雷帕霉素对符合米兰标准的肝细胞癌肝移植患者生存的影响

目的探讨雷帕霉素对符合米兰标准的肝细胞癌（HCC）肝移植患者生存的影响。方法回顾性分析2004年11月至2012年1月北京佑安医院移植中心收治的90例符合米兰标准的HCC肝移植患者的临床资料。按患者是否加用雷帕霉素分为两组。对照组45例,初始免疫抑制方案为：他克莫司（FK506）＋吗替麦考酚酯（MMF）＋甲泼尼龙（Pred）;维持期免疫抑制方案为：FK506＋/-MMF。雷帕霉素组45例,初始免疫抑制方案同对照组;维持期免疫抑制方案为：FK506＋雷帕霉素。比较两组患者术后生存时间、生存率、无瘤生存率和肿瘤复发率。结果至随访结束时,对照组45例,死亡11例,其中因肿瘤复发死亡9例;雷帕霉素组45例,死亡4例,其中因肿瘤复发死亡2例。对照组术后平均生存时间（72.6±5.8）月,明显低于雷帕霉素组（84.0±4.0）月,差异有统计学意义（P〈0.05）。对照组和雷帕霉素组术后1、2、3、5年的生存率分别为86.5%和97.8%（P=0.11）,76.5%和97.8%（P〈0.05）,73.6%和91.2%（P=0.06）,73.6%和87.0%（P=0.20）;术后1、2、3、5年的无瘤生存率分别为81.6%和97.7%（P〈0.05）,73.7%和97.7%（P〈0.05）,73.7%和88.1%（P=0.15）,73.7%和88.1%（P=0.15）;术后1、2、3、5年的肿瘤复发率分别为13.3%和2.2%（P=0.11）,18.6%和2.2%（P〈0.05）,21.6%和2.2%（P〈0.05）,21.6%和6.8%（P=0.06）。结论雷帕霉素能够显著提高符合米兰标准的HCC患者肝转移术后生存时间,降低肿瘤复发率并提高其术后生存率。

A retrospective cohort study on the effect of rapamycin-based immunosuppression protocol on the survival of hepatocellular carcinoma patients within Milan criteria after liver transplantation

Objective To evaluate the effect of rapamycin on the survival of hepatocellular carcinoma（HCC） patients within Milan criteria after orthotopic liver transplantation（OLT）. Methods Ninety HCC patients who received OLT in the liver transplantation center of Beijing You＇an Hospital from November 2004 to January 2012 were included in this study. Based on the immunosuppression protocol, subjects were divided into 2 groups（n =45）.The control group was given the initial immunosuppression with FK506 ＋ mycophenolate mofetil（MMF）＋methyl prednisolone（Pred）,and the maintain immunosuppression with FK506 ＋ mycophenolate mofetil（MMF）.The rapamycin group was given the same initial immunosuppression as the control, and the maintain immunosuppression with FK506 ＋ rapamycin. The postoperative survival time, survival rate, disease-free survival（DFS） rate and tumor recurrence rate were compared between the two groups. Results At the end of the study, 9 of 11 dead cases were caused by tumor recurrence in the control group.However, 2 of 4 dead cases were caused by tumor recurrence in the rapamycin group.The mean survival time of the rapamycin group was（84.0±4.0） months, which was longer than that of the control group （72.6±5.8） months, P〈0.05]. The 1-, 2-, 3-, and 5-year survival rates of the control group and the rapamycin group were86.5% vs. 97.8%（P = 0.11）, 76.5% vs. 97.8%（P〈0.05）; 73.6% vs. 91.2%（P = 0.06）, 73.6% vs. 87.0%（P = 0.20） respectively.The 1-, 2-, 3- and 5-year DFS rates of the two groups were 81.6% vs. 97.7%（P〈0.05）, 73.7% vs. 97.7%（P〈0.05）, 73.7%vs. 88.1%（P = 0.15）, 73.7% vs. 88.1%（ P = 0.15）respectively. The 1-, 2-, 3- and 5-year recurrence rates of the two groups were13.3% vs. 2.2%（P = 0.11）, 18.6% vs. 2.2%（P〈0.05）, 21.6% vs. 2.2%（P〈0.05）, 21.6% vs. 6.8%（P = 0.06）respectively. Conclusion The rapamycin-based immunosuppressive protocol could significantly prolong the survival time, increase the survival rate and d