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Chronic pancreatitis

Abstract

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

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Figure 1: Prevalence of chronic pancreatitis.
Figure 2: Pathophysiology of chronic pancreatitis.
Figure 3: Histological characteristics of alcoholic chronic pancreatitis.
Figure 4: Histological characteristics of autoimmune pancreatitis.
Figure 5: CT imaging in chronic pancreatitis.
Figure 6: ERCP and MRCP imaging in chronic pancreatitis.
Figure 7: Endoscopic management of chronic pancreatitis.
Figure 8: Surgical management of chronic pancreatitis.
Figure 9: A conceptual model of disease progression linked to the mechanistic definition of chronic pancreatitis.

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Acknowledgements

This work was partially supported by the COST action BM1204 “EUPancreas: An integrated European platform for pancreas cancer research: from basic science to clinical and public health interventions for a rare disease” (eupancreas.com) to J.K., I.E. and J.P.N., and by the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the US National Institutes of Health under award number U01DK108306 (to D.C.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Introduction (D.C.W.); Epidemiology (T.G.); Mechanisms/pathophysiology (V.R. and D.C.W.); Diagnosis, screening and prevention (J.M., I.E. and F.A.); Management (A.M.D., J.K., J.P.N., T.S., M.M.L. and J.E.D.M.); Quality of life (A.M.D.); Outlook (D.C.W.); Overview of the Primer (J.K. and J.P.N.).

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Correspondence to Jorg Kleeff.

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Competing interests

A.M.D. has received unrestricted funds for research from Mundipharma, AstraZeneca and Grünenthal, and has participated in advisory boards and received speaker fees from Almirall, Shire, Kyowa Kirin, Norgina and Allergan. V.R. received speaker fees from Laboratoires Mayoly Spindler. J.E.D.M. has received unrestricted grants for research from Abbott Laboratories and Mylan, and has participated in advisory boards and received speaker fees from Abbott Laboratories and Mylan. J.P.N. reports a consulting or advisory role for Boehringer Ingelheim Pharma; Novartis Pharma AG; KAEL GemVax and Astellas, research funding from Taiho Pharma (Japan), PI, paid to institution; KAEL GemVax (Korea), PI, paid to Institution; AstraZeneca, PI, paid to institution; Pharma Nord, PI, paid to institution, and travel expenses from NUCANA, Amgen and Mylan. D.C.W. reports participating in advisory boards for AbbVie, serving as a consultant for Ariel Precision Medicine, Clinical Outcome Solutions and Regeneron, research support from the National Institutes of Health (USA), the Department of Defense (USA), Shire, the Wayne Fusaro Pancreatic Cancer Research Fund and UPMC (USA), and has equity in Ariel Precision Medicine. All other authors declare no competing interests.

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Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60

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