General anesthesia is used. The goal of pancreaticoduodenectomy is to remove tumors in the periampullary region, including the head of pancreas, typically retaining the distal pancreas. The operation proceeds in a clockwise fashion consisting of six steps. At each step resectability is assessed. One is not committed to the resection until the last step when the pancreas is divided. Step 1 is to perform a Cattell-Braasch maneuver and expose the superior mesenteric vein. In this step the right colon is mobilized and the mesenteric attachment to the retroperitoneum is divided from the terminal ileum to the ligament of Treitz. This frees up the third and fourth portions of the duodenum. The lesser sac is opened via the gastrocolic omentum and the transverse colon is separated from the duodenum and stomach. The inferior edge of the pancreas is dissected out, as is the superior mesenteric vein as it courses under the neck of the pancreas, avoiding traction on the gastrocolic vein. Step 2 is to perform an extended Kocher maneuver where the duodenum and head of pancreas are dissected off the vena cava and aorta. At the completion of this step, tumor involvement of the major vessels can be assessed, as well as the origin of the superior mesenteric artery. Step 3 is to perform the portal dissection. A cholecystectomy is performed. The common bile duct is encircled and divided. A frozen section analysis of the bile duct margin is performed; if positive, more bile duct can be removed. The gastroduodenal artery is then dissected out and divided after clearly identifying its origin from the common hepatic artery. The portal vein is identified directly under the gastroduodenal artery. The portal vein is freed up at the neck of the pancreas superiorly and the entire neck of the pancreas is mobilized off the vein, taking great care not to damage the small venous tributaries entering the right side of this structure. Step 4 is to divide the stomach. Where the stomach is divided depends on whether a pylorus-preserving procedure, an antral-preserving procedure, or a classical Whipple procedure with antrectomy is performed. Step 5 is to divide the small bowel at the proximal jejunum. The ligament of Treitz is completely mobilized below the transverse mesocolon, and the small bowel, to be resected as part of the specimen, is rotated under the mesenteric vessels. Step 6 is to divide the pancreas in the region of the pancreatic neck. A frozen section analysis is performed over the pancreatic body margin, and if positive, additional pancreas is resected. Once the pancreas is divided, the superior mesenteric vein and portal vein are mobilized off the uncinate portion of the pancreas and divided along the medial border of the superior mesenteric artery. Extreme care is needed at this point as lateral traction on the head of pancreas may pull the superior mesenteric artery to the right side of the corresponding major vein. Reconstruction occurs in a counterclockwise fashion. Initially an end-to-side pancreaticojejunostomy is performed first, followed by the biliary anastomosis (usually an end-to-side choledochojejunostomy), and, finally, evidence leans towards performing a gastrojejunostomy in an antecolic fashion. It is thus distanced from the pancreas and may reduce the incidence of delayed gastric emptying. The pancreatic anastomosis can either be an invagination of the pancreas or a direct duct-to-mucosal anastomosis. The gastrojejunostomy can either be a loop or Roux-en-Y reconstruction. Partial pancreatectomy of the head of pancreas without duodenectomy is uncommon and restricted to situations where either benign disease is present or small tumors are localized to the head region only. Total pancreatectomy is uncommonly performed because of the severe endocrine and metabolic consequences that are often experienced and associated high morbidity and mortality. It may be used in some centers for multifocal secreting endocrine tumors, chronic pancreatitis, and intraductal papillary mucinous neoplasia, all of which are often associated with serious endocrine and metabolic disturbances as part of the disease processes. This may be performed with or without duodenectomy.

The major anatomical point that is important with pancreaticoduodenectomy is related to the hepatic arterial supply. Accessory or replaced right hepatic arteries arise off the superior mesenteric artery and course along the upper part of the uncinate, posterior and lateral to the common bile duct. Accessory or replaced left hepatic arteries arise off the left gastric artery and less commonly come into play during resection. Occasionally, the entire common hepatic trunk comes off the superior mesenteric artery. In this case it usually courses up in between the portal vein and the common bile duct. Usually these vessels can be preserved as part of the resection.