If a patient with a periampullary carcinoma is explored and found to have locally unresectable or disseminated tumor, duodenal and biliary bypasses should be performed, as well as a chemical splanchnicectomy. Today, this situation is encountered much less frequently than before. With thin-section, three-dimensional CT scans, unresectable disease can be detected in most patients prior to a formal laparotomy, and palliated with a variety of nonsurgical means. Nevertheless, it still occasionally happens that a patient with unresectable disease is explored. Even if the patient has had biliary decom­pression performed preoperatively, either endoscopically or percutaneously, an internal biliary bypass should be carried out to eliminate the need for an endoprosthesis or percutaneous biliary stent. In addition, even though it remains some­what controversial as to whether a duodenal bypass should be routinely performed, we support always performing a gas­trojejunostomy. Most studies have demonstrated that somewhere between 15 and 20% of patients who do not under­go a gastrojejunostomy will have to be re-explored and subsequently undergo a duodenal bypass. In addition, most stud­ies have shown little or no additional morbidity or mortality when also performing a gastrojejunostomy, as opposed to only a biliary bypass. If a gastrojejunostomy has not been performed, and the patient subsequently develops duodenal obstruction, they often are late in their course and nutritionally not able to withstand an operative procedure. For those reasons, we feel that both biliary and duodenal bypasses should be performed. Finally, in addition to biliary and duo­denal obstruction, most patients with unresectable periampullary cancer have substantial epigastric and back pain. We therefore routinely favor performing a chemical splanchnicectomy. In a prospective randomized study, the performance of a chemical splanchnicectomy with 50% alcohol clearly demonstrated a decrease in, or elimination of, subsequent epigas­tric and back pain.