Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer

Background: Pancreatic cancer, the fourth most common cause of cancer death in the United States, is hereditary in an estimated 10% of cases. Surveill ance of patients with a familial predisposition for pancreatic cancer has n ot been systematically evaluated. Objective: To develop a surveillance program that can identify and treat pa tients who have precancerous conditions of the pancreas and a family histor y of pancreatic cancer. Design: Prospective cohort study. Setting: University medical center. Patients: 14 patients from three kindreds with a history of pancreatic canc er. Interventions: Endoscopic ultrasonography, endoscopic retrograde cholangiop ancreatography (ERCP), spiral computed tomography, and serum carcinoembryon ic antigen and CA19-9 analysis were performed in all patients. Four affecte d patients were tested for the K-ras mutation. Main Outcome Measurement: Pancreatic dysplasia was determined by histologic evaluation. Results: Seven of the 14 patients were believed to have dysplasia on the ba sis of clinical history and abnormalities on endoscopic ultrasonography and ERCP and were referred for pancreatectomy. All 7 patients had histologic e vidence of dysplasia in pancreatectomy specimens. Findings on endoscopic ul trasonography were subtle, nonspecific, and similar to those seen in patien ts with chronic pancreatitis. Findings on ERCP ranged from mild and focal s ide-branch duct irregularities and small sacculations to main-duct strictur es and grapelike clusters of saccules. Some of these changes are typical of chronic pancreatitis, but others are more distinctive. Spiral computed tom ography and serum tumor markers had low sensitivity in the detection of pan creatic dysplasia. Analysis for the K-ras mutation yielded positive results in 3 of 4 patients with dysplasia. Conclusions: Thorough screening of patients with a family history of pancre atic cancer is feasible. Clinical data combined with imaging studies (endos copic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at t his time.