M, Bennathan M, Lecoroller T, Charrier A, Durieux O, Agostini S. Pancréatites inflammatoires. ACTA ACUST UNITED AC 2004. [DOI: 10.1016/j.emcrad.2004.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Saito T, Tanaka S, Yoshida H, Imamura T, Ukegawa J, Seki T, Ikegami A, Yamamura F, Mikami T, Aoyagi Y, Niikawa J, Mitamura K. A case of autoimmune pancreatitis responding to steroid therapy. Evidence of histologic recovery. Pancreatology 2003; 2:550-6. [PMID: 12435868 DOI: 10.1159/000066092] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
We report a case of autoimmune pancreatitis without obvious evidence of autoimmunological participation, which responded well to steroid treatment and provided histologic and radiographic evidence for this improvement. A 68-year-old woman presented abdominal fullness, diffuse pancreatic swelling on abdominal computed tomography and ultrasonography, and diffuse narrowing of the main pancreatic duct on endoscopic retrograde pancreatography. Transgastric aspiration needle biopsy of the body of the pancreas performed under endoscopic ultrasonography showed severe atrophy of acinar cells, infiltration of T lymphocytes. She was diagnosed as having autoimmune pancreatitis without obvious evidence of autoimmunological participation. Administration of 30 mg/day of predonisolone was started. Computed tomography showed marked improvement of the diffuse swelling of the pancreas, and endoscopic retrograde pancreatograpy showed amelioration of the narrowing of the main pancreatic duct after the start of treatment. Pancreatic tissue obtained by needle biopsy after the start of treatment with predonisolone revealed marked histologic improvement, including amelioration of the fibrosis, and infiltration of inflammatory lymphocytes, and a substantial increase in the number of pancreatic acinar cells. The present report is the first to demonstrate histologic recovery of autoimmune pancreatitis after steroid therapy.
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Affiliation(s)
- Takeshi Saito
- Second Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan
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Antón MD, Ortiz I, López A, Delgado F, Barrachina M, Moreno E. [Chronic pancreatitis as the initial presentation of Crohn's disease]. GASTROENTEROLOGIA Y HEPATOLOGIA 2003; 26:300-2. [PMID: 12732103 DOI: 10.1016/s0210-5705(03)70361-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
It has been suggested that pancreatitis could be an extrahepatic manifestation of inflammatory bowel disease, since its incidence in this disease is greater than that in the general population and in many cases no etiological factor is found. We present a case of chronic idiopathic pancreatitis as the initial presentation of Crohn's disease of the colon.
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Affiliation(s)
- M D Antón
- Servicio de Aparato Digestivo. Hospital Dr. Peset. Valencia. Spain
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Huang C, Lichtenstein DR. Pancreatic and biliary tract disorders in inflammatory bowel disease. Gastrointest Endosc Clin N Am 2002; 12:535-59. [PMID: 12486943 DOI: 10.1016/s1052-5157(02)00009-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Hepatobiliary disorders occur frequently in patients with IBD, with PSC and cholangiocarcinoma being the most clinically significant for endoscopists. Endoscopic therapy for PSC is effective in improving symptoms, biochemical parameters, and radiographic abnormalities. Endoscopic therapy may also confer survival benefit, but this has yet to be confirmed in randomized, controlled trials. Treatment should be restricted to those individuals with a rapid decline in liver function testing or those with recurrent cholangitis. Cholangiocarcinoma is a serious complication of PSC and carries an extremely poor prognosis. ERCP with brush cytology has a relatively low sensitivity and the diagnosis is usually made after the disease has become metastatic. Malignant biliary obstruction can be palliated by endoscopic stenting. Photodynamic therapy is a promising experimental technique that may confer symptomatic and survival benefit in patients with nonresectable, advanced cholangiocarcinoma. IBD patients also have an elevated risk for developing acute and chronic pancreatitis as well as pancreatic insufficiency. The majority of cases of acute pancreatitis are likely due to medication side effects and local structural complications of IBD. The remainder may possibly represent true extraintestinal manifestations of IBD. Chronic pancreatitis is frequently subclinical, but may be accompanied by clinically relevant exocrine insufficiency. ERCP is the test of choice for the diagnosis of chronic pancreatitis, but the role of endoscopy in the therapeutic management of IBD-associated chronic pancreatitis remains to be defined.
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Affiliation(s)
- Christopher Huang
- Boston University School of Medicine, Boston Medical Center, Section of Gastroenterology, 88 East Newton Street, Boston, MA 02118, USA
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Kugathasan S, Halabi I, Telega G, Werlin SL. Pancreatitis as a presenting manifestation of pediatric Crohn's disease: a report of three cases. J Pediatr Gastroenterol Nutr 2002; 35:96-8. [PMID: 12142820 DOI: 10.1097/00005176-200207000-00022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Subra Kugathasan
- Division of Gastroenterology & Nutrition, Department of Pediatrics, Medical College of Wisconsin, The Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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Le Large-Guiheneuf C, Hugot JP, Faure C, Munck A, Mougenot JF, Navarro J, Cézard JP. [Pancreatic involvement in inflammatory bowel diseases in children]. Arch Pediatr 2002; 9:469-77. [PMID: 12053540 DOI: 10.1016/s0929-693x(01)00828-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
UNLABELLED Pancreatitis in inflammatory bowel disease (IBD) in children is anecdotal. In adults, symptomatic pancreatitis occurs in 2% and asymptomatic in 8 to 21%. PATIENTS AND METHODS The aim of our study was to review retrospectively the frequency of pancreatitis in 124 pediatric patients (54.8% boys, 45.2% girls; 97 with Crohn disease, 16 with ulcerative colitis and 11 with undetermined colitis). Diagnostic criterion of pancreatitis was an increase of amylasemia > or = +2 SD of the normal with or without evocative clinical symptoms. RESULTS Symptomatic or asymptomatic pancreatitis was found in 27% (respectively 14.5 and 12.5%). Pancreatitis was significantly more frequent in girls as compared to boys (P = 0.04). Symptomatic pancreatitis was moderate and non complicated, often recurrent. It occurred mainly during active and severe diseases (P = 0.006). The localizations of IBD were not discriminant. Strong relation with drug was found in 25% of pancreatitis mainly due to azathioprine or 5-aminosalicylic acid, and salazopyrin. Duodenal localisation of Crohn disease or hepatobiliary complications were found associated with pancreatitis in 18% and 15% respectively. CONCLUSION These data suggest the high incidence of symptomatic and asymptomatic pancreatitis in children with IBD, the importance of its regular monitoring but also its multifactorial causes. Precise diagnosis of pancreatitis in pediatric IBD has to be done in order to avoid inappropriate drug pancreatitis diagnosis.
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Affiliation(s)
- C Le Large-Guiheneuf
- Service de gastroentérologie et nutrition pédiatriques, hôpital Robert-Debré, 48, Bd Sérurier 75019 Paris, France
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Sáez J, Martínez J, García C, Griñó P, Pérez-Mateo M. Idiopathic pancreatitis associated with ulcerative colitis. Am J Gastroenterol 2000; 95:3004-5. [PMID: 11051402 DOI: 10.1111/j.1572-0241.2000.03229.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Herrlinger KR, Stange EF. The pancreas and inflammatory bowel diseases. INTERNATIONAL JOURNAL OF PANCREATOLOGY : OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION OF PANCREATOLOGY 2000; 27:171-9. [PMID: 10952399 DOI: 10.1385/ijgc:27:3:171] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This article reviews the literature and gives an overview on prevalence and possible explanations for pancreatic involvement in inflammatory bowel diseases (IBD). IBD patients have a markedly elevated risk for developing acute pancreatitis as well as pancreatic insufficiency. Multiple potential causes for pancreatitis in IBD patients exist. In the majority of cases acute pancreatitis appears to be related to drug side effects or local structural complications rather than a true extraintestinal manifestation of IBD. Nevertheless, some cases of acute pancreatitis remain unexplained. Prevalence of chronic pancreatitis in IBD patients also seems to be relatively high. However, etiology of pancreatic duct changes and/or the occurrence of exocrine insufficiency remain unclear. In most cases chronic pancreatitis is clinically unapparent, although in some patients it may be accompanied by clinically relevant exocrine insufficiency.
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Affiliation(s)
- K R Herrlinger
- Department of Internal Medicine, Medical University of Luebeck, Germany.
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Abstract
This paper reviews the role of pancreatic proteases (focusing upon trypsin, chymotrypsin and elastase) in the diagnosis and management of chronic pancreatic insufficiency (CPI), emphasizing advances over the last 5 years. Some important novel aspects of these enzymes in acute pancreatitis are also described, including their role in diagnosis and their interaction with cholecystokinin in the pathogenesis of the disease. The recent interest in these enzymes as agents promoting the spread of cancer in animals and human subjects is also described. A hierarchical approach has been taken to explore the advantages and limitations of tests in different source materials: serum, feces, duodenal aspirate, and non-invasive pancreatic function tests. The practical usefulness of fecal elastase-1 and of fecal chymotrypsin concentrations in diagnosis and management of CPI, respectively, is one of the major lessons to be learned from analysis of the recent literature, and forms the principal message of this review.
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Affiliation(s)
- D M Goldberg
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College Street, Toronto, Canada.
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Barthet M, Hastier P, Bernard JP, Bordes G, Frederick J, Allio S, Mambrini P, Saint-Paul MC, Delmont JP, Salducci J, Grimaud JC, Sahel J. Chronic pancreatitis and inflammatory bowel disease: true or coincidental association? Am J Gastroenterol 1999; 94:2141-8. [PMID: 10445541 DOI: 10.1111/j.1572-0241.1999.01287.x] [Citation(s) in RCA: 93] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Several cases of pancreatitis have been described during the course of Crohn's disease (CD) or ulcerative colitis (UC), but many of them were related to either biliary lithiasis or drug intake. We tried to evaluate the clinical and morphological features of so-called idiopathic pancreatitis associated with inflammatory bowel disease and to define their pathological characteristics. METHODS Chronic idiopathic pancreatitis was diagnosed on the basis of abnormal pancreatograms suggestive of chronic pancreatitis associated with or without impaired exocrine pancreatic function, or pathological examination in patients undergoing pancreatic resection. We found 6 patients presenting with features of chronic idiopathic pancreatitis and UC and 2 patients with CD seen between 1981 and 1996 in three hospital centers of the south of France. A review of the literature has identified 6 cases of pancreatitis associated with UC and 14 cases of pancreatitis associated with CD based on the above criteria. RESULTS Hyperamylasemia was not a sensitive test since it was present in 44% and 64% of patients with UC or CD. In UC, pancreatitis was a prior manifestation in 58% of patients. In contrast, the pancreatitis appeared after the onset of CD in 56% of the cases. In patients with UC, pancreatitis were associated with severe disease revealed by pancolitis (42%) and subsequent surgery. Bile duct involvement was more frequent in patients with UC than with CD (58% vs 12%) mostly in the absence of sclerosing cholangitis (16% vs 6%). Weight loss and pancreatic duct stenosis were also more frequent in UC than in CD (41% vs 12% and 50% vs 23%, respectively). Pathological specimens were analyzed in 5 patients and demonstrated the presence of inter- and intralobular fibrosis with marked acinar regression in 3 and the presence of granulomas in 2 patients, both with CD. CONCLUSIONS Pancreatitis is a rare extraintestinal manifestation of inflammatory bowel disease. Chronic pancreatitis associated with UC differs from that observed in CD by the presence of more frequent bile duct involvement, weight loss, and pancreatic duct stenosis, possibly giving a pseudotumor pattern.
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Affiliation(s)
- M Barthet
- Department of Gastroenterology, Hopital Nord, Marseille, France
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Heikius B, Niemelä S, Lehtola J, Karttunen TJ. Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease. Am J Gastroenterol 1999; 94:1062-9. [PMID: 10201484 DOI: 10.1111/j.1572-0241.1999.01015.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Our aim was to perform a cross-sectional study to estimate the prevalence of elevated pancreatic enzymes in patients with inflammatory bowel disease and to correlate the enzyme activities with clinical, endoscopic, and histological findings. METHODS Two hundred thirty-seven patients diagnosed with inflammatory bowel disease (IBD), including a subgroup with known hepatobiliary disease, were studied crosssectionally. Serum and urinary pancreatic enzymes were prospectively sampled and compared to endoscopic and histological findings obtained previously. RESULTS Hyperamylasemia was found in 11% and hyperlipasemia in 7% of the total study group. The corresponding prevalences in patients with Crohn's disease were 17% and 9%, those in ulcerative colitis 9% and 7%, and those in indeterminate colitis 10% and 5%, respectively. High levels of serum amylase and pancreatic isoamylase were associated with extensive colonic disease (p < 0.005) and high histological activity (p < 0.05). Amylase, but not lipase, was significantly elevated in patients with primary sclerosing cholangitis. Smokers showed higher urinary amylase levels than non- and ex-smokers. The use of medication had no influence on the enzyme levels. CONCLUSIONS Pancreatic enzymes are elevated in a significant proportion of patients with IBD, and the enzyme increase is associated with a more extensive and active disease, and in some cases with primary sclerosing cholangitis.
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Affiliation(s)
- B Heikius
- Department of Internal Medicine, University Hospital of Oulu, Finland
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Takizawa H, Natsui M, Aoyagi Y, Asakura H. Pancreatitis in ulcerative colitis: a case report of improved stricture of the main pancreatic duct. J Clin Gastroenterol 1999; 28:74-6. [PMID: 9916675 DOI: 10.1097/00004836-199901000-00020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
We present one case with pancreatitis that synchronized with manifestations of ulcerative colitis, in which an improvement of stricture of the main pancreatic duct was observed. A 27-year-old man, having a history of nonalcoholic acute pancreatitis, complained of anal bleeding and pain in the epigastric region. The treatment for pancreatitis relieved the pain and decreased the serum levels of pancreatic enzymes to within normal ranges. Colonoscopy and histopathologic examination revealed ulcerative colitis in the rectum, and treatment with steroid enema made proctitis quiescent. Endoscopic retrograde pancreatography demonstrated a remarkable and short stricture of the main pancreatic duct, which improved at follow-up pancreatography. In a 20-month follow-up period, active proctitis relapsed with a episode of recurrent pancreatitis once, and without pancreatitis once.
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Affiliation(s)
- H Takizawa
- Department of Internal Medicine, Kido Hospital, Niigata, Japan
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Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, Sato F, Kato T, Kohli Y, Kuriyama M. Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 1997; 35:1710-4. [PMID: 9196179 PMCID: PMC229827 DOI: 10.1128/jcm.35.7.1710-1714.1997] [Citation(s) in RCA: 201] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.
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Affiliation(s)
- Y Ito
- Second Department of Internal Medicine, Fukui Medical School, Yoshida-gun, Japan
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Heikius B, Niemelä S, Lehtola J, Karttunen T, Lähde S. Hepatobiliary and coexisting pancreatic duct abnormalities in patients with inflammatory bowel disease. Scand J Gastroenterol 1997; 32:153-61. [PMID: 9051876 DOI: 10.3109/00365529709000186] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND We performed a cross-sectional study to evaluate the prevalence of hepatobiliary disease in unselected patients with inflammatory bowel disease (IBD), to estimate the frequency of coexisting cholangiographic and pancreatographic duct abnormalities, and to correlate the findings with clinical, endoscopic, and histologic variables. METHODS We screened 237 IBD patients for increased liver function values. Further, hepatobiliary evaluation consisted of transabdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), and a liver biopsy. In addition, we evaluated the ERCP findings of patients with abnormal pancreatic screening tests (pancreatic enzymes or para-aminobenzoic acid excretion). RESULTS Laboratory signs of hepatobiliary disease were found in 37 (16%) of our IBD patients. Abnormal liver test results were commoner in patients with Crohn's disease (CD) than in patients with ulcerative colitis (UC) (30.4% versus 11.2%, P < 0.05), and a similar trend was observed in the frequency of primary sclerosing cholangitis (PSC) in the respective groups of IBD patients. When the ERCP findings were combined with liver histology, 26 (11% of the whole study group) patients with PSC were found, with small-duct disease included. In 23 (10% of the whole study group) patients, definite cholangiographic changes consistent with PSC were found. Eleven (48%) of these showed coexisting pancreatic duct abnormalities. The prevalence of coexisting cholangiographic and pancreatographic duct changes in the whole study group was 4.6%. CONCLUSION Hepatobiliary disease is at least equally common in patients with UC and CD. Coexisting cholangiographic and pancreatographic duct abnormalities in patients with IBD are relatively frequent and are considered extraintestinal manifestations of IBD.
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Affiliation(s)
- B Heikius
- Dept. of Internal Medicine, University Hospital of Oulu, Finland
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