由于肝癌恶性程度高、起病隐匿，确诊时往往已是中晚期，因此对中晚期肝癌进行降期治疗是转化治疗的重要内容，也是提高肝癌切除率的重要方向。肝癌目前存在多种临床分期，在我国临床实践中应用最为广泛的是巴塞罗那分期（BCLC）［2］和中国分期［3］。两种分期标准存在着一定差异，但是主要的分期指标基本相同，如全身情况、肝外转移、脉管癌栓（主要为门静脉癌栓）、肿瘤数目、肝功能情况。肝癌降期治疗的意义主要通过完全控制转移灶从而让肿瘤获得根治性切除机会，且在降期治疗过程中依据肿瘤对治疗的反应筛选合适的转化后手术对象。由于肝移植标准严格，降期治疗在肝移植中较早开展，降期的成功率（11%~66%）主要取决于入组患者特征，无肝外转移、无门静脉癌栓、单个肿瘤直径小于10cm、肿瘤直径总和小于12cm的肝癌实现降期成功的比例更高，且降期成功后肝移植的预后接近于符合标准的一期肝移植［4］。有回顾性研究［5］表明降期后行肝切除及肝移植的总体生存率相当，降期手术切除的标准及效果能否参照降期后肝移植仍需更多的证据。在此，笔者主要探讨以肝脏切除为导向的肝癌降期治疗。
1.1经肝动脉化疗栓塞术（TACE）
1.2经肝动脉放疗性栓塞（TARE）
TARE通过往肝动脉内注射放射颗粒从而实现阻断肿瘤动脉供血，同时给与肿瘤内部放射线照射，对肿瘤起到双重杀伤作用，主要的栓塞剂为钇-90。Kulik等［12］报道了150例肝癌患者行钇-90栓塞放疗，其中34例中晚期肿瘤成功降期，揭示TARE在中晚期肝癌降期治疗中的重要价值。Iarrairaegui等［13］对使用钇-90栓塞放疗成功降期后的T3期肝癌患者采取了肝切除或肝移植的根治性手术，术后总生存期超过41.5个月，达到了根治性治疗的目的。Labgaa等［14］对319例不能手术切除的肝癌实施了TARE，其中32例患者降期成功后行根治性手术，包括肝移植（22例）和肝切除（10例），术后中位生存期超过41.5个月，进一步提示TARE在不可切除肿瘤降期治疗中的可行性。Lewandowski等［15］分别对两组数量相等的中晚期肝癌患者行TACE和TARE（各43例），发现肿瘤对TARE的应答率高于TACE（61%vs37%），TARE组降期成功率也明显占优势（58%vs31%）。此外，该研究提出由于放疗对肿瘤细胞杀伤作用的滞后性，TARE后3~6个月肿瘤坏死范围仍会增加，因此，TARE月内不需要重复应用，这也是其相对TACE的重要优势之一。
1.3体外放射治疗
1.4系统治疗
2剩余肝体积不足
解剖性肝切除因能够更好地保证肿瘤切缘以及切除相应的门静脉引流区域，逐渐被肝胆外科医生所接受。对于巨大肿瘤或者临近肝内重要管道的小肿瘤，仍需以切缘＞1cm为目标，必要时切除肿瘤临近血管及引流区域的肝脏组织，因此实施解剖性肝切除常需切除大块正常肝实质，由此也带来术后肝功能衰竭的风险。安全的肝切除范围一般为肝切除后至少保留1根肝静脉且剩余肝体积＞40%标准肝体积（伴有肝硬化）或者＞30%标准肝体积（不伴有肝硬化）。对于术前规划证实剩余肝脏体积不足者，可通过门静脉栓塞（PVE）或联合肝脏隔断和门静脉结扎的二步肝切除术（ALPPS）等方法刺激剩余肝脏快速增生从而获得根治性肝切除的机会。对于此类患者，虽然并未改变肿瘤的分期，但是将不能切除的肝癌转变为可切除或者将姑息性切除转化为根治性切除，降低围手术期死亡率并提高患者远期生存率，与降期治疗策略契合，也属于转化治疗的范畴。
2.1联合肝脏隔断和门静脉结扎的二步肝切除术（ALPPS）
2.2选择性PVE
3展望
参考文献:
［1］SCHLACHTERMANA,CRAFTWWJr,HILGENFELDTE,etal.Currentandfuturetreatmentsforhepatocellularcarcinoma［J］.WorldJGastroenterol,2015,21(28):8478-8491.
［2］EuropeanAssociationfortheStudyoftheLiver.EASLclinicalpracticeguidelines:Drug-inducedliverinjury［J］.JHepatol,2019,70(6):1222-1261.
［3］NationalHealthandFamilyPlanningCommissionofthePeople’sRepublicofChina.Diagnosis,management,andtreatmentofhepatocellularcarcinoma(V2017)［J］.JClinHepatol,2017,33(8):1419-1431.(inChinese)
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］PARIKHND,WALJEEAK,SINGALAG.Downstaginghepatocellularcarcinoma:Asystematicreviewandpooledanalysis［J］.LiverTranspl,2015,21(9):1142-1152.
［5］LEIJY,YANLN,WANGWT.Transplantationvsresectionforhepatocellularcarcinomawithcompensatedliverfunctionafterdownstagingtherapy［J］.WorldJGastroenterol,2013,19(27):4400-4408.
［6］ZHANGY,HUANGG,WANGY,etal.IssalvageliverresectionnecessaryforinitiallyunresectablehepatocellularcarcinomapatientsdownstagedbytransarterialchemoembolizationTenyearsofexperience［J］.Oncologist,2016,21(12):1442-1449.
［7］JIANGL,LEIJY,WANGWT,etal.ImmediateradicaltherapyorconservativetreatmentswhenmeetingtheMilancriteriaforadvancedHCCpatientsaftersuccessfulTACE［J］.JGastrointestSurg,2014,18(6):1125-1130.
［8］LEIJY,ZHONGJJ,YANLN,etal.Responsetotransarterialchemoembolizationasaselectioncriterionforresectionofhepatocellularcarcinomas［J］.BrJSurg,2016,103(7):881-890.
［9］LEEBH,LEEDS,CHOCW,etal.RoleandlimitationofneoadjuvanthepaticarterialinfusionchemotherapyinadvancedhepatocelluarcarcinomapatientswithChild-PughclassA［J］.WorldJSurgOncol,2019,17(1):143.
［10］AFFONSOBB,GALASTRIFL,daMOTTALEALFILHOJM,etal.Long-termoutcomesofhepatocellularcarcinomathatunderwentchemoembolizationforbridgingorDownstaging［J］.WorldJGastroenterol,2019,25(37):5687-5701.
［11］ALLARDMA,SEBAGHM,RUIZA,etal.Doespathologicalresponseaftertransarterialchemoembolizationforhepatocellularcarcinomaincirrhoticpatientswithcirrhosispredictoutcomeafterliverresectionortransplantation［J］.JHepatol,2015,63(1):83-92.
［12］KULIKLM,ATASSIB,vanHOLSBEECKL,etal.Yttrium-90microspheres(TheraSphere)treatmentofunresectablehepatocellularcarcinoma:Downstagingtoresection,RFAandbridgetotransplantation［J］.JSurgOncol,2006,94(7):572-586.
［13］IARRAIRAEGUIM,PARDOF,BILBAOJI,etal.Responsetoradioembolizationwithyttrium-90resinmicrospheresmayallowsurgicaltreatmentwithcurativeintentandprolongedsurvivalinpreviouslyunresectablehepatocellularcarcinoma［J］.EurJSurgOncol,2012,38(7):594-601.
［14］LABGAAI,TABRIZIANP,TITANOJ,etal.FeasibilityandsafetyoflivertransplantationorresectionaftertransarterialradioembolizationwithYttrium-90forunresectablehepatocellularcarcinoma［J］.HPB(Oxford),2019,21(11):1497-1504.
［15］LEWANDOWSKIRJ,KULIKLM,RIAZA,etal.Acomparativeanalysisoftransarterialdownstagingforhepatocellularcarcinoma:Chemoembolizationversusradioembolization［J］.AmJTransplant,2009,9(8):1920-1928.
［16］CHOSSH,SEONGJ.Strategicapplicationofradiotherapyforhepatocellularcarcinoma［J］.ClinMolHepatol,2018,24(2):114-134.
［17］CHONGJU,CHOIGH,HANDH,etal.Downstagingwithlocalizedconcurrentchemoradiotherapycanidentifyoptimalsurgicalcandidatesinhepatocellularcarcinomawithportalveintumorthrombus［J］.AnnSurgOncol,2018,25(11):3308-3315.
［18］LIN,FENGS,XUEJ,etal.Hepatocellularcarcinomawithmainportalveintumorthrombus:Acomparativestudycomparinghepatectomywithorwithoutneoadjuvantradiotherapy［J］.HPB(Oxford),2016,18(6):549-556.
［19］WEIX,JIANGY,ZHANGX,etal.Neoadjuvantthree-dimensionalconformalradiotherapyforresectablehepatocellularcarcinomawithportalveintumorthrombus:Arandomized,open-label,multicentercontrolledstudy［J］.JClinOncol,2019,37(24):2141-2151.
［20］YOSHIMOTOT,IMURAS,MORINEY,etal.Theoutcomeofsorafenibtherapyonunresectablehepatocellularcarcinoma:Experienceofconversionandsalvagehepatectomy［J］.AnticancerRes,2018,38(1):501-507.
［21］HEMK,ZOURH,LIQJ,etal.PhaseIIstudyofsorafenibcombinedwithconcurrenthepaticarterialinfusionofoxaliplatin,5-fluorouracilandleucovorinforunresectablehepatocellularcarcinomawithmajorportalveinthrombosis［J］.CardiovascInterventRadiol,2018,41(5):734-743.
［22］KUDOM,FINNRS,QINS,etal.Lenvatinibversussorafenibinfirst-linetreatmentofpatientswithunresectablehepatocellularcarcinoma:Arandomisedphase3non-inferioritytrial［J］.Lancet,2018,391(10126):1163-1173.
［23］ZAANANA,WILLIETN,HEBBARM,etal.Gemcitabineplusoxaliplatininadvancedhepatocellularcarcinoma:AlargemulticenterAGEOstudy［J］.JHepatol,2013,58(1):81-88.
［24］YEOW,MOKTS,ZEEB,etal.ArandomizedphaseIIIstudyofdoxorubicinversuscisplatin/interferonalpha-2b/doxorubicin/fluorouracil(PIAF)combinationchemotherapyforunresectablehepatocellularcarcinoma［J］.JNatlCancerInst,2005,97(20):1532-1538.
［25］LEUNGTW,PATTYZ,LAUWY,etal.Completepathologicalremissionispossiblewithsystemiccombinationchemotherapyforinoperablehepatocellularcarcinoma［J］.ClinCancerRes,1999,5(7):1676-1681.
［26］KASEBAO,SHINDOHJ,PATTYZ,etal.Modifiedcisplatin/interferonα-2b/doxorubicin/5-fluorouracil(PIAF)chemotherapyinpatientswithnohepatitisorcirrhosisisassociatedwithimprovedresponserate,resectability,andsurvivalofinitiallyunresectablehepatocellularcarcinoma［J］.Cancer,2013,119(18):3334-3342.
［27］HUANGZP,WANGZH,LIY,etal.Researchadvancesintwo-stephepatectomycombiningliverpartitionwithportalveinligation［J］.ChinJPractSurg,2018,38(4):456-459.(inChinese)
黄智平,王志恒,李曜,等.联合肝脏分隔和门静脉结扎的二步肝切除术研究进展［J］.中国实用外科杂志,2018,38(4):456-459.
［28］CHANA,ZHANGWY,CHOKK,etal.ALPPSversusportalveinembolizationforhepatitis-relatedhepatocellularcarcinoma:Achangingparadigminmodulationoffutureliverremnantbeforemajorhepatectomy［J］.AnnSurg,2019.［Epubaheadofprint］
［29］SCHADDEE,ARDILESV,SLANKAMENACK,etal.ALPPSoffersabetterchanceofcompleteresectioninpatientswithprimarilyunresectablelivertumorscomparedwithconventional-stagedhepatectomies:Resultsofamulticenteranalysis［J］.WorldJSurg,2014,38(6):1510-1519.
［30］WANGZ,PENGY,HUJ,etal.AssociatingliverpartitionandportalveinligationforstagedhepatectomyforunresectablehepatitisBvirus-relatedhepatocellularcarcinoma:Asinglecenterstudyof45patients［J］.AnnSurg,2018.［Epubaheadofprint］
［31］PENGC,LIC,LIUC,etal.TheoutcomeoftheHCCpatientsunderwentALPPS:Retrospectivestudy［J］.Medicine(Baltimore),2019,98(38):e17182.
［32］NADALINS,CAPOBIANCOI,LIJ,etal.Indicationsandlimitsforassociatingliverpartitionandportalveinligationforstagedhepatectomy(ALPPS).Lessonslearnedfrom15casesatasinglecentre［J］.ZGastroenterol,2014,52(1):35-42.
［33］XIANGF,HUZM.Chanceandchallengeofassociatingliverpartitionandportalveinligationforstagedhepatectomy［J］.HepatobiliaryPancreatDisInt,2019,18(3):214-222.
［34］CHIADKA,YEOZ,LOHSEK,etal.ALPPSforhepatocellularcarcinomaisassociatedwithdecreasedliverremnantgrowth［J］.JGastrointestSurg,2018,22(6):973-980.
［35］TRUANTS,BAILLETC,DESHORGUEAC,etal.ContributionofhepatobiliaryscintigraphyinassessingALPPSmostsuitedtiming［J］.UpdatesSurg,2017,69(3):411-419.
［36］MELANDROF,GIOVANARDIF,HASSANR,etal.MinimallyinvasiveapproachinthesettingofALPPSprocedure:Asystematicreviewoftheliterature［J］.JGastrointestSurg,2019,23(9):1917-1924.
［37］SIRIWARDANARC,LOCM,CHANSC,etal.Roleofportalveinembolizationinhepatocellularcarcinomamanagementanditseffectonrecurrence:Acase-controlstudy［J］.WorldJSurg,2012,36(7):1640-1646.
［38］YOOH,KIMJH,KOGY,etal.Sequentialtranscatheterarterialchemoembolizationandportalveinembolizationversusportalveinembolizationonlybeforemajorhepatectomyforpatientswithhepatocellularcarcinoma［J］.AnnSurgOncol,2011,18(5):1251-1257.
［39］TUSTUMIF,ERNANIL,COELHOFF,etal.Preoperativestrategiestoimproveresectabilityforhepatocellularcarcinoma:Asystematicreviewandmeta-analysis［J］.HPB(Oxford),2018,20(12):1109-1118.
［40］PENGSY,WANGXA,HUANGCY,etal.Evolutionofassociatingliverpartitionandportalveinligationforstagedhepatectomy:Simpler,saferandequallyeffectivemethods［J］.WorldJGastroenterol,2017,23(23):4140-4145.
［41］GARLIPPB,deBAERET,DAMMR,etal.Left-liverhypertrophyaftertherapeuticright-liverradioembolizationissubstantialbutlessthanafterportalveinembolization［J］.Hepatology,2014,59(5):1864-1873.
［42］GABRA,ABOUCHALEHN,ALIR,etal.Outcomesofsurgicalresectionafterradioembolizationforhepatocellularcarcinoma［J］.JVascIntervRadiol,2018,29(11):1502-1510.
［43］CHENGH,SUNG,CHENH,etal.Trendsinthetreatmentofadvancedhepatocellularcarcinoma:Immunecheckpointblockadeimmunotherapyandrelatedcombinationtherapies［J］.AmJCancerRes,2019,9(8):1536-1545.