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1、1,Endometrial Cancer,OB/GYN Hospital Fudan UniversityXin LU, MD, Ph.D.,2,Endometriod cancer-Contents,IncidenceRisk factorsClassificationSymptoms,PathologyFIGO StagingDiagnosisTreatment,3,WHO Cancer Report,Global cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th m

2、ost common cancer in womenNew Diagnosed cases: 142,000 Died cases each year: 42,000 incidence 2-3%Average age: 60s,4,Histologic Types,Endometrial CancersEndometrioid (87%)Adenosquamous (4%)Papillary Serous (3%)Clear Cell (2%)Mucinous (1%)Other (3%),5,Endometrial Cancer:Type I/II,Type IEstrogen Relat

3、edYounger and heavier patientsLow gradeBackground of HyperplasiaPerimenopausalExogenous estrogenFamilial/genetic (15% )Lynch II syndrome/HNPCCFamilial trend,Type II (10% )AggressiveHigh gradeUnfavorable HistologyUnrelated to estrogen stimulationOccurs in older & thinner women,6,Endometrial Cancer: R

4、isk Factors,From: Williams Gynecology 2009,7,Endometrium Carcinoma2009 Classification,Stage CharacteristicStage I* Tumor confined to the corpus uteri IA* No or less than half myometrial invasion IB* Invasion equal to or more than half of the myometriumStage II* Tumor invades cervical stroma, but doe

5、s not extend beyond the uterus*Stage III* Local and/or regional spread of the tumor IIIA* Tumor invades the serosa of the corpus uteri and/or adnexae# IIIB* Vaginal and/or parametrial involvement# IIIC* Metastases to pelvic and/or para-aortic lymph nodes#. IIIC1* Positive pelvic nodes IIIC2* Positiv

6、e paraaortic lymphnodes with or without positive pelvic lymph nodesStage IV* Tumor invades bladder and/or bowel mucosa, and/or distant metastases IVA* Tumor invasion of bladder and/or bowel mucosa IVB* Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes,8,Endometrial

7、 Cancer: FIGO Surgical Stage,9,Endometrial Cancer Prognosis:,Overall 5Yr Survival 84%Stage and Grade are the most important prognostic factorsAltered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept),10,Aggressive Histologic Subtypes (Clear-cell, Serous)Inc

8、reasing age (over 65)Vascular invasionAneuploidyAltered oncogene/tumor suppressor gene expression ( “molecular staging” concept- p53, PTEN, microsatellite instability, MDR-1, HER2/neu, ER/PR, Ki 67, PCNA, CD 31,EGF-R, MMR genes) Race?,Endometrial Cancer: Poor Prognostic Factors,11,Molecular Genetics

9、,PTEN mutations: 32%Tumor suppressor gene (chrom 10)PhosphataseEarly event in carcinogenesisAssociated with:endometrioid histologyearly stagefavorable survival,12,Molecular Genetics,p53 tumor suppressor geneCell cycle and apoptosis regulationMost commonly mutated gene in human cancersOverexpression

10、(marker for mutation)Associated with poor prognosisearly stage:10% have p53 mutationadvanced stage: 50% have p53 mutationnot found in hyperplasiaslate event in carcinogenesis,13,Genetic Syndromes: HNPCCHereditary Non-Polyposis Colon Cancer,Lynch II SyndromeAutosomal dominant inheritanceMMR (mismatch

11、 repair) mutationsGenetic instability leads to error-prone DNA replicationhMSH2 (chrom 2)hMLH1 (chrom 3)Early age of colon Ca: mean 45.2 yearsEndometrial Ca: second most common malignancy20% cumulative incidence by age 70Earlier age of onset than sporadic casesOther: ovary (3.5-8 fold), stomach, sma

12、ll bowel, pancreas, biliary tract,14,Diagnosis of disease: Patient Awareness*,More than 95% of patients with Endometrial Cancer report having symptomsPostmenapausal bleedingMenorrhagiaMetrorrhagiaBloody DischargeEndometrial biopsy is the main diagnostic tool performed either in the office or via D&C

13、 in OR,15,Uterine Cancer:Diagnosis/Screening,Patient Symptoms/Awareness*Cytology Not a satisfactory screening testSonography Not Cost effectiveHysteroscopy Not Cost effectiveHistology Secondary to symptoms (not as a screening test),16,Endometrial Cancer:Transvaginal Ultrasound Screening,17,Endometri

14、al Cancer:Transvaginal Ultrasound Screening,18,Endometrial Cancer:Transvaginal Ultrasound Screening,19,Normal endometrial stripe:Postmenopausal4- 8 mmPostmenopausal on HRT4- 10 mm U/S for Detection of any uterine pathologySensitivity:85-95%Specificity:60-80%PPV 2-10%NPV 99%,Summary: Endometrial Canc

15、er:Transvaginal Ultrasound Screening,20,Hysteroscopy Not satisfactory for screening test,Studies of the efficacy of hysteroscopy as a diagnostic tool vary widelySensitivity reported ranging from 60-95% compared to D&C obtained at the same timeSpecificity 50-99%,21,22,Hysteroscopy and Positive Cytolo

16、gy?,Studies have been mixed:Some studies suggest an increase in positive peritoneal cytology seen at staging laparotomy in patients who have had hysteroscopyOther studies have failed to find a difference in positive cytology in patients diagnosed via hysteroscopy as compared to office biopsy or D&C,

17、23,Hysteroscopy Not satisfactory,Too much cost and risk to be used as a screening test.Useful for evaluation of abnormal uterine bleeding where office biopsy is unrevealing. Use in conjunction with uterine curettageUseful to see and resect polyps and small submucous fibroidsUseful to perform directe

18、d biopsy of small lesions.,24,Endometrial Cancer:Who Needs an Endometrial Biopsy?,Postmenopausal bleedingPerimenopausal intermenstrual bleedingAbnormal bleeding with history of anovulationPostmenopausal women with endometrial cells on PapThickened endometrial stripe via sonography,25,Sampling of the

19、 Endometrium,Office biopsy procedures (Pipelle, Vabra aspirator, Karman cannula) will agree with a D40:553Patients with persistent PMB after negative office biopsy should have D&C (+/- hysteroscopy)D&C is the gold standard sampling method preoperative D&C will agree with diagnosis at hysterectomy 94

20、% of the time,26,27,28,29,Treatment for Endometrial Hyperplasia without atypia:,Progestin therapy continuous or cyclicalChildbearing age:Progestin dominant OCPs orDepo-Provera 150mg IM q3 months orProvera 10mg po 10 days/month andMay follow with ovulation induction after normal biopsy if pregnancy d

21、esiredPeri or Postmenopausal:Provera 20mg po 10 days/month orDepo-Provera 200mg IM q2 monthsRepeat biopsy in 3-4 months,30,Treatment for Atypical Endometrial Hyperplasia:,23% risk of progression to carcinoma (over 10 years) if untreated.Standard treatment when childbearing is complete is total hyste

22、rectomy (abdominal or vaginal)Frozen section to rule out carcinoma (up to 20% have coexisting endometrial cancer),31,Treatment for Atypical Endometrial Hyperplasia:,Conservative medical therapy can be attempted in younger patients who request preservation of fertility.D&C prior to initiation of medi

23、cal therapy to rule out carcinomaMegace 40-80mg/day, Norethindrone acetate 5mg/dayConservative therapy may also be attempted in young patients with early, well differentiated endometrial carcinomas.Megace 120-200mg/day, Norethindrone acetate 5-10mg/day,32,Endometroid carcinoma, Grading,FIGO- Gr 1 -

24、50% solid tumorNUCLEAR GRADESize, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point to FIGO grade,33,CA125Chest X-rayMammogramsColon EvaluationOthers as indicated,Uterine Cancer: Pre-op Evaluation,34,Uterine Cancer: Pre-op Evaluation,Transvaginal U/S?

25、CT Scan?MRI?,35,Uterine Cancer: Pre-op Evaluation,36,Uterine Cancer: Surgical Staging,Preoperative preparationAntimicrobial prophylaxisDVT prophylaxisSteep TrendelenburgLong instruments available,37,Availability of frozen section to determine the extent of staging procedure.Capability of complete su

26、rgical stagingCapability of tumor reduction if indicated,Endometrial Cancer: Intra-operative Surgical Principals,38,Endometrial Cancer: Surgical Approach,TAH-BSO/washings only Endometrioid*Grades 1 and 50% myometrial invasion*or Grade 2 and no or minimal invasion and 2 cm tumor diameter*,*Verified v

27、ia frozen section,39,Endometrial Cancer: Surgical Approach,Complete Surgical Staging*All Grade 3Any 50% myometrial invasionAny 2 cm tumor diameterAll Serous/clear cell subtype*Pre operative assessment of advanced disease (gross cervical or vaginal dz, etc),*TAH-BSO, washings, lymphadenectomy *omenta

28、l/peritoneal biopsy,40,Endometrial Cancer: Adjuvant Therapy,BrachytherapyExternal beam radiotherapyHormonal therapyCytotoxic chemotherapyCombination therapy,41,Endometrial Cancer: Recurrence,Pelvic examinationPap smearsCA125 (high-risk)Chest X-ray (high-risk),42,Endometrial Cancer: Site of RecurrenceIn Radiated Patients,43,Endometrial Cancer: Follow-Up,75-95% of recurrences are in first 36 months60% of patients have symptoms (pain, wgt loss, vaginal bleeding) Rare to cure distant recurrences50% vaginal recurrences cured,