卵巢癌診療英文專題知識專家講座

DiagnosisandTreatmentofOvarianCancerShenKengDepartmentofOB/GYNPekingUnionMedicalCollegeHospital卵巢癌診療英文專題知識第1頁EpidemiologyandGeneticFactorsOvariancanceristhesecondmostcommongynecologicalmalignancy,butthecommonestmalignancyofthefemalegenitaltracttoresultindeathIncidence:Ingeneralpopulationlifetimeriskforovariancancerinawomenisroughly1/70or1.4%.卵巢癌診療英文專題知識第2頁EpidemiologyandGeneticFactorsTheincidenceinAsia,AfricaandLatinAmericaislowerthaninWesterncountries.Themostcommontumortypeisepithelial(85%).卵巢癌診療英文專題知識第3頁卵巢癌危險(xiǎn)原因年紀(jì)危險(xiǎn)原因與子宮內(nèi)膜、結(jié)腸、乳腺癌關(guān)系家庭史生產(chǎn)史和激素水平卵巢癌診療英文專題知識第4頁EpidemiologyandGeneticFactorsHighriskfactors:

1.Morethan40yrs.2.Caucasianrace(white)3.Latemenopause.4.Infertility5.PositivefamilyhistoryofCAovary6.BRCAgene卵巢癌診療英文專題知識第5頁EpidemiologyandGeneticFactorsFamilyhistoryisthestrongestriskfactorforovariancancerWomenwithoneaffectedfirstclassrelative:riskrateforovariancanceris5%Womenwithtwoaffectedfirstclassrelative:riskrateforovariancanceris7%AmemberofHOCS:riskrateforovariancanceris20%--50%BRCA1&BRCA2geneassociatedwithHOCS卵巢癌診療英文專題知識第6頁EpidemiologyandGeneticFactorsPrevention&protectivefactorsforovariancancerappeartobeconditionsassociatedwithfewerlifetimeovulations

1.Useoforalcontraceptivepills2.Shorterdurationofreproductiveyears3.Conditionsofchronicanovulation4.Historyofbreastfeeding5.Multiparity卵巢癌診療英文專題知識第7頁HistopathologyEpithelialovariancancer,usuallyclassedsimplyasadenocarcinoma,includeanumberofspecifichistologicaltypes:SerousadenocarcinomaMuconousadenocarcinomaEndometrioidadenocarcinomaMalignantBrennertumor(transitionalcell)Clearcelladenocarcinoma卵巢癌診療英文專題知識第8頁HistopathologyMalignantGermCellTumoroftheOvaryincludeanumberofspecifichistologicaltypes:DysgerminomaYolk-SacTumor(endodermalsinustumor)TeratomasChoriocarcinomaMixedgermcelltumor卵巢癌診療英文專題知識第9頁HistopathologyMalignantTumoroftheGonadalstroma:Granulosal-celltumorsAdulttypeJuveniletypeSertoli-celltumorsLeydig-celltumorsSertoli-Leydig-celltumorsSexcordtumorwithannulartubules卵巢癌診療英文專題知識第10頁SpreadofovariancancerLocalspreadIntra-abdominalspreadlymphaticspreadhemtogenousspread卵巢癌診療英文專題知識第11頁SymptomsSymptoms

aremostoftenabsentwithearlystageovariancancer.Whenpresent,symptomstendtobenonspecificGItractcomplaints:

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

bigmass,omentalcake,ascitesintestinalobstruction卵巢癌診療英文專題知識第12頁SymptomsPostmenopausalbleeding

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

isassociatedwithtorsionofamobileovariantumor.Constantpain

maybeexperiencedwiththedistentionofhemorrhageintoatumor卵巢癌診療英文專題知識第13頁P(yáng)hysicalexaminationFixed,bilateralpelvicmassesAbdominalmass:omentalcake,bigovariantumorAbdominalpercussion:ascitesAnodulartumorinPODPleuraleffusionMeige’ssyndromeconsistsofascitesandhydrothoraxassociatedwithfibromaandthecoma.卵巢癌診療英文專題知識第14頁P(yáng)reoperativeworkupPapsmear(f)D&CTumormakers:CA125,CEA,HCG,AFP,LDHChestfilmtolookforlungmetastasisandpleuraleffusion卵巢癌診療英文專題知識第15頁P(yáng)reoperativeworkupBariumenematoevaluatethelowerGItractPlainfilmoftheabdomentoidentifyintestinalobstructionIVPtoassesstheurinarysystemUSG,CTscanorMRItodeterminatetheanatomyrelationshipbetweentheovariancancerandpelvicorgans卵巢癌診療英文專題知識第16頁卵巢癌MRICourtesyofBarryN.Siskind,MD,TheGraduateHospitalImagingCenter,Philadelphia,PA,USA子宮卵巢腫塊直腸卵巢癌診療英文專題知識第17頁P(yáng)reoperativeworkupPeritoneocentesisforrelivingabdominaldistentionandcytologyexamination.Laparoscopycanbeusedtoobtainedpathologicaldiagnosisofovariancancerpreoperatively卵巢癌診療英文專題知識第18頁TheroleofSurgeryinthemanagementofovariancancer

Diagnostic

EstablishdiagnosisanddeterminehistologyandgradeofthetumorSurgicalstagingReassessmentLaparotomyTherapeutic

PrimarycytoredutionSecondarycytoreductionProvisionofintravenousandintraperitonelaccessPalliative

Reductionoftumorbulk,Relievegastrointestinalobstruction卵巢癌診療英文專題知識第19頁SurgeriesforovariancancerComprehensivestaginglaparotomyRestaginglaparotomyPrimarycytoreductivesurgeryIntervaldebulkingSecond-looklaparotomySeconddebulking(Recytoreductivesurgery)卵巢癌診療英文專題知識第20頁StandardprocedureofcytoreductivesurgeryforovariancancerLongitudinalincisionAbdominalfluidforcytologyExplorationOmentectomyTotalhysterectomyBilateralsalpingo-oohporectomyPara-aorticandpelviclymphadenectomyLowanteriorresectionofcolonAppendectomy卵巢癌診療英文專題知識第21頁卵巢癌臨床分期卵巢癌診療英文專題知識第22頁卵巢癌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期卵巢癌診療英文專題知識第23頁卵巢癌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期卵巢癌診療英文專題知識第24頁卵巢癌診療英文專題知識第25頁卵巢癌診療英文專題知識第26頁卵巢癌診療英文專題知識第27頁卵巢癌診療英文專題知識第28頁卵巢癌診療英文專題知識第29頁卵巢癌診療英文專題知識第30頁卵巢癌治療:手術(shù)(I)DeVitaetal.Cancer:Principles&PracticeofOncology.1993全腹腔探查和活檢網(wǎng)膜幾乎全部病人進(jìn)行全子宮、雙側(cè)輸卵管及網(wǎng)膜切除術(shù)卵巢癌診療英文專題知識第31頁卵巢癌診療英文專題知識第32頁卵巢癌診療英文專題知識第33頁卵巢癌診療英文專題知識第34頁LymphnodesmetastasisandretroperitonallymphadenectomyinovariancancerLymphaticpathwayisanimportantrouteofmetastasisinovariancancer.Theoverallincidenceofretroperitonealpositivenodes54.3%Theincidenceofpositivepelvicnodes46.7%positivepara-aorticnodes37.5%Bothaorticandpelvicnodespositive48.7%卵巢癌診療英文專題知識第35頁卵巢癌診療英文專題知識第36頁卵巢癌診療英文專題知識第37頁卵巢癌診療英文專題知識第38頁卵巢癌診療英文專題知識第39頁IntestinalmetastasisandoperationinovariancancerRectosigmoidinvolved95.2%Metastasistosmallbowel41.9%Superficialandserosalinvasion64.5%Completeoroptimalresection74.2%resectionofthebowel31.2%Colostomy9.8%27.4%survivalwithmeansurvivaltime30.3months卵巢癌診療英文專題知識第40頁卵巢癌診療英文專題知識第41頁Conservativesurgeryinovariancancer

Germcelltumor(anystage)StageIgradeIgranulosalcelltumorForepithelialcancer:

1.Youngpatientanddesireofreproduction2StageIa,3.Grade14.Capsuleintake5.Noadhesion6.Peritonealcytologynegative7.Multiplebiopsiesofhighrisknegative8.Followupavailable卵巢癌診療英文專題知識第42頁ManagementofOvarianCancerEarlydiseaseStageIA/BgradeI/IIexploratoryoperation;conservativeresectionpreservefertilityinbilateralborderlinetumoursadjuvanttherapyunprovenUnfavourabletypepoorlydifferentiatedclearcelltumourscapsulepenetrationrupturedcapsulepositivewashingsstageII:standardoperation+adjuvanttherapy卵巢癌診療英文專題知識第43頁早期卵巢癌化療FIGOI，II期卵巢癌“預(yù)后好”患者90%以上可長久無瘤存活，而且不需要輔助化療。有高危原因患者，30%-40%有復(fù)發(fā)危險(xiǎn)，25%-30%在首次手術(shù)后5年內(nèi)死亡。與復(fù)發(fā)相關(guān)高危原因：（1）包膜破裂（2）腫瘤表面生長（3）低分化（G3）（4）與周圍組織粘連（5）透明細(xì)胞癌（6）腹腔沖洗液陽性（7）卵巢癌外轉(zhuǎn)移卵巢癌診療英文專題知識第44頁ManagementofOvarianCancer

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

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

Palliativetreatment(Radiotherapy,immunotherapy)unproven卵巢癌診療英文專題知識第45頁ChemotherapyinovariancancerFirstlinechemotherapyforepithelialovariancancer

CHexUPandThio-Tepaprotocol(1982-1985)PACorPC(1986-1990)DDP,5-FU,Ara-c,Bleomycin,CTX.IP&IVCombination(1991-1994)Taxol,DDP/Carpa(1995-)Weeklytaxol/Carpa(--)卵巢癌診療英文專題知識第46頁CombinationChemotherapyCisplatin

actsbybindingtoDNAandproducingcross-linksandDNAadducts.Cisplatin

isaveryeffectivedrugforovariancancer.Importantsideeffects

includeseverenauseaandvomiting,dose-relatednephrotoxicity,ototoxicity,peripheralnerutoxicityandmyelosuppresion卵巢癌診療英文專題知識第47頁CombinationChemotherapyThemechanismofactionof

carboplatin

isthesameasthatofcisplatin,thesideeffects,however,differgreatly.Themostimportantsideeffectisthrombocytopenia.Leukopeniaandanemiaalsooccurbutarelesssevere.NeurotoxicityandnephrotoxicityarelessseverewithcarboplatinthanwithcisplatinOtherimportantsideeffectincludealopeciaandmucositis.卵巢癌診療英文專題知識第48頁CombinationChemotherapyPaclitaxel

actsasamitoticspindlepoison.PaclitaxelisalsoaveryeffectivedrugforovariancanceratthepresenttimeSomepatientsexhibithypersensitivitytopaclitaxel.Othersideeffectincludemyelosuppression,nerotoxicity,mucositis,diarrhea,alopcianauseaandvomiting卵巢癌診療英文專題知識第49頁卵巢上皮癌化療鉑基礎(chǔ)治療方案通常聯(lián)合:紫杉醇環(huán)磷酰胺阿霉素通常需要間隔3-4周最少6個(gè)周期治療卵巢癌診療英文專題知識第50頁晚期卵巢癌化療一線治療國內(nèi)順鉑+環(huán)磷酰胺(PC)順鉑+阿霉素+環(huán)磷酰胺(PAC)國外泰素＋順鉑泰素＋卡鉑泰素每七天療法卵巢癌診療英文專題知識第51頁CombinationChemotherapyCombinationchemotherapy

mostoftenisusedaspostoperativetreatmentforadvancedepithelialovariancancer.Combinationchemotherapywithsixcoursesofcisplatinorcarboplatinpluspaclitaxelisthetreatmentofchoiceforpatientswithadvanceddisease.Courses

aregivenevery3to4weekswithmonitoringoftumorstatusbyphysicalexamination.CA125levels,andimagingstudiesifappropriate卵巢癌診療英文專題知識第52頁卵巢癌病人化療存活率McGuireWPetal.NEnglJMed.1996卵巢癌診療英文專題知識第53頁P(yáng)ost-TherapySurveillanceFollow-upaftertherapyinovariancancerispoorlydefined.AtthepresenttimethereisnodefinitivetestfordetectingthepresenceofmicroscopicrecurrentepithelialovariancancerForthisreasonthereremainssignificantcontroversyastowhatconstitutesoptimalposttherapysurveillance.卵巢癌診療英文專題知識第54頁P(yáng)ost-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)

卵巢癌診療英文專題知識第55頁卵巢癌診療英文專題知識第56頁卵巢癌診療英文專題知識第57頁卵巢癌診療英文專題知識第58頁卵巢癌復(fù)發(fā)診療和治療首次規(guī)范化治療(理想腫瘤細(xì)胞減滅術(shù)加上以足夠療程鉑類和/或紫杉醇為基礎(chǔ)聯(lián)合化療)70%-80%患者可取得臨床完全緩解.60%-70%患者最終還會復(fù)發(fā).對卵巢癌復(fù)發(fā)診療和治療是卵巢癌治療中最為棘手問題.怎樣合理處理復(fù)發(fā)性卵巢癌意見尚不統(tǒng)一卵巢癌診療英文專題知識第59頁卵巢癌復(fù)發(fā)類型(1)化療敏感型卵巢癌:定義為對早期以鉑類藥品為基礎(chǔ)治療有明確反應(yīng),且已經(jīng)到達(dá)臨床緩解,停用化療6個(gè)月以上,病灶復(fù)發(fā).卵巢癌診療英文專題知識第60頁卵巢癌復(fù)發(fā)類型(2)化療耐藥型卵巢癌:定義為患者對早期化療有反應(yīng),但在完成化療相對短時(shí)間內(nèi)證實(shí)復(fù)發(fā),普通認(rèn)為,完成化療后6個(gè)月內(nèi)復(fù)發(fā),應(yīng)考慮為鉑類藥品耐藥卵巢癌診療英文專題知識第61頁卵巢癌復(fù)發(fā)類型(3)頑固性卵巢癌:是指在早期化療時(shí)對化療有反應(yīng)或顯著反應(yīng)患者中發(fā)覺有殘余病灶,比如:“二探”陽性者.卵巢癌診療英文專題知識第62頁卵巢癌復(fù)發(fā)類型(4)難治性卵巢癌:是指對化療沒有產(chǎn)生最小有效反應(yīng)患者,包含在初始化療期間,腫瘤穩(wěn)定或腫瘤進(jìn)展者,大約發(fā)生于20%患者.這類患者對二線化療有效反應(yīng)率最低.卵巢癌診療英文專題知識第63頁卵巢癌復(fù)發(fā)治療治療前準(zhǔn)備:詳細(xì)復(fù)習(xí)病史包含:(1)手術(shù)分期.(2)組織學(xué)類型和分級.(3)手術(shù)徹底性.(4)和殘余瘤大小及部位.(5)術(shù)后化療方案,路徑,療程,療效.(6)停用化療時(shí)間.(7)出現(xiàn)復(fù)發(fā)時(shí)間等.對復(fù)發(fā)性卵巢癌進(jìn)行定性、分型、定位分析對患者生活狀態(tài)(PS)進(jìn)行評分,對患者主要器官功效進(jìn)行評定.卵巢癌診療英文專題知識第64頁

當(dāng)前觀點(diǎn)認(rèn)為:對于復(fù)發(fā)性卵巢癌治療目標(biāo)普通是趨于保守性,所以在選擇復(fù)發(fā)性卵巢癌治療方案時(shí),對所選擇方案預(yù)期毒性作用及其對整個(gè)生活質(zhì)量影響都應(yīng)該加以重點(diǎn)考慮.卵巢癌診療英文專題知識第65頁復(fù)發(fā)性卵巢癌手術(shù)治療手術(shù)對復(fù)發(fā)性卵巢癌治療價(jià)值還未確定,手術(shù)指征和時(shí)機(jī)還存在一些爭論.復(fù)發(fā)性卵巢癌手術(shù)治療主要用于三個(gè)方面:

1.解除腸梗阻

2.>12個(gè)月復(fù)發(fā)灶減滅.3.切除孤立復(fù)發(fā)灶.對晚期復(fù)發(fā)卵巢癌是先手術(shù)還是先化療仍有爭議.卵巢癌診療英文專題知識第66頁ChemotherapyinOvarianCancerSecondlinechemotherapyforepithelialovariancancer

Patientswithpersistentorrecurrentdiseasesshouldbetreatedwithsecondlinechemotherapy.Unfortunately,responseratesforsecondlinechemotherapyareonly10%to30%.Regardingoftheapproach,secondlinechemotherapyforpersistentorrecurrentovariancancerisnotcurative.卵巢癌診療英文專題知識第67頁Secondlinechemotherapyforepithelialovariancancer

Dependingontheinitialchemotherapy,secondlinechemotherapymayinclude:

TopotecanPaclitaxelPlatinumIfosfamideTaxotereHexamethylmelamineCombinationChemotherapy卵巢癌診療英文專題知識第68頁對復(fù)發(fā)卵巢癌有效新藥卵巢癌診療英文專題知識第69頁SurvivalEarly-stagediseaseFiveyearsurvivalrateforpatientswithstageIorstageIIdiseaseare80%to100,dependingonthetumorgradeAdvanceddiseaseFiveyearsurvivalrateforpatientswithstageIIIais30%to40%FiveyearsurvivalrateforpatientswithstageIIIbis20%FiveyearsurvivalrateforpatientswithstageIIIcorIVis5%RecurrentdiseaseFiveyearsurvivalrateforpatientswithnegativeSLLis50%

Fiveyearsurvivalrateforpatientswithmicroscopicdiseaseis35%Fiveyearsurvivalrateforpatientswithmacroscopicdiseaseis5%

卵巢癌診療英文專題知識第70頁MalignantGermCellTumoroftheOvaryTwentypercentto25%ofallmalignanttumoroftheovaryareofgermcellorigin.Inthefirstdecadesoflife,70%ofovariantumorsareofgermcelloriginandonethirdaremalignantGermcelltumorsarequiterareafterthethirddecadesoflife.卵巢癌診療英文專題知識第71頁1.Malignantgermcelltumoroftheovaryisverysensitivetothechemotherapy.Chemotherapyhasbeenaveryimportanttreatmentforthiskindovariantumor.2.ChemotherapyhasimprovedthesurvivalofpatientswithMalignantgermcelltumoroftheovarydramatically.Survivalratehasbeenincreasedfrom10%to90%3.ReproductivefunctioncanbepreservedforanystagepatientswithmalignantgermcelltumoroftheovaryMalignantGermCellTumoroftheOvary卵巢癌診療英文專題知識第72頁Management