影响原发性肝癌肝移植治疗的预后因素分析

目的分析影响肝癌肝移植术后生存率和无瘤生存率的危险因素，探讨国内肝移植治疗肝癌的选择标准。方法对67例接受同种异位原位肝移植治疗的原发性肝癌病人的基本资料和肿瘤相关资料包括术前病情分级、血清AFP水平、术前辅助治疗以及肝癌大小、数目、pTNM分期、肿瘤恶性程度分级等因素进行单因素和多因素分析。结果术后1年、2年累积生存率为77％、67％，6个月和12个月无瘤生存率为66％和58％。单因素分析显示对肝癌肝移植术后累积生存率影响有统计学意义的因素为CHILD分级（MELD积分）和肝外大血管侵犯；多因素分析影响肝癌肝移植术后无瘤生存率有统计学义的因素是肿瘤大小、大血管侵犯和肿瘤分化程度。结论影响肝癌肝移植术后生存率的因素仍是术前患者肝功能状态。对存在大血管侵犯的肝癌患者需严格控制肝移植术适应证，而无血管侵犯的患者在选择肝移植治疗时肿瘤大小指标可较米兰标准适当放宽。     

影响肝癌肝移植预后的因素

本文综述了肝癌接受肝移植术的适应症,围手术期的处理,以及影响患者预后的主要因素。     

影响原发性肝癌患者肝移植预后的危险因素分析

目的 评价肝移植对原发性肝癌的疗效，探讨影响预后的危险因素。方法 回顾性分析1999年1月至2005年12月间872例原发性肝癌患者行首次肝移植后的生存情况，应用单因素分析和多因素Cox回归分析各项临床及病理指标对预后的影响。结果 围手术期死亡率为3．9％；移植术后6个月、1年、2年、3年及4年累积生存率分别为87．3％、74．4％、63．3％、53．8％和48．4％；术后6个月、1年、2年及3年无瘤生存率分别为80．6％、68．9％、58．5％和52．6％；再次移植率为2．8％。多因素Cox回归分析发现，影响术后累积生存率的独立危险因素包括患者术前甲胎蛋白水平（Х^2=16．732，P=0．001）、肿瘤双叶分布（RR=7．274，P=0．007）、门静脉主干或分支癌栓（RR=4．349，P=0．034）及镜下微血管浸润（RR=10．162，P=0．002）；影响术后无瘤生存率的独立危险因素包括肿瘤双叶分布（RR=2．969，P=0．047）、门静脉主干或分支癌栓（RR=2．496，P=0．025）、镜下微血管浸润（RR=10．115，P=0．020）及合并淋巴结侵犯或远处转移（RR=4．750，P=0．013）。结论 肝移植是治疗原发性肝癌的有效方法，经严格筛选的适宜受者预后良好。     

肝移植治疗原发性肝癌的探讨

目的：探讨原位肝脏移植在原发性肝癌治疗中的意义。方法：回顾分析2000年1月至2001年12月9例原发性肝癌行原位肝移植的临床资料。结果：术后生存大于6个月有6例（66.6％），生存大于12个月有4例（44.4％），平均存活时间11.5个月。与肝癌相关的死亡率为66％。术后复发依次为肝癌复发3例、骨转移2例、盆腔转移1例。结论：严格选择肝癌病人行肝移植；对肝硬化肝癌，肝移植是有效的治疗。     

影响肝癌肝移植预后的主要因素和抗肿瘤治疗

目的：总结肝细胞癌（hepatocellular carcinoma，HCC）肝移植的临床经验，探讨影响HCC肝移植预后的主要因素和综合抗肿瘤措施。方法：回顾分析我院1999年2月至2004年12月施行的98例HCC肝移植的临床资料和随访结果。分别按是否有门静脉主干或分支癌栓（portal vein tumor thrombi，PVTT）和原发肿瘤是否＞6．5cm为标准将病例分为4组，用Kaplan—Meier方法计算全组和各组的累积生存率，用Log—Rank检验比较组间生存率的差异。结果：随访时间1～78个月，中位时间37．6个月，全组1、3和5年累计生存率分别为84．9％、49.3％和33．2％。1、3和5年无瘤生存率分别为71.2％、42．4％和29．1％。原发肿瘤＜6．5cm和无PVTT组与另外两组的生存率有显著性差异。结论：原发肿瘤大小和PV’丌是影响HCC肝移植预后的主要因素，综合抗肿瘤措施有助于提高HCC肝移植的整体疗效。     

影响肝癌肝移植预后的因素

本文综述了肝癌接受肝移植术的适应症，围手术期的处理，以及影响患者预后的主要因素。     

原发性肝癌肝移植治疗进展

近10年来，原发性肝癌（简称肝癌）的治疗选择发生了明显变化。和肝癌切除、消融治疗一样，肝移植同样提供了治愈肝癌的可能性，并且还可减少肝癌复发率，以及消除肝硬化带来的各种并发症。目前有关肝癌肝移植的争论主要集中在如何制定移植标准，是否肝穿刺活检，术前处理和肿瘤复发的治疗。本文拟对肝癌肝移植治疗的主要相关问题做一综述。     

原位肝移植治疗原发性肝癌

本文报告了３例原发性肝细胞性肝癌病人肝移植的临床资料和初步经验。３例存活时间均超过３个月，其中１例于移植术后９２天死于巨细胞病毒感染，另２例仍存活。作者结合国内外文献复习，对肝移植术在治疗原发性肝癌中的地位，手术适应证，手术中体外静脉转流牟增加手术安全性的重要意义及其术后防治巨细胞病毒感染和肝炎复发等问题作了讨论。     

超出米兰标准的原发性肝癌肝移植术后预后因素分析

目的探讨影响超出米兰标准的原发性肝癌肝移植术后的预后的主要因素。方法回顾分析2000年9月至2006年9月施行的43例超出米兰标准的HCC肝移植的临床资料和随访结果。用Kaplan-Meier方法计算全组和各组的累积生存率,用Log-Rank检验比较组间生存率的差异。结果随访时间从14个月至55个月,移植术后1、2、3和5年生存率分别为51％、33％、21％和15％;无瘤生存率：移植术后1、2、3和5年无瘤生存率分别为55．1％、37％、13％和5％。生存或复发都不受患者年龄或Child-Pugh分级或肿瘤相关因素（如肿瘤数量、直径和TNM分期）的影响。结论血管侵犯是影响HCC肝移植预后的丰要因素。     

肝移植治疗原发性肝癌60例

目的　评价肝移植治疗原发性肝癌的疗效和受体选择。方法　对 1993年 9月～ 2 0 0 2年 9月施行的 6 0例次肝癌肝移植患者的临床资料进行回顾性分析 ,比较不同时期肝癌肝移植的疗效和大、小肝癌的术后存活率。结果　 1993年 9月～ 2 0 0 0年 7月共实施肝癌肝移植 2 3例 ,1个月、1年、2年、3年存活率分别为 73 9%、6 0 9%、4 3 5 %和 2 9 0 %。 2 0 0 0年 8月～ 2 0 0 2年 9月共实施肝癌肝移植 37例 ,1个月、1年、2年存活率分别为 89 2 %、75 8%和 6 1 2 %。术前肝功能ClildA或B级受体的 1月存活率为 89 5 % ,较ClildC级的 72 7%差异有显著性意义 (P <0 0 5 )。大肝癌 4 1例 ,半数存活期为 18 0个月 ,1个月、1年、2年、3年存活率分别为 82 9%、6 3 1%、4 6 7%和 37 4 %。小肝癌 19例 ,存活期平均为 2 9 6个月 ,1个月、1年、2年、3年存活率分别为 84 2 %、76 6 %、6 5 6 %和6 5 6 % ,大、小肝癌累积存活率差异无显著意义。大、小肝癌的复发率分别为 2 7 7%和 15 8% ,获得长期存活的患者大部分生活质量良好。结论　肝移植是治疗原发性肝癌合并肝硬化的有效方法 ,对于明确合并有肝硬化门脉高压的小肝癌应提倡及时进行肝移植治疗 ,适当选择部分大肝癌作为移植受体仍有一定的合理性 ,血管侵犯或肝外     

Living related liver transplantation for recurrent hepatocellular carcinoma in a normal liver

The role of liver transplantation for hepatocellular carcinoma (HCC) is evolving. In patients with advanced liver disease and early stage HCC, transplantation offers the best hope for cure. A living donor offers the optimal approach to a timely transplant, before disease progression obviates the potential benefit. But extending the indications beyond those designated by the United Network for Organ Sharing (UNOS) for liver transplantation for HCC is controversial [Hepatology 2001: 33: 1073; Liver Transplant 2000: 6: S1]. Cadaver split techniques and use of living donors are potentially compelling ways to test the limitations of liver transplantation for HCC, without notably reducing the cadaver organ pool. Herein, we report a rare case of a patient who developed a well-differentiated HCC in a normal liver. After resection of the index lesion and, later, of a remote recurrent lesion, a living donor liver transplant was offered. The natural history of this lesion and the management of transplantation in this setting are discussed.     

Indication of liver transplantation for hepatocellular carcinoma in Japan

Approximately 20,000 patients die of hepatocellular carcinoma (HCC) annually in Japan and most of them are hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. Recently, small HCC, less than 3 cm in diameter, have frequently been found by ultrasonography in the follow-up of patients with chronic liver diseases. Such cases are mainly treated by either surgical resection or percutaneous ethanol injection therapy (PEIT) with a satisfactory 5 year survival rate of 50%. In addition, the survival rate of advanced cases has gradually improved thanks to transcatheter arterial chemo-embolization combined with PEIT, radiation, hyperthermia, or immune therapy. On the other hand, our autopsy study has indicated a high frequency of extrahepatic metastasis in advanced cases. From these results, liver transplantation for HCC does not seem to be the treatment of first choice, at present, in Japan. In the future, the means to control the underlying infection of HBV or HCV as well as making an accurate imaging diagnosis for the detection of extrahepatic metastasis will become inevitably more important for successful liver transplantation in HCC.This report is the gist of a paper read at the 91st Annual Meeting of the Japanese Surgical Society, Kyoto, Japan, 1991     

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目的分析超出加利福尼亚大学(UCSF)标准肝癌肝移植病人的生存情况,探讨影响预后的因素。方法对2006年1月至2010年12月间中山大学附属第一医院超过UCSF标准的肝癌肝移植病人的临床病历资料进行回顾性分析,应用Kaplan-Meier法计算病人存活率,应用Log-Rank检验进行单因素分析,应用Cox比例风险模型进行多因素分析,探讨临床和肿瘤病理因素与病人存活率之间的关系。结果单因素分析显示对存活率和(或)无瘤存活率有影响的有:肿瘤Edmondson分级、肿瘤TNM分期和肿瘤门静脉侵犯、术前AFP水平、术前淋巴结转移(P<0.05);Cox回归分析显示,肿瘤Edmondson分级Ⅲ-Ⅳ级和肿瘤门静脉侵犯(P<0.05)是与预后相关的独立因素。结论对于超出UCSF标准的肝癌病人,移植的总体效果是欠佳的,但也有部分病人可获得较长期的存活或带瘤生存,肿瘤Edmondson分级和门静脉侵犯是影响该组病人预后的重要因素。     

Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma

About 20% of the patients with advanced hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are eventually delisted as a result of local tumor progression. Herein, we report our experience with conformal radiotherapy (CRT) as a novel bridge to LT. From July 2006 to August 2008, CRT was delivered in five or six fractions to patients with HCC listed for LT in whom either prior local therapies had failed or those not suitable for standard local therapies because of poor liver function or anatomic issues. Radiotherapy (RT) volumes and doses were individualized to spare the uninvolved liver with the goal of stabilizing the most aggressive HCC(s) in an attempt to reduce the chance of delisting as a result of tumor progression. Ten patients with tumor diameters ranging from 25 to 108 mm were treated. Eight out of 10 tumors were beyond Milan criteria. The median age was 55 (range 36–64). Seventy percent of the patients were male subjects. The median medical MELD score was 11 (range 9–17). The median irradiated HCC volume was 79 cc (range 15–798 cc). The median RT delivered dose was 33 Gy (range 8.5–54 Gy), in one to six fractions. The median dose to the uninvolved liver was 13.3 Gy (range 1.8–16.5). Nine patients completed their CRT as planned and one patient was transplanted after the first fraction. The treatment was well tolerated: Grade 1 nausea was reported in three patients, the platelet count decreased from 154 to 98 in one patient, and there were no other complications. No treated tumors progressed during or after the treatment. Two tumors remained stable; the rest had 10–50% regression, which was sustained on follow‐up imaging. The median follow up was 14 months (range 3–20). Local tumor control was achieved in all treated tumors.Two patients were delisted as a result of cancer progression outside the treated field (one in the context of systemic metastases; yet another with progression of other untreated HCC in the liver). Three patients are still waiting for transplantation. Five patients underwent LT with no complications attributable to the CRT. Explant pathology, available for five patients, showed tumor necrosis and fibrosis with sparing of the untreated parenchyma. All transplanted patients treated with CRT are cancer‐free. CRT is a safe and efficacious local bridging therapy for patients with advanced HCC who are on the waiting list for LT. Further studies are warranted to compare the effectiveness of CRT to other local treatment regimens for HCC.     

Role of transarterial chemoembolization for hepatocellular carcinoma before liver transplantation with special consideration of tumor necrosis

Abstract:  Several authors suggest that local ablative therapies, specifically transarterial chemoembolization (TACE), may control tumor progression of hepatocellular carcinoma (HCC) in patients who are on the waiting list for liver transplantation (orthotopic liver transplantation, OLT). There is still no evidence if TACE followed by OLT is able to prevent recurrence of tumor, to prolong survival rate of the patients on the waiting list, or to improve the survival after OLT. We report 27 patients with HCC who underwent OLT. From these patients, 15 were pre-treated with TACE alone or in combination with percutaneous ethanol injection (PEI) or laser-induced thermo therapy (LITT). Mean time on the waiting list was 214 d for treated patients and 133 d for untreated patients. Comparing pre-operative imaging and histopathological staging post-transplant, we found 13 patients with tumor progression out of which five were treated with TACE. In two of the TACE patients a decrease of lesions could be achieved. In a single patient, there was no evidence of any residual tumor. Only one patient displayed tumor progression prior to OLT despite undergoing TACE. Comparison of outcome in patients undergoing TACE or having no TACE was not statisitically significant (p = 0.5). In addition, our analysis showed that progression either in the total study population or in the TACE group alone is associated with a significant poorer outcome concerning overall survival (p = 0.02 and p = 0.02).     

Feasibility of salvage liver transplantation for patients with recurrent hepatocellular carcinoma

BACKGROUND: Recurrence is the most frequent cause of treatment failure after hepatocellular carcinoma (HCC) resection. Salvage liver transplantation is an alternative treatment for recurrent HCC. The transplantability for patients with recurrent HCC has not been well studied. STUDY DESIGN: This study sought to determine how many patients with recurrent HCC are still candidates for liver transplantation, and to ascertain the possible time from HCC recurrence to the loss of transplantability. In an university hospital setting, 154 of the 252 patients receiving primary HCC resection, from January 1992 through December 1996, had recurrence and were analyzed. The mean follow-up time was 6 years. Among the 154 patients, 74 patients (group 1) were not eligible for liver transplantation according to the Milan criteria, while 80 patients were eligible (group 2). Demographic characteristics of both groups were compared and the curve of transplantability was calculated. RESULTS: When compared with group 1 patients, group 2 patients displayed more cirrhosis (p = 0.007), lower pTNM stage (p = 0.004), were older (p = 0.004), presented with smaller tumors (p < 0.001), and displayed a longer disease-free interval (p < 0.001). In group 1, only 47% (35/74) patients were eligible for liver transplantation at the time of index hepatectomy, in contrast to 84% (67/80) in the group 2 patients, p < 0.001. The median time from HCC recurrence to the time they were no longer transplantable was 38 months. The total time from the index HCC resection to the time of loss of transplantability was 83 months. CONCLUSION: In a cohort of patients after resection for their primary HCC, 33% patients had no recurrence and were not in need for liver transplantation in a mean follow-up of 72 months. About 52% of the patients with recurrent HCC still meet the criteria for liver transplantation. For patients with some certain characteristics, resection of the primary HCC may postpone the time of liver transplantation and prolong the time in which a suitable donor searched, while primary liver transplantation may be considered for those patients with factors of low transplantability after recurrence.     

Pattern and management of recurrent hepatocellular carcinoma after liver transplantation

A series of 132 patients who underwent liver transplantation for primary liver cancer was collected from three different Italian hospitals and studied for recurrence of hepatocellular carcinoma after liver replacement. Twenty-one patients (15.9%) had a neoplastic recurrence after an average follow-up period of 7.8 months after transplantation (range, 1–25 months); 15 (71%) occurred within the first 18 months after transplant and only two recurred later than 2 years. The sites of recurrence were grafted liver (19%), lung (19%), bone (14%), and other (5%). Eight patients (38%) had multiple organ involvement at the onset. After 1, 2, 3, and 4 years the overall survival rates were 62%, 43%, 29%, and 23%, respectively. The tumor factors related to early cancer recurrence after transplantation were diameter of nodules more than 3 cm (P < 0.05), tumor stage not meeting the "Milan criteria" (P < 0.03), and presence of peri-tumoral capsule (P < 0.05); the number of nodules, TNM stage, presence of vascular invasion, alpha-fetoprotein level more than 150 UI/l, pre-transplant chemoembolization and resectability of cancer deposits did not seem to be related to early recurrence. The prognosis differed in the 7 patients with resectable recurrences (57% 4-year survival) and the 14 patients with unresectable disease (14% 4-year survival) (P < 0.02). Better patient selection and new combined medical strategies could reduce the incidence of and mortality from liver cancer recurrence after transplantation. The role of surgical resection of recurrence should be further investigated. Received for publication on May 26, 1997; accepted on July 3, 1997