Intraparenchymal Penicillin G Injection Promotes Wound Healing and Lowers POPF in Pigs After Pancreatic Surgery

Background: Postoperative pancreatic fistula (POPF) is a significant complication following pancreatic surgery, considerably influenced by the texture of the pancreatic tissue. This study aims to explore the potential of Penicillin G (PG) in reducing the severity of POPF in a porcine surgical model. Study Design: After performing distal pancreatectomy with pancreaticojejunostomy (PJ), pigs were administered either normal saline or varying concentrations of PG (0.75, 1.5, and 3.0 mM) at the PJ site. The study estimated POPF by measuring pancreatic hardness, tensile force, fibrosis, and amylase levels in Jackson-Pratt (JP) drain samples. Results: Intraparenchymal PG injection significantly increased pancreatic hardness and tensile force (p < 0.05) while upregulating profibrotic markers like MMP2 and TGF-β1, indicating enhanced fibrosis (p < 0.05). Importantly, these profibrotic changes reverted to baseline levels by POD 14, suggesting reversible fibrosis without lasting consequences. The 0.75 PG and 1.5 PG groups exhibited significantly lower JP amylase levels than the control group on both POD 3 and POD 4 (p < 0.05). Notably, the 0.75 PG group also demonstrated the highest survival rate compared to the 1.5 PG and NS groups (p < 0.05). Conclusions: The intrapancreatic PG injection could effectively reduce the severity of POPF by promoting wound healing through intensified fibrosis around the PJ site.