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Knowledge of risk factors for development of pancreatic ductal adenocarcinoma (PDAC) is limited. To clarify the background condition of the pancreas for the development of PDAC, we analyzed pancreatic histological changes in noncancerous lesion specimens after pancreatectomy in PDAC patients.Seventy-six patients with PDAC were enrolled in this study. The PDAC was in the pancreatic head in 37 patients, in the body in 31, and in the tail in 8. No patients had a history of clinical chronic pancreatitis. As controls, 98 patients without PDAC were enrolled. The following parameters were examined: fibrosis, fatty degeneration, and inflammatory cell infiltration. More than 5% of fatty degeneration in the specimen, more than 10% of fibrosis, and more than 5% of inflammatory cell infiltration were considered positive changes.Pancreatectomy specimens showed a higher ratio of positive change in fibrosis (86% vs 42%), fatty degeneration (72% vs 44%), and inflammatory cell infiltration (14% vs 3%) than control samples. Multivariate analyses demonstrated that each histological change was a significant, independent determinant for PDAC.Our study demonstrated that cryptogenic pancreatic inflammation with fatty changes represents an important predisposing factor for PDAC. Screening for subclinical chronic pancreatitis in healthy populations may enable the detection of PDAC at an early stage.