卵巢癌的诊断和治疗

DiagnosisandTreatmentofOvarianCancerShenKengDepartmentofOB/GYNPekingUnionMedicalCollegeHospitalEpidemiologyandGeneticFactorsOvariancanceristhesecondmostcommongynecologicalmalignancy,butthecommonestmalignancyofthefemalegenitaltracttoresultindeathIncidence:Ingeneralpopulationlifetimeriskforovariancancerinawomenisroughly1/70or1.4%.EpidemiologyandGeneticFactorsTheincidenceinAsia,AfricaandLatinAmericaislowerthaninWesterncountries.Themostcommontumortypeisepithelial(85%).卵巢癌的危险因素年龄危险因素家庭史生产史和激素水平EpidemiologyandGeneticFactorsHighriskfactors:

1.Morethan40yrs.2.Caucasianrace(white)3.Latemenopause.4.Infertility5.PositivefamilyhistoryofCAovary6.BRCAgeneEpidemiologyandGeneticFactorsFamilyhistoryisthestrongestriskfactorforovariancancerWomenwithoneaffectedfirstclassrelative:riskrateforovariancanceris5%Womenwithtwoaffectedfirstclassrelative:riskrateforovariancanceris7%AmemberofHOCS:riskrateforovariancanceris20%--50%BRCA1&BRCA2geneassociatedwithHOCSEpidemiologyandGeneticFactorsPrevention&protectivefactorsforovariancancerappeartobeconditionsassociatedwithfewerlifetimeovulations

1.Useoforalcontraceptivepills2.Shorterdurationofreproductiveyears3.Conditionsofchronicanovulation4.Historyofbreastfeeding5.MultiparityHistopathologyEpithelialovariancancer,usuallyclassedsimplyasadenocarcinoma,includeanumberofspecifichistologicaltypes:SerousadenocarcinomaMuconousadenocarcinomaEndometrioidadenocarcinomaMalignantBrennertumor(transitionalcell)ClearcelladenocarcinomaHistopathologyMalignantGermCellTumoroftheOvaryincludeanumberofspecifichistologicaltypes:DysgerminomaYolk-SacTumor(endodermalsinustumor)TeratomasChoriocarcinomaMixedgermcelltumorHistopathologyMalignantTumoroftheGonadalstroma:Granulosal-celltumorsAdulttypeJuveniletypeSertoli-celltumorsLeydig-celltumorsSertoli-Leydig-celltumorsSexcordtumorwithannulartubulesSpreadofovariancancerLocalspreadIntra-abdominalspreadlymphaticspreadhemtogenousspreadSymptomsSymptoms

aremostoftenabsentwithearlystageovariancancer.Whenpresent,symptomstendtobenonspecificGItractcomplaints:

suchasnausea,abdominalcramping,orchangeinbowelhabits,areoftentheearlysymptomsofadvancedstagedisease.Bythistime,thediseasemaybewidelydisseminatedthroughouttheperitonealcavityAbdominaldistention:

bigmass,omentalcake,ascitesintestinalobstructionSymptomsPostmenopausalbleeding

mayoccurfromendometrialhyperplasiastimulatedbyestrogenfromaovariantumor.Virilizationisfoundin50%ofpatientswhohaveanandrogen-secretingSertoli-Leydig-celltumor.Colickypain

isassociatedwithtorsionofamobileovariantumor.Constantpain

maybeexperiencedwiththedistentionofhemorrhageintoatumorPhysicalexaminationFixed,bilateralpelvicmassesAbdominalmass:omentalcake,bigovariantumorAbdominalpercussion:ascitesAnodulartumorinPODPleuraleffusionMeige’ssyndromeconsistsofascitesandhydrothoraxassociatedwithfibromaandthecoma.PreoperativeworkupPapsmear(f)D&CTumormakers:CA125,CEA,HCG,AFP,LDHChestfilmtolookforlungmetastasisandpleuraleffusionPreoperativeworkupBariumenematoevaluatethelowerGItractPlainfilmoftheabdomentoidentifyintestinalobstructionIVPtoassesstheurinarysystemUSG,CTscanorMRItodeterminatetheanatomyrelationshipbetweentheovariancancerandpelvicorgans卵巢癌的MRICourtesyofBarryN.Siskind,MD,TheGraduateHospitalImagingCenter,Philadelphia,PA,USA卵巢肿块直肠PreoperativeworkupPeritoneocentesisforrelivingabdominaldistentionandcytologyexamination.LaparoscopycanbeusedtoobtainedpathologicaldiagnosisofovariancancerpreoperativelyTheroleofSurgeryinthemanagementofovariancancer

Diagnostic

EstablishdiagnosisanddeterminehistologyandgradeofthetumorSurgicalstagingReassessmentLaparotomyTherapeutic

PrimarycytoredutionSecondarycytoreductionProvisionofintravenousandintraperitonelaccessPalliative

Reductionoftumorbulk,RelievegastrointestinalobstructionSurgeriesforovariancancerComprehensivestaginglaparotomyRestaginglaparotomyPrimarycytoreductivesurgeryIntervaldebulkingSecond-looklaparotomySeconddebulking(Recytoreductivesurgery)StandardprocedureofcytoreductivesurgeryforovariancancerLongitudinalincisionAbdominalfluidforcytologyExplorationOmentectomyTotalhysterectomyBilateralsalpingo-oohporectomyPara-aorticandpelviclymphadenectomyLowanteriorresectionofcolonAppendectomy卵巢癌的临床分期卵巢癌I期和II期Ia期

Ic期腹水阳性或Ib期I期II期

IIa期

IIb期

IIc期卵巢癌III期和IV期BeechamSevigne,M閙entodeStadificationdesPrincipalesTumeursSolidesIII期种植性肝转移腹腔腹膜转移肝实质性转移恶性胸膜细胞前锁骨淋巴结IV期DeVitaetal.Cancer:Principles&PracticeofOncology.1993全腹腔探查和活检网膜LymphnodesmetastasisandretroperitonallymphadenectomyinovariancancerLymphaticpathwayisanimportantrouteofmetastasisinovariancancer.Theoverallincidenceofretroperitonealpositivenodes54.3%Theincidenceofpositivepelvicnodes46.7%positivepara-aorticnodes37.5%Bothaorticandpelvicnodespositive48.7%IntestinalmetastasisandoperationinovariancancerRectosigmoidinvolved95.2%Metastasistosmallbowel41.9%Superficialandserosalinvasion64.5%Completeoroptimalresection74.2%resectionofthebowel31.2%Colostomy9.8%27.4%survivalwithmeansurvivaltime30.3monthsConservativesurgeryinovariancancer

Germcelltumor(anystage)StageIgradeIgranulosalcelltumorForepithelialcancer:

1.Youngpatientanddesireofreproduction2StageIa,3.Grade14.Capsuleintake5.Noadhesion6.Peritonealcytologynegative7.Multiplebiopsiesofhighrisknegative8.FollowupavailableManagementofOvarianCancerEarlydiseaseStageIA/BgradeI/IIexploratoryoperation;conservativeresectionpreservefertilityinbilateralborderlinetumoursadjuvanttherapyunprovenUnfavourabletypepoorlydifferentiatedclearcelltumourscapsulepenetrationrupturedcapsulepositivewashingsstageII:standardoperation+adjuvanttherapy早期卵巢癌的化疗ManagementofOvarianCancer

AdvancedstagediseaseStageIII/IVPrimarycytoreductivesurgery/intervaldebulkingObtainedoptimaldebulkung(residualtumor<2cm)Firstlinechemotherapy(6--9courses)

RecurrentdiseasesProgressivedisease/resistantdisease-----salvageChemotherapySensitivedisease(recurrence>6months)---secondarydebunkingfollowingchemotherapy

Palliativetreatment(Radiotherapy,immunotherapy)unprovenChemotherapyinovariancancerFirstlinechemotherapyforepithelialovariancancer

CHexUPandThio-Tepaprotocol(1982-1985)PACorPC(1986-1990)DDP,5-FU,Ara-c,Bleomycin,CTX.IP&IVCombination(1991-1994)Taxol,DDP/Carpa(1995-2000)Weeklytaxol/Carpa(2000--)CombinationChemotherapyCisplatin

actsbybindingtoDNAandproducingcross-linksandDNAadducts.Cisplatin

isaveryeffectivedrugforovariancancer.Importantsideeffects

includeseverenauseaandvomiting,dose-relatednephrotoxicity,ototoxicity,peripheralnerutoxicityandmyelosuppresionCombinationChemotherapyThemechanismofactionof

carboplatin

isthesameasthatofcisplatin,thesideeffects,however,differgreatly.Themostimportantsideeffectisthrombocytopenia.Leukopeniaandanemiaalsooccurbutarelesssevere.NeurotoxicityandnephrotoxicityarelessseverewithcarboplatinthanwithcisplatinOtherimportantsideeffectincludealopeciaandmucositis.CombinationChemotherapyPaclitaxel

actsasamitoticspindlepoison.PaclitaxelisalsoaveryeffectivedrugforovariancanceratthepresenttimeSomepatientsexhibithypersensitivitytopaclitaxel.Othersideeffectincludemyelosuppression,nerotoxicity,mucositis,diarrhea,alopcianauseaandvomiting卵巢上皮癌的化疗晚期卵巢癌的化疗CombinationChemotherapyCombinationchemotherapy

mostoftenisusedaspostoperativetreatmentforadvancedepithelialovariancancer.Combinationchemotherapywithsixcoursesofcisplatinorcarboplatinpluspaclitaxelisthetreatmentofchoiceforpatientswithadvanceddisease.Courses

aregivenevery3to4weekswithmonitoringoftumorstatusbyphysicalexamination.CA125levels,andimagingstudiesifappropriate卵巢癌病人化疗存活率McGuireWPetal.NEnglJMed.1996Post-TherapySurveillanceFollow-upaftertherapyinovariancancerispoorlydefined.AtthepresenttimethereisnodefinitivetestfordetectingthepresenceofmicroscopicrecurrentepithelialovariancancerForthisreasonthereremainssignificantcontroversyastowhatconstitutesoptimalposttherapysurveillance.Post-TherapySurveillanceScreeningmodalities:1.PelvicExamination2.CA125

(44%sensitivity,96%specificity,65%accuracy)3.Ultrasound(20%-89%sensitivity,75%-100%specificity)

4.Second-looklaparotomy5.CTscan

(44%sensitivity,86%specificity,63%accuracy)

6.MIRimaging.6.Positionemissiontomography(PET)

(83%sensitivity,80%specificity,82%accuracy)

卵巢癌复发的诊断和治疗卵巢癌的复发类型(1)化疗敏感型卵巢癌:定义为对初期以铂类药物为基础的治疗有明确反应,且已经达到临床缓解,停用化疗6个月以上,病灶复发.卵巢癌的复发类型(2)化疗耐药型卵巢癌:定义为患者对初期的化疗有反应,但在完成化疗相对短的时间内证实复发,一般认为,完成化疗后6个月内的复发,应考虑为铂类药物耐药卵巢癌的复发类型(3)顽固性卵巢癌:是指在初期化疗时对化疗有反应或明显反应的患者中发现有残余病灶,例如:“二探”阳性者.卵巢癌的复发类型(4)难治性卵巢癌:是指对化疗没有产生最小有效反应的患者,包括在初始化疗期间,肿瘤稳定或肿瘤进展者,大约发生于20%的患者.这类患者对二线化疗的有效反应率最低.卵巢癌复发的治疗

目前观点认为:对于复发性卵巢癌的治疗目的一般是趋于保守性的,因此在选择复发性卵巢癌治疗方案时,对所选择方案的预期毒性作用及其对整个生活质量的影响都应该加以重点考虑.ChemotherapyinOvarianCancerSecondlinechemotherapyforepithelialovariancancer

Patientswithpersistentorrecurrentdiseasesshouldbetreatedwithsecondlinechemotherapy.Unfortunately,responseratesforsecondlinechemotherapyareonly10%to30%.Regardingoftheapproach,secondlinechemotherapyforpersistentorrecurrentovariancancerisnotcurative.Secondlinechemotherapyforepithelialovariancancer

Dependingontheinitialchemotherapy,secondlinechemotherapymayinclude:

TopotecanPaclitaxelPlatinumIfosfamideTaxotereHexamethylmelamineCombinationChemotherapy对复发卵巢癌有效的新药SurvivalEarly-stagediseaseFiveyearsurvivalrateforpatientswithstageIorstageIIdiseaseare80%to100,dependingonthetumorgradeAdvanceddiseaseFiveyearsurvivalrateforpatientswithstageIIIais30%to40%FiveyearsurvivalrateforpatientswithstageIIIbis20%FiveyearsurvivalrateforpatientswithstageIIIcorIVis5%RecurrentdiseaseFiveyearsurvivalrateforpatientswithnegativeSLLis50%

Fiveyearsurvivalrateforpatientswithmicroscopicdiseaseis35%Fiveyearsurvivalrateforpatientswithmacroscopicdiseaseis5%

MalignantGermCellTumoroftheOvaryTwentypercentto25%ofallmalignanttumoroftheovaryareofgermcellorigin.Inthefirstdecadesoflife,70%ofovariantumorsareofgermcelloriginandonethirdaremalignantGermcelltumorsarequiterareafterthethirddecadesoflife.1.Malignantgermcelltumoroftheovaryisverysensitivetothechemotherapy.Chemotherapyhasbeenaveryimportanttreatmentforthiskindovariantumor.2.ChemotherapyhasimprovedthesurvivalofpatientswithMalignantgermcelltumoroftheovarydramatically.Survivalratehasbeenincreasedfrom10%to90%3.ReproductivefunctioncanbepreservedforanystagepatientswithmalignantgermcelltumoroftheovaryMalignantGermCellTumoroftheOvaryManagementofmalignantgermcelltumoroftheovary

Primarytreatmentissurgical.Unilateraloophorectomywithpreservedreproductivefunctionis