Analysis for small-for-size liver transplantation ; strategy for safety living donorl liver transplantation in adult

为了探讨小尺寸肝移植的病理生理学和治疗方法，我们进行了实验和临床研究。为探讨肝容量的最小限度，在小鼠、大鼠、比格犬中进行了85%的肝切除术。这些研究表明，在小鼠、大鼠和狗中，肝切除术分别诱导TNF-α mRNA上调、内皮素-1产生增加和门静脉压力增加。在小鼠实验中，TNF-a抑制剂ONO-SM362和TNF-α单克隆抗体与未治疗的对照组相比，显著延长了动物的生存期。Real - time PCR分析显示，在85%肝切除术后24小时，ONO-SM362显著抑制肝组织中TNF-α mRNA的表达。非选择性内皮素受体拮抗剂TAK-044在术前给予85%的肝切除大鼠。治疗组存活超过2周，而未治疗组在术后24小时内死亡。在犬类实验中，虽然TAK-044和另一种k…更多的血管扩张剂、PDE III抑制剂（包括氨利诺酮和米利诺酮）和左腔静脉分流术抑制了门静脉压力，延长了动物的生存时间，但除了一只接受TAK-044治疗的狗在大量肝切除术后2年仍然存活外，其他治疗都没有超过2周的存活时间。综上所述，TNF-α抑制剂和血管扩张剂对大面积肝切除术后肝功能衰竭是有效的，但犬85%肝切除术后要获得较长的生存期还需要进一步的实验。在临床研究中，测量移植物体积和肝脏血流量，并从成人活体肝移植（LDLT）患者预后的角度对其进行评价。血运重建术后门静脉流量达到150 ~ 250 （ml/min 100 g肝移植）时，患者并发症较少。门静脉血范围与移植物与标准肝体积（GV/SV）之比超过40%相关。根据这一临床分析，我们建议在供体条件允许的情况下，成人LDLT患者行右叶移植。少

To investigate pathophisiology and treatment of small-for-size liver transplantation, we performed experimental and clinical studies.To investigate minimum limit of liver volume, 85% hepatectomy was performed in mice, rats, beagle dogs. These study revealed that massive hepatectomy induce TNF-α mRNA up-regulaton, increase endothelin-1 production, and augment portal vein pressure in mice, rats, and dogs, respectively. In mice experiment, TNF-a inhibitors, ONO-SM362, and TNF-α monoclonal antibody, prolonged animal survival significantly compared to untreated control. Real time PCR analysis has revealed that TNF-α mRNA expression in liver tissue was suppressed significantly by ONO-SM362 at 24hr after 85% hepatectomy. A non-selective endothelin recptor antagonist, TAK-044, was administered into 85% hepatectomized rats before surgery. The treated rats survived more than 2weeks, although the untreated rats died within 24hr after surgery. In canine experiments, although TAK-044, and another k … More ind of vasodilator, PDE III inhibitor including amrinone and milrinone, and port-caval shunt suppressed portal vein pressure and prolonged animal survival, the treatments did not get long survival more than 2weeks except one dog treated with TAK-044, which is still alive even 2year after the massive hepatectomy. Taking all things mentioned above into account, TNF-α inhibitors and vasodilators are effective for liver failure after massive hepatectomy, but further experiments are necessary to get long survivor in canine 85% hepatectomy.In clinical study, graft volume and hepatic blood flows were measured, and they were evaluated on the view point of patients prognosis after adult living donor liver transplantation (LDLT). When the portal venous flow reached the range from 150 to 250 (ml/min 100 g liver graft) after revascularization, the patients experienced fewer complications. The portal blood range correlated to over 40% graft versus standard liver volume (GV/SV) ratio. According to this clinical analysis, we recommend right lobe graft in adult LDLT, if conditions of donor are permissive. Less