PANCREATIC CANCER SURVEILLANCE IN A HIGH-RISK COHORT

Pancreatic adenocarcinoma remains a prevalent and particularly difficult health care problem. It is the 10th commonest malignancy and 4th largest cancer killer in adults.', 32 With an incidence of 9:100,000 persons, the number of new cases diagnosed each year essentially equals the mortality rate from this disease (1997 American Cancer Society estimates-27,600 new cases and 28,100 deaths).',32 This dismal track record persists in the face of advances in (1) technologies available for medical diagnosis, (2) understanding of tumor pathophysiology, and (3) availability of novel chemoradiation protocols. The inability to cure pancreatic adenocarcinoma successfully in 95% to 97% of cases is driven by two factors.25, 36 First, the retroperitoneal location of the pancreas dictates that in most cases patients do not become symptomatic until the tumor burden is sufficient to cause pain, anorexia, and weight loss. Infrequently, jaundice resulting from biliary obstruction or acute pancreatitis is the presenting manifestation." As a result of the insidious nature of disease onset, 85% to 90% of tumors are staged as unresectable at the time of diagnosis.46 Of those deemed potentially resectable for cure before surgery, 25% are deemed unresectable at the time of surgery.36 The 5-year survival rate in this cohort, even in the face of adjunctive chemoradiation therapy, is 30%.36, 50 The quoted overall 5-year survival rate is less than 5%.', 14, 25, 33 Second, advances in understanding of the roles of autocrine and paracrine growth factors and their receptors; mutational activation of oncogenes; mutational inactivation of tumor suppressors; functional inactivation of transforming growth factor (TGF)-P receptor signaling in the face of excessive TGF-P production; potential growthmodulatory roles of vasoactive intestinal peptide receptors; and factors regulat-