Background and Study Aims: Chronic pancreatitis is considered to be a predisposing factor for pancreatic ductal adenocarcinoma (PAC). The purpose of this study was to examine the prognostic value of a finding of mutated (K-ras) gene in predicting the development of PAC in patients with chronic pancreatitis. Patients and Methods: The pancreatic duct brushings of 146 patients with chronic pancreatitis were examined in order to identify K-ras gene mutations. A total of 112 patients were followed up (median duration 42 months) using clinical evaluation, serum CA19 - 9 levels, and imaging studies. Results: One or more K-ras mutations were found in 57 of the 146 patients with chronic pancreatitis (39 %). Patients harboring K-ras mutations had a higher incidence of persistent alcohol consumption (P = 0.041) and of prior rupture of the main pancreatic duct (P = 0.040). A finding of nuclear atypia in brushing cytology was also more common in patients with K-ras mutation (P = 0.048). Out of the 112 patients who were followed up, PAC occurred in four of the 44 patients who had a K-ras mutation, but in none of the 68 patients with the wild genotype (P = 0.022). PAC occurred in three of the 25 patients who did not have pancreatic calcifications (P = 0.034) and in four of the 54 patients who had demonstrated exocrine insufficiency, but in none of the 58 patients with preserved exocrine function (P = 0.051). Using stepwise logistic regression, the absence of calcifications, the presence of exocrine insufficiency, and the presence of K-ras mutation were identified as independent predictive factors for cancer development in all patients with chronic pancreatitis. Conclusions: K-ras gene mutations occur in chronic pancreatitis and are associated with evolution towards PAC. The absence of pancreatic calcifications and the presence of exocrine insufficiency were identified as additional predictive factors for the development of PAC.
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