Endometrial Intraepithelial Neoplasia Research Articles

Genomic Comparison of Endometrioid Endometrial Carcinoma and Its Precancerous Lesions in Chinese Patients by High-Depth Next Generation Sequencing.

Endometrial intraepithelial neoplasia (EIN), also known as endometrial atypical hyperplasia (EAH) is believed to be the precursor lesion of endometrioid endometrial carcinoma (EEC). Many genetic factors play important roles in the process of carcinogenesis, however, the key genetic alterations from dysplasia to endometrial cancer remains poorly understood. Germline mutations in Lynch syndrome genes are associated with hereditary endometrial carcinoma. The role of other cancer susceptibility genes is unclear. The aim of this study was to investigate the genomic alterations of premalignant endometrial lesion and EEC, and to determine the prevalence of cancer predisposition gene mutations in an unselected endometrial carcinoma patient cohort. Here, we applied a comprehensive cancer gene panel (363 cancer-related genes) to capture the exomes of cancer-related genes. Samples were collected from 79 patients with EEC and 36 patients with EIN. Our results demonstrate that EIN harbors most of the driver events reported in EEC and for the first time we reported a high frequency of the amplification of VEGFB gene in endometrial cancer. Moreover, we identified four novel candidate cancer-associated genes (CTCF, ARHGAP35, NF1, and KDR) which may be crucial in the carcinogenesis of EEC. In addition, we identified 2 patients who had a deleterious germline mutation in Lynch syndrome genes (MLH1 and MLH2), and another 8 patients harbored germline mutations of 6 non-Lynch syndrome genes (MUTYH, GALNT12, POLE, MPL, ATM, and ERCC4) which may be associated with endometrial cancer. Larger series will have to be investigated to assess the risks and the proportion of endometrial cancers attributable to other genes.

Prolonged conservative treatment in patients with recurrent endometrial cancer after primary fertility-sparing therapy: 15-year experience

To evaluate the efficacy and prognosis of repeated treatment on patients with recurrent endometrial cancer (EC) after complete remission for primary fertility-preserving therapy. We performed a retrospective study of patients with presumed stage IA endometrial cancer who had recurrence after achieving complete remission by fertility-preserving management at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2003 to April 2018. For each patient, medical records and pathology reports were reviewed. The demographic features, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed. Of the 41 recurrent patients with a median disease-free interval period of 16months (range, 5-55months), 23 were diagnosed at recurrence as EC, and 18 were diagnosed as atypical hyperplasia (AH) or endometrial intraepithelial neoplasia (EIN). 26 patients received repeated fertility-preserving treatment, and 23 patients were evaluable for efficacy. The complete response (CR) rate of repeated treatment (19/23, 82.6%) was lower than that of primary fertility-preserving treatment (161/170, 94.7%) with borderline significance (P = 0.053). The CR rate of AH/EIN patients was higher than that of EC patients with no statistical difference (92.9% vs 66.7%, P = 0.260). Among 19 patients achieved CR, 3 got pregnant and delivered successfully, while 3 had a second relapse. Four cases failed to response to the repeated treatment and underwent definitive surgery. 15 patients referred to definitive surgery directly after recurrence and one of them had a pelvic recurrence after 120months. All patients are alive without evidence of disease at last follow-up. For patients with recurrent EC after primary fertility-preserving treatment, repeated fertility-preserving treatment can still achieve a promising response and patients have possibilities of completing childbirth.

Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria.

Endometrial hyperplasia (EH) is classified into benign and precancerous according to two different histomorphological systems: the World Health Organisation (WHO) system (based on the subjective evaluation of cytological atypia) and the endometrial intraepithelial neoplasia (EIN) system (based on a combination of several parameters that are assessable subjectively, or objectively through computerised analysis). The American College of Obstetricians and Gynecologists recommends use of the EIN system. Nonetheless, a higher prognostic value for EIN criteria was demonstrated only with the objective assessment, which is not routinely applicable. The aim of this study was to evaluate which of the subjective classifications of EH (WHO or EIN) has better prognostic value, by assessing the risk of coexistent cancer. Electronic databases were searched for relevant articles from the inception of the databases to July 2018. All studies assessing the presence of cancer on hysterectomy specimens after a preoperative histological diagnosis of EH were included. Odds ratios (ORs), sensitivity and specificity were calculated with 95% confidence intervals (CIs). Sixteen cohort studies and three case-control studies, assessing 2582 EHs, were included. The WHO criteria showed an OR of 11.15 (95% CI 7.65-16.24), a sensitivity of 0.86 (95% CI 0.82-0.90) and a specificity of 0.67 (95% CI 0.64-0.70) for coexistent cancer. The subjective EIN system showed a similar OR (11.85, 95% CI 4.91-28.62; P = 0.90), higher sensitivity (0.98, 95% CI 0.94-0.99), and lower specificity (0.29, 95% CI 0.24-0.34). The WHO system and the subjective EIN system have similar prognostic values. However, the EIN criteria appear to be more sensitive and thus more suitable for selecting women who need to be treated, whereas the WHO criteria, based on cytological atypia, seem to be more specific for lesions at higher risk of cancer. Therefore, integration of the EIN system with cytological atypia should be considered.

Risk of malignancies among asymptomatic postmenopausal women with thickened endometrium: A cohort study.

The risk of malignancies and related factors among asymptomatic postmenopausal women with thickened endometrium in transvaginal sonography (TVS) are unclear.In this longitudinal study at a tertiary teaching hospital, all medical records of hysteroscopy were searched and retrospectively reviewed according to age, TVS results and diseases coded as International Classification of Diseases version 10. Asymptomatic postmenopausal women with endometrial thickness ≥5 mm from January 2006 to January 2016 were included. A follow-up was provided up to January 2017.Four hundred eighty-eight patients were included with a median endometrial thickness of 8 mm (range 5–30) in TVS. The most common pathologic findings were polyps (51.0%) and normal endometrium (34.2%). Fifteen (3.1%) and 10 cases (2.0%) had endometrial intraepithelial neoplasia (EIN) and carcinoma. Patients with carcinoma had significantly more abnormal serum CA125, thicker endometrium, and more lesions with positive Doppler flow signals. In receiver operating characteristic curve analysis, endometrial thickness of 12 mm had the best predictive ability for malignancies. In multivariate analysis, endometrial lesion with positive Doppler flow signals in TVS was the only independent factor for EIN/carcinoma (odds ratio [OR] 8.0, 95% confidence interval [CI] 1.4–45.1) and for carcinoma (OR 16.0, 95% CI 1.3–192.8). After a median follow-up of 45 months, carcinoma occurred in 1 of 35 (2.8%) women with repeated thickened endometrium.Among asymptomatic postmenopausal women with thickened endometrium, the risk of EIN and malignancy was minimal but worth of long-term follow-up. Endometrial lesions with positive Doppler flow signals in TVS suggested a high risk of malignancy.

PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta-analysis of diagnostic accuracy.

Benign and precancerous endometrial hyperplasias (EH) are differentiated according to two alternative histomorphologic classifications: World Health Organization (WHO) or endometrial intraepithelial neoplasia (EIN) system. The 2017 European Society of Gynaecological Oncology guidelines recommend paired box 2 protein (PAX2) immunohistochemistry to identify precancerous EH. However, methods for interpreting immunostaining and diagnostic accuracy are not defined, and the role of PAX2 in endometrial carcinogenesis is unclear. We aimed to assess: (a) PAX2 expression throughout endometrial carcinogenesis, from normal endometrium to benign EH, precancerous EH, and endometrial cancer (EC); (b) the diagnostic accuracy of PAX2 immunohistochemistry in diagnosing precancerous EH, defining criteria for its use. Electronic databases were searched for from their inception to July 2018. All studies evaluating PAX2 immunohistochemistry in normal endometrium, EH, and EC were included. Univariate comparisons of PAX2 expression were performed with Fisher's exact test (significant P<.05). Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve on summary receiver operating characteristic curves were calculated. Subgroup analyses were based on expression thresholds (decrease vs complete loss) and classifications used (WHO vs EIN). Six studies with 266 normal endometrium, 586 EH, and 114 EC were included. Both decrease and complete loss of PAX2 expression were significantly more common in EC and precancerous EH than benign EH. Diagnostic accuracy was moderate for both PAX2 complete loss and decrease (areas under the curve 0.829 and 0.876, respectively). PAX2 complete loss with EIN system showed the best results (sensitivity=0.72; specificity=0.95; DOR=43.13). PAX2 seems to behave as a tumor suppressor in endometrial carcinogenesis. PAX2 is an accurate marker of precancerous EH; complete loss of PAX2 and EIN classification appear as the optimal diagnostic criteria.

Loss of PTEN expression as diagnostic marker of endometrial precancer: A systematic review and meta-analysis.

Endometrial hyperplasia may be either a benign proliferation or a premalignant lesion. In order to differentiate these two conditions, two possible histologic classifications can be used: the World Health Organization (WHO) classification and the endometrial intraepithelial neoplasia (EIN) classification. The 2017 European Society of Gynaecological Oncology guidelines recommend the use of immunohistochemistry for tumor suppressor protein phosphatase and tensin homolog (PTEN) to improve the differential diagnosis. Nonetheless, its diagnostic accuracy has never been defined. We aimed to assess the diagnostic accuracy of immunohistochemistry for PTEN in the differential diagnosis between benign and premalignant endometrial hyperplasia. Electronic databases were searched from their inception to May 2018 for studies assessing immunohistochemical expression of PTEN in endometrial hyperplasia specimens. PTEN status ("loss" or "presence") was the index test; histological diagnosis ("precancer" or "benign") was the reference standard. Sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) on summary receiver operating characteristic curves were calculated (95% CI), with a subgroup analysis based on the histologic classification adopted (WHO vs EIN). Twenty-seven observational studies with 1736 cases of endometrial hyperplasia were included. Pooled estimates showed low diagnostic accuracy: sensitivity 54% (95% CI 50%-59%), specificity 66% (63%-69%), LR+ 1.55 (1.29-1.87), LR- 0.72 (0.62-0.83), DOR 3.56 (2.02-6.28), AUC 0.657. When the WHO subgroup was compared with the EIN subgroup, higher accuracy (AUC 0.694 vs. 0.621), and higher heterogeneity in all analyses, were observed. Immunohistochemistry for PTEN showed low diagnostic usefulness in the differential diagnosis between benign and premalignant endometrial hyperplasia. In the absence of further evidence, the recommendation about its use should be reconsidered.

Comparison of the Immunohistochemical Expression of Caveolin-1 in Endometrial Carcinoma, Endometrial Intraepithelial Neoplasia, Endometrial Hyperplasia, and Normal Endometrium

Comparison of the Immunohistochemical Expression of Caveolin-1 in Endometrial Carcinoma, Endometrial Intraepithelial Neoplasia, Endometrial Hyperplasia, and Normal Endometrium

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis.

In order to avoid the consequences of over- and under-treatment of endometrial hyperplasia, diagnostic accuracy and progression risk assessment must be improved. The aim of this study was to assess whether PAX2 or PTEN expression could predict progression-free survival in endometrial intraepithelial neoplasia (EIN) and endometrial endometrioid carcinoma (EEC). Immunohistochemistry for detection of PAX2 and PTEN was performed on 348 endometrial samples; 75 proliferative endometrium (PE), 36 EIN and 237 EEC. Cases classified as PTEN null (1 or more glands negatively stained) were more prevalent in EEC than in PE and EIN (64% EEC vs 11% PE/EIN). A progressive decrease in PAX2 expression was observed from PE to EIN to EEC. Long-term clinical follow-up (6-310 months, median: 126) was available for 62 PE cases, all 36 EIN cases and 178 EEC cases. No patients with PE demonstrated progression to EIN or EEC. Progression of disease was observed in 10 (28%) EIN patients. These patients had significantly lower PAX2 expression than those that regressed (P = 0.005). Progression-free survival analysis revealed that EIN patients with a high-risk PAX2 expression score (H-score ≤75) had a higher probability of progression of disease in comparison to those with a low-risk score (H-score >75). PAX2 expression was not prognostic in EEC nor was PTEN status of prognostic value in either EIN or EEC. PAX2 expression analysis by means of H-score has prognostic potential for the identification of high-risk progression cases in EIN but needs to be validated in a larger cohort.

Loss of B-cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment: A systematic review and meta-analysis.

Endometrial hyperplasia is differentiated into benign or premalignant. Two histological classifications are used for this purpose: World Health Organization (WHO) classification, based on cytological atypia, disregarding glandular complexity, and endometrial intraepithelial neoplasia (EIN) classification, based on several different parameters. B-cell lymphoma 2 (Bcl-2) loss has been studied as immunohistochemical marker with the aim of improving the differential diagnosis between benign and premalignant hyperplasia. We aimed to evaluate: (A) Bcl-2 loss as marker of endometrial precancer, by assessing it in proliferative endometrium, benign hyperplasia, premalignant hyperplasia, and endometrial cancer; (B) the diagnostic accuracy of Bcl-2 in the differential diagnosis between benign and premalignant endometrial hyperplasia; (c) how the results change according to the histological classification and the thresholds of Bcl-2 expression used. Electronic databases were searched from their inception to March 2018. All studies assessing Bcl-2 immunohistochemistry in endometrial specimens were included. In total, 20 observational studies assessing 1,278 specimens were included. Bcl-2 loss rates were not significantly different between proliferative endometrium and benign hyperplasia (P=0.12) and between premalignant hyperplasia and endometrial cancer (P=0.53). Among hyperplasias, Bcl-2 loss was significantly associated with premalignancy, according to both the WHO (OR=4.39; P<0.00001) and EIN classifications (OR=6.07; P=0.01), and also with architecture complexity (OR=2.06; P=0.02). Using the WHO classification, Bcl-2 loss showed low diagnostic accuracy in detecting premalignant hyperplasia (area under the curve [AUC]=0.708), with a sensitivityof 0.41, a specificityof0.81, a positive likelihood ratioof3.22, and a negative likelihood ratioof 0.69. Using the EIN classification, accuracy was high (AUC=0.938), with a sensitivityof 0.18, a specificityof 0.97, a positive likelihood ratioof5.16 and a negative likelihood ratioof0.86. Thresholds of Bcl-2 expression not involving a complete loss showed lower diagnostic accuracy with a slight increase in sensitivity, but a severe decrease in specificity. B-cell lymphoma 2 loss is a marker of endometrial precancer, with a high specificity and high diagnostic accuracy if the EIN classification is used. Thresholds of Bcl-2 expression not involving a complete loss should not be considered. Bcl-2 loss in endometrial hyperplasia may be a novel indication for treatment when precancerous features are ambiguous in a histological examination. Bcl-2 loss correlates better with EIN classification than with the WHO classification, suggesting that glandular complexity is an important precancerous feature.

Hysterectomy with sentinel lymph node biopsy in the setting of pre-operative diagnosis of endometrial intraepithelial neoplasia: A cost-effectiveness analysis

ObjectivesSentinel lymph node biopsy (SLNB) may be considered in the setting of a pre-operative diagnosis of endometrial intraepithelial neoplasia (EIN) due to high rates of concurrent invasive cancer. The aim of this study is to compare the cost-effectiveness of different surgical management strategies for a pre-operative diagnosis of EIN. MethodsA decision model was developed from a third party payer perspective to compare four surgical strategies for the management of EIN: (1) hysterectomy; (2) hysterectomy with frozen section (hysterectomy + frozen); (3) hysterectomy with SLNB (hysterectomy + SLNB); (4) hysterectomy with frozen section and SLNB (hysterectomy + frozen + SLNB). The probability that frozen section identifies high- or low-risk cancer, final pathology distribution, adjuvant treatments, and surgery/imaging costs were abstracted from the literature, Medicare reimbursement data, and the financial department of a private academic hospital. Adjuvant treatments were determined through NCCN guidelines and published studies. Effectiveness was quantified as percentage of patients who received the guideline-based treatment that aligned with their true stage. ResultsThe base case cost and effectiveness of each strategy was: hysterectomy-$4383/89%, hysterectomy + frozen-$5220/99.2%, hysterectomy + SLNB-$5354/94.7% and hysterectomy + frozen + SLNB-$5938/99.6%. Hysterectomy + frozen had an incremental cost effectiveness ratio of $8111 per patient who received adjuvant treatment that aligned with true stage compared to hysterectomy. Hysterectomy + frozen + SLNB had an ICER of $168,171 per additional patient who received adjuvant treatment that aligned with their true stage compared to hysterectomy + frozen. ConclusionHysterectomy + frozen + SLNB is a costly strategy for pre-operative EIN when compared to hysterectomy + frozen, with limited clinical benefit. Hysterectomy with frozen section and subsequent intraoperative staging decisions should continue to be standard of care.

Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer, Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective Study and Review of the Literature.

Objectives: To evaluate the efficacy and safety of gonadotropin-releasing hormone (GnRH) agonist after endometrial resection in women suffering early stage endometrial carcinoma (EC) and/or endometrial intra-epithelial neoplasia (EIN).Design: A retrospective review of clinical files between January 1999 and December 2016.Setting: University hospital.Patients: Eighteen women younger than 41 years with grade 1 endometrial carcinoma (G1EC) and/or Endometrial intra-epithelial neoplasia (EIN). Interventions: All patients received GnRH agonist for 3 months after an endometrial resection combined with a laparoscopy to exclude concomitant ovarian tumor and/or other extra-uterine disease. The patient underwent a follow-up of 3 months interval with endometrial sampling by hysteroscopy.Main Outcome Measure(s): The recurrence rate and the pregnancy rate after fertility sparing treatment.Results: We identified 9 patients with EIN (50%), 7 patients with G1EC (38.9%), 1 with combined histology (5.5%), and 1 with G2EC (5.5%). After a median follow-up of 40.7 months, 12 patients conserved their uterus (66.7%), and 8 (53.3%) patients were pregnant with a total of 14 pregnancies among those who tried to become pregnant. We observed a complete response rate in 12 patients (66.7%) but 3 of these patients relapsed (25%). We also found a stable disease in 6 patients (33.3%).Conclusions: Compared with other fertility sparing treatments, GnRH agonist after surgery is an effective fertility-sparing strategy for women with EIN and/or G1EC. We recommend hysterectomy once a family has been completed even if the literature does not clearly lead to radical surgery.

MOLECULAR PROFILES OF ENDOMETRIAL HYPERPLASIA AND ENDOMETRIAL INTRAEPITHELIAL NEOPLASIA

Objective: to assess molecular profiles of endometrial hyperplasia and endometrial intraepithelial neoplasia.Materials and methods. We conducted a retrospective study that included 77 patients with a morphologically verified hyperplastic process in the endometrium. Of them, 34 patients had endometrial hyperplasia and 33 patients had endometrial intraepithelial neoplasia. The control group comprised 30 women with no endometrial disorders according to the results of histological examination.Results. Patients with endometrial intraepithelial neoplasia are at high risk of developing cancer. High angiogenic activity, pronounced vascularization, and endometrial hypoxia are believed to be important risk factors contributing to tumor proliferation and transformation. The expression of inhibitors of apoptosis, such as survivin and Bcl-2, is usually increased in atypical cells, which may indicate their involvement in malignant transformation of cells and tumor invasive growth.Conclusion. Our findings confirm the important role of survivin and Bcl-2 in hyperplastic processes in the endometrium.

While women await surgery for type I endometrial cancer, depot medroxyprogesterone acetate reduces tumor glandular cellularity

Multiple population-level studies have demonstrated an adverse effect of long wait times to surgery on survival for women with endometrial cancer. Other retrospective and nonrandomized prospective studies have shown that preoperative administration of depot medroxyprogesterone acetate decreases tumor glandular cellularity, which may be a surrogate marker for clinically meaningful tumor response. We sought to determine whether preoperative injection with depot medroxyprogesterone acetate decreases tumor glandular cellularity when compared to placebo injection in women awaiting hysterectomy for endometrial intraepithelial neoplasia or type I endometrial cancer, and to determine whether depot medroxyprogesterone acetate injection affects quality of life while waiting for surgery. This was a double-blind, randomized controlled trial of 400-mg depot medroxyprogesterone acetate injection or 0.9% saline injection at the preoperative visit. Patients with recent use of progesterone analogs were excluded. A sample size of 76 patients (38 per arm) was calculated to detect a 20% difference in decreased glandular cellularity between arms. Pathologic characteristics including the primary outcome, tumor glandular cellularity, from patients' diagnostic biopsies were reviewed by 2 dedicated gynecologic pathologists and compared to posttreatment hysterectomy specimens. On the night prior to surgery, patients completed the Functional Assessment of Cancer Therapy-Endometrial Survey (Version 4) to report quality of life while waiting for surgery. In comparing characteristics between the intervention and control groups, t tests were used for continuous variables, and χ2 or Fisher exact tests were used where appropriate for categorical data. From March 2015 through March 2016, 148 women were screened and 76 patients were enrolled. In all, 38 patients were randomized to and received depot medroxyprogesterone acetate injection and 38 were randomized to and received placebo injection. Demographics were similar between groups. Patients who received depot medroxyprogesterone acetate injection experienced a larger decrease in tumor glandular cellularity (mean change -64 [-31.8%] vs -14 [-5.5%] cells per quarter high-powered field in depot medroxyprogesterone acetate vs placebo groups, P= .002). This effect was most pronounced in women waiting ≥3 weeks for surgery. Several additional histologic and immunohistochemical markers of tumor differentiation and decreased cell proliferation were more pronounced in the depot medroxyprogesterone acetate group than in the placebo group. There were no significant differences in quality of life between groups on the Functional Assessment of Cancer Therapy-Endometrial Survey. Only 5.3% of patients who were approached declined to participate due to concerns regarding an intramuscular injection. Administration of depot medroxyprogesterone acetate prior to surgery for type I endometrial cancers caused greater tumor effect than placebo injection. Injection of depot medroxyprogesterone acetate was acceptable to and well tolerated by patients. Depot medroxyprogesterone acetate may represent a meaningful bridge to surgery in women who can expect long wait times.

THE ANALYSIS OF METHYLATION OF DNA PROMOTER OF SFRP2 GENE IN PATIENTS WITH HYPERPLASTIC PROCESSES OF THE ENDOMETRIUM

The study groups were the following: I- patients with endometrial hyperplasia (EH, n=9); II- patients with endometrial intraepithelial neoplasia (EIN, n = 10), III- control groups: 1)with endometrial cancer (EC, n = 4), and 2) healthy women (n = 4). Determination of promoter methylation of SFRP2gene was carried out by the semiquantitative method of methylation-specific PCR assay. The maximum level of methylation of SFRP2gene promoter had been revealed in patients with EC- 42.80±3.55% (р&lt;0.05). The patients of the I group had the lowest values of methylation of SFRP2gene promoter- 10.66±0.85%, while in patients of the II group this indicator was higher- 20.60±0.95% (р &lt; 0.05). In healthy women of the control group, methylation of SFRP2gene promoter was detected in none of the samples. The content of the methylated SFRP2gene in endometrial tissue of patients with hyperplastic processes higher than 20-25% allows relate these women to the risk group of EC development and dictates the need of intensive observation of such patients.

Surgical outcomes of superobese women treated for endometrial intraepithelial neoplasia and endometrial cancer

Surgical outcomes of superobese women treated for endometrial intraepithelial neoplasia and endometrial cancer

ACOG Committee Opinion No. 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding.

Cancer of the endometrium is the most common type of gynecologic cancer in the United States. Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial carcinoma. Clinical risk factors for endometrial cancer, including but not limited to age, obesity, use of unopposed estrogen, specific medical comorbidities (eg, polycystic ovary syndrome, type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology), and family history of gynecologic malignancy also should be considered when evaluating postmenopausal bleeding. The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia. Transvaginal ultrasonography usually is sufficient for an initial evaluation of postmenopausal bleeding if the ultrasound images reveal a thin endometrial echo (less than or equal to 4 mm), given that an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for endometrial cancer. Transvaginal ultrasonography is a reasonable alternative to endometrial sampling as a first approach in evaluating a postmenopausal woman with an initial episode of bleeding. If blind sampling does not reveal endometrial hyperplasia or malignancy, further testing, such as hysteroscopy with dilation and curettage, is warranted in the evaluation of women with persistent or recurrent bleeding. An endometrial measurement greater than 4 mm that is incidentally discovered in a postmenopausal patient without bleeding need not routinely trigger evaluation, although an individualized assessment based on patient characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool for endometrial cancer in postmenopausal women without bleeding.

ACOG Committee Opinion No. 734 Summary: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding.

Cancer of the endometrium is the most common type of gynecologic cancer in the United States. Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial carcinoma. Clinical risk factors for endometrial cancer, including but not limited to age, obesity, use of unopposed estrogen, specific medical comorbidities (eg, polycystic ovary syndrome, type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology), and family history of gynecologic malignancy also should be considered when evaluating postmenopausal bleeding. The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia. Transvaginal ultrasonography usually is sufficient for an initial evaluation of postmenopausal bleeding if the ultrasound images reveal a thin endometrial echo (less than or equal to 4 mm), given that an endometrial thickness of 4 mm or less has a greater than 99% negative predictive value for endometrial cancer. Transvaginal ultrasonography is a reasonable alternative to endometrial sampling as a first approach in evaluating a postmenopausal woman with an initial episode of bleeding. If blind sampling does not reveal endometrial hyperplasia or malignancy, further testing, such as hysteroscopy with dilation and curettage, is warranted in the evaluation of women with persistent or recurrent bleeding. An endometrial measurement greater than 4 mm that is incidentally discovered in a postmenopausal patient without bleeding need not routinely trigger evaluation, although an individualized assessment based on patient characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool for endometrial cancer in postmenopausal women without bleeding.

104 - The Feasibility of Mini-Plus Percutaneous (MpPc) Endoscopy for Benign Gynecologic Procedures: Single Institution Experience

Study Objective: To evaluate the feasibility of Mini-plus percutaneous (MpPc) endoscopic surgery in different trocar settings for benign gynecologic operations. Design: Prospective observational study. Setting: Tertiary-care university-based teaching hospital and academic affiliated private hospital. Patients: Forty-nine women who underwent mini-plus percutaneous endoscopic surgery for benign gynecologic indications, between December 2015 and March 2017. Intervention: MpPc surgeries were performed through one optical transumbilical 5-mm trocar, one 5-mm ancillary port on the right-lower quadrant, one 2.4-mm percutaneous endoscopic instrument (MiniGrip Handle, Teleflex, USA) on the right-upper quadrant, and if it is required one 3.5-mm ancillary port on the left-lower quadrant. A 5-mm 30-degree and if it is needed 3.5-mm 30-degree pediatric telescope, 3.5 mm mini-laparoscopic instruments (Karl Storz, Tuttingen, Germany) and integrated bipolar and ultrasonic technology (Thunderbeat, Olympus, Japan) were used. The umbilical incision was closed with a 4/0 Monocryl, whereas other incisions were approximated by using sterile-strips. All operations were performed by the same surgeon. Measurements and Main Results: A total of 49 patients were conducted. The median age was 38 years (range,28–63 years); body-mass index was 26 kg/m2 (range, 22- 32 kg/m2). Of the 49 patients, 14 had uterine fibroids; 13 had benign adnexal mass; 5 had breast cancer plus BRCA1 carrier; 4 had endometrial intraepithelial neoplasia; 4 had adenomyosis + abnormal uterine bleeding; 4 had ectopic pregnancy; 3 had hydrosalpinx, and 2 had adnexal torsion. As MpPc surgical procedures had 27 total laparoscopic hysterectomies, 8 ovarian cystectomy, 7 salpingo-oophorectomy, and 7 salpingectomy The median operating time was 60 minutes (range, 20–185 min), and estimated blood loss was 40 ml (range, 10–180 ml). Conversion to 5-mm conventional laparoscopy or open surgery was not required. No Intra- and postoperative complications were recorded. Conclusion: MpPc is feasible and nearly “‘scar-free’” ultra-minimally invasive procedure for benign gynecologic operations.

Endometrial hyperplasia: Emergence of the EIN system

Background: The diagnosis of precancerous lesions of the endometrium remains unstandardized because, the existing World Health Organization classification categories do not correspond to distinctive biologic groups and are inadequately supported by reproducible histopathologic criteria. The objective of our study is to simplify the diagnosis of endometrial hyperplasia, make it more reproducible and stratify patients in to two risk groups instead of four using the recent EIN system.Materials &amp;Methods : All cases diagnosed as endometrial hyperplasia classified according to the WHO system in patients with abnormal uterine bleeding, during the 3 year period 2014-2016 were reclassified as benign hyperplasia and Endometrial intraepithelial neoplasia according to the EIN system. Results : 38 out of the 46 cases (82.6 %) of simple hyperplasia were reclassified as Benign hyperplasia. 8 out of the 46 cases (17.4%) of simple hyperplasia were reclassified as EIN.1 case of complex hyperplasia without atypia was reclassified as EIN. All the 11 cases of complex hyperplasia with atypia were reclassified as EIN.Conclusions : Application of the criteria for EIN successfully segregates patients into high and low cancer risk subgroups with better reproducibility than WHO classification. DOI: 10.21276/APALM.1026

Surgical Findings and Outcomes in Premenopausal Breast Cancer Patients Undergoing Oophorectomy: A Multicenter Review From the Society of Gynecologic Surgeons Fellows Pelvic Research Network

Study ObjectiveTo describe the procedures performed, intra-abdominal findings, and surgical pathology in a cohort of women with premenopausal breast cancer who underwent oopherectomy. DesignMulticenter retrospective chart review (Canadian Task Force classification II-3). SettingNine US academic medical centers participating in the Fellows' Pelvic Research Network (FPRN). PatientsOne hundred twenty-seven women with premenopausal breast cancer undergoing oophorectomy between January 2013 and March 2016. InterventionSurgical castration. Measurements and Main ResultsThe mean patient age was 45.8 years. Fourteen patients (11%) carried a BRCA mutations, and 22 (17%) carried another germline or acquired mutation, including multiple variants of uncertain significance. There was wide variation in surgical approach. Sixty-five patients (51%) underwent pelvic washings, and 43 (35%) underwent concurrent hysterectomy. Other concomitant procedures included midurethral sling placement, appendectomy, and hysteroscopy. Three patients experienced complications (transfusion, wound cellulitis, and vaginal cuff dehiscence). Thirteen patients (10%) had ovarian pathology detected on analysis of the surgical specimen, including metastatic tumor, serous cystadenomas, endometriomas, and Brenner tumor. Eight patients (6%) had Fallopian tube pathology, including 3 serous tubal intraepithelial cancers. Among the 44 uterine specimens, 1 endometrial adenocarcinoma and 1 multifocal endometrial intraepithelial neoplasia were noted. Regarding the entire study population, the number of patients meeting our study criteria and seen by gynecologic surgeons in the FPRN for oophorectomy increased by nearly 400% from 2013 to 2015. ConclusionSince publication of the Suppression of Ovarian Function Trial data, bilateral oophorectomy has been recommended for some women with premenopausal breast cancer to facilitate breast cancer treatment with aromatase inhibitors. These women may be at elevated risk for occult abdominal pathology compared with the general population. Gynecologic surgeons often perform castration oophorectomy in patients with breast cancer as an increasing number of oncologists are using aromatase inhibitors to treat premenopausal breast cancer. Our data suggest that other abdominal/pelvic cancers, precancerous conditions, and previously unrecognized metastatic disease are not uncommon findings in this patient population. Gynecologists serving this patient population may consider a careful abdominal survey, pelvic washings, endometrial sampling, and serial sectioning of fallopian tube specimens for a thorough evaluation.