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In this study, we developed radiomic models that utilize a combination of imaging features and clinical variables to distinguish endometrial cancer (EC) from normal endometrium on routine computed tomography (CT). A total of 926 patients consisting of 416 endometrial cancer (EC) and 510 normal endometrium were included. The CT images of these patients were segmented manually, and divided into training, validation, testing and external testing sets. Non-texture and texture features of these images with endometrium or uterus as region of interest were extracted. The clinical feature “age” was also included in the feature set. Feature selection and machine learning classifier were applied to normalized feature set. This manual optimized combination was then compared with the best pipeline exported by Tree-Based Pipeline Optimization Tool (TPOT) on testing and external testing set. The performances of these machine learning pipelines were compared to that of radiologists. The manual expert optimized pipeline using the “reliefF” feature selection method and “Bagging” classifier on the external testing set achieved a test ROC AUC of 0.73, accuracy of 0.73 (95% CI 0.62–0.82), sensitivity of 0.64 (95% CI 0.45–0.79), and specificity of 0.78 (95% CI 0.65–0.87), while TPOT achieved a test ROC AUC of 0.79, accuracy of 0.80 (95% CI 0.70–0.87), sensitivity of 0.61 (95% CI 0.43–0.77), and specificity of 0.90 (95% CI 0.78–0.96). When compared to average radiologist performance, the TPOT achieved higher test accuracy (0.80 vs. 0.49, p

PURPOSE OF REVIEW To clarify a lingering issue, the true incidence of repeated implantation failures (RIF) in women undergoing successive frozen euploid single embryo transfers (FE-SET). RECENT FINDINGS As not all Assisted reproductive techinique (ART) attempts are crowned by success, it has been questioned since incept of ART whether failures resulted from an embryonic or endometrial cause. RIF has received no precise definition but a trend has existed toward setting a more stringent definition, as reproductive biology has become more effective and ART success rates improved. No scientific society has yet convened on a universally accepted definition. The advent of effective and well tolerated pregestational testing of embryos for aneuploidy (PGT-A) has allowed to not transfer aneuploid embryos, which are bound not to succeed. This, therefore, justify revisiting the concept of RIF when only euploid embryos are transferred. SUMMARY Contrary to lingering beliefs, the results of our study indicate that RIF following three successive euploid embryo transfers in a morphologically normal endometrium is a rare occurrence (

Aim: This study aimed to investigate the role of endometrial thickness in endometrial pathologies and compare transvaginal ultrasonography (TvUSG) and histopathological results in pre-and post-menopausal women with abnormal uterine bleeding. Methods: We retrospectively reviewed the records of 1882 women with abnormal uterine bleeding between 2018 and 2020. After exclusions, the final study population consisted of 1088 women. The primary variable was the endometrial thickness. Secondary variables examined were final diagnosis, age, gravidity, parity, and menopausal status. Results: Results for 653 women (60.0%) with normal endometrium, 26 women (2.4%) with endometrial carcinoma, and 409 women (37.6%) with other endometrial pathology were analyzed. The mean endometrial thickness of the women with normal endometrium was 11.38±5.80 mm (range: 3-45 mm), while the mean endometrial thickness of the women with other endometrial pathology and endometrial carcinoma were 12.27±5.15 mm (range: 3-33 mm), and 17.24±7.19 mm (range: 5-33 mm), respectively. A statistically significant difference was detected between the groups concerning endometrial thickness (F=15.464, p

Given the involvement of different extracellular matrix (ECM) metalloproteinases (MMPs) in endometriosis, the protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) was analyzed in this study in endometriosis and normal endometrium. Tissue samples were collected prospectively from 64 premenopausal patients undergoing operative laparoscopy. Protein expression of TIMP3 was analyzed immunohistochemically in endometriotic lesions (

Estrogen receptors (ER) play an important role in mediating action. The ER α has a higher affinity for estrogen and the dominant form of the normal endometrium. A cross-sectional study from an ectopic tissue of endo-metriosis and normal was examined for immunohistochemistry. This research was conducted from November 2015 until the sample complete. The analysis was performed using Fisher Exact test, p

Endometrial cancer is the sixth most common neoplasm in women worldwide, with a rising incidence largely attributed to the ongoing obesity epidemic. TNF-Related Apoptosis-Inducing Ligand (TRAIL) and TRAIL receptors have been tested for their predictive, diagnostic, and prognostic values in various cancers, as well as for possible use in combination therapies. The roles of TRAIL and its receptors in endometrial tissue biology has not yet been cleared, and the potential of these molecules as biomarkers in endometrial cancer is yet to be defined. We investigated the expression profiles of TRAIL and its transmembrane receptors during endometrial carcinogenesis to evaluate their potential as prognostic markers. Paraffin-embedded normal endometrium (n=18), endometrial hyperplasia (n=27), and endometrioid endometrial adenocarcinoma tissues (n=100) were analysed for TRAIL and receptor expression profiles via immunohistochemical staining. Apoptotic indexes in the corresponding tissues were defined by TUNEL assay. Endometrial carcinoma displayed decreased TRAIL and DR4 expressions compared to the normal endometrium, while increased DR5 and decoy receptor (DcR1 and DcR2) expressions were evident. The complex atypical hyperplasia displayed the most similar expression profiles to the endometrial carcinoma, in accordance with the greatest risk of progression to endometrial carcinoma attributed to this tissue type. TRAIL/TRAIL receptor expression levels did not correlate with the prognostic factors of tumor stage or grade, or depth of myometrial invasion. Overall, distinct profiles of TRAIL and its receptor expressions were evident in progression from normal endometrium to hyperplasia and cancer, which may indicate significance of TRAIL signaling in the course of endo metrial carcinoma development. © 2019, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.

Study Objective The objective of this video is to demonstrate the feasibility of office hysteroscopy for the management of retained products of conception (POCs). Design N/A. Setting Two patients present weeks after early pregnancy loss with ongoing bleeding without fever or pain. Imaging is notable for heterogenous endometrial contents. After informed consent is obtained, office hysteroscopy is performed which visualizes retained POCs in the endometrial cavities. Patients or Participants Two patients with retained POCs are highlighted. Interventions A 5.5mm rigid hysteroscope with a 12-degree lens is used for office operative procedures so the working instrument is kept in the field of view. We routinely use vaginoscopy without a speculum or tenaculum to minimize patient discomfort. The first case has a smaller lesion which is taken down with blunt scissors in a targeted fashion. Given the large amount of products in the second case, a 5mm hysteroscopic morcellator facilitates efficient and directed removal, taking care to preserve normal endometrium. Measurements and Main Results Direct visualization of the endometrial cavities confirms complete removal of retained POCs. Conclusion Office hysteroscopy is a safe and effective approach for the management of retained POCs. It allows for targeted removal under visualization and reduces adhesion formation compared to traditional dilation and curettage. The vaginoscopic approach significantly reduces pain so no anesthesia is necessary, and patients are able to resume normal activities post-procedurally. It cost-effective compared to operating room procedures.

For decades, the primary focus of cancer research has been the cancer tissue itself. Advances in next-generation sequencing technologies have enabled identification and characterisation of driver mutations, provided insights into the tumour burdens and underlying mutational processes, sub-clonal diversification and tumour heterogeneity. However, all cancers arise from cells that were once normal. Over time, they acquired certain mutations which increased their fitness, giving them a selective advantage over their neighbours and allowing uncontrolled growth, clonal expansion and malignant transformation. Our understanding of somatic evolution occurring in normal tissues with age and in the early stages of tumourigenesis remains relatively poorly understood. In this thesis, I aimed to investigate somatic evolution in normal ageing human tissues. Firstly, I helped to establish a robust low DNA input whole-genome sequencing workflow for laser-capture micro-dissected cellular material. I then utilised this approach to explore the genomic and evolutionary landscapes of the normal human endometrium. In the first results chapter, I investigate the clonal composition of normal endometrial glands. The majority of glands are clonal cell populations that share a common recent ancestor and the monoclonality is independent of whether they have a driver mutation. In the second results chapter, I investigate the mutational landscape of normal endometrial glands. We show that somatic mutations (base substitutions, indels and genome rearrangements) accumulate with age in a more-or-less linear manner. A small number of ubiquitous mutational processes accounts for the majority of all mutations. A remarkably high proportion of normal endometrial glands carry at least one driver mutation (of the type that one is used to finding in cancers). Accumulation of drivers is negatively affected by parity. Through phylogenetic tree reconstruction of somatic mutations in endometrial glands, we show that driver mutations often occur early in life and continue to accumulate with age. This work identifies a distinct mutational landscape in the normal endometrium that is in keeping with the presence of early positive selection in this highly regenerative tissue., CRUK Cambridge Cancer Centre

The human endometrium is an essential component in human reproduction that has the unique characteristic of undergoing cyclic regeneration during each menstrual cycle. Vigorous regeneration after shedding may be sustained by stem/progenitor cells, for which molecular markers have not been fully identified. Although clonality analysis using X chromosome inactivation patterns has shown that normal human endometrial glands are composed of a monoclonal cell population, whether clonal expansion is derived from stem/progenitor cells remains unclear. Remarkable advances in next‐generation sequencing technology over the past decade have enabled somatic mutations to be detected in not only cancers, but also normal solid tissues. Unexpectedly frequent cancer‐associated mutations have been detected in a variety of normal tissues, and recent studies have clarified the mutational landscape of normal human endometrium. In epithelial glandular cells, representative cancer‐associated mutations are frequently observed in an age‐dependent manner, presumably leading to growth advantage. However, the extremely high mutation loads attributed to DNA mismatch repair deficiency and POLE mutations, as well as structural and copy number alterations, are specific to endometrial cancer, not to normal epithelial cells. The malignant conversion of normal epithelial cells requires these additional genetic hits, which are presumably accumulated during aging, and may therefore be a rare life event. These discoveries could be expected to shed light on the physiology and pathogenesis of the human endometrium and urge caution against the application of genetic screening for the early detection of endometrial cancer., Human endometrial gland exhibits clonal growth in each menstrual cycle possibly via stem/progenitor cells, with harboring frequent somatic gene mutations in cancer‐associated genes. These mutations may plays role in endometrial regeneration and pathogenesis of endometriosis or endometrial cancer.

Zhelezov D. M., Kossey T. V., Zarzhitskaya N. A. Features of myometrium remodeling after surgical inteventions on the uterus. Journal of Education, Health and Sport. 2020;10(2):204-211. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.02.025 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.02.025 https://zenodo.org/record/3733425 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 31.01.2020. Revised: 10.02.2020. Accepted: 28.02.2020. UDC 618.3-06 FEATURES OF MYOMETRIUM REMODELING AFTER SURGICAL INTEVENTIONS ON THE UTERUS D. M. Zhelezov, T. V. Kossey, N. A. Zarzhitskaya Odessa National Medical University, Odessa Abstract Introduction. Recently, the attention of researchers has again attracted the problem of pregnancy in the presence of scar on the uterus. The aim of the study is to evaluate the processes of myometrium remodeling in women with uterine scar using non-invasive ultrasonic monitoring. It is shown that the frequency of relative failure of yellowing in the uterus does not exceed 2.7% of the total number of women examined. The ratio of the thickness of the residual in the plane of the yellow and normal endometrium indicates complete remodeling and is in women after KP, this index was 0.96 ± 0.08, and after KME - 0.94 ± 0.06 (p> 0.05). The difference in maximum systolic velocity of arterial blood flow in patients after CR (38.8 ± 1.2 cm / s) and after CME (34.2 ± 1.4 cm / sec, p Keywords: scar on the uterus; remodeling; myometrium; diagnosis

Introduction/Background Endometrial carcinoma (EC) is traditionally diagnosed by histopathological assessment of an endometrial biopsy, leaving up to 30% of patients undiagnosed due to technical failure of the biopsy procedure or an inadequate amount of tissue. The aim of the current study is to assess whether mutational analyses of cervical cytology including self-samples or pipelle endometrial biopsies can improve the diagnostic accuracy of traditional histopathological diagnosis of EC. Methodology A prospective multicentre cohort study was performed in three hospitals in the Netherlands. Patients surgically treated for EC or a benign gynecological condition (control group) were included. A Pap brush sample, a cervicovaginal self-sample, a pipelle endometrial biopsy and the surgical specimen of the endometrial carcinoma (endometrial carcinoma group) or normal endometrium (control group) were obtained. A targeted next-generation sequencing panel was used to analyze these samples for mutations in eight genes. Diagnostic accuracy was determined by calculating sensitivity, specificity and predictive values. Results Fifty-nine EC patients and 31 control patients were included. In these patients traditional histopathological diagnosis by pipelle had a sensitivity of 78.9% and a specificity of 100%. For EC patients, 96.6% of surgical specimens contained at least 1 mutation. Mutational analysis of Pap brush samples, self-samples, and pipelle endometrial biopsies yielded a sensitivity of 78.0%, 67.3% and 96.5% with a specificity of 96.8%, 96.8% and 93.5%, respectively. Combining these three methods individually with histopathological pipelle endometrial biopsy evaluations yielded a sensitivity of 95.8%, 93.0% and 96.5, respectively. Conclusion This study has shown that mutational analysis of either cervical cytology, self-samples or pipelle endometrial biopsies improves diagnosis of EC, and is feasible for detection of endometrial pathology. Prospective validation will support implementation in routine clinical practice. Disclosure M.L.: advisory board AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen pharmaceuticals, Roche; sponsored research by Astra Zeneca, Bristol-Myers Squibb, llumina; royalties by Nimagen. Furthermore, no completing interests were declared.

Background: To determine whether diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) will help in differentiating endometrial cancer from normal endometrium and to determine whether the grades of endometrial cancer will show significant difference in ADC values.Methods: This is a retrospective study done in MOSC medical college hospital Kolencherry. on patients on whom preoperative MRI was done before hysterectomy. Cases from July 2017 to March 2021 were included. Study cases included 40 females with pathologically confirmed endometrial cancer and 30 females with pathologically proven normal endometrium in cases of uterine leiomyoma and cervical cancer. The exclusion criteria for the study were patients with endometrial cancer in whom surgery was not done within 2 weeks of MRI, patients who were treated with chemotherapy or radiotherapy before surgery, patients who had hydrometra or pyometra.Results: The mean ADC value (10−3 mm2/second) of endometrial cancer was 0.77±0.04, which was significantly lower (p0.05).Conclusions: Our study showed that ADC measurement can differentiate between normal endometrium and endometrial cancer. The ADC values of different grades of endometrial cancers did not show any statistically significant difference.

Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown.To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance.Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects.Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P=0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P=0.033).Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer.

Introduction Resectoscopic surgery requires high technological skill to perform the procedure in a limited field of vision. With the preoperative administration of dienogest, a good surgical field of vision can be secured. The lesion and the normal endometrium are easily distinguished, and therefore the removal of normal endometrium can be minimized. Methods Preoperative dienogest was administered to 28 patients with submucosal myomas, 18 patients with endometrial polyps, and one patient with Asherman's syndrome. The patients began taking oral dienogest (2 mg/d) on Day 5 of preoperative menstruation until the day before surgery. Use of dienogest before resectoscopic surgery was approved by the Institutional Review Board of Toho Medical Center Oomori Hospital (Tokyo, Japan; approval number 24-185). Results The duration of oral dienogest treatment was 14–72 days in patients with submucosal myoma and 18–85 days in patients with endometrial polyps. Slight thickening of the endometrium occurred in patients who were administered dienogest for 14 days. However, a thin endometrium occurred in patients who took the drug for 28 days or longer. Submucosal myomas and endometrial polyps were easily distinguished from the normal myometrium. A sufficient intrauterine surgical field was secured to minimize endometrial damage in all patients. Conclusion We found that preoperative dienogest effectively minimized endometrial damage in resectoscopic surgery by thinning the endometrium and clearing the surgical field of vision.

The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the picture of the correlation between the expression levels of PTEN and its targeting microRNAs in endometrial cancer is not fully presented. Our study investigated and analysed the expression levels of PTEN and PTEN-targeting miR-21, miR-181a, miR-214, miR-301a, and miR-1908 in total of 78 samples, out of which 26 samples were from normal endometrium, whereas the 52 samples were from endometrial cancer samples. Our results demonstrated a high variability of individual endometrial cancer samples in the levels of PTEN. The level of miR-181a showed significant increment in endometrial cancer tissues in comparison with normal endometrium. We did not observe any statistically significant correlation between levels of microRNAs and PTEN in a heterogeneous cohort of patients. At the same time, in samples collected from endometrial cancer patients, it was found out that the relationship between PTEN expression and body mass index had significant positive correlation. Moreover, our data demonstrated that the expression of PTEN was significantly decreased, whereas expression of miR-181a was significantly over-expressed in non-obese compared to obese endometrial cancer patients. Additionally, we observed the relationship between PTEN levels and miR-181a related to the cancerous tissues for non-obese patients was established to be negatively correlated. Our findings suggest that decrease of PTEN via increase of miR-181a may be important contributor to endometrial cancer in non-obese patients.

The normal endometrium has a wide spectrum of appearances according to the patient’s age and phase of menstruation; understanding this variability is essential in differentiating normal entities from pathologic processes that may require further workup.

Aim: To compare the single-layer endometrial thickness (obtained with sonohysterography [SHG]) with double-layer endometrial thickness (obtained with transvaginal sonography) in women without endometrial malignancy. Methods: We retrospectively studied consecutive patients from July 1, 2006, through June 30, 2007, who underwent SHG. The double-layer endometrial thickness was measured on longitudinal images of the uterus in the thickest portion of the fundus before saline infusion. The single-layer endometrial thickness was measured during SHG in the longitudinal-axis view in the thickest fundal portion anteriorly and posteriorly. Results: During the study period, 303 women underwent SHG. Pathology results were available for 128 women. In the 124 women with normal benign endometrium, the mean anterior endometrial thickness was 0.37 cm and the mean posterior endometrial thickness was 0.39 cm. The thickness of the mean anterior endometrium was not significantly different from the mean posterior thickness (P=.12). The difference between the mean double-layer endometrial thickness and the mean sum of single-layer thickness measures (i.e, sum of anterior and posterior layers) was 0.06 cm, even when intracavitary masses were excluded (P