Liver ischemia and reperfusion injury (IRI) is a major challenge in liver surgery. Diet restriction reduces liver damage by increasing stress resistance; however, the underlying molecular mechanisms remain unclear. We investigated the preventive effect of 12-h fasting on mouse liver IRI. Partial warm hepatic IRI model in wild-type male C57BL/6 mice was used. The control ischemia and reperfusion (IR) group of mice was given food and water ad libitum, while the fasting IR group was given water but not food for 12 h before ischemic insult. In 12-h fasting mice, serum liver-derived enzyme level and tissue damages due to IR were strongly suppressed. Serum β-hydroxybutyric acid (BHB) was significantly raised before ischemia and during reperfusion. Up-regulated BHB induced an increment in the expression of FOXO1 transcription factor by raising the level of acetylated histone. Antioxidative enzyme heme oxigenase 1 (HO-1), a target gene of FOXO1, then increased. Autophagy activity was also enhanced. Serum high-mobility group box 1 was remarkably lowered by the 12-h fasting, and activation of NF-κB and NLRP3 inflammasome was suppressed. Consequently, inflammatory cytokine production and liver injury were reduced. Exogenous BHB administration or histone deacetylase inhibitor administration into the control fed mice ameliorated liver IRI, while FOXO1 inhibitor administration to the 12-h fasting group exacerbated liver IRI. The 12-h fasting exerted beneficial effects on the prevention of liver IRI by increasing BHB, thus up-regulating FOXO1 and HO-1, and by reducing the inflammatory responses and apoptotic cell death via the down-regulation of NF-κB and NLRP3 inflammasome.

BackgroundFor left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the “artery-first approach”) has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC. However, owing to several technical difficulties in this procedure, its application remains uncommon. Moreover, the artery-first approach in L-RAMPS has not been reported. Here, we developed the artery-first approach L-RAMPS for left-sided PDAC and have presented the same in this report.Case presentationBetween June 2014 and July 2015, 16 patients with left-sided PDAC were referred to our division for pancreatic resection. The following technique was used for performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After opening the omental bursa, only the middle segment of the pancreas was initially separated from both the left renal vein and the SMA. We termed this procedure as the “artery-first approach using a dome-shaped dorsomedial dissection (3D) technique.” This 3D technique enabled the interruption of the entire arterial supply to the specimen while preserving the venous drainage through the splenic vein for preventing venous congestion. The technique also contributed to the early detection of no tumor infiltration into the SMA and the early determination of posterior dissection plane. After pancreatic neck transection, the splenic artery and vein were divided. Finally, the pancreatic tail and spleen were dissected in a right-to-left direction. All operations were completed without any intraoperative complications. The median blood loss and retrieved lymph node count were 75 mL and 37, respectively, which were superior to those reported by other previous studies on L-RAMPS. All resection margins were free of carcinoma. No severe postoperative complications were observed.ConclusionsThe artery-first approach L-RAMPS using 3D technique is safe and feasible to perform. The significance of our proposed procedure is minimal blood loss and precise lymphadenectomy. Therefore, this novel technique may become the preferred treatment for left-sided PDAC in selected cases.

BackgroundSurgeons, in general, underestimate the replaced left hepatic artery (rLHA) that arises from the left gastric artery (LGA), compared with the replaced right hepatic artery (rRHA), especially in standard gastric cancer surgery. During pancreaticoduodenectomy (PD), preservation of the rRHA arising from the superior mesenteric artery (SMA) is widely accepted to prevent critical postoperative complications, such as liver necrosis, bile duct ischemia, and biliary anastomotic leakage. In contrast, details of complication onset following rLHA resection remain unknown. We report two cases of postoperative liver necrosis shortly after rLHA resection during PD for advanced gastric cancer.Case presentationBoth cases had advanced gastric cancer with infiltration of the pancreatic head. In case 1, the rLHA comprised segment 2/3 artery (A2 + A3), which arose from the LGA. The rRHA originated from the SMA, and the segment 4 artery (A4) was a branch of the rRHA. We conducted PD with combined en bloc resection of both the rLHA and rRHA, and anastomosis between the distal and proximal stumps of the rRHA and LGA, respectively. The divided A2 + A3 was not reconstructed. In case 2, the rLHA comprised segment 2 artery (A2) only, which arose from the LGA. The segment 3/4 artery and the RHAs originated from the proper hepatic artery. We undertook PD with combined en bloc resection of A2 without vascular reconstruction. In both patients, serious necrosis of the lateral segment of the liver occurred within 6 days after PD. Case 1 recovered with conservative management, whereas case 2 required lateral segmentectomy of the liver. Pathologically, the necrotic area in case 2 was apparently circumscribed and confined to segment 2 of the liver, potentially implicating rLHA resection during PD as causing hepatic necrosis.ConclusionsDuring PD, rLHA resection can cause serious liver necrosis. Therefore, this artery should be preserved as far as oncologically acceptable. In cases that require rLHA resection during PD due to tumor conditions, surgeons should carefully monitor postoperative course while keeping in mind the possible necessity of urgent hepatectomy.

Antioxidative nutrient supplementation to an ordinary enteral diet may mitigate liver IRI by causing an antioxidant effect and suppressing inflammation.