Surgical resection provides the only chance for long-term survival for patients diagnosed with pancreatic and other associated periampullary adenocarcinomas. In the past, it had been suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection might have improved long-term survival for some patients. In response, six prospective trials have been performed and reported addressing this issue. These studies, including a large randomized trial of 280 patients from Johns Hopkins University, indicate that there is no demonstrable survival benefit to extended lymphadenectomy for periampullary cancer.