The lectin‐like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage

トロンボモジュリンのレクチン様ドメインはマウス肝虚血再灌流障害に対する予防及び治療薬の候補となり得る

京都大学新制・課程博士博士(医学)甲第23072号医博第4699号新制||医||1049(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 川口 義弥, 教授 浅野 雅秀, 教授 福田 和彦学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

New laparoscopic procedure for left-sided pancreatic cancer—artery-first approach laparoscopic RAMPS using 3D technique

Abstract Background For 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 presentation Between 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. Conclusions The 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

Liver necrosis shortly after pancreaticoduodenectomy with resection of the replaced left hepatic artery

Abstract Background Surgeons, 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 presentation Both 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. Conclusions During 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