婦產(chǎn)科-子宮內(nèi)膜異位癥

子宮內(nèi)膜異位癥EndometriosisEMTDefinition“Presenceofendometrialtissueoutsidetheliningoftheuterinecavity”or

“Proliferationofendometriuminanysiteotherthantheuterinemucosa”定義子宮內(nèi)膜異位癥——具有生長功能的子宮內(nèi)膜組織（腺體和間質(zhì)）出現(xiàn)在子宮腔被覆粘膜及宮體肌層以外的身體其他部位時。Age:commoninreproductiveperiodTrueIncidenceUnknown:?10-15%&30–50%infertility.DoesNOTDiscriminatebyRace.Histology:EndometrialGlandswithStroma+/-InflammatoryReaction.Herdietary(↑↑amongsisters).EpidemiologyAgeatDiagnosis<196%19–2524%26–3552%36–4515%>453%發(fā)病率年齡25—45歲婦女居多；明顯上升趨勢，育齡婦女多見；80%有明顯痛經(jīng)，

50%合倂不孕；妊娠可暫時阻止此病發(fā)展；與遺傳有關(guān)；可出現(xiàn)身體的各個部位，卵巢多見。-Pelvic-ExtrapelvicUmbilicus.Scars(Lap.).Lungs&plura.Others.SitesUterine=Adenomyosis(50%).Extraut:-Ovary30%-Pelvicperitoneum10%.-F.tube.-Vagina.-Bladder&rectum.-Pelviccolon.-Ligaments.PelvicEndometriosisIntroductionWhydoesendometriosishappen?

EndometrialimplantationtheoryRetrogradeVascularandlymphaticMechanicalImmunologicalandgenetictheoryCompositetheoryTheoriesofhistiogenesisPathogenesisEctopictransplantationtheory(異位種植學說）

(DirectImplantation)

70-90%womenhaveretrogrademenstruation(經(jīng)血逆流).Viableendometrialcellsexistintheperitonealfluidinmorethan50%womanduringmenstruation.Implantationofmenstrualtissuehasbeendemonstratedexperimentally(inthemonkeys)andiatrogenic(醫(yī)源性的)implantationoccurs(e.g.endometriosisinthescarofabdominalwallafteranabdominalcesareansection).Oftenpelvicdepositsofendometriosisoccurclosetotheendsofthefallopiantubes.MetaplasiaofCoelomicEpithelium(體腔上皮化生學說)Serosa(漿膜)andperitoneum(腹膜)originatefrommultipotentcoelomicepitheliumPredisposingfactorsGeneticinfluencesIncidenceis6.9%infirst-graderelativesofpatientswithendometriosiscomparedwith1%inacontrolgroup.Incidenceis75%ifoneofthetwinsistershasendometriosis.ImmunedeficiencyMonkeyswithspontaneousendometriosiswerefoundtohaveloweredcell-mediatedresponsetoautologous(自體的)endometrialtissue.Pathogenesis發(fā)病機制

1

子宮內(nèi)膜種植學說：異位內(nèi)膜來源于在位的子宮內(nèi)膜。

經(jīng)血逆流醫(yī)源性種植

淋巴及靜脈播散學說：遠離盆腔的EM

2體腔上皮化生學說：異位內(nèi)膜來源于盆腔腹膜的體腔上皮化生臨床依據(jù)?

3誘導學說：異位內(nèi)膜釋放某種物質(zhì)，如生長因子、巨噬細胞等4相關(guān)因素：遺傳因素、免疫因素、炎癥因素在位內(nèi)膜的特性：在位內(nèi)膜決定論determinantofuterineeutopicendometrium在位內(nèi)膜的特點：功能活躍，血管增生及侵襲力強，易于種植

發(fā)病機制EM是個遺傳性疾?。籈M是個免疫性疾??；EM是個炎癥性疾??；EM是個由于出血性疾??；EM是個器官依賴性疾??；EM是個激素依賴性疾??；Histology:Endometriosisoftheovary:-Theovaryisenlargedandcystic.-Surfaceburntmatchheadappearance.-Tunicaalbuginea--->thickened.Chocolateortarrycysts.EndometrialGlandswithStroma+/-InflammatoryReaction病理特點：廣泛性和多形（多樣）性。主要變化：異位內(nèi)膜隨卵巢激素的變化發(fā)生周期性出血，伴纖維組織增生和粘連形成。

紫褐色斑點

小泡

紫藍色結(jié)節(jié)

囊腫病理卵巢子宮內(nèi)膜異位癥腹膜子宮內(nèi)膜異位癥深部侵潤型內(nèi)異癥其他部位的內(nèi)異癥PathologyGrossappearancePathologyGrossappearanceEndometrioma(子宮內(nèi)膜異位囊腫）Chocolatecyst(巧克力囊腫）PathologyGrossappearance病理——鏡下檢查病灶中子宮內(nèi)膜腺體，子宮內(nèi)膜間質(zhì)，纖維素和紅細胞/含鐵血紅素。反復出血，結(jié)構(gòu)破壞，僅有少量內(nèi)膜間質(zhì)細胞，即可確診斷；手術(shù)及肉眼典型，僅在卵巢壁中發(fā)現(xiàn)紅細胞或含鐵血黃素巨噬細胞，應視內(nèi)異癥。MicroscopicappearancePathologyMicroscopicappearanceSiderocyte(含鐵血黃素細胞)Clinical

FeaturesSymptomsandsignsvaryaccordingtositeoflesions.25%asymptomatic.MenstrualpainorlowerabdominalpainDyspareunia(性交痛)InfertilityAbnormaluterinebleedingPaincausedbyruptureofendometriomaSymptomsandsignsinothersystemscausedbyendometriosis

InfertilityInpatientswithinfertility,incidenceofendometriosisis25%-35%.Inpatientswithendometriosis,infertilityrateis40%.Causes:1)Mechanicalreason2)EnvironmentalchangeintheperitonealcavityActivitychangesofmacrophageAutoimmuneinjuryIncreaseinprostaglandinsClinical

FeaturesCauses(Continued):3)AbnormalovarianfunctionOvulationdefects:17-27%Inadequatedevelopmentofcorporalutea(黃體)Luteinizedunrupturedfolliclesyndrome,LUFS(未破裂卵泡黃素化綜合征):18-79%4)Increaseinspontaneousabortion:40%(vs.normal15%)ClinicalFeaturesInfertility

Menstrualdisorders

15-30%Heavymenses,prolongedmenstruationorpremenstrualspotting.Causes:Damageofovariancortexandadhesionresultsinovariandysfunction,anovulationanddysfunctionofcorporalutea.ClinicalFeaturesSigns

RetrovertedandfixeduterusTendernodulesinrectouterinepouch,uterosacralligament,posteriorwall(lowersegment)andrectovaginalseptumFixedmassalongthesideofuterusClinicalFeatures臨床表現(xiàn)1癥狀（25%患者無癥狀）疼痛：痛經(jīng)和持續(xù)性下腹痛；繼發(fā)性、非正比；月經(jīng)失調(diào)：15—30%經(jīng)量經(jīng)期點滴出血；不孕：50%其他；囊腫破裂，腸道，膀胱，腹壁……。2體征DiagnosisLaparoscopy(“GoldStandard)LaparotomyInconclusive:CA-125,PelvicExam,History,ImagingStudiesBiopsyPreferableOverVisualInspectionClinicalclassificationRevisedAmericanFertilitySociety(R-AFS),1985Usefulfor:AssessmentofseveritySelectionoftherapeuticregimenComparisonPrognosisDiagnosis診斷——輔助檢查病史婦科檢查輔助檢查：B型超聲盆腔核磁+強化CA125測定：<100U/ml；監(jiān)測指標；抗子宮內(nèi)膜抗體：60%以上呈陽性。腹腔鏡檢查：金標準，確診，分期。DiagnosisBultrasound臨床分期1973年Acosta輕、中、重；1985年美國生育協(xié)會RAFS分期標準：病灶大小、粘連程度、直腸窩封閉情況。臨床意義：病變類型（腹膜、卵巢、深部）病變活動狀態(tài)（紅色、白色）

RAFS分期

1.Ovariancysts.2.Pelvicinflammatorydisease.3.OthercausesofnodularityinDouglaspouchastuberculousperitoni-tisandmetastasesofovariancancer.4.Causesofhaematuria,bleedingperrectumandacuteabdominalpainifthepatientispresentedbyoneofthesesymptoms.5.Asymmetricalenlargeduterus.Differentialdiagnosis鑒別診斷卵巢惡性腫瘤：診斷不明，盡快手術(shù)；盆腔炎性包塊：抗炎有效；子宮腺肌癥：可同時存在；治療——目標任何卵巢腫物均應除外惡性縮小和去除病灶減輕和控制疼痛減少卵巢損傷，保護卵泡治療和促進生育預防和減少復發(fā)子宮內(nèi)膜異位癥的藥物治療短效避孕藥:高效孕激素:丹那唑:17?—乙炔睪丸酮衍生物(假絕經(jīng)療法)孕三烯酮:19—去甲睪酮甾類藥物,抗雌,抗孕,GnRH?:合成的十肽類化合物.PainManagement:MedicalTherapyNSAIDsOCPs(Continuous)ProgestinsDanazolGnRH-aGnRH-a+Add-BackTherapyMisc:Opoids,TCAs,SSRIs卵巢抑制是最好的治療GnRHa

降調(diào)節(jié)

垂體FSHLH

卵巢E(低雌激素狀態(tài))

“反向添加”治療

什么是“反向添加”治療在用GnRHa的同時補充雌激素

2—3個月后補多少?

抑制血管神經(jīng)癥狀30pg/ml抑制骨丟失20—40pg/mlEM生長>40pg/ml窗口劑量Treatment

PrinciplesoftreatmentTreatmentshouldbeindividualizedaccordingtothepatient’sage,severityoftheconditionanddesireforchildbearing.Forthosewithmildsymptom:expectanttherapyForthosewhodesirechildbearing:ifconditionismild:medicaltreatmentifconditionissevere:fertilitypreservationsurgeryForthosewhodonotdesirechildbearing:Surgicaltreatment:ovarypreservationorradical

ExpectantTherapyEndometriosistendstoimproveduringpregnancyandmenopause.Follow-upandsymptomsmanagementwithprostaglandinsynthetaseinhibitors(前列腺素合成酶抑制劑)suchas:a)Indomethacin(吲哚美辛)/Indocin(消炎痛)25mgtidp.o.b)Naproxen(萘普生)c)Ibuprofen(布洛芬)300mgtipp.o.d)Diclofenacpotassium(雙氯芬酸鉀片)/Kaflan(凱扶蘭)25-50mgtidp.o.TreatmentTreatment

MedicaltreatmentObjective:causeatrophicchangesintheectopicendometriumProgestins(孕激素)Mechanism:InhibitionofuterinecontractionInhibitionongrowthoftheendometrium1.Pseudopregnancy(假孕)withoralcontraceptives

Atabletoncedailyfor6-12days

2.PseudopregnancywithProgestins(孕激素)

Medicaltreatment

Drugs(Progestins)usedDerivatives(衍生物)fromhydroxyprogesterone(羥孕酮)：(1)Medroxyprogesteroneacetate/provera(醋酸甲羥孕酮/醋酸甲孕酮/安宮黃體酮）30mgdaily(2)Megestrol(甲地孕酮/婦寧片)40mgdaily(3)Longactingdrugsa)Depo-provera(醋酸甲羥孕酮避孕針)150mgmonthlyb)Hydroxyprogesterone(羥孕酮)250mgoncefor2weeksTreatment

Medicaltreatment

Drugs(Progestins)usedDerivativesfrom19-demethyltestosterone(1)Norethindrone(炔諾酮)5mgdaily(2)Gestrinone(孕三烯酮/內(nèi)美通)2.5mgtwiceaweekTreatmentwithprogestinsusuallylast6months.Sideeffects:Intermittentbreakthroughbleeding,nausea,breasttenderness,fluidretention,weightgainTreatment

Medicaltreatment

Danazol（達/丹那唑）AveryfrequentlyuseddrugforendometriosisAweakandrogenAderivativeof17-α-ethinyltestosterone(17-α乙炔睪酮）Mechanism:AnantigonadotrophicagentDirectlysuppressingovariansteroidogenesis(甾體激素生成）

DirectinhibitingendometrialgrowthTreatment

MedicaltreatmentDoses:400-800mg/dayfor6monthsSideeffects:Hypoestrogenicenvironment:deceasedbreastsize,atrophicvaginitis,hotflashes,emotionalswings.Virilism(男性化):weightgain,growthoffacialhair,acne,oilyskin,etc.Treatment

Medicaltreatment

GnRHa(促性腺激素釋放激素激動劑)Mechanism:DesensitizationofthepituitaryMedicalhypophysectomy(藥物性垂體切除)→Medicaloophorectomy(藥物性卵巢切除)Drugsused:Leuprorelin(亮丙瑞林/抑那通）3.75mg,Triptorelin/Decapreptyl(曲譜瑞林/達必佳/達菲林)3.75mg,Goserelin/Zoladex（戈舍瑞林/諾雷德）3.6mg,injection,oncepermonthTreatment

Treatment

MedicaltreatmentSideeffects:(1)Menopausalsymptoms(絕經(jīng)期癥狀):hotflashes,drynessinvagina,lossoflibido(2)Osteoporosis(骨質(zhì)疏松)Expensive子宮內(nèi)膜異位癥的手術(shù)治療

術(shù)式范圍適應征有效率復發(fā)率保守性手術(shù)剝除“巧囊”、切或燒病灶年輕（保留生育功能）分離粘連，卵管整型渴望生育80—90%50%輕、中度40%半根治手術(shù)切除子宮、卵巢病變，保較年輕（保留卵巢功能）留一側(cè)卵巢。無生育要求80%20%中、重度5%根治性手術(shù)切除子宮、雙側(cè)附件年齡較大可見病變無生育要求95%0-1%重度

SurgicaltreatmentIndications:(1)Failedmedicaltreatment(2)Largeendmetrioma(largerthan5-6cm)Modesofsurgicaloperation(1)Fertili