意大利帕多瓦大学医院 Alessandro Vitale教授

 

　　编者按：肝细胞肝癌（HCC）是最常见的恶性肿瘤之一。近年来，随着肿瘤研究取得了长足进步，传统的单一外科治疗已被“多学科综合治疗模式”所代替。此外，随着肿瘤筛查技术的普及和提高，早期发现和有效治疗能够明显提高其临床疗效，特别是使肝癌的临床诊断和治疗效果均得到明显改观。然而，目前针对早期HCC治疗的选择标准尚存争议。在第51届EASL年会上，来自意大利帕多瓦大学医院的Alessandro Vitale教授针对早期肝癌患者的治疗选择进行了专题报告，会后并接受了《国际肝病》的采访。

 

　　不同治疗方案的利与弊

 

　　目前，存在很多关于早期HCC最佳治疗方案的标准，是肝切除、肝移植，还是局部消融，我们先来看看这几种治疗方案的优缺点。

 

　　1. 射频消融

 

　　射频消融的优点是治疗后的病死率低，花费少。如果病灶直径<3cm，位于肝脏深部，射频消融将是最佳的治疗选择。射频消融治疗的适应征与肿瘤大小有关，如果直径>3cm，局部复发的风险会非常高。

 

　　2. 手术切除

 

　　肝切除术的优点是肿瘤根除率较射频消融更高，问题是只有肝功能处于代偿期的患者可接受手术切除，对于肝功能不全的患者存在局限性。手术切除的其他缺点是相比肝移植来说，它的术后复发风险很高。

 

　　3. TACE

 

　　TACE的适应征和禁忌征和手术切除是一样的。例如，肿瘤越小，肝功能越好，TACE的效果就越好。

 

　　4. 肝移植

 

　　理论上讲，对每一个HCC患者来说最好的治疗方法是肝移植。但是由于目前在全世界范围内，肝移植供体明显缺乏，需要漫长的等待；而且除了HCC患者以外，还有很多终末期的肝病患者也在等待可用的肝源；再次，肝移植手术费用昂贵，因此肝移植对于很多HCC患者来说“可望而不可及”。

 

　　选择标准及其考虑因素

 

　　当然，我们应该看到针对每位患者的个体情况，还是可以选择其最适合的治疗方案。例如，射频消融是门静脉高压患者的最佳治疗方案；手术切除是对于肝功能尚未失代偿单个病灶的最佳治疗方法。

 

　　对于HCC患者来说，TACE是极其有价值的，这取决于手术切除中哪些是可切除的肿瘤。在现代外科治疗策略中，这意味着TACE作为一线治疗的应用空间非常小，更多的是将其作为外科手术或其他治疗方法的补救性治疗措施。

 

　　从大数据来看，支持各种治疗方法的证据不尽相同，其适应征也会各种各样。其中首要的一个要考虑的因素就是肿瘤位置，如果肿瘤位于肝脏表面，最好的治疗措施是腹腔镜下切除术。如果肿瘤位于肝脏深处，患者肝功能正常，最好的选择则是射频消融。肝移植应该仅作为一线治疗后肿瘤复发或肝功能失代偿的补救治疗。

 

　　正在完善的HCC分期标准

 

　　如果根据临床证据最多的BCLC分类标准，通常只有在患者符合米兰标准的情况下才会选择肝移植。但是如果我们实行个体化的治疗方案，事实就会大相径庭。

 

　　在去年的ILCA年会上，香港专家潘冬平教授就肝癌分期标准提出了自己的见解，本届大会上韩国学者进一步论证其可行性。Vitale对该标准表示了高度的认可，他说：“我认为香港肝癌分期系统是HCC分期标准的一个显著的进步，它优于BCLC分期的地方在于它针对HCC治疗的评估较BCLC分期系统更完善。但是两者本身都仍存在缺陷，原因是在真实世界中，患者是不可能使用严格算法的，我们只能针对每一位患者的实际情况来考虑不同的选择。

 

　　原文链接：

 

　　1.For early stage liver cancer patients，How to choose liver resection, radiofrequency ablation（RFA）, or transplant？What is the criteria?

 

　　This is a very important question. We have many criteria to choose the best therapy. If we look at the evidence-based criteria of the BCLC classification, usually we have the choice of liver transplantation only for patients within the Milan criteria.Radiofrequency ablation is the best therapy for patients who have portal hypertension. Resection is the best therapy for single nodes without liver decompensation. But if we personalize the approach to treatment of HCC, the reality is different. Looking at big data, the evidence is different and the indications are also probably different. The first variable is tumor location. If the tumor is located on the surface of the liver, the best solution is a laparoscopic resection. If the tumor is deep in the liver with good liver function, the best option is radiofrequency ablation. Liver transplantation, in my opinion and the opinion of many experts in the field, should be used only as salvage therapy for recurrent tumors or liver decompensation after first-line therapies.

 

　　2.What are the pros and cons of each therapeutic program?

 

　　The advantages of radiofrequency ablation are the very low morbidity and mortality after the procedure and the low costs. If there is a single lesion <3cm, deep in the liver, then RFA is probably the best approach. The con of radiofrequency ablation is tumor size. If the tumor size is >3cm, the risk of local recurrence is very high. The advantage of liver resection is the higher oncological eradication rate compared to RFA. The problem is the limitations of liver dysfunction; we can apply liver resection only in patients with good liver compensation. The other disadvantage of liver resection is that we leave the rest of the liver intact so the risk of recurrence is very high compared to transplantation. Theoretically, the best solution for every patient with HCC is liver transplantation but the limitation of this procedure is the shortage of donors and the competition of patients with HCC with all the other patients without tumors but with end-stage liver disease for the available livers.

 

　　3.On last year's annual meeting of ILCA, Professor Jordi Bruix and Roony Poon（from Hong Kong）had a wonderful discussion on the topic of liver cancer staging criteria. On this assembly, South Korean scholars further demonstrate the feasibility of Hong Kong standards. How do you think the Hong Kong Standards and BCLC criteria?

 

　　Dr Vitale: I think the Hong Kong Liver Cancer Staging System is a great improvement in the staging classification for HCC patients. I consider this staging better than the BCLC classification because the algorithm proposed for treatment is more modern than the BCLC. But the limit of the Hong Kong liver staging and treatment algorithm, and also for the BCLC treatment algorithm, is in the algorithm itself. In my opinion, it is not possible to use the strict algorithm in HCC patients but to consider different options for each stage of disease so we don’t have just one therapeutic option for a certain stage, but different options. This is a limitation of both of these systems in my opinion.

 

　　4.According to current indications of TACE for HCC, what is the proportion of patients suitable to this regimen?

 

　　Dr Vitale: TACE is not my area of expertise but I think the indications and contraindications for TACE are the same for liver resection. For example, TACE has better results when the tumor is smaller and liver function is well-preserved. For that population of patients, TACE is extremely valuable and depends on the concept of resectability and what is considered a resectable tumor. This definition is important in modern surgical approachesto HCC and means the place for TACE is very small as a first-line therapy but more as a complementary therapy to surgery or other approaches.