November 12, 2014
Notes: Abdo, Emilio Elias
Coelho, Ana Maria Mendonca
Patzina, Rosely Antunes
Sampietre, Sandra Nassa
Cunha, Jose Eduardo Monteiro
Machado, Marcel Cerqueira Cesar
D’Albuquerque, Luiz Augusto Carneiro
Pancreatology. 2013 May-Jun;13(3):225-9. doi: 10.1016/j.pan.2013.04.001. Epub 2013 Apr 11.
Author Address: Department of Gastroenterology (LIM/37), Medical School, University of Sao Paulo, Sao Paulo, Brazil.
Reference Type: Journal Article
Record Number: 5228Author: Acharya, C., Cline, R. A., Jaligama, D., Noel, P., Delany, J. P., Bae, K., Furlan, A., Baty, C. J., Karlsson, J. M., Rosario, B. L., Patel, K., Mishra, V., Dugampudi, C., Yadav, D., Navina, S. and Singh, V. P.
Title: Fibrosis reduces severity of acute-on-chronic pancreatitis in humans
Short Title: Fibrosis reduces severity of acute-on-chronic pancreatitis in humans
Alternate Journal: Gastroenterology
ISSN: 1528-0012 (Electronic)
Accession Number: 23684709
Keywords: Acinar Cells/drug effects
Aged, 80 and over
Fatty Acids, Nonesterified/pharmacology
Pancreatitis, Acute Necrotizing/complications/*pathology
Severity of Illness Index
Abstract: BACKGROUND & AIMS: Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and is associated with a higher rate of mortality. We investigated features of CP that protect against severe disease. The amount of intrapancreatic fat (IPF) is increased in obese patients and fibrosis is increased in patients with CP, so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP. METHODS: We reviewed records from the University of Pittsburgh Medical Center/Presbyterian Hospital Autopsy Database (1998-2008) for patients with a diagnosis of AP (n = 23), CP (n = 35), or both (AP-on-CP; n = 15). Pancreatic histology samples from these patients and 50 randomly selected controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell Transwell coculture system, with or without collagen type I, was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of nonesterified fatty acids (NEFAs) and adipokines on acinar cells in culture. RESULTS: Levels of IPF were significantly higher in nonobese patients with CP than in nonobese controls. In patients with CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in controls or patients with AP. Fat necrosis-associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in samples from patients with AP; however, findings of peri-fat acinar necrosis and total necrosis were significantly lower in samples from patients with CP or AP-on-CP. Fibrosis appeared to wall off the fat necrosis and limit peri-fat acinar necrosis, reducing acinar necrosis. In vitro, collagen I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFAs, but not adipokines, caused acinar cell necrosis. CONCLUSIONS: Based on analysis of pancreatic samples from patients with CP, AP, or AP-on-CP and in vitro studies, fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells.