Objective: To identify the most effective individual drug in an established triple-drug therapy (TDT) using a POPF rat model. Summary of background data: POPF is the major complication of pancreatectomy that causes intraperitoneal abscess, sepsis, and pseudo-aneurysm rupture, all of which may prolong hospital stays and cause potentially serious events or death. We previously demonstrated that TDT with a somatostatin analog, gabexate mesilate, and imipenem/cilastatin effectively prevents POPF, especially in high-risk patients. Methods: POPF-induced rats were euthanized on postoperative day 3 after control (C), gabexate mesilate (G), imipenem/cilastatin (I), and somatostatin analog (S) treatments. Levels of serum amylase and lipase or ascitic amylase and lipase were measured. Intraperitoneal adhesion between the abdominal wall and pancreas and pancreatic inflammation were evaluated. Results: Serum amylase levels did not significantly differ among the groups. Serum lipase level was significantly higher in group I than in the other groups (p < 0.01). Both ascitic amylase and lipase levels were significantly lower in group S than in the other groups (p < 0.01). Median inflammation scores were significantly lower in groups G, I, and S than in group C (p < 0.01). Moreover, adhesion score was lower in group S than in the other groups (groups C, G, I, and S with scores 3, 2, 3 and 1, respectively, p < 0.01). Conclusion: Among the three drugs, the somatostatin analog was the most effective against POPF.

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