Non-atypical Endometrial Hyperplasia Research Articles

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Comparison of Frozen and Final Pathology Results in Patients Operated for Endometrial Hyperplasia

OBJECTIVE: Our study aimed to determine the frequency of endometrial cancer in patients undergoing surgery with a diagnosis of endometrial hyperplasia and to evaluate the concordance between preoperative diagnosis, frozen section examination, and final pathology results. STUDY DESIGN: The clinical findings, imaging results, and all pathology reports of patients who underwent total abdominal hysterectomy for endometrial hyperplasia (atypical or non-atypical) between January 2020 and January 2023 at our hospital were retrospectively evaluated. Demographic and clinical characteristics (age, menopausal status, parity, body mass index, presence of diabetes and hypertension) and pathology results were recorded from patient records. RESULTS: 144 patients diagnosed with endometrial hyperplasia were included in the study. The frozen section and final pathology results of all patients diagnosed with non-atypical endometrial hyperplasia were reported as benign lesions. In the atypia group, the intraoperative frozen section results of 80.7% of the patients were classified as benign lesions, while the results of 19.3% were reported as malignant pathology. A statistically significant difference was found between the benign and malignant lesion groups, which were classified based on the final pathology results, with respect to age, menopausal status, and average endometrial thickness before biopsy. CONCLUSION: In cases of endometrial hyperplasia with atypia, the possibility of cancer appearing in the final pathology results should be taken into consideration. In the preoperative evaluation of patients, characteristics such as endometrial thickness, age, and menopausal status may suggest the likelihood of encountering endometrial cancer during surgery in this patient group.

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.

Unusual Scenario: Ipsilateral Pelvic Lymph Node Metastasis in High- Grade Serous Ovarian Carcinoma without Peritoneal Extension - A Case Report

Introduction:: Ovarian cancers are the third most common gynecological cancers worldwide with serous carcinomas being the most common subtype with 90% of them as high-grade carcinomas. Case Presentation:: In the present case report a 60 years postmenopausal, nulliparous woman presented with complaints of bleeding per vaginum for 1-2 months with a left-sided solid-cystic ovarian mass of size 4x5 cm and ipsilateral enlarged external iliac and obturator lymph nodes which were diagnosed on histopathological examination as high-grade serous ovarian carcinoma (HGSOCs) with ipsilateral pelvic lymph node metastasis in presence of intact ovarian capsule and no metastatic deposits over the uterus, contralateral ovary and fallopian tubes, omentum, or any other gross peritoneal deposits. There was coexisting non-atypical endometrial hyperplasia. The patient was managed successfully with staging laparotomy with modified radical hysterectomy, and bilateral pelvic lymphadenectomy followed by six cycles of adjuvant chemotherapy with Paclitaxel and Carboplatin injections. Conclusion:: Patients with HGSOCs can have varied presentations with unusual involvement of lymph nodes in the absence of peritoneal spread. Hence, the clinician must be aware of these unusual presentations for the successful management of such cases.

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

ObjectiveIt 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. MethodsThe 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. ResultsThe 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. ConclusionsThe 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.

Effects of melatonin on disease improvement and serum levels of pro-inflammatory cytokines in patients with non-atypical endometrial hyperplasia

ABSTRACT Background Endometrial hyperplasia (EH), an abnormal proliferation of the endometrial cells, is considered as one of the most common causes of abnormal uterine bleeding. Previous studies have reported that melatonin plays a fundamental role in disease treatment. This study aimed the comparison of the effects of progesterone, as the most common therapeutic approach, and melatonin with progesterone alone in improvement of non-atypical endometrial hyperplasia (NEH) and changes in pro-inflammatory cytokine levels. Methods Study population consisted of 40 patients with NEH. Patients were divided into two groups, including 20 subjects treated with melatonin and progesterone and 20 individuals treated with progesterone alone. The blood and endometrial sampling was performed from participants before and after a three-month treatment. The histological examination was microscopically done. The serum levels of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured using ELISA. Results There was no significant difference in the diabetes status and mean age between patients treated with progesterone and melatonin and those treated with progesterone alone. The improvement rate in the EH was significantly higher in individuals treated with progesterone and melatonin than those treated with progesterone alone (p < 0.05). Additionally, the patients treated with progesterone and melatonin showed significant increases inIFN-γ and TNF-αlevels compared to the control group (p < 0.001-P < 0.05). Conclusion Melatonin supplementation has a beneficial effect in the treatment of EH due perhaps to enhance the level of IFN-γ and TNF-α.

Genetic and epigenetic alterations in precursor lesions of endometrial endometrioid carcinoma.

The hyperplasia-carcinoma sequence is a stepwise tumourigenic programme towards endometrial cancer in which normal endometrial epithelium becomes neoplastic through non-atypical endometrial hyperplasia (NAEH) and atypical endometrial hyperplasia (AEH), under the influence of unopposed oestrogen. NAEH and AEH are known to exhibit polyclonal and monoclonal cell growth, respectively; yet, aside from focal PTEN protein loss, the genetic and epigenetic alterations that occur during the cellular transition remain largely unknown. We sought to explore the potential molecular mechanisms that promote the NAEH-AEH transition and identify molecular markers that could help to differentiate between these two states. We conducted target-panel sequencing on the coding exons of 596 genes, including 96 endometrial cancer driver genes, and DNA methylome microarrays for 48 NAEH and 44 AEH lesions that were separately collected via macro- or micro-dissection from the endometrial tissues of 30 cases. Sequencing analyses revealed acquisition of the PTEN mutation and the clonal expansion of tumour cells in AEH samples. Further, across the transition, alterations to the DNA methylome were characterised by hypermethylation of promoter/enhancer regions and CpG islands, as well as hypo- and hyper-methylation of DNA-binding regions for transcription factors relevant to endometrial cell differentiation and/or tumourigenesis, including FOXA2, SOX17, and HAND2. The identified DNA methylation signature distinguishing NAEH and AEH lesions was reproducible in a validation cohort with modest discriminative capability. These findings not only support the concept that the transition from NAEH to AEH is an essential step within neoplastic cell transformation of endometrial epithelium but also provide deep insight into the molecular mechanism of the tumourigenic programme. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012-2020.

Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer.

Histopathology of endometrium in women presenting with abnormal uterine bleeding in Vindhya region

: Any alteration in frequency, flow duration/blood loss amount of menstruation is known as Abnormal uterine bleeding/AUB. Almost 30% of all patient attending gynaecology OPD are for AUB. This study was conducted in Vindhya region to study endometrial histopathology amongst women complaining of abnormal bleeding pattern: This retrospective study was conducted on 200 women presenting with AUB who undergone endometrial biopsy or hysterectomy in the Obstetrics and Gynaecology Department and sent to Histopathology section of Pathology department, SSMC, Rewa (MP) from Jan 2020 to June 2021. The formalin fixed specimens were received grossing done, followed by processing and then staining with H&amp; E stain, followed by microscopy. Data &amp; history was taken from the patient herself and attenders.: AUB was observed in all age groups. Menorrhagia (105 patients, 52.5%) was commonest bleeding pattern observed in cases of AUB, followed by Metrorrhagia (54 patients, 27%). In our study Proliferative endometrium (71 patients,35.5%) was most common histopathological diagnosis found, followed by Non-Atypical endometrial Hyperplasia (45 patients, 22.5%), Secretory phase (20 patients,10%), DPE (20 patients,10%), Atrophic endometrium (12 patients,6%), Exogenous hormone (pill endometrium 10 patients, 5%), Benign Adenomatous polyp (9 patients, 4.5%), Atypical endometrial Hyperplasia (5 patients, 2.5%), chronic endometritis (5 patients, 2.5%), Endometrial carcinoma (3 patients, 1.5%).Variable Histopathological findings are found in endometrial biopsy and curettage done in AUB patient. This study emphasizes the significance of endometrial biopsy and its histopathological diagnosis for proper patient management.

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

ER and COX2 expression in endometrial hyperplasia processes.

Endometrial hyperplastic processes (EHPs) encompass various morphological changes, characterized by an increased ratio of endometrial glands to stroma. These changes manifest as endometrial hyperplasia (EH) and endometrial polyps. The objective of this study was to investigate the expressions of ER and Cyclooxygenase-2 (COX2) in EH and endometrial polyps, and determine their correlation with histological and anthropometric parameters. Tissue samples were obtained during hysteroresectoscopy and divided into 3 groups: non-atypical EH, glandular EP, and glandular-fibrous EP. We examined the immunoprofile of epithelial and stromal cells using rabbit polyclonal anti-COX2 antibodies and rabbit monoclonal anti-ER antibodies (clone SP1). Our results indicate that there is no association between the expressions of ER and COX2 and the type of EHP. Furthermore, the expression levels of ER and COX2 are not influenced by the patients anthropometric parameters. However, tissues with EHPs exhibited significantly higher COX2 expression compared to intact tissues. We also observed a direct correlation between ER and COX2 expression in the endometrial epithelium. The variability in ER and COX2 expressions observed in hyperplastic processes of the endometrium potentially suggests their synergistic involvement in the initiation and progression of EHPs, as well as their potential role in subsequent tumor transformation.

Abstract CT044: KGOG2031 A phase II trial of repeated high dose luteal hormone therapy for intrauterine recurrence following fertility preserving therapy for atypical endometrial hyperplasia or endometrial cancer

Abstract Background: Atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) are common disease in menopausal women, however, are gradually increasing in women aged under 40 years. The standard treatment for AEH/EC is hysterectomy, but hormonal therapy is performed for preserving fertility. In general, fertility-preserving treatment is considered for AEH or EEC with well-differentiation and lesions confined to the endometrium without myometrial invasion. According to previous studies, hormonal therapy in these patients responded relatively well. Nevertheless, recurrence was not uncommon, accounting for 26.0% in AEH and 40.6% in EC. The standard treatment for these recurrent patients is hysterectomy, but if there is no myometrial invasion and no extrauterine lesions, repeated hormonal treatment can be considered. However, studies targeting these patients have been very scarce. The purpose of this study was to evaluate the efficacy and safety of high-dose progesterone therapy in recurrence following fertility preserving therapy for AEH or EEC. Methods: KGOG2031 is a multi-center and prospective phase 2 trial. The primary endpoint is a 2-year disease free survival. The secondary endpoints were duration of disease-free survival, overall survival, response rate, adverse events, and infertile rates. Patients with recurrent AEH or EEC without myometrial invasion or extrauterine lesions who underwent high-dose MPA therapy for primary lesions were included. The inclusion criteria are limited to patients with less than two recurrences. The pathologic type for EEC was confined to endometrioid type. The patients should be confirmed histologically at least one complete remission after first treatment. Patients with myometrial invasion, cervical involvement, or extrauterine lesions observed on abdominal/chest computed tomography or pelvic magnetic resonance imaging were excluded. Furthermore, grade 2 or 3 of endometrioid or any grade of other pathologic type of endometrial cancer or non-atypical endometrial hyperplasia were excluded. The enrolled patients should take medroxyprogesterone acetate 500mg every day. D&amp;CB will be performed after anesthesia every 8 weeks to determine the effectiveness, and treatment will be continued for up to 40 weeks until complete remission is achieved. The target number of enrollment is 115 cases, and the recruitment period is 3 years. The follow-up duration is 2 years after the end of treatment, and the total study duration was up to 5 years. Citation Format: Min Kyu Kim, Yung-Taek Ouh. KGOG2031 A phase II trial of repeated high dose luteal hormone therapy for intrauterine recurrence following fertility preserving therapy for atypical endometrial hyperplasia or endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT044.

Molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy based on the study of the expression of estrogen and progesterone receptors and paracrine cellular markers of cellular interaction

The problem of resistance of non atypical endometrial hyperplasia (NEH) to traditionally accepted, pathogenetically sound therapy with different types of progestins is currently an unsolved problem. In about 17-20% of cases there is a recurrence or even progression of atypical forms of endometrial hyperplasia (AEH), which required the use of surgical treatments. The aim of the study was to investigate the results of hormone therapy with different types of progestins for the treatment of endometrial hyperplasia in women with different types of expression of estrogen and progesterone receptors in combination with the expression of intercellular adhesion molecules E-cadherin and β-catenin to determine the cause of hormonal resistance, formation of groups of women with progestogen-sensitive endometrial hyperplasia (EH) non atypical type NEH (+), which can use progestogens for treatment, and progestogen-resistant forms of endometrial hyperplasia with non atypical NEH (-), which should be offered alternative therapy. The study was performed on the morphological material of the endometrium obtained by diagnostic biopsy in women with abnormal uterine bleeding who were diagnosed with NEH by histological examination. For immunohistochemical study, 80 endometrial samples were taken from women with abnormal uterine bleeding (AUВ) and in the same women after treatment of endometrial hyperplasia without atypia in 3 and 6 months of therapy. The control group (CG) consisted of a group of 20 women who were followed-up without treatment tactics. All women were divided into 3 groups in which different types of progestins were used for treatment: group I – continuous intake of 100 mg of micronized progesterone per os twice a day for 6 months, group II – 20 mg of dihydrogesterone per os twice a day for 6 months, group III – in which LNG-IUD was used. The state of proliferation and differentiation in the studied tissues was assessed by the expression of their key molecular participants – estrogen receptors (ERα) and progesterone (PGR), transmembrane glycoproteins of E-cadherin and β-catenin. ERα and PGR expression were determined by immu­nohistochemistry and calculated by the semi-quantitative H-index method. Evaluation of the expression of E-cadherin and β-catenin was performed by determining the percentage of IHH-positive cells to these antigens depending on the degree of their color. The criterion for the effectiveness of NEH treatment was considered to be a biopsy in 3 and 6 months of treatment in the absence of pathological changes in the endometrium. The results showed that after the use of progestogens in group I there was a change in the endometrium to the secretory type in 45% of cases, in group II with dydrogesterone therapy – in 55% there was a reduction of EH to normal histological picture. The intrauterine system with levonorgestrel (LNG-IUD) showed the greatest efficiency, with the use of which in 75% of cases normalization of the endometrial structure was observed. In the control group in 32% of cases the structure of the endometrium normalized. After 6 months of treatment with gestagens, both oral forms (micronized progesterone, dydrogesterone) and the use of LNG-IUDs showed a positive effect from their use; the therapeutic form of gestagens for therapy is not significant in reducing excessive endometrial proliferation. In the control group of patients who did not receive therapy or discontinued therapy for various reasons, it was shown that 47% of patients had spontaneous regression of EH. The overall percentage of no effect from treatment was 20% in groups I, II and III. Determination of ERα expression in all groups showed a pronounced expression in glands and stroma, which did not differ significantly in the group with NEH (+) and in NEH (-). Analysis of PGR expression of NEH in endometrium (-) showed that in glandular cells (50.82±0.73) and in the stroma (47.34±0.82) it was lower than in the endometrium of women with NEH (+) (gland 187±3.1; stroma 166.4±2.3; p&lt;0.05), as well as in the unchanged endometrium in the proliferative phase (glands 193.2±8.5; stroma 178.7±6.3; p&lt;0.05) and the secretory phase (glands 140.2±4.4; stroma 116.6±3.1; p&lt;0.05). A study of E-cadherin expression in women with EH (-) showed that in 86.4% of cases the expression was absent and in 13.6% it decreased. In NEH (+) women, 49.2% of E-cadherin expression was weak, in 34.4% – moderate, and in 16.4% – negative, indicating an association between PGR and E-cadherin expression. In women with NEH (-) there was marked cytoplasmic expression of β-catenin up to 80%, which can be interpreted as potentially threatening the progression of NEH in atypical forms and relapses. Thus, the study of molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy will help to develop a differential approach to its diagnosis and treatment.

Massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical and non-atypical endometrial hyperplasia.

Endometrial hyperplasia (EH), particularly with atypia, is considered an antecedent of endometrial adenocarcinoma. In this study, we aimed to apply massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical (AEH) and non-atypical endometrial hyperplasia (NEH). The identified alterations were compared with those detected in tissue samples. Endometrial lavage specimens and parallel biopsy samples (n = 11 for AEH and n = 9 for NEH) were obtained from 18 women (9 with AEH and 9 with NEH) who received an office hysteroscopy for suspected endometrial lesions. All samples were tested for somatic mutations in hotspot regions of 72 cancer-associated genes by massively parallel sequencing. On analyzing sequencing data, the presence of at least one cancer-associated gene mutation was identified in 72.7 and 44.4% of endometrial lavage specimens obtained from women with AEH and NEH, respectively (p = 0.362, 95% confidence interval = 0.72-3.70). The concordance rates between mutations identified in endometrial lavage specimens and endometrial biopsies were 54.5 and 0% from women with AEH and NEH, respectively (p = 0.014). A patient with NEH harbored mutations in endometrial lavage with the same mutations found in the tissue specimen at low allele frequency below detection cutoff, raising the suspicion of missed focal atypia. Endometrial hyperplasia is characterized by a high burden of cancer-associated mutations, particularly in the presence of atypia. Our study, albeit performed with a relatively small number of samples, indicates that their detection by massively parallel sequencing of endometrial lavage is feasible. Our findings may allow tailoring of endometrial biopsies to the individual risk of AEH; additionally, they can pave the way toward less invasive surveillance protocols in patients with known EH.

Preliminary study of confocal laser endomicroscopy for in vitro specimens of the endometrium

BackgroundThis 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.MethodsThis 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.ResultsA 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.ConclusionConfocal 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.

Новая стратегия поиска гормональной терапии пролиферативных процессов эндометрия у пациенток в постменопаузе

The limited efficacy of hormone therapy for endometrial proliferative process (EPP) in postmenopausal patients and its side effects on the immune system functionalities have not been studied in detail. Here we assess the feasibility of hormone therapy for EPP in postmenopausal patients through evaluation of estradiol and progesterone receptor gene expression in endometrial tissue and peripheral blood mononuclear cells (PBMC). The study enrolled 92 postmenopausal patients with EPP, including 37 pts with glandular-fibrous polyps, 7 pts with non-atypical endometrial hyperplasia (EH), 8 pts with atypical endometrial hyperplasia (AEH), 31 pts with moderately differentiated adenocarcinoma and 9 pts with highly differentiated adenocarcinoma. The PBMC isolates and endometrial samples were tested for ER⍺, ERβ, mER, PRA, PRB, mPR and PGRmC1 expression by reverse real time polymerase chain reaction (RT–PCR). Differential changes in PBMC receptor profiles upon in vitro exposure to progesterone or mifepristone were determined for patients with endometrial polyps and healthy women. The results indicate elevated expression of ERα, ERβ, PRA, PRB, mPR and PGRmC1 by endometrial tissues in EH and elevated expression of mER, ER⍺ and PRA by PBMC in AEH, apparently reflecting suppressed functionalities of monocytes, macrophages, Т-cells and natural killer cells. Unaltered expression of the studied genes by PBMC in endometrial adenocarcinoma may reflect the incrementing tumor autonomy. In vitro, mifepristone inhibited ER⍺, ERβ, mPR, PGRmC1, PRA and PRB expression in PBMC isolated from patients with endometrial polyps. We suppose that such effects can mitigate the negative influence of sex steroid hormones on immunocompetent cells.

Risk of atypical hyperplasia and endometrial carcinoma after initial diagnosis of non-atypical endometrial hyperplasia: A long-term follow-up study

ObjectivesThe strong association between atypical endometrial hyperplasia and endometrial carcinoma is well established, but data on the risk of atypical hyperplasia and carcinoma in Danish women with non-atypical endometrial hyperplasia are almost non-existent. This study aimed to investigate the prevalence of atypical hyperplasia and endometrial carcinoma diagnosed within 3 months of initial diagnosis (defined as concurrent disease) and the risk of atypical hyperplasia and carcinoma more than 3 months after initial diagnosis (classified as progressive disease) in Danish women initially diagnosed with non-atypical endometrial hyperplasia.DesignThis cohort study recruited 102 women diagnosed with non-atypical endometrial hyperplasia at Randers Regional Hospital in Randers, Denmark, between 2000 and 2015.MethodsThe endometrium was evaluated by transvaginal ultrasound examination and office mini-hysteroscopy with biopsies in all non-hysterectomized women. Data regarding subsequent hysterectomy or endometrial sampling were obtained from medical records and the Danish Pathology Registry (Patobank).ResultsA total of 15 women were diagnosed with atypical hyperplasia or carcinoma during follow-up. Concurrent atypical hyperplasia or carcinoma was seen in 2.9% (3/102), and among women who remained at risk for more than 3 months after initial diagnosis of non-atypical endometrial hyperplasia (n = 94), progression to atypical hyperplasia or carcinoma was seen in 13% (median follow-up 5.2 years, range 3.6 months to 15.1 years). Sixty-six percent of the women with progressive disease were diagnosed with atypical hyperplasia or carcinoma more than 1 year after initial diagnosis, but only two were diagnosed later than 5 years (5.2 and 9 years).ConclusionsThe risk of being diagnosed with atypical endometrial hyperplasia or endometrial carcinoma more than 5 years after an initial diagnosis of non-atypical endometrial hyperplasia seems to be low in Danish women. Specialized follow-up more than 5 years after diagnosis of non-atypical endometrial hyperplasia may not be warranted.

Restoration of endometrial receptivity and reproductive function in infertile women with excess body weightand complex non-atypical endometrial hyperplasia

To date, there are several approaches to the treatment of endometrial hyperplasia, but it is quite unclear which approach provides a higher clinical response with a lower recurrence rate, in addition to preservation and restoration of fertility in infertile women with complex non-atypical endometrial hyperplasia (NEH) and excess body weight. The purpose of the study was to evaluate the effectiveness of the restoration of reproductive function in patients with infertility, complex NEH and with excess body weight according to the proposed method. Material and methods. 74 women of reproductive age with complex NEH, infertility and excess body weight were under observation, of which 34 patients of the main group after hysteroscopic resection of the lesion at the first stage of treatment, at the second stage of treatment received gonadotropin-releasing hormone agonists (aGnRH) and adjuvant therapy with drugs indole-3-carbinol, metformin, fenofibrate for three months, and then at the third stage of treatment dydrogesterone, metformin, a vitamin-mineral complex that included myo-inositol, banaba leaves, extract of 1% corosolic acid, vitamin D3, methylfolate-quatrafolic, chromium for 6 months. 40 patients of the control group after hysteroscopic resection of the lesion at the first stage of treatment were prescribed aGnRH for 3 months in the second stage of treatment, then methylfolate-mvatrafolic for 6 months. Anthropometric data, echometric and morphofunctional characteristics of the endometrium during the expected window of implantation, hormonal profile and levels of peripheral blood lipokines in the dynamics of treatment were studied. Reproductive results were evaluated within a year after the end of treatment. The results. Treatment of complex NEH in the main group led, compared to the control group, to a decrease in body mass index, improvement in echometric and morphofunctional characteristics of the endometrium, its receptivity during the expected window of implantation, hormonal profile and lipokines level in peripheral blood, a decrease in insulin resistance, and an increase in the frequency of pregnancy. Conclusion. The proposed scheme for the treatment of complex NEH in infertile women with excess body weight allowed to improve their reproductive results, is effective and can be recommended for implementation in wide clinical practice.

Профилактика гиперплазий эндометрия в репродуктивном периоде

Objective. A systemic review of current literature on the efficacy and safety of combined oral contraceptives (COCs) for the prevention of endometrial hyperplasia (EH) in women of reproductive age. The possibilities and perspectives of using COCs for the prevention of EH according to scientific data on the grounds of evidence-based medicine over the past 5 years were considered. It was proven that expanding the range of effective treatment options for EH allows adapting treatment to patients’ needs and offers a personalized approach to their management. Conclusion. Gestodene-containing COCs are an effective and safe method for the prevention of non-atypical EH, carrying a wide range of therapeutic benefits associated with reliable contraceptive capacity and favorable fertility prognosis, especially in young women. Key words: endometrial hyperplasia, COCs, gestodene, polycystic ovary syndrome

Hysteroscopic Endometrial Resection in Women Treated With Tamoxifen for Breast Cancer Provides Definitive Diagnosis and Effective Long-Term Therapy

We evaluated resectoscopic surgery for definitive diagnosis and long-term therapy in 16 symptomatic tamoxifen-treated women with breast cancer who presented with abnormal uterine bleeding and/or intrauterine anomalies. Seven pre-menopausal women had benign pre- and post-operative endometrial biopsy, and 4 had benign polyps. At a median of 7 years of follow-up (range 2–8 y), all remained amenorrheic. Of 9 post-menopausal women, pre-operative biopsy was inadequate in 4, benign endometrium was found in 4, and non-atypical endometrial hyperplasia was found in 1. Post-operatively, all had benign pathology, 8 having polyp and 1 leiomyoma. At a median follow-up of 7 years (range 2–13 y), all were amenorrheic, with no recurrence of breast cancer or uterine pathology.