Neoplasms of the exocrine pancreas

Neoplasms of the Pancreas Vic V Vernenkar, D.O St Barnabas Hospital Dept Of Surgery From Greenfield’s Surgery 2006 4th edition Introduction • Estimates:33000 cases, 32000 die in 2005 • 4th leading cause of cancer death • Non-specific symptoms, inaccessibility to examination, aggressiveness, technical difficulties associated with surgery Epidemiology/Risk Factors • Increase threefold since the beginning of the century • Age, race, sex, tobacco, diet, specific genetic syndromes • More than 80% of cases between 60-80 years of age, rare under 40 • African-American of both sexes Epidemiology/Risk Factors • Men over women • Cigarette smoking increased risk 1.5-5 times • Increased consumption of total calories, CHO, cholesterol, meat, salt, fried food, refined sugar, soy beans, nitrosamines Epidemiology/Risk Factors • A protective effect for dietary fiber, vitamin C fruits and veggies • Long standing diabetes is not a risk factor Epidemiology/Risk Factors • Chronic pancreatitis of any cause has been associated with a 25-year cumulative risk of 4% Other conditions for which a possible connection to pancreatic cancer are: thyroid cancer, cystic fibrosis, pernicious anemia • Most cases of pancreatic cancer have no predisposing factors, however it is estimated that between 5-10% arise because of a familial disposition Epidemiology/Risk Factors • Six genetic syndromes associated with an increased risk of pancreatic cancer are: • HNCC, BRCA-2 associated familial breast cancer, PJ syndrome, ataxia-telangietasia, hereditary pancreatitis, familial molemelanoma syndrome Molecular Genetics • Tumor suppressor genes: p53, p16, DPC4, BCA2 • P53 is inactivated in 75% of all pancreatic cancers Molecular Genetics • DPC4 is on Chromosome 18q The Chromosome is missing in 90% of all pancreatic cancers, the gene inactive in 50% The mutations are more specific for pancreatic cancer than p53 or p16 mutations • Oncogenes, when over expressed encode proteins with transforming qualities Activating point mutations in the k-ras oncogene is the most common genetic alteration in pancreatic cancer, found in 80-90% of pancreatic cancers Pathology • Classified based on cell of origin Most common are ductal adenocarcinomas • 65% of ductal cancers arise in the head, neck, or uncinate process; 15% originate in the body or tail; 20% diffuse Kocherizing Determining Resectability Resected Head Pylorus Preserving Postoperative Results • During the 1960s and 1970s, many centers reported operative mortality in range of 2040%, with postoperative morbidity rates of 40-60% Postoperative Results • During last two decades rates reported down to 2-3% mortality Reasons why fewer, more experienced surgeons are performing the operation on a more frequent basis, pre and post op care has improved, anesthesia has improved, large number of patients are being treated at high volume centers Postoperative Results • Complication rates remain high (30%) Pancreatic fistula remains the most frequent serious complication (5-15%) The mortality from this has decreased though • Other common complications include delayed gastric emptying, abscess, bleeding, infection, diabetes, exocrine insufficiency Long-term Survival • Historically, 5% 5-year survival post resection More recent studies suggest improved survival Long-term Survival • In 2000, Sohn, et al on 616 patients resected with a 17% 5-year survival, median survival of 17 months Factors found to be important predictors of survival included tumor diameter (