活体肝移植治疗肝细胞癌

目的 探讨活体肝移植治疗肝细胞癌的疗效及其影响因素.方法 回顾分析180例肝癌患者接受肝移植治疗(活体肝移植34例,尸体肝移植146例)的临床资料,比较受者术后肿瘤复发率、总体存活率及无瘤存活率,并通过单因素和多因素分析明确其影响因素.结果 尸体肝移植受者术后5年的总体存活率和无瘤存活率分别为53 %和58 %,活体肝移植者均为60 %,两组间比较,差异无统计学意义(P＞0.05).活体肝移植和尸体肝移植术后肝癌的复发率分别为26.5 %和17.8 %,两组间比较,差异也无统计学意义(P＞0.05).经COX多因素分析显示,肿瘤血管侵犯(相对危险度2.118,95 %可信区间1.201~4.353,P＜0.05)和是否符合UCSF标准(相对危险度3.490,95 %可信区间1.862~8.207,P＜0.05)是影响肝癌复发的独立危险因素,而影响受者术后存活率的独立危险因素为是否符合UCSF标准(相对危险度8.573,95 %可信区间3.016~18.261,P＜0.01).结论 活体肝移植是治疗肝细胞癌的一项安全、有效的措施,但受者的选择标准和术后肝癌的高复发率现象需要进一步的临床和基础研究.

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Objective To evaluate the outcome of living donor liver transplantation(LDLT)for hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the clinical data of 180 patients,who had received LDLT(n=34)or deceased donor liver transplantation(DDLT,n=146)for HCC,compared overall and recurrence-free survival between LDLT and DDLT,and identified the risk factors of tumor recurrence and prognosis by univariate and multivariate analysis.Results The 5-year overall survival and recurrence-free survival rate were 53 % and 58 %,respectively,in DDLT group,and 60 % and 60 %,respectively,in LDLT group.There was no significant difference in overall (P=0.85)and recurrence-free(P=0.89)survival between these two groups.The tumor recurrence rate was 26.5 % in LDLT group,and 17.8 % in DDLT group,respectively(P=0.25).Multivariate COX regression model analysis identified vascular invasion(relative risk 2.118,95 % confidential interval 1.201-4.353,P=0.032)and tumor beyond UCSF criteria(relative risk 3.490,95 % confidential interval 1.862-8.207,P=0.015)as independent risk factors of tumor recurrence,and tumor beyond UCSF criteria(relative risk 8.573,95 % confidential interval 3.016-18.261,P=0.006)as independent predictors of prognosis.Conclusion LDLT is a safe and effective procedure for patients with HCC,but further studies are required for selection criteria of recipients and higher HCC recurrence rate after LDLT.     

肝移植治疗终末期肝病的单中心生存分析

目的 总结肝移植受者长期生存状态,探讨影响受者长期存活的因素.方法 对391例接受肝移植治疗的终末期肝病患者的临床资料进行回顾性分析.根据受者的基础疾病分类分别计算其存活率,并对随访期间原发疾病复发、死亡原因、并发症发生率及其病种和时间分布等资料进行分析,评价影响移植后原发疾病复发和并发症的相关因素.结果 进入随访期的受者共有331例,随访时间8～120个月.良性终末期肝病受者术后1、3、5和10年总体存活率分别为86%、85%、83%和83%,乙型肝炎病毒(HBV)相关肝硬化与重型肝炎受者术后长期存活率的差异无统计学意义(P＞0.05).符合米兰标准的肝癌患者术后1、3、5和10年存活率分别为96%、87%、87、%和87%,超出米兰标准的肝癌患者分别为42%、26%、24%和24%,二者间同期存活率的差异有统计学意义(P＜0.01).原发性肝癌患者肝移植后总体肿瘤复发率为54.3%,符合和超出米兰标准的肝癌患者肝移植后肿瘤复发率分别为4.3%和72.7%(P＜0.01),肿瘤复发是肝癌患者随访期主要的死亡原因,占所有死亡事件的95.5%.全组HBV再感染率为6.0%,且多存在HBV DNA的变异,调整抗病毒药物可有效控制HBV再感染.胆道并发症总体发生率为11.8%,肝内胆道狭窄为主要表现形式(占56.5%),严重影响移植肝功能及受者生存质量.钙调磷酸酶抑制剂相关性肾损害发生率为8.2%,早期发现和处理可避免进展为不可逆肾损害.结论 肝移植是治疗终末期肝病的安全、有效手段,在严格选择适应证、有序随访管理前提下,肝移植受者可长期存活,且存活质量良好.

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Objective To investigate the survival condition of the liver transplant recipients and determine the factors which influence the long time survival. Methods Retrospective study of the follow-up data of the orthotopic liver transplantation recipients during 1999-2009 was performed.The survival rate of different primary disease was analyzed respectively. The recurrence of the primary disease, mortality and morbidity was also analyzed. Results 331 recipients were follwed up. The follow-up duration ranged from 8-120 months. The 1-, 3-, 5-, and 10-year survival rate of patients with benign end-stage liver disease was 86 %, 85 %, 83 %, and 83 %, respectively. There was no difference in the long- term survival rate between the patients with hepatitis B virus (HBV)-related cirrhosis and severe liver failure. The 1-, 3-, 5-, and 10-year survival rate of patients with HCC matching Millan criteria was 96 %, 87 %, 87 %, and 87 0%, while those of HCC exceeding Millan criteria were 42 % ,26 % ,24 % ,24 % resepectively. There was significant difference between them at the same period (P＜0. 01). The total recurrent rate of HCC recipient was 54. 3 %, and that of HCC matching and exceeding Millan criteria was 4.3 % and 72. 7 0% respectively (P＜0. 01 ). Tumor recurrence was the main cause of death of the malignancy. The HBV recurrent rate was 6. 0 0%, and all the cases were controlled by changing the antivirus regimen. The morbidity of billiary complication was 11.8 %, and intrahepatic biliary stricture was the most common type. CNIs-related renal impairment morbidity was 8. 2 % and the damage was reversible in condition of early diagnosis and treatment. Conclusion Orthotopic liver transplantation is an effective and safe treatment for end stage liver disease. The LTx recipients can get long time survival with perfect quallity life under proper medical supervision.     

肝移植治疗肝脏恶性肿瘤的长期疗效及预后危险因素

目的 总结肝移植治疗肝脏恶性肿瘤的长期疗效,筛选影响移植后肿瘤复发的危险因素.方法 对单中心189例肝脏恶性肿瘤患者行肝移植的临床资料进行回顾性分析.根据肿瘤临床病理类型分别计算受者累积存活率,分析肿瘤临床病理类型与肝移植术后肿瘤复发间的关系,筛选影响肿瘤复发的相关危险因素.结果 189例中围手术期死亡19例,170例进入随访期,随访率为98.8 %.其中166例的原发疾病为原发性肝癌,3例为肝门部胆管癌,1例肝转移癌.166例原发性肝癌肝移植者术后1、3、5和10年的总体存活率分别为52 %、38 %、36 %和36 %,其中符合米兰标准者(49例)的存活率分别为96 %、87 %、87 %和87 %,超出米兰标准者(136例)的存活率分别为42 %、26 %、24 %和24 %(P＜0.05).肿瘤复发是造成肝癌肝移植受者随访期死亡的最主要原因(92.5 %).3例肝门部胆管癌和1例肝转移癌肝移植受者均于术后2年内肿瘤复发.符合米兰标准的肝癌肝移植受者术后肿瘤复发率(10.2 %)显著低于超出米兰标准者(68.4 %,P＜0.05).而在超出米兰标准者中,无大血管侵犯者移植后肿瘤复发率(95.3 %)显著低于肿瘤侵犯大血管者(55.9 %,P＜0.05).以他克莫司为主要免疫抑制剂的受者的肿瘤复发率(46.2 %)低于应用环孢素A者(68.3 %,P＜0.05).移植术前肝肿瘤经皮穿刺射频消融(RF)治疗可降低受者术后肿瘤复发风险(P=0.039,OR=0.293),而术前外周血乙型肝炎病毒(HBV)DNA＞104拷贝/L是移植术后肿瘤复发的高危因素(P=0.016,OR=2.294).结论 对于符合米兰标准的肝癌患者而言,肝移植的远期疗效较好;而合并大血管侵犯者肝移植的预后不佳.移植前RF治疗有助于降低术后肿瘤复发风险,移植等待期应高度重视抗HBV治疗.

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Objective To investigate the long-term survival of the recipients with liver malignant tumors receiving liver transplantation and determine the risk factors of tumor recurrence after liver transplantation.Methods The follow-up data of the orthotopic liver transplantation for liver malignant tumors during 1999-2010 were retrospectively analyzed.The survival rate of different pathological tumor types was analyzed respectively.The tumor recurrence rate,mortality and morbidity,and the risk factors of the tumor recurrence were also analyzed.Results 170 recipients were followed up.The follow-up duration ranged from 8-132 months.The general 1-,3-,5-,10-year survival rate was 52 %,38 %,36 %,and 36 % respectively.The 1-,3-,5-,10-year survival rate of HCC matching Millan Criteria was 96 %,87 %,87 %,87 %,while that of HCC exceeding Millan Criteria was 42 %,26 %,24 %,24 % respectively(P<0.05).Tumor recurrence was the main course of the death during follow-up period(92.5 %).The recurrence rate of HCC matching and exceeding Millan Criteria was 10.2 %,and 68.4 % respectively(P<0.05).Among the recipients exceeding Millan Criteria,the recurrence rate of HCC with and without blood vessel invasion was 95.3 %,55.9 % respectively(P<0.05).Radiofrequency ablation before transplantation could decrease the risk of tumor recurrence post-transplantation(P=0.039,OR=0.293),while the high HBV-DNA load (>104 copy/L)was the risk factor of tumor recurrence.Conclusion Orthotopic liver transplantation is an effective and safe treatment for hepatocellular carcinoma matching Millan criteria.Blood vessel invasion is regarded as the contraindication of the liver transplantation of HCC.RF is an effective bridging therapy for the HCC patients,and anti-virus therapy is important during transplant waiting period.     

活体肝移植治疗儿童胆道闭锁44例

目的 观察活体肝移植治疗儿童胆道闭锁的效果,总结其临床经验.方法 2006年10月至2010年12月间共有44例胆道闭锁患儿接受了活体肝移植,其中男性26例,女性18例,年龄(12.1±9.0)个月,中位数为9个月(6～60个月);44名供者全部为患者直系亲属,年龄(32.7±8.0)岁,中位数为31岁(20～54岁).供、受者ABO血型相容,供肝均为供者肝脏的左外叶.对供、受者术前评估过程、手术方法、术后管理以及预后等临床资料进行总结.结果 术后对全部供者进行系统随访,随访时间(17.5±13.3)个月,无供者发生严重并发症和死亡,所有供者均恢复健康.44例受者中,死亡9例,死因分别为门静脉栓塞3例、肝动脉栓塞1例、胆道并发症2例、切口感染1例、腹腔出血1例及肺部感染1例,其余35例健康存活.术后1年和2年累积存活率分别为81.2%和76.1%,无一例受者接受再次肝移植.术后主要并发症有门静脉血栓、肝动脉血栓、胆汁漏及逆行性胆管炎、肺部感染、切口感染及急性排斥反应等.结论 活体肝移植是治疗儿童胆道闭锁的有效方法,预后良好.完善缜密的术前评估,熟练精细的手术操作以及精心的术后管理是改善受者预后的关键因素.

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Objective To observe the outcomes of living donor liver transplantation (LDLT) for children with biliary atresia (BA) and to summarize the clinical experiences. Methods Forty-four BA patients (26 boys and 18 girls) underwent LDLT between October 2006 and December 2010. Mean (SD) and median (range) age at operation was (12.1 ± 9.0) months and 9 (6-60) months,respectively. The 44 donors were lineal relatives to the consorted recipients. Their mean (SD) and median (range) age at operation was (32. 7 ± 8. 0) months and 31 (20～54) years, respectively. All donor graft types were the left lateral segments with compatible ABO blood groups. Clinical data,including pre-operative evaluations, surgical technique, postoperative management and outcomes in all donors and recipients were retrospectively analyzed. Results All donors were followed up for (17. 5 ± 13. 3) months. No donor mortality was encountered, with a minimal morbidity and no long-term sequelae. Nine out of 44 recipients died. Three patients died of portal vein thrombosis (PVT), one of hepatic artery thrombosis (HAT), two of biliary complications, one of surgical site infections, one of abdominal bleeding and one of pulmonary infection. The overall 1-year and 2-year cumulative survival rate in recipients was 81. 2% and 76. 1 %, respectively. No re-transplantation was done. Postoperative complications included PVT, HAT, biliary leakage and refluxing cholangitis, pulmonary infections,surgical site infections and acute rejection. Conclusion LDLT has been the effective treatment for pediatric recipients with BA and provides favorable prognosis. To improve prognosis of recipients, the key points are pre-operative evaluations, surgical technique, and postoperative management     

挽救性肝移植治疗肝癌切除术后肿瘤复发

目的 分析挽救性肝移植治疗肝癌切除术后肿瘤复发患者的疗效.方法 2004年1月至2008年12月,单中心376例肝癌患者接受了肝移植,其中36例(9.6 %)为行根治性肿瘤切除术后因肿瘤肝内复发而接受挽救性肝移植者(挽救性肝移植组).挽救性肝移植组中男性29例,女性7例;16例接受右半肝切除,10例接受左半肝切除,其余10例接受不规则肝切除或肝段切除.首次肝切除至行挽救性肝移植的时间为(34.9±16.2)个月(1～63个月).以同期符合米兰标准并接受首次肝移植的147例作为对照组,比较两组受者的术中情况及术后生存情况、肿瘤复发情况等.结果 挽救性移植组术中出血量和输血量明显多于对照组(P＜0.05),手术时间也长于对照组(P＜0.05).随访期间,挽救性肝移植组死亡11例,其中围手术期死亡1例;对照组共死亡36例,其中围手术期死亡3例.两组手术后并发症、肿瘤复发率、受者存活率以及无瘤存活率的差异无统计学意义(P＞0.05).结论 挽救性肝移植虽然较首次肝移植手术难度增加,但不影响患者预后,是根治性肝癌切除术后肿瘤复发患者的有效治疗手段.

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Objective To summarize the experience with salvage liver transplantation for patients with recurrent hetaptocellular carcinoma(HCC)after primary liver resection.Methods From 2004 to 2008,376 patients with HCC received liver transplantation in our single center.Among these patients,36 (9.6 %)underwent salvage liver transplantation after primary liver curative resection due to intrahepatic recurrence.There were 29 males and 7 females with the mean age of 46 years old.Sixteen received right lobectomy,10 received left lobectomy and the others received sectionectomy or segmentectomy.As a control group for comparison,we used clinical data of the 147 patients who underwent primary OLT for HCC within Milan Criteria.Results The mean interval between initial liver resection and salvage transplantation was 34.9±16.2 months(1-63 months).Intraoperative bleeding volume,transfusion volume and operative time in the salvage group were significantly different from those in control group (P<0.05).There were no significant difference in post-operative complications,tumor recurrence rate,survival rate and tumor-free survival between these two groups(P>0.05).Conclusion In comparison with primary OLT,although salvage liver transplantation would increase the operation difficulties,it still remains a good option for patients with HCC recurrence after curative resection.     

婴幼儿活体肝移植33例

目的 探讨活体肝移植治疗婴幼儿终末期肝病的疗效.方法 回顾性分析2006年10月至2009年9月上海交通大学医学院附属仁济医院33例实施活体肝移植的婴幼儿的临床资料.本组患儿中位年龄10.9个月,平均体质量8.2 kg,供肝均采用肝左外叶.术后采用他克莫司或环孢素A+激素二联方案或在此基础上再加用吗替麦考酚酯的三联方案行免疫抑制治疗.分析评价手术方法、围手术期处理和随访结果.结果 供者和受者手术时间、术中出血量、术中输血量分别为(384±108)min、(183±35)ml、0和(500±103)min、(296±163)ml、(292±159)ml,供肝冷缺血时间为(64±23)min,移植物质量为(249±52)g,移植物质量与受者体质量比为2.1%±0.4%.全部供者均顺利康复,无手术并发症.受者出现肝动脉栓塞3例,门静脉栓塞2例,各类胆道并发症9例,感染11例,急性排斥反应2例,围手术期死亡5例.本组患儿1年累积生存率为85%(28/33).结论 婴幼儿终末期肝病可通过活体肝移植取得理想的效果.外科技术的提高、围手术期管理经验的积累和规范的随访可提高手术成功率和长期生存率.

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Objective To evaluate the efficacy of living donor liver transplantation in the treatment of infants with end-stage liver diseases. Methods The clinical data of 33 infants who received living donor liver transplantation at the Renji Hospital of Shanghai Jiaotong University from October 2006 to September 2009 were retrospectively analyzed. The median age of the infants was 10.9 months, and the mean body weight was 8.2 kg.All of the grafts were left lateral lobes. Tacrolimus (or cyclosporine A) + steroid or tacrolimus (or cyclosporine A)+ steroid + mycophenolate mofeti] were applied to the infants to suppress the immune reaction. Operative techniques, perioperative management and results of follow-up were analyzed. Results The mean operation time,blood loss and blood transfusion of the donors were (384±108)minutes, (183±35) ml and O, and the three indexes of the recipients were (500± 103) minutes, (296±163) ml and (292 ± 159) ml , respectively. The cold preservation time of the grafts was (64 ±23)minutes, the mean weight of the grafts was (249 ±52)g, and the mean graft to recipient weight ratio was 2.1% ± 0.4%. All donors recovered smoothly and no complication occurred. Of the recipients, three were complicated with hepatic artery thrombosis, two with portal vein thrombosis,nine with biliary complications, 11 with infection, two with acute rejection and five infants died perioperatively.The one-year cumulative survival rate of the infants was 85% (28/33). Conclusions Infants with end-stage liver diseases could be treated by living donor liver transplantation. The development of surgical techniques and perioperative managements improves the success rate of operation and the long-term survival rate.     

大鼠30%小体积肝移植模型手术技巧

目的 建立稳定、理想的大鼠30%体积肝移植模型.方法 二袖套法和体内切肝法建立非动脉化30%体积肝移植模型,对100只SD大鼠施行50例30%体积肝移植(10例前期操作,不列入统计),对手术操作技巧和细节、术后存活及原因等进行探讨.结果 手术成功率100%(40/40),术后1周、2周存活率均40%(16/40),死亡原因主要为肝功能失代偿、胆管梗阻或胆漏、肝上下腔静脉血栓形成、肝叶坏死和腹腔感染等.结论 30%体积肝移植模型改进后供肝残面出血率低,机械损伤小,供肝再灌注色红均匀,存活率好,可作为小体积肝移植有关实验研究的动物模型.

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Objective To establish a reliable and ideal model of 30% size graft liver transplantation in rats. Methods The model of 30% size graft liver transplantation in vivo was established by using male SD rats according to Kamada's two-cuff method. The operative techniques and ditails, and survival rate were explored and analyzed. Results The rate of successful surgery was 100% (40/40). The one- and two-week survival rate both were 40% (16/40), and the causes of deaths included liver function decompensation, bile duct stenosis or bile leakage, thrombosis of super inferior vena cava, liver necrosis and celiac infection.Conclusion Improved model of 30% small-for-size liver transplantation had a low hemorrhage rate of residual liver surface, reduced mechanical damage in small-for-size graft, high success rate and survival rate, and was an ideal animal model on the study of experiments related to the small-for-size liver transplantation.     

终末期良性肝病患者肝移植后免疫抑制治疗单中心经验总结

目的 总结单中心原发病为良性终末期肝病患者肝移植后免疫抑制剂的应用经验,探讨个体化治疗方案.方法 回顾性分析单中心1400例肝移植中645例原发病为良性终末期肝病者的资料.2002年4月至2004年12月为第1阶段(共146例),受者均采用常规三联用药方案,即他克莫司(Tac)+吗替麦考酚酯(MMF)+甲泼尼龙(MP);2005年1月至2007年12月为第2阶段(共273例),受者用药量较前减少;2008年1月至2010年8月为第3阶段(共226例),根据术前终末期肝病模型(MELD)评分及受者状况分为常规组和重症组,采用个体化免疫抑制方案.结果 3个阶段中,MELD评分<25分者的存活率分别为88.9%、94.2%和95.4%,MELD评分≥25分者的存活率分别为67.7%、73.4%和82.0%.3个阶段中MELD评分<25分者排斥反应发生率的差异无统计学意义(P>0.05),MELD评分≥25分者第2阶段和第3阶段排斥反应发生率稍高于第1阶段(P<0.05).结论 肝移植术后免疫抑制剂的应用可根据受者的具体情况进行个体化应用,有利于提高其存活率.

Abstract：

Objective To analyze the individual immunosuppressive protocol (IP) after liver transplantation (LT) in benign end-stage liver disease. Methods The clinical data of 645 patients with benign end-stage liver disease undergoing LT in our institute from April 2002 to Aug 2010 wen analyzed retrospectively. 146 cases from Apr. 2002 to Dec. 2004 were in stage one, and triple therapy containing tacrolimus (Tac), mycophenolate mofetil (MMF) and methylprednisolone (MP) was used;273 cases from Jan. 2005 to Dec 2007 were in stage two, and the less dose of immunosuppressant than stage one was used; 226 cases from Jan. 2008 to Aug. 2010 were in stage three, and they wen divided into conventional group and severe patient group according to their preoperative model for endstage liver disease (MELD) score and patient condition, the individual IP was used. Results The overall survival rate of patients with MELD score <25 was 88. 9 % in stage one, 94. 2 % in stage two, and 95. 4 % in stage three; The overall survival rate of patients with MELD score ≥25 was 67. 7 % in stage one, 73. 4 % in stage two, and 82. 0 % in stage three. The incidence of rejection ir cases with MELD score <25 had no significant difference (P>0. 05). The incidence of rejection in cases with MELD score ≥25 in stage two and stage three was higher slightly than in stage one (P<0. 05). Conclusion The IP after liver transplantation should be individualized according to recipient conditions, which can increase survival rate.     

单中心11例肝内胆管细胞癌肝移植疗效分析

Objective To evaluate the effect of liver transplantation(LT)on the prognosis in patients with intrahepatic cholangiocarcinoma(ICC).Methods A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution.The overall and disease-free survival rates were calculated by the Kaplan-Mayer method.Results The median survival time Was 9.0 months(2.5-53 months).The 1-,2-,3-and 4-year disease-free survival rate and overall survival rate of all the patients were 51.9%、51.9%、51.9%、51.9%and 50.5%、50.5%、50.5%、50.5%,respectively.The perioperative mortality and the recurrence rate were 0 and 43.5%,respectively.The survival rate and disease-free survival time of patients with recurrence were 2.5-10 months(mean 7.5 months)and 1-8 months(mean 3.8 months).Conclusions The prognosis of LT for ICC is rather poor.ICC patients with lymph node metastasis.vascular or bile duct invasion is contraindicated for LT.     

应用MRCP术前评估活体肝移植供者胆管系统

Objective To determine the clinical value of MRCP for peroperative evaluation of donor biliary system in living donor liver transplantation (LDLT). Methods A total of 60 living donors for the LDLT were enrolled in this study. Of the 60 donors with a mean age of 32.2 (19-60), 50were male and 10 female. MRCP was performed before and cholangiography was done during the right lobectomy in these donors. The results of MRCP were compared with those of cholangiography to determine the value of MRCP for typing the biliary system in the donors. Results The preoperative MRCP showed that 40 donors were of type Ⅰ biliary tract, 12 of type Ⅱ , 5 of type Ⅲ and 3 of other types. The intraoperative cholangiography showed that the accordance rate of MRCP was 97.4%,91% and 89% for type Ⅰ , type Ⅱ and other types, respectively. The overall rate of accuracy of MRCP was 95% (57/60). Conlusion MRCP can show types of biliary tract in living donors for liver transplantation to provide evidence for plan of surgery.     

肝细胞肝癌肝移植受者术后生存及肿瘤复发临床分析

目的比较符合米兰标准和杭州标准的肝细胞肝癌(HCC)肝移植受者术后生存及肿瘤复发情况,分析移植术后生存和肿瘤复发影响因素。 方法回顾性分析青岛大学附属医院器官移植中心2014年2月1日至2018年12月31日符合米兰标准和杭州标准的119例HCC肝移植受者临床资料。符合米兰标准受者79例(米兰标准组),超出米兰标准但符合杭州标准者受者40例(杭州标准组)。所有受者肝移植术后均规律随访,收集受者性别、年龄和手术时间等临床资料。无瘤生存时间以受者移植术后发现肿瘤复发转移为观察终点,累积生存时间以受者移植术后死亡为观察终点。采用Kaplan-Meier法绘制生存曲线,采用log-rank检验比较组间累积生存率和无瘤生存率。采用Cox比例风险模型进行影响累积生存时间和无瘤生存时间的单因素和多因素分析。P<0.05为差异有统计学意义。 结果截至2019年7月31日,119例受者术后中位随访时间为27个月(15～43个月),其中术后因肿瘤复发死亡11例复发转移27例。米兰标准组受者1、3和5年累积生存率分别为98.7%、90.2%和90.2%,杭州标准组分别为97.2%、73.9%和73.9%,差异均无统计学意义(χ²＝0.219、1.598和1.598,P均>0.05)。米兰标准组受者1、3和5年累积无瘤生存率分别为90.3%、82.1%和68.6%,杭州标准组分别为81.6%、56.0%和56.0%,两组受者术后1年和5年累积无瘤生存率差异均无统计学意义(χ²＝1.587和3.707,P均>0.05),3年累积无瘤生存率差异有统计学意义(χ²＝5.543,P<0.05)。多因素分析结果证实术前有无脉管癌栓是影响其累积生存率的独立危险因素,差异有统计学意义(HR＝0.159,P<0.05);术前有无脉管癌栓和病理分化类型是影响无瘤生存的独立危险因素,差异均有统计学意义(HR＝0.338和0.395,P均<0.05)。 结论符合杭州标准的HCC肝移植受者移植术后可获得较好的累积生存率及无瘤生存率,受者术前是否存在脉管癌栓及病理分化程度可以指导移植术后肿瘤复发的预防。     

Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. METHODS: A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. RESULTS: Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter >5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value >300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. CONCLUSIONS: LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors <5 cm.     

肝移植治疗原发性肝癌103例疗效观察

目的 比较不同受体选择标准肝癌肝移植的远期疗效,分析肝痛肝移植术后肿瘤复发相关因素.方法 总结北京佑安医院2004年4月至2008年3月间的103例肝癌肝移植的临床资料,按照肿瘤的特征将其分为3组:符合米兰标准组(A组)、超出米兰标准但满足UCSF标准组(B组)和超出UCSF标准组(C组),比较3组的总体生存率及无瘤生存率,并分析影响远期预后的相关因素.结果 103例肝癌肝移植总体1、2、3年存活率分别为84.0%、70.5%和60.2%.其中A组50例,1、2、3年生存率和无瘤生存率分别为93.4%、83.8%、73.2%和97.3%、93.9%、88.7%;B组17例,1、2、3年生存率和无瘤生存率分别为93.3%、79.4%、66.2%和86.7%、79.4%、66.2%;C组36例,1、2、3年生存率和无瘤牛存率分别为67.0%、45.5%、34.1%和65.8%、50.0%、41.7%.远期生存率A组与B组比较无差异(P=0.631),A组、B组与C组比较具有统计学差异(P值分别为0.001,0.045).结论 米兰标准是肝癌肝移植最佳适应证,超出米兰标准但满足UCSF标准也可获得满意的远期疗效;肿瘤的分期和微血管侵犯是影响远期预后的风险因素.     

Living donor liver transplantation for hepatocellular carcinoma: a single-center experience in Taiwan

BACKGROUND: Living donor liver transplantation (LDLT) demonstrates certain survival benefits over deceased donor liver transplantation for hepatocellular carcinoma (HCC) but there is no consensus on criteria for the use of LDLT for HCC for hepatocellular carcinoma (HCC) taking into account strategies to improve survival. METHODS: Thirty-five patients (89% men) underwent LDLT for HCC. The mean age was 51 years (range, 22-61). The median disease severity scores were B, 11-20, and 2B for Child-Turcotte-Pugh, Model for End-stage Liver Disease, and United Network for Organ Sharing, respectively. The transplant records were retrospectively analyzed. RESULTS: All were within Milan criteria at time of transplantation. A novel approach to downstaging tumors initially beyond the Milan criteria was evaluated using transarterial embolization or percutaneous ethanol injection. Our initial results were encouraging as recipients whose tumors had been downstaged had not had recurrence to date. Seven (20%) patients underwent hepatectomy for HCC before undergoing transplant. The overall mean posttransplant follow-up in this series was 40.3 months (range, 23-75). The overall posttransplant complication rate requiring intervention was 11%. There was only one malignancy recurrence for an overall recurrence rate of 3%. Vascular invasion and small- for-size transplants did not seem to influence tumor recurrence. The nonestimated recipient 1-year, 3-year, and 5-year survivals were 98%, 96%, and 90%, respectively. CONCLUSION: This review emphasizes the need for early disease recognition and prompt intervention when Milan criteria are met to improve survival from HCC after LDLT.     

Predictors of Outcome of Living Donor Liver Transplantation for Hepatocellular Carcinoma

The aim of this work is to study the different factors that affect the outcome of living donor liver transplantation for patients with hepatocellular carcinoma (HCC). Between April 2003 to November 2014, 62 patients with liver cirrhosis and HCC underwent living donor liver transplantation (LDLT) in the National Liver Institute, Menoufia University, Egypt. The preoperative, operative, and postoperative data were analyzed. After studying the pathology of explanted liver; 44 (71 %) patients were within the Milan criteria, and 18 (29 %) patients were beyond Milan; 13 (21.7 %) of patients beyond the Milan criteria were also beyond the University of California San Francisco criteria (UCSF) criteria. Preoperative ablative therapy for HCC was done in 22 patients (35.5 %), four patients had complete ablation with no residual tumor tissues. Microvascular invasion was present in ten patients (16 %) in histopathological study. Seven (11.3 %) patients had recurrent HCC post transplantation. The 1, 3, 5 years total survival was 88.7, 77.9, 67.2 %, respectively, while the tumor-free survival was 87.3, 82.5, 77.6 %, respectively. Expansion of selection criteria beyond Milan and UCSF had no increased risk effect on recurrence of HCC but had less survival rate than patients within the Milan criteria. Microvascular invasion was an independent risk factor for tumor recurrence.     

肝癌肝移植术后应用亚砷酸化疗的临床效果观察

目的 探讨超出米兰标准的肝癌病人肝移植术后应用亚砷酸全身化疗对肿瘤复发的意义.方法 对23例超出米兰标准的肝癌病人肝移植术后采用亚砷酸化疗:静脉滴注10 mg/d,连续使用7 d后间隔7 d,重复4次为1疗程.以上病人接受1～4个疗程治疗.观察化疗病人的生存情况、肿瘤复发情况以及化疗副作用,并与同期16例未使用化疗的肝癌肝移植病人相比较.结果 经过3～32个月随访,共有30例病人出现肝癌复发,化疗组16例,非化疗组14例,复发部位最常见于肺部、移植肝及骨骼.化疗组与非化疗组肿瘤复发率无明显差异,出现肝癌复发的时间分别为移植术后(14.5±7.5)个月和(10.2±4.6)个月,化疗组复发时间明显延迟(P=0.026);6个月、1年生存率分别为91.3%、87.0%和93.7%、87.5%,两组间无明显差异,化疗组2年生存率明显高于非化疗组(73.9% vs 50.0%,P=0.037);6个月无瘤生存率无明显差别(87.0% vs 81.2%)、1、2年无瘤生存率化疗组明显高于非化疗组(82.6% vs 50.0%,P=0.030;65.2% vs 43.7%,P=0.023).亚砷酸使用过程中未发现严重副作用.结论 静脉使用亚砷酸化疗在超出米兰标准的肝癌肝移植病人中可以延迟肿瘤复发,改善病人长期存活情况.     

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma

Background/Purpose The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. Methods Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. Results (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045). Conclusions HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.     

Living donor liver transplantation for hepatocellular carcinoma: a single center analysis of outcomes and impact of different selection criteria

We examined the outcomes of patients who received living donor liver transplantation (LDLT) for HCC comparing the impact of up‐to‐seven criteria and Asan Criteria (AC) with Milan Criteria (MC). Between July 2004 and July 2009, of 175 consecutive LDLT, there were 45 consecutive patients with HCC. Forty patients who completed 12 months follow‐up were enrolled. In search for the highest number of expansion, we selected AC as the extended criteria. Patients were divided into having tumors within MC, beyond MC within AC and Beyond Criteria (BC) groups. With a median follow‐up of 46 months, overall 1, 3, and 5 years survival was ?90%, ?81%, and ?70%, respectively. In patients within AC, estimated mean survival was 49.8 vs. 40.5 months for BC group (P = 0.2). Disease‐free survival was significantly higher in patients within AC comparing with BC group; 48.0 vs. 38.6 months (P = 0.04). Preoperative AFP level >400 and poor tumor differentiation were factors adversely effecting recipient survival. On multivariate analysis, the presence of poor tumor differentiation (P = 0.018 RR: 2.48) was the only independent predictor of survival. Extension of tumor size and number to AC is feasible, without significantly compromising outcomes; however, the presence of poor tumor differentiation was associated with worse outcomes after LDLT.     

Response to Transarterial Chemoembolization in Candidates With Hepatocellular Carcinoma Within Milan Criteria Does not Predict Post-Transplant Disease-Free Survival

Introduction

Few groups have studied the impact of pretransplant transarterial chemoembolization (TACE) in the outcomes of liver transplant recipients with hepatocellular carcinoma (HCC). We verified whether response to TACE in HCC candidates impacts post-transplant disease-free survival.

Methods

This a single center retrospective study of patients who underwent liver transplantation from 2006–2013. Included were those transplanted due to HCC within the Milan criteria who were treated with TACE in the pre-transplant period. Response to TACE followed the modified RECIST (mRECIST) criteria. Disease free-survival was the main endpoint of the study.

Results

We included 187 patients in this study. The population had an average age of 57.5 years, predominantly formed by men (82.5%), with an average IMC of 26.7, MELD of 13, with viral hepatitis as main cause of liver disease. Average waiting time was 253 days and follow-up was 27.3 months. Based on response to TACE, 3-year disease-free survival was 84.1% for those with complete response to TACE, 84.1% for those with partial response to TACE, 85.7% for those with stable disease and 100% for patients with progressive disease. Multivariate analysis did not identify response to TACE as a predictor of disease-free post-transplant survival.

Conclusions

Response to TACE in candidates with HCC within Milan criteria does not predict post-transplant disease-free survival.     

Survival outcomes in liver transplantation for hepatocellular carcinoma, comparing impact of hepatitis C versus other etiology of cirrhosis.

The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide as the most common primary hepatic malignancy. In the US approximately one half of all HCC is related to Hepatitis C virus (HCV) infection. The relationship between the primary disease and HCC recurrence after liver transplantation is unknown. We hypothesized that the primary hepatic disease underlying the development of cirrhosis and HCC would be associated with the risk of recurrent HCC after transplantation. A retrospective review was conducted of all primary liver transplants performed at the University of Rochester Medical Center from May 1995 through June 2004. The pathology reports from the native livers of 727 recipients were examined for the presence of HCC. There were 71 liver transplant recipients with histopathological evidence of HCC. These patients were divided in two groups on the basis of HCV status. Group 1 consisted of 37 patients that were both HCV and HCC positive, and Group 2 consisted of 34 patients that were HCC positive but HCV negative. Patient characteristics were analyzed, as well as number of tumors, tumor size, presence of vascular invasion, lobe involvement, recipient demographics, donor factors, pretransplantation HCC therapy, rejection episodes, and documented HCC recurrence and treatment. There were no statistically significant differences between the 2 groups, with the exception of recipient age and the presence of hepatitis B coinfection. The tumor characteristics of both groups were similar in numbers of tumors, Milan criteria status, vascular invasion, incidental HCC differentiation, and largest tumor size. The HCV positive population had a far lower patient survival rate with patient survival in Group 1 at 1, 3, and 5 years being 81.1%, 57.4%, and 49.3% respectively, compared with 94.1%, 82.8%, and 76.4% in Group 2 (p = 0.049). Tumor-free survival in Group 1 at 1, 3, and 5 years was 70.3%, 43%, and 36.8% respectively, vs. 88.1%, 73%, and 60.8% in Group 2. In a subgroup analysis, tumor-free survival was further examined by stratifying the patients on the basis of Milan criteria. Group 1 patients outside of Milan criteria had a statistically lower tumor-free survival. By contrast, there was no statistical difference in tumor-free survival in Group 2 patients stratified according to Milan criteria. Cox regression analysis identified HCV and vascular invasion as significant independent predictors of tumor-free survival. Our results suggest that Milan selection criteria may be too limiting and lose their predictive power when applied to patients without HCV infection.