肝细胞癌治疗的新发展
New progress of hepatocellular carcinoma treatment
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摘要: 我国是肝癌大国,肝癌病例数多,医师治疗肝癌经验多,同时国家投入了大量资源进行相关研究,因此,我国肝癌诊断与治疗水平在很多方面都已走到世界前沿。肝癌治疗方式主要分为3大类:(1)局部治疗,包括肝切除、消融治疗和肝移植。肝部分切除手术已非常成熟。最新研究结果显示:对于肝癌合并微血管侵犯的患者,解剖性肝切除长远生存比非解剖性肝切除好;而对于无微血管侵犯的肝癌患者,两者的长期生存率比较,差异无统计学意义。我国已发表多个预测模型,使用术前检查数据,可预测肝癌患者在肝切除术后的标本中是否合并微血管侵犯,因此,外科医师可在术前决定是否为患者行解剖性肝切除术。此外,国内大量研究结果显示:腹腔镜肝切除术或机器人肝切除术比开腹肝切除术的手术创伤小、恢复快。也有研究者建立和验证了有效预测肝癌患者术后复发的风险模型。对于风险高的患者,可进行术后辅助治疗的研究,希望能找出降低肝癌术后复发的治疗方案。有大量研究结果显示:肿瘤长径<2 cm的单发小肝癌,局部消融可达到肝切除的长远生存效果;而较大的单发肝癌(肿瘤长径为3~5 cm),应合并经导管动脉化疗栓塞术(TACE)或局部无水酒精注射;如肿瘤长径>5 cm时,手术切除的远期生存效果较好。肝移植近年在我国发展得很好,不但发表了超越米兰标准的不同适应证,还探索了不同研究方向以期改善肝癌患者肝移植后的生存结果。(2)区域性治疗:TACE在我国发展得也很好,通过高选择性TACE的治疗,不但治疗反应更好,不良反应相应减少。钇90微球是刚引进我国的治疗方法,主要适用于不适合TACE治疗的患者或 TACE治疗失败的患者,用以延长患者等候肝移植的时间和作为肝癌降期治疗的手段。钇90微球治疗肝癌的再发展为放射性半肝、肝区、肝段的放射性肝切除术,以及消融性经肝动脉内放射栓塞。这两个新发展是通过高选择性把导管插入供应肝癌的肝动脉分支,注入大剂量的钇90微球,达到整个肝癌受充分辐射而发生坏死的目的,最终使患者获得治愈的机会。(3) 全身性治疗:这是近年发展最快的治疗肝癌领域。采用化疗、靶向或免疫治疗进行单独或联合使用,能控制肝癌发展。目前还要解决的问题是,在肝癌多个基因突变下,经治疗阻断一条信号通路的传递后,如何能阻止肝癌从另一条信号通路进行传递,从而继续控制肝癌的发展。笔者认为:目前肝癌治疗长远生存结果已快速得以改善,希望通过医学研究者的不懈努力,将肝癌这一顽疾变成一种可完全治愈的疾病。Abstract: Hepatocellular carcinoma (HCC) is common in China. With the large number of HCC patients, experienced clinicians in managing this disease and the huge amounts of resources by the government to put into researches on HCC, the treatment of HCC in China has reached to the forefront of international standards in many aspects. The treatment of HCC can roughly be divided into three levels: (1) local treatment which includes liver resection, local ablative therapy and liver transplantation. The technical aspect of liver resection has become very matured. A recent study indicated that in HCC patients with microvascular invasion (MVI), anatomic liver resection resulted in significantly better long-term survival than non-anatomic liver resection. However, no significant difference could be found in HCC patients without MVI. As there are now models using preoperative data to predict presence or absence of MVI after surgery, surgeons can now decide on whether to use anatomic resection for a particular patient before surgery. Furthermore, medical evidences are accumulating on the effective and safe use of laparoscopic and robotic liver resection for selected HCC patients, which has less trauma and faster recovery compared with open hepatectomy. As the ability in predicting HCC recurrence improves, HCC patients predicted to have high risks of developing HCC recurrence can now be put into studies to investigate the treatment strategy for reducing recurrence after R0 liver resection. There are now a lot of high level evidence studies on the use of local ablative therapy in treating HCC. Size of lesion is an important factor in choosing radiofrequency ablation (RFA) treatment alone (for diameter of HCC <2 cm), or RFA combined with transcatheter arterial chemoembolization (TACE) or percutaneous ethanol injection (for diameter of HCC with 3 to 5 cm), or to use surgery instead of RFA (for diameter of HCC >5 cm). Liver transplanta-tion has progressed rapidly in China. To supplement the Milan criteria, other criteria have been reported in China to select suitable candidates for liver transplantation beyond the Milan criteria. Furthermore, a lot of basic and clinical researches have been carried out attempting to improve the clinical outcomes of liver transplantation. (2) Regional therapies. The recent developments in TACE has focused on the use of increasingly highly selective canalization of branches of the hepatic artery to achieve bitter treatment outcomes and to decrease adverse treatment effects. Resin yttrium 90 microsphere has just been approved for clinical use in China. The indications of yttrium 90 microspheres are treatment for patients who are unsuitable to undergo TACE, failure of TACE, bridging therapy for HCC patients waiting for liver transplantation, and tumor downstaging followed by salvage liver resection. Recent developments in yttrium 90 microsphere therapies include radiation hepatectomy and ablative transarterial radioembolization. These two procedures can offer a chance of cure to patients who cannot undergo curative treatment because of poor general status, compromised liver function and unfavorable locations of HCC. (3) Systemic therapy. This is a rapidly advancing field in HCC management, which includes the use of chemotherapy, targeted therapy and immunotherapy. These therapies when used either alone, or in combination, have improved the long-term survival outcomes of patients with intermediate or late stages of HCC. A major hurdle to overcome for systemic therapy is related to the multiple gene mutations in HCC, which even with successful blockade of a tumor signal pathway, can lead to an alternate signal pathway being opened for tumor progression. In conclusions, management of HCC has rapidly improved through the enormous efforts put in by researchers in China and all around the world. It is my sincere hope that in the near future, HCC will become a very healable disease through tireless efforts of researchers.