肝癌切除术后复发的补救性肝移植

目的 评估肝癌患者肝癌切除术后肝癌复发行补救性肝移植术的临床治疗效果及预后影响因素.方法 回顾性分析本治疗组自2000年4月至2008年6月间实施的88例肝癌切除术后复发行补救性肝移植术病例,分析该组病例手术特征、生存状况、病理因素对预后影响.结果 肝癌切除术后复发行补救性肝移植病例平均年龄为52.4±9.2岁(26....     

肝癌术后复发补救性肝移植的意义

目前,被广泛接受的补救性肝移植(salvage liver transplantation,SLT)的定义是指对肝功能良好的可切除的原发性肝细胞癌(肝癌)(单个肿瘤直径≤5cm或肿瘤数目≤3个、单个肿瘤直径≤3 cm)首先采取肝癌切除治疗,术后肝癌肝内复发(单个肿瘤直径≤5 cm;多个肿瘤数目≤3个、单个肿瘤直径≤     

补救性肝移植对原发性肝癌肝切除术后复发患者的疗效分析

目的初步探讨采用补救性肝移植(SLT)治疗肝切除术后复发性原发性肝癌(肝癌)的临床效果。方法回顾性分析2005年4月至2012年12月在西安交通大学医学院第一附属医院连续施行的68例肝癌肝移植患者的临床资料。其中60例患者行首选肝移植(PLT),即PLT组;8例患者行SLT,即SLT组。比较两组患者的手术时间、无肝期时间、术中出血和输血量;比较两组患者重症监护室(ICU)入住时间和总住院时间;比较两组患者术后并发症发生情况。根据两组患者的随访结果绘制Kaplan-Meier生存曲线,采用Log-rank检验比较两组患者累积生存率和无瘤生存率。结果 SLT组患者的手术时间、无肝期时间、术中出血量及输血量均明显长于或多于PLT组(均为P0.05),两组的ICU入住时间和总住院时间比较,差异均无统计学意义(均为P0.05)。两组术后出血、感染、急性排斥反应、肾衰竭及胆道并发症发生率比较,差异均无统计学意义(均为P0.05)。随访时间1～90个月,平均随访时间为33个月。SLT组术后的1、2、3年累积生存率分别为87.5%、75.0%、62.5%,PLT组分别为80.0%、73.8%、67.8%,两组Kaplan-Meier生存分析比较差异无统计学意义(P0.05)。SLT组术后1、2、3年无瘤生存率分别为75.0%、62.5%、50.0%,PLT组分别为81.2%、68.6%、64.6%,两组Kaplan-Meier生存分析比较差异亦无统计学意义(P0.05)。结论SLT治疗肝癌切除术后肝内复发疗效较好,在供体短缺的情况下选择实施补救性肝移植不失为一种有效可行的治疗策略。     

原发性肝癌切除术后复发的肝移植治疗

目的探讨原发性肝癌切除术后复发病人的肝移植手术指征和注意事项。方法总结2003年7月至2005年8月59例因肝癌接受肝移植的临床资料，其中肝癌切除术后复发12例（复发组），移植术前未接受手术治疗47例（对照组），分析两组病人移植术前肝功能、治疗情况、术中探查、手术时间、无肝期时间、出血量以及术后恢复情况。结果复发组病人移植手术时间、术中出血量及输血量均明显大于对照组，但两组无肝期时间以及1、2年存活率（75％vs．86％，P〉0．05；70．8％vs．83，3％，P〉0．05）差异无显著性意义。结论肝移植是肝癌切除术后复发病人的有效治疗方法，合理掌握肝移植指征是治疗肝癌切除术后复发的关键。     

原发性肝癌切除术后复发的肝移植治疗

目的总结原发性肝癌切除术后复发行肝移植治疗的经验。方法2002年8月至2004年11月上海交通大学医学院附属瑞金医院对4例肝癌切除术后复发病例（其中1例合并急性肝功能衰竭）行同种异体肝移植治疗。结果3例移植术后已分别无瘤存活17个月、12个月和27个月至今。1例术后第3天死于多器官功能衰竭。结论对原发性肝癌切除术后复发病例的肝移植治疗，小肝癌切除后复发肿瘤仍符合Milan标准者有着良好的预后；个别合并门静脉癌栓者预后较好；合并急性肝功能衰竭者应相当谨慎。     

补救性肝移植的疗效

目的探讨补救陛肝移植的适应证及其临床疗效。方法回顾性分析2003年10月至2006年3月中山大学附属第三医院35例肝癌肝切除术后行肝移植患者的临床资料。比较补救性肝移植组（19例）和超补救性肝移植组（16例）患者的手术情况、术后并发症及预后等指标。计数和计量资料分别采用X^2和t检验,非正态分布采用秩和检验,Kaplan-Meier法进行生存分析,生存率的比较采用Log-rank检验。结果补救性肝移植组和超补救性肝移植组患者的无肝期、冷缺血时间、手术时间、术中出血量、术中输注红细胞量、术中输注新鲜冰冻血浆量、肝移植并发症发生率、再移植率分别为（32±9）rain、（8．0±2．1）h、（7．6±1．5）h、2300ml、8U、23U、6／19、2／19和（34±7）min、（7．4±2．3）h、（7．4±2．0）h、2750ml、12U、20U、4／16、1／16,两组比较,差异无统计学意义（t=0．726,-0．804,-0．366,Z=-0．348,-0．549,-0．149,）（X^2=0．184,0．203,P〉0．05）。补救性肝移植组和超补救性肝移植组患者围术期死亡率、术后肿瘤复发率分别为0、2／19和4／16、9／16,两组比较,差异有统计学意义（X^2=5．363,8．426,P〈0．05）。补救性肝移植组和超补救性肝移植组患者1、3、5年累积生存率分别为100％、84％、84％和75％、33％、33％;1、3、5年无瘤生存率分别为100％、89％、89％和48％、29％、19％,两组比较,差异有统计学意义（X^2=11．58,19．31,P〈0．05）。结论补救性肝移植是肝癌治疗过程中的一种有效策略,米兰标准是目前补救性肝移植的最佳适应证。     

肝切除术后复发性肝癌的肝脏移植

目的 初步评估肝移植治疗肝切除术后复发性肝癌的效果.方法 收集四川大学华西医院2001年4月至2008年3月期间23例肝切除术后复发性肝癌接受肝移植病例的资料并进行回顾性分析.结果 首次部分肝切除对以后的肝移植手术无明显不利影响,肝移植术后肝功能迅速恢复.17例移植前AFP升高者中13例术后1个月内恢复正常; 23例中有5例出现术后并发症,发生率为21.74%; 19例完成随访,4例失访,随访率为82.61%.随访截至2008年3月31日,平均随访时间610 d.5例于随访期内发现肝癌复发,复发率为26.32%(5/19); 6例于随访期内死亡,生存率为68.42%(13/19),最长存活已达3年2个月.结论 对肝切除术后复发性肝癌,肝移植不失为一种较好的治疗方法.     

补救性肝移植的疗效

目的 探讨补救性肝移植的适应证及其临床疗效.方法 回顾性分析2003年10月至2006年3月中山大学附属第三医院35例肝癌肝切除术后行肝移植患者的临床资料.比较补救性肝移植组(19例)和超补救性肝移植组(16例)患者的手术情况、术后并发症及预后等指标.计数和计量资料分别采用x2和t检验,非正态分布采用秩和检验,Kaplan-Meier法进行生存分析,生存率的比较采用Log-rank检验.结果 补救性肝移植组和超补救性肝移植组患者的无肝期、冷缺血时间、手术时间、术中出血量、术中输注红细胞量、术中输注新鲜冰冻血浆量、肝移植并发症发生率、再移植率分别为(32±9)min、(8.0±2.1)h、(7.6±1.5)h、2300ml、8 U、23 U、6/19、2/19和(34±7)min、(7.4±2.3)h、(7.4±2.0)h、2750ml、12 U、20U、4/16、1/16,两组比较,差异无统计学意义(t=0.726,-0.804,-0.366,Z=-0.348,-0.549,-0.149,x2=0.184,0.203,P＞0.05).补救性肝移植组和超补救性肝移植组患者围术期死亡率、术后肿瘤复发率分别为0、2/19和4/16、9/16,两组比较,差异有统计学意义(x2=5.363,8.426,P＜0.05).补救性肝移植组和超补救性肝移植组患者1、3、5年累积生存率分别为100%、84%、84%和75%、33%、33%;1、3、5年无瘤生存率分别为100%、89%、89%和48%、29%、19%,两组比较,差异有统计学意义(x2=11.58,19.31,P＜0.05).结论 补救性肝移植是肝癌治疗过程中的一种有效策略,米兰标准是目前补救性肝移植的最佳适应证.     

肝癌肝移植术后复发机制及其研究进展

本文综述了肝癌患者在肝移植后肝癌复发的机制，原发肿瘤病灶、治疗措施对复发的影响，以及预防复发的防治方法与患者的预后。     

挽救性肝移植治疗肝癌切除术后复发的价值研究

目的 探讨挽救性肝移植(SLT)的手术安全性及对患者预后的影响.方法 回顾性分析复旦大学附属中山医院肝外科2001年6月至2008年12月期间连续289例肝癌肝移植(符合UCSF标准)患者的临床资料,其中242例患者行初始肝移植(PLT),即PLT组,47例患者行SLT,即SLT组,比较2组患者围手术期及长期生存情况的差异.结果 2组患者的平均年龄、性别构成及肿瘤情况差异均无统计学意义(P>0.05).SLT组的手术时间要长于PLT组[(7.1±1.8)h比(6.4±1.4)h,P=0.004],但2组患者的术中出血量[(2 560.5±2 683.6)ml比(2 042.9±2 006.2)ml,P=0.173]及术中输血量[(13.8±12.9)U比(9.9±12.6)U,P=0.087]比较差异均无统计学意义,SLT组患者从第1次手术切除至行肝移植的间隔时间为(32.8±32.4)个月.截至2009年12月,2组患者中位随访时间为38.7个月,SLT组与PLT组患者的3年生存率(82.3%比75.5%,P=0.312)和3年无瘤生存率(78.8%比70.1%,P＝0.755)之间比较差异均无统计学意义.但按意向性治疗分析,SLT组患者的3年生存率明显优于PLT组(88.4%比76.2%,P＝0.047).结论 SLT并不增加移植手术的风险,也不影响患者的长期预后,对部分病例,先行手术切除再行肝移植可作为肝癌治疗的一种有效策略.     

Liver Transplantation for Hepatocellular Carcinoma: Validation of the UCSF-Expanded Criteria Based on Preoperative Imaging

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.     

Liver Transplantation for Hepatocellular Carcinoma: Beyond the Milan Criteria

Liver transplantation represents a cornerstone in the management of early‐stage hepatocellular carcinoma (HCC). Expansion beyond the Milan criteria for liver transplantation (1 lesion ≤ 5 cm, or 2 to 3 lesions each ≤ 3 cm) remains controversial. This review covers several key areas: (1) Recent developments and published data on expanded criteria for deceased donor and live‐donor liver transplantation, with emphasis on criteria that have been applied to preoperative imaging. (2) Independent testing of expanded criteria, where published data are largely limited to the proposed University of California, San Francisco criteria (1 lesion ≤ 6.5 cm, 2–3 lesions each ≤ 4.5 cm with total tumor diameter ≤ 8 cm). (3) Response to loco‐regional therapy and tumor downstaging. (4) The fundamental questions and answers in resolving the controversy over expanded criteria. The key issue pertains to whether acceptable outcome can be achieved on a broader scale beyond single center experience, which appears to support modest expansion beyond the Milan criteria. The foundation of the debate over expanded criteria may rest upon what the transplant community would consider to be the acceptable threshold for patient survival using expanded criteria, without causing significant harm to other transplant candidates without HCC.     

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.     

肝癌解剖性肝切除的初步经验

目的总结行解剖性肝切除的经验及结果。方法2004年1月至2005年6月期间,我们对93例肝细胞癌患者进行解剖性肝切除,对相应外科技术进行改进以减少术中出血、输血及术后并发症。切肝采用血管钳钳夹肝组织,暴露肝内管道后再结扎,选择性阻断出、入肝血流;对13例巨大肿瘤行半肝切除时采用肝脏悬吊法,切肝时采用间断Pringle法阻断肝门。结果93例肝癌患者中82例(88%)伴有不同程度的肝硬变,平均出血量300ml(100~6000ml),71%(66/93)病例不需输血。术后并发症发生率为34%(32/93),膈下积液多发,共8例。术后30d内无手术死亡。结论解剖性肝切除可能提高手术疗效。     

The Impact of Pre-Operative Loco-Regional Therapy on Outcome After Liver Transplantation for Hepatocellular Carcinoma

No prior studies have shown that pre-operative loco-regional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that pre-operative loco-regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5-year recurrence-free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5-year recurrence-free survival was 93.8% for the 85 patients who received pre-operative loco-regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5-year recurrence-free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre-operative loco-regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.     

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.     

Rho-Associated Kinase Inhibitor Reduces Tumor Recurrence After Liver Transplantation in a Rat Hepatoma Model

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.     

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。     

Liver Transplantation for Hepatocellular Carcinoma: Five Steps to Prevent Recurrence

Liver transplantation is the best treatment of patients with unresectable early hepatocellular carcinoma, allowing disease‐free survival rates of 60–80% at 5 years. Despite these good results, some 10% of recipients experience a posttransplant HCC recurrence, which leads to death in almost all patients. Recurrence is either due to the growth of occult metastases or to the engraftment of circulating tumor cells. It can be hypothesized that strategies to decrease the engraftment of circulating tumor cells could decrease the risk of recurrence and, in addition, extend access to transplantation to patients with more advanced HCC. These potential strategies can be schematized into five steps, including (1) selecting recipients with low baseline levels of circulating HCC cells, by adding biological markers (such as alpha fetoprotein or molecular signatures) to the accepted combination of morphological criteria; (2) decreasing the perioperative release of HCC cells, with careful perioperative handling of the tumors; (3) preventing the engraftment of circulating HCC cells by decreasing liver graft ischemia‐reperfusion injury, which has been shown to promote cancer cell engraftment and growth; (4) using anticancer drugs, including mammalian target of rapamycin inhibitors and (5) tuning immunity toward HCC clearance.