The influence of chronic pancreatitis on carcinogenesis: an experimental study in rats.

Abstract

The literature contains many controversial or unclearly defined opinions about the risk of development of carcinoma of the exocrine part of the pancreas in patients with chronic pancreatitis. This and our own clinical observations based on analysis of patients with chronic pancreatitis treated surgically (anastomotic and resectional procedures) formed the background to an experimental study to define the risk of carcinogenesis in the course of chronic pancreatitis in rats. In Wistar rats with chronic pancreatitis induced by etionine and then exposed to carcinogenic action of azaserine, proliferation, adenomas and acinic cell carcinomas of the exocrine part of the pancreas were diagnosed; the carcinomas were transplantable. In rats treated with azaserine only, benign proliferative lesions and adenomas were found. The presence of the p53 mutation protein was observed in carcinomatous pancreatic cells in malignant lesions of the pancreas in primary and transplantable cancers, but was not detected in benign proliferative lesions and adenomas. Chronic pancreatitis in Wistar rats predisposes the exocrine part of pancreas to malignant transformation. Growth of cancers of the exocrine part of the pancreas in male rats, but not in female rats, suggests hormonal determination of experimental pancreatic cancer. Results demonstrate that chronic pancreatitis in rats predisposes to malignant proliferative lesions, including acinic cell carcinoma. Expression of the protein product of p53 gene mutations correlated with neoplastic transformation of pancreas preceded by chronic pancreatitis, and was also detected in transplantable tumours.