DiagnosisandTreatmentofOvarianCancerShenKengDepartmentofOB/GYNPekingUnionMedicalCollegeHospitalEpidemiologyandGeneticFactorsOvariancanceristhesecondmostcommongynecologicalmalignancy,butthecommonestmalignancyofthefemalegenitaltracttoresultindeathIncidence:Ingeneralpopulationlifetimeriskforovariancancerinawomenisroughly1/70or1.4%.EpidemiologyandGeneticFactorsTheincidenceinAsia,AfricaandLatinAmericaislowerthaninWesterncountries.Themostcommontumortypeisepithelial(85%).卵巢癌的危險因素年齡危險因素家庭史生產史和激素水平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期種植性肝轉移腹腔腹膜轉移肝實質性轉移惡性胸膜細胞前鎖骨淋巴結IV期DeVitaetal.Cancer:Principles&PracticeofOncology.1993全腹腔探查和活檢網膜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)

卵巢癌復發的診斷和治療卵巢癌的復發類型(1)化療敏感型卵巢癌:定義為對初期以鉑類藥物為基礎的治療有明確反應,且已經達到臨床緩解,停用化療6個月以上,病灶復發.卵巢癌的復發類型(2)化療耐藥型卵巢癌:定義為患者對初期的化療有反應,但在完成化療相對短的時間內證實復發,一般認為,完成化療后6個月內的復發,應考慮為鉑類藥物耐藥卵巢癌的復發類型(3)頑固性卵巢癌:是指在初期化療時對化療有反應或明顯反應的患者中發現有殘余病灶,例如:“二探”陽性者.卵巢癌的復發類型(4)難治性卵巢癌:是指對化療沒有產生最小有效反應的患者,包括在初始化療期間,腫瘤穩定或腫瘤進展者,大約發生于20%的患者.這類患者對二線化療的有效反應率最低.卵巢癌復發的治療

目前觀點認為:對于復發性卵巢癌的治療目的一般是趨于保守性的,因此在選擇復發性卵巢癌治療方案時,對所選擇方案的預期毒性作用及其對整個生活質量的影響都應該加以重點考慮.ChemotherapyinOvarianCancerSecondlinechemotherapyforepithelialovariancancer

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

Dependingontheinitialchemotherapy,secondlinechemotherapymayinclude:

TopotecanPaclitaxelPlatinumIfosfamideTaxotereHexamethylmelamineCombinationChemotherapy對復發卵巢癌有效的新藥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