1、肝移植治疗原发性肝癌肝移植治疗原发性肝癌 主要内容主要内容 肝癌肝移植的疗效 肝癌肝移植的手术适应证选择 肝癌肝移植术后肿瘤复发的影响因素 肝癌肝移植术后肿瘤复发的预防 肝癌肝移植术后肿瘤复发的治疗肝癌肝移植的疗效肝癌肝移植的疗效中国大陆肝癌肝移植效果中国大陆肝癌肝移植效果Benign (51.8%) 76.7 %83.8 %78.8%76.1%71.6 %55.8 %49.2 %Malignant (48.2%)Cumulative survival (%)Survival time (month)Benign diseases vs Malignant diseases: P Log ra
2、nk 0.001我中心肝癌肝移植的结果我中心肝癌肝移植的结果n=1717我中心肝癌肝移植的结果我中心肝癌肝移植的结果合并门静脉癌栓的肝癌合并门静脉癌栓的肝癌605448423630241812601. 00. 80. 60. 40. 20. 0累累积积生生存存率率（% %）组组时间（月）组（75例）：癌栓未累及门静脉主干组（53例）：癌栓累及门静脉主干郑虹，高伟，朱志军，等。 肝移植治疗肝细胞癌合并门静脉癌栓的疗效评价。中华器官移植杂志，2009，30：484-486。伴淋巴结转移的肝癌伴淋巴结转移的肝癌N=28混合细胞型肝癌混合细胞型肝癌生存期(月)726660544842363024181
3、260累积生存率1.11.0.9.8.7.6.5.4cHCC-CCcHCC-CC-删失去存（n=14）陈洪磊，郑虹，王政禄，等。肝移植治疗混合细胞型肝癌14例。中国肿瘤临床，2009，36：486-489肝癌肝移植的手术适应证选择肝癌肝移植的手术适应证选择肝癌肝移植的手术适应证肝癌肝移植的手术适应证肝癌肝移植的手术适应证肝癌肝移植的手术适应证Authorsn筛选标准5y-OSMazzaferro, NEJM 1996Milan 标准标准 48Single5cm, 3 nodles 3cm74%(4y)Yao, Hepatology 2001UCSF64Single6.5cm, 3 nodles
4、 4.5cm73%Mazzaferro, Lancet Oncol 20091556Up-to-seven, without microvascular invasion71.2%关于关于Milan标准标准 1996年提出，5年存活率达70% 影像学检查对Milan标准的误诊率高达15%46% 很多超出Milan标准的患者可因肝脏移植获益关于关于Milan标准标准关于关于Milan标准标准关于关于Milan标准标准关于关于Milan标准标准关于关于Milan标准标准UCSF标准标准 2001年，California大学提出 单发肿瘤直径6.5cm多发肿瘤3个，每个肿瘤直径4.5cm肿瘤直径总和
5、8cm 5年存活率达75%Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394 1403.UCSF标准标准Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular
6、 carcinoma should be expanded：A 22-year experience with 467 patients at UCLA. Annals of Surgery, 2007, 246: 502-511.UCSF标准标准UCSF标准标准Ju MK, Choi GH, Huh KH, et al. UCSF criteria by pre-transplant radiologic study can not assure similar post-transplant results of hepatocellular carcinoma within Milan
7、criteria. Hepatogastroenterology. 2010 Jul-Aug;57(101):819-25.UCSF标准标准 法国14个移植中心，459例患者 1985年至1998年 符合UCSF标准的患者5年生存率低于符合Milan标准的患者，但无统计学差异 5年生存率低于50%，不宜使用 UCSF报道5年无瘤生存率80%Decaens T，Roudot-Thoraval F, Hadni-Bresson S, et al. Impact of UCSF criteria according to pre- and post-OLT tumor features: analy
8、sis of 479 patients listed for HCC with a short waiting time. Liver Transpl. 2006 Dec;12(12):1761-9.Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007, 7(11):2587-96. 新新Mila
9、n标准标准 Up-to-seven criteria 肿瘤最大直径与肿瘤个数之和不超过7 5年生存率达71.2%Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10: 35.肝癌肝移植的手术适应证肝癌肝移植的手术适
10、应证新Milan标准Contour plot of the 5-year overall-survival probability according to size of the largest tumour, number of tumours, and presence or absence of microvascular invasion新新Milan标准标准新新Milan标准标准l无门静脉癌栓l肿瘤累计直径8 cml术前AFP50%肝癌肝移植术后肿瘤复发肝癌肝移植术后肿瘤复发的影响因素的影响因素预后相关因素预后相关因素肿瘤大小淋巴结转移情况血管侵润情况 影像学检查结果 显微镜检查结
11、果组织学分级原发病灶数量年龄60岁羧基凝血酶原血清浓度（研究中）TNM分期对预后的影响分期对预后的影响Marsh JW, Dvorchik I, Bonham CA, et al. Is the pathologic TNM staging system for patients with hepatoma predictive of outcome? Cancer 2000; 88(3):53843.手术方式手术方式对预后的影响对预后的影响Fishera RA, Kulikb LM, Freisec CE, et al. Hepatocellular carcinoma recurrence
12、 and death following living and deceased donor liver transplantation. American Journal of Transplantation 2007; 7: 16011608.手术方式手术方式对预后的影响对预后的影响Li C, Wen TF, Yan LN, et al. Outcome of hepatocellular carcinoma treated by liver transplantation: comparison of living donor and deceased donor transplanta
13、tion. Hepatobiliary Pancreat Dis Int，2010, 9:366-369.手术方式手术方式对预后的影响对预后的影响Vakili K, Pomposelli JJ, Cheah YL, et al. Living Donor Liver Transplantation for Hepatocellular Carcinoma: Increased Recurrence but Improved Survival. Liver transplantation,2009,15:1861-1866.手术方式手术方式对预后的影响对预后的影响Hwang S, Lee SG,
14、 Ahn CS, et al. Small-sized liver graft does not increase the risk of hepatocellular carcinoma recurrence after living donor liver transplantation. Transplantation Proceedings, 2007, 39:15261529.手术方式手术方式对预后的影响对预后的影响 理论上讲，小体积移植物的缺血再灌注损伤和肝再生导致的血管生成可能促进肿瘤进展 但目前临床实际影响并不明确 目前临床证据表明，移植物类型对肝移植术后肿瘤进展并无或仅有轻微
15、影响等待时间等待时间对预后的影响对预后的影响Chao SD, Roberts JP, Farr M, et al. Short waitlist time does not adversely impact outcome following liver transplantation for hepatocellular carcinoma. American Journal of Transplantation 2007; 7: 15941600.肝癌肝移植术后肿瘤肝癌肝移植术后肿瘤复发的预防复发的预防术术 前前 治治 疗疗术前治疗的目的 控制肿瘤生长和血管侵润 新辅助治疗减少患者移植术后
16、复发风险 肿瘤降期，使移植成为可能术前治疗术前治疗TACE No convincing arguments showing that TACE reduces the rate of drop out before LT No convincing arguments showing that TACE improves the survival after LT Although TACE induced complete tumor necrosis in some patientsBelghiti J, Carr BI, Greig PD, et al. Treatment before
17、 Liver Transplantation for HCC. Annals of Surgical Oncology, 2008,15: 9931000.术前治疗术前治疗TACE Downstaging of HCC by TACE is possible in one-third to one-half of LT candidates But these patients have higher dropout rates, higher recurrence rates There is no sufficient evidence that pretransplant TACE ma
18、y delineate the possibility of expanding current selection criteria for OLT in patients with HCCBelghiti J, Carr BI, Greig PD, et al. Treatment before Liver Transplantation for HCC. Annals of Surgical Oncology, 2008,15: 9931000.术前治疗术前治疗射频消融射频消融 Pretransplant RF ablation for HCC as a strategy to redu
19、ce dropout has been addressed in three studies there is no data demonstrating that RF improves the survival after LTBelghiti J, Carr BI, Greig PD, et al. Treatment before Liver Transplantation for HCC. Annals of Surgical Oncology, 2008,15: 9931000.术前治疗术前治疗肝切除肝切除 合并HBV感染的肝癌患者，行肝切除后肿瘤复发，80%符合Milan标准，可
20、行挽救性肝移植 合并HCV感染的肝癌患者，行肝切除后肿瘤复发，60%超出Milan标准Poon RT, Fan ST, Lo CM, et al. long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002; 235:37382.Chirica
21、 M, Durand F, Sommacale D, et al. Long-term outcome after resection for small HCC in patients with hepatitis C virus infection: arguments for a strategy of resection as a bridge to transplantation rather than salvage transplantation. Hepatology 2004; (suppl 4);40:162A.术前治疗术前治疗肝切除肝切除优势 可以得到更多的病理学证据（如
22、分化程度，有无微血管侵犯，有无卫星灶等），更有效的预测肝移植的预后并选择手术时机术前治疗术前治疗新辅助化疗新辅助化疗Soderdahl G, Backman, Isoniemi H, et al. A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular arcinoma. European Society for Organ Transplan
23、tation, 2006 ,19: 288294.TACE联合索拉菲尼联合索拉菲尼BMC Cancer 2008, 8:349 doi:10.1186/1471-2407-8-349免疫抑制方案的选择免疫抑制方案的选择Toso C,Merani S, Bigam DL, et al. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology 2010;51:1237-124
24、3.免疫抑制方案的选择免疫抑制方案的选择Vivarelli M, Cucchetti A, Barba GL, et al. Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors. Ann Surg 2008;248: 857862.免疫抑制方案的选择免疫抑制方案的选择Chinnakotla S, Davis GL, Vasani S, Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver
25、 transplantation. Liver Transpl,2009,15:1834-1842.免疫抑制方案的选择免疫抑制方案的选择Hepatocellular carcinoma recurrencefree survival in recipients treated with sirolimus-based immunosuppression. Abbreviation: CNI, calcineurin inhibitor.Zimmerman MA, Trotter JF, Wachs et al. Sirolimus-based immunosuppression followi
26、ng liver transplantation for hepatocellular carcinoma. Liver Transpl 2008,14:633-638. 免疫抑制方案的选择免疫抑制方案的选择Vivarelli M, Dazzi A, Zanello M, et al. Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma. Transplantation 2010;8
27、9: 227231.免疫抑制方案的选择免疫抑制方案的选择免疫抑制方案的选择免疫抑制方案的选择肝癌肝移植术后肿瘤肝癌肝移植术后肿瘤复发的治疗复发的治疗肿瘤复发后的生存率肿瘤复发后的生存率Shin WY, Suh KS, Lee HW, et al. Prognostic factors affecting survival after recurrence in adult living donor liver transplantation for hepatocellular Carcinoma. Liver transplantation, 16:678-684, 2010.肿瘤复发后生存
28、的影响因素肿瘤复发后生存的影响因素Shin WY, Suh KS, Lee HW, et al. Prognostic factors affecting survival after recurrence in adult living donor liver transplantation for hepatocellular Carcinoma. Liver transplantation, 16:678-684, 2010.治疗方法对预后的影响治疗方法对预后的影响Kornberg A, Kupper B, Tannapfel A, et al. Long-term survival a
29、fter recurrent hepatocellular carcinoma in liver transplant patients: Clinical patterns and outcome variables. Eur J Surg Oncol. 2010;36(3):275-80. 全身化疗全身化疗Overall survival (OS) KaplanMeier curve (n = 24) in patients receiving palliative chemotherapy for recurrent hepatocellular carcinoma after live
30、r transplantation. Median OS was 16.6 weeks.化疗副作用可以耐受但疗效不满意Lee JO, Kim DY, Lim JH, et al. Palliative chemotherapy for patients with recurrent hepatocellular carcinoma after liver transplantation. Journal of Gastroenterology and Hepatology, 2009, 24: 800805.索拉菲尼治疗肝移植术后肿瘤复发索拉菲尼治疗肝移植术后肿瘤复发索拉菲尼治疗肝移植术后肿瘤
31、复发索拉菲尼治疗肝移植术后肿瘤复发Kim R, Aucejo F. Radiologic complete response with sirolimus and sorafenib in a hepatocellular carcinoma patient who relapsed after orthotopic liver transplantation. J Gastrointest Canc, 2010, Aug 18.索拉菲尼治疗肝移植术后肿瘤复发索拉菲尼治疗肝移植术后肿瘤复发Bhoori S, ToffaninS, Sposito C, et al. Personalized m
32、olecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation:A proof of principle. Journal of Hepatology, 2010,52: 771775.I125联合索拉菲尼治疗肺转移瘤联合索拉菲尼治疗肺转移瘤Li CX, Zhang FJ, Zhang WD, et al. Feasibility of 125I brachytherapy combined with sorafenib treatment in pati
33、ents with multiple lung metastases after liver transplantation for hepatocellular carcinoma. J Cancer Res Clin Oncol (2010) 136:16331640.TACE联合索拉菲尼联合索拉菲尼Tan WF, Qiu ZQ, Yu Y, Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation. Acta Pharmacologica Sinica, 2010, 31: 16431648.
