经肝动脉化疗栓塞术治疗肝细胞癌合并门静脉癌栓的预后影响因素分析

目的评估肝细胞癌(HCC)合并门静脉癌栓患者经肝动脉化疗栓塞术(TACE)治疗后的效果及影响预后的因素。方法回顾性分析2006年1月-2010年12月第四军医大学西京医院收治的152例行TACE治疗的HCC合并门静脉癌栓患者的临床资料。观察TACE术后肝衰竭、上消化道大出血、栓塞后综合征等发生情况,分析生存期资料与影响预后的因素。Kaplan-Meier法计算累积生存率,采用Log-Rank法进行单因素分析,Cox比例风险模型进行多因素分析。结果患者中位生存时间为5.0(95%可信区间:4.4~5.6)个月,6、12、18个月的累积生存率分别为37%、18%和9%。单因素分析显示肿瘤大小、肿瘤类型、肝两叶累及、远处转移和Child-Pugh分级是HCC合并门静脉癌栓患者行TACE治疗预后的影响因素(χ2值分别为5.108、11.542、6.036、12.319、22.574,P值均0.05);多因素分析显示肿瘤大小、肿瘤类型、远处转移和Child-Pugh分级是影响患者预后的独立危险因素(Wald值分别为11.243、5.021、7.651、25.876,P值均0.05);而HCC合并门静脉癌栓患者发生肝衰竭的唯一影响因素是Child-Pugh分级(P=0.015)。结论在肝功能良好的HCC合并门静脉癌栓患者中,TACE是安全有效的。肿瘤大小、肿瘤类型、远处转移、Child-Pugh分级是影响患者生存的最主要因素,为临床医生选择合适的介入治疗患者提供了有力证据。     

肝细胞癌伴门静脉癌栓的降期治疗

肝细胞癌伴门静脉癌栓发生率高,病情进展快,现有治疗方法有限且效果不佳。虽然国外指南推荐索拉非尼为唯一治疗手段,但临床研究显示部分患者,尤其是伴癌栓侵犯至门静脉一级或二级分支的患者(程氏分型Ⅰ/Ⅱ型),通过手术切除可以取得比其他非手术疗法更好的效果。然而临床实践中相当一部分患者由于病灶范围较广无法根治性切除,或者由于癌栓侵犯到门静脉主干(程氏Ⅲ型),术后癌栓残留可能性高,需要通过降期切除的方法改善预后。研究发现通过新辅助三维适形放疗、经肝动脉钇-90微球放射性栓塞、肝动脉灌注化疗等姑息性治疗方法,部分患者(5.7%~26.5%)可出现门静脉癌栓消退乃至消失、肿瘤体积缩小、卫星灶消失等现象,从而使病灶降期,提高手术切除率并延长患者生存时间。多学科综合治疗对于进一步提高肝细胞癌伴门静脉癌栓患者的降期切除率至关重要。     

Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5–37 months; 1-year OS rate, 46.8–100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.     

Clinical significance of removal of tumor thrombi in the main portal vein in patients with hepatocellular carcinoma

Twenty-two patients with portal vein tumor thrombi secondary to hepatocellular carcinoma were studied to evaluate the effectiveness of diagnostic and treatment procedures. B-mode ultrasonography is a simple and accurate means for the detection of tumor thrombus in the portal vein. All of the 22 patients were correctly diagnosed by this method, which should be used as the initial screening procedure in such patients. Fourteen of the 22 patients underwent surgical procedures, including embolectomy from the portal trunk; removal of the tumor thrombi combined with hepatectomy or through the rechanneled umbilical vein; and operative transcatheter arterial chemotherapy. The other 8 patients were treated by transcatheter arterial embolization or were not treated. The surgical treatment effectively prevented acute variceal bleeding in the patients who underwent the procedures successfully. The mean value of the portal venous pressure was reduced from 46 cmH₂O to 32 cmH₂O after the surgery. As a result of the effective portal decompression, the patients in the surgical group had a better prognosis and longer mean survival than the others. Our study suggests that portal vein tumor thrombus is not an absolute contraindication for surgery, and that accurate detection and prompt treatment are the keys to the achievement of better clinical results.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement

AIM: The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT). METHODS: The combined therapy was performed in 24 HCC patients with extensive PVTT. External radiation targeted for PVTT (50 Gy in 2 Gy fractions) was performed in combination with repetitive TACE for intralobar lesions using 30-60 mg epirubicin every 3 months, and associations of the following variables with the survival rate were evaluated: gender, age, viral etiology, Child's class, performance status, extrahepatic metastasis, size and number of HCC, and location of PVTT. RESULTS: The local response confined to PVTT was complete response (CR) in four patients, partial response (PR) in eight patients, no change (NC) in eight patients, and progressive disease (PD) in four patients. By using the stepwise Cox's regression analysis, only Child's class was associated with the survival rate. The survival rates after 1 and 2 years were 73 and 21% in Child's A, 10 and 0% in Child B or C, and 61 and 21% in patients in whom the local response was CR or PR, and 19 and 9% in those in whom the local response was NC or PD, respectively. By using the multiple logistic regression analysis, Child's class was the only factor associated with the local response (P = 0.006). CONCLUSIONS: The combined therapy is feasible and may be useful to reverse PVTT in patients with good hepatic function reserve.     

经肝动脉化疗栓塞术联合微波消融成功治疗晚期大肝癌伴肝-门静脉癌栓1例报告

随着影像学技术的不断发展,以射频消融（radiofrequency ablation,RFA）和微波消融（microwave ablation,MWA）为代表的热消融治疗,是继外科治疗后,近20年来应用最为广泛的肝癌治疗方式,不但能够完成早期肝癌的根治,还能够针对中晚期肝癌进行姑息治疗^（[1]）。相对传统的外科治疗,局部热消融具有适应证广、创伤小、可多次治疗、治疗效果好等优点,     

原发性肝细胞癌伴门静脉癌栓患者接受立体定向放射治疗的疗效观察

目的评价原发性肝细胞癌伴门静脉癌栓患者接受立体定向放射治疗(射波刀)的疗效。方法收集我院2011年1月—2015年5月原发性肝细胞癌伴门静脉癌栓患者59例,均接受射波刀治疗。门静脉癌栓的大体肿瘤体积为24.6~1265.0 cm3,中位数399.0 cm3,单次分割剂量5~13 Gy/次(中位数10 Gy),照射次数4~8次(中位数6次),肿瘤剂量35~56 Gy(中位数49 Gy),每d或隔1~2 d照射1次。采用寿命表法进行生存分析,Cox回归模型分析生存相关的影响因素。结果 59例肝癌伴门静脉癌栓患者接受射波刀治疗,中位无疾病进展生存期为5.19个月,中位总生存期为11.84个月,疾病控制率为62.71%(37/59),治疗后1年、2年、3年的累积生存率分别为49.15%(29/59)、20.34%(12/59)、11.86%(7/59)。Cox回归分析显示:术前AFP水平、性别、年龄、病灶大小、肿瘤数目、肝功能Child-Pugh分级、腹水、癌栓类型及总剂量大小对患者生存期无明显影响。结论射波刀是肝癌伴门静脉癌栓患者较理想的治疗方法,可显著延长患者生存期。     

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.     

Hepatocellular carcinoma with portal vein tumor thrombosis: Improved treatment outcomes with external beam radiation therapy

The treatment of advanced hepatocellular carcinoma (HCC) associated with portal vein tumor thrombosis (PVTT) is very challenging because of HCC's grave prognosis. Despite many efforts to improve the treatment results, patient survival has been limited to several months. In this situation, radiotherapy has been considered as an alternative treatment modality because of the growth of knowledge about the radiotolerance of normal tissue and the advances of radiotherapy techniques such as three dimensional conformal radiotherapy, intensity modulated radiotherapy, stereotactic body radiotherapy and proton therapy. More restoration of the liver function and longer survival of the patients can be achieved by the better response after radiotherapy. However, considering the high risk of intrahepatic advanced tumor or extrahepatic dissemination by PVTT at disease presentation, a combination of radiation therapy and systemic agents will be desirable. Therefore, performing prospective randomized clinical trials is important to assess the benefits of radiotherapy and to develop combination treatment strategies.     

原发性肝癌合并门静脉癌栓的外科治疗

肝癌是常见恶性肿瘤之一，其发病率和病死率居我国恶性肿瘤第二位。门静脉侵犯是肝癌重要的生物学特性。肝癌倾向于侵袭门静脉，并继而形成癌栓。临床报道肝癌门静脉癌栓（PVTT）发生率为44．0％～62．2％。肝癌侵袭门静脉是肝内播散及根治性切除术后早期复发的根源。此外，癌栓阻塞门静脉，门静脉高压加剧，继而引发食道胃底静脉破裂出血，甚至导致肝功能衰竭。因此，肝癌合并PVTT患者总体预后差，中位生存时间仅2．7个月。     

Transcatheter arterial embolization for hepatocellular carcinoma with portal vein thrombosis

Abstract In order to evaluate the possible benefits of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients with peripheral portal vein thrombosis, 96 consecutive HCC cases with peripheral portal vein thrombosis were analysed. Of them, 35 cases received TAE and 61 cases did not. Most (77.8%) of the TAE-treated cases showed decreased α-fetoprotein (AFP) levels after treatment, but 57.1% of them suffered another rise in AFP levels and subsequently died. One patient (2.8%) developed progressive jaundice after TAE and died within 1 month, while four of the non-TAE cases died within 1 month after diagnosis. In general, TAE is safe for HCC patients with peripheral portal vein thrombosis. In addition, using Cox's regression model for multivariate survival analysis, serum total bilirubin (≤, > 2 mg/dL; P = 0.0254), AFP (≤ 3155 ng/mL, > 3155 ng/mL; P = 0.0002) and treatments (TAE, non-TAE; P = 0.0059) were found to affect their prognosis. There was significant difference in survival between TAE and non-TAE groups, the 6 month, 1 year and 2 year survival rates were 91.4 versus 62.3%, 51.4 versus 26.2% and 17.1 versus 4.9% ( P = 0.0017). The median survival times of TAE and non-TAE groups were 10.3 versus 3.7 months, respectively. Though TAE only provided palliative treatment, it did prolong survival in HCC patients with peripheral portal vein thrombosis.     

肝细胞癌门静脉癌栓相关血清小分子量蛋白质标志物的筛选

目的筛选肝细胞癌门静脉癌栓相关的血清小分子量蛋白质标志物。方法收集健康志愿者、肝细胞癌无癌栓患者和肝细胞癌门静脉癌栓患者3组血清各l2份，用16％SDS-PAGE进行双向电泳，得到3组血清小分子量蛋白质表达图谱；经Image Master软件比对分析后，用基质辅助激光解析飞行时间质谱对差异点进行鉴定。结果在16％SDS-PAGE凝胶中，3×10^3～20×10^3区域内蛋白质条带间距较12．5％SDS-PAGE明显增宽，条带数目明显增多，且3组血清小分子量蛋白质表达图谱中均可清晰显示〈20×10^3的小分子量蛋白质斑点。组间比较显示，3组血清共有15个小分子量差异蛋白质点，经鉴定为5种蛋白质。与健康组比较，无癌栓组中载脂蛋白A-I、脂蛋白CⅢ、转甲状腺素蛋白和DNA拓扑异构酶Ⅱ表达降低，而结合珠蛋白-2表达增高；门静脉癌栓组5种蛋白质表达均较无癌栓组降低。结论在肝细胞癌的发生和发展过程中，血清小分子量蛋白质表达谱发生明显变化，差异表达的小分子量蛋白质有可能为肝细胞癌和门静脉癌栓早期预测及治疗监测提供参考。