Despite advances in perioperative care, pancreatoduodenectomy (PD) remains associated with substantial morbidity and mortality. The primary cause of both is postoperative pancreatic fistula (POPF), particularly in high-risk patients with a small (≤3 mm) main pancreatic duct and soft pancreatic texture. In this subgroup, the pancreato-enteric anastomosis is inherently vulnerable, increasing the risk of leakage and subsequent complications such as postpancreatectomy hemorrhage (PPH), sepsis, and multi-organ failure.

Over the past decade, several interventions have individually demonstrated efficacy in reducing POPF or its sequelae. However, despite being pragmatic and low-cost, these strategies have not reached consensus and are not widely implemented in international guidelines or routine clinical practice.

The PANENCA trial was designed to address this gap by evaluating a pragmatic bundle approach combining three promising interventions: hydrocortisone, octreotide, and a ligamentum teres patch (the HOP bundle). These interventions have expected complementary mechanisms of action without interaction. Hydrocortisone reduces the inflammatory response involved in fistula formation and has been associated with a significant reduction in major complications in a randomized trial; octreotide reduces pancreatic exocrine secretion, thereby limiting enzymatic damage; and the ligamentum teres patch provides mechanical protection of the gastroduodenal artery stump against enzymatic erosion in the event of a leak.