肝细胞癌合并门静脉癌栓多学科诊治创新体系建立及应用
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摘要
门静脉癌栓是肝细胞癌发展到进展期最重要的标志之一,在初次就诊的肝细胞癌患者中门静脉癌栓的发生率高达44%～66.2%,在中晚期肝细胞癌患者中的这一比例更高(80%～90%)。肝细胞癌患者一旦发生门静脉癌栓,预后极差,自然生存时间仅为2.7～4个月。目前对于此类患者的治疗存在较大争议。欧美地区提倡索拉非尼是唯一的治疗方式;亚洲地区提倡多种治疗方式,包括手术治疗、经导管肝动脉化学栓塞治疗、放射治疗、系统化学治疗等。目前针对肝细胞癌合并门静脉癌栓的诊治尚未达成共识,本团队建立了肝细胞癌合并门静脉癌栓多学科诊治创新体系并对此展开了系统化的研究和应用。本文就肝细胞癌患者门静脉癌栓的发生机制、临床诊疗和多学科诊治创新体系的建立及应用展开讨论。
Portal vein tumor thrombus(PVTT) is one of the most important clinical characteristics of advanced hepatocellular carcinoma(HCC). The incidence of PVTT has been reported to be 44%-66.2% in patients with HCC who were firstly diagnosed, and 80%-90% were patients with advanced HCC. Once PVTT occurs in patients with HCC, the prognosis is very poor, and the natural survival time is only 2.7-4 months. The current treatment strategy for HCC patients with PVTT remains controversial. Sorafenib is recommended as the only treatment option in Europe and America; and a variety of treatment methods, including surgical treatment, transcatheter arterial chemoembolization, radiotherapy, and systemic chemotherapy, were advocated in Asia. At present, there is no consensus on diagnosis and treatment of HCC with PVTT. Our team has established a multidisciplinary team approach for diagnosis and treatment of HCC with PVTT, and has carried out systematic research and application. This article reviews the molecular mechanism of PVTT in patients with HCC, clinical diagnosis and treatment of PVTT, and the establishment and application of a multidisciplinary team approach.
Portal vein tumor thrombus(PVTT) is one of the most important clinical characteristics of advanced hepatocellular carcinoma(HCC). The incidence of PVTT has been reported to be 44%-66.2% in patients with HCC who were firstly diagnosed, and 80%-90% were patients with advanced HCC. Once PVTT occurs in patients with HCC, the prognosis is very poor, and the natural survival time is only 2.7-4 months. The current treatment strategy for HCC patients with PVTT remains controversial. Sorafenib is recommended as the only treatment option in Europe and America; and a variety of treatment methods, including surgical treatment, transcatheter arterial chemoembolization, radiotherapy, and systemic chemotherapy, were advocated in Asia. At present, there is no consensus on diagnosis and treatment of HCC with PVTT. Our team has established a multidisciplinary team approach for diagnosis and treatment of HCC with PVTT, and has carried out systematic research and application. This article reviews the molecular mechanism of PVTT in patients with HCC, clinical diagnosis and treatment of PVTT, and the establishment and application of a multidisciplinary team approach.
引文
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[18]ZHANG Y,GUAN D X,SHI J,GAO H,LI J J,ZHAO J S,et al.All-trans retinoic acid potentiates the chemotherapeutic effect of cisplatin by inducing differentiation of tumor initiating cells in liver cancer[J].J Hepatol,2013,59:1255-1263.
[19]GUAN D X,SHI J,ZHANG Y,ZHAO J S,LONG LY,CHEN T W,et al.Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade[J].Hepatology,2015,62:1791-1803.
[20]CHENG S,CHEN M,CAI J;National Research Cooperative Group for Diagnosis and Treatment of Hepatocellular Carcinoma with Tumor Thrombus.Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus:2016 edition[J].Oncotarget,2017,8:8867-8876.
[21]AMIN M B,GREENE F L,EDGE S B,COMPTON CC,GERSHENWALD J E,BROOKLAND R K,et al.The Eighth Edition AJCC Cancer Staging Manual:continuing to build a bridge from a population-based to a more“personalized”approach to cancer staging[J].CA Cancer J Clin,2017,67:93-99.
[22]A new prognostic system for hepatocellular carcinoma:a retrospective study of 435 patients:the Cancer of the Liver Italian Program(CLIP)investigators[J].Hepatology,1998,28:751-755.
[23]KUDO M,CHUNG H,HAJI S,OSAKI Y,OKA H,SEKIT,et al.Validation of a new prognostic staging system for hepatocellular carcinoma:the JIS score compared with the CLIP score[J].Hepatology,2004,40:1396-1405.
[24]ZHANG X P,WANG K,CHEN Z H,CHENG S Q.Hepatocellular carcinoma with hepatic vein invasion should not be considered a contraindication for liver resection[J/OL].Hepatology,2017.doi:10.1002/hep.29665.
[25]ZHANG X P,WANG K,GUO W X,CHEN Z H,CHENG S Q.Is sorafenib an optimal treatment for hepatocellular carcinoma with macrovascular invasion or metastatic disease?[J/OL].Hepatology,2018,68:786.doi:10.1002/hep.29862.
[26]LI N,FENG S,XUE J,WEI X B,SHI J,GUO W X,et al.Hepatocellular carcinoma with main portal vein tumor thrombus:a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy[J].HPB(Oxford),2016,18:549-556.
[27]SU F,CHEN K H,LIANG Z G,WU C H,LI L,QUS,et al.Comparison of three-dimensional conformal radiotherapy and hepatic resection in hepatocellular carcinoma with portal vein tumor thrombus[J].Cancer Med,2018,7:4387-4395.
[28]WEI X B,XU J,LI N,YU Y,SHI J,GUO W X,et al.The role of three-dimensional imaging in optimizing diagnosis,classification and surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus[J].HPB(Oxford),2016,18:287-295.
[29]LI X L,GUO W X,HONG X D,YANG L,WANG K,SHI J,et al.Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus:a propensity score analysis[J].Hepatol Res,2016,46:1088-1098.
[30]CHENG S,YANG J,SHEN F,ZHOU W,WANG Y,CONGW,et al.Multidisciplinary management of hepatocellular carcinoma with portal vein tumor thrombus―Eastern Hepatobiliary Surgical Hospital consensus statement[J].Oncotarget,2016,7:40816-40829.
[31]MARRERO J A,KULIK L M,SIRLIN C B,ZHU A X,FINN R S,ABECASSIS M M,et al.Diagnosis,staging and management of hepatocellular carcinoma:2018 practice guidance by the American Association for the Study of Liver Diseases[J].Hepatology,2018,68:723-750.
[32]GIANNINI E G,BUCCI L,GARUTI F,BRUNACCIM,LENZI B,VALENTE M,et al;Italian Liver Cancer(ITA.LI.CA)group.Patients with advanced hepatocellular carcinoma need a personalized management:a lesson from clinical practice[J].Hepatology,2018,67:1784-1796.
[2]ZHANG Z M,LAI E C,ZHANG C,YU H W,LIUZ,WAN B J,et al.The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus[J].Int J Surg,2015,20:8-16.
[3]CHENG A L,KANG Y K,CHEN Z,TSAO C J,QIN S,KIM J S,et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phaseⅢrandomised,double-blind,placebocontrolled trial[J].Lancet Oncol,2009,10:25-34.
[4]SCHWARTZ J D.Sorafenib in advanced hepatocellular carcinoma[J].N Engl J Med,2008,359:378-390.
[5]KOKUDO T,HASEGAWA K,MATSUYAMA Y,TAKAYAMA T,IZUMI N,KADOYA M,et al;Liver Cancer Study Group of Japan.Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion[J].J Hepatol,2016,65:938-943.
[6]YANG M,FANG Z,YAN Z,LUO J,LIU L,ZHANG W,et al.Transarterial chemoembolisation(TACE)combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone:a two-arm,randomised clinical trial[J].J Cancer Res Clin Oncol,2014,140:211-219.
[7]WANG T,HU H S,FENG Y X,SHI J,LI N,GUO W X,et al.Characterisation of a novel cell line(CSQT-2)with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma[J].Br J Cancer,2010,102:1618-1626.
[8]LIU S,LI N,YU X,XIAO X,CHENG K,HU J,et al.Expression of intercellular adhesion molecule 1 by hepatocellular carcinoma stem cells and circulating tumor cells[J/OL].Gastroenterology,2013,144:1031-1041.e10.doi:10.1053/j.gastro.2013.01.046.
[9]GUO W,LIU S,CHENG Y,LU L,SHI J,XU G,et al.ICAM-1-related noncoding RNA in cancer stem cells maintains ICAM-1 expression in hepatocellular carcinoma[J].Clin Cancer Res,2016,22:2041-2050.
[10]LIU S,GUO W,SHI J,LI N,YU X,XUE J,et al.MicroRNA-135a contributes to the development of portal vein tumor thrombus by promoting metastasis in hepatocellular carcinoma[J].J Hepatol,2012,56:389-396.
[11]TANG Y,LIU S,LI N,GUO W,SHI J,YU H,et al.14-3-3ζpromotes hepatocellular carcinoma venous metastasis by modulating hypoxia-inducible factor-1α[J].Oncotarget,2016,7:15854-15867.
[12]WANG K,GUO W,LI N,SHI J,ZHANG C,LAU WY,et al.Alpha-L-fucosidase as a prognostic indicator for hepatocellular carcinoma following hepatectomy:a large-scale,long-term study[J].Br J Cancer,2014,110:1811-1819.
[13]YANG P,LI Q J,FENG Y,ZHANG Y,MARKOWITZG J,NING S,et al.TGF-β-miR-34a-CCL22 signalinginduced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma[J].Cancer Cell,2012,22:291-303.
[14]LI N,LAI E C,SHI J,GUO W X,XUE J,HUANG B,et al.A comparative study of antiviral therapy after resection of hepatocellular carcinoma in the immune-active phase of hepatitis B virus infection[J].Ann Surg Oncol,2010,17:179-185.
[15]YU L H,LI N,SHI J,GUO W X,WU M C,CHENGS Q.Does anti-HBV therapy benefit the prognosis of HBV-related hepatocellular carcinoma following hepatectomy?[J].Ann Surg Oncol,2014,21:1010-1015.
[16]YU L H,LI N,CHENG S Q.The role of antiviral therapy for HBV-related hepatocellular carcinoma[J/OL].Int JHepatol,2011,2011:416459.doi:10.4061/2011/416459.
[17]FENG Y X,WANG T,DENG Y Z,YANG P,LI J J,GUAN D X,et al.Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model[J].Hepatology,2011,53:483-492.
[18]ZHANG Y,GUAN D X,SHI J,GAO H,LI J J,ZHAO J S,et al.All-trans retinoic acid potentiates the chemotherapeutic effect of cisplatin by inducing differentiation of tumor initiating cells in liver cancer[J].J Hepatol,2013,59:1255-1263.
[19]GUAN D X,SHI J,ZHANG Y,ZHAO J S,LONG LY,CHEN T W,et al.Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade[J].Hepatology,2015,62:1791-1803.
[20]CHENG S,CHEN M,CAI J;National Research Cooperative Group for Diagnosis and Treatment of Hepatocellular Carcinoma with Tumor Thrombus.Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus:2016 edition[J].Oncotarget,2017,8:8867-8876.
[21]AMIN M B,GREENE F L,EDGE S B,COMPTON CC,GERSHENWALD J E,BROOKLAND R K,et al.The Eighth Edition AJCC Cancer Staging Manual:continuing to build a bridge from a population-based to a more“personalized”approach to cancer staging[J].CA Cancer J Clin,2017,67:93-99.
[22]A new prognostic system for hepatocellular carcinoma:a retrospective study of 435 patients:the Cancer of the Liver Italian Program(CLIP)investigators[J].Hepatology,1998,28:751-755.
[23]KUDO M,CHUNG H,HAJI S,OSAKI Y,OKA H,SEKIT,et al.Validation of a new prognostic staging system for hepatocellular carcinoma:the JIS score compared with the CLIP score[J].Hepatology,2004,40:1396-1405.
[24]ZHANG X P,WANG K,CHEN Z H,CHENG S Q.Hepatocellular carcinoma with hepatic vein invasion should not be considered a contraindication for liver resection[J/OL].Hepatology,2017.doi:10.1002/hep.29665.
[25]ZHANG X P,WANG K,GUO W X,CHEN Z H,CHENG S Q.Is sorafenib an optimal treatment for hepatocellular carcinoma with macrovascular invasion or metastatic disease?[J/OL].Hepatology,2018,68:786.doi:10.1002/hep.29862.
[26]LI N,FENG S,XUE J,WEI X B,SHI J,GUO W X,et al.Hepatocellular carcinoma with main portal vein tumor thrombus:a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy[J].HPB(Oxford),2016,18:549-556.
[27]SU F,CHEN K H,LIANG Z G,WU C H,LI L,QUS,et al.Comparison of three-dimensional conformal radiotherapy and hepatic resection in hepatocellular carcinoma with portal vein tumor thrombus[J].Cancer Med,2018,7:4387-4395.
[28]WEI X B,XU J,LI N,YU Y,SHI J,GUO W X,et al.The role of three-dimensional imaging in optimizing diagnosis,classification and surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus[J].HPB(Oxford),2016,18:287-295.
[29]LI X L,GUO W X,HONG X D,YANG L,WANG K,SHI J,et al.Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus:a propensity score analysis[J].Hepatol Res,2016,46:1088-1098.
[30]CHENG S,YANG J,SHEN F,ZHOU W,WANG Y,CONGW,et al.Multidisciplinary management of hepatocellular carcinoma with portal vein tumor thrombus―Eastern Hepatobiliary Surgical Hospital consensus statement[J].Oncotarget,2016,7:40816-40829.
[31]MARRERO J A,KULIK L M,SIRLIN C B,ZHU A X,FINN R S,ABECASSIS M M,et al.Diagnosis,staging and management of hepatocellular carcinoma:2018 practice guidance by the American Association for the Study of Liver Diseases[J].Hepatology,2018,68:723-750.
[32]GIANNINI E G,BUCCI L,GARUTI F,BRUNACCIM,LENZI B,VALENTE M,et al;Italian Liver Cancer(ITA.LI.CA)group.Patients with advanced hepatocellular carcinoma need a personalized management:a lesson from clinical practice[J].Hepatology,2018,67:1784-1796.