肝癌肝移植——进展与展望

<正>原发性肝癌(肝癌)的发病率和死亡率均高居我国恶性肿瘤的第2位,因其恶性程度高、预后差而被称为"癌中之王"。随着肝移植手术技术和术后管理水平的不断提高,肝移植治疗肝癌的作用受到愈来愈多的关注。我国在1980年至2011年间共实施肝移植手术20 877例[1],其中肝癌肝移植手术8 874例(42.51%),但肝癌肝移植受者术后1、3、5年累积生存率分别为76.57%、57.00%、49.80%,明显低于良性肝脏疾病受者的累积生存率(分别为81.42%、76.48%、73.19%),其中31.68%的肝癌患者死亡原因为肝癌肝移植术后复     

肝癌肝移植纳入标准研究现状及展望

肝癌是目前全球范围内最常见的恶性肿瘤之一,其死亡率居所有恶性肿瘤第4位,即使乙肝疫苗的广泛使用,在全球范围内,肝癌的形式仍不容乐观,每年有超过70万新发病例心。肝移植、肝切除及射频消融是被公认对肝癌唯一有效的三种外科治疗手段。由于肝癌的发生大多数都伴有肝硬变,而肝移植能同时移除肿瘤以及肿瘤的“土壤”而被公认为是治疗肝癌的最佳治疗手段。     

符合米兰标准和杭州标准的肝癌肝移植受者预后回顾性分析

目的比较符合米兰标准和符合杭州标准的肝细胞肝癌(HCC)患者行肝移植术后生存和肿瘤复发情况,验证杭州标准的临床应用价值。方法回顾性分析2006年1月至2011年12月中国肝移植注册登记的肝移植手术,并在浙江大学医学院附属第一医院、重庆医科大学附属第一医院两家肝移植中心接受随访调查受者的临床资料,196例肝癌肝移植受者纳入研究。将符合米兰标准的HCC患者作为米兰标准组,共90例(45.9%);超出米兰标准但符合杭州标准者作为杭州标准组,共40例(20.4%);肿瘤结节直径之和8 cm,术前AFP400 ng/m L且组织学分级为低度分化者作为超出杭州标准组,共66例(33.7%)。比较3组受者术后生存率、无瘤生存率,并评判预后。结果米兰标准组受者术后1、3、5年生存率和1、3、5年无瘤生存率分别为88.9%、73.3%、60.0%和84.4%、66.7%、51.1%,杭州标准组受者术后1、3、5年生存率和1、3、5年无瘤生存率分别为80.0%、65.0%、50.0%和75.0%、55.0%、45.0%,超出杭州标准组受者术后1、3、5年生存率和1、3、5年无瘤生存率分别为57.6%、30.3%、18.1%和45.5%、27.3%、18.1%。对3组受者术后累积生存率和无瘤生存率进行比较,米兰标准组和杭州标准组受者术后1、3、5年生存率和1、3、5年无瘤生存率差异均无统计学意义(P均0.05),米兰标准组受者术后1、3、5年生存率和无瘤生存率均显著高于超出杭州标准组受者(P均0.05),杭州标准组受者术后1、3、5年生存率和1、3、5年无瘤生存率均显著高于超出杭州标准组受者(P均0.05)。结论同米兰标准一样,杭州标准也具有很强的科学性,能够显著拓展受益人群,让更多未符合米兰标准的患者能够施行肝移植术。同时杭州标准能有效预测肝移植受者预后,其创新性提出的生物学标准AFP水平和肿瘤分化程度是影响肝癌肝移植受者术后预后的关键性因素。     

肝癌肝移植适应证标准的发展及展望

<正>肝移植是目前公认的治疗终末期肝病的有效措施之一。自1963年第1例人原位肝移植术成功实施以来,肝移植术已经历了50余年的发展历史,迄今全世界已累积实施肝移植手术超过10万例。随着外科技术的不断发展、新型免疫抑制剂的应用和临床经验的不断积累,肝移植围手术期并发症和死亡率显著下降,术后存活率不断提高、存活时间不断延长。因此,肝移植术的适应证亦逐步扩大。对于原发性肝癌(肝癌)患者,在合理掌握适应     

中国肝癌肝移植临床实践指南

据统计中国每年超过30万人死于肝细胞肝癌（以下简称肝癌）,占全球肝癌死亡人数的一半左右。而肝移植是被全世界认可的治疗终末期肝病最有效的手段之一。我国自20世纪90年代掀起第二次肝移植热潮以来,肝移植事业发展迅猛,呈专业化和规模化发展态势,在移植数量和质量方面已接近或达到西方发达国家水平。     

中国肝癌肝移植现状

<正>由于缺乏器官分配相关国家条例,中国内地对肝移植受者选择标准尚未达成共识。中国肝移植受者相当大一部分为肝癌患者,其中约一半超出米兰     

肝癌肝移植

原发性肝癌是临床上常见的恶性肿瘤,其特点是早期无症状,不易发现,但肿瘤多为散见多发,生长发展迅速,60%～90%伴有肝硬化,因此肝癌的可切除率非常低,不足30%,肝癌的非切除治疗方法很多,如化疗、栓塞、放疗、激光、微波、低温等,种种疗法效果均不甚理想,理论上肝移植为其提供了最佳治疗选择。事实上,肝癌历来就是肝移植的适应证之一,这从肝移植的发展史与现状便可得知。世界上最初的11例临床肝移植(1967年以前),其中9例是肝癌,而我国第一阶段(90年代前)的57例肝移植,52例也是肝癌,虽然随着时间的推移,肝移植的适应证逐渐转变为以良性肝病为主…     

肝移植在肝癌治疗中的地位与评价

以肝移植治疗原发性肝细胞性肝癌(简称肝癌)，应严格地选择适当的病例：单个肿瘤直径不超过5cm，多发性肿瘤直径小于3cm和肿瘤总数不超过3个，肿瘤没有血管和淋巴结侵犯和肝外转移。如果病人患乙型或丙型肝炎，适当地以有效的抗病毒治疗，病人长期存活率可高达79％。这存活率和肝移植治疗良性末期肝硬化十分接近。没有足够证据显示手术前、后辅助性化疗可提高肝移植治疗肝癌的疗效，适量的免疫功能抑制，有助减低肝癌的复发率。如肝癌病人等待肝移植的时间长，可考虑以TACE，射频或微波治疗以减慢肝癌生长速度。肝移植和部分肝切除的长期治疗结果相差不大，在一小部分病人，如肝硬化程度严重，肝移植可比部分肝切除疗效好。肝移植用于治疗纤维板层肝癌和偶然发现肝癌疗效好。由于肝移植对于其它肝肿瘤例如胆管癌，血管肉瘤和转移性肝肿瘤疗效甚差，因此这些肝肿瘤不宜用肝移植作治疗。     

原发性肝癌肝移植围手术期辅助治疗

目的探讨原发性肝癌肝移植围手术期治疗的现状及研究进展。方法采用文献回顾的方法对原发性肝癌肝移植围手术期治疗的现状及研究进展进行综述。结果原发性肝癌肝移植围手术期治疗的方法包括：肝动脉栓塞化疗、全身化疗、放疗、瘤内无水乙醇注射以及射频毁损等。结论原发性肝癌肝移植围手术期辅助治疗不仅为肝移植患者赢得了手术时间，而且明显提高术后生存率。     

Bridging Locoregional Therapy for Hepatocellular Carcinoma Prior to Liver Transplantation

Introduction  The impact of locoregional therapy prior to liver transplantation for hepatocellular carcinoma utilizing either transcatheter arterial chemoembolization (TACE), yttrium-90 (⁹⁰Y), radiofrequency ablation (RFA), or resection prior to orthotopic liver transplantation (OLT) is largely unknown. We sought to examine locoregional therapies and their effect on survival compared with transplantation alone. Methods  A retrospective review of a prospectively collected database. Results  123 patients were included. Patients were analyzed in two groups. Group I consisted of 50 patients that received therapy (20 TACE; 16 ⁹⁰Y; 13 RFA, 3 resections). Group II consisted of 73 patients transplanted without therapy. Median list time was 28 days (range 2–260 days ) in group I, and 24 days (range 1–380 days) in group II. Median time from therapy to OLT was 3.8 months (range 9 days to 68 months). Twelve patients (24%) were successfully downstaged (8 TACE, 2 ⁹⁰Y, 2 RFA/resection). Overall 1-, 3-, and 5-year survival were 81%, 74%, and 74%, respectively. Survival was not statistically significantly different between the two groups (P = 0.53). The 12 patients downstaged did not have a significant difference in survival as compared with the patients who received therapy but did not respond or the patients who were transplanted without therapy (P = 0.76). Conclusion  Our report addresses locoregional therapy for hepatocellular carcinoma as a bridge to transplant. There was no statistical difference in overall survival between patients treated and those not treated prior to transplant. We provide further evidence that locoregional therapy is a safe tool for patients on the transplant list, does not impact survival, and can downstage selected patients to allow life-saving liver transplantation.     

Two Rare Metachronous Metastases of Hepatocellular Carcinoma After Liver Transplantation

A 59-year-old male with hepatocellular carcinoma (HCC) due to liver cirrhosis caused by the hepatitis C virus underwent cadaveric whole liver transplantation. Two years later, he had a metastatic HCC in the superior mediastinum. Over the following postoperative year, he underwent transcatheter arterial chemoembolization (TACE) for 4 tumors in the implanted liver. In the third post-TACE month, he was emergently hospitalized due to intracerebral hematoma with a tumor invading the bone in the medial frontal segment. He underwent emergency intracranial tumorectomy and hemorrhage removal. The histopathologic diagnosis was metastatic HCC. He regained consciousness as well as the ability to speak and to feed himself, resulting in an improved quality of life. The incidence of HCC recurrence after liver transplantation is observed in approximately 8% to 11% of selected cases, with frequent relapses observed in the implanted liver, bones, adrenal glands, and lungs. Mediastinal and intracranial metastases from HCC post-liver transplantation are very rare.     

肝癌肝移植的适应证及应用前景

肝细胞癌是最常见的肝脏原发性恶性肿瘤，全世界每年大约有新发病例54．1万，其中31．8万发生在我国，占全球肝癌的58．8％。由于肝细胞癌早期诊断困难，且常常伴有肝硬变，所以预后较差，未经治疗的肝癌患者的自然生存时间仅为6个月。肝癌常规的治疗方法主要包括手术切除、放疗、化疗、介入治疗等，虽然手术切除是肝癌患者的首选治疗方法，但由于85％～90％的肝癌患者伴有肝硬变、较差的肝功能和肿瘤的多中心性生长，患者往往不能耐受较大范围的肝脏切除术，而接受手术治疗的50％病例在3年中肿瘤复发，手术切除率低及治疗后较高的复发率是肝癌治疗效果差的主要原因。     

肝癌肝移植术后复发的危险因素分析

目的探讨原发性肝癌(HCC)肝移植术后肿瘤复发或转移的危险因素。方法回顾性我院2003年4月至2007年11月期间76例HCC患者行肝移植的临床资料,根据随访期间是否有复发分为复发组(n=23)和未复发组(n=53),总结肿瘤复发的特点。结果 76例患者中23例(30.3%)术后复发。单因素分析显示患者性别(P=0.449)、年龄(P=0.091)、术前是否治疗(P=0.958)、肿瘤数目(P=0.212)和是否伴有HBV/HCV感染(P=0.220)与肿瘤的复发无关,而肿瘤包膜完整性(P=0.009)、肿瘤分期(P=0.002)、肿瘤直径(P<0.001)、血管侵犯(P<0.001)以及术前AFP水平(P=0.044)与肿瘤的复发有关,其中肿瘤直径<5.0 cm(P=0.001)和术后2个月AFP水平恢复正常者(P<0.001)1年复发率更低。多因素分析显示肿瘤直径(P=0.001,OR=6.456,95%CI为2.356～17.680)、血管侵犯(P=0.030,OR=10.653,95%CI为1.248～90.910)以及术前AFP水平(P=0.017,OR=2.601,95%CI为2.196～5.658)是肝移植术后肿瘤复发的独立危险因素。结论对于肿瘤直径>5.0 cm、伴有血管侵犯以及术前AFP水平≥400μg/L尤其术后2个月AFP水平仍高于正常者术后需加强监测,必要时尽早给予抗肿瘤治疗。     

Prognostic Impact of Sarcomatous Change of Hepatocellular Carcinoma in Patients Undergoing Liver Resection and Liver Transplantation

Sarcomatous change has been rarely observed in hepatocellular carcinoma (HCC), but it is usually associated with very aggressive tumor behavior and widespread metastasis. To assess the impact of sarcomatous changes, we analyzed the outcomes of 15 patients with sarcomatous HCC after resection (n = 11) or liver transplantation (LT) (n = 4). No imaging findings characteristic of sarcomatous changes were observed. According to modified pathological tumor-node metastasis staging, the HCC lesions were classified as stage II in five patients, stage III in six, stage IVa2 in two, and stage IVb in one. The Milan criteria were met in 7 of 15 patients, including 3 of 4 in the LT group. R0 resection was achieved in 9 of 11 resected patients, and their 3-year overall and disease-free survival rates were both 18.2%. In the LT group, 3-year overall and disease-free survival rates were 37.5 and 25%, respectively. In patients within the Milan criteria, 2-year overall survival rate was 25% after resection and 33% after LT, showing no prognostic difference. Extrahepatic metastasis as initial recurrence was detected in 80% after resection and 66.7% after LT. In conclusion, we found that the prognosis of patients with sarcomatous HCC was very unfavorable after either resection or LT and that, except for liver biopsy, no diagnostic method could distinguish between sarcomatous and ordinary HCC. Vigorous postoperative systemic surveillance may be helpful for timely detection and treatment of localized metastases.     

mTOR抑制剂对肝细胞癌肝移植患者术后生存的影响

目的研究肝细胞癌患者肝移植术后使用mTOR抑制剂为主的免疫抑制剂方案对肿瘤复发及生存期的影响。方法收集我中心2005年1月至2008年12月期间因肝细胞癌行肝移植手术的病例建立数据库。根据患者术后所使用的免疫抑制方案分为两组,单CNIs免疫抑制剂组和含西罗莫司(Rapa)组。按照术前肿瘤所符合的移植标准(米兰标准、UCSF标准以及超标准)对组内病例分层分析,对比各组病例之间在肿瘤复率发、无瘤生存期及总生存期方面的差别。结果对于米兰标准及UCSF标准患者,两组间在肿瘤复发率、无瘤生存期和总生存期方面差别无统计学意义;超标准患者两组无瘤生存率无显著差异,含Rapa组总生存期优于单CNIs组(P0.05)。结论超标准肝癌患者术后使用mTOR抑制剂对于延长患者生存期具有一定作用。     

Applicability of the Milan Criteria for Determining Liver Transplantation as a First-Line Treatment for Hepatocellular Carcinoma

Background To determine whether or not the Milan criteria (MC) should be used to determine the applicability of liver transplantation (LT) as a first-line treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are able to endure hepatectomy.Methods Retrospective analysis of 82 patients with cirrhosis with HCC who were treated by hepatectomy without LT at our institution between 1990 and 2003.Results Of these 82 patients, 48 met the MC. Proportional hazard regression analyses to determine the independent prognostic factors for postoperative cumulative patient and disease-free survival showed that meeting the MC is the strongest prognostic factor for both patient and disease-free survival. The cumulative patient and disease-free survival rates were 76.7% and 28.9%, respectively, at 5 years in patients who met the MC. The cumulative disease-free survival was markedly inferior to those in previously reported series of LT for HCC who met the MC, but the cumulative patient survival was comparable to those in the previously reported series. A comparison of cumulative postoperative survival between patients who met the MC and fulfilled all five factors listed below and patients who met the MC but did not fulfill any of the five factors demonstrated that the latter patients showed statistically significantly worse postoperative patient survival than the former. The five factors included: Model for End-Stage Liver Disease score <10, indocyanine green retention rate at 15 minutes <20%, absence of microscopic fibrous capsular invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of American Joint Committee on Cancer tumor classification.Conclusions The MC should not be used to determine the applicability of LT as a first-line treatment for patients with HCC considered able to endure hepatectomy. However, modifying MC with some clinicopathological factors could satisfy the appropriate criteria for applying LT as a first-line treatment for these patients.     

原发性肝癌肝移植术后化疗效果的初步观察

目的：探讨原发性肝癌肝移植后化疗的安全性和疗效。方法：回顾性分析22例因原发性肝癌而行肝移植病人的临床资料，以求进一步探明肝癌的肝移植指征，术后化疗时机、化疗方案、化疗的副作用及化疗对近、远期生存率的影响。结果：2002年6月至2003年7月，共有22例原发性肝癌进行肝移植；18例最迟于术后5周内进行第1次全身化疗，累计完成化疗41次；其余4例因各种原因未行化疗，包括1例意外发现的癌和1例小肝癌。8例出现肝功能损害，6例发生白细胞减少，仅2例需重组人集落刺激生长因子治疗。结论：原发性肝癌是肝移植的一个主要适应证；结合术后化疗可延长复发时间，提高生存率；且病人可以安全耐受。