分子靶向治疗在肝癌降期治疗中的运用

肝细胞肝癌的流行病学及治疗现状肝细胞肝癌(hepatocellular carcinoma,HCC,以下简称"肝癌")是我国常见的恶性肿瘤之一,在肿瘤相关死因中占第2位,仅次于肺癌。我国的肝癌病人大部分是由乙肝后肝硬化发展而来。虽然随着常规体检的逐步推广,早、中期肝癌的临床诊断率有明显提高,但大部分病人被发现时均已晚期阶段,这一现状仍无显著改变。晚期肝癌错失了根     

肝移植治疗肝癌

肝细胞肝癌是最常见的恶性肿瘤之一，全世界每年有近100万人死于该疾病，居肿瘤死亡原因的第三位。目前部分肝切除在许多肝病中心仍是首选治疗方法。但由于病人的肝功能不佳、肿瘤多发、部位特殊，往往限制了传统的肝切除治疗。肝移植的开展为这些病人提供了治愈的可能性，目前世界上愈来愈多的肝移植中心将肝癌作为肝移植的适应证之一。但就具体肝癌病人的选择上尚缺乏统一的标准，因此各中心报道的治疗效果存在很大差异。     

多模式治疗肝细胞肝癌的共识与争议

随着医疗技术的进步,肝细胞肝癌的治疗已经进入多学科、多模式共存阶段。针对肝癌的治疗方法有很多种,包括手术切除、肝移植、动脉化疗栓塞、消融、分子靶向药物治疗、放疗、化疗、免疫治疗等。应根据不同个体制定相应治疗方案,利用多学科优势,提高肝癌病人的整体疗效。目前,手术仍然是肝癌最好的根治性治疗手段,可手术切除病人应尽量争取手术治疗。综合治疗可作为手术治疗的重要补充,增加外科手术切除机会,减少术后复发转移,为晚期肝细胞肝癌病人提供良好的治疗机会,延长病人的生存期。     

肝移植治疗肝细胞肝癌六例

分析本院器官移植中心2001年3月至2003年10月期间6例原发性肝癌肝移植的临床资料,探讨原位肝移植在原发性肝癌治疗中的意义。临床资料与方法:原发性肝癌患者6例,均为男性,年龄31-63岁,全部合并乙型肝炎后肝硬化。TNM分期标准:术前T1N0M0 1例,Child C级,T3N0M0期1例,Child B级,T4 N0M04例,Child C级1例,B级3例,其中2例有门静脉癌栓形成,所有患者经腹部超声、CT、头颅CT、胸部CT及全身骨扫描等检查后证实,无远处转移。移植前行不规则肝切除术4 例;经肝动脉行栓塞化疗(TACE)2次者1例,5次者1例。6例患者均采取无静脉转流下经典原位肝移植术。供肝热缺血时间3-7 min,平均4.2mm,冷缺血时间3.5-11     

以手术治疗为主的肝癌个体化综合治疗

肝细胞癌是我国常见的消化道恶性肿瘤。经过多年努力,肝癌的临床治疗效果尽管有了长足的进步,但其总体效果依然不甚理想。目前,针对肝癌的治疗方法有很多种,包括手术切除、经导管动脉化疗栓塞（TACE）、消融治疗、分子靶向疗法、放疗、化疗、免疫治疗等。应根据不同个体制定相应治疗方案,利用多学科优势,从而提高肝癌的整体疗效。     

ChildA级单个直径≤5cm肝细胞肝癌行肝移植与肝切除的预后比较

目的比较ChildA级、单个、直径≤5cm肝细胞肝癌行肝移植与肝切除术的预后。方法回顾性分析笔者所在医院肝移植中心2007～2011年期间行肝切除术及肝移植术的ChildA级、单个、直径≤5cm肝细胞肝癌患者的临床资料,比较2组患者术后无瘤生存率及总体生存率。结果本研究共纳入263例患者,其中肝移植组36例,肝切除组227例。肝移植组与肝切除组患者术后1、3及5年无瘤生存率分别为91．7％、85．3％及81．0％和80．6％、59．8％及50．8％,肝移植组高于肝切除组（P=-0．003）;术后1、3及5年总体生存率分别为100％、87．5％及83．1％和96．9％、83．8％及76．1％,2组间差异无统计学意义伊=0．391）。以肿瘤直径〈3em为标准再予以分析,其肝移植组与肝切除组术后1、3及5年无瘤生存率分别为92．3％、92．3％及92．3％和80．2％、62．5％及50．5％,肝移植组高于肝切除组（P=-0．019）;术后1、3及5年总体生存率分别为100％、91．7％及91．7％和97．7％、87．5％及79．5％,2组间差异也无统计学意义（p0．470）。结论ChildA级、单个、直径≤5cm肝细胞肝癌患者肝切除术后复发率高于肝移植,但两种治疗方式的术后总体生存率相似。     

原发性肝癌肝移植治疗进展

近10年来，原发性肝癌（简称肝癌）的治疗选择发生了明显变化。和肝癌切除、消融治疗一样，肝移植同样提供了治愈肝癌的可能性，并且还可减少肝癌复发率，以及消除肝硬化带来的各种并发症。目前有关肝癌肝移植的争论主要集中在如何制定移植标准，是否肝穿刺活检，术前处理和肿瘤复发的治疗。本文拟对肝癌肝移植治疗的主要相关问题做一综述。     

原发性肝癌的治疗进展及展望

原发性肝癌是我国和某些亚非地区常见的恶性肿瘤之一 ,近年其发病率呈增高趋势。 2 0年来 ,随着医学物理学、影像学、麻醉学、免疫学、分子生物学的不断发展及外科技术的日益成熟 ,我国原发性肝癌的治疗取得了长足的进步 ,手术切除率、术后生存率及术后生活质量均有较大提高。尤其是进入 2 0世纪 90年代以后 ,以外科治疗为主的综合治疗理念已占主导地位 ,在分子生物学研究基础上发展迅速的生物治疗策略以及肝移植研究更令人关注。笔者对目前我国原发性肝癌的治疗作一概述。1　手术切除治疗手术切除是目前治疗肝癌的最有效方法[1] 。第二军医…     

肝癌的转化治疗策略

手术切除是实现肝癌根治获得长期生存的重要手段,我国大部分肝癌患者初诊时即为中晚期,丧失了手术机会。近年来,随着局部治疗的进步、靶向药物的研发、免疫治疗的成功及联合治疗的协同效应,转化治疗应运而生,其已成为中晚期肝癌治疗新焦点。部分不可切除肝癌患者经过转化治疗后肝脏功能改善、剩余肝脏体积增大、肿瘤负荷减少,为序贯根治性手...     

Surgical Treatment for Hepatocellular Carcinoma Detected After Successful Interferon Therapy

Purpose Interferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC. Methods Risk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response). Results According to a univariate analysis, large tumor (>2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (<5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery. Conclusion An anatomic resection with an appropriate surgical margin (≥5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.     

Referrals for Surgical Therapy in Patients with Hepatocellular Carcinoma: A Community Experience

The treatment of hepatocellular carcinoma (HCC) is notoriously difficult. Either because of oncogenic behavior or the frequent association of cirrhosis, successful therapy is elusive, particularly in cirrhotic patients. Surgical removal has been the only modality that has produced long-term, disease-free survival. In a large series of patients from specialty institutions, median survival in those who underwent resection of HCC lesions has ranged from 30 to 70 months. Similarly, liver transplantation has been shown to be an effective treatment when HCC is favorable (limited in size and number), producing long-term survival in greater than 70% of patients. However, less information is known about community-based treatment of HCC. Reports from referral centers may not accurately reflect the community experience. We have retrospectively reviewed patients with HCC seen in surgical referral from three teaching hospitals in a medium-size urban community from 1995 to 2004 who were not felt to be candidates for liver transplantation and who were not sent to referral centers. We sought to examine their suitability for operation and resection. The study group comprised 61 patients, whose ages ranged from 35 to 83 years old. There were 44 patients (72%) with cirrhosis (Childs A, B, and C in 27, 15, and 2 patients, respectively), 21 from hepatitic C virus (HCV) infection. Three recognized staging systems were used that incorporated the estimation of hepatic reserve and tumor burden. Seven patients (11%) were deemed nonoperable (five advanced disease by imaging, two comorbidities). Of the 54 patients who underwent surgical procedures, 32 underwent resection (28 patients) or cryoablation (4 patients). The reasons for unresectability were unrecognized multifocality (ten patients), poor risk for major hepatectomy (five patients), portal vein/hepatic vein involvement (three patients), metastatic disease (two patients), and excessive blood loss prior to hepatectomy (two patients). Eleven of 17 (65%) noncirrhotic patients and 21 of 44 (48%) cirrhotic patients were resectable or ablatable. There were ten postoperative deaths: six following resection, two following cryoablation, and two following exploratory celiotomy. All deaths were in cirrhotic patients (Childs A in four patients, B in five patients, and C in one patient), 10 of 44 patients (23%); 3 of 11 (27%) patients died following segmentectomy and 3 of 9 (33%) following major hepatectomy. Seven deaths that occurred were in patients with HCV; (P = NS). From this series, the difficulty in surgically treating cirrhotic patients in an urban practice is evident. From 39 to 73% of patients had advanced local disease. Less than half were resectable and, for cirrhotic patients, the postoperative mortality was high, even after “minor” hepatectomies. Noncirrhotic patients fared somewhat better. While HCC in community practice can be treated surgically in the majority of noncirrhotic patients, cirrhotic patients are less likely candidates, and surgical treatment is associated with significant postoperative mortality. This frequently reflected advanced disease and HCV but may be associated with access to preventative and surveillance measures. Only those with optimum hepatic reserve and small tumor burden should be considered for surgical resection. Presented at the 2006 Spring Meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, FL, March 9–12, 2006 (poster of distinction).     

Bridging Locoregional Therapy for Hepatocellular Carcinoma Prior to Liver Transplantation

Introduction  The impact of locoregional therapy prior to liver transplantation for hepatocellular carcinoma utilizing either transcatheter arterial chemoembolization (TACE), yttrium-90 (⁹⁰Y), radiofrequency ablation (RFA), or resection prior to orthotopic liver transplantation (OLT) is largely unknown. We sought to examine locoregional therapies and their effect on survival compared with transplantation alone. Methods  A retrospective review of a prospectively collected database. Results  123 patients were included. Patients were analyzed in two groups. Group I consisted of 50 patients that received therapy (20 TACE; 16 ⁹⁰Y; 13 RFA, 3 resections). Group II consisted of 73 patients transplanted without therapy. Median list time was 28 days (range 2–260 days ) in group I, and 24 days (range 1–380 days) in group II. Median time from therapy to OLT was 3.8 months (range 9 days to 68 months). Twelve patients (24%) were successfully downstaged (8 TACE, 2 ⁹⁰Y, 2 RFA/resection). Overall 1-, 3-, and 5-year survival were 81%, 74%, and 74%, respectively. Survival was not statistically significantly different between the two groups (P = 0.53). The 12 patients downstaged did not have a significant difference in survival as compared with the patients who received therapy but did not respond or the patients who were transplanted without therapy (P = 0.76). Conclusion  Our report addresses locoregional therapy for hepatocellular carcinoma as a bridge to transplant. There was no statistical difference in overall survival between patients treated and those not treated prior to transplant. We provide further evidence that locoregional therapy is a safe tool for patients on the transplant list, does not impact survival, and can downstage selected patients to allow life-saving liver transplantation.     

原发性肝癌肝移植围手术期辅助治疗

目的探讨原发性肝癌肝移植围手术期治疗的现状及研究进展。方法采用文献回顾的方法对原发性肝癌肝移植围手术期治疗的现状及研究进展进行综述。结果原发性肝癌肝移植围手术期治疗的方法包括：肝动脉栓塞化疗、全身化疗、放疗、瘤内无水乙醇注射以及射频毁损等。结论原发性肝癌肝移植围手术期辅助治疗不仅为肝移植患者赢得了手术时间，而且明显提高术后生存率。     

Repeat Liver Resection for Hepatocellular Carcinoma Complicating Primary Biliary Cirrhosis

The incidence of hepatocellular carcinoma (HCC) complicating primary biliary cirrhosis (PBC) is between 0.7% and 16%. Repeat liver resection for recurrent HCC complicating PBC is not usually performed and not published because this approach is not generally applicable due to liver dysfunction. We applied repeat liver resection for these diseases. Three patients were diagnosed with PBC. The first HCC was noted at a mean of 6 years (4–17 years) after diagnosis of PBC. The second HCC occurred at a mean of 2.5 years (0.4–3 years) after the first surgery. All patients were treated with curative resection on first and second surgery. The mean overall survival time after the first liver resection was 46 months. Repeat liver resection for recurrent HCC complicating PBC is an option and may improve the outcome.     

外侵性肝癌扩大切除术的术式探讨

目的：探讨外侵性肝癌扩大切除手术治疗的经验,以期提高手术成功率和患者的生存率。方法：回顾性分析１９９７年元月～１９９９年６月间施行扩大切除术的４１例外侵性肝癌的临床资料。结果：施行扩大切除术的４１例中除肝癌切除外,还包括联合切除：部分十二指肠１例,部分膈肌６例,右肾上腺２例,胆囊１８例,部分胃１例,右半结肠２例,脾脏２例。结论：严格掌握扩大切除术的指征,恰当地选择手术进路,同时注重病人的围手术期处理,是降低并发症、提高手术成功率及远期生存率的重要因素。     

Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.     

射频消融在肝细胞肝癌根治性治疗中的临床价值

目的探索射频消融术（RFA）在肝细胞肝癌（简称肝癌）根治性治疗中的临床应用价值。方法检索近年来有关RFA在肝癌治疗中应用的文献并进行综述。结果肝脏移植、肝切除术和RFA是目前被认为具有治愈性治疗效果的3种方法,其中RFA由于具有较好的局部肿瘤控制效果,近年来较多地用于肝脏移植术前的减瘤治疗,在延长患者的等待期的同时不增加病例脱落及死亡的危险。虽然RFA与肝脏切除术对小肝癌的疗效目前尚有争论,但是RFA联合肝脏切除术,扩大了肝癌患者的手术指征,提高了疗效。结论由于RFA技术良好的局部肿瘤控制能力和微创特点,使其在肝癌的各种治疗策略中发挥越来越重要的作用,并与肝移植及肝部分切除术的优点相互补充,使更多的肝癌患者受益。无论是哪一种治疗方法,术中最大程度地减少残癌的发生率,术后密切随访,复发后积极地治疗才是提高疗效的根本。     

人类基因治疗的背景与肝癌基因治疗的研究概况

目的 了解人类基因治疗的背景与肝癌基因治疗的研究概况。方法 采用文献复习的方法对人类基因治疗的临床研究历史与发展，以及肝癌基因治疗方面的一些基础研究进展进行综述和分析。结果 基因治疗作为人类某些遗传疾病的替代治疗方法在临床研究中已取得了较好,冲锋枪量在肿瘤的治疗研究中基本上不处于基础研究阶段。在胆癌的基因治疗研究中，所有的病毒载体如逆转录病毒、腺病毒以及腺病毒的相关病毒各有优缺点，逆转录病毒邕有提高滴度，应该更有前景；所有目的基因TK及p53基因等已在体外及动物实验中取得了较好的效果，但在治疗的特异性和安全性方面还存在较大的缺陷。结论 人类基因治疗的前景是乐观的，肝癌的基因治疗研究也取得了一定成果，但距临床应用还有一段距离。