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Tang C, Zhou J, Song Y, Liu S. Etiologies of exocrine pancreatic insufficiency. Gastroenterol Rep (Oxf) 2025; 13:goaf019. [PMID: 40066317 PMCID: PMC11893156 DOI: 10.1093/gastro/goaf019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/30/2024] [Accepted: 11/12/2024] [Indexed: 04/11/2025] Open
Abstract
Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.
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Affiliation(s)
- Chengji Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
| | - Jia Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
- Central Laboratory of Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P. R. China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P. R. China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
- Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha, Hunan, P. R. China
- Hunan Key Laboratory for the Prevention and Treatment of Biliary Tract Diseases, Changsha, Hunan, P. R. China
- Research Center for Hepatobiliary and Pancreatic Diseases of Furong Laboratory, Changsha, Hunan, P. R. China
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Pan J, Li Z, Ye C, Zhang X, Yang Q, Zhang X, Zhou Y, Zhang J. Mesalazine-Induced Acute Pancreatitis in Inflammatory Bowel Disease Patients: A Systematic Review. Ther Clin Risk Manag 2025; 21:113-123. [PMID: 39897345 PMCID: PMC11784256 DOI: 10.2147/tcrm.s493371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/13/2025] [Indexed: 02/04/2025] Open
Abstract
Objective Mesalazine is a widely used medication for treating mild to moderate inflammatory bowel disease (IBD). First identified as a potential cause of acute pancreatitis (AP) in 1989, the link between mesalazine and AP has primarily been established through case reports and a limited number of retrospective studies. This study aims to explore the characteristics of mesalazine-induced AP. Methods The databases of CNKI, Wanfang Data, VIP, PubMed and Web of Science were searched (up to March, 2024), and the case reports of mesalazine-related AP in IBD patients were collected and descriptively analyzed. Results Thirty-four reports were included, describing 42 patients (22 males, 16 females, 4 unspecified) with mesalazine-related AP. The onset of pancreatitis occurred a median of 14 days (range 1-730 days) after starting mesalazine. Common symptoms included abdominal pain (100%), vomiting (38.1%), fever (21.4%), and nausea (21.4%). Most patients had elevated serum amylase and lipase levels, with some showing raised C-reactive protein and erythrocyte sedimentation rate. Imaging tests, such as computed tomography and B-scan ultrasonography, revealed edematous infiltration and inflammation. Discontinuation of mesalazine led to symptom resolution in all patients, with 93.3% improving within a week. Alternative treatments or switching to other forms of 5-aminosalicylic acid may be considered for ongoing management. Rechallenge with mesalazine led to recurrence of AP in 21 cases, with a shorter median time to symptom onset. Conclusion Mesalazine-induced AP is a rare but significant adverse reaction, not related to drug dosage, and can occur at any point during treatment, typically within two weeks. The reaction can recur upon rechallenge. Discontinuation of mesalazine and symptomatic treatment typically resolves the condition.
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Affiliation(s)
- Juan Pan
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, 410300, People’s Republic of China
| | - Zuyi Li
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, 410300, People’s Republic of China
| | - Chao Ye
- Department of Pharmacy, Guangdong Provincial second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, Guangdong, 510095, People’s Republic of China
| | - Xiaojuan Zhang
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, 410300, People’s Republic of China
| | - Qiongliang Yang
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, 410300, People’s Republic of China
| | - Xu Zhang
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, 410300, People’s Republic of China
| | - Ya Zhou
- Department of Pharmacy, People’s Hospital of Ningxiang City Affiliated to Hunan University of Chinese Medicine, Changsha, Hunan, 410600, People’s Republic of China
| | - Jianjun Zhang
- Department of Pharmacy, Guangdong Provincial second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, Guangdong, 510095, People’s Republic of China
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Kurebayashi M, Hashimoto A, Kawachi M, Sawai S, Ono T, Tahara Y, Kuroda N, Yoshizawa N, Fuke H, Shimizu A. A case of ulcerative colitis with a variety of autoimmune diseases including ankylosing spondylitis, type 2 autoimmune pancreatitis, and primary sclerosing cholangitis. Clin J Gastroenterol 2024; 17:928-935. [PMID: 38861196 DOI: 10.1007/s12328-024-02001-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 06/05/2024] [Indexed: 06/12/2024]
Abstract
Ankylosing spondylitis (AS), primary sclerosing cholangitis (PSC), and autoimmune pancreatitis (AIP) are known as extraintestinal manifestations (EIMs) of ulcerative colitis (UC). A 74-year-old Japanese man visited our hospital because of white stool. He had been diagnosed with AS when he was 30 years old, and he was HLA-B27-positive. Based on various examination results, it was suspected that AIP had caused bile duct stricture. During the clinical course, he was diagnosed with UC and PSC. Then, AIP was diagnosed because he had localized pancreatic enlargement, irregular stenosis of the main pancreatic duct, PSC, and no tumor cells of pancreas. A patient with all four of these diseases, AS, AIP, PSC, and UC, is very rare. Therefore, we report a quite rare case with three EIMs (AS, PSC, and AIP) of UC.
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Affiliation(s)
- Marie Kurebayashi
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan.
| | - Akira Hashimoto
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Mizuki Kawachi
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Shoma Sawai
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Takahiro Ono
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Yuichi Tahara
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Naoki Kuroda
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Naohiko Yoshizawa
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Hiroyuki Fuke
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Atsuya Shimizu
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
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Yang T, Feng J, Yao R, Feng Q, Shen J. CT-based pancreatic radiomics predicts secondary loss of response to infliximab in biologically naïve patients with Crohn's disease. Insights Imaging 2024; 15:69. [PMID: 38472447 DOI: 10.1186/s13244-024-01637-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 01/27/2024] [Indexed: 03/14/2024] Open
Abstract
OBJECTIVES Predicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn's disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD. METHODS Three models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation. RESULTS In total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872. CONCLUSIONS The first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients. CRITICAL RELEVANCE STATEMENT This study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD. KEY POINTS • The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn's disease. • The model achieved satisfactory predictive accuracy, calibration ability, and clinical value. • The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens.
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Affiliation(s)
- Tian Yang
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai, 200127, China
- NHC Key Laboratory of Digestive Diseases (Renji Hospital, Shanghai Jiaotong University School of Medicine), Shanghai, China
| | - Jing Feng
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai, 200127, China
- NHC Key Laboratory of Digestive Diseases (Renji Hospital, Shanghai Jiaotong University School of Medicine), Shanghai, China
| | - Ruchen Yao
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai, 200127, China
- NHC Key Laboratory of Digestive Diseases (Renji Hospital, Shanghai Jiaotong University School of Medicine), Shanghai, China
| | - Qi Feng
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu Jian Road, Shanghai, 200127, China.
| | - Jun Shen
- Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai, 200127, China.
- NHC Key Laboratory of Digestive Diseases (Renji Hospital, Shanghai Jiaotong University School of Medicine), Shanghai, China.
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Fujita Y, Tominaga K, Tanaka T, Yamamiya A, Irisawa A, Ishida K, Ishige T, Yoshihara S. Acute Pancreatitis Leading to the Diagnosis of Presymptomatic Crohn's Disease: A Pediatric Case Report. Cureus 2024; 16:e53397. [PMID: 38435224 PMCID: PMC10908432 DOI: 10.7759/cureus.53397] [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: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
A 14-year-old boy presented with fever and abdominal pain and was diagnosed with acute pancreatitis based on computed tomography findings. The patient had neither diarrhea nor bloody stool but was diagnosed with microcytic anemia. Endoscopic examination revealed a cobblestone pattern and longitudinal ulcer scars in the jejunum. However, no abnormal findings were observed in the ileum or colon. Endoscopic ultrasound-guided fine-needle aspiration was performed from pancreatic body-tail. Pathological examination revealed no evidence of autoimmune pancreatitis (AIP). It was unclear from pathological examination whether idiopathic pancreatitis had self-limitedly improved or whether it was AIP localized to the pancreatic head. The patient was diagnosed with asymptomatic small-bowel Crohn's disease (CD), which may have been two unrelated events of acute pancreatitis. Acute pancreatitis may precede a diagnosis of inflammatory bowel disease. CD with only jejunal involvement (Montreal classification L4) is extremely rare, and we were able to diagnose it early.
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Affiliation(s)
- Yuji Fujita
- Department of Pediatrics, Dokkyo Medical University, Mibu, JPN
| | - Keiichi Tominaga
- Department of Gastroenterology, Dokkyo Medical University, Mibu, JPN
| | - Takanao Tanaka
- Department of Gastroenterology, Dokkyo Medical University, Mibu, JPN
| | - Akira Yamamiya
- Department of Gastroenterology, Dokkyo Medical University, Mibu, JPN
| | - Atsushi Irisawa
- Department of Gastroenterology, Dokkyo Medical University, Mibu, JPN
| | - Kazuyuki Ishida
- Department of Diagnostic Pathology, Dokkyo Medical University, Mibu, JPN
| | - Takashi Ishige
- Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, JPN
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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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Moroi R, Tarasawa K, Ikeda M, Matsumoto R, Shimoyama Y, Naito T, Takikawa T, Shiga H, Hamada S, Kakuta Y, Kikuta K, Fushimi K, Fujimori K, Kinouchi Y, Masamune A. Severity of acute pancreatitis in patients with inflammatory bowel disease in the era of biologics: A propensity-score-matched analysis using a nationwide database in Japan. JGH Open 2022; 7:40-47. [PMID: 36660049 PMCID: PMC9840197 DOI: 10.1002/jgh3.12849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/04/2022] [Accepted: 11/18/2022] [Indexed: 12/31/2022]
Abstract
Background and Aim Acute pancreatitis (AP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD). Several studies from Western countries have reported that the severity of AP in patients with IBD is similar to that in the general population; however, its severity in patients from Eastern countries in the era of biologics remains unclear. This study aimed to investigate the severity of AP in patients with IBD and the effect of biologics on the severity of AP using a nationwide database. Methods We divided 1138 eligible AP admissions from the Diagnosis Procedure Combination database system into IBD and non-IBD groups after propensity score matching, and compared the severity of AP. We divided the IBD group into ulcerative colitis (UC) and Crohn's disease (CD) subgroups and compared each with the non-IBD group. Logistic regression analysis was conducted to identify the clinical factors affecting acute pancreatitis. Results IBD and UC groups had lower rate of severe AP compared to the non-IBD group (13.7% vs 28.3%, P < 0.0001 and 11.0% vs 28.3%, P < 0.0001, respectively). There were no differences in the rates of severe AP between the CD and non-IBD groups. Multivariate analysis showed that biologics did not affect the severity of AP. Conclusion The severity of AP in patients with IBD may be lower than that in the general population; biologics for IBD may not worsen its severity. Further prospective studies are required to clarify the severity of AP in patients with IBD.
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Affiliation(s)
- Rintaro Moroi
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Kunio Tarasawa
- Department of Health Administration and PolicyTohoku University Graduate School of MedicineSendaiJapan
| | - Mio Ikeda
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Ryotaro Matsumoto
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Yusuke Shimoyama
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Takeo Naito
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Tetsuya Takikawa
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Hisashi Shiga
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Shin Hamada
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Yoichi Kakuta
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Kazuhiro Kikuta
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Kiyohide Fushimi
- Department of Health Policy and InformaticsTokyo Medical and Dental University Graduate School of MedicineBunkyo‐kuTokyoJapan
| | - Kenji Fujimori
- Department of Health Administration and PolicyTohoku University Graduate School of MedicineSendaiJapan
| | - Yoshitaka Kinouchi
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
| | - Atsushi Masamune
- Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
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8
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Dohos D, Farkas N, Váradi A, Erőss B, Párniczky A, Szentesi A, Hegyi P, Sarlós P. Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis. Pancreatology 2022; 22:1071-1078. [PMID: 36202731 DOI: 10.1016/j.pan.2022.09.241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/30/2022] [Accepted: 09/17/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVE AND AIMS Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases. DESIGN We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease. RESULTS No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease. CONCLUSION No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.
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Affiliation(s)
- Dóra Dohos
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Centre, University of Pécs, Pécs, Hungary; Heim Pál National Institute of Pediatrics, Budapest, Hungary
| | - Nelli Farkas
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Alex Váradi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Andrea Párniczky
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Institute of Pediatrics, Budapest, Hungary
| | - Andrea Szentesi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Centre, University of Pécs, Pécs, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Patrícia Sarlós
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Hungary.
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Massironi S, Fanetti I, Viganò C, Pirola L, Fichera M, Cristoferi L, Capurso G, Invernizzi P, Danese S. Systematic review-pancreatic involvement in inflammatory bowel disease. Aliment Pharmacol Ther 2022; 55:1478-1491. [PMID: 35505465 PMCID: PMC9322673 DOI: 10.1111/apt.16949] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/28/2022] [Accepted: 04/18/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous. METHOD PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD. RESULTS Four thousand one hundred and twenty-one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune-mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting. CONCLUSION This is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible.
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Affiliation(s)
- Sara Massironi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Ilaria Fanetti
- Gastroenterology and Endoscopy Unit, ASST Ovest MilaneseLegnano HospitalLegnanoItaly
| | - Chiara Viganò
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Lorena Pirola
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Maria Fichera
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Laura Cristoferi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Gabriele Capurso
- Pancreas Translational & Clinical Research Center, Pancreato‐Biliary Endoscopy & Endosonography DivisionSan Raffaele Scientific Institute IRCCSMilanItaly
| | - Pietro Invernizzi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Silvio Danese
- Gastroenterology and EndoscopyIRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele UniversityMilanItaly
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Freitas M, Lima Capela T, Macedo Silva V, Arieira C, Cúrdia Gonçalves T, Dias de Castro F, Moreira MJ, Firmino-Machado J, Cotter J. Finding Predictors of Azathioprine-Induced Pancreatitis in Patients With Inflammatory Bowel Disease. Pancreas 2022; 51:288-294. [PMID: 35584388 DOI: 10.1097/mpa.0000000000002012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP. METHODS A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered. RESULTS Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP. CONCLUSIONS Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.
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Hosoi K, Minowa K, Suzuki M, Kudo T, Ohtsuka Y, Tomomasa T, Tajiri H, Ishige T, Yamada H, Arai K, Yoden A, Ushijima K, Aomatsu T, Nagata S, Uchida K, Takeuchi K, Shimizu T. Characteristics and Frequency of Pediatric Inflammatory Bowel Disease-Associated Pancreatitis: A Japanese Nationwide Survey. JPGN REPORTS 2022; 3:e162. [PMID: 37168759 PMCID: PMC10158371 DOI: 10.1097/pg9.0000000000000162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 11/03/2021] [Indexed: 05/13/2023]
Abstract
Acute pancreatitis (AP) develops in approximately 2% of patients with the diagnosis of inflammatory bowel disease (IBD), but the characteristics and frequency of childhood-onset IBD-associated AP in Japan have not been studied. The present study aimed to clarify the characteristics of IBD-associated AP in Japan. Methods A nationwide survey of pediatric patients with IBD (age, <17 years) was conducted from December 2012 to March 2013 at 683 hospitals and medical centers in Japan. A secondary survey was also sent to the centers with the target patients to evaluate their characteristics. Results The response rate to the first part of the survey was 61.2% (n = 418). In total, 871 patients with Crohn disease and 1671 patients with ulcerative colitis were enrolled. The second part of the survey found that 11 (1.3%) patients with Crohn disease and 23 (1.4%) patients with ulcerative colitis experienced IBD-associated AP caused by medication (n = 18, 53%), a primary disease (n = 11, 32%), autoimmune pancreatitis (n = 1, 3%), or an anatomical abnormality (n = 1, 3%). All the patients had only mild AP. Conclusions IBD-associated AP was not very frequent and was generally mild. The major cause of the pancreatitis was the medication used to treat the IBD.
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Affiliation(s)
- Kenji Hosoi
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
- Division of Gastroenterology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
| | - Kei Minowa
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mitsuyoshi Suzuki
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
| | - Takahiro Kudo
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
| | - Yoshikazu Ohtsuka
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
| | - Takeshi Tomomasa
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- PAL Children’s Clinic, Gunma, Japan
| | - Hitoshi Tajiri
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Kinki University Faculty of Medicine, Osaka, Japan
| | - Takashi Ishige
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Hiroyuki Yamada
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Osaka Hospital, Japan Community of Healthcare Organization, Osaka, Japan
| | - Katsuhiro Arai
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Atsushi Yoden
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
- Department of Pediatrics, Dainikyoritsu Hospital, Hyogo, Japan
| | - Kosuke Ushijima
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics and Child Health, Kurume University, Fukuoka, Japan
| | - Tomoki Aomatsu
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Satoru Nagata
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Pediatrics, Tokyo Women’s Medical University Hospital, Tokyo, Japan
| | - Keiichi Uchida
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Mie, Japan
| | - Kazuo Takeuchi
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
- General Health Support Center, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Toshiaki Shimizu
- From the Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
- Members of the Japanese Society for Pediatric Inflammatory Bowel Disease Working Group
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Montenegro ML, Corral JE, Lukens FJ, Ji B, Kröner PT, Farraye FA, Bi Y. Pancreatic Disorders in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2022; 67:423-436. [PMID: 33625614 DOI: 10.1007/s10620-021-06899-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 02/08/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) can involve multiple organ systems, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases is more frequent in patients with Crohn's disease and ulcerative colitis than in the general population. Pancreatic manifestations in IBD include a heterogeneous group of disorders and abnormalities ranging from mild, self-limited disorders to severe diseases. Asymptomatic elevation of amylase and/or lipase is common. The risk of acute pancreatitis in patients with IBD is increased due to the higher incidence of cholelithiasis and drug-induced pancreatitis in this population. Patients with IBD commonly have altered pancreatic histology and chronic pancreatic exocrine dysfunction. Diagnosing acute pancreatitis in patients with IBD is challenging. In this review, we discuss the manifestations and possible causes of pancreatic abnormalities in patients with IBD.
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Affiliation(s)
- Marilia L Montenegro
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Juan E Corral
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Frank J Lukens
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Baoan Ji
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
| | - Paul T Kröner
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Yan Bi
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
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Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Gastroenterology 2021; 161:1118-1132. [PMID: 34358489 PMCID: PMC8564770 DOI: 10.1053/j.gastro.2021.07.042] [Citation(s) in RCA: 431] [Impact Index Per Article: 107.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 07/28/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.
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Affiliation(s)
- Gerhard Rogler
- Department of Gastroenterology & Hepatology, Department of Medicine, Zurich University Hospital, Zurich, Switzerland
| | - Abha Singh
- University of California, San Diego, La Jolla, CA, USA
| | | | - David T. Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
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14
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Pancreatic Disorders in Children with Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2021; 57:medicina57050473. [PMID: 34064706 PMCID: PMC8151997 DOI: 10.3390/medicina57050473] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/26/2021] [Accepted: 05/09/2021] [Indexed: 02/06/2023]
Abstract
Background and Objectives: Inflammatory bowel disease (IBD) is a chronic condition and mainly affects the intestines, however, the involvement of the other organs of the gastrointestinal tract (upper part, pancreas, and liver) have been observed. The coexistence of IBD with pancreatic pathology is rare, however, it has been diagnosed more frequently during recent years in the pediatric population. This article reviews the current literature on the most common pancreatic diseases associated with IBD in the pediatric population and their relationship with IBD activity and treatment. Materials and Methods: We performed a systematic review of data from published studies on pancreatic disorders, also reported as extraintestinal manifestations (EIMs), among children with IBD. We searched PubMed and Web of Science to identify eligible studies published prior to 25 April 2020. Results: Forty-four papers were chosen for analysis after a detailed inspection, which aimed to keep only the research studies (case control studies and cohort studies) or case reports on children and only those which were written in English. The manifestations of IBD-associated pancreatic disorders range from asymptomatic increase in pancreatic enzymes activity to severe disease such as acute pancreatitis. Acute pancreatitis (AP) induced by drugs, mainly thiopurine, seems to be the most- often-reported pancreatic disease associated with IBD in children. AP associated with other than drug etiologies, and chronic pancreatitis (CP), are rarely observed in the course of pediatric IBD. The pancreatic involvement can be strictly related to the activity of IBD and can also precede the diagnosis of IBD in some pediatric patients. The course of AP is mild in most cases and may occasionally lead to the development of CP, mainly in cases with a genetic predisposition. Conclusions: The involvement of the pancreas in the course of IBD may be considered as an EIM or a separate co-morbid disease, but it can also be a side effect of IBD therapy, therefore a differential diagnosis should always be performed. As the number of IBD incidences with concomitant pancreatic diseases is constantly increasing in the pediatric population, it is important to include pancreatic enzymes level measurement in the workup of IBD.
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15
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Forman MA, Steiner JM, Armstrong PJ, Camus MS, Gaschen L, Hill SL, Mansfield CS, Steiger K. ACVIM consensus statement on pancreatitis in cats. J Vet Intern Med 2021; 35:703-723. [PMID: 33587762 PMCID: PMC7995362 DOI: 10.1111/jvim.16053] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 12/16/2022] Open
Abstract
Background Pancreatitis in cats, although commonly diagnosed, still presents many diagnostic and management challenges. Objective To summarize the current literature as it relates to etiology, pathogenesis, diagnosis, and management of pancreatitis in cats and to arrive at clinically relevant suggestions for veterinary clinicians that are based on evidence, and where such evidence is lacking, based on consensus of experts in the field. Animals None. Methods A panel of 8 experts in the field (5 internists, 1 radiologist, 1 clinical pathologist, and 1 anatomic pathologist), with support from a librarian, was formed to assess and summarize evidence in the peer reviewed literature and complement it with consensus clinical recommendations. Results There was little literature on the etiology and pathogenesis of spontaneous pancreatitis in cats, but there was much in the literature about the disease in humans, along with some experimental evidence in cats and nonfeline species. Most evidence was in the area of diagnosis of pancreatitis in cats, which was summarized carefully. In contrast, there was little evidence on the management of pancreatitis in cats. Conclusions and Clinical Importance Pancreatitis is amenable to antemortem diagnosis by integrating all clinical and diagnostic information available, and recognizing that acute pancreatitis is far easier to diagnose than chronic pancreatitis. Although both forms of pancreatitis can be managed successfully in many cats, management measures are far less clearly defined for chronic pancreatitis.
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Affiliation(s)
- Marnin A Forman
- Cornell University Veterinary Specialists, Stamford, Connecticut, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | - P Jane Armstrong
- College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA
| | - Melinda S Camus
- Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
| | - Lorrie Gaschen
- Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Louisiana, USA
| | - Steve L Hill
- Flagstaff Veterinary Internal Medicine Consulting, Flagstaff, Arizona, USA
| | | | - Katja Steiger
- Institute of Pathology, School of Medicine, Technical University of Munich, Munich, Germany
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Pitchumoni CS. Acute Pancreatitis. GERIATRIC GASTROENTEROLOGY 2021:1449-1481. [DOI: 10.1007/978-3-030-30192-7_55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Benign Duodenal Stricture Treated with Surgical Correction and Dietary Therapy in a Golden Retriever. Case Rep Vet Med 2020; 2020:4283175. [PMID: 32318308 PMCID: PMC7165342 DOI: 10.1155/2020/4283175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 03/11/2020] [Indexed: 11/18/2022] Open
Abstract
A benign duodenal stricture is a well-documented condition of humans that has not been characterized in dogs. In this case report, the clinical, radiographic, ultrasonographic, endoscopic, surgical, and histopathologic findings of a single benign duodenal stricture in a Golden Retriever are reported. Definitive diagnosis was made possible with the utilization of esophagogastroduodenoscopy (EGD). Surgical correction of the stricture, paired with dietary therapy that utilized a highly digestible diet, resolved the clinical signs in the case reported. Several inciting causes were identified as possible drivers of stricture formation, including nonsteroidal anti-inflammatory drug (NSAID) administration, mucosal ulceration, traumatic injury, or inflammatory intestinal disease. A benign duodenal stricture should be considered an infrequent cause of intermittent, chronic gastrointestinal signs that may have a favorable outcome via surgical correction and dietary management.
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18
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Unusual intestinal and extra intestinal findings in Crohn's disease seen on abdominal computed tomography and magnetic resonance enterography. Clin Imaging 2020; 59:30-38. [PMID: 31715515 DOI: 10.1016/j.clinimag.2019.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 04/09/2019] [Accepted: 04/22/2019] [Indexed: 01/16/2023]
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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, Katsanos KH, Theopistos VI, Baltayiannis G, Kosmidou M, Glantzounis G, Christou L, Tsianos EV, Christodoulou DK. Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study. BMC Gastroenterol 2019; 19:48. [PMID: 30943899 PMCID: PMC6446300 DOI: 10.1186/s12876-019-0967-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/27/2019] [Indexed: 02/04/2023] Open
Abstract
Background Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn’s disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used. Methods Data were retrospectively extracted from the clinical records of patients followed up at our tertiary IBD referral Center. Results Our study included 602 IBD patients, with liver function tests at regular intervals. The mean follow-up was 5.8 years (Std. Dev.: 6.72). Abdominal imaging examinations were present in 220 patients and revealed findings from the liver, biliary tract and pancreas in 55% of examined patients (120/220). The most frequent findings or manifestations from the liver, biliary tract and pancreas were fatty liver (20%, 44/220), cholelithiasis (14.5%, 32/220) and acute pancreatitis (0.6%, 4/602), respectively. There were 7 patients with primary sclerosing cholangitis. Regarding hepatitis viruses, one-third of the patients had been tested for hepatitis B and C. 5% (12/225) of them had positive hepatitis B surface antigen and 13.4% had past infection with hepatitis B virus (positive anti-HBcore). In addition, most of the patients were not immune against hepatitis B (negative anti-HBs), while 3% of patients were anti-HCV positive and only one patient had active hepatitis C. Furthermore, 24 patients had drug-related side effects from the liver and pancreas. The side effects included 21 cases of hepatotoxicity and 3 cases of acute pancreatitis. Moreover, there were two cases of HBV reactivation and one case of chronic hepatitis C, which were successfully treated. Conclusion In our study, approximately one out of four patients had some kind by a hepatobiliary or pancreatic manifestation. Therefore, it is essential to monitor liver function at regular intervals and differential diagnosis should range from benign diseases and various drug related side effects to severe disorders, such as primary sclerosing cholangitis.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical school and University of Ioannina, Ioannina, Greece
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, Medical school and University of Ioannina, Ioannina, Greece
| | - Vasileios I Theopistos
- Department of Gastroenterology and Hepatology, Medical school and University of Ioannina, Ioannina, Greece
| | - Gerasimos Baltayiannis
- Department of Gastroenterology and Hepatology, Medical school and University of Ioannina, Ioannina, Greece
| | - Maria Kosmidou
- Department of Internal Medicine, Medical school and University of Ioannina, Ioannina, Greece
| | - Georgios Glantzounis
- Department of Surgery, Medical school and University of Ioannina, Ioannina, Greece
| | - Leonidas Christou
- Department of Internal Medicine, Medical school and University of Ioannina, Ioannina, Greece
| | - Epameinondas V Tsianos
- Department of Internal Medicine, Medical school and University of Ioannina, Ioannina, Greece
| | - Dimitrios K Christodoulou
- Department of Gastroenterology and Hepatology, Medical school and University of Ioannina, Ioannina, Greece.
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Almarri N, Alobaidli A, Almarhabi A, Alshammari M. Acute pancreatitis as an initial presentation of Crohn's disease: A case report. J Family Med Prim Care 2019; 8:3752-3754. [PMID: 31803686 PMCID: PMC6881938 DOI: 10.4103/jfmpc.jfmpc_753_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 09/16/2019] [Accepted: 09/30/2019] [Indexed: 12/04/2022] Open
Abstract
Acute pancreatitis (AP) is not commonly known to be an extra-intestinal manifestations of Crohn's disease (CD). Several cases have been reported discussing the relation of AP with CD. However, no specific etiological factors for pancreatitis were found, which appears to support the possibility of a relationship between AP and CD. We report a 30-year-old male present with generalized abdominal pain associated with watery diarrhea. Diagnosis of AP was made. A CT abdomen showed pancreatic inflammation with a terminal ileum thickening. Colonoscopy with multiple biopsy was done for the patient, which confirmed the diagnosis of CD. The patient started on adalimumab for 6 months, showed good response, and became symptomatically free. No recurrent attacks after 2 years of follow-up. The association between AP and CD is not yet clear. Therefore, patients presenting with idiopathic pancreatitis should be investigated to rule out the coexistence of IBD for better outcome.
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Abstract
OBJECTIVES The aim of this study was to analyze causes of drug-induced acute pancreatitis (DIAP) in Korea and factors associated with serious DIAP. METHODS Case records of DIAP voluntarily reported to the Korea Adverse Event Reporting System from 2004 to 2013 were reviewed. When a patient took 2 or more drugs, each drug was identified as a potential cause. The seriousness of each case was determined based on the International Conference on Harmonization E2D Guideline. Logistic regression was performed to identify factors associated with the seriousness of DIAP. RESULTS During the study period, 210 (0.05%) of 442,523 adverse event reports were (0.05%) DIAP. The most common causative medication of the DIAP cases with certain, probable/likely, and possible causality (n = 74) was L-asparaginase (n = 18), followed by azathioprine (n = 6), methylprednisolone (n = 6), and fenofibrate (n = 5). Serious events occurred in 43 cases (58%) with certain, probable/likely, and possible causality. They were significantly associated with the year of report (odds ratio, 0.572; P = 0.025) and the number of concurrently used medications (odds ratio, 2.659; P = 0.006). CONCLUSIONS L-Asparaginase is the most common cause of DIAP in Korea. Serious DIAP is more likely to occur in patients taking multiple medications.
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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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25
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Schneider A, Hirth M, Weiss C, Weidner P, Antoni C, Thomann A, Reindl W, Ebert MP, Pfützer RH. Prevalence of inflammatory bowel disease in alcoholic, non-alcoholic and autoimmune pancreatitis. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2018; 56:469-478. [PMID: 29734447 DOI: 10.1055/s-0043-123881] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown. AIMS Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD. METHODS We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic. RESULTS Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fisher's exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fisher's exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fisher's exact test). CONCLUSIONS Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation.
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Affiliation(s)
- Alexander Schneider
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Christel Weiss
- Department of Medical Statistics, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Christoph Antoni
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Anne Thomann
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Wolfgang Reindl
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
| | - Roland H Pfützer
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany
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Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas. Pancreas 2018; 47:561-567. [PMID: 29683978 DOI: 10.1097/mpa.0000000000001054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). METHODS Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). RESULTS Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. CONCLUSIONS Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.
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Kim SE, Lee JY, Shim KS, Lee S, Min K, Bae JH, Kim HJ, Park K, Song HR. Attenuation of inflammation and cartilage degradation by sulfasalazine-containing hyaluronic acid on osteoarthritis rat model. Int J Biol Macromol 2018; 114:341-348. [PMID: 29548914 DOI: 10.1016/j.ijbiomac.2018.03.059] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/05/2018] [Accepted: 03/12/2018] [Indexed: 01/16/2023]
Abstract
The aim of this study was to investigate the effects of a sulfasalazine-containing hyaluronic acid (SASP/HA) systems on in vitro anti-inflammation and the alleviation of cartilage degradation in both lipopolysaccharide (LPS)-stimulated synoviocytes and a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The SASP/HA resulted in long-term release of SASP from the SASP/HA for up to 60 days in a sustained manner. In vitro studies performed using real-time polymerase chain reaction (PCR) assay revealed that the SASP/HA was able to effectively and dose-dependently inhibit the mRNA expression levels of pro-inflammatory cytokines such as matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-stimulated synoviocytes. In vivo studies showed that intra articular injection of SASP/HA greatly reduced the MIA-stimulated mRNA expression of MMP-3, COX-2, IL-6, and TNF-α in blood. Furthermore, these significant anti-inflammatory effects of SASP/HA contributed markedly to the alleviation of progression of MIA-induced OA and cartilage degradation, as demonstrated by X-ray, micro-computed tomography (micro-CT), gross findings, and histological evaluations. Therefore, our findings indicated that the long-term and sustained delivery of SASP using HA can play a therapeutic role in alleviating inflammation as well as protecting against cartilage damage in OA.
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Affiliation(s)
- Sung Eun Kim
- Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul 08308, Republic of Korea
| | - Jae Yong Lee
- Department of Biomedical Science, Korea University College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Kyu-Sik Shim
- Department of Biomedical Science, Korea University College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Sunghee Lee
- BMI Korea R&D Center, Plant 11, Cheomdanro 7 Gil, Jeju City, Jeju-do 63309, Republic of Korea
| | - Kyoengwoo Min
- BMI Korea R&D Center, Plant 11, Cheomdanro 7 Gil, Jeju City, Jeju-do 63309, Republic of Korea
| | - Ji-Hoon Bae
- Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul 08308, Republic of Korea
| | - Hak-Jun Kim
- Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul 08308, Republic of Korea
| | - Kyeongsoon Park
- Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea.
| | - Hae-Ryong Song
- Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul 08308, Republic of Korea.
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Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr 2018; 66:159-176. [PMID: 29280782 PMCID: PMC5755713 DOI: 10.1097/mpg.0000000000001715] [Citation(s) in RCA: 159] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
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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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DALLAS DAVIDC, SANCTUARY MEGANR, QU YUNYAO, KHAJAVI SHABNAMHAGHIGHAT, VAN ZANDT ALEXANDRIAE, DYANDRA MELISSA, FRESE STEVENA, BARILE DANIELA, GERMAN JBRUCE. Personalizing protein nourishment. Crit Rev Food Sci Nutr 2017; 57:3313-3331. [PMID: 26713355 PMCID: PMC4927412 DOI: 10.1080/10408398.2015.1117412] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Proteins are not equally digestible-their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources, and processing methods must be tailored to the consumer's digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiological conditions alter digestive capacity. Possible solutions to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermentation are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein analysis of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health.
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Affiliation(s)
- DAVID C. DALLAS
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - MEGAN R. SANCTUARY
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - YUNYAO QU
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - SHABNAM HAGHIGHAT KHAJAVI
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Department of Food Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - ALEXANDRIA E. VAN ZANDT
- Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - MELISSA DYANDRA
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - STEVEN A. FRESE
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - DANIELA BARILE
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - J. BRUCE GERMAN
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
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Novel indoline derivatives prevent inflammation and ulceration in dinitro-benzene sulfonic acid-induced colitis in rats. Pharmacol Rep 2016; 68:1312-1318. [PMID: 27710861 DOI: 10.1016/j.pharep.2016.08.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/26/2016] [Accepted: 08/30/2016] [Indexed: 12/25/2022]
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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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Alexoff A, Roginsky G, Zhou Y, Kalenda M, Minuskin K, Ehrenpreis ED. Inpatient Costs for Patients with Inflammatory Bowel Disease and Acute Pancreatitis. Inflamm Bowel Dis 2016; 22:1095-1100. [PMID: 26914437 DOI: 10.1097/mib.0000000000000739] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is associated with an increased risk of acute pancreatitis (AP). Our group examined differences in length of stay and costs for patients with IBD hospitalized for AP and the general population. METHODS Using the National Inpatient Sample, we examined all admissions during 2005 to 2011 with a primary diagnosis of AP and codiagnosis of IBD. Continuous variables were reported as mean ± SD and compared between IBD and controls. To compare the outcomes of interest, we conducted a 1:3 propensity score matching using a greedy algorithm based on age, gender, race, number of comorbidities, procedures, insurance, income quartiles, hospital bed size, hospital location, and teaching status. Statistical analyses were performed on SAS 9.3 (Cary, NC). RESULTS There were 4291 hospitalizations of patients with IBD and AP over the 7-year period and 379,627 hospitalizations of patients without IBD and with AP. More patients with Crohn's disease developed AP than patients with ulcerative colitis (2145 versus 1219). The length of stay and costs for patients with AP and IBD were significantly higher than controls (5.7 days versus 4.9 days, P < 0.0001 and $29,724.89 versus $27,916.76, P < 0.0001). The percentage of patients with alcohol abuse was lower in patients with IBD than that of controls (11.8% versus 21.7%, P < 0.0001). However, the percentage of patients with IBD who were drug abusers was higher than controls (5.8% versus 4.3%, P < 0.0005). CONCLUSIONS Our study suggests that a codiagnosis of Crohn's disease or ulcerative colitis incurs a greater economic burden in patients with AP.
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Affiliation(s)
- Aimee Alexoff
- *Center for the Study of Complex Diseases, Research Institute, NorthShore University HealthSystem, Evanston, Illinois; †Department of Medicine, Evanston Hospital, NorthShore University HealthSystem, Evanston, Illinois; ‡Center for Biomedical Research Informatics, Research Institute, NorthShore University HealthSystem, Evanston, Illinois; §Department of Medicine, University of Chicago, Chicago, Illinois; and ‖Department of Gastroenterology, NorthShore University HealthSystem, Evanston, Illinois
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Zerra P, Bergsagel J, Keller FG, Lew G, Pauly M. Maintenance Treatment With Low-Dose Mercaptopurine in Combination With Allopurinol in Children With Acute Lymphoblastic Leukemia and Mercaptopurine-Induced Pancreatitis. Pediatr Blood Cancer 2016; 63:712-5. [PMID: 26878433 DOI: 10.1002/pbc.25841] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Revised: 10/02/2015] [Accepted: 10/07/2015] [Indexed: 12/19/2022]
Abstract
Mercaptopurine (6-mercaptopurine, 6MP) is a mainstay of curative therapy in childhood acute lymphoblastic leukemia (ALL), and contributes to its 90% overall survival rate. We present two patients with ALL who suffered with severe pancreatitis secondary to 6MP. Through the use of allopurinol in conjunction with reduced dose 6MP, we were able to continue 6MP without further pancreatitis. This report contributes to the small body of literature on 6MP associated pancreatitis in childhood ALL and describes a novel approach to continued use of 6MP during therapy.
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Affiliation(s)
- Patricia Zerra
- Emory University/Children's Healthcare of Atlanta, Aflac Cancer Center and Blood Disorders Service, Atlanta, Georgia
| | - John Bergsagel
- Emory University/Children's Healthcare of Atlanta, Aflac Cancer Center and Blood Disorders Service, Atlanta, Georgia
| | - Frank G Keller
- Emory University/Children's Healthcare of Atlanta, Aflac Cancer Center and Blood Disorders Service, Atlanta, Georgia
| | - Glen Lew
- Emory University/Children's Healthcare of Atlanta, Aflac Cancer Center and Blood Disorders Service, Atlanta, Georgia
| | - Melinda Pauly
- Emory University/Children's Healthcare of Atlanta, Aflac Cancer Center and Blood Disorders Service, Atlanta, Georgia
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Abstract
Inflammatory bowel disease (IBD) has been increasingly diagnosed in children and adults. Similarly, acute and chronic pancreatitis are increasingly prevalent conditions with potentially devastating consequences. There is a growing body of literature linking these 2 conditions. The purpose of this review is to provide a comprehensive outline of the association between IBD and pancreatitis and to explore their putative pathophysiology. Based on the collective reports, 2 outstanding reasons for pancreatitis in patients with IBD are medications and IBD complications.
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Limb C, Ibrahim IAK, Fitzsimmons S, Harper AJ. Recurrent pancreatitis after unremarkable colonoscopy, temporalised by CT imaging: an unusual case. BMJ Case Rep 2016; 2016:bcr-2015-213192. [PMID: 26746831 DOI: 10.1136/bcr-2015-213192] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Acute pancreatitis is a common surgical presentation, frequently caused by gallstones and alcohol. Here we present an unusual case of a recurrent episode of pancreatitis after an unremarkable colonoscopy, in a patient with several pre-existing risk factors for pancreatitis. Before and after abdominal CT scans clearly demonstrate the acute inflammatory process affecting the pancreas and temporalise its development. Early resuscitation and appropriate involvement of high dependency care is advocated by all current guidelines to improve patient outcome. We consider possible aetiology and how early diagnosis and recognition of possible high-risk situations can expedite its investigation and management, helping to provide the best possible care.
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Affiliation(s)
- Christopher Limb
- Department of Digestive Diseases, Royal Sussex County Hospital, Brighton, East Sussex, UK
| | - Ibrahim A K Ibrahim
- Department of Digestive Diseases, Royal Sussex County Hospital, Brighton, East Sussex, UK
| | - Sophie Fitzsimmons
- Department of Digestive Diseases, Royal Sussex County Hospital, Brighton, East Sussex, UK
| | - Ashton J Harper
- Department of Digestive Diseases, Royal Sussex County Hospital, Brighton, East Sussex, UK
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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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Cardile S, Randazzo A, Valenti S, Romano C. Pancreatic involvement in pediatric inflammatory bowel diseases. World J Pediatr 2015; 11:207-11. [PMID: 26253411 DOI: 10.1007/s12519-015-0029-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 11/18/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are a group of chronic diseases affecting the gastrointestinal tract, with a disabling course. The incidence of IBDs is increasing in different geographical areas, indicating its emergence as a global disease, especially in children. Many patients with IBDs develop extraintestinal manifestations (EIMs) during follow-up, as IBDs have a potential risk of systemic involvement.. DATA SOURCES A systematic review of the literature was made to analyze latest studies on pancreatic involvement in children with IBD including our experience in assessing possible implications and its future application. RESULTS The involvement of the hepatobiliary system is considered a rare EIM of children with IBD, with an incidence much higher than that in the general population. Isolated pancreatic hyperenzymemia, which occurs in the absence of typical symptoms and/or characteristic imaging findings, may be found in many patients with IBD. The frequent causes of pancreatitis are drugs, bilio-pancreatic disorders, immunologic disturbances and pancreatic auto-antibodies, although in some cases idiopathic forms have been described. CONCLUSIONS It is important to establish a correct diagnostic approach based on etiology and to assess the most appropriate therapeutic strategy, thus avoiding complications and improving the quality of life of children with IBD.
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Affiliation(s)
- Sabrina Cardile
- Department of Pediatrics, IBD Unit, University of Messina, Via Consolare Valeria, Messina, 98125, Italy
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Kawa S, Okazaki K, Notohara K, Watanabe M, Shimosegawa T. Autoimmune pancreatitis complicated with inflammatory bowel disease and comparative study of type 1 and type 2 autoimmune pancreatitis. J Gastroenterol 2015; 50:805-815. [PMID: 25399203 DOI: 10.1007/s00535-014-1012-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 10/27/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Two types of autoimmune pancreatitis (AIP) have been reported, lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic pancreatitis (IDCP), which are now recognized as type 1 and type 2 AIP, respectively. Since the clinical features of type 2 AIP have not been fully elucidated and this condition is frequently accompanied by inflammatory bowel disease (IBD), we performed a nationwide survey of patients with AIP complicated with IBD to precisely characterize this disease entity. METHODS We collected 138 cases of pancreatitis with complicating IBD from affiliated institutes specializing in AIP or IBD, and comparative study between the IDCP groups and type 1 AIP was performed. RESULTS Histological examination revealed 15 AIP cases to be IDCP of institutional diagnosis, among which 11 cases were upgraded to IDCP of central diagnosis by an expert pathologist. The IDCP group exhibited younger onset age, no gender bias, frequent abdominal pain, and normal IgG4 value, similar to those of type 2 AIP reported previously. We also witnessed a lower prevalence of jaundice in type 2 AIP than in type 1 AIP that corresponded to imaging findings of less frequent pancreatic head swelling and scarce bile duct stenosis. CONCLUSIONS A characteristic feature of type 2 AIP compared with type 1 AIP is a low frequency of obstructive jaundice that is related to rare lower bile duct stricture due to lower prevalence of pancreatic head swelling. Contrary to type 1 AIP, lower bile duct stricture in this condition has no apparent relation to sclerosing cholangitis.
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Affiliation(s)
- Shigeyuki Kawa
- Center for Health, Safety, and Environmental Management, Shinshu University, 3-1-1 Asahi, Matsumoto, 390-8621, Japan,
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40
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Natural history of pancreatic involvement in paediatric inflammatory bowel disease. Dig Liver Dis 2015; 47:384-9. [PMID: 25704068 DOI: 10.1016/j.dld.2015.01.155] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 01/01/2015] [Accepted: 01/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few case reports describe the clinical features of pancreatic involvement in inflammatory bowel disease. AIM To investigate prevalence and disease course of inflammatory bowel disease children with pancreatitis and with exclusive hyperamylasemia and hyperlipasemia. METHODS We used a web-registry to retrospectively identify paediatric inflammatory bowel disease patients with hyperamylasemia and hyperlipasemia. Participants were re-evaluated at 6 months and 1 year. RESULTS From a total of 649 paediatric patients, we found 27 with hyperamylasemia and hyperlipasemia (4.1%). Eleven patients (1.6%) fulfilled diagnostic criteria for acute pancreatitis. Female gender was significantly associated with acute pancreatitis (p=0.04). Twenty-five children (92.5%) had colonic disease. At 6 months 1/11 children with acute pancreatitis (9%) showed acute recurrent pancreatitis, while 1 patient (9%) had persistent hyperamylasemia and hyperlipasemia. At 12 months, 1 patient showed chronic pancreatitis (9.1%). Of the 16 children with exclusive hyperamylasemia and hyperlipasemia, 4 developed acute pancreatitis (25%), while 1 patient (6.2%) still presented exclusive hyperamylasemia and hyperlipasemia at 6 months. At 12 months, 11/16 patients (68.7%) reached a remission of pancreatic involvement, whereas 5 remaining patients (32.3%) had persistent hyperamylasemia and hyperlipasemia. CONCLUSIONS In inflammatory bowel disease children, acute pancreatitis is more common in colonic disease and in female gender. Pancreatic function should be monitored, considering that pancreatic damage may evolve.
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Abstract
Crohn's disease and ulcerative colitis are chronic inflammatory conditions affecting the gut and can present at any age with increased numbers of diagnoses seen in many countries in recent years. The thiopurine drugs, azathioprine and 6-mercaptopurine, are commonly used to maintain remission in Crohn's disease and ulcerative colitis; however, the use of these drugs may be limited by the development of pancreatitis in some individuals. Recent data indicate a genetic risk factor and provides a potential immune-mediated mechanism for thiopurine-induced pancreatitis. Management of thiopurine-induced pancreatitis requires exclusion of the triggering drug, which leads to prompt resolution of symptoms. This thiopurine side-effect may limit therapeutic options for future management of patients.
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Affiliation(s)
- Oren Ledder
- Department of Paediatric Gastroenterology, Shaare Zedek Medical Centre, Jerusalem, Israel
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High- and low-dose oral delayed-release mesalamine in children with mild-to-moderately active ulcerative colitis. J Pediatr Gastroenterol Nutr 2014; 59:767-72. [PMID: 25419597 PMCID: PMC4255757 DOI: 10.1097/mpg.0000000000000530] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. METHODS Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. RESULTS The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. CONCLUSIONS Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.
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Alsubaie S, Almalki MH. Metformin induced acute pancreatitis. DERMATO-ENDOCRINOLOGY 2013; 5:317-8. [PMID: 24194972 PMCID: PMC3772920 DOI: 10.4161/derm.23792] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Revised: 01/24/2013] [Accepted: 01/26/2013] [Indexed: 12/13/2022]
Abstract
Acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely, pancreatic panniculitis. Metformin, one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases. Here, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function.
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Affiliation(s)
- Sadeem Alsubaie
- College of Medicine; King Saud University; Riyadh, Saudi Arabia
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Ledder OD, Lemberg DA, Ooi CY, Day AS. Are thiopurines always contraindicated after thiopurine-induced pancreatitis in inflammatory bowel disease? J Pediatr Gastroenterol Nutr 2013; 57:583-586. [PMID: 23783022 DOI: 10.1097/mpg.0b013e31829f16fc] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND AND AIMS Thiopurine use in inflammatory bowel disease (IBD) is well established for maintenance of disease remission. Approximately 3% of patients with IBD develop thiopurine-induced pancreatitis (TIP) as an idiosyncratic reaction. Patients diagnosed as having TIP are largely considered not to be candidates for future use of this drug. We hypothesize that previous TIP is not an absolute contraindication to retrialing a different thiopurine. METHODS This case series is a retrospective chart review of those patients with IBD in whom thiopurines were successfully reintroduced following suspected TIP. The patients were all cared for in 2 Australasian pediatric IBD services. Four cases are presented of TIP appropriately related temporally to azathioprine commencement, with no other apparent cause of pancreatitis identified. All of these patients were trialled on 6-mercaptopurine according to clinical need and this was well tolerated in all cases. RESULTS AND CONCLUSIONS This report is the largest case series to date focusing on the reintroduction of a thiopurine following suspected thiopurine induced pancreatitis. All of the patients had a typical presentation of TIP. This case series should call into question the assumption that suspected TIP is an absolute contraindication for the future use of this class of drug. Cautious reintroduction of a thiopurine, in a controlled setting, should be considered in certain circumstances. The clinical relevance of this option is most marked in patients with complicated disease requiring long-term immunosuppression, in whom other therapies are poorly tolerated or contraindicated.
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Affiliation(s)
- Oren D Ledder
- *Department of Pediatric Gastroenterology, Shaare Zedek Medical Centre, Jerusalem, Israel †Department of Gastroenterology, Sydney Children's Hospital, Sydney, Australia
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Abstract
More than one-third of patients with IBD are affected by extraintestinal manifestations or extraintestinal complications beyond the intestinal manifestation of the disease. The most common manifestations include arthropathies, mucocutaneous and ophthalmological manifestations, as well as conditions affecting the hepatobiliary system, both in Crohn's disease and ulcerative colitis. However, less frequent manifestations, such as pulmonary or neurological manifestations, should also be considered in patients with IBD. Several extraintestinal manifestations follow the course of the underlying intestinal activity, whereas others are independent from the intestinal inflammation. Extraintestinal complications such as iron-deficiency anaemia and osteoporosis are consequences of the intestinal disease or of disease-specific treatment. As extraintestinal manifestations and complications strongly influence quality of life, and to avoid severe complications, adequate treatment is mandatory in affected patients. We provide a comprehensive overview of different extraintestinal manifestations and complications, including their management, in patients with IBD.
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Affiliation(s)
- Claudia Ott
- Department of Internal Medicine I, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany
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6-Mercaptopurine-induced recurrent acute pancreatitis in children with acute lymphoblastic leukemia/lymphoma. J Pediatr Hematol Oncol 2013; 35:470-2. [PMID: 23138114 DOI: 10.1097/mph.0b013e318271c92f] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Two children with acute lymphoblastic leukemia/lymphoma developed recurrent acute pancreatitis during treatment; the etiology was presumed to be secondary to 6-mercaptopurine (6MP). Both had no further attacks after discontinuation of 6MP. Acute pancreatitis secondary to 6MP is extremely rare in acute leukemia/lymphoma although it has been reported in patients with other conditions like inflammatory bowel disease; the reason for this difference is not clearly understood.
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Kubat E, Mahajan S, Liao M, Ackerman L, Ohara PT, Grady EF, Bhargava A. Corticotropin-releasing factor receptor 2 mediates sex-specific cellular stress responses. Mol Med 2013; 19:212-22. [PMID: 23835907 DOI: 10.2119/molmed.2013.00036] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Accepted: 07/01/2013] [Indexed: 01/11/2023] Open
Abstract
Although females suffer twice as much as males from stress-related disorders, sex-specific participating and pathogenic cellular stress mechanisms remain uncharacterized. Using corticotropin-releasing factor receptor 2-deficient (Crhr2-/-) and wild-type (WT) mice, we show that CRF receptor type 2 (CRF2) and its high-affinity ligand, urocortin 1 (Ucn1), are key mediators of the endoplasmic reticulum (ER) stress response in a murine model of acute pancreatic inflammation. Ucn1 was expressed de novo in acinar cells of male, but not female WT mice during acute inflammation. Upon insult, acinar Ucn1 induction was markedly attenuated in male but not female Crhr2-/- mice. Crhr2-/- mice of both sexes show exacerbated acinar cell inflammation and necrosis. Electron microscopy showed mild ER damage in WT male mice and markedly distorted ER structure in Crhr2-/- male mice during pancreatitis. WT and Crhr2-/- female mice showed similarly distorted ER ultrastructure that was less severe than distortion seen in Crhr2-/- male mice. Damage in ER structure was accompanied by increased ubiquitination, peIF2, and mistargeted localization of vimentin in WT mice that was further exacerbated in Crhr2-/- mice of both sexes during pancreatitis. Exogenous Ucn1 rescued many aspects of histological damage and cellular stress response, including restoration of ER structure in male WT and Crhr2-/- mice, but not in females. Instead, females often showed increased damage. Thus, specific cellular pathways involved in coping and resolution seem to be distinct to each sex. Our results demonstrate the importance of identifying sex-specific pathogenic mechanisms and their value in designing effective therapeutics.
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Affiliation(s)
- Eric Kubat
- Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA
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Abstract
GOALS To determine the prevalence of ulcerative colitis (UC) in autoimmune pancreatitis (AIP) patients in a tertiary referral hospital and to compare the clinical and pathologic characteristics and outcomes of UC associated with AIP (AIP-UC) and UC patients. BACKGROUND Recently, it was suggested that UC is associated with AIP. However, the prevalence of UC in AIP, together with the clinical characteristics and outcomes of AIP-UC are not clear. STUDY We retrospectively reviewed the medical records of AIP patients diagnosed at the Asan Medical Center. RESULTS Of the 104 patients with AIP, 6 (5.8%) were also diagnosed with UC. Serum immunoglobulin G (IgG) and IgG4 were elevated in 1 patient (16.7%), respectively, and 4 (66.7%) showed idiopathic duct-centric pancreatitis (type 2 AIP). Compared with 24 matched patients with UC only, AIP-UC patients had a lower body mass index (P=0.003), higher C-reactive protein levels (P=0.048), and higher Mayo scores (P=0.006) at diagnosis of UC. Two AIP-UC patients (33.3%), but none with UC only showed increased infiltration of IgG4-positive cells into the colonic tissues (P=0.006). During follow-up, 2 AIP-UC patients (33.3%) underwent colectomy and 1 (16.7%) died, but no colectomies or deaths occurred in the UC only group. CONCLUSIONS AIP patients seem to have a higher risk of UC compared with the general population. The increased IgG4-positive cellular infiltration in the colonic tissue suggests that UC may be an extrapancreatic manifestation of AIP.
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Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis 2013; 19:1404-10. [PMID: 23665964 DOI: 10.1097/mib.0b013e318281f28f] [Citation(s) in RCA: 228] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. METHODS Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. RESULTS Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. CONCLUSIONS As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.
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