IDENTIFICATION OF K-RAS MUTATIONS IN PANCREATIC-JUICE IN THE EARLY DIAGNOSIS OF PANCREATIC-CANCER

Objective: To develop an early diagnostic test for pancreatic cancer b ased on the identification of K-ras mutations in pure pancreatic juice collected during endoscopic retrograde pancreatography. Design: Prosp ective study with masked comparison. The standard criteria for the dia gnosis of pancreatic cancer were pancreatography or surgery (or both) and histopathology, with follow-up ranging from 6 to 40 months. Settin g: Referral center. Patients: 24 patients with no pancreatic disease ( group 1); 29 patients with nontumoral pancreatic disease (group 2); an d 22 patients with pancreatic tumor (group 3). Endoscopic ductal aspir ation of cells or brush cytology was done on patients having endoscopi c retrograde pancreatography for diagnostic or therapeutic reasons. Ma in Outcome Measure: Confirmation of mutation rates in patients with pa ncreatic cancer. Results: K-ras gene analysis was done by polymerase c hain reaction-mediated restriction fragment length polymorphism analys is and direct sequencing. AH patients from groups 1 and 2 (n = 53) had a normal sequence for the K-ras 12th codon (group 1, 0% [95% CI, 0% t o 14%]; group 2, 0% [CI, 0% to 12%]). Mutations were seen in 17 of the 22 patients in group 3 (77% [CI, 55% to 92%]). Two of the 17 had no e vidence of pancreatic cancer when K-ras was first studied. One had chr onic abdominal pain and the other presented with acute pancreatitis. B oth were initially free of any pancreatic mass, but they developed tum ors 18 and 40 months, respectively, after the K-ras mutations were ide ntified. Conclusion: Identification of K-ras mutations in samples of p ancreatic juice may be useful in differentiating between pancreatic ca ncer and noncancerous pancreatic diseases. K-ras mutation can precede clinical evidence of pancreatic cancer, hut the clinical implications of this finding need further study.