Gringeri E, Polacco M, D'Amico F E, Scopelliti M, Bassi D, Bonsignore P, Luisetto R, Lodo E, Carraro A, Zanus G, Cillo U
Department of Surgical and Gastroenterological Sciences, Hepatobiliary and Liver Transplant Unit, University of Padova, Italy.
Transplant Proc. 2011 May;43(4):997-1000. doi: 10.1016/j.transproceed.2011.01.139.
Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation.
Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage.
All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage.
This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery.
肝切除术是原发性和继发性肝肿瘤治疗的金标准，但由于肿瘤范围，很少有患者适合该手术。肝移植（OLT）、肝切除术以及亚常温机器灌注（MP）保存的手术经验的改进促使了一种新的大型动物自体移植模型的发展。
本实验使用长白猪。插管后，按照经典技术进行肝切除术。肝内腔静脉用一段猪胸主动脉同源血管替换。肝脏先用低温Celsior溶液灌注，然后在20℃用含氧的 Krebs 溶液进行机器灌注。在持续120分钟的保存期内进行肝切除术，然后将肝脏以逆时针90°旋转的位置重新植入同一动物体内。按照经典顺序进行吻合。在机器灌注保存期末以及肝再灌注后1小时和3小时获取血管内液体、血液和肝脏活检样本，以评估移植物功能和微观损伤。
所有动物均在手术后存活。再灌注后60分钟记录到天冬氨酸转氨酶峰值，180分钟后记录到丙氨酸转氨酶和乳酸脱氢酶峰值。光镜下组织病理学检查未发现坏死或充血。术中彩色多普勒超声显示吻合口通畅良好且静脉引流正常。
该系统使得在体外进行肝切除和血管重建成为可能，同时通过机械灌注保存器官（体外、异位手术）。改进自体移植的手术技术以及我们对缺血再灌注损伤的理解，可能为积极的手术治疗或放化疗方案开拓有趣的前景，以治疗不适合传统原位手术的原发性和继发性肝肿瘤。
