Early detection of pancreatic cancer in patients with chronic pancreatitis: Diagnostic utility of a K-ras point mutation in the pancreatic juice

OBJECTIVE: Point mutations of the K-ras oncogene at codon 12 have been desc ribed several months before the onset of pancreatic cancer in isolated case s of chronic pancreatitis (CP). The aim of this study was to evaluate the i nterest of a prospective follow-up of patients with CP and K-ras mutations at codon 12 in the detection of early pancreatic cancer. METHODS: From February 1996 to March 1998, 36 patients (mean age 52.6 yr, 3 1 men, five women) with CP (alcoholic: 61.1%, pancreas divisum: 5.6%, autoi mmune: 5.6%, un known origin: 27.7%) were included and then prospectively m onitored (median duration of 22 months) for detection of pancreatic carcino ma. K-ras point mutations were examined by two-step polymerase chain reacti on combined with restriction enzyme digestion in pancreatic juice collected during endoscopic retrograde pancreatography. RESULTS: Ten patients (27.8%) were positive fur K-ras mutation. Patients wi th and without the mutation were not different with respect to age and sex ratio. K-ras mutations were homogeneously distributed according to the etio logy (alcoholic vs nonalcoholic) and morphological characteristics (ductal stricture or mass vs none) of CP. A pancreatic carcinoma was discovered at an invasive stage in two patients, respectively at 7 and 17 months: after d isclosure of a K-ras mutation, versus none in patients without the mutation (p < 0.02). CONCLUSIONS: Presence of a K-ras gene mutation is not rare in patients with CP and represents an increased risk of developing pancreatic cancer. Howev er, its utility for the detection of early pancreatic cancer remains doubtf ul in clinical practice. <(c)> 2001 by Am. Cell. of Gastroenterology.