肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

骨桥蛋白及 CD44 v6在肺腺癌侵袭转移中的作用

目的：探讨骨桥蛋白（ OPN）及其受体CD44v6在肺腺癌侵袭转移中的作用。方法应用免疫组化方法检测129例癌旁组织、肺原位腺癌（AIS）、伏壁样生长为主型腺癌（LPA）患者手术切除标本中OPN、CD44v6的表达情况。检测H358细胞（原位癌细胞系）和A549细胞中OPN、CD44v6蛋白及mRNA的表达,Transwell 试验观察OPN、CD44 v6对H358细胞、A549细胞侵袭力的影响。结果 OPN、CD44 v6在LPA组织中的表达阳性率显著高于AIS及癌旁组织,AIS高于癌旁组织,OPN与CD44v6的表达呈显著正相关（ P＜0．05）。 OPN、CD44v6及OPN mR-NA、CD44v6 mRNA在A549细胞中的表达水平高于H358细胞。 Transwell试验提示OPN对A549细胞的趋化作用高于H358细胞。使用OPN抗体阻断OPN对两种细胞的趋化作用,两种细胞穿过数均减少;阻断CD44 v6受体通道后,OPN对两种细胞的趋化作用明显减弱。结论 OPN-CD44 v6复合体对肺腺癌的侵袭能力具有重要作用,OPN有望成为评估肺腺癌进展及预测肿瘤转移潜能的指标。     

应用组织芯片研究凋亡抑制基因Survivin在胃癌中的表达

目的　检测Survivin和CD44v6在胃癌中的表达,以探讨二者在胃癌中表达的相关性及其与预后的关系。方法　利用组织芯片技术构建胃癌组织芯片,应用免疫组织化学S P法检测Survivin和CD44v6蛋白在胃癌中的表达。结果　胃癌中Survivin及CD44v6的总表达率分别为 58 6% (58 /99)和 35 4% (35 /99)。Survivin在早期胃癌中的表达显著高于进展期胃癌 (P<0 05 ),与胃癌的其它临床病理特征无相关性。CD44v6阳性表达与胃癌生长方式(P<0 001)、浸润深度 (P<0 05 )及淋巴结转移 (P<0 001 )密切相关。Sur vivin和CD44v6在胃癌中的表达无相关性(r=-0 065,P>0 05)。Survivin与胃癌患者的生存率无显著相关,而CD44v6表达阳性组 5年生存率(16 13% )显著低于CD44v6表达阴性组 5年生存率(60 67% ) (P<0 001 )。结论　Survivin和CD44v6在胃癌中均有过量表达。Survivin可能参与胃癌发生、发展的早期过程;而CD44v6阳性表达与胃癌的浸润和转移密切相关,同时可以提示胃癌的不良预后。     

骨桥蛋白和CD44v6在肝癌中的表达及意义

骨桥蛋白(osteopontin，OPN)是一种分泌型钙结合磷酸化糖蛋白，其中含有特异的与细胞黏附有关的RGD(Arg-Gly-Asp)序列，通过与其受体整合素、CD44等结合来促进细胞的趋化、黏附和迁移，从而介导肿瘤细胞的侵袭转移，在肿瘤的复发与转移中起到重要作用。OPN过表达与肝癌的复发和转移有关，并认为是早期预测肿瘤复发的一个指标。现对OPN和CD44v6在肝癌中的表达进行研究，以了解其临床意义。     

E-选择素及其配体表达对肝癌转移的临床意义

目的 探讨E-选择索(E-selectin)及其配体在肝癌细胞与内皮细胞黏附中的作用和二者表达的临床意义;并筛选可能阻断黏附作用的药物. 方法 收集78例肝细胞癌患者的临床资料,采用免疫组织化学方法检测E-selectin、sLeX、sLeA、CD44v6的表达情况,按临床特征分组并比较各组E-selectin、sLeX、sLeA、CD44v6的阳性表达率差异.体外实验采用实时荧光定量PCR检测E-selectin和细胞间黏附分子(ICAM)-1在ED25、ECV304两种内皮细胞中的表达;黏附实验检测肝癌细胞HepG2与ED25、ECV304两种内皮细胞的黏附活性,并检测不同药物对黏附作用的影响.对临床资料数据采用χ2检验、Kaplan-Meier生存分析与Wilcoxon检验;对体外实验计量数据进行方差分析.结果 E-selectin在肝癌病灶内血管内皮细胞中的阳性表达率为70.51%,sLeX、sLeA、CDJ44v6在肝癌细胞中的阳性表达率分别为64.10%、69.23%、62.90%.sLeX、sLeA、CD44v6表达阴性患者的平均生存期显著长于阳性患者(P值均<0.05).有门静脉癌栓、术前肝外转移、卫星病灶、术后3个月内复发各组E-selectin、sLeX、sLeA的阳性表达率差异均有统计学意义(P值均<0.05);而肿瘤大小、血清AFP水平均与E-selectin、sLeX、sLeA的阳性表达率无相关性;病理分级Ⅲ～Ⅳ级组与Ⅰ～Ⅱ级组的E-selectin和CD44v6的阳性表达率差异均有统计学意义(P值均<0.05).CD44v6的表达特点是术后3个月内复发者有较高的阳性率,有卫星灶者阳性率也较高.E-selectin和ICAM-1可高表达于活化后的ED25和ECV304细胞;且能介导HepG2细胞与ED25和ECV304细胞的黏附,地塞米松,丹参酮ⅡA都具有较强的抗黏附能力,且抗黏附作用随着浓度的增加而增强.结论 E-selectin、sLeX.sLeA、CD44v6的表达与患者的预后,门静脉癌栓等临床特征密切相关,可作为临床预后和术后早期复发的评估依据.E-selectin、ICAM-1及其配体可增强肝癌细胞与内皮细胞的黏附,促进肝癌转移;地塞米松、丹参酮ⅡA可阻断其黏附作用.     

E-选择素及其配体表达对肝癌转移的临床意义

目的 探讨E-选择索(E-selectin)及其配体在肝癌细胞与内皮细胞黏附中的作用和二者表达的临床意义;并筛选可能阻断黏附作用的药物. 方法 收集78例肝细胞癌患者的临床资料,采用免疫组织化学方法检测E-selectin、sLeX、sLeA、CD44v6的表达情况,按临床特征分组并比较各组E-selectin、sLeX、sLeA、CD44v6的阳性表达率差异.体外实验采用实时荧光定量PCR检测E-selectin和细胞间黏附分子(ICAM)-1在ED25、ECV304两种内皮细胞中的表达;黏附实验检测肝癌细胞HepG2与ED25、ECV304两种内皮细胞的黏附活性,并检测不同药物对黏附作用的影响.对临床资料数据采用χ2检验、Kaplan-Meier生存分析与Wilcoxon检验;对体外实验计量数据进行方差分析.结果 E-selectin在肝癌病灶内血管内皮细胞中的阳性表达率为70.51%,sLeX、sLeA、CDJ44v6在肝癌细胞中的阳性表达率分别为64.10%、69.23%、62.90%.sLeX、sLeA、CD44v6表达阴性患者的平均生存期显著长于阳性患者(P值均<0.05).有门静脉癌栓、术前肝外转移、卫星病灶、术后3个月内复发各组E-selectin、sLeX、sLeA的阳性表达率差异均有统计学意义(P值均<0.05);而肿瘤大小、血清AFP水平均与E-selectin、sLeX、sLeA的阳性表达率无相关性;病理分级Ⅲ～Ⅳ级组与Ⅰ～Ⅱ级组的E-selectin和CD44v6的阳性表达率差异均有统计学意义(P值均<0.05).CD44v6的表达特点是术后3个月内复发者有较高的阳性率,有卫星灶者阳性率也较高.E-selectin和ICAM-1可高表达于活化后的ED25和ECV304细胞;且能介导HepG2细胞与ED25和ECV304细胞的黏附,地塞米松,丹参酮ⅡA都具有较强的抗黏附能力,且抗黏附作用随着浓度的增加而增强.结论 E-selectin、sLeX.sLeA、CD44v6的表达与患者的预后,门静脉癌栓等临床特征密切相关,可作为临床预后和术后早期复发的评估依据.E-selectin、ICAM-1及其配体可增强肝癌细胞与内皮细胞的黏附,促进肝癌转移;地塞米松、丹参酮ⅡA可阻断其黏附作用.     

E-选择素及其配体表达对肝癌转移的临床意义

目的 探讨E-选择索(E-selectin)及其配体在肝癌细胞与内皮细胞黏附中的作用和二者表达的临床意义;并筛选可能阻断黏附作用的药物. 方法 收集78例肝细胞癌患者的临床资料,采用免疫组织化学方法检测E-selectin、sLeX、sLeA、CD44v6的表达情况,按临床特征分组并比较各组E-selectin、sLeX、sLeA、CD44v6的阳性表达率差异.体外实验采用实时荧光定量PCR检测E-selectin和细胞间黏附分子(ICAM)-1在ED25、ECV304两种内皮细胞中的表达;黏附实验检测肝癌细胞HepG2与ED25、ECV304两种内皮细胞的黏附活性,并检测不同药物对黏附作用的影响.对临床资料数据采用χ2检验、Kaplan-Meier生存分析与Wilcoxon检验;对体外实验计量数据进行方差分析.结果 E-selectin在肝癌病灶内血管内皮细胞中的阳性表达率为70.51%,sLeX、sLeA、CDJ44v6在肝癌细胞中的阳性表达率分别为64.10%、69.23%、62.90%.sLeX、sLeA、CD44v6表达阴性患者的平均生存期显著长于阳性患者(P值均<0.05).有门静脉癌栓、术前肝外转移、卫星病灶、术后3个月内复发各组E-selectin、sLeX、sLeA的阳性表达率差异均有统计学意义(P值均<0.05);而肿瘤大小、血清AFP水平均与E-selectin、sLeX、sLeA的阳性表达率无相关性;病理分级Ⅲ～Ⅳ级组与Ⅰ～Ⅱ级组的E-selectin和CD44v6的阳性表达率差异均有统计学意义(P值均<0.05).CD44v6的表达特点是术后3个月内复发者有较高的阳性率,有卫星灶者阳性率也较高.E-selectin和ICAM-1可高表达于活化后的ED25和ECV304细胞;且能介导HepG2细胞与ED25和ECV304细胞的黏附,地塞米松,丹参酮ⅡA都具有较强的抗黏附能力,且抗黏附作用随着浓度的增加而增强.结论 E-selectin、sLeX.sLeA、CD44v6的表达与患者的预后,门静脉癌栓等临床特征密切相关,可作为临床预后和术后早期复发的评估依据.E-selectin、ICAM-1及其配体可增强肝癌细胞与内皮细胞的黏附,促进肝癌转移;地塞米松、丹参酮ⅡA可阻断其黏附作用.     

膀胱移行细胞癌组织中CD44v6的表达及意义

采用免疫组化SABC法检测64例膀胱移行细胞癌和癌旁膀胱组织中的CD4v6。结果显示,64例膀胱移行细胞癌组织中CD44v6阳性表达率为56.3%,癌旁膀胱组织中未见CD44v6蛋白表达;CD44v6表达水平与膀胱移行细胞癌组织学分级、临床分期及复发有关。认为CD44v6可作为判断膀胱移行细胞癌的恶性程度和复发的参考依据。     

结直肠癌组织中CD44V3,v6蛋白的表达意义

目的研究CD44v3,v6蛋白在结直肠癌组织中的表达及其预后意义.方法应用EnvisionTM免疫组化法,回顾性分析121例结直肠癌石蜡组织CD44v3,v6的表达.患者中位随访时间为67.77mo.结果CD44v3,v6在结直肠癌中的阳性率分别为60.3%和57.9%.CD44v3的阳性表达与患者肿瘤部位,淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).CD44v6的阳性表达与患者性别、淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).Kaplan-Meier生存曲线,Log-rank检验单因素生存分析结果显示,CD44v3阴性、阳性患者的五年生存率分别为81.25%,60.27%,两者之间存在显著性差异(P=0.035);CD44v6阴性、阳性患者的5 a生存率分别为80.39%,60.00%,两者之间亦存在显著性差异(P=0.0299).Cox模型多因素生存分析结果显示,CD44v3表达是影响结直肠癌预后的独立因素.结论CD44v3,v6蛋白与结直肠癌转移、预后相关,CD44v3是影响结直肠癌预后的独立因素.     

骨桥蛋白下游信号分子在肝细胞癌中的表达

目的 通过肝癌组织芯片检测骨桥蛋白(OPN)下游的信号蛋白,以确定其在肝癌组织中的信号传导途径.方法构建肝细胞癌组织芯片,用免疫组织化学染色法检测并分析OPN及其相关分子、整合素αV、CD44v6、磷酸化黏着斑激酶(p-FAK)、p-Src、磷酸化细胞外信号调节激酶(p-ERK)、磷酸化蛋白激酶B(p-AKT)的表达水平及其关系.计数资料用卡方检验(或Fisher's确切概率法),各指标之间的相关性采用Spearman相关分析.结果OPN及其受体整合素αV、CD44v6和相关信号分子p-FAK、p-Src、Src、p-ERK、p-AKT在肝癌组织的表达水平均明显高于癌周正常肝组织(P＜0.05).FAK在肝癌和癌周组织中的表达差异无统计学意义(P＞0.05).OPN的表达与整合素oV(P＜0.01)、p-ERK(P＜0.01)、CD44v6(P＜0.05)密切相关,与p-FAK、p-Src、p-AKT无相关性(P＞0.05).但p-FAK(P＜0.05)、p-Src(P＜0.01)和p-AKT(P＜0.05)均与OPN受体整合素αV密切相关,p-FAK还与OPN的受体CD44v6密切相关(P＜0.01).结论 OPN通过其受体整合素αV、CD44v6激活下游的丝裂原活化蛋白激酶途径以促进肝癌转移.

Abstract：

Objective Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. Methods The expressions of OPN, intergrin α V, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis. The relationship of OPN with P-ERK, P-Src and P-AKT were explored and the role in HCC metastasis was analysed. Results The expression levels of OPN, intergrin α V, CD44v6, P-FAK, P-Src, Src, P-ERK and P-AKT in HCC tissue were significantly higher than that in normal tissue (P ＜ 0.05). No significant difference was found between the expression levels of FAK in HCC tissue and normal tissue (P ＞0.05). OPN expression was significantly associated with Integrin α v (P ＜ 0.01 ), CD44V6 (P ＜ 0.01) and P-ERK (P ＜ 0.05) but not with P-Stc, P-FAK and P-AKT (P ＞ 0.05). The expressions of P-FAK (P ＜ 0.05), P-Src (P ＜ 0.01) and P-AKT (P ＜ 0.05) were significantly associated with Integrin α v and the P-FAK expression was also significantly associated with CD44V6 (P ＜ 0.01). Conclusion OPN promotes HCC metastasis though Integrin α v/CD44V6/MAPK pathway in human HCC.     

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria

Background:

The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution.

Objective:

The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis.

Methods:

During 1997–2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child–Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT).

Results:

The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis.

Conclusions:

Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.     

Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation

AIM： To assess the outcome of patients, who underwent transarterial chemoembolization （TACE） for hepatocellular carcinoma （HCC） and subsequently liver transplantation （OLT） irrespective of tumor size when no tumor progression was observed. METHODS： Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT. Tumor progression was monitored by ultrasound and AFP level every 6 wk. Fifteen patients showed signs of tumor progression without transplantation. The remaining 20 patients underwent OLT. Further records of 7 patients with HCC seen in histological examination after OLT were included. RESULTS： The patients after TACE without tumor progression underwent transplantation and had a median survival of 92.3 too. Patients, who did not qualify for liver transplantation or had signs of tumor progression had a median survival of 8.4 mo. The patients without treatment had a median survival of 3.8 mo. Independent of International Union Against Cancer （UICC） stages, the patients without tumor progression and subsequent OLT had longer median survival. No significant difference was seen in the OLT treated patients if they did not fulfill the Milan criteria. CONCLUSION： Selection of patients for OLT based on tumor progression results in good survival. The evaluation of HCC patients should not only be based on tumor size and number of foci but also on tumor progression and growth behavior under therapy.     

Liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early,unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results, the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study, the"Milan criteria" were applied achieving a 4-year survival rate similar to OLT for benign disease.Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade, particularly in Asia,and published outcome data is comparable to that of OLT. This article will review the evidence, indications,and the future direction of liver transplantation for liver cancer.     

Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival

BACKGROUND/AIMS: Members of the CD44 family are transmembrane glycoproteins which act mainly as receptors for hyaluronan. We have examined the expression of CD44s and several CD44v and the relationship between these and hepatocellular carcinoma (HCC) grade, clinicopathological parameters, p53 expression, and patient survival in HCC. METHODS: Formalin-fixed, paraffin-embedded tissue sections from 107 surgically resected HCC were examined immunohistochemically using a semi-quantitative scoring system to detect the expression of different forms of CD44. RESULTS: The number of CD44s-positive cases was 36 (34%), CD44v5 52 (49%), CD44v6 29 (27%), CD44v7-8 41 (38%), and CD44v10 26 (24%). Expression of these molecules correlated with high histological grade, being the highest in poorly-differentiated HCC. High CD44v6 expression significantly correlated with the presence of vascular invasion and p53 overexpression. Kaplan-Meier examination of patient survival revealed that HCC patients with positivity of each of these five molecules had a reduced survival rate, and that HCC patients positive for all the five CD44 molecules had worse survival than HCC patients positive for four or less of these CD44 molecules. In multivariate survival analysis, CD44s positivity was an independent factor. However, positivity for one or more CD44 isoforms was the most useful independent factor for overall survival. CONCLUSION: These results suggest that up-regulation of CD44 isoforms is associated with poorly-differentiated HCC and shortened survival.     

Liver transplantation for hepatocellular carcinoma

In patients with cirrhosis and hepatocellular carcinoma (HCC), orthotopic liver transplantation (OLT) offers hope for cure of both the complicating HCC and the underlying chronic liver disease. Excellent 5 year survival has been reported when the restrictive Milan criteria are used to select transplant candidates. Alternative recommendations have recently been proposed by groups at University of California San Francisco, University of Pittsburgh and Mount Sinai. We review current and evolving concepts regarding selection criteria for OLT in patients with HCC, along with strategies to reduce waiting times, such as the impact of the implementation of the model for end-stage liver disease (MELD) scoring system on organ distribution and the role of living donor OLT for this indication. The possible efficacy of adjuvant anti-tumour therapies in limiting HCC growth while waiting for OLT, along with factors influencing the risk of HCC recurrence post-OLT, the major cause of death in this setting, are also discussed.     

18F-FDG PET/CT纳入肝细胞癌肝移植标准的趋势与价值

肝移植是治疗肝细胞癌(HCC)的有效方法,为降低HCC肝移植术后可能出现较高肿瘤复发率,有学者率先提出著名的Milan标准。但该标准过于严格,部分患者因其肿瘤病变较大或多个结节,虽其生物行为相对“温良”,也被排除在等待肝移植名单之外,随之世界各地出现了众多的“扩大Milan版标准”。HCC组织病理学的微血管侵犯(MVI)、肿瘤组织低分化与HCC肝移植术后较高复发率有显著相关性。复习总结了近年来国内外18氟-脱氧葡萄糖(18F-FDG)PET/CT在HCC肝移植方面的应用文献,发现18F-FDG在HCC病变部位不同的摄取程度,反映了肿瘤组织生物学行为特征即侵袭性的差异;18F-FDG高摄取与HCC病变的MVI、低分化呈正相关;18F-FDG还能敏感、准确地发现HCC肝外转移灶。认为术前18F-FDG PET/CT结果对HCC肝移植预后评估有巨大价值,将其结果纳入HCC肝移植标准是趋势所归,也有望统一“扩大Milan版标准”。建议新的肝移植标准可定义为,原则上遵循Milan标准;对超出Milan标准者,满足HCC病变18F-FDG PET/CT阴性,且排除大血管侵犯和肝外转移。     

Living donor liver transplantation in hepatocellular carcinoma beyond the Milan criteria

Background/Aims: In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria. Methods: Pre‐operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated. Results: The 1‐ and 3‐year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface (P=0.014) and progressive disease after pretransplant treatment (P=0.038). The 2‐year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively (P<0.001). The 2‐year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors (P=0.022). Conclusions: In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface.     

Criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation

AIM: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT).METHODS: Two hundred and twenty-three patients with HCC were followed for at least six years to identify independent risk factors for long-term survival after liver transplantation (LT). The criteria for HCC liver transplantation included the Milan, University of California San Francisco, Hangzhou and Shanghai Fudan criteria. The Cox regression model was used to build MHCAT specifying these criteria. A survival analysis was carried out for patients with high or low risk.RESULTS: The one-, three- and five-year cumulative survival of HCC patients after LT was 78.9%, 53.2% and 46.4%, respectively. Of the HCC patients, the proportion meeting the Hangzhou and Fudan criteria was significantly higher than the proportion meeting the Milan criteria (64.6% vs 39.5%, 52.0% vs 39.5%, P < 0.05). Moreover, the proportion meeting the Hangzhou criteria was also significantly higher than the proportion meeting other criteria (P < 0.01). Pre-operative alfa-fetoprotein level, intraoperative blood loss and retransplantation were common significant predictors of long-term survival in HCC patients with reference to the Milan, University of California San Francisco and Fudan criteria, whereas in MHCAT based on the Hangzhou criteria, total bilirubin, intraoperative blood loss and retransplantation were independent predictors. The c-statistic for MHCAT was 0.773-0.824, with no statistical difference among these four criteria. According to the MHCAT scoring system, patients with low risk showed a higher five-year survival than those with high risk (P < 0.001).CONCLUSION: MHCAT can effectively predict long-term survival for HCC patients, but needs to be verified by multi-center retrospective or randomized controlled trials.