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.

Abstract：

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.     

肝移植治疗肝癌的受者选择杭州标准在亲属活体供肝移植中的应用价值

目的 探讨肝移植治疗肝癌的受者选择杭州标准在亲属活体供肝移植中的应用价值,及其对术后存活的影响.方法 回顾分析43例亲属活体供肝移植受者的临床资料.按照是否符合米兰标准、Up-To-Seven标准及杭州标准将受者分组,比较各组纳入受者的例数、术后总体存活率及无瘤存活率.结果 符合杭州标准的受者例数比米兰标准增加了61.5 %(8/13),比Up-to-Seven标准增加了23.5 %(4/17).符合米兰标准的受者(13例)术后1、3年总体存活率和无瘤存活率分别为100 %、80.0 %和84.6 %、84.6 %;符合Up-to-Seven标准的受者(17例)术后1、3年总体存活率和无瘤存活率分别为100 %、75.2 %和87.5 %、81.2 %;符合杭州标准的受者(21例)术后1、3年总体存活率和无瘤存活率分别为100 %、80.0 %和89.5 %、84.2 %.3组间总体存活率和无瘤存活率的比较,差异均无统计学意义(P＞0.05).结论 杭州标准能将更多的肝癌患者纳入肝移植,且不影响术后总体存活率和无瘤存活率,是筛选肝癌患者接受亲属活体肝移植的有效标准.

Abstract：

Objective To investigate the clinical value of Hangzhou Criteria in selection of patients with hepatocellular carcinoma(HCC)for living donor liver transplantation(LDLT)and their effects on recipient's post-transplant survival.Methods A retrospective analysis was conducted on 43 patients with HCC who underwent LDLT in our center.All of the recipients were classified into subgroups according to Milan Criteria,Up-to-Seven Criteria and Hangzhou Criteria,and post-transplant total survival rate and tumor-free survival rate were compared among the criteria.Results The number of patients within Hangzhou Criteria was 61.5 %(8/13)more than that within Milan Criteria and 23.5 %(4/17)more than that within Up-to-Seven Criteria.The 1-,and 3-years total survival rate and tumor-free survival rate of the recipients within Milan Criteria(n=13)were 100 %,80.0 % and 84.6 %,84.6 %,those of the recipients within Up-to-Seven Criteria(n=17)were 100 %,75.2 % and 87.5 %,81.2 %,and those of the recipients within Hangzhou Criteria(n=21)were 100 %,80.0 % and 89.5 %,84.2 %,respectively.There was no significant difference among the three criteria in total survival rate and tumor-free survival rate(P>0.05).Conclusion Hangzhou Criteria further enrolled more liver transplantation candidates without decline of total survival rate and tumor-free survival.It is a more effective selection of HCC recipients for LDLT.     

维生素K2预防肝癌根治术后肿瘤复发

Objective To study the preventive effects of vitamin K2 on tumor recurrence in patients with hepatocellalar carcinoma (HCC) after radical resection. Methods The clinical data of 50 patients with HCC who received radical resection from March 2006 to March 2007 in No. 181 Hospital of PLA were analyzed retrospec-tively. All the patients were divided into 2 groups according to the random number table. Twenty-six patients in vitamin K2 group were administered with menatetrenone (45 mg per day), and the rest 24 pateints were in the control group. The accumulative and tumor-free survival rates, differences between the 2 groups, multivariate factors for prognosis were analyzed by Kaplan-Meier curve, Log-rank test and Cox regression model, respectively. Results During a period of 36 month follow-up, 10 patients died and 28 had tunor recurrence. The 1-, 2-, 3-year accumulative survival rates were 96%, 92% and 83% in vitamin K2 group, and 96%, 82% and 63% in control group (χ2 = 3.61, P > 0.05). The 1-, 2-, 3-year tumor-free survival rates were 92%, 60% and 38% in vitamin K2 group, and 75%, 42% and 12% in control group, with significant difference between the 2 groups (χ2 =5.61, P <0.05). Univariate and multivariate Cox proportional hazard analysis showed that without taking menate-trenone, the preoperative level of alpha fetoprotein (AFP) ≥800 μg/L and vascular invasion were the indepen-dent risk factors for tumor recurrence. Conclusions Vitamin K2 has a suppressive effect on tumor recurrence of HCC, while patients with AFP≥800 μg/L before operation or with vascular invasion have poor prognosis.     

活体肝移植治疗原发性肝癌的疗效分析

目的 通过活体肝移植(LDLT)与尸体肝移植(DDLT)治疗原发性肝癌(HCC)的比较,探讨LDLT治疗HCC的疗效.方法 分析2007年1月至2008年12月间我院实施的105例肝癌肝移植手术(其中LDLT38例,DDLT67例)的临床资料和随访结果.结果 LDLT患者1年及3年生存率分别为92.1％及78.9％,...     

肝癌肝移植术后肿瘤复发转移的防治

肝癌肝移植术后肿瘤复发转移是影响肝移植治疗肝癌疗效的主要因素.深入研究肝癌的生物学特性和肝移植术后患者免疫状态与肿瘤复发转移的关系,筛选准确预测肝癌肝移植的预后指标,对高危复发风险的患者进行有效的干预治疗,对复发转移者进行个体化综合治疗有助于进一步提高肝移植治疗肝癌的疗效.

Abstract：

Post-transplant tumor recurrence and metastasis remain the main obstacles for long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC). Measures to explore the HCC biological characteristics and the relationship between post-transplant immuno-suppression and tumor recurrence, to determine precisely the prognostic factors associated with post-transplant recurrence, to intervene effectively for those with high risk of recurrence, and to use individualized multimodality treatment for recurrence and metastasis may improve the therapeutic results of LT for HCC.     

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.

Abstract：

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.     

美国活体肝移植受者的终末期肾病风险

<正>自从采用基于终末期肝病模型(MELD)的供肝分配原则后,肝移植术后终末期肾病(ESRD)的风险相应增加。近期美国的临床数据显示活体肝移植(LDLT)受者的生存率与尸体肝移植(DDLT)受者相近,甚至优于后者。但LDLT术后受者ESRD的发生率报道较少。美国宾夕法尼亚大学学者分析了器官移植科学注册系统(SRTR)和美国肾病数据系统(USRDS)中2002年2月27日至2011年3月1日首次接受单独肝脏移植且术前MELD≤25分未接受透析治疗的受者,分析LDLT后ESRD的发生率并与DDLT受     

浆膜受侵的结直肠癌术后腹腔化疗联合静脉化疗的临床研究

Objective To compare the clinical efficacy of postoperative intraperitoneal chemotherapy combined with systemic chemotherapy to systemic chemotherapy alone for serosa-involved colorectal cancer. Methods According to the criteria of serosa-involving in colorectal cancer, 332 cases were divided into 2 groups prospectively without randomization. Study group (n=166) was treated with intraperitoneal chemotherapy combined with systemic chemotherapy, and control group (n=166) with systemic chemotherapy alone. Incidence of local recurrence, peritoneal metastasis, hepatic metastasis, other distant metastasis and 3-year, 5-year overall survival (OS) rate of two groups were compared. Results 3-year and 5-year OS rates of stage Ⅱ B in study group were similar to those in control group (χ2=0.612,P=0.434). The above rates of stage Ⅲ in study group were higher than those in control group (χ2=3.989,P=0.046). Either the study group or the control group, the 3-year and 5-year OS rates of patients undergone laparoscopic surgery or open surgery were similar (P=0.839, P=0.172). Incidences of local recurrence, peritoneal metastasis and hepatic metastasis in study group were 1.9%, 3.8% and 3.8% respetively, lower than those in control group (8.2%,9.5% and 10.1%,P<0.05). Distant metastasis rate in study group was similar to that in control group. In study group, intraperitoneal chemotherapy regimen with Oxaliplatin had lower rates of peritoneal metastasis and hepatic metastasis as compared to that with Cisplatin (0.9% vs 8.8% ,P=0.019), while the incidences of local recurrence and other distant metastasis were similar. Conclusions Postoperative intraperitoneal chemotherapy combined with systemic chemotherapy improves 3-year and 5-year overall survival rates in patients with stage Ⅲ serosa-involved colorectal cancer, and decreases local recurrence, peritoneal metastasis and liver metastasis rate, especially when intraperitoneal chemotherapy regimen contains Oxaliphtin. Comparing with open surgery, laparoscopic surgery dose not improve 3-year and S-year overall survival rates in patients receiving combined chemotherapy or systemic chemotherapy alone.     

浆膜受侵的结直肠癌术后腹腔化疗联合静脉化疗的临床研究

Objective To compare the clinical efficacy of postoperative intraperitoneal chemotherapy combined with systemic chemotherapy to systemic chemotherapy alone for serosa-involved colorectal cancer. Methods According to the criteria of serosa-involving in colorectal cancer, 332 cases were divided into 2 groups prospectively without randomization. Study group (n=166) was treated with intraperitoneal chemotherapy combined with systemic chemotherapy, and control group (n=166) with systemic chemotherapy alone. Incidence of local recurrence, peritoneal metastasis, hepatic metastasis, other distant metastasis and 3-year, 5-year overall survival (OS) rate of two groups were compared. Results 3-year and 5-year OS rates of stage Ⅱ B in study group were similar to those in control group (χ2=0.612,P=0.434). The above rates of stage Ⅲ in study group were higher than those in control group (χ2=3.989,P=0.046). Either the study group or the control group, the 3-year and 5-year OS rates of patients undergone laparoscopic surgery or open surgery were similar (P=0.839, P=0.172). Incidences of local recurrence, peritoneal metastasis and hepatic metastasis in study group were 1.9%, 3.8% and 3.8% respetively, lower than those in control group (8.2%,9.5% and 10.1%,P<0.05). Distant metastasis rate in study group was similar to that in control group. In study group, intraperitoneal chemotherapy regimen with Oxaliplatin had lower rates of peritoneal metastasis and hepatic metastasis as compared to that with Cisplatin (0.9% vs 8.8% ,P=0.019), while the incidences of local recurrence and other distant metastasis were similar. Conclusions Postoperative intraperitoneal chemotherapy combined with systemic chemotherapy improves 3-year and 5-year overall survival rates in patients with stage Ⅲ serosa-involved colorectal cancer, and decreases local recurrence, peritoneal metastasis and liver metastasis rate, especially when intraperitoneal chemotherapy regimen contains Oxaliphtin. Comparing with open surgery, laparoscopic surgery dose not improve 3-year and S-year overall survival rates in patients receiving combined chemotherapy or systemic chemotherapy alone.     

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.

Abstract：

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.     

Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma

BACKGROUND: Hypothetical studies that favour living donor liver transplantation (LDLT) for early hepatocellular carcinoma (HCC) assumed a comparable outcome after LDLT and deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcome after LDLT with that after DDLT, and to identify factors that might account for any differences. METHODS: The study included 60 patients who met the radiological Milan or University of California at San Francisco (UCSF) criteria and underwent LDLT (43 patients) or DDLT (17). RESULTS: The LDLT group had fewer incidental tumours and a lower rate of pretransplant transarterial chemoembolization but a higher rate of salvage transplantation. Waiting time was shorter and graft weight to standard liver weight (GW : SLW) ratio was lower in this group. The perioperative course, and histopathological tumour size, number, grade and stage were comparable. Median follow-up was 33 (range 4-120) months. The cumulative 5-year recurrence rate was 29 per cent in the LDLT group and 0 per cent in the DDLT group (P = 0.029). A GW : SLW ratio of 0.6 or less, salvage transplantation, three or more tumour nodules, microscopic vascular invasion, and pathological stage beyond the Milan or UCSF criteria were significant confounding risk factors. Multivariable analysis identified salvage transplantation (relative risk 5.16 (95 per cent confidence interval (c.i.) 1.48 to 18.02); P = 0.010) and pathological stage beyond the UCSF criteria (relative risk 4.10 (95 per cent c.i. 1.02 to 16.48); P = 0.047) as independent predictors of recurrence. CONCLUSION: Despite standard radiological selection criteria based on number and size, patients who underwent LDLT for HCC had more recurrence because of selection bias for other clinical characteristics.     

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: comparable survival and recurrence

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow-up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1-, 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC.     

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.     

Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation.

In this retrospective study of hepatitis C virus (HCV)-infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.     

Living Donor Liver Transplantation for Hepatocellular Carcinoma: Long-Term Results Compared With Deceased Donor Liver Transplantation

Objective

Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC.

Patients and Methods

Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT.

Results

The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS).

Conclusions

LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.     

A revised scoring system utilizing serum alphafetoprotein levels to expand candidates for living donor transplantation in hepatocellular carcinoma

BACKGROUND: The development of living donor liver transplantation has stimulated discussion about the expansion of tumor burden limits for patients with hepatocellular carcinoma (HCC). Although serum alphafetoprotein (AFP) level is an important predictor of tumor recurrence, it is not included in the existing selection criteria for HCC in transplantation. METHODS: We performed a retrospective study of 63 consecutive adults with HCC diagnosed preoperatively who received living donor liver transplantation from February 1999 to September 2005 and survived over 1 month. The authors devised new scoring criteria that included tumor size, tumor number, and pretransplant AFP level as prognostic factors. The score of each parameter was classified from 1 to 4 points (tumor size, < or =3, 3.1 to 5, 5.1 to 6.5, >6.5 cm; tumor number, 1, 2 or 3, 4 or 5, or > or =6 nodules; and AFP, < or =20, 20.1 to 200, 200.1 to 1000, >1000 ng/mL, respectively). We defined that 3 to 6 points and 7 to 12 points were "transplantable" and "nontransplantable," respectively. The usefulness of the devised criteria was then investigated as a method of selecting candidates with HCC for transplantation. RESULTS: The candidates' overall 3-year survival rate and recurrence-free survival rate were 67% and 70% after transplantation, respectively. Based on pretransplant imaging, 37 (59%), 41 (65%), and 44 (70%) of the 63 patients met the Milan criteria, University of Californica, San Francisco (UCSF) criteria, and the new scoring criteria. Their 3-year survival rates were 80%, 78%, and 79%, respectively. Moreover, based on posttransplant data, the scoring criteria correlated with the risk of death and HCC recurrence (Milan criteria, P = .005 and .001; UCSF criteria, P = .013 and .001 for death and recurrence; scoring criteria, P < .001 for both). CONCLUSIONS: The newly devised scoring criteria could expand usefully current selection criteria for transplantation without detrimentally affecting outcome in the living donor transplantation setting for HCC.     

Outcomes of Living and Deceased Donor Liver Transplant Recipients With Hepatocellular Carcinoma: Results of the A2ALL Cohort†

Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5‐year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five‐year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time.     

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.     

Younger age and presence of macrovascular invasion were independent significant factors associated with poor disease-free survival in hepatocellular carcinoma patients undergoing living donor liver transplantation

Objective

Patients with hepatocellular carcinoma (HCC) exceeding the University of California, San Francisco (UCSF) criteria are normally rejected for cadaveric liver transplants. However, whether they should be allowed to undergo living donor liver transplantation (LDLT) has been controversial. We reviewed the outcome of patients with advanced HCC who underwent LDLT at our center.

Methods

From April 2002 to May 2011, 176 patients underwent LDLT at our center; of these, 77 (44%) had HCC at the explant liver. Patient overall survival and recurrence-free survival (RFS) was analyzed using Kaplan-Meier method. Multivariate analysis was performed by Cox analysis.

Results

Age was 56 ± 1 (56, 29-71) years; 62 (80.5%) were male; Model for End-stage Liver Disease Score was 11 ± 1 (9, 6-36), alpha fetoprotein (AFP) was 3683 ± 2019 (69, 3-139,591) ng/L; maximum tumor size was 4.5 (0.5-15) cm. Number or tumor nodules was 5 (1-10), and 32 (42%) had macrovascular invasion diagnosed pretransplant. Eleven (14%) were within UCSF criteria. After follow-up of 953 ± 90 (744, 2-2989) days, 53 (69%) were alive and 48 (62%) were recurrence-free. One-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) were 80%, 70%, and 57% and 80%, 65%, and 48%, respectively. Five-year OS and RFS for those within UCSF criteria were both 78% versus 55% and 46% outside UCSF criteria (P = not significant). At multivariate analysis, high AFP, younger age, and macrovascular invasion were associated with both poor RFS.

Conclusion

In HCC patients exceeding UCSF criteria, a reasonable 5-year overall survival of 55% post-LDLT can be obtained. Patients with HCC exceeding the UCSF criteria, especially in the older age group with no portal vein invasion and lower AFP level, should be actively considered for LDLT.     

Two-step Selection Criteria for Living Donor Liver Transplantation in Patients With Hepatocellular Carcinoma

We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P = .003 and P = .002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence.