编者按：近年来系统治疗在进展期肝细胞癌（HCC）的突破，使HCC治疗格局发生了改变。手术联合系统治疗探索也随之进入到充满希望的新阶段。第33届亚太肝脏研究学会年会（APASL 2024）上，日本东京国立全球健康与医学中心主席、东京大学医学部附属医院肝胆胰外科Norihiro Kokudo教授应邀发表了题为“肝切除在HCC进展期系统治疗时代的角色”的报告，并于会后就我们关注的相关热点话题进行深度专访。

 

《国际肝病》

首先请您介绍下手术联合系统治疗方向在近年来取得的重磅进展。

 

Norihiro Kokudo教授：日本目前有多种针对HCC的治疗方案可供选择。我们确实遇到过一些病例，在病灶大幅缩小或血管性丧失后，治疗效果显著。十多年前，我们就成功地采用化疗策略，实现了对肝转移灶的有效治疗，这种策略也可能适用于肝细胞癌。因此，我们一直在努力开展前瞻性研究，旨在验证在日本，仅使用免疫检查点抑制剂进行系统治疗的效果。

 

<Hepatology Digest>: Could you introduce the significant progress made in the direction of surgery combined with systemic therapy in recent years?

 

Dr. Norihiro Kokudo: For Japan, we have seven regiments available for episode carcinoma now. And we have it is not very rare where we experience a very effective cases after too much shrinkage or lose loss of vascularity. So probably in ten years ago, more than 10 years ago, we experience a successful who strategy of conversion by the use of chemotherapy for collateral labor Mets. And this strategy may be applied for the SEC as well. So, we have been trying to do a prospective study to test the use of system therapy merely on the immune checkpoint inhibitors in Japan.

 

《国际肝病》

据悉，日本肝癌协会（JLCA）和日本肝细胞癌外科学会（JSHPBS）就“所谓的临界可切除肝癌”相关问题编写了共识。请您为中国读者介绍下这一新术语的定义、分类、适用范围，并谈谈该定义确定的主要依据，或者背后考虑？

 

Norihiro Kokudo教授：随着手术联合全身治疗的突破进展，HCC转化治疗也进入了新的探索阶段。日本肝癌协会和日本肝细胞癌外科学会针对“临界可切除肝癌”这一问题编写了2023年日本HCC共识声明，旨在为HCC的手术治疗提供更清晰、更科学的指导。在共识中，针对可切除性肿瘤学标准制定了3个明确的类别：R、BR 1和BR 2。

 

R类别：代表可切除的肿瘤状态，包括单发病灶或多发病灶（但每个病灶不超过3个结节且每个结节≤3厘米），且未检测到影像学上的大血管侵犯和肝外疾病。对于此类情况，手术相比其他治疗方式可能带来更好的生存效果，因此我们推荐直接进行手术，无需额外系统治疗。

 

BR 1类别：属于临界可切除状态，其标准稍微宽松，包括多发病灶（超过R的标准但不超过5个结节且直径不超过5厘米），或存在大血管侵犯，或局部肝外疾病。对于这类情况，手术作为多学科治疗的一部分可能带来生存益处，因此在手术前可能会考虑采用BR 1的系统疗法。

 

BR 2类别：这是最初不适合切除的临界可切除状态，涉及多发病灶超过5个结节或直径超过5厘米，或主要血管侵犯，或不符合BR 1分类的局部肝外疾病。对于此类复杂的病例，手术的疗效尚不确定，因此需要在标准的多学科管理下仔细评估手术指征。这可能意味着，我们需要集合各学科的专家意见，决定是否在可能的系统治疗后进行肝脏手术。

 

这一共识的确定主要基于对国家数据的深入研究，以及专家小组会议和问卷调查的结果。日本肝癌协会有着悠久的历史和丰富的患者数据资源，这为明确患者选择标准和治疗效果提供了有力支持。

 

<Hepatology Digest>: It is reported that Japan Liver Cancer Association (JLCA) and the Japanese Society of HPB Surgery (JSHPBS) have compiled a consensus on issues related to "so-called borderline resectable HCC". Please introduce the definition, classification and scope of application of this new term for Chinese readers.

 

Dr. Norihiro Kokudo: We created a working group of the two societies, Japan, liver Cancer Society, and the Japanese society of hpp surgery. And we very recently we reached a consensus. We defined three categories, r and bl one and bl two. For the r regard category, a surgery may offer better suburb outcome for compared to other treatments. That means we recommend upfront surgery, whether any systemic therapy and we are one category is a surgical intervention as a part of multidisciplinary treatment may offer survivor benefit.

 

So probably, we may think about the near as one therapy system therapy before surgery and br two is a very difficult case. For this category. Efficacy of surgery is indeterminate. So surgical indications should be carefully determined under the standard multi disparity management of that means we may need a consensus among the all disciplines to undergo liver surgery, probably after the systemic therapy.

 

<Hepatology Digest>: In addition, could you please talk about the main basis for determining this definition or the consideration behind it?

 

Dr. Norihiro Kokudo: First, we explore the national data. We have a long history of Japan liver cancer association and the patient registry started more than 50 years ago. And we analyzed and that means the our particle, our selection, patient selection, in daily practice, and also the outcome of the patient. And then we did a question survey on the receptivity. And then we gathered expert panel meeting. We took three steps.

 

《国际肝病》

中国肝癌患者数量巨大，且初诊中晚期肝癌患者占比大（70%～80%），迫切需要提高外科治疗带来的临床获益，因此较早开始了潜在可切除人群的转化治疗探索。能否请您谈谈既往与中国专家学者就手术联合系统治疗领域的合作或交流，以及未来期待？

 

Norihiro Kokudo教授：在东京大学任教期间，我有幸与众多中国医生建立了长期的合作关系。这些年来，我接待了超过一百位中国医生前来交流，我们分享经验、探讨学术，建立了深厚的友谊。关于肝癌肝切除手术的使用前景，我相信我们双方可能有着相似的见解，但由于HCC的病因和对HCC的认知理念存在差异，实际处理方式可能有所不同。

 

在中国，HCC与乙型肝炎病毒（HBV）感染的关系极为密切，大约90%的肝细胞癌病例与HBV有关。而在日本，这一比例则相对较低，HBV感染者只占大约15%。过去，日本的HCC多与丙型肝炎病毒（HCV）相关，但近年来这一比例也在逐渐下降。现在，日本超过一半的HCC病例既不是由HBV也不是由HCV引起的，它们更多地与代谢相关脂肪性肝炎（MASH）或其他病因相关。

 

这种病因上的差异可能导致中日两国医生在处理HCC时采取不同，甚至是截然不同的方法。但正是这种差异，为我们的合作与交流提供了广阔的空间。通过分享彼此的经验和研究成果，我们可以更全面地了解HCC的多样性和复杂性，为患者提供更加精准和有效的治疗方案。

 

<Hepatology Digest>: There is a large number of patients with liver cancer in China, and the proportion of patients with middle and advanced stage HCC in initial diagnosis is high (70%-80%). There is an urgent need to improve the clinical benefits brought by surgical treatment, so the exploration of conversion therapy for the potentially resectable population has been started earlier. Could you talk about your previous cooperation or exchanges with Chinese experts and scholars in the field of surgery combined with systemic therapy and your expectations for the future?

 

Dr. Norihiro Kokudo: I have a long history of collaboration with Chinese doctors. When I was in universe of Tokyo, II welcome more than five one hundred Chinese doctors at my department and we had the exchange of our experience and our where to go our thoughts or and I think we probably we may have a similar prospects of the use of liver resection for liver cancer, hcc but the major difference may be the ideology of the SEC because I know that probably 90 % of hcc in China is hbv related.

 

But in Japan, probably hpb is the minority only around 15 %. And majority used to be ahcv related one. But now the number is declining, and probably more than half of the cases in respected ACC now is non b non c so most of them are related to mash I Nash cases or other ideology. This may be a slightly different approach, may read a different approach for Japanese and Chinese doctors.

 

《国际肝病》

聚焦本届大会收录的摘要，您认为手术联合系统治疗方向有哪些非常值得关注的研究，能否请您作简要点评？

 

Norihiro Kokudo教授：本次大会入选的摘要显示，手术联合系统治疗方向的研究呈现出多样化和深入化的趋势。然而，目前仍缺乏针对患者选择的有效生物标志物，这使得治疗方案的选择仍存在一定的盲目性。因此，未来研究应更加注重患者个体差异和生物标志物的探索，以提高治疗的针对性和有效性，这是一项艰巨而充满挑战的任务。

 

此外，鉴于每位晚期肝癌患者的病情都独具特性，为了获得更加准确和可靠的研究结果，我们可能需要更多的患者样本量。在这方面，中国拥有庞大的患者群体，具备开展深入且重要的前瞻性临床试验的优越条件。我们期望中国能够充分利用这一优势，积极推动HCC治疗领域的研究进展，为全球的肝癌患者带来更好的治疗选择和生存希望。

 

<Hepatology Digest>: Focusing on the abstracts included in this congress, what research in the direction of surgery combined with systemic therapy do you think is worthy of attention? Could you make a brief comment?

 

Dr. Norihiro Kokudo: What is lacking is a patient selection. We have been studying more than ten ten or 15 years on the system with therapy. But still we don't have BIO markers for the patient selection for each regiments. So we may need this. It would be very difficult, II know. And also we may need more patient volume, because most of the patients with a advantages is very unique in for each patient. So we need more patients, so probably the China. You have a man, many largest number of the anticipation. So you can do a very vertical, very important clinical trial prospectively.

 

（来源：《国际肝病》编辑部）

 

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