婦產(chǎn)科-子宮內膜癌英文課件

1、Endometrial CancerOB/GYN Hospital Fudan UniversityXin LU, MD, Ph.D.1Endometriod cancer-ContentsIncidenceRisk factorsClassificationSymptomsPathologyFIGO StagingDiagnosisTreatment2WHO Cancer ReportGlobal cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th most common

2、 cancer in womenNew Diagnosed cases: 142,000 Died cases each year: 42,000 incidence 2-3%Average age: 60s3Histologic TypesEndometrial CancersEndometrioid (87%)Adenosquamous (4%)Papillary Serous (3%)Clear Cell (2%)Mucinous (1%)Other (3%)4 Endometrial Cancer:Type I/IIType IEstrogen RelatedYounger and h

3、eavier patientsLow gradeBackground of HyperplasiaPerimenopausalExogenous estrogenFamilial/genetic (15% )Lynch II syndrome/HNPCCFamilial trendType II (10% )AggressiveHigh gradeUnfavorable HistologyUnrelated to estrogen stimulationOccurs in older & thinner women5Endometrial Cancer: Risk FactorsRisk Fa

4、ctorsRelative Risk X Obesity 2-5 PCOS 5Estrogen use10-20Nulliparous3Infertility2-3Diabetes/Hypertension1.3-3Nulliparous3Early Menarche (12 y/o)1.5-2Atypical Hyperplasia OC0.3-0.5From: Williams Gynecology 20096Endometrium Carcinoma2009 ClassificationStage CharacteristicStage I* Tumor confined to the

5、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 does not extend beyond the uterus*Stage III* Local and/or regional spread of the tumor IIIA* Tumor invades the serosa of the corpus uteri an

6、d/or adnexae# IIIB* Vaginal and/or parametrial involvement# IIIC* Metastases to pelvic and/or para-aortic lymph nodes#. IIIC1* Positive pelvic nodes IIIC2* Positive paraaortic lymphnodes with or without positive pelvic lymph nodesStage IV* Tumor invades bladder and/or bowel mucosa, and/or distant me

7、tastases IVA* Tumor invasion of bladder and/or bowel mucosa IVB* Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes 7Stage I(73%)Confined to uterusStage II(11%)Cervix involvedStage III(13%)Uterine serosa, adnexae, positive cytology, vaginal metastases, pelvic/aortic

8、 node metastasesStage IV(3%)Bladder, bowel, inguinal node, distant metastasisEndometrial Cancer: FIGO Surgical Stage8Endometrial Cancer Prognosis:Survival by Stage:Stage% 5yr survivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5Survival by Grade:Grade% 5yr survival192287374Overall 5Yr Survival 8

9、4%Stage and Grade are the most important prognostic factorsAltered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept)9Aggressive Histologic Subtypes (Clear-cell, Serous)Increasing age (over 65)Vascular invasionAneuploidyAltered oncogene/tumor suppressor gene

10、 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 Factors10Molecular GeneticsPTEN mutations: 32%Tumor suppressor gene (chrom 10)PhosphataseEarly event in carcinogene

11、sisAssociated with:endometrioid histologyearly stagefavorable survival 11Molecular Geneticsp53 tumor suppressor geneCell cycle and apoptosis regulationMost commonly mutated gene in human cancersOverexpression (marker for mutation)Associated with poor prognosisearly stage:10% have p53 mutationadvance

12、d stage: 50% have p53 mutationnot found in hyperplasiaslate event in carcinogenesis12Genetic Syndromes: HNPCCHereditary Non-Polyposis Colon CancerLynch II SyndromeAutosomal dominant inheritanceMMR (mismatch repair) mutationsGenetic instability leads to error-prone DNA replicationhMSH2 (chrom 2)hMLH1

13、 (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, small bowel, pancreas, biliary tract13Diagnosis of disease: Patient Awareness*More than 95% of pa

14、tients with Endometrial Cancer report having symptomsPostmenapausal bleedingMenorrhagiaMetrorrhagiaBloody DischargeEndometrial biopsy is the main diagnostic tool performed either in the office or via D&C in OR14Uterine Cancer:Diagnosis/ScreeningPatient Symptoms/Awareness*Cytology Not a satisfactory

15、screening testSonography Not Cost effectiveHysteroscopy Not Cost effectiveHistology Secondary to symptoms (not as a screening test)15Endometrial Cancer:Transvaginal Ultrasound Screening16Endometrial Cancer:Transvaginal Ultrasound Screening17Endometrial Cancer:Transvaginal Ultrasound Screening18Norma

16、l 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 Cancer:Transvaginal Ultrasound Screening19Hysteroscopy Not satisfactory for screening testStudies of the efficacy

17、 of hysteroscopy as a diagnostic tool vary widelySensitivity reported ranging from 60-95% compared to D&C obtained at the same timeSpecificity 50-99%2021Hysteroscopy and Positive Cytology?Studies have been mixed:Some studies suggest an increase in positive peritoneal cytology seen at staging laparot

18、omy 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&C22Hysteroscopy Not satisfactoryToo much cost and risk to be used as a screening test.Useful for evaluation of abnorma

19、l uterine bleeding where office biopsy is unrevealing. Use in conjunction with uterine curettageUseful to see and resect polyps and small submucous fibroidsUseful to perform directed biopsy of small lesions.23Endometrial Cancer:Who Needs an Endometrial Biopsy?Postmenopausal bleedingPerimenopausal in

20、termenstrual bleedingAbnormal bleeding with history of anovulationPostmenopausal women with endometrial cells on PapThickened endometrial stripe via sonography24Sampling of the EndometriumOffice biopsy procedures (Pipelle, Vabra aspirator, Karman cannula) will agree with a D&C performed in the OR 95

21、% of the timeOffice biopsy has a 16% false negative rate when the lesion is in a polyp or the cancer covers less than 50% of the endometriumGuido et al. J Reprod Med. 1995;40:553Patients with persistent PMB after negative office biopsy should have D&C (+/- hysteroscopy)D&C is the gold standard sampl

22、ing method preoperative D&C will agree with diagnosis at hysterectomy 94% of the time25262728Treatment 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

23、follow with ovulation induction after normal biopsy if pregnancy desiredPeri or Postmenopausal:Provera 20mg po 10 days/month orDepo-Provera 200mg IM q2 monthsRepeat biopsy in 3-4 months29Treatment for Atypical Endometrial Hyperplasia:23% risk of progression to carcinoma (over 10 years) if untreated.

24、Standard treatment when childbearing is complete is total hysterectomy (abdominal or vaginal)Frozen section to rule out carcinoma (up to 20% have coexisting endometrial cancer)30Treatment for Atypical Endometrial Hyperplasia:Conservative medical therapy can be attempted in younger patients who reque

25、st preservation of fertility.D&C prior to initiation of medical 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 acetat

26、e 5-10mg/day31Endometroid carcinoma, GradingFIGO- Gr 1 - 50% solid tumorNUCLEAR GRADESize, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point to FIGO grade32CA125Chest X-rayMammogramsColon EvaluationOthers as indicatedUterine Cancer: Pre-op Evaluation3

27、3Uterine Cancer: Pre-op EvaluationTransvaginal U/S?CT Scan?MRI?34Uterine Cancer: Pre-op Evaluation35Uterine Cancer: Surgical StagingPreoperative preparationAntimicrobial prophylaxisDVT prophylaxisSteep TrendelenburgLong instruments available36Availability of frozen section to determine the extent of staging procedure.Capability of complete surgical stagingCapability of tumor reduction if indicatedEndometrial Cancer: Intra-operative Surgical Principals37End