The PANENCA trial aims to reduce postoperative complications for patients who need a pancreatoduodenectomy (also known as a Whipple procedure), which is a complex operation to remove a tumor from or near the head of the pancreas. One of the most serious and common complications after this surgery is a leak from the pancreas, called a postoperative pancreatic fistula (POPF). Such leaks can cause infection, bleeding, or inflammation in the abdomen, often leading to delayed recovery and postponement of the next phase of treatment. In severe cases, these complications can even result in death. Patients with a small pancreatic duct (3 millimeters or less) are known to have a higher risk of developing a leak. Previous studies suggest that several existing treatments may help to prevent these complications. These include hydrocortisone, a medicine that reduces inflammation; octreotide, a medicine that decreases the production of pancreatic juices; and a surgical technique called the teres ligament patch, which uses the patient's own tissue to protect nearby blood vessels if a leak occurs. Because pancreatic fistulas are complex and multifactorial, we believe that a combination therapy targeting different mechanisms may provide a complementary and stronger protective effect. Therefore, the PANENCA trial will investigate whether using these three interventions together can reduce major complications after surgery. Patients who take part in the study will be randomly assigned to receive either the combination treatment or standard care. The medicines are given only during the first few days after surgery, and the patch is placed during the operation. No additional tests, monitoring, or hospital visits are required beyond normal care. This international, multicenter trial includes high-risk patients undergoing pancreatoduodenectomy. The main goal is to determine whether the combination therapy can lower the rate of major postoperative complications. If proven effective, this approach will be implemented consistently across Europe and incorporated into international treatment guidelines for pancreatic surgery.