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1、Endometrial CancerEndometriod cancer-ContentsIncidenceRisk factorsClassificationSymptomsPathologyFIGO StagingDiagnosisTreatmentWHO Cancer Report Global cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th most common cancer in women New Diagnosed cases: 142,000 Died

2、 cases each year: 42,000 incidence 2-3% Average age: 60sHistologic Types Endometrial Cancers Endometrioid (87%) Adenosquamous (4%) Papillary Serous (3%) Clear Cell (2%) Mucinous (1%) Other (3%) Endometrial Cancer:Type I/II Type I Estrogen Related Younger and heavier patients Low grade Background of

3、Hyperplasia Perimenopausal Exogenous estrogen Familial/genetic (15% ) Lynch II syndrome/HNPCC Familial trend Type II (10% ) Aggressive High grade Unfavorable Histology Unrelated to estrogen stimulation Occurs in older & thinner womenEndometrial Cancer: Risk FactorsRisk FactorsRelative Risk X Obe

4、sity 2-5 PCOS 5Estrogen use10-20Nulliparous3Infertility2-3Diabetes/Hypertension1.3-3Nulliparous3Early Menarche (12 y/o)1.5-2Atypical Hyperplasia OC0.3-0.5From: Williams Gynecology 2009Endometrium Carcinoma2009 Classification Stage Characteristic Stage I* Tumor confined to the corpus uteri IA* No or

5、less than half myometrial invasion IB* Invasion equal to or more than half of the myometrium Stage 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 and/or adnexae# IIIB* V

6、aginal 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 nodes Stage IV* Tumor invades bladder and/or bowel mucosa, and/or distant metastases IVA* Tumor

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

8、 IV(3%)Bladder, bowel, inguinal node, distant metastasisEndometrial Cancer: FIGO Surgical StageEndometrial Cancer Prognosis:Survival by Stage:Stage% 5yr survivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5Survival by Grade:Grade% 5yr survival192287374Overall 5Yr Survival 84%Stage and Grade are

9、the most important prognostic factorsAltered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept) Aggressive Histologic Subtypes (Clear-cell, Serous) Increasing age (over 65) Vascular invasion Aneuploidy Altered oncogene/tumor suppressor gene expression ( “mol

10、ecular 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 FactorsMolecular Genetics PTEN mutations: 32% Tumor suppressor gene (chrom 10) Phosphatase Early event in carcinogenesis Associated w

11、ith: endometrioid histology early stage favorable survival Molecular Genetics p53 tumor suppressor gene Cell cycle and apoptosis regulation Most commonly mutated gene in human cancers Overexpression (marker for mutation) Associated with poor prognosis early stage:10% have p53 mutation advanced stage

12、: 50% have p53 mutation not found in hyperplasias late event in carcinogenesisGenetic Syndromes: HNPCCHereditary Non-Polyposis Colon CancerLynch II Syndrome Autosomal dominant inheritance MMR (mismatch repair) mutations Genetic instability leads to error-prone DNA replication hMSH2 (chrom 2) hMLH1 (

13、chrom 3) Early age of colon Ca: mean 45.2 years Endometrial Ca: second most common malignancy 20% cumulative incidence by age 70 Earlier age of onset than sporadic cases Other: ovary (3.5-8 fold), stomach, small bowel, pancreas, biliary tractDiagnosis of disease: Patient Awareness* More than 95% of

14、patients with Endometrial Cancer report having symptoms Postmenapausal bleeding Menorrhagia Metrorrhagia Bloody Discharge Endometrial biopsy is the main diagnostic tool performed either in the office or via D&C in ORUterine Cancer:Diagnosis/Screening Patient Symptoms/Awareness* Cytology Not a sa

15、tisfactory screening test Sonography Not Cost effective Hysteroscopy Not Cost effective Histology Secondary to symptoms (not as a screening test)Endometrial Cancer:Transvaginal Ultrasound ScreeningEndometrial Cancer:Transvaginal Ultrasound ScreeningEndometrial Cancer:Transvaginal Ultrasound Screenin

16、g Normal endometrial stripe: Postmenopausal4- 8 mm Postmenopausal on HRT4- 10 mm U/S for Detection of any uterine pathology Sensitivity:85-95% Specificity:60-80% PPV 2-10% NPV 99%Summary: Endometrial Cancer:Transvaginal Ultrasound ScreeningHysteroscopy Not satisfactory for screening testStudies of t

17、he 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%Hysteroscopy and Positive Cytology?Studies have been mixed:Some studies suggest an increase in positive peritoneal cytology seen at stag

18、ing 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&CHysteroscopy Not satisfactory Too much cost and risk to be used as a screening test. Useful for evalua

19、tion of abnormal uterine bleeding where office biopsy is unrevealing. Use in conjunction with uterine curettage Useful to see and resect polyps and small submucous fibroids Useful to perform directed biopsy of small lesions.Endometrial Cancer:Who Needs an Endometrial Biopsy? Postmenopausal bleeding

20、Perimenopausal intermenstrual bleeding Abnormal bleeding with history of anovulation Postmenopausal women with endometrial cells on Pap Thickened endometrial stripe via sonographySampling of the Endometrium Office biopsy procedures (Pipelle, Vabra aspirator, Karman cannula) will agree with a D&C

21、 performed in the OR 95% of the time Office biopsy has a 16% false negative rate when the lesion is in a polyp or the cancer covers less than 50% of the endometrium Guido et al. J Reprod Med. 1995;40:553 Patients with persistent PMB after negative office biopsy should have D&C (+/- hysteroscopy)

22、 D&C is the gold standard sampling method preoperative D&C will agree with diagnosis at hysterectomy 94% of the timeTreatment for Endometrial Hyperplasia without atypia:Progestin therapy continuous or cyclicalChildbearing age:Progestin dominant OCPs orDepo-Provera 150mg IM q3 months orProver

23、a 10mg po 10 days/month andMay 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 monthsTreatment for Atypical Endometrial Hyperplasia:23% risk of progression to carcinoma

24、(over 10 years) if untreated.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)Treatment for Atypical Endometrial Hyperplasia: Conservative medical therapy can be attempted i

25、n younger patients who request preservation of fertility. D&C prior to initiation of medical therapy to rule out carcinoma Megace 40-80mg/day, Norethindrone acetate 5mg/day Conservative therapy may also be attempted in young patients with early, well differentiated endometrial carcinomas. Megace

26、 120-200mg/day, Norethindrone acetate 5-10mg/dayEndometroid carcinoma, Grading FIGO- Gr 1 - 50% solid tumor NUCLEAR GRADE Size, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point to FIGO gradeCA125Chest X-rayMammogramsColon EvaluationOthers as indicate

27、dUterine Cancer: Pre-op EvaluationUterine Cancer: Pre-op EvaluationTransvaginal U/S?CT Scan?MRI?Uterine Cancer: Pre-op EvaluationUterine Cancer: Surgical Staging Preoperative preparation Antimicrobial prophylaxis DVT prophylaxis Steep Trendelenburg Long instruments available Availability of frozen s

28、ection to determine the extent of staging procedure. Capability of complete surgical staging Capability of tumor reduction if indicatedEndometrial Cancer: Intra-operative Surgical PrincipalsEndometrial Cancer: Surgical Approach TAH-BSO/washings only Endometrioid* Grades 1 and 50% myometrial invasion

29、* or Grade 2 and no or minimal invasion and 50% myometrial invasion Any 2 cm tumor diameter All Serous/clear cell subtype* Pre operative assessment of advanced disease (gross cervical or vaginal dz, etc)*TAH-BSO, washings, lymphadenectomy *omental/peritoneal biopsyEndometrial Cancer: Adjuvant Therap

30、y Brachytherapy External beam radiotherapy Hormonal therapy Cytotoxic chemotherapy Combination therapyEndometrial Cancer: Recurrence Pelvic examination Pap smears CA125 (high-risk) Chest X-ray (high-risk)Endometrial Cancer: Site of RecurrenceIn Radiated PatientsSite%Distant65Pelvic and distant15Pelvis only15Vagina5Endometrial Cancer: Follow-Up 75-95% of recurrences are in first 36 months 60% of patients have symptoms (pain, wgt loss, vaginal bleeding) Rare to cure distant recurre