| Project/Area Number |
07407035
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YAMAOKA Yoshio Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90089102)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yuzo Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70281730)
SAKAI Yoshiharu Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (60273455)
OZAKI Nobuhiro Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (50211818)
IKAI Iwao Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60263084)
田中 明 京都大学, 医学研究科, 講師 (00240820)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥21,400,000 (Direct Cost: ¥21,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥20,100,000 (Direct Cost: ¥20,100,000)
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| Keywords | Extra-corporeal hepatectomy / Extended hepatectomy / Artificial vessels / Heat shock protein / Ischemic tolerance of the liver / Damaged liver protection / Fatty liver / Stress response / 対外肝切除 / 障害肝 / フリーラジカル / 対外抗癌療法 / 四塩化炭素 |
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| Research Abstract |
Technical aspects for the development of 'Non-touch isolation method' of hepatectomy for hepatic malignancies were investigated. The liver lobe without malignant tumor was first procured according to the technique for the donation of living-related partial liver transplantation without manipulating the tumor bearing parts of the liver in order to prevent the tumor ce11 dissemination during hepatectomy. The tumor bearing part of the liver was then extirpated in one piece with IVC.For the re-implantation of the preserved healthy liver lobe, reconstructions of the IVC and hepatic vein were of difficulty in this new technique. In the anastomosis between the Gore-Tex vessel for the replaced IVC and hepatic vein, direct anastomosis of the hepatic vein to the lateral wall of Gore-Tex vessel was most suitable both for hepatic drainage and for stabilization of the implanted liver. In the reconstruction of the hepatic artery, end-to-end micro-anastomosis between the hepatic artery and peripheral
… More
end of the splenic artery using micro-chip for vascular anastomosis was effective to obtain rapid procedure and the good patency. The high rate occurrence of postoperative coagulopathy was the other problem in this technique. Since elastase was easily activated after operation, protease inhibitor was administered throughout the operative period so that the initiation of DIC was not triggered. This prophylactic administration of protease inhibitor made postoperative hemostasis quite easy. As a result, animals could survive more than 10 days overwhelming the postoperative acute phase. The remaining problem is the contro1 of infection due to complicated operative procedure and the usage of artificial vessels.
In the part of study for the protection of damaged liver during opertion, activation of 'self-protection mechanism' of the cells utilizing the 'stress response' was most promising. In this study, it was proven that the induction of heat shock protein (HSP) in the liver tissue prior to stressful intervention could confer excellent protection against warm-ischemia reperfusion injury. In the normal livers, 50% mortality in rats due to 30-minute warm ischemia of the liver was improved to more than 95% survival. Recovery of energy metabolism after reperfusion was better maintained as well. This effects was realized even after the induction of HSPs by other methods than heat shock, such as ischemic or pharmacological preconditioning. This protective effects were also demonstrated also in the damaged liver models. In the fibrotic livers produced by carbon tetrachloride, the postischemic survival was improved from 50% to 90%. The survival of the animals with fatty livers, which was produced by the choline deficient diet, was also improved from 33% to 87%. Less
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