Segmental liver transplantation from living donors. Report of the technique and preliminary results in dogs

A technique of orthotopic liver transplantation using a segmental graft from living donors was developed in the dog. Male mongrel dogs weighing 25-30 kg were used as donors and 10-15 kg as recipients. The donor operation consists of harvesting the left lobe of the liver (left medial and left lateral segments) with the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The grafts are perfused in situ through the left protal branch to prevent warm ischemia. The recipient operation consists of two phases: total hepatectomy with preservation of the inferior vena cava using total vascular exclusion of the liver and veno-venous bypass, implantation of the graft in the orthotopic position with anastomosis of the left hepatic vein to the inferior vena cava and portal, arterial and biliary reconstruction. Preliminary experiments consisted of four autologous left lobe transplants and nine non survival allogenic left lobe transplants. Ten survival experiments were conducted. There were no intraoperative deaths in the donors and none required transfusions. One donor died of sepsis, but all the other donor dogs survived without complication. Among the 10 grafts harvested, one was not used because of insufficient bile duct and artery. Two recipients died intraoperatively of air embolus and cardiac arrest at the time of reperfusion. Three dogs survived, two for 24 hours and one for 48 hours. They were awake and alert a few hours after surgery, but eventually died of pulmonary edema in 2 cases and of an unknown reason in the other. Four dogs died 2-12 hours postoperatively as a result of hemorrhage for the graft's transected surface. An outflow block after reperfusion was deemed to be the cause of hemorrhage in these cases. On histologic examination of the grafts, there were no signs of ischemic necrosis or preservation damage. This study demonstrates the technical feasibility of living hepatic allograft donation. It shows that it is possible, in the dog, to safely harvest non ischemic segmental grafts with adequate pedicles without altering the vascularization and the biliary drainage of the remaining liver. We propose that this technique is applicable to human anatomy.     

Orthotopic transplantation of segmental hepatic graft from living donors in the dog. Technic and results

The authors describe new technic of non-auxiliary orthotopic transplantation of segmental liver harvested from living dogs. 32 dogs were utilized. In the donor dogs, the left medial and lateral lobes were mibilized. The left portal branch, left hepatic artery, left biliary branch and the left hepatic vein were dissected free. The segmental liver graft was perfused and cooled in-situ through the left portal vein. The recipient dogs underwent two steps total hepatectomy: First the segments I, II, III, IV and V were resected. The segments VI and VII were maintained as well as the right portal vein and the retro-hepatic inferior vena cava order to keep the splanchnic and caval flux and to avoid the spleno-cavo-jugular by-pass. The segmental liver graft was then transplanted in an orthotopic position. Termino-lateral hepatico-caval anastomosis and left porto-portal anastomosis as well as arterial and biliary reconstruction were executed. All the donors survived more than 30 days. Nine recipient dogs died during the first three post-operative days from hemorrhage (3 dogs), fibrinolysis (2 dogs), primary non function of the graft (2 dogs) and hepatic artery thrombosis (1 dog). Seven recipients survived more than 30 days.     

The measurement of hepatic circulation before and after orthotopic liver transplantation in dog--by using transit-time blood flow meter and H2 clearance method

Orthotopic liver transplantation was successfully carried out in 40 mongrel dogs, in which hepatic circulation was investigated before and after grafting. Blood flows in hepatic artery, portal vein and intrahepatic inferior vena cava were measured by using transit-time ultrasonic blood flow meter and regional tissue blood flow was determined by hydrogen gas clearance method. Before transplantation the mean blood flows were 234 +/- 95mg/min in portal vein, 118 +/- 76ml/min in hepatic artery and 291 +/- 103ml/min in inferior vena cava in 40 recipients. The blood flow ratio of portal vein and hepatic artery was 2.9 +/- 2.2. The mean regional blood flow of the liver was 63 +/- 24ml/min/100g. After transplantation, the mean blood flows decreased to 189 +/- 86ml/min in portal vein, 77 +/- 51ml/min in hepatic artery and 179 +/- 111ml/min in inferior vena cava and the regional tissue blood flow was 57 +/- 25ml/min/100g. Hepatic arterial flow decreased by 37 percent after transplantation, however, portal venous flow decreased by 24 percent and the regional blood flow decreased by 9 percent after transplantation of the liver. These data suggested that the microcirculation of the liver was slightly disturbed after liver transplantation in dog, which was in part due to the decreased blood flows of the hepatic artery and portal vein.     

门静脉-下腔静脉吻合术预防活体肝移植术后小肝综合征3例报道

目的探讨门静脉-下腔静脉吻合术用于预防活体肝移植术后小肝综合征(small-for-size liver syndrome,SFSS)的效果。方法 3例活体肝移植均采用不含肝中静脉的右半肝作为移植物。术中发现实测移植物(肝)重量/受体的体质量(体重)的比值(graft to recipient weight ratio,GRWR)为0.58%、0.77%及0.71%,均<0.8%,符合小移植物的诊断。处理:首先吻合肝静脉流出道,其次吻合门静脉,将受体门静脉右支与移植肝门静脉右支端端吻合,将受体门静脉左支与下腔静脉行端侧吻合达到门腔分流的作用,之后按顺序吻合动脉和胆道。术中均未行脾静脉结扎或脾切除等处理。术后定期随访。结果 3例患者术后均未发生SFSS并顺利出院,出院时间分别为术后25d、34d及56d。移植肝功能逐步好转,术后1d门静脉流速理想。移植肝增长良好。门静脉-下腔静脉短路通畅时间:除1例通畅持续仅104d,其余2例持续通畅。结论 LDLT术中进行门静脉-下腔静脉吻合术可以及时有效预防小移植物背景下的SFSS,受体门静脉左支与下腔静脉行端侧吻合的分流技术安全可靠。     

肝移植术后并发症的介入治疗

目的评价肝移植术后多种并发症的介入治疗。方法回顾性的分析肝移植术后出现各种并发症并进行介入治疗的82例患者,胆管病变62例;肝动脉病变8例;下腔静脉病变13例;肝静脉狭窄7例;门静脉病变9例。胆管并发症采用经T管置入引流管、经皮肝穿刺胆管行胆汁引流或球囊扩张术。球囊扩张成形术或(和)金属支架植入术处理血管狭窄的患者;局部溶栓治疗用于术后血管内血栓形成的病例。结果在胆管并发症患者中,41例经T管置入引流管,34例行经皮穿刺胆汁引流(PTBD),球囊扩张胆道成形术9例。3例肝动脉狭窄的患者接受了球囊扩张成形术或支架植入术,1例肝动脉形成血栓者行插管溶栓,效果良好。9例下腔静脉狭窄患者行支架植入术,1例接受了球囊扩张成形术。5例肝静脉狭窄患者接受了球囊扩张成形术或支架治疗。门静脉狭窄患者中6例接受支架治疗,1例门脉血栓形成行局部溶栓,治疗不满意。结论介入治疗是处理肝移植术后胆管和血管并发症不可或缺的临床治疗方法。     

猪辅助性部分肝移植模型制作及比较

目的建立猪的辅助性部分肝移植模型,观察其肝功能和术中血流动力学变化。方法 24头健康良种家猪,体质量23-30 kg,被随机分为供体(n=12)和受体(n=12)。气管插管 全麻,硫喷妥钠静脉维持。移植前切除受体肝左叶,供肝右叶作为植入肝。预实验2例行经体位转流的原位辅助性部分肝移植,对照组(5例)行简易转流下的原位辅助性部分肝移植。模型组(5例)行异位辅助性部分肝移植, 供肝被植入受体肝下间隙,供肝肝上下腔静脉与受体肝下下腔静脉端侧吻合,供肝门静脉与受体门静脉行端侧吻合,供肝肝动脉与受体脾动脉行端端吻合。供肝胆总管置管外引流。结果预实验中行体位静脉转流的原位辅助性部分肝移植的2例受体在肝上下腔静脉阻断后很快陷入血流动力学紊乱死亡。5例行简易静脉转流的原位辅助性部分肝移植的受体,2例在24 h内死亡,1例28 h,2侧超过48 h。而模型组受体 5例中有4例存活超过24 h。AST,ALT指标手术开始至术后24 h呈持续升高。模型组术中血流动力学较其他组稳定。结论该辅助性肝移植模型简明易建且具有不需静脉转流等优点,为研究辅助性部分肝移植原肝和供肝功能及血流变化提供了理想的平台。     

A prolongation of hepatic vascular exclusion by in situ hypothermic perfusion in dogs.

In situ hypothermic hepatic perfusion was performed in dogs to explore whether the time limit of hepatic vascular exclusion could be prolonged. During hepatic vascular exclusion, hepatic hypothermic perfusion was performed via portal vein using various perfusates under active bypass from the portal vein and infrahepatic inferior vena cava area to the superior vena cava system. Dogs receiving hepatic hypothermic perfusion for 1 hour died when given Ringer's solution but survived more than 7 days when given Euro-Collins' and University of Wisconsin solutions. Although dogs tolerated 2 hours of hepatic hypothermic perfusion when give University of Wisconsin solution, all dogs died by 2 hours of hepatic hypothermic perfusion when given Euro-Collins' solution. The hepatic energy charge and arterial ketone body ratio of dogs that died were significantly lower than for those that survived. This suggests that the regimen of hepatic hypothermic perfusion with University of Wisconsin solution is able to maintain the energy metabolism of the liver under hepatic vascular exclusion for prolonged periods, hence, its possible clinical application.     

Short hepatic vein reconstruction in biliary atresia patients with absent inferior vena cava

Liver transplantation in patients with biliary atresia and polysplenia syndrome requires some technical adjustments. During eight yr, 75 biliary atresia patients underwent living donor liver transplantation. Of these, two patients were complicated by absent inferior vena cava with azygos continuation. Both patients received hemi-liver grafts with short hepatic veins. Outflow was reconstructed using a cryopreserved vena cava. In both patients, the short hepatic vein was anastomosed to the vein graft end-to-end and the end of the vein graft was anastomosed with the common orifices of recipient's hepatic veins. Both of the patients survived the operation with satisfactory graft function. A hemi-liver graft with short hepatic veins can be used for patients with biliary atresia with inferior vena cava agenesia using the current technique.     

自体原位肝移植逆行灌注法对大鼠急性肾损伤的影响

目的探讨自体原位肝移植术中经下腔静脉逆行灌注对大鼠肾功能的影响,为临床肝移植应用经下腔静脉逆行灌注法提供实验依据。方法 60只自体原位肝移植大鼠随机分为逆行灌注组、门静脉灌注组与假手术组各20只。前两组建立自体肝移植模型,其中逆行灌注组采用经下腔静脉逆行灌注法,先开放下腔静脉,再开放门静脉,最后开放肝动脉。门静脉灌注组采用常规经门静脉正向灌注法,先开放门静脉,再开放下腔静脉,最后开放肝动脉。假手术组开腹后游离肝门处门静脉、肝动脉及肝上、下下腔静脉,不予阻断,17min后关腹。分别检测3组术前1h、术后1h、8h及术后1d、5d的血清肌酐(Scr)、血尿素氮(BUN)水平;无肝期结束后1h、8h、1d取左肾组织行光镜检查观察肾组织病理形态学变化。结果术前1h,各组肾功能指标比较差异均无统计学意义(均为P>0.05);与假手术组比较,逆行灌注组、门静脉灌注组术后1h、8h及1d的Scr、BUN水平显著增高,而且逆行灌注组上述两指标明显低于门静脉灌注组(均为P<0.05),但术后5d3组比较差异均无统计学意义(均为P>0.05)。无肝期结束后1h,逆行灌注组和门静脉灌注组肾组织病理学检查发现肾间质充血,8h出现明显的肾小管上皮细胞水肿及肾间质充血,逆行灌注组明显轻于门静脉灌注组;无肝期结束后1d两组肾组织损伤呈现好转趋势,且逆行灌注组明显优于门静脉灌注组。结论自体原位肝移植术中实施逆行灌注可减轻大鼠急性肾损伤,改善大鼠早期肾功能。     

A new method of segmental orthotopic liver transplantation in children

Orthotopic liver transplantation requires matching of the donor and recipient for size. The rarity of suitable pediatric and infant donors in many countries has resulted in the acceptance of the principle of a reduced-sized adult liver graft for children. A new method of segmental orthotopic liver transplant is described. This method involves resecting the recipient liver off the inferior vena cava, which is left in situ, and the donor hepatic vein is anastomosed end to side to the inferior vena cava. The technique allows orthotopic liver transplantation with widely mismatched sizes from adults to infants.     

20%小体积的大鼠肝脏移植模型

目的 应用显微外科技术建立20%小体积移植物的大鼠原位肝脏移植模型.方法 原位移植建立20%小体积大鼠肝脏移植模型.雄性Lewis大鼠40只,供体20只,受体20只.供肝经门静脉用4℃ UW液灌注.肝上下腔静脉用端端吻合连续缝合的方法.肝下下腔静脉和门静脉分别用套管方法固定.套叠缝合法重建肝动脉.胆管重建采用内支架管端端连接的方法.观察移植物的存活率.免疫组化检测肝细胞摄取溴脱氧尿核苷的情况.结果 共施行肝脏移植手术20例,移植手术成功率为100%.20%小体积肝脏移植物的存活率为93.8%(＞14 d).组织学检查移植后的肝脏组织结构良好.移植术后72 h溴脱氧尿核苷染色阳性的肝细胞计数明显增多.结论 20%小体积大鼠肝脏移植物可启动完成移植后的肝脏再生.显微外科技术是移植模型成功的关键.该模型稳定性强,适合于部分肝脏移植领域的基础研究.     

Severe outflow block syndrome caused by compression by the swollen caudate lobe after living donor liver transplantation: report of a case

A 50-year-old man with primary biliary cirrhosis underwent living-donor liver transplantation (LDLT) using a graft of a left hemiliver with a left caudate lobe and duct-to-duct hepaticocholedochostomy. Postoperative bile leakage necessitated percutaneous drainage 22 days after LDLT. The patient presented to our hospital 205 days after the LDLT with abdominal distension and fever. Computed tomography showed ascites and a diffusely mottled pattern in the graft. The caudate lobe was swollen, and its bile ducts were dilated. The inferior vena cava was forced to the right by the swollen caudate lobe, and the root of the hepatic vein was stretched. The hepatic vein was not contrasted. Endoscopic retrograde cholangiography showed a biliary anastomotic stricture. Based on these findings, we diagnosed a severe outflow block of the hepatic vein and biliary anastomotic stricture. We performed balloon dilation of the biliary anastomosis and implanted a metallic stent in the hepatic vein. Thereafter, his clinical symptoms improved dramatically.     

Orthotopic liver transplantation and living donors. An experimental study in the dog

Orthotopic liver transplantation (OLT) using partial grafts harvested from living donors would represent a further alternative to the limited supply of hepatic grafts, especially in pediatrics. We report herein the results of an original technique of living donor OLT that we have developed in the dog. This study was conducted in male mongrel dogs weighing 25-30 kg for the donors and 10-15 kg for the recipients. The donor operation consisted in harvesting the left lobe of the liver as a graft. The recipient operation consisted in the implantation of the graft in the orthotopic position after total hepatectomy with preservation of the inferior vena cava. Ten survival experiments were undertaken. The first donor died of infected liver necrosis of the quadrate lobe. All other donors survived without major complication. Among the 10 grafts, only 9 were used. Substantial survival could be obtained in 3 dogs. On recipient survived for 48 hours and 2 for 24 hours but their graft was functioning and producing bile. Two dogs died intraoperatively. The 4 other recipients developed an outflow block of the graft after reperfusion leading to lethal hemorrhage from the transected surface. This work is, to our knowledge, the first experimental study of OLT using living donors. It provides a technical basis to the clinical use of living hepatic allograft donors which otherwise depends on ethical issues.     

大鼠原位肝移植胆道并发症的原因分析

目的研究胆道并发症的发生原因,建立稳定的大鼠原位肝移植模型。方法“二袖套法”行大鼠原位肝脏移植180例,即肝上下腔静脉（SVC）采用连续缝合法吻合,门静脉（PV）以及肝下下腔静脉（IVC）采用袖套法吻合,胆总管采用内支架胆管端端吻合法。结果模型稳定后,供肝冷缺血时间为（50．1±12．0）min,无肝期为（16．0±3．1）min,受体手术时间为（54．4±10．6）min,术后胆道并发症的发生率为40％,主要表现为肝脓肿、肝内外胆管扩张、胆泥形成等。结论胆管内支架管的选择以及手术技巧是影响大鼠肝移植术后胆道并发症发生发展的重要因素。     

肝移植治疗晚期肝硬化

目的 肝移植治疗肝脏终末期病变。方法 采用改良的背驮式肝移植技术即保留肝后下腔静脉的全病肝切除,将供肝植于受肝原位,供、受体肝上下腔静脉,供、受体门静脉,供、受肝动脉行对端吻合;结扎供肝肝下下腔静脉。用ＦＫ５０６、晓翻和强的松三联免疫抑制剂抗排斥反应,加强术后监护和感染的控制。结果 例１、例２目前分别存活１１个月、８个月余,生活自理,例３因术后并发急性肾功能衰竭死亡,存活１４d。结论 肝移植是治愈肝脏终末期病谱的可靠方法。     

A simple method of orthotopic liver transplantation in dogs.

Orthotopic liver transplantations were performed by one team in 18 dogs using a cuff method to anastomose the portal vein, the suprahepatic vena cava and the infrahepatic vena cava without external or internal shunts. Total and warm ischemic times of donor liver averaged 124 and 32 minutes, respectively. The average occlusion time of the portal vein and the infrahepatic vena cava were 9.7 and 13.9 minutes, respectively. During this time, uncontrolled hypotension, petechiae or hemorrhagic enterogastritis did not develop. Sixteen of 18 dogs survived more than five days, and five dogs lived more than three weeks. The cause of death was not related to the cuff method in any instance. This approach proved to be a technically simple and satisfactory procedure.     

小鼠肝动脉重建对长时间冷保存移植肝存活率的影响

目的研究小鼠肝动脉重建(hepatic arterial reconstruction,HAR)对长时间冷保存移植肝存活率的影响。方法同系雄性C57BL/6小鼠68只,分为冷保存时间(cold preservation time,CPT)1 h组、CPT4 h组、CPT8 h组、CPT16 h组、CPT16 h+HAR组(供、受体小鼠各一半)。小鼠供肝经门静脉灌注4℃UW液后保存。肝脏移植采用缝合法(肝上下腔静脉)和袖套法(门静脉、肝下下腔静脉)吻合,胆管采用内支架管重建法。小鼠HAR采用含供体肝动脉的腹主动脉与受体腹主动脉端侧吻合的方法。观察术后5组受体小鼠移植肝的存活时间,用组织学检查肝细胞损伤情况,用免疫组织化学法观察肝细胞再生功能。结果 CPT1 h、4 h、8 h组受体术后12 d移植物的存活率分别为7/7、10/10、9/9。CPT16 h组除1例小鼠存活外,其余均在移植术后36 h内死亡,存活率为10%(1/10),CPT16 h+HAR组受体90%(9/10)存活,两组存活率相比,差异有统计学意义(P0.01)。CPT1 h、4 h组的移植物组织损伤程度轻,CPT8 h组的移植物组织损伤程度较前两组严重,但肝细胞再生活跃。CRT16 h组的移植肝组织表现为广泛肝细胞空泡变性、坏死,肝细胞再生不明显。CPT16 h+HAR组仅有轻度的肝窦淤血,肝细胞空泡变性、坏死改变,肝细胞再生活跃。结论 HAR可提高长时间冷保存移植肝的存活率。     

Hemodynamic changes with initiation of veno-venous bypass in orthotopic liver transplant patients

Removal of the liver to start the anhepatic stage of liver transplantation requires cross-clamping of the portal vein, inferior vena cava, and hepatic artery. Adverse effects occur from engorged splanchnic beds and decreased venous return. A veno-venous bypass from the inferior vena cava and portal vein to the axillary vein is used in an attempt to ameliorate these changes. The purpose of this study was to evaluate the effect of institution of veno-venous bypass on hemodynamics. Eight randomly selected adult patients undergoing orthotopic liver transplantation had general anesthesia induced with thiamylal and maintained with nitrous oxide and isoflurane. Cardiopulmonary data and arterial and mixed venous blood gases were measured prospectively using radial artery and pulmonary artery catheters. Measurements were taken under four conditions: (1) 10 minutes before bypass; (2) after partial bypass (vena cava to the axillary vein); (3) after partial bypass with portal vein clamping; and (4) after full bypass (vena cava and portal vein to the axillary vein). Statistically significant changes seen were a 22% decrease in cardiac output and a 47% increase in systemic vascular resistance (SVR). Bypass flow was lower than predicted. Venovenous bypass ameliorates, but does not fully prevent, the reduction of cardiac output and rise in SVR seen with initiation of the anhepatic stage. However, bypass does prevent the hypotension experienced during cross-clamping and for these reasons should be used routinely.     

�������ֲ��Ѫ�ܱ������ƴ���

目的：分析10例活体肝移植术中的血管变异，总结其外科处理经验，进一步提高手术成功率，减少并发症。方法：2001年1月至12月，行活体肝移植10例，其中左半肝8例，左外叶1例，右半肝1例，供肝者均为其母，经术中B超及胆管造影以确定肝切线。供体单支肝动脉分支与受体肝动脉吻合，两支肝动脉分别与受体肝左、右动脉吻合。门静脉分支与受体门静脉主干吻合。供体肝静脉与受体下腔静脉行端侧吻合。胆管重建均采用肝管分支与受体胆总管端端吻合，置T管引流。结果：10例活体肝移植，1例因肝动脉血栓形成，术后5天需次肝移植；1例发生排斥；其余8例均康复出院，5例已上学。结论：活体肝移植术中血管重建技术是其重要环节，术前和术中了解供受体解剖变异并正确处理，可减少术后血管和胆道的并发症。     

Successful hepatic transplantation in congenital absence of recipient portal vein

The first case of hepatic transplantation in a patient with congenital absence of the portal vein (CAPV) is reported. A 10-year-old girl with biliary atresia and CAPV underwent successful hepatic transplantation and has normal liver function 9 months after transplantation. This case is only the seventh reported case of CAPV. Patients with CAPV commonly have additional liver anomalies, cardiac and inferior vena cava anomalies, and polysplenia. Surprisingly, hepatic encephalopathy is not a prominent feature in patients with CAPV despite systemic drainage of mesenteric venous blood. CAPV should not be considered a contraindication to hepatic transplantation.