Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

Witt, Heiko; Apte, Minoti V.; Keim, Volker; Wilson, Jeremy S.

doi:10.1053/j.gastro.2007.03.001

Cited by 513Pancreatitis Pathology and TreatmentPancreatic and Hepatic Oncology ResearchIgG4-Related and Inflammatory Diseases

Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

Witt, Heiko, Apte, Minoti V., Keim, Volker, Wilson, Jeremy S.·2007·Gastroenterology

DOI 10.1053/j.gastro.2007.03.001

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Abstract

Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

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In chronic pancreatitis, metabolism of alcohol leads to production of reactive oxygen species and fatty acid ethyl esters that activate stellate cells and damage acinar cells of the pancreas.
“Specifically, in chronic pancreatitis, metabolism of alcohol leads to production of reactive oxygen species 304 and fatty acid ethyl esters 305, 306 that activate stellate cells and damage acinar cells of the pancreas.”
From The relationship between different dimensions of alcohol use and the burden of disease—an update (2017) · cites this paper as [306]

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Authors: Witt, H., Apte, M. V., Keim, V., & Wilson, J. S.
Affiliations: Charité – Universitätsmedizin Berlin (DE)
UNSW Sydney (AU)
University Hospital Leipzig (DE)
Corresponding author: Wilson, Jeremy S.
ORCID: Witt, Heiko
Apte, Minoti V.
Wilson, Jeremy S.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2007-04
Volume: 132
Issue: 4
Pages: 1557-1573
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2007.03.001
OpenAlex: W1993211081
Cited by: 513
References: 123
Citations by year: 2026: 7 · 2025: 11 · 2024: 7 · 2023: 16 · 2022: 17 · 2021: 23 · 2020: 23 · 2019: 20 · 2018: 18 · 2017: 37 · 2016: 33 · 2015: 48 · 2014: 24 · 2013: 35 · 2012: 33
FWCI: 7.69
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
Keywords: chronic pancreatitis, pathogenesis, pancreatic fibrosis, necroinflammation, pancreatic stellate cells, fibrogenesis, alcohol abuse, trypsinogen activation, CFTR, genetic susceptibility, tropical pancreatitis, idiopathic pancreatitis, pain management, maldigestion, diabetes mellitus, pseudocyst, endoscopy, surgical treatment
MeSH terms: Animals, Diagnostic Imaging, Humans, Treatment Outcome, Genetic Predisposition to Disease, Pancreatitis, Chronic

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Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

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