Clinical and experimental studies of intraperitoneal lipolysis and the development of clinically relevant pancreatic fistula after pancreatic surgery

Abstract

Background: Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula.Methods: The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor).Results: Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0⋅004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0⋅009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. Conclusion: Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevanceClinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated.Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula.Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.

Usefulness of the abdominal fat area-based risk score for postoperative pancreatic fistula after pancreatoduodenectomy

“…Moreover, an abundant amount of abdominal fat around the pancreaticojejunostomy anastomosis site may be catalysed into triglycerides and free fatty acids by pancreatic lipase. This may have a deteriorating impact on a developing CR-POPF, according to recent clinical and experimental studies on intraabdominal lipolysis 19 . This may be why there was no signi cant difference in the rate of CR-POPF between the trainees and skilled surgeons (CR-POPF vs non-CR-POPF, 23.4% vs 27.6%, P = 0.63) in this study.…”

Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model

“…The supernatant was collected and frozen at −80℃ until analysis. The amount of EPA in the supernatant was measured according to previous report using high‐performance liquid chromatography (HPLC) 20 . The mass of EPA obtained by HPLC at each time‐point was measured, and the ratio of the mass compared with that at time‐point when gelatin hydrogel was completely dissolved was calculated and this assay was repeated five times.…”

Combination of postoperative C-reactive protein value and computed tomography imaging can predict severe pancreatic fistula after pancreatoduodenectomy

“…Resection was performed as described previously. 17,18 All pancreatic anastomoses to the alimentary tract were accomplished using end-to-side duct-to-mucosa pancreatojejunostomy with an external stent. Two closed-suction drainage tubes were routinely placed behind the choledocho-and pancreatojejunostomy anastomoses.…”