原发性肝癌伴门静脉癌栓的预后分析
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摘要
背景
     原发性肝细胞癌是我国最常见的恶性肿瘤之一,其生长到一定程度很容易侵犯门静脉,并向门静脉转移而形成门静脉癌栓(以下简称PVTT),目前临床上还缺乏针对门静脉癌栓分型所建立的肝癌分型和分期。临床上权威并且常用的肝癌分期,如UICC的TNM分期,意大利的CLIP评分系统,日本的JIS评分系统等,虽然将门脉癌栓列为了肝癌分期和分值评定的一个重要参数,但也只是针对门脉癌栓有或无的考虑,并没有进一步的分层和细化,缺乏针对门脉癌栓的不同分型做出不同分期的判断标准,无法对不同分型的门脉癌栓做出更细化的预后判断和临床指导作用。2004年,程树群教授等根据癌栓的发展程度(即侵犯不同门静脉部位),将癌栓分为Ⅰ-Ⅳ型。此分型客观反映了癌栓的不同发展阶段和预后的关系,对不同类型癌栓的病人的临床预后分析有较好的指导意义,但还缺乏大样本病例对其论证。本课题我们根据程树群等提出的门脉癌栓Ⅰ~Ⅳ型分型标准,对我院2000年1月至2003年12月住院并手术治疗的肝癌伴门脉癌栓患者进行了大样本、系统性研究。对肝癌伴门静脉癌栓患者的术前检验、肿瘤性状、癌栓特征、病理特征以及术后治疗等进行了普及性调查,对其肿瘤复发时间、癌栓复发时间以及病人生存时间进行了统计分析。并对比TNM分期、CLIP评分系统、JIS评分系统,对不同癌栓分型的患者进行了生存分析。
     目的
     这一工作目的是为了进一步探讨不同分型门脉癌栓的外科疗效,以此进一步验证门脉癌栓分型的实用性;探讨合并门静脉癌栓的原发性肝癌的临床分期的细化,为门脉癌栓的预后做出更加科学和细化的预测,为肝癌伴门脉癌栓的临床诊治提供指南和参考标准,对肝癌分期标准提供更科学的分类。
     方法
     对我院2000年1月至2003年12月收治入院并手术根治的406例肝癌伴门静脉癌栓患者进行回顾性分析,以程树群等制定的癌栓分型标准设定为Ⅰ~Ⅳ型。对所有资料进行随访,对调查结果分别以门脉癌栓分型、TNM分期、CLIP评分系统、JIS评分系统分析各组病人的生存时间并绘制生存曲线。对比各系统的分层能力和预后预测能力。通过TNM分期和门脉癌栓分型的联合分析,绘制门脉癌栓患者生存曲线,找出适合门脉癌栓分型的TNM分期。
     结果
     门脉癌栓分型中Ⅰ型、Ⅱ型、Ⅲ型、Ⅳ型的一年、二年、三年生存率分别为:52.1%,31.8%和25.1%;38.2%,26.6%和17.7%;24.7%,11.4%和3.6%;18.3%,0%和0%,各型生存曲线Log-Rank P<.0001。
     TNM分期中Ⅱ期、Ⅲ期、Ⅳ期的一年、二年、三年生存率分别为:55.4%,37.5%和30.5%;36.4%,21.8%和12.8%;0%,0%和0%;各型生存曲线Log-Rank P<.0001.
     CLIP评分系统中1分、2分、3分、4分和5分的一年、二年、三年生存率分别为:61.5%,46.5%和40.7%;38.0%,20.3%和14.5%:36.7%,21.8%和13.7%;28.8%,16.4%和8.2%;0%,0%和0%,各型生存曲线Log-Rank P<.0001。
     JIS评分系统中1分、2分、3分和4分的一年、二年、三年生存率分别为:55.6%,36.4%和32.4%;36.0%,21.6%和13.6%;39.1%,23.0%和11.2%;0%,0%和0%,各型生存曲线Log-Rank P=0.0158。
     TNM分期和癌栓分型联合分析后病人的生存曲线Log-Rank P<0.0001。
     结论
     门脉癌栓的分型代表了癌栓的不同发展阶段,对比其他分期系统,对门脉癌栓的预后具有更好的预测能力和分层能力。TNM分期结合癌栓的分型,将更为客观的反映不同类型门脉癌栓病人的预后,祢补TNM分期对门脉癌栓病人分期中的不足,更好的为临床门脉癌栓的治疗以及术后抗复发治疗提供了临床参考标准和指导指南。
Background
     Primary hepatocelluar carcinoma,one of the most common malignant tumor in China, can easily invade portal vein to cause portal vein tumor thrombus(hereinafter referred to PVTT) after portal venous metastasis when the tumor grows to some extent. Although at present hepatocarcinoma typing and staging is widely used in clinical practice,there is still a lack of hepatocarcinoma typing and staging for PVTT.Even though the clinically authoritative and widely used hepatocarcinoma staging,such as TNM staging by UICC,CLIP score system in Italy,JIS score system in Japan,etc., include PVTT as an important parameter for hepatocarcinoma staging and scoring, they only consider the presence or non-presence of PVTT,without further stratification and refinement.And thus they all fail to establish diagnostic standards against different PVTT subtypes,accordingly unable to make more detailed prognosis and of clinical significance guidance.The group led by Professor Cheng Shuqun is the first one at home and abroad who in 2004 classified tumor thrombi intoⅠ-Ⅳsubtypes based on the degree of progress(different portal vein invasion).This typing method which objectively reflects the relation between different tumor thrombus stages and prognosis has a good clinical significance guidance for the prognosis analysis of the tumor thrombus patients with different types.Based on the standards for PVTTⅠ-Ⅳtyping put forth by Professor Cheng,a systemic study with large samples was done on the hepatocarcinoma patients with PVTT who were hospitalized and underwent surgeries during the period of January 2000 to December 2003 in our hospital. Comprehensive investigations on pre-surgery examination of the hepatocarcinoma patients with PVTT,tumor characteristics and tumor thrombus features,as well as pathological features and after-surgery treatment etc.,were carried out,statistical analysis was done of the timing of tumor recurrence and tumor thrombus recurrence as well as the survival time of the patients.Survival analysis was also done on the patient with different tumor thrombus types by comparing with TNM staging,CLIP scoring system and JIS scoring system.
     Objective:
     The present study is to further verify the applicability of portal vein tumor thrombus by discussing the surgical efficacy of tumor thrombus with different typing methods. The study also aims to aid in the more scientific and detailed prediction of the prognosis of portal vein tumor thrombus,and provide guidance and reference standards for clinical diagnosis of hepatocarcinoma with portal vein tumor thrombus by discussing the clinical stratification of the typing of primary hepatocelluar carcinoma with portal vein tumor thrombus.
     Method:
     Retrospective analysis was done on 406 hepatocarcinoma patients with portal vein tumor thrombus who were hospitalized and had undergone surgeries during the period of January 2000 to December 2003 in our hospital.Tumor thrombi were defined as typeⅠ-Ⅳaccording to the typing standards of the tumor thrombus set by Professor Cheng.Follow-up study was done on all patients.Analysis of survival time was carried out by using portal vein tumor thrombus typing,TNM staging,CLIP scoring system and JIS scoring system,and survival curve was plotted.The stratification capability and prognosis predictability of each system was also compared.The TNM staging suitable for portal vein tumor thrombus typing was found out by plotting survival curve of the patients with portal vein tumor thrombus and combined analysis of the TNM staging and portal vein tumor thrombus typing.
     Result;
     With portal vein tumor thrombus typing,the 1、2、3 years survival rates were 52.1%, 31.8%and 25.1%respectivly for typeⅠpatients;38.2%,26.6%and 17.7% respectively for typeⅡpatients;24.7%,11.4%and 3.6%respectively for typeⅢpatients;and 18.3%,0%and 0%respectivly in typeⅣpatients.The Log-Rank of various types' survival curve was P<.0001.
     With TNM staging,the 1、2、3 years survival rates were 55.4%,37.5%and 30.5% respectively for typeⅡpatients,36.4%,21.8%and 12.8%respectively for typeⅢpatients;0%,0%and 0%respectively for typeⅣpatients.The Log-Rank of various types' survival curve was P<.0001.
     With CLIP scoring system,the 1、2、3 years survival rates were 61.5%,46.5%and 40.7%respectively for patients had 1 score;38.0%,20.3%and 14.5%respectively for patients had 2 scores;36.7%,21.8%and 13.7%respectively for patients had 3 scords;28.8%,16.4%and 8.2%respectively for patients had 4 scords;and 0%,0 %and 0%respectively for patients had 5 scords.The Log-Rank of various types' survival curve was P<.0001.
     With JIS scoring system,the 1、2、3 years survival rates were 55.6%,36.4%and 32.4 %respectively for patients had 1 score;36.0%,21.6%and 13.6%respectively for patients had 2 score;39.1%,23.0%and 11.2%respectively for patients had 3 score;and 0%,0%and 0%respectively for patients had 4 score,The Log-Rank of various types' survival curve was P =0.0158.
     Discussion
     Portal vein tumor thrombus typing is better capable of stratifying portal vein tumor thrombus and predicting the prognosis compared with other staging systems because it can represent different development stages of tumor thrombus.TNM staging combined with tumor thrombus typing provides a better clinical reference standard and guidance on the treatment of the patients with portal vein tumor thrombus and the recurrence treatment after surgery since it can more objectively reflect the prognosis of the patients with portal vein tumor thrombus of different types and compensating the deficiency with TNM staging.
引文
1.Toshiro Nakashima.Pathology of hepatocellar carcinoma-tumor thrombus of the portal vein.Acta Hepathologica Japonica,1984,25:120-126
    2.Tang ZY,Ye SL,Lin YK,et al.A decade's studio on metastasis of hepatocellular carcinoma.J Cancer Res Clin Oncol,2004,130:187-196
    3.Moon WS,Chang K,Tarnawski AS.Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma:Relationship to vascular invasion and estrogen receptor-alpha.Hum Pathol,2004,35:424-429
    4.Chung TW,Lee YC,Kim CH.Hepatitis B viral HBx induces matrix metalloproteinase-9gene expression through activation of ERKs and PI-3K/AKT pathways:Involvement of invasive potential.FASEB J,2004,7[Epub ahead of print]
    5.Ren Y,Tsui HT,Poon RT,et al.Macrophage migration inhibitory factor:roles in regulatingtumor cell migration and expression of angiogenic factors in hepatocellular carcinoma.Int J Cancer,2003,107:22-29
    6.WaKanishi K,Sakamoto M,Yamasaki S,et al.Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma.Cancer,2005,103:307-312
    7.Ye QH,Qin LX,Forgues M,et al.Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning.Nature Medicine,2003,9:416-423
    8.程树群,吴孟超,程红岩。原发性肝癌门静脉癌栓生长特征的研究。中国现代普通外科进展,2003,6:103-105
    9.程树群,吴孟超,陈汉,等。肝癌门静脉癌栓分型的影像学意义。中华普通外科杂志,2004,19:200-201
    10.程树群,吴孟超,陈汉,等。癌栓分型对肝细胞性肝癌合并门静脉癌栓治疗及预后的指导意义。中华医学杂志,2004,84:3-5
    11. Cheng SQ, Wu MC, Chen H, et al. Tumor thrombus types influence the prognosis of hepatocellular carcinoma with tumor thrombi in the portal vein. Hepato-Gastroenterology 2007; 54:499-502
    1.吴孟超,陈汉,沈锋。原发性肝癌的外科治疗--附5524例报告。中华外科杂志,2001,39:25-28
    2.Car-Yang Chau,Wing-Yiu Lui,et al.Spectrum and significance of microscopic vascular invasion in hepatocellular.Surg Oncol Clin N Am,2003,12:25-34.
    3.Fan J,Wu ZQ,Tang ZY,et al.Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein.World J Gastroenterol 2001;7:28-32.
    4.Patt YZ,Hassan MM,Lozano RD,et al.Phase Ⅱ trial of systemic continuous fluorouracil and subcutaneous recombination interferon alfa-2b for treatment of hepatocellular carcinoma.J Clin Oncol 2003;21:421-7.
    5.Fukuda S,Okuda K,Imamura M,Imamura I,Eriguchi N,Aoyagi S.Surgical resection combined with chemotherapy for advanced hepatocellular carcinoma with tumor thrombus:Report of 19 cases.Surgery 2002;131:300-310.
    6.Farges O,Belghiti J,Kianmanesh R,et al.Portal vein embolization before right hepatectomy:Prospective clinical trial.Ann Surg 2003;237:208-217.
    7.Eiji A,Masatoshi T,Fumihiko Y,et al.Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases.Cancer,2002,95:588-595.
    8.Masato S,Hiroaki N,Keizo D,et al.combined intraarterial 5-fluorouracil and subcutaneous inferferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal brancheso Cancer,2002,94:435-442.
    9.程树群,吴孟超,程红岩。原发性肝癌门静脉癌栓生长特征的研究。中国现代普通外科进展,2003,6:103-105
    10.程树群,吴孟超,陈汉,等。肝癌门静脉癌栓分型的影像学意义。中华普通外科杂志,2004,19:200-201
    11.Cancer of the Liver Italian Program Investigators.Prospective validation of the CLIP score:a new prognostic system for patients with cirrhosis and hepatocellular carcinoma,the Cancer of the Liver Italian Program(CLIP)investigators.Hepatology 2000;31:840-5.
    12.Llovet JM,Bru C,Bruix J.Prognosis of hepatocellular carcinoma:the BCLC staging classification.Semin Liver Dis 1999;19:329-38.
    13.Sala A,Forner A,Varela M,Bruix J.Prognostic prediction in patients with hepatocellular carcinoma.Semin Liver Dis 2005;25:171-80.
    14.Leung TW,Tang AM,Zee B,Lau WY,Lai PB,Leung KL,et al.Construction of the Chinese University Prognostic Indices for hepatocellular carcinoma and comparison with the TNM staging system,the Okuda staging system and the Cancer of the Liver Italian Program staging system:a study based on 926 patients.Cancer 2002;94:1760-9.
    15.Tateishi R,Yoshida H,Shiina S,Imamura H,Hasegawa K,Teratani T,et al.Proposal of a new prognostic model for hepatocellular carcinoma:an analysis of 403 patients.Gut 2005;54:419-25.
    16.程树群。原发性肝癌癌栓分型的探讨。中国现代普通外科进展2003;6:171-173.
    17.程树群,吴孟超,陈汉,等。癌栓分型对肝细胞性肝癌合并门静脉癌栓治疗及预后的指导意义。中华医学杂志,2004,84:3-5.
    1.吴孟超主编.肝脏外科学.第2版,上海:上海科学技术文献出版社,上海科技教育出版社,2000.306.
    2.Car-Yang Chau,Wing-Yiu Lui,et al.Spectrum and significance of microscopic vascular invasion in hepatocellular.Surg Oncol Clin N Am,2003,12:25-34.
    3.Tang ZY,Ye SL,Lin YK,et al.A decade's studio on metastasis of hepatocellular carcinoma.J Cancer Res Clin Oncol,2004,130:187-196.
    4.Moon WS,Chang K,Tarnawski AS.Overexpression of metastatic tumor antigen 1in hepatocellular carcinoma:Relationship to vascular invasion and estrogen receptor-alpha.Hum Pathol,2004,35:424-429.
    5.WaKanishi K,Sakamoto M,Yamasaki S,et al.Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular arcinoma.Cancer,2005,103:307-312.
    6.樊嘉,炅志全,周俭,等.肝细胞癌伴门静脉癌栓不同治疗方法的比较[J].中华肿瘤杂志.2000,22:247-249.
    7.Chung YH,Song 1 Hart,Song BC,et al.Combined therapy consisting of intraarterial eight in infusion and sysiemie inteferona for hepatoelluar carcinoma patients with major portal vein thrombosis or distant metastasis[J].Cancer.2000,88:1986-1991.
    8.Lee HS,Kim JS,Choi 1I J.et al.The safety and eficacy oftranscatheter arterial chemoembo lization in the treatment of patients with hepatocellular carcinoma and main portal vein bstruction[J].Cancer,1997,79:2087-2094.
    10.程树群,吴孟超,程红岩.原发性肝癌门静脉癌栓生长特征的研究.中国现代普通外科进展,2003,6:103-105.
    11.程树群,吴孟超,陈汉,等.肝癌门静脉癌栓分型的影像学意义.中华普通外科杂志,2004,19:200-201.
    12.程树群,吴孟超,陈汉,等.癌栓分型对肝细胞性肝癌合并门静脉癌栓治疗及预后的指导意义.中华医学杂志,2004,84:3-5.
    13.Cheng SQ,Wu MC,Chen H,et al.Tumor thrombus types influence the prognosis of hepatocellular carcinoma with tumor thrombi in the portal vein. Hepato-Gastroenterology.2007;54:499-502
    14.童颖,杨甲梅.原发性肝癌门静脉癌栓的形成及治疗.中国实用外科杂志.2003;23:4373-375.
    15.Itamoto T,Nakahara H,Tashiro H,et al.Hepatic arterial infusion of 5-fluorouracil and cisplatin for unresectable or recurrent hepatocellular carcinoma with tumor thrombus of the portal vein.J Surg Oncol,2002,80(3):143.
    16.张毅,冯志毅,王胜甲,等.经腹肝动脉门静脉双置泵栓塞灌注化疗中晚期肝癌[J].中国普通外科杂志,1999,8:89.
    17.Okuda K,Tanaka M,Shibata J,et al.Hepatic carterial intfusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouraeil for multiple l'-3ul Tente of hepatocellular carcinoma after surgical treatment[J].Oncol Rep,1999,6:587-591.
    18.樊嘉,周偷,吴志全,等.不同化疗模式及不同给药途径对肝癌合并门静脉癌栓术后化疗作用的比较研究[j].中华肝胆外科杂志,2003,9:334-337.
    19.Ishikura S,Ogino T,Fumse J,et al.Radiotherapy after trasatheter arterial chemoembofization for patients with hepatoeellular carcinoma and portal vein tumorthrombus[J].Am J Clin Oncol,2002,25:189-193.
    20.Tazawaj,Maeda M,Sakai Y,et al.Radiation therapy in combination with trmmcatheter arterial chemoembolization for hepatoeellular careinoma with extensive portal vein involvement[J].J Gastroenterol Hepatol,2001,16:660-665.
    21.YamadaK,SoejimaT,Sugimnto K,etal.P t studyoflLx,al radiotherspy for portal vein tumor thrombus in patients with unresec table hepatocellular carcinoma[J].Jpn J Clin Oncol.2001.31:147-152.

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