Uterine-Conserving Treatment Options for Atypical Endometrial Hyperplasia and Early Endometrial Cancer.

PURPOSE OF REVIEW: This review aims to synthesize available literature on uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma while highlighting remaining unanswered questions. RECENT FINDINGS: The need for uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma is growing with the increasing number of cases in younger patients or those who cannot undergo surgery. We reviewed the oncological and reproductive outcomes associated with endocrine therapies used for atypical endometrial hyperplasia and grade 1 endometrial carcinoma. The rising prevalence of delayed childbearing, obesity, and diabetes in reproductive-age individuals and of medical comorbidities associated with high surgical risk continues to amplify the demand for uterine-conserving therapies. Appropriate patient selection for such therapies is imperative to maximize likelihood of treatment response. The ideal candidates are patients with atypical endometrial hyperplasia or early-stage, low-grade endometrial cancer with no evidence of myometrial invasion or extrauterine disease. The most accepted conservative therapeutic approach is hormonal therapy with close surveillance, with or without eventual hysterectomy following childbearing or failure of treatment. Further prospective and randomized trials are needed to address optimal patient and treatment selection, as well as the use of molecular profiling for treatment individualization and prognostication.

Red cell distribution width and mean platelet volume detection in patients with endometrial cancer and endometrial hyperplasia.

Background: Endometrial cancer is the most common malignancy in women in developed countries, and its incidence is increasing annually. Due to the availability and cost-effectiveness of serum markers of red cell distribution width (RDW), and mean platelet volume (MPV), we decided to investigate these two important markers in patients with endometrial cancer and assess their role in diagnosing the tumor and differentiate it from endometrial hyperplasia and other causes of bleeding. Methods: This is a case-control study that examined the data of patients who were referred to Al-Zahra Hospital during 2022-2023 with complaints of abnormal bleeding and underwent diagnostic curettage. Based on the pathology findings, the patients were divided into 3 groups, including endometrial cancer, endometrial hyperplasia, and control. The clinical characteristics and results of MPV and RDW were compared in these three groups. The IBM SPSS Statistics for Windows, Version 21.0. was used for data analysis. Results: In this study, 87 women were examined in three groups endometrial cancer, endometrial hyperplasia, and control with a mean age of 52.70 ± 11.63 years. The results showed that the endometrial cancer group, had higher gravida, underlying disease, history of radiation therapy, anticoagulant therapy, blood transfusion, surgery, and family history of cancer (p < 0.05). Meanwhile, the endometrial cancer group had lower menstrual age and history of using contraceptives than other groups (p < 0.05). In addition, in this study, the results indicated that the levels of MPV and RDW in the endometrial cancer group were significantly higher than in the endometrial hyperplasia and control groups (p < 0.05). Conclusion: Since MPV and RDW are cheap and accessible and can be easily obtained from complete blood count panels, they can be used as suitable diagnostic markers for endometrial cancer. However, conducting comprehensive multicenter prospective studies with a larger sample size can be helpful.

Should we prioritise proper surgical staging for patients with Atypical endometrial hyperplasia (AEH)? Experience from a single-institution tertiary care oncology centre.

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.

Comparison of B-cell lymphoma 2 (BCL-2) expression in disordered proliferative endometrium and simple endometrial hyperplasia.

BACKGROUND AND OBJECTIVE: B-cell lymphoma-2 (BCL-2) is an anti-apoptotic protein that may play a role in disordered proliferative endometrium (DPE) and endometrial hyperplasia (EH). Several studies have investigated BCL-2 expression in normal, hyperplastic endometrium and endometrial adenocarcinoma, with conflicting results. Therefore, the present study aimed to compare the expression of BCL-2 in disordered proliferative endometrium and simple EH. METHODS: In this cross-sectional study, 63 DPE and 67 SEH samples from patients referred to Mostafa Khomeini Hospital between 2017 and 2022 were immunohistochemically stained by BCL-2 antibody. BCL-2 expression in each sample was reported as negative, weak positive, and strong positive. The findings were analyzed using SPSS version 16 software. RESULTS: Negative, weakly positive, and strongly positive BCL-2 expression was observed in 55.6%, 38.1%, and 6.3% of DPE samples, and 61.2%, 31.3%, and 7.5% of SEH samples, respectively, which does not show a statistically significant difference (p=0.718). There was no relationship between the age of patients and BCL-2 expression in any of the two groups of DPE and SEH (p=0.378 and p=0.178, respectively). CONCLUSION: BCL-2 expression is observed with a relatively similar frequency in DPE and SEH samples, and it is probably under the control of oestrogen hormone as the main factor involved in the pathogenesis of these lesions.

Treating endometrial hyperplasia (EH) post-tamoxifen treatment in breast cancer survivors: what are our options?

Tamoxifen is known to raise the risk of endometrial hyperplasia and cancer. There is virtually limited literature on how to handle Tamoxifen-induced endometrial hyperplasia (EH) in a breast cancer survivor. Levonorgestrel-releasing intrauterine system (LNG-IUS) has been explored as preventive strategies, but its impact on breast cancer recurrence especially in Progesterone receptor (PR)-positive patient is not clear. Aromatase Inhibitors (AIs) have shown beneficial results in EH after tamoxifen and their role should be explored in further trials.

Quantitative Assessment of Polarization and Elastic Properties of Endometrial Tissue for Precancer/Cancer Diagnostics Using Multimodal Optical Coherence Tomography.

Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young's elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm-1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm-1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies.

Endometrial Adenocarcinoma After a Benign Biopsy Without Atypia: A Case Report.

Endometrial biopsy is a highly effective screening procedure used to determine endometrial cancer and its precursors. This is often used to rule out endometrial cancer, the most common gynecologic cancer in the United States, before a total hysterectomy. This is a case of a benign endometrial biopsy that was ultimately malignant in the post-operative pathology report. A 37-year-old female presents with a six-month history of dysmenorrhea, passage of large clots, and pelvic pain, seeking definitive treatment with a hysterectomy. The pre-operative assessment included ultrasound, hysteroscopic exam, and endometrial biopsy. The ultrasound demonstrated evidence of adenomyosis due to the heterogeneous appearance of the myometrium and an endometrial stripe of 36 mm. Endometrial biopsy using pipelle was performed alongside an in-office hysteroscopic exam, which had a hyperplastic appearance of the endometrium. The biopsy resulted in hyperplasia without atypia and scant polypoid endometrial tissue. The patient underwent a total laparoscopic hysterectomy and bilateral salpingectomy without complications. The post-operative pathology report indicated a grade 2 invasive endometrial adenocarcinoma extending through 75% of the myometrium. Incidental diagnosis of endometrial adenocarcinoma following total hysterectomy is rare and poses significant medical implications. Endometrial hyperplasia without atypia has a low risk of progressing to endometrial carcinoma over time.

DNA hypermethylation of tumor suppressor genes TWIST1, GATA4, MUS81 and NTRK1 in endometrial hyperplasia.

OBJECTIVE: To investigate DNA methylation of specific tumor suppressor genes in endometrial hyperplasia compared to normal endometrial tissue. File and methodology: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 40 tissue samples with atypical endometrial hyperplasia, 40 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with a normal endometrium. RESULTS AND CONCLUSION: Differences in DNA methylation among the groups were found in TWIST1, GATA4, MUS81, and NTRK1 genes (TWIST1: atypical hyperplasia 67.5%, benign hyperplasia 2.5%, normal endometrium 22.5%; P < 0.00001; GATA4: atypical hyperplasia 95%, benign hyperplasia 65%, normal endometrium 22.5%; P < 0.00001; MUS81: atypical hyperplasia 57.5%, benign hyperplasia 22.5%, normal endometrium 5%; P < 0.00001; NTRK1: atypical hyperplasia 65%, benign hyperplasia 27.5%, normal endometrium 10%; P < 0.00001). Higher methylation rates were observed for the tumor suppressor genes of TWIST1, GATA4, MUS81, and NTRK1 in samples with atypical endometrial hyperplasia compared to samples with normal endometrial tissue, and higher methylation rates were found in samples with atypical endometrial hyperplasia compared to samples of benign endometrial hyperplasia. DNA methylation of TWIST1, GATA4, MUS81, and NTRK1 is involved in the pathogenesis of atypical endometrial hyperplasia.

A Review of the Risk Factors Associated with Endometrial Hyperplasia During Perimenopause.

Background: Endometrial hyperplasia, characterized by excessive growth leading to endometrial thickening, is commonly observed in the premenopausal period. Its prevalence in postmenopausal women is approximately 15%, peaking between ages 50 and 60. This condition often manifests as abnormal uterine bleeding and can progress to malignancy, with varying risks depending on the type of hyperplasia. Purpose: This study aims to investigate the factors influencing endometrial thickness during the perimenopausal period and raise awareness among healthcare professionals about the importance of evaluating and caring for individuals with endometrial hyperplasia. Methods: Studies examining the association between various factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, genetic factors, and endocrine-related proteins and the development of endometrial hyperplasia were reviewed. The literature search encompassed relevant databases, including PubMed, Scopus, and Web of Science. Results: Research findings indicate significant associations between changes in gene expression of several factors and the development of endometrial hyperplasia. Notably, the risk of progression to cancer varies between non-atypical and atypical hyperplasia cases. Factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, Lynch syndrome, tamoxifen use, and alterations in gene expression of TNF-α, EGF, IGF-1, IGF-1R, and PTEN have been implicated in the pathogenesis of endometrial hyperplasia. Conclusion: This study underscores the importance of understanding the factors influencing endometrial thickness during the perimenopausal period. It emphasizes the pivotal role of healthcare professionals in evaluating and caring for individuals with this condition.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol.

BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

SHP2-Triggered Endothelial Cell Activation Fuels Estradiol-Independent Endometrial Sterile Inflammation.

Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen-induced sterile inflammation regulates EH remains unclear. Here, a single-cell RNA-Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1ß and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell-macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA-Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1Tyr380. This event activates downstream activator protein 1 (AP-1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial-specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol-driven acute inflammation to macrophage-amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen-related diseases.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

OBJECTIVE: To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. METHOD: This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. RESULTS: The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. CONCLUSION: For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1.

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.

Few-shot learning to identify atypical endometrial hyperplasia and endometrial cancer based on transvaginal ultrasonic images.

Objective: It is challenging to accurately distinguish atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) under routine transvaginal ultrasonic (TVU) detection. Our research aims to use the few-shot learning (FSL) method to identify non-atypical endometrial hyperplasia (NAEH), AEH, and EC based on limited TVU images. Methods: The TVU images of pathologically confirmed NAEH, AEH, and EC patients (n = 33 per class) were split into the support set (SS, n = 3 per class) and the query set (QS, n = 30 per class). Next, we used dual pretrained ResNet50 V2 which pretrained on ImageNet first and then on extra collected TVU images to extract 1*64 eigenvectors from the TVU images in SS and QS. Then, the Euclidean distances were calculated between each TVU image in QS and nine TVU images of SS. Finally, the k-nearest neighbor (KNN) algorithm was used to diagnose the TVU images in QS. Results: The overall accuracy and macro precision of the proposed FSL model in QS were 0.878 and 0.882 respectively, superior to the automated machine learning models, traditional ResNet50 V2 model, junior sonographer, and senior sonographer. When identifying EC, the proposed FSL model achieved the highest precision of 0.964, the highest recall of 0.900, and the highest F1-score of 0.931. Conclusions: The proposed FSL model combining dual pretrained ResNet50 V2 eigenvectors extractor and KNN classifier presented well in identifying NAEH, AEH, and EC patients with limited TVU images, showing potential in the application of computer-aided disease diagnosis.

Evaluation of autophagy related ATG4B gene, protein and miR-655-3p expression levels in endometrial cancer and hyperplasia.

OBJECTIVE: The pathogenesis of endometrial cancer (EC) and hyperplasia is complex and poorly understood. Autophagy has emerged as a crucial aspect of this process. METHODS: This study examines the role of autophagy in the pathogenesis of EC and hyperplasia by investigating the expression of the autophagy-related 4B cysteine peptidase (ATG4B) gene, protein, and miR-665-3p levels in patients compared to a control group. This cross-sectional case control study analyzed 90 endometrial tissues, including 30 tumors, 30 normal controls, and 30 hyperplasia, using quantitative reverse transcription polymerase chain reaction and Western blot to assess ATG4B gene and protein levels. RESULTS: Higher ATG4B gene expression levels were found in the endometrial tissue of EC patients than in hyperplasia patients and controls. Furthermore, protein levels of ATG4B were also higher in EC and hyperplasia patients than in controls. ATG4B gene expression and protein levels were positively correlated in EC patients. However, in EC patients, miR-655-3p showed a significant negative correlation with the ATG4B gene and protein levels. CONCLUSION: ATG4B gene and protein expression is elevated in EC tissue, suggesting their role as a tumor promoter. Evaluating their levels could serve as markers for monitoring EC progression and prognosis.

Model Predicting the Risk of Endometrial Hyperplasia Developing into Endometrial Cancer.

Background: This study retrospectively analyzed the medical records of 200 patients with endometrial hyperplasia to predict the risk of concurrent endometrial cancer. Methods: Patients were categorized into either the endometrial cancer group or the endometrial hyperplasia group based on post-hysterectomy pathology. The investigation compared general information, tumor indices, fertility history, preoperative endometrial sampling methods, comorbidities, and clinical symptoms between the groups to identify risk factors for endometrial hyperplasia complicating endometrial cancer. Results: (1) Of the 200 patients, 68 (34.0%) were diagnosed with concurrent endometrial cancer post-hysterectomy. Among these, 60 (88.24%) had endometrioid adenocarcinoma, while 8 (11.76%) had other types. Stage I was identified in 58 patients (85.29%) and Stage II in 10 patients (14.71%). High differentiation was observed in 57 cases (83.82%), moderate differentiation in 7 cases (10.29%), and poor differentiation in 4 cases (5.89%), indicating that most endometrial cancers complicated by hyperplasia were early-stage, well-differentiated endometrioid carcinomas; (2) Univariate analysis revealed statistically significant differences in age, menopausal status, length of menopause, and preoperative endometrial pathology of severe atypical hyperplasia between the groups; (3) Multivariate analysis indicated significant differences for age ≥ 53.5 years (OR: 4.307, 95% CI: 2.018-9.192, p < 0.05), menopausal status (OR: 5.250, 95% CI: 2.449-11.252, p < 0.05), and severe atypical endometrial hyperplasia (OR: 4.817, 95% CI: 1.260-18.419, p < 0.05); (4) Significant differences were observed among patients with endometrial hyperplasia when stratified by the presence of zero, one, two, or three high-risk factors. Conclusion: In conclusion, patients aged ≥ 53.5 years, those who are menopausal, and those with severe atypical endometrial hyperplasia preoperatively are at higher risk for endometrial cancer. The risk increases with the number of high-risk factors present in patients with atypical endometrial hyperplasia.

Weight-loss therapy in patients with obesity with endometrial intraepithelial neoplasia and uterine cancer.

OBJECTIVE: Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer. METHODS: The Merative MarketScan Database was used to identify patients aged 18-70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use. RESULTS: Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P < .001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P < .001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy. CONCLUSIONS: Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer.

Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer.

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.

Assessing the Role of Transvaginal Sonography in Post-menopausal Bleeding: A Less Invasive Approach to Identify Endometrial Carcinoma.

Background Post-menopausal bleeding (PMB) is a very common complaint seen in current practice. Endometrial carcinoma (EC) commonly presents with PMB. Endometrial biopsy is the tool for definitive diagnosis, but it is invasive. Transvaginal sonography (TVS) is a non-invasive tool that can help us in the initial evaluation of such patients. Methods A prospective observational study was conducted on 76 women with PMB. TVS and histopathological study, along with basic evaluation and investigations, were performed on all participants, followed by necessary treatment and follow-up. Data collected were studied and statistically analyzed. Results A maximum of 27.63% (n=21) of patients had endometrial atrophy causing their PMB. Proliferative endometrium was observed in 21.06% (n=16) of cases, 13.15% (n=10) of women had secretory endometrium, 23.68% (n=18) had simple endometrial hyperplasia, 3.94% (n=3) had complex endometrial hyperplasia without atypia, and another 3.94% (n=3) had complex endometrial hyperplasia with atypia. Further classifying, women with benign hyperplasia included 27.63% (n=21) and those with atypical hyperplasia included 3.94% (n=3). Out of the 5.26% (n=4) patients diagnosed with EC on histopathology, TVS identified carcinoma in 75% (n=3) cases. This indicates that the sensitivity and specificity of TVS in detecting EC are 75% and 100%, respectively. The positive predictive value (PPV) is 100%, the negative predictive value (NPV) is 98.63%, and the accuracy is 98.68%. Conclusion If the cut-off for endometrial thickness is set at 4 mm, then TVS proves to be an effective and reliable tool for screening and diagnosing EC. It can thus serve as a safe threshold to screen patients with PMB using TVS.