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Objective: The study aimed to evaluate the incidence of concurrent endometrial cancer (EC) and lymph node positivity in patients with Atypical Endometrial Hyperplasia (AEH) who underwent surgical staging with sentinel lymph node evaluation. It also sought to identify the risk factors associated with detecting concurrent endometrial cancer in patients with a preoperative diagnosis of AEH., Study Design: A retrospective study was conducted at Amrita Institute of Medical Sciences, involving 54 cases of AEH diagnosed on pre-operative biopsy specimens and undergoing staging surgery between January 1, 2015, and December 31, 2020. The study analysed demographic parameters, clinical presentations, pathological features, and clinical outcomes. Categorical variables were expressed in numbers and percentages, normal distribution data were presented as mean, and non-normal distribution data were presented as median and range., Results: Fifty-four patients diagnosed with AEH underwent surgical staging. The median age was 54 years. Final HistoPathology Report (HPR) showed 48.14 % with AEH and 51.85 % with concurrent EC. Among those with concurrent EC, 96.4 % had type I EC, and one patient was upgraded to type 2 EC. Among them, 17.8 % patients belonged to high-intermediate and high-risk categories. Patients with AEH and concurrent EC were more likely to be diabetic (OR: 3.56, p = 0.04), have a BMI ≥25 kg/m2 (OR: 1.47, p = 0.04), exhibit a thickened endometrial lining of ≥9 mm (OR: 3.13, p = 0.05) on ultrasound, and undergo preoperative biopsy at a non-oncology centre (OR: 8.33, p = 0.001) whereas experiencing heavy menstrual bleeding had a substantially lower likelihood (OR: 0.29, p = 0.01) of developing concurrent EC., Conclusion: The study revealed that more than half of patients undergoing staging surgery for AEH were found to be at risk of having concurrent EC in their final HPR. The research also pointed out that surgical staging can help identify both low-risk and high-risk ECs, which may require additional treatment. Higher BMI, diabetes mellitus, and an endometrial thickness of ≥9 mm were identified as significant risk factors for concurrent EC. Additionally, heavy menstrual bleeding was associated with a decreased risk of concurrent EC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration., Methods: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598)., Results: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed., Conclusions: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy., Competing Interests: Declaration of competing interest C·N, O.L and Y·S declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the risk of endometrial carcinoma following a diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasia by endometrial biopsy, stratified based on integrated histological parameters., Methods: All women with atypical hyperplasia/endometrioid intraepithelial neoplasia undergoing hysterectomy within 1 year of diagnosis without progestin treatment were included. Patients were subdivided into three study groups, based on two criteria: (a) grade of nuclear atypia and (b) foci (<2 mm) of confluent glands with no intervening stroma: low-grade, high-grade, and confluent glands. The rate of endometrial carcinoma on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher's exact test, with a significant p value <0.05. Reproducibility was assessed by using Cohen's κ., Results: Ninety-six patients were included. Overall, 36 of 96 patients (37.5%) had endometrial carcinoma on the subsequent hysterectomy. The number of endometrial carcinomas was 4 of 42 (9.5%) in the low-grade group, 14 of 28 (50.0%) in the high-grade group, and 18 of 26 (69.2%) in the confluent glands group. The rate of endometrial carcinoma was significantly higher in the high-grade group than in the low-grade group (p<0.001), whereas it did not significantly differ between the high-grade group and the confluent glands group (p=0.176). The reproducibility among pathologists was moderate for low-grade versus high-grade (κ=0.58) and substantial for confluent glands versus low-grade (κ=0.63) and high-grade (κ=0.63)., Conclusion: Atypical hyperplasia/endometrioid intraepithelial neoplasia can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR)., Material and Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR)., Results: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m 2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m 2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth)., Conclusions: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: This study aimed to evaluate the prevalence of concurrent endometrial cancer in patients pre-operatively diagnosed with atypical endometrial hyperplasia undergoing hysterectomy. Additionally, we assessed the occurrence of high to intermediate-risk and high-risk tumors according to the ESGO-ESTRO-ESP classification. The study also compared surgical outcomes and complications between patients undergoing simple hysterectomy and those undergoing hysterectomy with sentinel lymph node biopsy., Methods: In this multicenter retrospective study, patients with a pre-operative diagnosis of atypical endometrial hyperplasia were identified and divided into two groups: Group 1, which included patients treated with total hysterectomy with or without bilateral salpingo-oophorectomy, and Group 2, where sentinel lymph node biopsy was incorporated into the standard surgical treatment., Results: Among 460 patients with atypical endometrial hyperplasia, 192 received standard surgical management (Group 1) and 268 underwent sentinel lymph node biopsy (Group 2). A total of 47.2% (95% CI 42.6% to 51.7%) of patients were upgraded to endometrial cancer on final histopathological examination. High to intermediate-risk and high-risk tumors constituted 12.3% and 9.2% in Group 2 and 7.4% and 3.7% in Group 1. Lymph node metastases were identified in 7.6% of patients with concurrent endometrial cancer who underwent nodal assessment with at least unilateral mapping. Of the 12 sentinel lymph node metastases, 75.0% were micrometastases, 16.7% macrometastases, and 8.3% isolated tumor cells. No significant differences were found in estimated blood loss, operative time, and intra-operative and post-operative complications between the two groups. The rate of patients undergoing sentinel lymph node biopsy doubled every 2 years (OR 2.010, p<0.001), reaching 79.1% in the last 2 years., Conclusion: This study found a prevalence of concurrent endometrial cancer of 47.2%, and sentinel lymph node biopsy provided prognostic and therapeutic information in 60.8% of cases. It also allowed for the adjustment of adjuvant therapy in 12.3% of high to intermediate-risk patients without increasing operative time or complication rates., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To examine the utilization and characteristics related to the use of hysteroscopy at the time of endometrial evaluation for endometrial hyperplasia in the outpatient surgery setting., Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population was 3218 patients with endometrial hyperplasia who underwent endometrial evaluation from January 2016 to December 2019. Performance and clinical characteristics of hysteroscopic endometrial evaluation were assessed with multivariable binary logistic regression models., Results: A total of 2654 (82.5%) patients had hysteroscopic endometrial tissue evaluation. Patients with postmenopausal bleeding, heavy menstrual bleeding, and polycystic ovary syndrome were more likely to undergo hysteroscopic endometrial evaluation in multivariable analysis (all, adjusted-P < 0.001). Uterine injury occurred in 4.9 per 1000 hysteroscopic endometrial evaluations; none had uterine injury in the non-hysteroscopy cohort. Among the 2654 patients who had hysteroscopic endometrial evaluation, 106 (4.0%) patients had intrauterine device insertion at surgery, and the utilization increased from 2.9 to 5.8% during the study period (P-trend < 0.001). Younger age, more recent year surgery, and obesity were independently associated with increased utilization of intrauterine device insertion at hysteroscopic endometrial evaluation (all, adjusted-P < 0.05). Among 2023 reproductive-age patients with endometrial hyperplasia, 1666 (82.4%) patients underwent hysteroscopic endometrial evaluation. On multivariable analysis, patients with heavy menstrual bleeding were more likely to have hysteroscopic endometrial evaluation (adjusted-P < 0.05). Intrauterine device insertion increased from 3.7% in 2016 to 8.0% in 2019 (P-trend = 0.007)., Conclusion: This nationwide analysis suggests that the insertion of intrauterine devices at the time of hysteroscopic endometrial tissue evaluation for endometrial hyperplasia is increasing among reproductive-age population., (© 2024. The Author(s).)

Objective: To identify predictive clinico-pathologic factors for concurrent endometrial carcinoma (EC) among patients with endometrial intraepithelial neoplasia (EIN) using machine learning., Methods: a retrospective analysis of 160 patients with a biopsy proven EIN. We analyzed the performance of multiple machine learning models (n = 48) with different parameters to predict the diagnosis of postoperative EC. The prediction variables included: parity, gestations, sampling method, endometrial thickness, age, body mass index, diabetes, hypertension, serum CA-125, preoperative histology and preoperative hormonal therapy. Python 'sklearn' library was used to train and test the models. The model performance was evaluated by sensitivity, specificity, PPV, NPV and AUC. Five iterations of internal cross-validation were performed, and the mean values were used to compare between the models., Results: Of the 160 women with a preoperative diagnosis of EIN, 37.5% (60) had a post-op diagnosis of EC. In univariable analysis, there were no significant predictors of EIN. For the five best machine learning models, all the models had a high specificity (71%-88%) and a low sensitivity (23%-51%). Logistic regression model had the highest specificity 88%, XG Boost had the highest sensitivity 51%, and the highest positive predictive value 62% and negative predictive value 73%. The highest area under the curve was achieved by the random forest model 0.646., Conclusions: Even using the most elaborate AI algorithms, it is not possible currently to predict concurrent EC in women with a preoperative diagnosis of EIN. As women with EIN have a high risk of concurrent EC, there may be a value of surgical staging including sentinel lymph node evaluation, to more precisely direct adjuvant treatment in the event EC is identified on final pathology., (© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens., Methods: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment., Results: Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I 2 =27.6%, 2 studies, 342 participants, 304 events) and 79% (I 2 =89.2%, 2 studies, 342 participants, 271 events), respectively. The rate of involved SLNs was 1.6% (I 2 =0%, 3 studies, 424 participants, 7 involved SLN) and 3.5% (I 2 =0%, 3 studies, 197 participants, 7 involved SLN) in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia as the denominator and in those with endometrial cancer in the hysterectomy specimen, respectively. The cancer rate in the hysterectomy specimen was 45% (I 2 =72.8%, 3 studies, 503 participants, 224 events) and the most frequent endometrial cancer International Federation of Gynecology and Obstetrics 2009 stage was IA in 199 (89.2%) patients. The complication rate was similar between the groups., Conclusion: The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This meta-analysis aimed to evaluate the effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer (EC), atypical endometrial hyperplasia (AEH), or endometrial intraepithelial neoplasia (EIN)., Methods: Studies on hysteroscopic surgery combined with progesterone therapy for patients with early-stage EC, AEH, or EIN were searched from Embase, Web of Science, PubMed, and Cochrane Library databases. The included studies contained one or more of the following outcome variables: pregnancy rate, live birth rate, complete response (CR) rate, and recurrence rate after conservative treatment. The meta-analysis was performed using Stata., Results: 13 pieces of literature containing 239 patients with EC and 199 patients with AEH/EIN were included. As per the results of meta-analysis, the pregnancy rates of EC patients and AEH/EIN patients were 49% (95% CI 33-65%) and 47% (95% CI 31-64%), respectively, and the live birth rates were 45% (95% CI 32-58%) and 44% (95% CI 34-54%), respectively. CR rates of EC patients and AEH/EIN patients were 90% (95% CI 85-94%) and 100% (95% CI 97-100%), respectively, and the disease recurrence rates were 17% (95% CI 8-28%) and 11% (95% CI 3-23%), respectively., Conclusion: Hysteroscopic surgery combined with progesterone was linked to an improved overall response rate, reduced disease recurrence rate, and increased pregnancy and live birth rates among patients with EC and AEH/EIN., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR., Methods: We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy., Results: The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities., Conclusions: We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children., (© 2023. The Author(s).)

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P =0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P =0.005). Multi-variant analysis showed PTEN gene multi-loci mutation ( HR =0.413, 95% CI : 0.259-0.658; P <0.001) and PIK3CA gene mutation ( HR =0.499, 95% CI : 0.310-0.804; P =0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity ( HR =3.825, 95% CI : 1.570-9.317; P =0.003) and MMR-d ( HR =9.014, 95% CI : 1.734-46.873; P =0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Purpose: Endometrial premalignancies are among the common reasons for outpatient gynecology visits among women in reproductive ages. Due to the continued increase in global obesity incidence among them, endometrial malignancies are expected to become even further prevalent. Hence, fertility-sparing interventions are essential and needed. In this semi-systematic literature review, we aimed to investigate the role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia. Our secondary goal is to analyze the pregnancy outcomes following fertility preservation., Methods: We conducted a computed search in PubMed. We included original research articles including hysteroscopic interventions in pre-menopausal patients with endometrial malignancies and premalignancies who underwent fertility-preserving treatments. We collected data on medical treatment, response, pregnancy outcomes, and hysteroscopy., Results: Of the query results (n = 364), our final analysis included 24 studies. Overall, 1186 patients with endometrial premalignancies and endometrial cancer (EC) were included. More than half of the studies were retrospective design. They included almost ten different forms of progestins. Of the reported pregnancies (n = 392), the overall pregnancy rate was 33.1%. The majority of the studies used operative hysteroscopy (87.5%). Only three (12.5%) reported their hysteroscopy technique in detail. Although more than half of the studies did not provide any information on adverse effects due to hysteroscopy, there were no serious adverse effects among the reported ones., Conclusion: Hysteroscopic resection may increase the success rate of fertility-preserving treatment of EC and atypical endometrial hyperplasia. The clinical significance of the theoretical concern of the dissemination of cancer is not known. Standardization of the use of hysteroscopy in fertility-preserving treatment is needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the rate of atypical hyperplasia (AH) underestimating endometrial cancer (EC) comparing endometrial biopsy (EB) accomplished by hysteroscopic biopsy with dilatation and curettage (D&C). Second, to compare the two techniques to foresee EC grading., Methods: This trial was based on the findings of two Gynecological Departments within the same Public Utility, sharing pathological service and database but routinely performing EB under hysteroscopic visualization (group A) or hysteroscopy followed by D&C (group B). We retrieved the clinical data of patients showing EC on hysterectomy throughout a 10-year period. The accuracy of hysteroscopic-view diagnosis and EB pathology were compared, having the pathologic findings of hysterectomy as reference., Results: A total of 161 patients met the inclusion criteria. Among these, 109 and 52 were included in groups A and B, respectively. In group A, 32.1% of patients underwent EB in an out-patient setting. To foresee EC, hysteroscopic view showed a sensitivity of 82.5% and 70.2% in groups A and B, respectively (P = 0.019). An underestimation of EC diagnosed as AH on EB was found in 20 patients (12.4%). Among these, 18 (16.5%) and 2 (3.8%) were included in groups A and B, respectively (P = 0.022). In group A, a fault diagnosis of AH resulted higher when EB was performed as out-patient setting (P = 0.006). EB allowed the grading of EC in 73.3% and 90.3% of patients in groups A and B, respectively. The agreement was 73.7% and 85.1%, leading to moderate (κ = 0.56) and good (κ = 0.77) "κ" coefficient of concordance for groups A and B, respectively., Conclusions: EB performed by D&C lowers the rate of AH underestimating concurrent EC and improves the grading agreement when compared with hysteroscopic sampling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting., Methods: The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation., Results: Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P < 0.05). Among those independent factors, presence of atypia exhibited the largest association for lymph node evaluation (adjusted odds ratio 3.75, 95% confidence interval 3.39-4.16). There were 20 unique patterns of lymph node evaluation based on histology, hysterectomy type, patient age, year of surgery, and hospital bed capacity, ranging from 0 to 20.3% (absolute rate difference, 20.3%)., Conclusion: Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines., (© 2023. The Author(s).)

Objective: Obesity is a risk factor for endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and early type 1 endometrial cancer (EC) in 70%-90% of patients and is often a significant contributor to overall morbidity and mortality due to comorbidities. In 2011, bariatric surgery (BS) with lifestyle modification was identified as an intervention for reduction in overall mortality as well as risk for gynecologic cancers (Tsui et al., 2021). Our aim was to assess awareness of obesity as a risk factor and understanding of BS in an underinsured obese patient population with EC or EH., Method: This IRB-approved survey was distributed to patients with type I EC or EH within the past 5 years and a BMI >30. Questions addressed demographics, health habits, cancer and obesity awareness, as well as benefits and concerns about undergoing BS. Information was provided about dietary requirements after BS, and then interest in BS was surveyed., Results: 61.2% of surveyed patients were interested in bariatric surgery for weight loss after receiving education about the procedure. Interest in bariatric surgery was correlated with higher BMI, higher ideal and comfortable weight loss in pounds and higher estimated weight loss that could be obtained with bariatric surgery. Additionally, patients who were interested in BS had better understanding of the risks of obesity with cancer overall., Conclusion: Obese patients with history of EC/EIN/EH are aware of hazards associated with excess weight and understand the relationship between EC/EIN/EH diagnosis and obesity, and overall are very interested in BS as a modality to improve their health., Competing Interests: Declaration of Competing Interest none to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Purpose: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility., Methods: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed., Results: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m 2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001)., Conclusion: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles., Methods: We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017-12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used., Results: Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1-2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE-ultramutated, and 1 (3%) copy number-high disease., Conclusions: SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Jewell reports personal fee from Covidien/Medtronic; Dr. Abu-Rustum reports grant money from GRAIL paid to the institution; and Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Progestin therapy is the main fertility-sparing treatment for women with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). However, still 15-25% of these women failed to achieve complete response (CR) and then lost their fertility after definitive surgery. Metformin has been demonstrated to play an anti-cancer role in multiple cancers including EC. Several studies also suggested metformin had potential benefit in improving the therapeutic outcome of fertility-preserving treatment alongside with progestin. This review has discussed existed evidence regarding the effect of metformin combined with progestin for women with AEH and EC who desire childbearing. Nevertheless, the therapeutic effect of metformin varied in different studies due to the high heterogeneity in the patient's characteristics, the inconsistency in dose and treatment duration of metformin, the combined use of hysteroscopy, the insufficient sample size and underpowered study-design. Therefore, care should be taken when interpreting the current results on this issue. Till now, there is still no strong evidence supporting the use of metformin in fertility-preserving treatment in AEH and EEC patients. Further research is needed to provide high-quality data to validate the role of metformin as adjunctive therapy alongside with progestin to preserve fertility for AEH and EEC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guan and Chen.)

Background: This study observed and described the morphological characteristics of the endometrium of the resected uterus using confocal laser endomicroscopy. This included benign endometrium, non-atypical endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma, thereby laying a foundation for finding the precise localization and resection of endometrial lesions, given the feasibility of confocal laser endomicroscopy-assisted hysteroscopy., Methods: This prospective study included 32 patients who underwent hysterectomy. We used confocal laser endomicroscopy to observe the endometrium of resected uteruses and described the characteristics of endometrium in different states by comparing histopathological findings (primary objects). The secondary objects of observation were the myometrium, endocervical canal, and surface of the external os of the cervix., Results: A total of 32 patients who underwent hysterectomy for different diseases were included: 9 with endometrial carcinoma (5 with endometrioid carcinoma, 1 with endometrial serous carcinoma, 2 with clear cell carcinoma, and 1 with carcinosarcoma), 2 with atypical endometrial hyperplasia, 9 with benign diseases, 7 with cervical cancer, and 5 with ovarian cancer and borderline tumor. The dynamic images of the endometrium were observed and recorded using probe-based confocal laser endomicroscopy (pCLE). Considering histopathology as the gold standard, the diagnostic concordance rate of pCLE was 96.9% in patients with endometrial carcinoma and precancerous lesions and 100% in patients with endometrial carcinoma., Conclusion: Confocal laser endomicroscopy provides real-time high-resolution images of the benign endometrium and endometrial lesions. Compared with histopathology, confocal laser endomicroscopy has high diagnostic accuracy and may become an auxiliary examination tool for hysteroscopy, as it is useful for early identification of endometrial lesions, real-time diagnosis of tumor, and detection of tumor boundaries for complete tumor resection. These findings can lay a foundation for the feasible use of fertility-sparing local excision of tumor lesions by hysteroscopy., (© 2022. The Author(s).)

Background: Standard treatment for patients with endometrial intraepithelial neoplasia (EIN) is a hysterectomy, which has a 43% risk of concomitant endometrial cancer on final pathology. General gynecologists and gynecologic-oncologists perform hysterectomies; however, patients who have a hysterectomy for EIN with a general gynecologist and are found to have cancer may require a second surgery by a gynecologic-oncologist to complete staging. There is ongoing discussion regarding whether patients with EIN should be provided the option to receive the initial hysterectomy with a gynecologic-oncologist., Objective: This study aimed to better understand if patients with EIN should be initially referred to a gynecologic-oncologist for treatment. We examined the cost-effectiveness of hysterectomy by general gynecologists vs gynecologic-oncologists for patients with EIN., Study Design: We created a decision-analytical model using TreeAge Pro software to compare outcomes between hysterectomies by general gynecologists and those by gynecologic-oncologists in patients with EIN. Our theoretical cohort contained 200,000 patients, an estimate of the number of individuals diagnosed with EIN each year in the United States. Outcomes included costs, quality-adjusted life years, primary lymph node dissection, secondary lymph node dissection, surgical site infection, and perioperative mortality. We assumed that surgical morbidity and mortality were the same under generalist and specialist care and applied costs of travel and lost work for those seeing a gynecologic-oncologist. We performed univariable sensitivity analyses and multivariable probabilistic sensitivity analysis to assess the model's robustness given the uncertainty of model inputs., Results: In our theoretical cohort of 200,000 patients with EIN, hysterectomy with a gynecologic-oncologist was associated with a decrease of 10,811 second surgeries for lymph node dissection, 87 surgical site infections, and 9 perioperative mortalities. When hysterectomy was performed by a general gynecologist, 9 fewer patients had a lymph node dissection because of perioperative mortalities that occurred before lymph node dissection with a gynecologic-oncologist. Hysterectomy with a gynecologic-oncologist was the dominant, cost-effective strategy because it saved $116 million and increased quality-adjusted life years by 180. In our univariable analyses, hysterectomy with a gynecologic-oncologist was cost-saving and increased quality-adjusted life years over a wide range of probabilities and costs for lymph node dissection, surgical site infection, and perioperative mortality. However, hysterectomy with a gynecologic-oncologist was only a cost-effective and cost-saving strategy in just over 50% of multivariable simulations, demonstrating that there is significant uncertainty in the model's cost-effectiveness., Conclusion: In our model, hysterectomy with a gynecologic-oncologist for patients with EIN was associated with cost savings and increased quality-adjusted life years. Our study supports that patients undergoing hysterectomy for EIN at institutions using Mayo criteria to determine need for lymphadenectomy may benefit from surgery with a gynecologic-oncologist rather than a general gynecologist to reduce costs and adverse events associated with a second surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Due to the increasing popularity of minipigs as pets, the frequency of presentation to the veterinarian is increasing as well. In addition to routine measures such as claw trimming, vaccination and antiparasitic treatment, diagnostics, and therapy of diseased minipigs are also common activities in the veterinary practice. In recent years, we have noticed more and more pathological changes of the female genital tract of uncastrated minipigs. There are also some case reports available in the international literature in this regard. The following case report describes the diagnostic procedures and ovariohysterectomies of 2 13-year-old female minipigs in detail. In these cases, uterine adenocarcinoma, and uterine carcinoma, respectively, combined with cystic endometrial hyperplasia (CEH) of the endometrium were diagnosed., Competing Interests: The authors declare no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The risk of undertreating occult endometrial cancer is a problem faced by gynecologists when treating endometrial hyperplasia. The objective of this study is to highlight diagnostic adjuncts to endometrial sampling techniques to improve preoperative detection of co-existing cancer. A systematic search of databases till July 2021: PubMed, ISI-Clarivate Web of Science, Scopus, and CENTRAL. A search of the related literature was also carried out. Two authors screened potential studies. Studies were included if they examined the diagnostic performance of any predictors of concurrent cancer in patients diagnosed with endometrial hyperplasia. Authors charted variables related to literature characteristics (e.g., authors, year of publication), population characteristics (e.g., preoperative diagnoses), and variables related to our research questions (e.g., postoperative diagnoses, risk predictors). After screening 591 potential studies, 28 studies were included. Studies included the data of 7409 endometrial hyperplasia patients with 2377 concurrent endometrial cancer cases (32.1%). Forty potential predictors of concurrent cancer were investigated. We examined three categories of potential predictors: clinical (22 studies), histopathologic/imaging (16 studies), and molecular (six studies) predictors. The proposed predictors, age, menopausal status, diabetes, WHO and endometrial intraepithelial neoplasia histopathologic criteria, pelvic magnetic resonance imaging, and molecular profiling are promising diagnostic adjuncts., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Atypical endometrial hyperplasia (AEH) is the precursor lesion in endometrial carcinoma, the most common gynaecological malignancy in New Zealand, with inequities in disease burden and outcome for Māori and Pacific women., Aims: In women diagnosed with AEH at two hospitals, to audit five standards of care for surgical management and time-to-treatment, and identify variation in care by ethnicity and other factors., Materials and Methods: Demographic, referral, diagnostic and treatment characteristics were collected for women with a new AEH diagnosis between 1/1/2019 and 31/12/2020. Surgical management and time-to-treatment were audited against Royal College of Obstetricians and Gynaecologists and New Zealand Ministry of Health Faster Cancer Treatment recommendations., Results: Of 124 participants, 60% were Pacific, 86% premenopausal, and 80% had obesity. For 55 women managed surgically, surgical standards of care were met. There were delays between referral, diagnosis and treatment - only 18% and 56% of women met the 62-day (referral to treatment) and 31-day (decision-to-treat to treatment) targets, respectively. Wait times were prolonged for women who had dilation and curettage (vs pipelle), magnetic resonance imaging (MRI) (vs no MRI), and surgery (vs medical management). Ethnic disparities were not identified for any standard., Discussion: Delays to treatment were found throughout women's journeys. Hospital services can streamline their clinical pathways for women referred for abnormal uterine bleeding, flagging obesity as a high suspicion for cancer indicator, increasing access to endometrial sampling in primary care and establishing 'one-stop-shop' outpatient assessment with empiric initiation of intrauterine progestogen., (© 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC., Methods: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve., Results: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53)., Conclusion: Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: Although ovarian conservation at hysterectomy for benign gynecologic disease has demonstrated mortality benefit in young patients and this benefit may be sustained up to age 65 years, there is a scarcity of data regarding ovarian conservation in those with a diagnosis of endometrial hyperplasia, a premalignant uterine condition., Objective: This study aimed to examine patient, hospital, treatment, and histology characteristics related to ovarian conservation at the time of inpatient hysterectomy for endometrial hyperplasia., Study Design: The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine patients aged ≤65 years with endometrial hyperplasia who had inpatient hysterectomy from January 2016 to December 2019. The exclusion criteria included concurrent gynecologic malignancy, adnexal pathology, and lymphadenectomy. Cases were grouped by adnexal surgery status (ovarian conservation or oophorectomy). A multivariable binary logistic regression model was used to identify independent characteristics for ovarian conservation. A classification tree was constructed with recursive partitioning analysis to examine utilization patterns of ovarian conservation., Results: Overall, 3105 patients (31.1%) underwent ovarian conservation at hysterectomy among 9975 patients. The utilization of ovarian conservation decreased gradually until age 45 years and then markedly decreased by age 52 years (63.3%-15.3%; P<.001). In a multivariable analysis, younger age, non-White, urban nonteaching centers, and vaginal hysterectomy were associated with increased utilization of ovarian conservation, whereas endometrial hyperplasia with atypia, obesity, comorbidity, large bed capacity centers, and Midwest and South regions were associated with decreased utilization of ovarian conservation (all, P<.05). A classification tree identified 17 utilization patterns for ovarian conservation, ranging from 7.8% to 100.0% (absolute rate difference, 92.2%)., Conclusion: The utilization of ovarian conservation at the time of inpatient hysterectomy in patients undergoing surgical management for endometrial hyperplasia started decreasing in their mid-40s and seemed to occur earlier than in benign hysterectomy. There was substantial variability in ovarian conservation at the time of hysterectomy for endometrial hyperplasia based on patient, hospital, surgical, and histology factors, suggesting the possible benefit of clinical practice guidelines for ovarian conservation in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg-320 mg for MA and 250 mg-600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo-oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient's age and whether they fulfil the strict criteria selection.

Pyometra is a common disease in intact bitches and queens and occurs, although less frequently,in most other female pets. The illness is generally diagnosed within 4 months after estrus, in middle-aged to older bitches and queens. Hormonal and bacterial factors are important for the disease development, and progesterone plays a key role. The diagnosis is based on case history, clinical signs, and findings on physical examination, laboratory analyses and diagnostic imaging. Pyometra is potentially life-threatening and considered a medical emergency. Surgical ovariohysterectomy is the safest and most efficient treatment, but purely pharmacologic options are possible in less severe cases., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Clinical application of exogenous hormone as a method of contraception and/or treatment of various gynecologic disorders is exceedingly common. Unfortunately, the concurrent use of these agents also complicates the interpretation of pathology specimens. Various studies have shown that morphologic changes induced by hormonal therapies are present in both non-neoplastic and neoplastic tissues within the women's reproductive tract. It is important to understand the exogenous hormone induced morphologic changes, as it helps the pathologists make the accurate diagnosis, and in turn, guide clinicians to make optimal clinical decisions. In this review, we summarize the morphologic changes in both neoplastic and non-neoplastic endometrial, cervical, and myometrial surgical specimens after hormonal therapies, particularly after progestin treatment. In the endometrium, particularly in the scenario of progestin-treated atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN), there is notoriously poor interobserver agreement and difficulty in assessing for the residual disease. We summarize current literature and propose our recommended approach in assessing these challenging endometrial biopsies, including a diagnostic algorism, the use of PAX-2, PTEN, beta-catenin immunohistochemistry panel, as well as consistency in diagnostic wording of the report. In the cervix, progestin makes dysplastic lesions appear metaplastic, thus high-grade squamous dysplastic lesions may be easily missed. Within the myometrium, lesions such as adenomyosis may show various degree of decidualization, while smooth muscle neoplasms may show apoplectic changes, and stromal lesions including endometrial stromal sarcoma may show more eosinophilic cytoplasm. All such changes may pose more or less diagnostic challenges in our daily practice. However, most are readily recognizable when we understand particular hormone related scenarios., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To analyze the clinical efficacy of fertility-preserving therapy in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC). Methods: The general condition, pathological type, treatment plan, tumor outcomes and pregnancy outcomes of 110 patients with AEH and EC treated with fertility-preserving therapy in Peking University People's Hospital from December 2005 to September 2019 were retrospectively analyzed. Kaplan-Meier and Log rank tests were used for survival analysis. Results: The response rate of 110 cases of AEH (62 cases) and EC (48 cases) was 94.5% (104/110) after fertility-preserving therapy. There were 93 cases (84.5%) achieved complete response and 11 cases (10.0%) achieved partial response, and the recurrence rate was 29.0% (27/93). The complete response rates of AEH and EC were 90.3% (56/62) and 77.1% (37/48), respectively, without significant difference ( P =0.057). The recurrence rates of EC were significantly higher than that of AEH (40.5% vs 21.4%; P =0.022). Forty-one patients with complete response had pregnancy intention, the pregnancy rate was 70.7% (29/41), and the live birth rate was 56.1% (23/41). The live birth rate of AEH was 68.2% (15/22) and that of EC was 42.1% (8/19), the difference was statistically significant ( P =0.032). The pathological type was related with the recurrence ( P =0.044). Conclusions: Patients with AEH and EC can obtain high complete response rate and pregnancy rate after fertility-preserving therapy. The recurrence rate of EC is higher than that of AEH, while the live birth rate of AEH is higher than that of EC.

Objective: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25-50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging., Methods: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases., Design: This was a retrospective study., Results: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29-6.48) in AUB, 2.7 (95% CI: 1.06-6.92) in hypertension, and 3.1 (95% CI: 1.19-7.97) in endometrial thickness ≥20 mm cases., Limitations: The present study has limitations inherent in its retrospective nature., Conclusion: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested., (© 2022 S. Karger AG, Basel.)

Background: The incidence of endometrial carcinoma (EC) is rising worldwide due to an increased life expectancy and obesity. Approximately 2% of patients with EC is under the age of 45. Because the incidence is also rising in young women, there is a clinical need for safe fertility sparing alternative treatments., Case Description: A 32-year-old women was diagnosed with low-grade endometrioid EC. Hysteroscopic tumour resection and progestin treatment resulted in complete tumour regression. The patient became pregnant through in vitro fertilisation (IVF)., Conclusion: This case illustrates that fertility sparing treatment, with oral progestin treatment is an alternative treatment option in selected young women with low grade, early stage endometrial carcinoma to achieve pregnancy. This treatment is internationally accepted.

In humans, atypical endometrial hyperplasia (AEH) is considered as a precancerous lesion of endometrial adenocarcinoma (EA), from which it must be distinguished. Precancerous lesions have not been reported in cats with EA. We now document the histopathological features of endometrial lesions in six cats, which histopathologically resembled human AEH and had a good prognosis following ovariohysterectomy. Grossly, one cat presented with papillomatous nodules and three cats had pyometra. Histopathologically, proliferation of endometrial epithelial cells without atypia was observed in all cases. In some regions of the endometrium, cells had increased atypia and were arranged in stratified layers, which formed irregular ducts and papillary structures. No invasive behaviour or vascular invasion was observed. On the basis of these findings, the cats were diagnosed with non-invasive or early-stage adenocarcinoma. Immunohistochemistry for oestrogen receptor and progesterone receptor revealed an inverse correlation with the severity of the endometrial lesions and degree of malignancy of tumour cells. Ki67 labelling revealed that mitotic activity increased as the lesion developed. All cats survived, with a median survival time of 385 days (range: 229-744 days). The distribution of the histopathological endometrial changes and the non-invasive behaviour in these feline cases resemble cases of AEH in humans., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To illustrate the effectiveness of hysteroscopic endometrial resection in conservative treatment of early endometrial cancer/atypical hyperplasia in women of reproductive age., Methods: Review of outcomes of women of reproductive age who underwent fertility sparing treatment (hysteroscopic superficial endometrectomy followed by progestin therapy) in early endometrial cancer., Results: Eight women with Stage I endometrial cancer and three with atypical endometrial hyperplasia underwent hysteroscopic superficial endometrial resection, followed by 1-year treatment with oral megestrol acetate. One patient had a synchronous endometrioid ovarian carcinoma. One patient with Grade 2 carcinoma opted for conservative treatment and had hysterectomy 3 months later for persisting disease. Ten patients showed no evidence of residual disease during a 12-month follow-up period with regular hysteroscopy. Five patients had seven pregnancies without assisted reproductive technology. One patient got pregnant after one attempt of in-vitro fertilization and oocyte donation. Pregnancy rate was 54.5%; two patients had two successful pregnancies and deliveries. Average time to pregnancy was 16 months from the end of treatment. All babies were delivered vaginally., Conclusion: Total superficial endometrial resection followed by progestin can be considered in patients with early endometrial cancer/atypical hyperplasia who still want to conceive. It does not seem to impair fertility nor pregnancy outcomes in women of reproductive age., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives : Endometrial hyperplasia (EH) is a precursor lesion to endometrial cancer (EC), and when cellular atypia is present, in 40% of cases, they are diagnosed with EC on hysterectomy. Usually, EH is clinically manifested by uterine bleeding. In patients with oral anticoagulant therapy (OAT), the uterus is the second most common source of bleeding. The aim of the study was to show that uterine bleeding in postmenopausal patients undergoing OAT may reveal precancerous endometrial lesions with atypia, or neoplastic lesions in patients with an initial diagnosis of endometrial hyperplasia without atypia (non-atypical endometrial hyperplasia, NAEH) on dilation and curettage (D&C). We will be able to estimate the risk of a postmenopausal female patient with uterine bleeding during an OAT to have a precancerous endometrial lesion. Materials and Methods : The subjects of the study were 173 female patients with uterine bleeding, who have had total hysterectomy with bilateral salpingoovarectomy, of whom 99 underwent an OAT. There were 101 female patients initially diagnosed with NAEH, of which 60 did not have anticoagulant treatment (mean age 57.36 ± 6.51) and 41 had anticoagulant treatment (mean age 60.39 ± 7.35) ( p = 0.006). From the pathology diagnosis moment, the surgery was performed at 42.09 ± 14.54 days in patients without OAT and after 35.39 ± 11.29 days in those who received such treatment ( p = 0.724). Results : Initial diagnosis of NAEH established at D&C was changed at the final diagnosis after hysterectomy in EH with cellular atypia (atypical endometrial hyperplasia AEH) or EC in 18.18% of patients without OAT, and in 40.54% of patients who received this treatment. Conclusions : Based on a logistic regression model, it is estimated that female patients with an initial histopathological diagnosis of NAEH and who underwent OAT have, on average, 4.85 times greater odds (OR = 4.85, 95% CI 1.79-14.06) than the others of being identified postoperatively with more advanced lesions.

Objective: The objective of this study was to determine the proportion of patients with a pre-invasive endometrial lesion who meet Mayo criteria for lymph node dissection on final pathology to determine if the use of sentinel lymph node biopsy in patients with pre-invasive lesions would be warranted., Methods: All women who underwent hysterectomy for a pre-invasive endometrial lesion (atypical hyperplasia or endometrial intra-epithelial neoplasia) between 2009 and 2019 were included for analysis. Relevant statistical tests were utilized to test the associations between patient, operative, and pathologic characteristics., Results: 141 patients met inclusion criteria. 51 patients (36%) had a final diagnosis of cancer, the majority (96%) of which were Stage IA grade 1 endometrioid carcinomas. Seven patients (5%) met Mayo criteria on final pathology (one grade 3, seven size >2 cm, one >50% myoinvasive). Three of these seven patients had lymph nodes assessed of which 0% had metastases. Six of these patients had frozen section performed, and 2 met (33%) Mayo criteria intraoperatively. Of the seven patients in the overall cohort that had lymph node sampling, six had a final diagnosis of cancer and none had positive lymph nodes. Of the 51 patients with cancer, only 10 had cancer diagnosed using frozen section, and only two met intra-operative Mayo criteria. Age > 55 was predictive of meeting Mayo criteria on final pathology (p = 0.007). No patients experienced a cancer recurrence across a median follow up of 24.3 months., Conclusions: Atypical hyperplasia and endometrial intra-epithelial neoplasia portend low risk disease and universal nodal assessment is of limited value., Competing Interests: Declaration of Competing Interest The authors declare no relevant conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Endometrial hyperplasia (EH) is commonly-seen in the patients with endometrial cancer (EC), we aimed to evaluated the risk factors of EC in patients with EH, to provide evidence to the clinical prevention and treatment of EC., Methods: This study was a retrospective study design. EH patients confirmed by pathological examinations and treated with hysterectomy in our hospital from June 1, 2018 to February 28, 2021 were included. The clinical characteristics of EC and no-EC patients were compared and analyzed. Logistics regression analyses were conducted to evaluate the risk factors of EC in patients with EH., Results: A total of 228 EH patients were included, the incidence of EC in the EH patients was 31.58%. There were significant differences in the age, BMI, diabetes, hypertension and pathology of EH between EC and no EC groups (all P < 0.05), no significant differences in the hyperlipidemia, preoperative CA 125 , number of deliveries, menopause and endometrial thickness between EC and no EC groups were found (all P > 0.05). Logistic regression analyses indicated that age > 50 y (OR 3.064, 95% CI 1.945-5.931), BMI ≥ 25 kg/m 2 (OR 2.705, 95% CI 1.121-3.889), diabetes (OR 3.049, 95% CI 1.781-5.114), hypertension (OR 2.725, 95% CI 1.108-3.431) and severe hyperplasia (OR 3.181, 95% CI 1.496-4.228) were the risk factors of EC in patients with EH (all P < 0.05)., Conclusions: The risk of EC in EH patients is high, especially for those patients with age > 50 y, BMI ≥ 25 kg/m 2 , diabetes, hypertension and severe hyperplasia, special attentions should be paid for occurrence of EC and early diagnosis and early treatment are needed for those patients., (© 2021. The Author(s).)

Objectives: to compare the accuracy of preoperative and postoperative endometrial sampling obtained by dilatation and curettage (D&C), Pipelle and hysteroscopy to diagnose endometrial malignancies and to evaluate the adequacy of surgical treatment for these patients., Study Design: This retrospective record-based study was conducted at Gynecology Oncology Unit, Ain Shams University Maternity Hospital, Cairo, Egypt. Records of patients with an initial preoperative or a final postoperative pathological diagnosis of endometrial hyperplasia or endometrial malignancies were retrieved over a six year period from January 2013 until March 2019. The preoperative biopsy methods, results, postoperative pathology diagnosis and treatment received were recorded and analyzed., Results: Records of 395 patients were retrieved. Rates of agreement between initial and postoperative pathology for endometrial hyperplasia (with and without atypia) were 10% by D&C, 7.8% by Pipelle and zero % by hysteroscopy; for endometrioid adenocarcinoma grade 1, they were 40.7% by D&C, 40.6% by Pipelle and 20% by hysteroscopy; for endometrioid adenocarcinoma grades 2 and 3, they were 83.7% and 84.6% by D&C, 97% and 60% by Pipelle, and 100% by hysteroscopy, respectively. For type II endometrial cancer and endometrial stromal sarcoma, agreement rates were 100% by all biopsy methods. Out of 13 cases diagnosed with atrophic endometrium preoperatively, 11 cases were diagnosed as endometrial stromal sarcoma. Comparing accuracy of the three biopsy methods, D&C had highest sensitivity of 61.9%; hysteroscopy showed 100% specificity, while Pipelle was the least accurate method. Finally, 61.4% of the patients received adequate surgical treatment., Conclusion: There were excellent concordance rates between initial biopsy and postoperative pathology in diagnosis of high grade endometrioid and other endometrial malignancies compared to endometrial hyperplasia and low grade endometrioid adenocarcinoma. Patients diagnosed initially with atrophic endometrium or hyperplasia warranted more surveillance before their surgical treatment. It is crucial to develop protocols for increasing accuracy of endometrial sampling such as performing molecular studies for preoperative pathology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To identify clinicopathological preoperative factors associated with concurrent endometrial carcinoma in patients undergoing surgical management of atypical endometrial hyperplasia., Methods: The records of all patients who underwent hysterectomy for preoperatively diagnosed atypical endometrial hyperplasia at a tertiary care hospital from April 2017 to April 2020 were retrospectively reviewed. Clinicopathological characteristics of patients were extracted. Patients who did not undergo hysterectomy or who had evidence of simple hyperplasia or carcinoma on initial biopsy were excluded. Univariate analysis was performed. A multivariate regression model for progression to endometrial carcinoma was developed., Results: A total of 126 patients were included. Of these patients, 19 (15.1%) had a final diagnosis of endometrial carcinoma, whereas 86 (68.2%) retained the diagnosis of atypical endometrial hyperplasia and 21 (16.7%) were found to have no residual atypical endometrial hyperplasia. The odds of a patient being diagnosed with endometrial carcinoma were 6.1 times higher (95% CI 1.32-27.68) if they had an endometrial stripe thickness >1.1 cm and 13.5 times higher (95% CI 3.56-51.1) if there was histological suspicion of carcinoma. The odds of a patient being diagnosed with endometrial carcinoma were significantly lower if the patient had an initial diagnosis of atypical endometrial hyperplasia in a polyp (OR 0.07; 95% CI 0.02-0.34)., Conclusion: Our results suggest that an endometrial stripe thickness >1.1 cm, a histological suspicion of carcinoma on preoperative pathology, and the absence of polyp involvement on initial diagnosis are the strongest predictors of endometrial carcinoma at the time of hysterectomy in patients with atypical endometrial hyperplasia., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Atypical endometrial hyperplasia (AEH) is considered a precursor of endometrioid carcinoma. The 2020 World Health Organization (WHO) classification divides endometrial hyperplasia into 2 categories: hyperplasia without atypia and atypical hyperplasia/endometrioid intraepithelial neoplasia (EIN); however, this classification does not consider the degree of nuclear atypia. We graded nuclear atypia for estimating the risk of finding carcinoma at hysterectomy. Also, we investigated genes involved in endometrial carcinogenesis including mismatch repair (MMR) genes and ARID1A, PIK3CA, PTEN, KRAS, and CTNNB1. We reviewed 79 biopsies of AEH from 79 patients who underwent hysterectomy within a 1-year interval. Intraobserver and interobserver agreement of grading nuclear atypia and the relationship between the grade of nuclear atypia at biopsy and the findings at hysterectomy were evaluated. Immunohistochemistry for MMR status was performed in all cases and targeted sequencing in 11. Using low-grade versus high-grade nuclear atypia, κ values ranged from 0.74 to 0.91 (89% to 96%) and from 0.72 to 0.81 (87% to 91%) for the intraobserver and the interobserver agreement, respectively. The degree of nuclear atypia at biopsy was highly predictive of the findings at hysterectomy (P=1.6×10-15). Of 53 patients with low-grade AEH, none had carcinoma at hysterectomy, whereas 6 (6/26; 23%) with high-grade AEH in the biopsy also had high-grade AEH in the uterus and 16 (16/26; 61%) had FIGO grade 1 carcinoma. MMR deficiency was found in 3 of the 79 patients. None of the genes showed a mutational load significantly associated with the degree of nuclear atypia. In summary, our data show high reproducibility within and between observers for the diagnosis of low-grade and high-grade AEH. Most cases of AEH had low-grade nuclear atypia and neither high-grade AEH nor carcinoma was encountered in the corresponding hysterectomy specimens., Competing Interests: Conflicts of Interest and Source of Funding: Supported by Grants FIS PI16-00902 and RTICC RD06/0020/0015, Department of Health, Spain, Fundación de la Asociación Española Contra el Cáncer (AECC), Grupos Estables. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: The immunohistochemical expression of isoform B of the progesterone receptor (PRB) has shown promising results in predicting the response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. We aimed to calculate the accuracy of PRB as a predictive marker of conservative treatment outcome in AEH or EEC., Design: Retrospective cohort study., Setting: University of Naples Federico II, Naples, Italy., Patients: Thirty-six consecutive premenopausal women <45 years of age with AEH (n = 29) or EEC (n = 7) conservatively treated from January 2007 to June 2018 were retrospectively assessed., Interventions: All patients had been treated with hysteroscopic resection plus levonorgestrel-releasing intrauterine device insertion and followed for at least 1 year. The immunohistochemical expression of PRB was separately assessed in the glands and stroma of the lesion and dichotomized as "weak" or "normal.", Measurement and Main Results: The treatment outcomes considered were (1) treatment failure (i.e., a combined outcome including no regression or recurrence); (2) no regression; and (3) recurrence. The predictive accuracy of PRB immunohistochemistry was assessed by calculating sensitivity (SE), specificity (SP), and area under the receiver operating characteristic curve (AUC). A weak glandular PRB expression showed SE = 70%, SP = 77%, and AUC = 0.74 for treatment failure; SE = 66.7%, SP = 70%, and AUC = 0.68 for no regression; and SE = 75%, SP = 68.8%, and AUC = 0.72 for recurrence. A weak stromal PRB expression showed SE = 100%, SP = 53.8%, and AUC = 0.77 for treatment failure; SE = 100%, SP = 46.7%, and AUC = 0.73 for no regression; and SE = 100%, SP = 43.8%, and AUC = 0.72 for recurrence., Conclusion: A weak stromal PRB expression is a highly sensitive predictive marker of both no response and recurrence of AEH and EEC conservatively treated., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Surgery is the mainstay treatment for endometrial cancer and complex atypical endometrial hyperplasia. These conditions are more common in the obese women and as such these patients pose additional risks and challenges to surgery. Laparoscopic hysterectomy (LH) is preferred over open surgery in obese patients as it reduces surgical morbidity. However, more recently, robotic-assisted hysterectomy (RH) has been used in morbidly obese patients to overcome the limitations of conventional laparoscopy. To compare the surgical outcomes of morbidly obese patients undergoing LH or RH for endometrial cancer or complex atypical hyperplasia. A retrospective analysis of morbidly obese patients (BMI > 40 kg/m 2 ) who underwent LH or RH for endometrial cancer or complex atypical hyperplasia at the Chris O'Brien Lifehouse Gynaecological Oncology Unit from 2015 to 2019 was performed. Data was collected from the prospectively maintained gynaecology oncology database and descriptive analysis was performed. 33 (51.6%) underwent LH and 31 (48.4%) had RH. More LHs were performed 2015-2017 period, whereas there were more RHs performed in 2018-2019 period (p = 0.01). The difference between theatre time use and operating time for LH surgery compared to RH was significantly shorter (45.7 for LH versus 61.9 min for RH, p = 0.009). RH was performed more commonly when BMI was > 50 kg/m 2 (p = 0.02). There has been an increase in the use of RH in morbidly obese patients, particularly for women with a BMI > 50 kg/m 2 .

Aim: Conventional endometrial examination by dilatation and curettage (D&C) is not accepted by many patients because it is associated with pain and risk of injury and typically requires anesthesia and hospitalization. While several less invasive endometrial screening tools have been developed, their diagnostic value is generally inferior to D&C. Therefore, the purpose of this study was to evaluate the effectiveness of a new, minimally invasive device, called the ES Sampler, for outpatient endometrial screening., Methods: This was a single-blind study of 96 patients (age: 36.8 ± 8.1 years) who attended Peking Union Medical College Hospital from March 2015 to August 2016. Specimens were collected from each participant using the ES Sampler, followed by traditional D&C by hysteroscopy, and evaluated by histology and/or cytology. The sampling adequacy, sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were compared, and patient acceptability was assessed., Results: Compared to traditional D&C, the ES Sampler exhibited 99.0% sampling adequacy, and the combined (histology and cytology) results demonstrated 88.9% sensitivity, 95.6% specificity, 88.9% positive predictive value, 95.6% negative predictive value, and 93.7% accuracy. Moreover, the majority of study participants reported mild or no pain associated with the ES Sampler, and blood loss was minimal., Conclusions: Our findings suggest that the minimally invasive ES Sampler is a reliable and accurate endometrial screening tool that is easily accepted by patients. The ES Sampler could be useful for screening high-risk patients who may need further, more invasive examination, thereby conserving medical resources and minimizing patient discomfort., (© 2021 Japan Society of Obstetrics and Gynecology.)

Objective: To describe the outcomes of patients undergoing robotic-assisted laparoscopic hysterectomy for grade-1 endometroid endometrial cancer or endometrial hyperplasia at our centre., Methods: Retrospective chart review was completed for 160 patients who underwent robotic-assisted laparoscopic hysterectomy by 5 general gynaecologists in a tertiary care setting between September 2008 and September 2018. Outcomes collected included operative time, estimated blood loss, length of stay, perioperative complications, readmissions, and recurrences. Subgroup analysis was completed after stratifying by body mass index (BMI; 3 groups: A, <40 kg/m 2 ; B, 40-50 kg/m 2 ; and C, >50 kg/m 2 ). Subgroups were compared with ANOVA or Fisher exact test., Results: The intraoperative complication rate was 3%. The rate of conversion to laparotomy was 2%, and the rate of bowel injury, 1%. The postoperative complication rate was 8%. The rate of major postoperative complications was 4%, and 3% of patients required readmission postoperatively. The mean BMI was 43 (range 21-71) kg/m 2 . There were no differences in perioperative complication, readmission, or recurrence rates between subgroups. Groups B and C were more likely to have had an ASA of 3-4, suggesting a higher burden of comorbidity. Operating room time, procedure time, and estimated blood loss were higher in group C., Conclusion: Despite this cohort's mean BMI falling within the category of class III obesity, complication and conversion rates were similar to those reported in the literature and did not increase with BMI, despite an increased comorbidity burden. These results suggest that robotic surgery is a safe and effective method for providing minimally invasive surgery to a technically challenging population., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Introduction: Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stage IA grade 1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point., Methods: We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life., Planned Outcomes: This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy., Results: The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia., Systematic Review Registration: Prospero 2019 number CRD42019145991.

Aim: Our objective was to assess clinical and pathological factors associated with a final diagnosis of endometrial carcinoma in patients with atypical endometrial hyperplasia with a particular emphasis on the grading of atypia., Materials and Methods: A retrospective review over five years on patients (N = 97) who underwent hysterectomy for a diagnosis of atypical endometrial hyperplasia at a statewide public tertiary gynaecologic oncology centre. Clinical and pathological characteristics were obtained., Results: The rate of concurrent endometrial carcinoma was 34% (n = 33) with most being stage 1A endometrioid. A significant group difference was reported for age at diagnosis (t = -2.20 P = 0.031 d = 0.43) with carcinoma patients on average older (M age  = 60.2 (8.9) years) than patients without carcinoma (M age  = 55.5 (12.3) years). No significant group differences were found for body mass index, endometrial thickness or time between diagnosis and treatment. Significantly higher rates of carcinoma were reported in patients with moderate atypical hyperplasia (27.6%) and severe atypical hyperplasia (66.7%), compared to mild atypical hyperplasia (7.1%). Only severe atypical hyperplasia (odds ratio (OR) = 21.5, 95% CI 2.8-163.1, P = 0.003) and postmenopausal status (OR = 13.2, 95% CI 1.3-139.0, P = 0.032) significantly increased the risk of carcinoma in a multivariate model., Conclusion: Severe atypical hyperplasia and postmenopausal status were significant predictors of concurrent endometrial carcinoma in patients with atypical endometrial hyperplasia. The grading of atypical hyperplasia may be utilised by gynaecologic oncologists in the triage and referral process of managing these patients; however, the grading system requires external validation in larger prospective studies., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: To compare the diagnostic accuracy of aspiration biopsy and dilatation and curettage (D&C) in patients diagnosed with endometrial hyperplasia prior to hysterectomy., Methods: We retrospectively reviewed medical records of 250 patients diagnosed with endometrial hyperplasia by endometrial sampling between July 2003 and March 2020. Endometrial sampling was performed by aspiration biopsy (n = 150) or D&C (n = 100), followed by hysterectomy within 6 months. Pathological findings of hysterectomy specimens of the two groups were compared to preoperative findings., Results: The overall diagnostic concordance between endometrial sampling specimen including D&C and aspiration biopsy, and hysterectomy specimen was 51.0% (51/100) and 41.3% (62/150), respectively. Patients whose preoperative specimen was obtained by D&C were upgraded less significantly than those who underwent aspiration biopsy (21.0% vs 36.7%; P = 0.008). In particular, significantly fewer patients were upgraded after D&C than after aspiration biopsy in hyperplasia without atypia (12.5% vs 29.0%; P = 0.028). In addition, when the final pathological upgrade rate to endometrial carcinoma was evaluated between the two methods of endometrial sampling, significantly fewer cases were noted after D&C than after aspiration biopsy (15.0% vs 27.3%; P = 0.022)., Conclusions: In our study, D&C more accurately reflected the final diagnosis in patients with endometrial hyperplasia than aspiration biopsy based on the histological examination of hysterectomy specimens. When considering the management strategy for women with an endometrial hyperplasia diagnosis obtained by aspiration biopsy, physicians should consider the significant rate of upgraded diseases with this method of endometrial sampling.

Backround: Ultrasonography is difficult to distinguish between endometrial pathologies and often requires curettage. ARFI (Acoustic Radiation Force-Based Elasticity Imaging) is a new ultrasonography elastography method. Using ARFI, it is possible to obtain information about the likelihood of the tissue benign or malignant., Aim: The aim of this study is to evaluate the contribution of ARFI to differentiate endometrial pathologies in hysterectomy specimens., Subjects and Methods: Our study was prospectively, January-May 2017, performed in randomly 45 cases of 41-91 years of age (mean 58.3 years) who have decided to have hysterectomy. Hysterectomy was performed for uterine prolapse and endometrial hyperplasia in elderly patients and menorrhagia in young patients. Pathology results were compared with ARFI values and endometrial thickness. ANNOVA test was used for the comparison of ARFI values., Results: Pathology revealed 14 cases of endometrial atrophy, 11 cases of proliferative phase, 10 cases of polyp, 6 cases of endometrial hyperplasia, and 4 cases of endometrium cancer. There is a statistically significant difference between mean ARFI values of endometrium, subendometrium, and myometrium of the groups (P < 0.05). There was a statistically significant difference between the mean endometrial thickness of the groups (P < 0.05)., Conclusion: Endometrium ARFI contributes to the differential diagnosis of endometrial pathologies. Subendometrial and myometrial ARFI values decrease in polyps and increase in hyperplasia. Our study shows that the addition of subendometrium ARFI to gray-scale sonography before deciding on invasive procedures in endometrial pathologies may improve diagnostic accuracy. We concluded that further in vivo studies will establish the usefulness of this technique for preoperative diagnostic measures., Competing Interests: None

Background: In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens., Objectives: To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment., Search Methods: We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020., Selection Criteria: Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment., Data Collection and Analysis: Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods., Main Results: Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome., Authors' Conclusions: There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)