重视中晚期肝癌的降期转化治疗

外科手术治疗是肝癌获得根治和长期生存的最有效途径。目前,大部分中晚期肝癌患者不能获得根治性手术治疗。临床实践中需高度关注并深入探讨中晚期肝癌的降期转化治疗策略,进一步提高疗效。根据中晚期肝癌患者的不同分期和具体病情,多学科团队协作,优化降期转化治疗方案,有望使不能手术切除的患者获得手术治疗,姑息性治疗转化为根治性手术切除,不能抗肿瘤治疗的患者可接受姑息性治疗,更多的中晚期肝癌患者疗效提高,预后改善,长期生存。     

原发性肝癌转化治疗研究进展

根治性肝切除及肝移植术是改善原发性肝癌远期预后的最佳选择,然而我国大部分肝癌患者确诊时已丧失手术治疗机会。因此,转化治疗成为提高中晚期肝癌患者生存率的研究热点。简述了肝癌转化治疗的评估内容,并归纳了目前不可切除性肝癌的转化治疗方案。随着对原发性肝癌及个体化治疗的进一步了解,精准医疗联合多学科诊疗团队制定出个体化的转化治疗方案,认为能够有效提高中晚期肝癌患者手术切除率及治疗效果,改善远期预后。     

根治性肝切除联合索拉非尼治疗肝细胞癌的研究进展

根治性肝切除仍然是肝细胞癌(hepatocellularcarcinoma,HCC)的主要治疗手段,但术后转移复发导致肝切除的疗效进入瓶颈期.探索术后复发的治疗措施是有效延长患者生存时间的重要课题.目前,以经皮肝动脉化疗栓塞为代表的多种治疗措施已在临床广泛开展,但尚缺乏大规模、多中心随机对照临床试验的循证医学证据.分子靶向药物索拉非尼的出现为改善HCC预后开辟了新局面,对于已接受过根治性肝切除治疗的HCC患者,索拉非尼可能是一种有效的辅助治疗方法,值得深入探索.     

肝细胞癌的非手术治疗

肝细胞癌（HCC）是原发性肝癌的最主要类型。肝切除术可根治 HCC,使患者长期生存,但肝切除术受到一定的限制,主要在于：（1）肿瘤细胞恶性程度高、病情进展快,极易发生播散和转移;（2）HCC 患者多存在严重的肝硬化基础,因为肝功能失代偿而无法手术;（3）大部分肿瘤为多中心发生,很难切除完全。因此,切除率低和复发率高乃是制约手术治疗 HCC 患者的主要障碍。联合应用手术治疗与各种非手术治疗,多种方案的优化组合将成为综合治疗 HCC 患者的优先选择,提高疗效[1,2]。目前,常用的非手术治疗方法主要有肝动脉化疗栓塞（TACE）、局部消融、放射治疗、系统化疗和分子靶向治疗等。     

多模式治疗伴门静脉癌栓的进展期肝细胞癌

日本大阪大学医学院Morito Monden等认为，HCC的预后一般很差，即使是根治性切除后5年的生存率局限在25％～58％。虽然已经发展了各种治疗方法，但治疗后复发率非常高，许多患者病情进展到晚期伴血管侵犯和肝内多发转移。合并有门静脉主要分支癌栓（Vp3）的患者预后极差。几乎所有不能手术切除的患者，生活质量较差，多在几个月内死亡。即使是能够冒险手术切除，预后也很差。况且，常规的治疗方法不适合这些患者。尝试动脉灌注化疗，但效果不能令人满意。所以对这些难治性HCC伴门静脉癌栓的患者需要新的治疗策略。     

肝细胞癌综合治疗的现状和前景

肝细胞癌(HCC)在全世界有很高的发病率和病死率,因为HCC发生发展的复杂性,到目前为止,HCC的管理策略尚未完全统一。特别近十年来,HCC的治疗方案已发展为以外科手术为主的多学科综合治疗。除了肝切除和肝移植以外,消融治疗是另外一种根治性治疗方法,目前针对肿瘤直径3 cm且不能接受肝移植的肝癌患者,可作为一线治疗方案;肝动脉化疗栓塞术是针对不适合根治性治疗的中晚期肝癌的首选治疗方法,可联合消融治疗和化疗,显示出良好的疗效;对于诊断为晚期HCC或在其他治疗失败后进展到晚期HCC患者可以选择分子靶向治疗;细胞免疫治疗是HCC新型治疗方法,可以为进展性HCC患者带来有效的缓解率和生存获益。充分解析HCC各种治疗方法特点,制订个体化治疗方案,合理综合治疗HCC,以提高HCC整体疗效。     

肝细胞癌治疗策略的循证学方法

美国纽约西奈山医学院Josep M．uovet教授在报告中总结了HCC治疗有效的证据。早期发现的HCC患者可以接受根治性治疗方法如肝切除术、肝移植和经皮消融术。在高度选择的患者中，肝切除术和肝移植效果最好（5年生存率为60％～70％），从意向治疗和前瞻性角度，认为其是首选方法。如果不能手术，可以选择局部、非手术治疗。     

肝多房棘球蚴病的综合治疗现状和进展

多房棘球蚴病是一种危害严重的人兽共患寄生虫病。根治性手术切除是目前治疗肝多房棘球蚴病的首选方法,难以根治性切除的晚期肝多房棘球蚴病可行包括姑息性手术联合药物治疗、肝脏移植、单纯药物治疗、射频微波消融术等治疗手段。本文就肝多房棘球蚴病综合治疗现状和进展进行综述。     

肝多房棘球蚴病的综合治疗现状和进展

多房棘球蚴病是一种危害严重的人兽共患寄生虫病。根治性手术切除是目前治疗肝多房棘球蚴病的首选方法，难以根治性切除的晚期肝多房棘球蚴病可行包括姑息性手术联合药物治疗、肝脏移植、单纯药物治疗、射频微波消融术等治疗手段。本文就肝多房棘球蚴病综合治疗现状和进展进行综述。     

巴塞罗那C期巨大肝癌成功转化治疗后行根治性切除一例

背景原发性肝癌(hepatocellular carcinoma,HCC)患者初诊时大都已进展为中晚期,失去最佳手术时机,而且术后复发率高,预后差.随着近年来全身治疗的发展,对于初诊不可切除的患者先行转化治疗可改变围手术期患者的诊疗方式.本文报道1例初诊时累及门静脉右支的巨大肝癌经过术前转化治疗后行根治性右半肝切除术.病例简介本例患者以“间断性右上腹隐痛2月余”之主诉于入院.初诊时考虑原发性肝癌进展为巴塞罗那临床肝癌(Barcelona Clinic Liver Cancer,BCLC)C期(BCLC-C),既往合并乙肝及肝硬化病史,未接受系统抗病毒治疗,肿瘤为巨块型(肿瘤直径超过10 cm),门静脉右支闭塞,左支癌栓形成,已失去手术机会,单一治疗效果有限.结论对于中晚期肝癌患者,转化治疗将给他们带来根治希望.尤其是初始不可切除的患者,系统治疗将逐步在肝癌的治疗体系中起到更为重要的作用.     

Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement

Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.     

门静脉免疫化疗对原发性肝癌切除术后患者预后的影响

目的观察门静脉免疫化疗对原发性肝癌切除后患者预后的影响。方法收集湖北医药学院附属太和医院2010年1月-2013年6月住院的48例手术切除并行术后门静脉免疫化疗患者,对其临床资料进行回顾性分析,并与同期未行门静脉免疫化疗的59例患者进行对比。计量资料的分析采用两样本资料的t检验,率的检验采用卡方检验。生存分析采用Kaplan-Meirer法计算平均生存时间,采用log-rank检验分析不同组之间的差异性。将107例患者合并,采用Cox回归模型分析对可能影响预后的因素进行多因素分析。结果免疫化疗组和对照组的1、2、3年的无瘤生存率分别为87.5%(42/48)和67.8%(40/59)(χ2=5.739,P=0.017)、52.1%(25/48)和32.2%(19/59)(χ2=4.320,P=0.038)、16.7%(8/48)和10.2%(6/59)(χ2=0.982,P=0.322),平均生存时间分别为(32.4±2.3)个月和(24.7±2.3)个月(χ2=4.044,P=0.044)。合并门静脉癌栓者术后行门静脉免疫化疗其平均生存时间(12.4±1.3)个月,而未行门静脉免疫化疗者为(4.8±0.4)个月(χ2=15.535,P0.001)。经Cox回归分析显示,肿瘤的分化程度、肿瘤的大小、肝功能分级、是否存在门静脉癌栓是影响肝细胞切除术后复发的独立危险因素,而是否采用门静脉免疫化疗对影响肝癌术后的复发时间有重要影响,具有统计学意义(P0.001)。结论门静脉免疫化疗可改善原发性肝癌切除后的无瘤生存率和生存时间。     

Hepatectomy for hepatocellular carcinoma in the era of liver transplantation

The aim of management of hepatocellular carcinoma (HCC) is to improve the prognosis of the patients by radical resection and preserve remnant liver function. Although liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications. Therefore, hepatectomy could be the first choice of treatment in selected patients with HCC. However, the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis. New strategies are required to improve the long-term outcome of HCC after hepatectomy. In this paper, we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence. Some aggressive treatments for tumor recurrence to extend long-term survival are also involved. We believe that hepatectomy combined with other therapies, such as portal vein embolization, transarterial chemoembolization, radioembolization, antiviral treatment, radiofrequency ablation and salvage transplantation, is a promising treatment modality for HCC and may improve survival greatly.     

Surgical treatment of hepatocellular carcinoma

Surgery for hepatocellular carcinoma (HCC) includes partial liver resection (LR) and liver transplantation (LT). Although LT represents the most efficient treatment in patients with small HCC, <30% of patients are eligible for LT because of restrictive criteria (one nodule <5 cm or two to three nodules <3 cm without macroscopic vascular invasion), graft unavailability and the high cost of the procedure. For large HCC, LR remains the only potential curative treatment. LR is now safer, with a low rate of mortality. Selective preoperative morphological assessment, preoperative use of portal vein embolization for increasing future remnant liver volume and the improvement of surgical techniques such as the use of intermittent clamping and anterior approach are factors that improve the safety and tolerance of LR. In patients with small HCCs and a preserved liver function (Child-Pugh grade A), good long-term survival can be achieved after anatomical resection that removes the tumor(s) and its portal vein territory. These good results of LR for small HCC and the increasing duration of the waiting list for candidates of LT have renewed the place of LR as a bridge treatment before LT.     

肝包虫病合并门静脉海绵样变性的研究进展

肝包虫病灶压迫侵犯门静脉可引起门静脉海绵样变性(CTPV),其手术难度大,风险高,常规肝切除不能有效根治。简述了肝包虫病合并CTPV的病因、分型、临床表现、辅助检查,总结了其治疗策略。认为肝包虫病合并CTPV的治疗应在包虫病灶切除的基础上有效缓解门静脉高压,血管重建、离体肝切除和自体肝移植的应用在根治性切除方面发挥了重要作用。     

肝癌肝移植

肝移植和肝切除是目前肝癌的2种主要治疗方法。早期肝癌合并晚期肝病患者肝移植后疗效评估最佳;但是对于肝功能代偿尚可、不伴门静脉高压的早期肝癌患者来说,最佳的治疗方案仍存在争议。大量的研究证明肝移植后无病生存率更高,但是尚不清楚长期生存率如何。通过改进手术技术和实行补救性肝移植的方法可明显改善肝切除后患者生存率,且避免了可因切除治愈的患者因等待移植时间过长而失去机会。     

Effective treatment strategies other than sorafenib for the patients with advanced hepatocellular carcinoma invading portal vein

Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization(TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent metaanalysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization(TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resectionbased multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.     

Treatment of portal vein tumor thrombus using ¹²5Iodine seed implantation brachytherapy

We reported two cases of liver metastasis with portal vein tumor thrombus that developed after liver transplantation for hepatocellular carcinoma (HCC). Both the patients were women aged 43 and 55 years, who had liver metastasis and portal vein tumor thrombus formation after liver transplantations for HCC. For the treatment of portal vein tumor thrombus, (125)I seeds were implanted into the hepatic tissue under the guidance of preoperative computed tomography (CT) images with a total radiation dose of 130 Gy. Enhanced spiral CT scan was performed for evaluation of the liver at 12 and 16 wk after treatment. Thereafter, upper abdominal CT examination was performed every 2-3 mo. No severe complications associated with the (125)I seeds were seen in these two patients. The upper abdominal CT images (obtained after 3 and 4 mo of treatment) showed that the thrombosis reactions were complete reaction and restoration of the patency of the partially obstructed portal vein with partial obstruction. In the case with complete obstruction of the portal vein, the thrombosis was resolved completely, but blood flow could not be restored. After this treatment, one of the patients is still alive, while the other died within 6 mo after the treatment due to lung metastasis complicated with lung infection, leading to respiratory failure.     

Strategies to increase the resectability of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is best treated by liver transplantation, but the applicability of transplantation is greatly limited. Tumor resection in partial hepatectomy is hence resorted to. However, in most parts of the world, only 20%-30% of HCCs are resectable. The main reason for such a low resectability is a future liver remnant too small to be sufficient for the patient. To allow more HCC patients to undergo curative hepatectomy, a variety of ways have been developed to increase the resectability of HCC, mainly ways to increase the future liver remnants in patients through hypertrophy. They include portal vein embolization, sequential transarterial chemoembolization and portal vein embolization, staged hepatectomy, two-staged hepatectomy with portal vein ligation, and Associating Liver Partition and Portal Vein Ligation in Staged Hepatectomy. Herein we review, describe and evaluate these different ways, ways that can be life-saving.