Abstract
'Background: Postoperative pancreatic fistula remains the most significant complication following pancreatoduodenectomy contributing to major morbidity and mortality. Despite extensive research, incidence rates have not substantially declined, prompting a re-evaluation of its pathophysiology from a purely mechanical problem to a biologically driven process involving postoperative pancreatitis. Materials and Methods: This narrative review synthesizes current evidence on postoperative pancreatic fistula prediction, prevention, and management after pancreatoduodenectomy. It examines established risk factors, preventive strategies (surgical, pharmacological, and perioperative care], and novel concepts highlighting the central role of postoperative pancreatitis. Supporting clinical context is provided by a single-center analysis of 128 patients who developed postoperative pancreatic fistula. Results: Traditional risk factors (soft gland texture, smal duct, high blood loss) are well-vaidated. Preventive measures such as meticulous anastomotic technique, selective drain mana- 'gement, and goal-directed fluid therapy are foundational, but no single intervention is universally effective. Emerging evidence implicates earty acinar cell injury, intraoperative enzyme leakage, and localized ischemia as triggers for postoperative pancreatitis, which appears to be a precursor to fistula formation. Institutional data confirmed a high burden of postoperative pancreatic fistula (grade B: 52.3%] and reveated a significant association between fernale gender and mortality (p = 0.0202], whereas drain amylase levels were not predictive of death. Conclusion: Effective postoperative pancreatic fistula prevention requires a multimodal approach. Future strategies should integrate traditional risk mitigation with novel, biology-tar-