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Endometrial hyperplasia

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Aboubakr Elnashar

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Endometrial hyperplasia

  2. 2. INTRODUCTION ▪ Incidence ▪ increases with age ▪ 133 per 100 000 woman-years ▪ Rarely seen in women under the age of 30 ▪ Its peak in women aged 50 to 54. ABOUBAKR ELNASHAR ▪ Risk factors 1. Menstrual factors: 1. Older age or postmenopausal status 2. Nulliparity or infertility 3. Early menarche or later menopause 4. Anovulation or PCOS 2. Iatrogenic factors: 1. Unopposed exogenous estrogen therapy 2. Tamoxifen ABOUBAKR ELNASHAR 3. Comorbidities: 1. Obesity: important risk factor 2. DM 3. Hypertension 4. Lynch syndrome
  3. 3. ▪ Classification & histopathology In 2014, WHO modified the classification to include only 2 categories: 1. Hyperplasia without atypia 2. Hyperplasia with atypia: ▪ Atypical hyperplasia or ▪ Endometrial intraepithelial neoplasia (EIN). ▪ Health care providers should use the 2014 WHO histopathologic classification of endometrial hyperplasia (strong). ABOUBAKR ELNASHAR
  4. 4. ABOUBAKR ELNASHAR ▪ Hyperplasia without atypia ▪ Not share the same genetic mutations as its counterpart. ▪ Rarely progresses to endo carcinoma (1%−3%) ▪ Can be managed conservatively. ABOUBAKR ELNASHAR ▪ Hyperplasia with atypia ▪ Precursor to type I endom carcinomas as both share a similar profile of genetic alterations and monoclonal growth. ▪ 60% have already developed or will develop endometrial cancer. ▪ More definitive treatment approach
  5. 5. DIAGNOSIS ❑ Symptoms ▪ In premenopausal women: ▪ AUB: ▪ Disturbances in regularity, frequency, duration& heaviness of menstrual bleeding ▪ Intermenstrual bleeding (IMB) ▪ Risk of endom carcinoma is higher with IMB compared with HMB ▪ Postmenopausal bleeding ABOUBAKR ELNASHAR ❑ Physical Findings ▪ Can be normal or ▪ Obesity ▪ Features of PCOS. ▪ Bimanual exam of the uterus ▪ Speculum exam for Pap testing ABOUBAKR ELNASHAR
  6. 6. ❑ Investigation: 1. Endometrial tissue sampling ▪ Indication: Any woman with suspected endometrial hyperplasia or endometrial cancer ▪ 40 ys or older ▪ BMI of 30 kg/m 2 or greater (moderate). ▪ No response to medical therapy ▪ Young women based on their risk factors. ▪ Using a Pipelle device in an outpatient setting is the most appropriate first step for diagnosis (strong, high). ABOUBAKR ELNASHAR Endocurette Pipelle
  7. 7. 2. Hysteroscopy with directed sampling & curettage ▪ The preferred method of investigation in. 1. Non-diagnostic or benign endometrial sample with remaining high suspicion of endometrial hyperplasia or cancer 2. Cervical stenosis, failed endometrial biopsy 3. Persistent bleeding, or excessive pain/anxiety 4. Recurrent symptoms of AUB after initial observation or medical treatment (strong, high). ABOUBAKR ELNASHAR ▪ Risk of Tumour Spillage ▪ Through Hysteroscopy or Saline Infusion, there were concerns about tumour spillage and cancer upstaging in women previously investigated with hysteroscopy or saline US for endometrial hyperplasia or cancer. ▪ There is no study showing any adverse outcome for patients with a previous endoscopic diagnostic procedure. ▪ Since 2014, peritoneal washing has not been part of the International Federation of Gynecology and Obstetrics staging for endometrial cancer. ABOUBAKR ELNASHAR
  8. 8. MANAGEMENT ▪ Addressing the Risk Factors ▪ Encouraging obese to lose weight. ▪ Correction of those medical conditions (strong, high).. ABOUBAKR ELNASHAR I. ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA 1. Conservative Management ▪ Supported by 1. Long-term risk for progression to endomet carcinoma≤5% 2. Spontaneous regression rates of 75 to 100%. 2. Hormonal TT ▪ Indication: ▪ Hyperplasia does not resolve with observation ▪ AUB (weak, low). ▪ Majority of cases are successfully managed medically ▪ Hysterectomy is not considered first-line TT & is reserved for specific circumstances (moderate). ABOUBAKR ELNASHAR
  9. 9. 1. Levonorgestrel IUD should be 1 st line TT due to: 1. Its effectiveness (81% to 94% regression) 2. Favourable side effect profile (strong, high) 3. It can be kept in place for 5 y in patients showing TT response (strong, moderate). ▪ Treating pre & postmenopausal women ▪ Follow-up by ▪ endometrial sampling ▪ performed with the IU device in place ABOUBAKR ELNASHAR 2. Progrstins: ▪ Low-dose oral (regression rate 67 to72%) and ▪ Injectable progestins (DMP: regression rate after 6 m: 92%) remain an acceptable TT option for endometrial hyperplasia with & without atypia desiring an alternative TT modality (strong, high). ▪ Treating both pre & postmenopausal women ABOUBAKR ELNASHAR
  10. 10. ▪ Oral progestins: start on a low dose for a minimum of 6 months. ▪ Assessment of the endometrium Endometrial biopsy (strong, very low). ▪ Mid-therapy after 3 months ▪ 3 w after completion of TT to ensure proper interpretation ▪ Relapse rate is higher in patients ▪ Treated with progestins ▪ Those with a BMI 35 kg/m 2 . ▪ The follow-up duration for those patients should therefore be extended. ABOUBAKR ELNASHAR 3. Aromatase inhibitors ▪ An effective TT option for patients with endometrial hyperplasia without atypia. ▪ Letrozole ▪ comparable effectiveness to megestrol acetate ▪ favourable side effect profile ▪ used in pre & postmenopausal women. ABOUBAKR ELNASHAR
  11. 11. Dydrogesterone 10 mg, 2 tablets twice daily from fifth day of menstruation for 21 days for 6 months ABOUBAKR ELNASHAR 3. Surgical Treatment ▪ Indication: 1. Persistent (fails to regress after 12 months) or Recurrent hyperplasia despite progestin use 2. Progression to atypical hyperplasia or carcinoma 3. Ongoing AUB despite TT 4. Patient preference. 5. Contraindication or intolerance to medical TT 6. Unwillingness to comply with surveillance 7. No desire for future fertility 8. High baseline risk for endometrial carcinoma. ABOUBAKR ELNASHAR
  12. 12. ▪ Total hysterectomy with opportunistic salpingectomy, with bilateral oophorectomy in postmenopause & (strong, moderate) & ▪ without oophorectomy in premenopausal women {increased mortality & morbidity associated with removal of the ovaries in young women with benign disease} (moderate). ▪ Surgical approach ▪ Vaginal, laparoscopic,& open approaches are all acceptable {it is considered non-neoplastic entity}, ▪ Vag or laparoscopic route: fewer perioperative complications ABOUBAKR ELNASHAR 4. Endometrial Ablation ▪ There is insufficient evidence to support as first-lineTT except in circumstances where major surgery is contraindicated (low). ▪ Safe option for treatment ▪ Limitation 1. Difficulty in confirming complete destruction of the endometrium. 2. Surveillance can be challenging due to obliteration of the endometrial cavity ▪ Patients should be followed up at regular intervals& investigated if AUB persists or recurs. ABOUBAKR ELNASHAR
  13. 13. II. ATYPICAL ENDOMETRIAL HYPERPLASIA/EIN 1. Hysterectomy & Bilateral Salpingo-oophorectomy ▪ are the recommended TT in pre&postmenopausal {underlying risk of malignancy or progression to endometrial cancer. 60% of patients with EIN already have developed or will develop an invasive endometrial cancer} ▪ Retention of ovaries in premenopausal may be considered (low). ▪ The increased risk of mortality&morbidity associated with bilateral oophorectomy in premenopausal women with benign disease should be discussed thoroughly ▪ TT tailored to each individual. ABOUBAKR ELNASHAR ▪ Laparoscopic hysterectomy is preferred for endometrial hyperplasia as it decreases perioperative morbidity& mortality (high) ▪ Laparotomy limited to cases where this is not feasible. ▪ Laparoscopy vs laparotomy: ▪ fewer perioperative complications, shorter hospital stay, quicker return to normal activity ▪ Survival outcomes are similar ▪ Evaluation of the adnexa& other pelvic structures for signs of invasive disease. {Atypical endometrial hyperplasia is associated with higher risk of underlying carcinoma} ABOUBAKR ELNASHAR
  14. 14. ▪ Not recommended: 1. Subtotal hysterectomy & morcellation (strong, low) due to concern about malignancy & dissemination of disease 2. Routine intraoperative frozen section analysis (low) 3. Routine lymphadenectomy (moderate). ABOUBAKR ELNASHAR ▪ Endometrial Ablation is generally avoided in patients with atypical hyperplasia because it is a pre-malignant condition. ABOUBAKR ELNASHAR
  15. 15. ▪ Fertility preservation TT of EIN: ▪ Options: 1. Oocyte or embryo cryopreservation prior to hysterectomy with BSO 2. Hysterectomy with ovarian preservation& future use of a surrogate. 3. Medical TT followed by ART ▪ Encourage to maintain a BMI below 30 kg/m 2 , as relapse is much more common in obese patients. ABOUBAKR ELNASHAR ▪ Cancer incidence does not increase when comparing patients undergoing primary hysterectomy& delayed hysterectomy for fertility-sparing purposes. ▪ Infertility TT do not increase the relapse rate of EIN. ▪ LBR associated with conservative TT of EIN: 7- 26% ▪ Pregnancy: lower chance of disease recurrence. ▪ Hysterectomy with BSO is recommended when childbearing is no longer desired {The risk of disease recurrence being high} ABOUBAKR ELNASHAR
  16. 16. 2. Medical treatment options & follow-up ▪ Uterine preservation may be considered in 1. Patients who wish to preserve their fertility or 2. Who are medically unfit for surgery. ▪ Counselling: Important ▪ should include 1. Risks of 1. Endometrial cancer higher than stage I (2%) 2. Coexisting ovarian cancer (4%) 3. Death (0.5%) 2. Those outcomes could not easily be predicted by pre- treatment investigations. ABOUBAKR ELNASHAR ▪ Conservative treatment options ▪ Progestins (oral or local) ▪ Aromatase inhibitors, or ▪ GnRHa. ▪ Table shows types of progestins and dosages that can be used in treatment of EIN. ABOUBAKR ELNASHAR
  17. 17. ▪ Metformin ▪ May also be added to increase TT effect, even in the absence of metabolic syndrome. ▪ Obesity: lower chance of disease remission. ▪ A trial of 6 months ▪ is generally necessary to see TT response, with a plateau at around 12 months. ▪ Regression rates: 55% to 92% ▪ Recurrence rates: 3% to 55% ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR ▪ Metformin anticancer effect: ▪ Affects endometrial maturation, proliferation& implantation. ▪ Delay estrogen-mediated endometrial proliferation
  18. 18. ▪ Endometrial biopsy ▪ Every 3 months until at least 2 negative specimens are obtained. ▪ The highest risk of recurrence in the first 2 ys after treatment cessation ▪ Every 6 months for 2 years and ▪ Every year thereafter until ▪ Risk factors are corrected or ▪ Total hysterectomy with BSO is performed. ABOUBAKR ELNASHAR ▪ Definitive surgical treatment indicated if 1. Progression to carcinoma during follow-up, 2. Hyperplasia fails to regress after 12 months of medical TT 3. Relapses after TT with progestins 4. Continuous AUB despite treatment 5. Decline of surveillance or medical TT ABOUBAKR ELNASHAR
  19. 19. Endometrial Hyperplasia in an Endometrial Polyp 1. Should be treated acc to its histologic classification. 2. Sampling of the background endometrium, even when its hysteroscopic appearance is normal. Why? ▪ Endom hyperplasia either with or without atypia will be found in background endometrium in up to 52% ▪ Risk of concurrent endom cancer in patients found to have an atypical endometrial polyp: 5.6%. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR TAKE HOME MESSAGE I. Introduction: ▪ Risk factors: obesity is important risk factor ▪ Classification: hyperplasia without atypia & with atypia II. Diagnosis: ▪ Endometrial tissue sampling if suspected end hyperplasia ▪ Hysteroscopy if persistent bleeding III. Management ▪ First line ▪ Without atypia: Hormonal TT ▪ With atypia: Hysterectomy with BSO

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