卵巢腫瘤教案

中南大學教案紙【科目】婦產科學【授課教師】陶光實【授課對象】2002級七年制.【授課地點】第1教室【授課章節(jié)】第三十二章【學時】2學時【授課內容】卵巢腫瘤【授課時間】2006.11.29一、教學目的與要求1.了解卵巢腫瘤的組織學分類，常見卵巢腫瘤的病理和臨床特點。2．熟悉卵巢良、惡性腫瘤的鑒別診斷。3．掌握卵巢腫瘤的臨床表現(xiàn)、診斷、鑒別診斷、治療原則、常見并發(fā)癥及其處理。4．熟悉妊娠合并卵巢腫瘤的危害及處理原則。二、教學重點重點：常見卵巢腫瘤的病理和臨床特點；良、惡性腫瘤的鑒別診斷；常見的并發(fā)癥及其診斷；惡性腫瘤的分期和處理原則。三、教學難點難點：卵巢腫瘤的分類；惡性腫瘤的分期和處理原則；常用化療方案及藥物。四、授課類型及方法1．大課講授法。2．采用雙語教學結合病例式、問題式、討論式等教學方法，培養(yǎng)學生臨床思維方式及解決實際問題的能力。3．一般了解的內容學生自習。五、教具多媒體課件、電腦、投影儀、激光筆、揚聲器、粉筆及粉筆刷。六、教學內容與步驟分配時間導言（preambl）：卵巢腫瘤的現(xiàn)狀、發(fā)病率及診治情況。卵巢腫瘤（variantumor）一、卵巢的解剖及生理特點(anatomyandphysiology)2minComplexstructureandfunction：中南大學教案紙Celomicepithelium(體腔上皮)--單層立方.supportivestroma(支持間質)—白膜,性索間質,結締組織,血管、神經和淋巴.Functionalgermcells(生殖細胞).Endocrineandreproductivefunction.二、卵巢腫瘤概論(generalconsideration)25min一).Incidence,Epidemiology●Morbidityisabout2.4-5.6%inourcountry.Ovariancanceristhesecondmostcommontumorinfemalepelvicreproductiveorgans,Accountsfor5%ofallcancersamongwomen.Generalconsideration,Theoverallriskofovariancancerisabout1.7%inthegeneralpopulation,itwilldevelopin1ofevery58women(1/58).In5%to7%thereisaninheritedpredispositionincreasingtheriskforotherfamilymembersinsomesyndromestoashighas50%.●Deaths----occuratrateof1every45minutes.●Liabletogettumors（多事之秋）.●Mostinkindsoftumors（種類之多居全身各器官腫瘤之冠）.●Deepinpelvic（深居盆腔），stealthilyoccuring(悄悄地來）.●Destituteinearlydiagnosismethods缺乏早期診斷方法.●Poorprognosisingynecologiconcology:5-yearssurvivalrateisabout30%（是預后最差的婦科腫瘤，死亡率是宮頸癌和內膜癌之和）.二).Classification（分類）ThesimplifiedWHOclassification（簡化的WHO分類）iswidelyacceptedinourcountry.Accordingthehistogenensis（組織發(fā)生）ovarianneoplasmsareclassifiedintoninegroups（九大類）.三).Routeofmetastasis（轉移途徑）●Directspreading（直接蔓延）●Inta-abdominalimplantation（腹腔種殖）●Lymphogenousmetastasis（淋巴轉移）●Hematogenousmetastasis（血行轉移）Directspreadingandinta-abdominalimplantationarethemainroutesofmetastasis.中南大學教案紙四).Clinicalfeature(臨床表現(xiàn))1.Symptoms(癥狀):●Benign(良性):Inearlystagenosymptoms. Amassnearbytheuterusfoundduringroutinepelvicexamination(往往婦查時發(fā)現(xiàn),在子宮一側捫及包塊).pressuresymptomssuchasabdominalswelling（腹脹）,frequencyofuring（尿頻）andconstipation（便秘）.Symptomswhenoccuringcomplications.Malignant（惡性）:Inearlystagenosymptoms，whenappearingsymptoms,itisofteninlatestageabout70%ofpatients.Symptomsincluding:Vaginalbleeding---postmenopausal(絕經后)Abdominalswelling（腹脹）Abdominalmass(腹部包塊）pressuresymptoms:abdominalpain(腹痛)lumbago（腰痛）lowerlimbs’painandedema(下肢疼痛或水腫）●三聯(lián)癥:A.Over40yearsage(40歲以上婦女)B.Symptomsofalimentarytract(不明原因胃腸道癥狀)C.Disorderofovarianfunction(卵巢功能紊亂)2．Sign(體征):Mass(Unilateralorbilateral,solid,immovable)捫及單側或雙側包塊,質硬,不活動。Ascites腹水征(+)Cancercellsinascites（腹水癌細胞,異常染色體核型）。五）.Complications（并發(fā)癥）:1.Torsionofthepedicle(蒂扭轉):Acutesymptomssuchassevereabdominalpain(腹痛)、nausea(惡心)、vomiting(嘔吐)andfever(發(fā)熱).Palpabledatendermass(壓痛包塊)inpelvicexamination(盆腔檢查).中南大學教案紙Incidenceisabout10%ofovariantumors.Itisthemostcommonemergencydiseaseofgynecology,surgicaltreatmentshallbegivenassoonasdiagnosis(一經確診需立即手術治療.)Thepedicle(蒂)----theroundligamentofovary,infundibulopelvicligament,fallopiantube.手術注意點:鉗夾前不可回復扭轉,以防止發(fā)生栓塞脫落.2.Rupture（破裂）Spontaneous（自發(fā)性）rupture:腫瘤浸潤、生長過速.Traumatic（外傷性）rupture:重擊、分娩、性交、婦科檢查及穿刺.eritonealirritation（腹膜刺激癥）3.Infection（感染）:Seeninthepuerperium（產褥期）.bruisedduringlabor（分娩期損傷）.Temperatureishigher,cystmoretender（體溫升高、囊腫變軟）.Adhesion（粘連）oftenfollowtorsionorinfection(扭轉和感染).4.Malignantchange（惡變）:Therateofmalignantchangeis:Serouscystadenoma(漿液性囊腺瘤)--30-45%mucinouscystadenoma(粘液性囊腺瘤)--15%Dermoidcyst(皮樣囊腫)--2-5%Themajorsymptoms(主要癥狀)areabdominalswellingandpain六)．Staging（分期）:StagingClassificationusingtheFIGONonmenclature.Itissurgicalandbasedontheoperativefindings.七).Diagnosisanddifferentialdiagnosis(診斷及鑒別診斷):1.Diagnosis1).History(病史):不育、子宮內膜癌或乳腺癌病史、卵巢癌家族史.2).Clinicalsigns(臨床依據):50-60歲圍絕經期、腹脹、腹痛及胃腸不適、盆腹腔包塊、子宮直腸窩結節(jié)、腹水.注意絕經后卵巢大小的生理變化，絕經晚期婦查捫及卵巢應高度懷疑,探查指征.3).Assistantdiagnosismethods(輔助診斷方法):中南大學教案紙①Ultrosography(B超):②Irradiation（放射檢查):X-rayfilm:diagnosisofteratomaBariummeal(鋇餐):排除胃腸道腫瘤或侵犯情況IVP(intravenouspyelogram)盆腔腎、尿管阻塞或移位Lymphangiography：淋巴有無轉移CT：侵犯及轉移情況，腸梗阻診斷③Cyologicexamination(細胞學檢查):約80-90%腹水細胞學(+)④Laparoscopy(腹腔鏡):比較直觀,但有一定的限制.⑤Tumormarkers(腫瘤標志物):Epitheliumneoplasms(上皮性卵巢腫瘤)----CA125,LDHEndodermalsinustumor(內胚竇瘤)----AFP(未成數(shù)畸胎瘤,混和性無性細胞瘤含卵黃囊成分).Choriocarcinoma(卵巢絨癌)----HCGSexcordstromaltumors(性索間質腫瘤)----Estrogen2．Differentialdiagnosis1).benignovarianneoplasm:Non-neoplasticcystoftheovary.tuboovariancyst.Subserousmyomaofuterus（子宮肌瘤）.Earlypregnancy.Distendedbladder.Ascites（腹水）.2).malignantovarianneoplasm:Endometriosis(子宮內膜異位癥).Pelvictuberculesis(盆腔結核).Tumorsofotherorgans-mesenteric（腸系膜）,renal,omental（網膜）andpancreatictumors.Retroperitonealtumors（腹膜后腫瘤）.Metastasistumors(轉移性腫瘤).3).Differentiationbetweenbenignandmalignantovariantumors(良惡中南大學教案紙性卵巢性卵巢腫瘤鑒別診斷).4).DifferentiationDiagnosisofAdnexalMass(附件包塊的鑒別診斷)●GynecologicOrigin(婦科來源)aUterineMasses(子宮包塊)bOvarianMasses(卵巢包塊)FunctionalCysts(功能囊腫)OvarianNeoplasms(腫瘤)cEndometriosis(子宮內膜異位癥)dTubalMasses(卵管包塊)●NongynecologicOriginaBowelbMiscellaneous八).Treatment(治療):1.Forbenigntumors(良性):1).Observation（觀察）:Under5cm---nonneoplasticandmaydisappearspontaneouslywithin60days（直徑小于5CM可觀察）.Ifenlargementsover5cm,treatmentrequired（直徑大于5CM需治療）.2).Surgicaltreatment(手術治療).aSurgerymodelselectiondependuponages(根據年齡決定手術方式)bUnilateralcystectomyorcystoophorectomy（單側腫瘤或卵巢切除）cBilateralsalpingo-oophorectomyandhysterectomy（雙附件和子宮切除）over50yearsofageserouscystadenomas術中注意排除惡性腫瘤,必要時送快速切片.2.Formalignantovariantumor(惡性):以手術(surgicaltreatment)和化療(chemotherapy)為主,放療(radiationtherapy),(immunotherapy)免疫治療為輔的綜合治療.三、上皮性腫瘤(epithelialovariancancer)23min一).Serouscystoma1.serouscystadenoma（漿液性囊腺瘤）.Mostcommonofallbenignovarianneoplasm,Accountsfor25%ofbenignovariantumors.中南大學教案紙Unilocular（單房）ormultilocular（多房）.Bilateralin15%ofcases.Notexceed10cmindiameter.Thecystfluid（囊液）isusuallythinandserous（稀薄清亮）.Theliningepitheliumislowcolumar（上皮為低柱狀排列）.Psammomabodies（沙粒體）aresometimespresentinthecystwall（囊壁）.2.Borderline（交界性）serouscystoma:Bilateral（雙側）inmostofcases.Papillarygrowth（乳頭生長）—External（外生）orEnternal（內生）Macroscopicfeatures（鏡下特征）:Epitheliumcelllayers（上皮細胞層）<3；Lowgradeproliferativeactivity(低增殖活性)；Nuclearabnormalities（核異型）；Nostromainvasion(無間質浸潤).3.Serouscystadnocarcinoma(漿液性囊腺癌）:Mostcommonofallmaliagnantovariantumor.Instituteabout40-50%.Usuallyappearduringthe40-60yearsandbilateral.Ascites（腹水）usuallypresentandimplyapoorprognosis（不良預后）.Microscopicfeatures:Theepitheliumishighlyintricate（高度紊亂）over4-5celllayersAnaplastic（異型）andatypicalstromalinvasion（典型間質浸潤）.Thegeneral5-yearsurvivalrate（5年存活率）isabout20-30%.二).Mucinouscystomas1.Mucinouscystadenoma（粘液性囊腺瘤）:Accountfor20-30%.Usuallymultilocular（多房）andmaygrowtoaverylargesize.Cancerationrate（癌變率）is5-10%.Thecystfluidismucinousmateralasgelatinous（膠凍狀粘液）.Spontaneousrupture（自發(fā)破裂）rateis2-5%.Ifrupture,theepitheliumcellsmayseedontotheperitoneumandproduceapseudumyxomaperitonei(假性腹膜粘液瘤）.中南大學教案紙Microscopicfeatures:Thecellsliningthecystcavityaretallandcolumnar（高柱狀）.2.Borderlinemucinouscystadenoma:Majorsize,bilateral（雙側）infewofcases,multilocular（多房）.Proliferativeactivity（增生活躍）.Nuclearabnormalities（核異型）.Epitheliumofcelllayers〈3.Nostromainvasion（無間質浸潤）.Prognosisisbetter.3.Mucinouscystadenocarcinoma（粘液性囊腺癌）:Instituteabout10%ofallmalignantovariantumors.Unilateralinmostofcases（多為單側）.Majorsize,thecystcavityissolidlyfilledwithmassofpapillaryprojections（乳頭狀腫塊）.Microscopicfeatures:Lesionwithmorethan4mitoses（核分裂）perhighpowerfield（每高倍視野）hasapoorprognosis,eveninstagIdisease.三）.上皮性卵巢癌的治療(management)：1.早期患者（forstageI-II)----全面確定分期的探查手術（comprehensivestaginglaparotomy):a.腹部縱切口；b.全面盆腹探查；c.腹腔細胞學；d.大網膜切除；e.全子宮+雙附件切除（卵巢動靜脈高位結扎）；f.仔細探查及活檢；g.盆腔及腹主動脈旁淋巴活檢.2.晚期患者(forstageIIandover)----腫瘤細胞減滅術(cytoreductivesurgery,debulking):1).最大努力切除原發(fā)灶及一切轉移瘤，使殘余癌灶<1cm.●切除范圍：a.足夠大的腹部縱切口；b.腹水或腹腔沖洗液細胞學檢查，全面盆腹探查；c.全子宮+雙附或盆腔腫物切除（卵巢動靜脈高位結扎）；d.大網膜切除，注意肝、脾區(qū)轉移并切除；e.高危區(qū)轉移灶切除及多點活檢；f.肝、脾轉移灶處理；g.盆腔及腹主動脈旁淋巴切除；h.闌尾切除及腸轉移處理.2).再分期手術（restaginglaparotomy)中南大學教案紙3).開腹活檢術4).中間性腫瘤細胞減滅術(intervalcytoredution)5).二次探查術(second-looklaparotomy)3.化療(Chemotherapy)：主要輔助治療?；熋舾蓄A防復發(fā)適合于各期患者,以鉑類為主的化療方案方案-----PC（順鉑+環(huán)磷酰胺）PT（順鉑+泰素）手術前化療-----應在有病理結果后進行4).免疫治療(Immunitherapy)：適合于各期患者，輔助性。四、Non-epithelialovarianneuplasm(非上皮性腫瘤)20min1.Ovariangermcelltumor（生殖細胞腫瘤）1).Teratoma（畸胎瘤）①Mature（成熟性）teratoma(orcystic[囊性]teratoma,dermoidcyst[皮樣囊腫]):Comprises10-20%ofalltrueovarianneoplasm.Constituteabout85-97%ofovariangermcelltumor,about95%ofteratoma.Mostarefoundduringtheearlyreproductiveyears(20-40).Usuallyamoderatesizeandwithbilateralin10-17%,unilocular（單房）.Cystcontentsareusuallyskin,hair,adiposeandsebaceousmaterial,bone,teethandcartilage（軟骨）.Oftenvisibleonx-rayfilm.Microscopically,variousofallthreegermcelllayers（3種胚層）maybefound.Cancerationrateis2-4%(mostinpostmenopause).Malignantchangeusuallysquamouscellcarcinomadevelopinginoneoftheepidermalelements（頭節(jié)）ofthecyst.②Immatureteratoma（未成熟畸胎瘤）:Derivedfrom（起源于）allthreegermlayersusually2-3layers.Accountfor1-3%ofovarianteratoma.中南大學教案紙Thedegreeofmalignancyiscloselycorrelatedwiththeproportionofimmaturetissue（未成熟組織比例）,degreeofdifferentiation（分化程度）andneurepithelium（神經上皮）.Mostduringinjuvenility(meanageis11-19).2).Dysgerminoma（無性細胞瘤）About80%arefoundinpatientsunder25yearsofage.Comprisesabout5%ofallmalignantovarianneoplasms.Radiosensitiveand5-yearssurvivalrateis90%.3).Endodermalsinustumor(yolksactumor)[內胚竇瘤]Usuallyoccurinenfantandyoungwomen.ProducingAFP.poorprognosis.2.Ovariansexcordstromaltumor（性索間質腫瘤）1).Granulosacelltumor（顆粒細胞瘤）Institute3-6%ofovariantumors,80%ofsexcordstromaltumors.Usuallyoccuringin45-55yearsofage.Secreteestrogen,alsocalledfeminizingtumors（女性化腫瘤）.2).Thecacelltumor(卵泡膜細胞)SecreteestrogenSolidtumorBenign3).Fibroma(纖維瘤)Comprisesabout2-5%ofovariantumors.Benign,constitutetheMeigssyndrome(wheninconjunctionwithascitesandrighthydrothorax).3).Krukenbergstumor（庫肯勃瘤）Fromcarcinomaofthestomach.Usuallybilateral,moderatesize.Cutsurfacetypicallyexhibitsgelatinousnecrosis（膠凍狀壞死物）andmucin-filledcysticcavities.Singnetcell.病例討論：中南大學教案紙患者女性，26歲，未婚。平素月經規(guī)律，7/35天,量中，有輕微痛經。2005-4出現(xiàn)月經紊亂4/15天，量少，無痛經。當?shù)蒯t(yī)院超聲檢查提示：雙側卵巢增大。于2005-5-30外院行腹腔鏡檢查術、術中見雙卵巢腎形增大約右：6*5*4cm，左5*5*4cm。包膜均勻完整、但皮質略厚，表面散在毛細血管增生，余未見異常。行雙卵巢活檢術。術后病理報告：雙側卵巢Krukenberg瘤。術后嚴密隨診。術后2個月內無明顯變化。術后4個月超聲提示雙側卵巢增大、伴腹水癥。查T由4個月前的1.663ng/ml上升至5.718ng/ml，伴毛發(fā)加重、閉經3月。復查胃鏡顯微結腸鏡未見異常。2005-11-8在全麻下行次全子宮切除術、雙附件切除術。手術順利。術后病理報告：雙卵巢krukenberg瘤。免疫組化顯示腫瘤細胞：AE1：（-），AE3：（+），P170（-），CK7（灶狀+），CK20（-），Inhibin（-），P53（-），Top-Ⅱa（+〈1%〉，CEA（灶狀+）。后患者強烈要求出院，拒絕進一步檢查。4.non-neoplasticcyst（非贅生性囊腫）oftheovary:1).Folliclecyst2).Granulosaluteincysts3).Thecaluteincysts4).Polycysticovary5).Endometriosis5.Treatment(治療):1).良性生殖細胞及性索間質腫瘤：手術2).惡性生殖細胞及性索間質腫瘤：手術+化療(VACBEPBVP)3).無性細胞瘤:輔加放療4).轉移性:腫瘤細胞減滅加原發(fā)灶切除五、Guidelinesonmanagementforovariantumor(卵巢腫瘤處理原則)20min1.卵巢囊性腫塊:直徑<5cm者，可定期觀察2-3個月經周期。若>5cm直徑則為手術指征。2.確診為卵巢腫瘤者(混和性、實性腫塊)原則上應手術切除腫瘤，術中鑒別良惡性，可疑惡性時立即冰凍切片病檢確定手術范圍。3.懷疑惡性腫瘤，尤其是實質性腫瘤，無論腫塊大小均應及時手術。4.惡性腫瘤手術范圍:原則上對早期卵巢癌應行全面確定分期的探查手術，晚期卵巢癌則行腫瘤細胞減滅術，術后輔以化療，少數(shù)輔以放療和免疫治療的綜合治療方案。中南大學教案紙5.卵巢腫瘤并發(fā)癥屬急腹癥，一旦確診，無論良惡性及腫瘤大小均應立即手術。年青未生育的Ⅰa期，低度惡性腫瘤及生殖細胞腫瘤需保留生育功能者可行單附件切除術。6.保留生育功能的指征：1).上皮性卵巢腫瘤應具備以下條件:①年輕渴望生育；②Ia期；③細胞分化好（G1）或交界瘤；④對側卵巢外觀正常、活檢陰性；⑤腹腔細胞學陰性；⑥高危區(qū)域探查及活檢陰性；⑦有條件隨診；⑧完成生育后視情況再行手術切除子宮及對側附件。2).生殖細胞腫瘤不論期別早晚都可保留生育功能3).顆粒細胞瘤如為單側、包膜完整、腫瘤活動、對側卵巢正常、內膜術前診刮排除惡性者可保留生育功能。六、Etiologyandpathogenesisa(病因和發(fā)病機制)Geneticfactorssuchas:BRCA1[mutationin80%familyovarianarcinoma],BRCA2,P53[mutation14-44%],p16,NOEY2(normalovarianepithelialgenecloney2)[LOH>50%],Her-2/neuarenoticeableinnowadays,Telomeresandtelomerase.七、病例分析5min1、病史摘要：①患者×××，女，27歲，離異，2001年12月足月剖宮產1女嬰。②患者因“下腹痛半月，發(fā)現(xiàn)盆腔包塊8天”于2005-12-6收住院，患者月經規(guī)則，半月前出現(xiàn)下腹墜脹痛，程度輕，11月28日覺腹痛較前加重，伴肛門墜脹感，出現(xiàn)大便次數(shù)增多，2-3次/天，稀爛便，無粘液及膿血，無里急后重，無明顯消瘦，門診靜滴藥物抗感染治療無好轉。③體查：T36.3℃恥聯(lián)上見一陳舊橫形手術疤痕長8cm，下腹軟，輕壓痛，肝脾肋下未及，移動性中南大學教案紙濁音陰性，外陰發(fā)育正常，已婚式，陰道暢，宮頸光滑，有舉痛及觸痛，程度輕，子宮前位，大小、形狀、邊界不清，宮體壓痛，右側宮旁可捫及一囊實性包塊，大小如8×5cm2，邊界不清，活動差，局部壓痛明顯，左側附件區(qū)輕壓痛，觸診不清。④2001-11-28B超：子宮右后方囊實性包塊⑤術前肝、脾、膽、腎、輸尿管、膀胱B超未見異常，胸片、心電圖、凝血4項、血常規(guī)、尿常規(guī)、大便常規(guī)等術前檢查正常。⑥入院前及手術前均多次建議查腫瘤標志物明確腫瘤性質，患者均不同意。2、入院診斷：①盆腔包塊查因：右側卵巢腫瘤并感染？炎癥包塊？②疤痕子宮診斷依據：①下腹痛半月，發(fā)現(xiàn)盆腔包塊8天；②右側宮旁捫及一囊實性包塊大小如8×5cm2，邊界不清，活動差，局部壓痛；③B超：子宮右后方囊實性包塊可疑畸胎瘤。鑒別診斷：1).卵巢腫瘤并蒂扭轉：支持點：下腹痛且發(fā)現(xiàn)盆腔包塊，下腹輕壓痛，以右下腹明顯，右側宮旁可捫及一囊實性包塊大小如8×5cm2，邊界不清，活動差，局部壓痛明顯，B超示卵巢畸胎瘤。不支持點：患者下腹痛無明顯加劇，無惡心嘔吐，腹軟。結論：未能完全排除，需剖腹探查明確診斷。2).卵巢惡性腫瘤：支持點：下腹痛且發(fā)現(xiàn)盆腔包塊，婦檢：右側宮旁可捫及一囊實性包塊大小如8×5cm2，邊界不清，活動差，B超：子宮右后方囊實性包塊，左側卵巢內囊性腫塊（雙側卵巢均見包塊）。不支持點：患者年齡27歲，發(fā)病以來無明顯消瘦，胃納可，B超提示右側卵巢包塊疑畸胎瘤，體查腹水征陰性。結論：未能排除，需術中標本冰凍