恶性嗜铬细胞瘤的治疗

TherapyofMalignantPheochromocytoma恶性嗜铬细胞瘤的治疗LiteratureReport2020/1/12Introductionruleof10sforpheochromocytoma(PCC)10%bilateral10%extra-adrenal10%extra-abdomen10%malignant10%familial10%children10%normalbloodpressure2020/1/13IntroductionThemostfrequentsiteofmetastasesistheskeletonAdditionalsitesareliver,retroperitoneumwithlymphnodes,CNS,pleura,andkidney2020/1/14Malignantvs.BenignCurrently,thereisnoeffectivecureformalignantpheochromocytoma.Therearealsonoreliablehistopathologicalmethodsfordistinguishingbenignfrommalignanttumors.Malignancyrequiresevidenceofmetastasesatnon-chromaffinsitesdistantfromthatoftheprimarytumor.2020/1/15Metastaticdiseaseinpheochromocytomamaybepresentatthetimeofinitialdiagnosisormayonlybecameevidentaftersurgicalremovaloftheprimarytumor,usuallywithin5years,butsometimes16ormoreyearslater.2020/1/16Duetotherarityofthetumor,clinicalstudiesaboutpheochromocytomasufferfromafragmentednatureandusuallyinvolvetoosmallanumberofcasestoreachconclusiveresults.2020/1/17Becausethereiscurrentlynoeffectivecureformalignantpheochromocytoma,mosttreatmentarepalliative,butinsomecasesmayreducetumorburdenandprolongsurvival.Withouttreatment,the5-yearsurvivalisgenerallylessthan50%.Thecourse,however,canbehighlyvariablewithoccasionalpatientslivingmorethan20yearsafterdiagnosis.2020/1/18Oncemalignancyisdiagnosed,therapyisgenerallydirectedatcontrollingbloodpressure,butmayalsoincludetumordebulking.2020/1/19AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization2020/1/110AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization2020/1/111PrimarysurgicalresectionisthetreatmentofchoicewheneverpossibleLimiteddisease:curativeintentionExtendeddisease:stilltobeconsideredinthefirstplacefordebulkingandaspalliativetreatment(Mundschenketal.1998)2020/1/112ProblemWhensignsofregionalinvolvementordistantdiseaseareabsent,thereiscurrentlynoreliablepreoperativediagnostictestthatcandifferentiatebetweenmalignantandbenignpheochromocytomasShouldpheochromocytomasizeinfluencesurgicalapproach?2020/1/113Acomparisonof90malignantand60benignpheochromocytomas(WenT.Shenetal.2004)ComparisonoftumorsizeforbenignpheochromocytomasandmalignantpheochromocytomaswithlocaldiseaseonlySizedoesnotreliablypredictmalignancyinpheochromocytomaswithlocaldiseaseonly2020/1/114Malignant(n=29)Benign(n=55)Tumorsize(mean±SD)6.1±3.1cm5.3±2.3cm2cm012.0-3.9cm9104.0-5.9cm6256.0-7.9cm5138.0-9.9cm53≥10cm432020/1/115MalignantPCCspresentingwithonlylocaldiseasecannotbediscriminatedfrombenignPCCsbysizealone.WhenPCCsdonothaveevidenceofinvasionordistantmetastasesandthesurgeonacquiresanappropriatelevelofexperience,themajorityofthesetumorscanbesafelyresectedlaparoscopically.2020/1/116Laparoscopicadrenalectomyforpheochromocytomashouldbeconvertedtoopenadrenalectomyfordifficultdissection,invasion,adhesions,orsurgeoninexperience2020/1/117SurgicalapproachTransabdominalapproachisnecessaryminimallyinvasiveproceduresretroperitonealapproachesshouldbeabandonedtodefinitelypreservethetumorcapsuleandperformtotallymphadecectomy(Orchardetal.1993)2020/1/118SecondaryTumorsNoexperiencewithadjuvantpreandpostoperativeradiationexistsGenerallyaremultipleRadicalsurgicalresectionisoftenimpossibleOthertreatmentmodalitieshavetobeconsidered2020/1/119AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization2020/1/1202020/1/121131I-MIBGisthetreatmentofchoiceforallunresectable,MIBGpositivetumors58casesofmalignantPCCtreatedby131I-MIBG—therapeuticresultsandadverseevents(ZHURuisenetal.1999)2020/1/122Patientswereclassifiedinto3groupsaccordingtotheirtumorsize8cm3(11cases),8～20cm3(21cases),20cm3(26cases)Ingroup1,themeanabsorptiondosepergramoftumorwasabove1000cGy.Aftertreatment,tumorsdisappearedorshrinkedinallpatients2020/1/123Ingroup2,theabsorptiondosewassimilartothatofgroup1,butthemeanabsorptiondosepergramwas717.6cGy,andtumormassregressionwas36%;76%reducedurinarycatecholamineIngroup3,theabsorptiondosepergramtumortissuewas277cGy,and30%tumorenlargement,20%died;theremaining50%symptomaticimprovementwithoutanychangeintumorsize2020/1/124131I-MIBGisofcertaintherapeuticeffectivenessofsymptomaticimprovementCompletetumormassdisappearancehasonlybeenfoundinsmalltumorsTreatmentwith131I-MIBGshouldbeinstitutedimmediatelyaftersurgicalresectiontoeradicatetheresidualtumorcellsandtopreventrecurrencesBonemarrowsuppressionistemporaryandnotdosagerelated2020/1/125In1997,Lohetal.publishedareviewoftheworldwideexperienceinvolving116patientstreatedwith131I-MIBGformalignantpheochromocytoma.Overall,therewasasymptomaticresponsein76%,ahormonalresponsein45%,andtumorregressionin30%.Theactivityof131I-MIBGpersingledosewas96–300mCi,andthemeancumulativeactivitywas490±350mCi.OnlyfiveCRsto131I-MIBGwerereported.2020/1/126LimitationsNotallpatientswithmultiplemetastasesofmalignantpheochromocytomashavesufficientuptakeofMIBGtoallowMIBGtherapyMIBGnegativelesionscoexistwithMIBGpostivelesion