Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.

Liver transplantation for hepatocellular carcinoma： is zero recurrence theoretically possible？

BACKGROUND： Hepatocellular carcinoma（HCC） recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation.METHODS： Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence.RESULTS： Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven（6.1%） patients recurred within a delay of 19±22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level 〉400 ng/m L, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors.CONCLUSIONS： Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion,and cholangiocarcinoma component.

Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels

AIM To investigate the impact of alpha-fetoprotein(AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival.METHODS Data of adult patients who received liver transplant(LT) for hepatocellular carcinoma(HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/m L, high AFP level was defined as AFP value ≥ 10 to < 400 ng/m L, and very highAFP level was defined as AFP ≥ 400 ng/m L. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median(interquartile range). Categorical variables were compared by Spearman's test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05.RESULTS Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceaseddonor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/m L(n = 83); Group B, AFP ≥ 10 to < 400 ng/m L(n = 131); Group C, AFP ≥ 400 ng/m L(n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar(median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer(median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality(P = 0.626) and postoperative complication(P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger(A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria(P = 0.010). Poor differentiation and vascular permeation were also more common in this group(P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival(A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/m L for AFP(C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/m L was shown to affect the overall survival of the patients.CONCLUSION HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/m L was associated with disease recurrence, and AFP level of 105 ng/m L was found to be the cut-off value for overall survival difference.

Present status and recent advances in living donor liver transplantation for malignant hepatic tumors

BACKGROUND: Living donor liver transplantation (LDLT) has been increasingly used to treat hepatic tumors worldwide in recent years, and is currently the most effective alternative to deceased donor liver transplantation to overcome the problem of organ shortage. LDLT has played an enormous role in treating early malignant hepatic tumors. But the indication of LDLT for malignant hepatic tumors is based on indefinite criteria. This review summarizes the recent studies in LDLT for treating malignant hepatic tumors. DATA SOURCES: A literature research of the PubMed database was conducted and research articles were reviewed. RESULTS: The current data on LDLT for malignant hepatic tumors, combined with our hospital experience, indicated that if a patient with hepatocellular carcinoma (HCC) who meets with the conventional Milan criteria cannot undergo tumor resection because of poorly preserved liver function, and a cadaveric graft is difficult to obtain within six months, LDLT may be selected. In a patient with recurrence of HCC after conventional therapies, feasibility, optimal timing, and efficacy of LDLT as a second-line treatment should be determined. CONCLUSIONS: Tumor recurrence is related to the biological behavior and staging of the tumor. New immunosuppressors which have anti-tumor effects and inhibit the immune system need to be developed. The indications of LDLT for hepatic malignant tumors should be selected meticulously.

Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models

AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).

Transcatheter arterial chemoembolization in recurrent unresectable hepatocellular carcinoma after orthotopic liver transplantation

Aim: To investigate the survivals and efficacy of the doxorubicin drug eluting beads transcatheter arterial chemoembolization (TACE) in patients with recurrent hepatocellular carcinoma (HCC) status post orthotopic liver transplantation. Methods: Consecutive patients with HCC who underwent orthotopic liver transplantation from 2005 to 2012 were reviewed. Patients who developed recurrent HCC after orthotopic liver transplantation and received doxorubicin drug eluting beads TACE therapy were identified and included in the study. Survivals were calculated from the time of 1st doxorubicin drug eluting beads TACE of recurrent HCC. Kaplan Meier estimator with log rank test was used for survival analysis. Results: Eight patients had recurrent HCC after orthotopic liver transplantation and received doxorubicin drug eluting beads TACE. The overall median survival of these patients was 15.6 months. Two patients had significantly poorer overall median survival from doxorubicin drug eluting beads TACE (3.4 months) and both showed elevated serum alpha-fetoprotein levels (> 400 ng/mL) and extra-hepatic metastases (P = 0.03). Patients with poorly differentiated HCC in explant liver had the poor median overall survival (3.6 months) compared to the patients with well-to-moderately differentiated HCC (21.7 months, P = 0.004). Conclusion:Doxorubicin drug eluting beads TACE appears to be an effective treatment option for patients with recurrent HCC after orthotopic liver transplantation.

Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice

AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.

Prevention and treatment of hepatitis B relapse after liver transplantation

OBJECTIVES: To investigate the effect of orthotopic liver transplantation (OLT) on hepatitis B(HB)-related diseases and the efficiency of prevention and treatment with lamivudine on recurrence of hepatitis B posttransplant in China. METHODS: Orthotopic liver transplantation (OLT) under veno-venous bypass was performed in 10, of whom 9 males had hepatitis B and 1 female had hepatocellular cancer (HCC) without HB pretransplant. Eight of the 9 males had fulminant hepatitis B (FHB) and they all had preoperative serious jaundice, ascites and coagulopathy. Six had encephalopathy; 1 was associated with acute renal failure, and 1 with gastrointestinal hemorrhage. Seven of the 10 patients had lamivudine to prevent reinfection with hepatitis B. RESULTS: Of the 8 patients who have survived for 2-12 months, 7 have survived for 6-12 months. Two died, one of recurrent FHB and the other from multi-organ failure (MOF). Seven preoprative HB patients of the 8 survivors have excellent liver function through 1 has positive HBsAg 6 months after OLT. One of the 8 survivors, the female with HCC pretransplant, suffered hepatitis B 6 months after OLT and her hepatic function has been gradually improving with lamivudine therapy. CONCLUSIONS: OLT is an effective therapy for certain cases of FHB and HCC and lamivudine may prevent recurrence of hepatitis B after OLT.

索拉非尼治疗肝癌肝移植术后肿瘤复发的临床疗效观察

目的探讨索拉非尼治疗原发性肝癌(肝癌)肝移植术后肿瘤复发晚期患者的治疗效果及不良反应。方法回顾性分析2010年3月至2012年5月郑州人民医院肝脏外科中心收治的9例肝癌肝移植术后肿瘤复发晚期患者的临床资料。确诊肝癌复发后仍然继续原免疫抑制方案,抗肿瘤治疗予索拉非尼口服每次400mg,每日2次,直至病情进展、发生严重不良反应或死亡中止用药。9例患者每月至少随访1次,全面评价病情,同时检测血清甲胎蛋白(AFP)水平、排斥反应及药物不良反应等情况。结果 9例患者中部分缓解2例,疾病稳定4例,疾病进展3例。用药后2例患者AFP进行性上升,4例患者AFP水平稳定(升高≤10%),3例AFP水平明显下降(下降≥50%)。中位肿瘤进展时间为4.2个月,总生存期为6.9个月。不良反应的严重程度主要为1或2级,包括皮疹、腹泻、手足皮肤反应、恶心、呕吐、脱发、食欲减退、乏力、高血压等。经对症处理后患者均能耐受,无1例因药物不良反应而终止治疗。9例患者服用索拉非尼后均未发生排斥反应。结论索拉非尼作为一种新型多靶向性抗肿瘤药物,对肝癌肝移植术后肿瘤复发的晚期患者有一定的疗效。

原发性肝癌切除术后复发患者的补救性肝移植治疗疗效分析

目的:比较原发性肝癌切除术后复发患者与初次发生肝癌患者肝移植术后生存率的差异,筛选肝移植术后病死率相关的危险因素。方法:回顾性分析2003年7月至2005年8月收治的77例原发性肝癌患者,其中15例为术后复发肿瘤患者(复发组),62例为初发肿瘤患者(对照组),比较两组患者术后生存率。对所有患者的临床数据进行分析,并通过Cox风险比例模型筛选患者移植术后生存率的影响因素。结果:患者平均年龄为(48.6±4.3)岁,术后随访(20±3.7)个月,复发组和对照组分别有3例(20%)和15例(24.2%)患者死亡,移植术后30d内病死率分别为6.7%和1.6%。Cox风险比例模型提示,术前高胆红素、最大肿瘤直径较大、肉眼癌栓、术后输血以及肿瘤家族史是术后死亡的危险因素。结论:复发和初发肝移植患者术后生存率无显著差异;术前高胆红素、最大肿瘤直径较大、肉眼癌栓、术后输血以及肿瘤家族史是移植术后病死的危险因素。

单中心565例肝移植病例分析

目的:总结肝移植患者预后的影响因素,探讨进一步提高肝移植疗效的措施。方法:回顾性分析565例原位肝移植患者资料,统计患者生存率及并发症发生率。结果:565例肝移植患者的随访时间为3～104个月。2000年5月至2003年12月完成的171例患者术后1个月、1年、3年、5年的存活率分别为87.8%、73.2%、60.2%、57.7%;2004年1月至2009年1月完成的394例患者术后1个月、1年、3年、5年的存活率分别为91.2%、84.9%、69.2%、66.1%,存活率显著提高;良性肝病患者术后1年、3年、5年的存活率分别为83.3%、79.8%、78.5%;肝癌患者术后1年、3年、5年的存活率分别为78.4%、49.1%、45.1%。肝移植术后早期因腹腔内出血接受二次手术、血管性并发症、严重感染、急性肾功能衰竭、移植物原发无功能的发生率分别为1.1%、1.6%、13.6%、7.4%、1.2%。术后的远期并发症主要有:肝癌复发、胆道并发症、乙肝复发、新发恶性肿瘤、移植物慢性失功能、慢性肾功能损伤等,发生率分别为40.3%、6.7%、2.1%、0.9%、0.9%、1.1%;其中,符合和超出米兰标准的肝癌患者的肝癌复发率分别为8.1%和62.5%,所有肝癌复发患者的中位生存时间为19.6个月。结论:肝移植是治疗各种终末期肝病的有效措施,在供肝短缺的情况下,应优先将供肝分配给良性肝病患者和符合米兰标准的肝癌患者。

肝癌患者肝移植术前外周血AFP mRNA的表达与肿瘤复发及患者生存的关系

目的：探讨原发性肝细胞肝癌患者在肝移植术前外周血AFP mRNA的表达及其与术后肿瘤复发、患者预后的关系.方法：以2003年2月～2004年2月收入天津市第一中心医院的31例肝细胞肝癌行原位肝移植患者为研究对象,采用实时定量RT-PCR检测患者术前外周血AFP mRNA表达水平,均采用尸体供肝经典原位肝移植.以SPSS 12.0软件分析AFP mRNA的表达与患者术后肿瘤复发及生存的相关性.结果：31例患者中有10例AFP mRNA表达阳性,表达量为57～10 400 copy/μg,中位数为360 copy/μg.患者Child-pugh分级,肿瘤的大小、个数,病理Edmond分级与术前AFP mRNA的表达水平无关.肿瘤TNM分期为Ⅲ～Ⅳ期的患者AFP mRNA的阳性表达率显著高于Ⅰ～Ⅱ期患者（P=0.001）;脉管浸润的患者AFP mRNA的表达水平显著高于无脉管浸润者（P=0.029）.肝移植术前AFP mRNA阴性组的无瘤生存及总体生存显著高于AFP mRNA阳性组.结论：术前AFP mRNA表达的水平是肿瘤复发的危险因素,是术前可能存在肝外微转移的指标,可作为预后的判断因子.

符合Milan标准肝细胞癌患者行肝移植和肝切除术预后分析

目的：比较符合Milan标准肝细胞癌患者行肝移植和肝切除术后的生存和复发情况，分析影响患者肿瘤复发转移的相关危险因素。方法回顾性分析南方医院从2006年1月-2011年12月88例符合Milan标准肝细胞癌患者行肝移植或肝切除术的临床资料，比较两种术式的生存率及无瘤生存率；对围手术期的12个变量进行单因素分析，筛选影响术后肿瘤复发和转移的危险因素。结果移植组患者1、3、5年生存率与切除组差别无统计学意义（P＆gt;0.05）；移植组患者1、3、5年无瘤生存率优于切除组（P＆lt;0.05）；肝移植组肿瘤复发率明显低于肝切除组（P＆lt;0.05）；多因素分析提示性别、肿瘤大小、肿瘤病理分化程度、镜下微血管癌栓是影响无瘤生存率的重要预后因素。结论治疗符合Milan标准肝细胞癌，肝移植比肝切除能获得较长的无瘤生存时间；男性、肿瘤直径越大、有镜下血管癌栓、肿瘤病理分化程度低的患者术后更容易发生肿瘤复发和转移。

肝细胞癌患者肝移植术后肿瘤复发转移的防治

肝细胞癌(HCC)仍是目前发病率较高的消化道肿瘤,肝移植能从根本上切除肿瘤病灶,是HCC综合治疗方案中的主要手段之一。移植后肿瘤的复发和转移问题,是影响受体长期生存的主要因素。近年来,得益于全球范围的技术改进和经验积累,在HCC的诊疗方面取得了的长足的发展和进步。针对HCC肝移植适应证、复发转移预测、肝移植围手术期干预和术后HCC复发的综合治疗等方面进行探讨。

肝细胞癌肝移植术后肿瘤复发的危险因素与防治策略

肝细胞癌肝移植术后肿瘤的复发是造成患者和移植物存活率显著下降的主要原因。影响肝移植术后肿瘤复发的危险因素主要包括肿瘤的病理和生物学特性、受者相关因素、供者和供肝相关因素、手术相关因素等。免疫抑制方案的管理以及多种辅助治疗有助于预防肿瘤复发。针对肝细胞癌肝移植患者,如何早期识别肿瘤复发的危险因素并进行综合防治值得进一步探讨。

生物学标记物应用于肝癌原位肝移植预后的研究

目的:探讨生物学标记物对预测肝癌移植术后复发的价值。方法:回顾性分析2002年4月至2005年11月50例肝癌移植病例,存活者至少随访12月,石蜡切片做免疫组化检测E-cadherin、β-catenin、Ki-67的表达,分析其与复发、生存时间的相关性并与一些主要临床病理指标进行比较。结果:TNM分期、门静脉癌栓仅在单变量分析中对预测复发、生存时间有意义(P<0.05),术前血清AFP仅在多变量分析中与复发有关(OR=2.552,P<0.05);胞膜E-cadherin低表达、核β-catenin阳性、核Ki-67高增殖指数在单变量分析中对预测复发、生存时间的统计学意义均显著,而且在多变量分析中结果类似(均P<0.01),但胞膜β-catenin表达和预后无关(P>0.05)。结论:这3个生物学标记物有前景成为肝癌移植术后复发的预后因子,且价值可能优于临床病理指标。

术前调节性T细胞水平与肝癌肝移植术后肿瘤复发的关系

目的:探讨术前调节性T细胞(Treg)水平与肝癌肝移植术后肿瘤复发的关系。方法:搜集2006年1月至2007年2月在我院实施的32例肝癌肝移植病人术前外周血及肿瘤组织,采用流式细胞技术检测外周血CD4+CD25+调节性T细胞的比例,采用免疫组织化学方法检测肿瘤组织中FoxP3+细胞浸润的比例,以正常人的外周血、正常肝组织及肝硬化组织作对照。对32例病人随访18个月,观察肿瘤复发时间。分析术前Treg水平与肝癌肝移植术后肿瘤复发时间的相关性,单因素回归判断术前Treg水平对肿瘤复发时间的影响。结果:肝癌病人外周血及肝脏中Treg的水平较正常人为高;术前外周血Treg水平与肝移植术后肿瘤复发时间呈负相关(r=-0.87);术前Treg水平是影响术后肿瘤复发时间的独立危险因素(P<0.01);高Treg组病人肝移植术后一年肿瘤复发率高于低Treg组者,差异有统计学意义(P<0.05)。结论:术前调节性T细胞水平可作为肝癌肝移植术后肿瘤复发的预测指标之一。

肝癌的综合治疗

1 肝癌治疗的基本原则 1.1 综合治疗 由于肝癌至今尚无特效疗法,包括手术切除在内的各种疗法,均非100％根治,为此必须采用综合治疗的方针。近年资料表明,无论通过外科或内科手段进行的各种非切除治疗,由于较合理地综合使用一些单独使用时无根治希望的方法而使治疗效果明显提高,即“三联”的疗效优于“二联”,而“二联”又优于单一治疗。综合治疗不仅有量的变化,而且有质的差别,即1+1可>2;除不同治疗方法的同时应用外,尚可序贯应用。综合治疗可根据患者的肿瘤及肝功能状况、术者的临床经验及单位所具备的具体条件灵活开展。 1.2 积极治疗 积极治疗包括几个方面的内容:①对于没有黄疸、腹水和远处转移者,应积极手术探查并力争一期切除;

肝细胞癌肝移植术后免疫抑制剂的应用

肝移植已经成为肝细胞癌根治性治疗的重要手段,但术后复发与转移严重限制了肝细胞癌肝移植的疗效。近年来,国内外学者围绕肝移植术后免疫抑制剂的应用与肝细胞癌复发转移的关系进行了一系列研究。现就肝细胞癌肝移植术后免疫抑制剂的临床应用策略及建议作一简述,以更好地指导临床。