卵巢癌的診斷和治療

DiagnosisandTreatmentofOvarianCancerShenKengDepartmentofOB/GYNPekingUnionMedicalCollegeHospitalEpidemiologyandGeneticFactorsOvariancanceristhesecondmostcommongynecologicalmalignancy,butthecommonestmalignancyofthefemalegenitaltracttoresultindeathIncidence:Ingeneralpopulationlifetimeriskforovariancancerinawomenisroughly1/70or1.4%.EpidemiologyandGeneticFactorsTheincidenceinAsia,AfricaandLatinAmericaislowerthaninWesterncountries.Themostcommontumortypeisepithelial(85%).卵巢癌的危險(xiǎn)因素年齡危險(xiǎn)因素家庭史生產(chǎn)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卵巢腫塊直腸PreoperativeworkupPeritoneocentesisforrelivingabdominaldistentionandcytologyexamination.LaparoscopycanbeusedtoobtainedpathologicaldiagnosisofovariancancerpreoperativelyTheroleofSurgeryinthemanagementofovariancancer

Diagnostic

EstablishdiagnosisanddeterminehistologyandgradeofthetumorSurgicalstagingReassessmentLaparotomyTherapeutic

PrimarycytoredutionSecondarycytoreductionProvisionofintravenousandintraperitonelaccessPalliative

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

Ic期腹水陽性或Ib期I期II期

IIa期

IIb期

IIc期卵巢癌III期和IV期BeechamSevigne,M閙entodeStadificationdesPrincipalesTumeursSolidesIII期種植性肝轉(zhuǎn)移腹腔腹膜轉(zhuǎn)移肝實(shí)質(zhì)性轉(zhuǎn)移惡性胸膜細(xì)胞前鎖骨淋巴結(jié)IV期DeVitaetal.Cancer:Principles&PracticeofOncology.1993全腹腔探查和活檢網(wǎng)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早期卵巢癌的化療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卵巢上皮癌的化療晚期卵巢癌的化療CombinationChemotherapyCombinationchemotherapy

mostoftenisusedaspostoperativetreatmentforadvancedepithelialovariancancer.Combinationchemotherapywithsixcoursesofcisplatinorcarboplatinpluspaclitaxelisthetreatmentofchoiceforpatientswithadvanceddisease.Courses

aregivenevery3to4weekswithmonitoringoftumorstatusbyphysicalexamination.CA125levels,andimagingstudiesifappropriate卵巢癌病人化療存活率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)

卵巢癌復(fù)發(fā)的診斷和治療卵巢癌的復(fù)發(fā)類型(1)化療敏感型卵巢癌:定義為對(duì)初期以鉑類藥物為基礎(chǔ)的治療有明確反應(yīng),且已經(jīng)達(dá)到臨床緩解,停用化療6個(gè)月以上,病灶復(fù)發(fā).卵巢癌的復(fù)發(fā)類型(2)化療耐藥型卵巢癌:定義為患者對(duì)初期的化療有反應(yīng),但在完成化療相對(duì)短的時(shí)間內(nèi)證實(shí)復(fù)發(fā),一般認(rèn)為,完成化療后6個(gè)月內(nèi)的復(fù)發(fā),應(yīng)考慮為鉑類藥物耐藥卵巢癌的復(fù)發(fā)類型(3)頑固性卵巢癌:是指在初期化療時(shí)對(duì)化療有反應(yīng)或明顯反應(yīng)的患者中發(fā)現(xiàn)有殘余病灶,例如:“二探”陽性者.卵巢癌的復(fù)發(fā)類型(4)難治性卵巢癌:是指對(duì)化療沒有產(chǎn)生最小有效反應(yīng)的患者,包括在初始化療期間,腫瘤穩(wěn)定或腫瘤進(jìn)展者,大約發(fā)生于20%的患者.這類患者對(duì)二線化療的有效反應(yīng)率最低.卵巢癌復(fù)發(fā)的治療

目前觀點(diǎn)認(rèn)為:對(duì)于復(fù)發(fā)性卵巢癌的治療目的一般是趨于保守性的,因此在選擇復(fù)發(fā)性卵巢癌治療方案時(shí),對(duì)所選擇方案的預(yù)期毒性作用及其對(duì)整個(gè)生活質(zhì)量的影響都應(yīng)該加以重點(diǎn)考慮.ChemotherapyinOvarianCancerSecondlinechemotherapyforepithelialovariancancer

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

Dependingontheinitialchemotherapy,secondlinechemotherapymayinclude:

TopotecanPaclitaxelPlatinumIfosfamideTaxotereHexamethylmelamineCombinationChemotherapy對(duì)復(fù)發(fā)卵巢癌有效的新藥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