肝细胞癌肝移植术后肿瘤复发的危险因素与防治策略

郑卫萍; 沈中阳

doi:10.3969/j.issn.1001-5256.2019.11.003

肝细胞癌肝移植术后肿瘤复发的危险因素与防治策略

DOI: 10.3969/j.issn.1001-5256.2019.11.003

天津市第一中心医院器官移植中心

基金项目:

天津市器官移植临床医学研究中心项目(15ZXLCSY00070)；中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2019PT320016)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 1161
- HTML全文浏览量: 14
- PDF下载量: 373
- 被引次数: 0
出版历程
- 收稿日期: 2019-10-07
- 出版日期: 2019-11-20

Risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma and related control strategies

Center of Organ Transplantation,Tianjin First Central Hospital

Research funding:

摘要

摘要: 肝细胞癌肝移植术后肿瘤的复发是造成患者和移植物存活率显著下降的主要原因。影响肝移植术后肿瘤复发的危险因素主要包括肿瘤的病理和生物学特性、受者相关因素、供者和供肝相关因素、手术相关因素等。免疫抑制方案的管理以及多种辅助治疗有助于预防肿瘤复发。针对肝细胞癌肝移植患者,如何早期识别肿瘤复发的危险因素并进行综合防治值得进一步探讨。
- 癌,肝细胞 /
- 肝移植 /
- 肿瘤复发,局部 /
- 危险因素 /
- 二级预防
Abstract: Tumor recurrence after liver transplantation for hepatocellular carcinoma is the main cause of significant reductions in the survival rates of patients and grafts. Risk factors for tumor recurrence after liver transplantation include pathological and biological features,factors associated with the recipient,factors associated with the donor and donor liver,and surgery-related factors. Immunosuppression regimen and various adjuvant therapies may help to prevent tumor recurrence. For patients undergoing liver transplantation for hepatocellular carcinoma,further studies are needed to investigate early identification of risk factors for tumor recurrence and related comprehensive prevention and treatment measures.
- carcinoma,hepatocellular /
- liver transplantation /
- neoplasm recurrence,local /
- risk factors /
- secondary prevention

HTML全文

参考文献(50)

[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424.

[2] ZHENG RS,SUN KX,ZHANG SW,et al. Report of cancer epidemiology in China,2015[J]. Chin J Oncol,2019,41(1):19-28.(in Chinese)郑荣寿，孙可欣，张思维，等．2015年中国恶性肿瘤流行情况分析[J]．中华肿瘤杂志，2019,41(1):19-28.

[3] National Health and Family Planning Commission of the People’s Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会．原发性肝癌诊疗规范(2017年版)[J]．临床肝胆病杂志，2017,33(8):1419-1431.

[4] Organ Transplantation Branch,Chinese Medical Doctor Association; Chinese Society of Organ Transplantation,Chinese Medical Association. The Chinese clinical practice guideline on liver transplantation for hepatocellular carcinoma(2018)[J]. J Clin Hepatol,2019,35(2):275-280.(in Chinese)中国医师协会器官移植医师分会，中华医学会器官移植学分会．中国肝癌肝移植临床实践指南(2018版)[J]．临床肝胆病杂志，2019,35(2):275-280.

[5] China Liver Transplantation Registration Center. China liver transplantation science report 2016[M]. Hangzhou:China Liver Transplantation Registration Center,2017:6.(in Chinese)中国肝移植注册中心．2016中国肝移植科学报告[M]．杭州:中国肝移植注册中心，2017:6.

[6] MAZZAFERRO V,REGALIA E,DOCI R,et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. N Engl J Med,1996,334(11):693-699.

[7] YAO FY,FERRELL L,BASS NM,et al. Liver transplantation for hepatocellular carcinoma:Expansion of the tumor size limits does not adversely impact survival[J]. Hepatology,2001,33(6):1394-1403.

[8] MAZZAFERRO V,LLOVET JM,MICELI R,et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria:A retrospective,exploratory analysis[J]. Lancet Oncol,2009,10(1):35-43.

[9] FAN J,ZHOU J,XU Y,et al. Indication of liver transplantation for hepatocellular carcinoma:Shanghai Fudan Criteria[J].Natl Med J China,2006,86(18):1227-1231.(in Chinese)樊嘉，周俭，徐泱，等．肝癌肝移植适应证的选择:上海复旦标准[J]．中华医学杂志，2006,86(18):1227-1231.

[10] ZHENG SS,XU X,WU J,et al. Liver transplantation for hepatocellular carcinoma:Hangzhou experiences[J]. Transplantation,2008,85(12):1726-1732.

[11] SHEN ZY,DONG C,JIANG WT,et al. Evaluation of criteria in liver transplantation for hepatocellular carcinoma:2393 cases report of liver transplantation for hepatocellular carcinoma[J].Chin J Organ Transplant,2013,34(9):516-520.(in Chinese)沈中阳，董冲，蒋文涛，等．肝细胞癌肝移植适应证标准的评价—2393例临床病例总结[J]．中华器官移植杂志，2013,34(9):516-520.

[12] TOSO C,MENTHA G,MAJNO P. Liver transplantation for hepatocellular carcinoma:Five steps to prevent recurrence[J]. Am J Transplant,2011,11(10):2031-2035.

[13] BODZIN AS,LUNSFORD KE,MARKOVIC D,et al. Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation:Impact of treatment modality and recurrence characteristics[J]. Ann Surg,2017,266(1):118-125.

[14] SAPISOCHIN G,GOLDARACENA N,ASTETE S,et al. Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series[J]. Ann Surg Oncol,2015,22(7):2286-2294.

[15] SOTIROPOULOS GC,MOLMENTI EP,LOSCH C,et al. Meta-analysis of tumor recurrence after liver transplantation for hepatocellular carcinoma based on 1,198 cases[J]. Eur J Med Res,2007,12(10):527-534.

[16] SOTIROPOULOS GC,LANG H,NADALIN S,et al. Liver transplantation for hepatocellular carcinoma:University Hospital Essen experience and metaanalysis of prognostic factors[J]. J Am Coll Surg,2007,205(5):661-675.

[17] TOSO C,MEEBERG G,HERNANDEZ-ALEJANDRO R,et al.Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma:A prospective validation[J]. Hepatology,2015,62(1):158-165.

[18] HAMEED B,MEHTA N,SAPISOCHIN G,et al. Alpha-fetoprotein level> 1000 ng/m L as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria[J]. Liver Transpl,2014,20(8):945-951.

[19] POTEN,CAUCHY F,ALBUQUERQUE M,et al. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion[J]. J Hepatol,2015,62(4):848-854.

[20] SHINDOH J,SUGAWARA Y,NAGATA R,et al. Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma[J]. Transpl Int,2014,27(4):391-398.

[21] FUJIKI M,TAKADA Y,OGURA Y,et al. Significance of desgamma-carboxy prothrombin in selection criteria for living donor liver transplantation for hepatocellular carcinoma[J]. Am J Transplant,2009,9(10):2362-2361.

[22] MILTIADOUS O,SIA D,HOSHIDA Y,et al. Progenitor cell markers predict outcome of patients with hepatocellular carcinoma beyond Milan criteria undergoing liver transplantation[J]. J Hepatol,2015,63(6):1368-1377.

[23] LI MR,CHEN GH,CAI CJ,et al. High hepatitis B virus DNA level in serum before liver transplantation increases the risk of hepatocellular carcinoma recurrence[J]. Digestion,2011,84(2):134-141.

[24] SAAB S,YEGANEH M,NGUYEN K,et al. Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation[J]. Liver Transpl,2009,15(11):1525-1534.

[25] REIG M,MARINO Z,PERELLOC,et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy[J]. J Hepatol,2016,65(4):719-726.

[26] YANG JD,AQEL BA,PUNGPAPONG S,et al. Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma[J]. J Hepatol,2016,65(4):859-860.

[27] NAULT JC,COLOMBO M. Hepatocellular carcinoma and direct acting antiviral treatments:Controversy after the revolution[J]. J Hepatol,2016,65(4):663-665.

[28] ANRS collaborative study group on hepatocellular carcinoma(ANRS CO22 HEPATHER,CO12 Cir Vir and CO23 CUPILT cohorts). Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma:Data from three ANRS cohorts[J]. J Hepatol,2016,65(4):734-740.

[29] HUANG AC,MEHTA N,DODGE JL,et al. Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout[J]. Hepatology,2018,68(2):449-461.

[30] AN HJ,JANG JW,BAE SH,et al. Serum C-reactive protein is a useful biomarker for predicting outcomes after liver transplantation in patients with hepatocellular carcinoma[J]. Liver Transpl,2012,18(12):1406-1414.

[31] KORNBERG A,WITT U,KORNBERG J,et al. Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma[J].Biomarkers,2016,21(2):152-159.

[32] HALAZUN KJ,HARDY MA,RANA AA,et al. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma[J]. Ann Surg,2009,250(1):141-151.

[33] AGOPIAN VG,HARLANDER-LOCKE M,ZARRINPAR A,et al. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation:Analysis of 865 consecutive liver transplant recipients[J]. J Am Coll Surg,2015,220(4):416-427.

[34] LAI Q,MELANDRO F,LARGHI LAUREIRO Z,et al. Plateletto-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer:A systematic review and meta-analysis[J]. World J Gastroenterol,2018,24(15):1658-1665.

[35] ORCI LA,BERNEY T,MAJNO PE,et al. Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation[J]. Br J Surg,2015,102(10):1250-1257.

[36] NAGAI S,YOSHIDA A,FACCIUTO M,et al. Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation[J]. Hepatology,2015,61(3):895-904.

[37] MAN K,NG KT,LO CM,et al. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastasesactivation of cell invasion and migration pathways[J]. Liver Transpl,2007,13(12):1669-1677.

[38] HARRIS AL. Hypoxia-a key regulatory factor in tumour growth[J]. Nat Rev Cancer,2002,2(1):38-47.

[39] ORCI LA,LACOTTE S,OLDANI G,et al. Effect of ischaemic preconditioning on recurrence of hepatocellular carcinoma in an experimental model of liver steatosis[J]. Br J Surg,2016,103(4):417-426.

[40] RODRIGUEZ-PERALVAREZ M,de la MATA M,BURROUGHS AK. Liver transplantation:Immunosuppression and oncology[J].Curr Opin Organ Transplant,2014,19(3):253-260.

[41] RODRIGUEZ-PERALVAREZ M,TSOCHATZIS E,NAVEAS MC,et al. Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma[J]. J Hepatol,2013,59(6):1193-1199.

[42] VILLANUEVA A,CHIANG DY,NEWELL P,et al. Pivotal role of m TOR signaling in hepatocellular carcinoma[J]. Gastroenterology,2008,135(6):1972-1983,1983. e1-11.

[43] TOSO C,MERANI S,BIGAM DL,et al. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma[J]. Hepatology,2010,51(4):1237-1243.

[44] YANIK EL,CHINNAKOTLA S,GUSTAFSON SK,et al. Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma[J]. Liver Transpl,2016,22(5):627-634.

[45] MENON KV,HAKEEM AR,HEATON ND. Meta-analysis:Recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma[J]. Aliment Pharmacol Ther,2013,37(4):411-419.

[46] LIANG W,WANG D,LING X,et al. Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma:A meta-analysis[J]. Liver Transpl,2012,18(1):62-69.

[47] GEISSLER EK,SCHNITZBAUER AA,ZULKE C,et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma:A randomized,multicenter,open-label phase 3 trial[J]. Transplantation,2016,100(1):116-125.

[48] WEI Q,GAO F,ZHUANG R,et al. A national report from China Liver Transplant Registry:Steroid avoidance after liver transplantation for hepatocellular carcinoma[J]. Chin J Cancer Res,2017,29(5):426-437.

[49] ROAYAIE S,SCHWARTZ JD,SUNG MW,et al. Recurrence of hepatocellular carcinoma after liver transplant:Patterns and prognosis[J]. Liver Transpl,2004,10(4):534-540.

[50] FENG K,YAN J,LI X,et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma[J]. J Hepatol,2012,57(4):794-802.

施引文献

资源附件(0)

访问统计