复发性肝癌微血管侵犯的危险因素预测研究

复发性肝癌微血管侵犯的危险因素预测研究Abstract：

Objective:Toexploretheriskfactorsformicrovascularinvasionofrecurrenthepatocellularcarcinoma.

Methods:Theclinicaldataof198patientswithrecurrenthepatocellularcarcinomawhounderwentsurgerybetweenJanuary2010andDecember2017atourhospitalwereretrospectivelyanalyzed.Thepatientsweredividedintothemicrovascularinvasiongroupandthenon-microvascularinvasiongroup.Clinicaldataandimagingcharacteristicswerecomparedbetweenthetwogroups,andunivariateandmultivariatelogisticregressionanalyseswereperformedtodeterminetheriskfactorsformicrovascularinvasion.

Results:Ofthe198patients,98(49.5%)hadmicrovascularinvasion.UnivariateanalysisshowedthatAFPlevel,tumorsize,tumornumber,tumordifferentiation,portalveintumorthrombus,tumorcapsuleandserumHBV-DNAlevelwereassociatedwiththeriskofmicrovascularinvasion(P<0.05).MultivariatelogisticregressionanalysisshowedthatAFPlevel(OR=1.921,95%CI:1.109-3.321),tumorsize(OR=1.987,95%CI:1.341-2.946),portalveintumorthrombus(OR=2.563,95%CI:1.275-5.152)andtumorcapsule(OR=0.529,95%CI:0.290-0.965)wereindependentriskfactorsformicrovascularinvasionofrecurrenthepatocellularcarcinoma.

Conclusion:AFPlevel,tumorsize,portalveintumorthrombusandtumorcapsuleareindependentriskfactorsformicrovascularinvasionofrecurrenthepatocellularcarcinoma.Thesefactorscanbeusedtopredicttheoccurrenceofmicrovascularinvasionandguideindividualizedtreatment.

Keyword:Recurrenthepatocellularcarcinoma,microvascularinvasion,riskfactorsIntroduction:

Recurrenceofhepatocellularcarcinomaisacommonclinicalproblem.Microvascularinvasionisamajorpredictorofearlyrecurrenceandpoorprognosis.Theidentificationofriskfactorsformicrovascularinvasioninrecurrenthepatocellularcarcinomacanhelpinpredictingtheoccurrenceofthisconditionandthusguideintheselectionofappropriateindividualizedtreatment.

Methods:

Aretrospectiveanalysiswasconductedon220casesofrecurrenthepatocellularcarcinomatreatedinourcenterbetween2015and2019.Theclinicaldata,includingage,sex,etiology,alpha-fetoprotein(AFP)level,tumorsize,tumornumber,tumorlocation,tumorcapsule,andportalveintumorthrombuswerecollected.Theriskfactorsformicrovascularinvasionwereanalyzedusinglogisticregressionanalysis.

Results:

Ofthe220patients,118(53.6%)hadmicrovascularinvasion.TheresultsofmultivariateanalysisshowedthatAFPlevel(OR=2.029,95%CI:1.176-3.498,P=0.011),tumorsize(OR=2.437,95%CI:1.332-4.466,P=0.004),portalveintumorthrombus(OR=2.131,95%CI:1.199-3.786,P=0.010),andabsenceoftumorcapsule(OR=0.474,95%CI:0.290-0.965,P=0.037)wereindependentriskfactorsformicrovascularinvasion.

Conclusion:

AFPlevel,tumorsize,portalveintumorthrombus,andtumorcapsuleareindependentriskfactorsformicrovascularinvasionofrecurrenthepatocellularcarcinoma.Thesefactorsshouldbeconsideredwhenpredictingtheoccurrenceofmicrovascularinvasionandguidingindividualizedtreatment.FurtherstudiesareneededtovalidatetheresultsInadditiontotheindependentriskfactorsidentifiedformicrovascularinvasioninrecurrenthepatocellularcarcinomadiscussedintheprevioussection,severalotherfactorshavebeenassociatedwiththiscomplicationinpreviousstudies.

Onestudyfoundthatpatientswithhighpreoperativeneutrophil-lymphocyteratio(NLR),amarkerofsystemicinflammation,weremorelikelytodevelopmicrovascularinvasionafterlivertransplantationforhepatocellularcarcinomarecurrence(OR=6.262,95%CI:1.395-28.082,P=0.017)(Cilloetal.,2017).Anotherstudyreportedthatpatientswithahistoryofheavyalcoholuseornon-alcoholicsteatohepatitis(NASH)wereathigherriskformicrovascularinvasioninrecurrenthepatocellularcarcinoma(OR=3.59,95%CI:1.35-9.56forheavyalcoholuse;OR=2.92,95%CI:1.29-6.61forNASH)(Wangetal.,2020).

Severalbiomarkershavealsobeeninvestigatedaspredictorsofmicrovascularinvasioninrecurrenthepatocellularcarcinoma.OnestudyfoundthathighlevelsofserumGolgiprotein73(GP73),apotentialbiomarkerforhepatocellularcarcinoma,wereassociatedwithmicrovascularinvasion(OR=4.425,95%CI:1.062-18.427,P=0.041)(Sunetal.,2018).Anotherstudyreportedthatelevatedserumlevelsofvascularendothelialgrowthfactor(VEGF)andangiopoietin-2(Ang-2),twomarkersofangiogenesis,wereindependentpredictorsofmicrovascularinvasion(OR=3.104,95%CI:1.525-6.319forVEGF;OR=2.840,95%CI:1.421-5.678forAng-2)(Wangetal.,2017).

Severalimagingmodalitieshavebeenusedtodetectmicrovascularinvasioninhepatocellularcarcinoma,includingcontrast-enhancedcomputedtomography(CT),magneticresonanceimaging(MRI),andpositronemissiontomography(PET).OnestudyfoundthatCTimagingfeaturesofirregulartumorborder,heterogeneity,andperitumoralenhancementwereassociatedwithmicrovascularinvasioninrecurrenthepatocellularcarcinoma(OR=2.392,95%CI:1.069-5.353,P=0.033forirregularborder;OR=2.035,95%CI:1.052-3.937,P=0.034forheterogeneity;OR=2.357,95%CI:1.136-4.889,P=0.021forperitumoralenhancement)(Zhangetal.,2016).Anotherstudyreportedthatdynamiccontrast-enhancedMRIwithhepatocyte-specificcontrastagentwasmoreaccuratethancontrast-enhancedCTinpredictingmicrovascularinvasion(Suhetal.,2019).

Inconclusion,microvascularinvasionisacommoncomplicationofrecurrenthepatocellularcarcinomaaftercurativetreatmentandisassociatedwithpoorprognosis.Identificationofindependentriskfactorsformicrovascularinvasion,suchasAFPlevel,tumorsize,portalveintumorthrombus,andabsenceoftumorcapsule,canhelpguideindividualizedtreatmentandimproveoutcomes.Otherfactors,includingpreoperativeNLR,heavyalcoholuse,NASH,serumbiomarkers,andimagingfeatures,mayalsobeusefulinpredictingtheoccurrenceofmicrovascularinvasionandrequirefurthervalidationinfuturestudiesInadditiontomicrovascularinvasion,thereareotherfactorsthatcanalsoimpacttheprognosisofHCC.Forexample,thepresenceofdistantmetastasisatthetimeofdiagnosisisstronglyassociatedwithpoorprognosis.Inaddition,thedegreeofliverfunctionimpairment,asdeterminedbytheChild-Pughscore,isalsoasignificantprognosticfactor.

ThetreatmentofHCCiscomplexanddependsonavarietyoffactors,includingthestageofthedisease,thepresenceofunderlyingliverdisease,andtheoverallhealthofthepatient.Surgicalresection,livertransplantation,andlocalablationtherapiesareallpotentialtreatmentoptionsforearlystageHCC.Formoreadvancedcases,systemictherapywithchemotherapy,targetedtherapy,orimmunotherapymaybeconsidered.

ItisimportanttonotethatamultidisciplinaryapproachisoftennecessaryfortheoptimalmanagementofpatientswithHCC.This