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。     

肝细胞癌合并门静脉癌栓治疗现状与展望

门静脉癌栓是进展期肝细胞癌的常见并发症之一,严重影响肝癌患者的治疗和预后生存。近年来,随着外科手术方式、局部介入治疗、放射治疗、靶向药物治疗以及免疫治疗等学科的发展和进步,合并门静脉癌栓的进展期肝癌不再是临床治疗禁区,无论采取单一治疗方法或是联合治疗都取得了良好的效果。阐述了合并门静脉癌栓的进展期肝癌的治疗现状和治疗难点以及未来的治疗方向。     

肝细胞癌门静脉主干癌栓微血管形成和细胞增殖的关系

目的 研究肝细胞癌血管内皮生长因子（vascular endothelial growth factor,VEGF)、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)和微血管密度（micro-vessel density,MVD)的关系，及其对肝癌门静脉主干癌栓形成和转移的影响。方法 用原位杂交等技术检测16例肝癌PVTT（A1组）、其原发癌（A2组）和20例无转移肝癌（B组）VEGF、PCNA表达。结果 A1组、A2组VEGF mRNA和蛋白质阳性表达率均高于B组，A1组细胞平均吸光度高于A2组（t=8.83,P值均＜0．01）。B组、A2组、A1组PCNA阳性表达和MVD均呈升高趋势（P值均＜0．01）。A1组、A2组VEGF mNRA、蛋白质表达与MVD、增殖细胞核抗原标记指数（PCNA－LI）有良好相关性，r在0.65-0.95范围，P值均＜0．01。在A1、A2、B组MVD、PCNA－LI之间存在良好的相关性，r在0．78－0．97范围，P值均＜0．01。结论 VEGF过量表达是肝细胞癌微血管形成和癌细胞增生活跃的重要原因；丰富的微血管形成和癌细胞的快速生长是肝癌转移和门静脉主干癌栓形成的重要机制之一。     

肝细胞癌伴门静脉左支癌栓形成多学科综合治疗1例报告

肝细胞癌(简称肝癌)是一类常见的消化系统恶性肿瘤,在我国的恶性肿瘤中肝癌发病率和死亡率分别位居第4位和第2位,目前针对肝癌的主要治疗方式仍然是外科手术切除。但肝癌起病隐匿,早期缺乏典型临床表现,导致患者就诊时已经失去最佳手术时机,并且由于肝功能异常、并发症以及患者意愿,能够行使手术切除或者肝移植的患者仅占20%[1]。单一诊疗方法存在疗效差、患者生存期短、生活质量低等缺点,随着综合治疗的理念逐步兴起,使得肝癌治疗的效果得到明显提高。本院收治了1例肝癌Ⅲa期的患者,经多学科综合治疗(multi-disciplinary team,MDT)讨论后,采取了以手术为主,介入治疗及靶向药物为辅的综合治疗,现将其诊疗经过进行总结。     

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。     

原发性肝癌并发门静脉癌栓的立体定向放射治疗

原发性肝癌易侵犯门静脉形成门静脉癌栓（PVTT）,引起肝内转移,加重门静脉高压,食道静脉曲张破裂大出血,导致临床治疗困难和治疗后复发.为探讨肝癌伴PVTT的立体定向放射治疗（SRT）,2002年6月至2004年6月对86例肝癌伴PVTT无手术指征的患者进行SRT临床治疗,报道如下.     

肝细胞癌常用血清肿瘤标志物研究进展

肿瘤标志物是癌细胞产生和释放的某种物质,根据其生化或免疫特性可以筛查或诊断肿瘤。本文主要对肝细胞癌常用肿瘤标志物甲胎蛋白、甲胎蛋白异质体及异常凝血酶原的特点及各自在肝细胞癌筛查、诊断、预后和复发判断方面所起的作用及优缺点作一概述。     

门静脉癌栓影像学诊断的比较

比较术前各影像学检查对门静脉癌栓诊断的敏感性和特异性。回顾性分析110例肝细胞肝癌(HCC)伴门静脉癌栓患者的术前影像学特征及诊断。以同期100例HCC不伴门静脉癌栓患者为阴性对照。US、CT和MRL／MRA诊断门静脉癌栓的敏感性分别为88%、、93％和94％,其特异性分别为95％、96％和98％。经x2检验,各影像学诊断门静脉癌栓敏感性和特异性的差异无统计学意义(P>0．05)。各影像学检查对门静脉癌栓诊断的敏感性和特异性相近。     

肝细胞癌生物标志物研究进展

原发性肝细胞癌(HCC)发病率较高,早期确诊比较困难,致使其预后较差。近年来,随着医学影像学的发展,许多小肝癌可以被早期发现,这使患者的预后及生存质量有了明显改善,但HCC患者的5年生存率仍然在5%左右。生物标志物作为肿瘤诊断的重要依据备受关注。为了提高HCC的早期检出率,有关HCC生物标志物的研究也一直在进行中。现将相关指标的研究进展情况综述如下。     

Screening and detection of portal vein tumor thrombi-associated serum low molecular weight protein biomarkers in human hepatocellular carcinoma

Purpose Serum low molecular weight protein biomarkers might be important in relation to portal vein tumor thrombi (PVTT) in hepatocellular carcinoma (HCC). This study aimed to screen and to detect these biomarkers. Methods We selected sera of 3 groups from 12 healthy volunteers, 12 HCC patients without PVTT and 12 HCC patients with PVTT, respectively. By using two-dimensional gel electrophoresis (2-DE) in which the first dimension was 16% SDS-PAGE, serum protein images of 3 groups were analyzed by Image Master Software. The differential protein spots were further identified by MALDI-TOF MS/MS. Results Compared with 12.5% SDS-PAGE gel, there were more protein bands between 3 and 20 kDa in 16% SDS-PAGE gel and low molecular weight (MW) protein spots (<20 kDa) were clearly shown. Fifteen differential protein spots representing five proteins were found in the three groups by inter-class comparison and were then identified. Compared with the healthy group, apolipoprotein A-I, lipoprotein CIII, transthyretin and DNA topoisomerase II were down regulated in HCC groups while haptoglobin-2 was over expressed. All the five proteins were less in PVTT group than in non-PVTT group. Conclusion The expression of low MW serum protein changes obviously in the beginning and progressive stage of HCC, and differentially expressed low MW proteins might be the potential biomarkers in early prognostication and surveillance of treatment for HCC and PVTT.     

门静脉支架联合动脉化学栓塞疗法治疗肝癌合并门静脉主干癌栓

肝癌(HCC)伴有门静脉主干癌栓(MPVTT)预后极差.由被阻塞门静脉供血的正常肝组织缺血,从而损害肝功能并限制了经肝动脉化疗栓塞(TACE)在治疗HCC中的应用.经皮穿刺肝脏门静脉支架植入(PTPVS)可姑息性解除门静脉阻塞.     

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein

AIM To compare the therapeutic effect andsignificances of multimodality treatment forhepatocellular carcinoma (HCC) with tumorthrombi in portal vein (PVTT).METHODS HCC patients (n=147) with tumortrombi in the main portal vein or the first branchof portal vein were divided into four groups bythe several therapeutic methods. There wereconservative treatment group in 18 out ofpatients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI)group in 18 patients (group B), in whompostoberative chemoembolization was doneperiodically; group of removal of HCC with PVTTin 79 (group C) and group of transcatheterhepatic arterial chemoembolization (TACE) orHAI and/or portal vein infusion (PVI) afteroperation in 32 (group D).RESULTS The median survival period was 12months in our series and the 1-, 3-, and 5-yearsurvival rates were 44.3%, 24.5% and 15.2%,respectively. The median survival times were 2,5, 12 and 16 months in group A, B, C and D,respectively. The 1-, 3- and 5-year survival rateswere 5.6%, 0% and 0% in group A; 23.2%,5.6% and 0% in group B; 53.9%, 26.9% and16.6% in group C; 79.3%, 38.9% and 26.8% ingroup D, respectively. Significant differenceappeared in the survival rates among the groups (P<0.05).CONCLUSION Hepatic resection with removalof tumor thrombi and HCC should increase thecurative effects and be encouraged for theprolongation of life span and quality of life forHCC patients with PVTT, whereas the besttherapeutic method for HCC with PVTT is withregional hepatic chemotherapy orchemoemblization after hepatic resection withremoval of tumor thrombi.     

金属内支架置入联合三维适形放射治疗肝癌合并门静脉癌栓

目的 研究金属内支架置入联合三维适形放射治疗对原发性肝癌合并门静脉癌栓的治疗效果. 方法回顾性分析22例肝癌伴门静脉癌栓患者,其中门静脉支架置入联合适型放射治疗组(A组)10例,门静脉支架置入和经动脉化疗柃塞组(B组)12例.比较两组患者治疗后的不良反应发生情况及治疗前后肝功能变化情况,随访4、6、12个月的支架通畅率和3、6、12个月的生存率.肝功能比较采用Wilcoxon符号秩检验,支架通畅率曲线和生存率曲线的比较采用Log rank检验. 结果两组患者均成功建成门静脉通路,并通过经皮肝穿刺门静脉分支路径成功置放支架,门静脉狭窄均得到开通.患者均未发生腹腔出血,但术后均有不同程度的腹痛、发热、恶心、呕吐、肠胀气等症状,通过对症处理均在l周内缓解.A组患者均完成治疗,Ⅰ～Ⅱ度胃肠反应3例,Ⅰ～Ⅱ度骨髓抑制2例,对症处理后完全缓解.A组患者的4、6、12个月支架通畅率分别为90%,70%、30%,B组分别为50%,25%.16.7%,两组的通畅率曲线差异有统计学意义(χ<'2>=4.33,P<0.05).A组患者的3、6、12个月生存率分别为100%、80%、30%,B组分别为91.7%、41.7%,16.7%,对两组的生存率曲线差异有统计学意义(χ<'2>=4.05,P<0.05). 结论采用支架置入并联合三维适形放射治疗对肝癌伴门静脉癌栓有较好的疗效,且对肝脏的损害相对较小.     

门静脉支架及经动脉药物治疗栓塞联合或未联合血管内植入碘-125粒子条治疗肝癌合并门静脉主干癌栓的比较

目的 比较门静脉支架及经动脉药物治疗栓塞(TACE)联合或未联合血管内植入碘-125(125I)粒子条治疗原发性肝癌伴门静脉主干癌栓的疗效.方法 对106例(男94例,女12例,平均年龄53.23岁)在我院接受TACE治疗的原发性肝癌合并门静脉主干癌栓患者的资料进行回顾性分析,其中56例(A组)在门静脉内植入支架及125I粒子条,余50例(B组)仅在门静脉内植入支架.分别对两组患者的生存期、支架通畅率及相关不良事件进行分析.对治疗前后各测量值的改变采用配对样本t检验,计数资料采用x2检验,用Kaplan-Meier法分析生存时间及支架通畅期.结果 门静脉内植入支架及125I粒子条的技术成功率为100％,无严重相关不良事件发生.两组患者中位生存期分别为335 d(A组)及146 d(B组),P=0.001(P＜0.05)及HR=2.244;两组患者支架的中位通畅期分别为400d (A组)及190d(B组),P=0.005(P＜0.05)及HR=2.479.结论 门静脉支架及TACE联合血管内植入125I粒子条能显著延长原发性肝癌伴门静脉主干癌栓患者的生存期.     

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.     

联合介入治疗对原发性肝癌合并门静脉主支瘤栓的疗效观察

目的 探讨肝动脉化疗栓塞(TACE)联合瘤栓内经皮无水乙醇注射(PEI)治疗原发性肝癌(HCC)伴门静脉主支瘤栓的临床疗效. 方法 回顾性分析2007年1月至2010年1月收治的51例HCC伴门静脉主支瘤栓患者资料,男性38例,女性13例,年龄24 ～ 73岁,平均50.1岁.其中采用TACE联合瘤栓内PEI治疗26例(A组),只接受TACE治疗25例(B组),两组临床资料差异无统计学意义.对比观察两组患者近期内门静脉瘤栓及肿瘤变化,随访生存时间.统计学分析应用SPSS18.0软件包,计量资料采用两样本均数t检验,计数资料采用x2检验或Fisher1s精确概率法,采用Kaplan-Meier计算中位生存期,log-rank法检验组间差异,以P＜0.05为差异有统计学意义. 结果 两组均未发生与治疗有关的严重并发症,51例患者随访3 ～ 24个月.A、B两组TACE治疗次数分别为(3.2士1.4)次对比(2.4±0.9)次,t=2.22,P=0.032;A组瘤栓内PEI治疗2～8次.对瘤栓有效率为19/26对比10/25,x2=5.685,P=0.019.治疗3个月及6个月时肿瘤治疗反应(CR+ PR+ SD)为20/26对比18/25,x2=0.163,P=0.705;17/20对比10/19,x2=2.58,P=0.027.生存时间:A组5～ 23 (12.85±6.02)个月,B组4～ 16(8.65土3.39)个月,t=3.051,P=0.004.结论 对于HCC合并门静脉主支瘤栓患者,TACE联合瘤栓内PEI治疗优于单用TACE治疗,联合治疗可以较好地控制门静脉瘤栓,增加TACE机会并延长患者生存期.