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Background. Epithelial-mesenchymal transition (EMT) is a conserved mechanism in the process of morphogenesis and organogenesis. EMT provides cells with migratory and invasive properties, which is a necessary condition for the formation of endometrioid heterotopias. Aim. To confirm the presence of EMT features in different types of endometriosis. Materials and methods. During a period of five years (2012–2017) we analyzed 43 cases of extragenital endometriosis: appendix (3 case), colon (5 cases), ileum (1 case), abdominal scar endometriosis after caesarean section (24 cases), and inguinal hernia (10 cases). The material was processed according to histological and immunohistochemical technique using monoclonal E-cadherin and polyclonal Vimentin antibodies to assess local invasiveness. Results. In peritoneal endometriosis, the ratio of E-cadherin to Vimentin expression was 10.3, in the colon = 9.1, in the appendix 8.6, in the ileum 5.5, in the hernial sac 4.2. Thus, in diffuse infiltrative forms of endometriosis, the lesion phenotype is characterized by low expression of E-cadherin, while expression of Vimentin is at a high level (p0.05). Conclusion. The results of our study confirmed involvement of the epithelial-mesenchymal transition process in the pathogenesis of extragenital endometriosis lesions, on the one hand, and they certify its invasive potential in these localizations, on the other hand.

Aim. To identify clinical and history features of patients with recurrent deep endometriosis (RDE). Materials and methods. A retrospective study of clinical and history data of 200 patients with DE undergoing surgical treatment at the Department of General Surgery of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in 2020–2021. Group 1 included 80 patients with RDE, group 2 included 120 patients with newly diagnosed DE. All patients underwent surgical treatment followed by immunohistochemical examination and DE confirmation. Results. An association was found between the young age of the patient at the time of the first surgery and the type of endometriosis. It was found that women with a history of endometriosis surgery in early reproductive years (29.22±5.3 years) are at risk of recurrent endometriosis. Two or more surgeries were reported in 33.7% of RDE patients. In 90.2% of patients, endometriosis recurred with clinical manifestations; in 9.8%, it was asymptomatic and diagnosed on pelvic ultrasound. The group of RDE patients showed a longer period of infertility (5.432±3.53 years) than the group with newly diagnosed DE (2.953±1.29 years). It was found that the surgeries performed in RDE patients were longer, more complex, and associated with more blood loss. Intestinal resection, ureterolysis, adhesiolysis, and salpingectomy were significantly more common in the RDE group than in patients without a history of endometriosis surgery. Conclusion. In most cases, RDE is clinically manifested, rarely asymptomatic and diagnosed by visualization methods. Patients with a history of surgery at a younger age are at risk of RDE, and their surgical interventions are more complicated with more blood loss. Currently, surgical treatment of DE is the optimal method; however, it has serious disadvantages with severe and even life-threatening postoperative complications.

IntroductionHuman papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state.MethodsIn this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(−) n = 11], LSIL [HPV(+) n = 32; HPV(−) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(−) n = 22].Results and DiscussionHPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

Aim. To analyze the profile of anti-Mllerian hormone (AMH) and the expression level of the transmembrane AMH receptor type II (AMHRII) in the eutopic and ectopic endometrium of patients with deep infiltrative endometriosis (DIE). Materials and methods. A comparative analysis of AMHRII expression in epithelial and stromal cells of eutopic and ectopic endometrial samples and the level of serum AMH in patients of reproductive age with DIE (n=50) and tuboperitoneal infertility (n=9) was performed. Results. AMHRII expression in eutopic endometrial stromal cells of DIE patients was significantly higher compared to glandular cells in all study groups (p0.5). AMHRII expression was found to be significantly higher in glandular cells of the eutopic endometrium compared to the ectopic endometrium of pelvic peritoneal foci in DIE patients: 1.600.77 and 1.090.68 points, respectively (p=0.001). Conclusion. The inhibitory effect of AMH on cell proliferation and the proven expression of AMHRII by eutopic and ectopic endometrioid cells may indicate the role of AMH in the pathogenesis of endometriosis and endometriosis-associated infertility.

Aim. To study the regulation of apoptosis in the endometrium of women with chronic endometritis (CE) and external genital endometriosis (EGE) based on the study of the expression of its regulators such as transcription factor (NF-), Bcl-2 and Caspase-8. Materials and methods. The study evaluated the expression of apoptosis factors such as Caspase-8, NF-B transcription factor, and Bcl-2, in patients with chronic endometritis (CE, n=23), external genital endometriosis (EGE, n=20), and intact endometrium (control group; n=7). Statistically significant differences were found for all test markers (p0.05). Results. The increased expression of apoptosis factors is probably related to high endometrial pro-inflammatory activity in both CE and EGE. For EGE, this effect is more pronounced at the transcription level in the form of an increase in the expression of the transcription factor NF-B in both glandular and stromal endometrial cells. It is probably due to the systemic nature of the chronic inflammatory process. For CE, despite the antiapoptotic activity of Bcl-2, an increase in Caspase-8 expression in the endometrium may also indicate a predominance of innate immunity activation. Conclusion. The imbalance of pro- and antiapoptotic factors can be an inducer of both cytotoxic and cytoprotective mechanisms of EGE and CE. However, it requires further research.

Aim. To assess the reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods. Materials and methods. Cytological smears prepared using the liquid cytology method on the Becton Dickinson device (SurePath technology) were studied. An immunocytochemical study was carried out using a Ventana BenchMark Ultra automatic immunostainer with a commercial CINtec kit (determination of p16/Ki-67 co-expression). In total, 100 cytological slides (50 pairs of Pap-smears and immunocytochemical slides) were studied. The diagnostic kit was reviewed by five cytologists independently, and the cytologic slides were evaluated using four categories according to the Bethesda system (2014) and according to the categories of normal/abnormal. The co-expression of p16/Ki-67 was assessed per the manufacturer's recommendations (Roche) using the manual method (light microscope) and the automatic Vision Cyto Pap ICC system. Statistical processing of the results was performed using the SPSS software package version 26.0.0.0 with the calculation of the reproducibility indices of Cohen's kappa and Fleiss' kappa. Results. When assessing the reproducibility of four categories of cytological diagnoses according to the Bethesda system (2014), Cohen's kappa was 0.0480.265. The overall Fleiss' kappa between all cytologists was 0.103. When only two categories (normal/abnormal) were used, the reproducibility ranged from 0.058 to 0.377. When assessing the co-expression of p16 and Ki-67, Cohen's kappa reproducibility was from 0.196 to 0.574, while the overall Fleiss' kappa was 0.407. When comparing the evaluation results of each of the cytologists with the neural network, Cohen's kappa reproducibility ranged from 0.103 to 0.436. Conclusion. The reproducibility of cytological diagnoses according to the Bethesda system (2014) and two categories (normal/abnormal) based on the Pap smear study was low. Such results are primarily due to a large number of abnormal smears in the study. The immunocytochemical method has diagnosis reproducibility three times higher, indicating the need to measure the co-expression of p16 and Ki-67 to increase the sensitivity and specificity of the cytological method. Similar reproducibility when comparing the manual and automatic evaluation of the "double label" suggests that the neural network algorithm can currently help in decision support rather than replace the cytologist at the diagnostic stage.

Aim. To analyze the incidence and types of adverse outcomes and complications of laparoscopic myomectomies. Materials and methods. This work is a retrospective study based on data from the Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology. We analyzed 711 case histories of patients diagnosed with uterine myoma who received surgical treatment in the Department of Innovative Oncology and Gynecology from 2015 to 2019. The frequency of malignant neoplasms, verified by pathomorphological examination, and the characteristics of surgical interventions performed in these patients were comparatively evaluated. Results. Surgical interventions for uterine myoma are leading in gynecology due to the high prevalence of such disorders. Conservative myomectomy remains the "gold standard" in organ-sparing surgery. However, during surgeries for suspected benign neoplasms, there is a risk of morcellation of the malignant tumor, significantly worsening patient survival outcomes. In our study, the incidence of uterine leiomyosarcoma in suspected benign neoplasms was 0.98%. The probability of parasitic myomas or disseminated perineal leiomyomatosis after myomatous nodule morcellation is 0.19%. Conclusion. No reliable information about the malignant potential of the tumor and its proliferative activity can be obtained until a definitive pathomorphological examination. The above considerations warrant the routine use of prophylactic measures to prevent tumor cell dissemination.

The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.

Abstract Background Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (

Recent studies have attempted to develop molecular signatures of epithelial ovarian cancer (EOC) based on the quantitation of protein-coding and non-coding RNAs to predict disease prognosis. Due to the heterogeneity of EOC, none of the developed prognostic signatures were directly applied in clinical practice. Our work focuses on high-grade serous ovarian carcinoma (HGSOC) due to the highest mortality rate relative to other types of EOC. Using deep sequencing of small non-coding RNAs in combination with quantitative real-time PCR, we confirm the dualistic classification of epithelial ovarian cancers based on the miRNA signature of HGSOC (type 2), which differs from benign cystadenoma and borderline cystadenoma—precursors of low-grade serous ovarian carcinoma (type 1)—and identified two subtypes of HGSOC, which significantly differ in the level of expression of the progesterone receptor in the tumor tissue, the secretion of miR-16-5p, miR-17-5p, miR-93-5p, miR-20a-5p, the level of serum CA125, tumor size, surgical outcome (optimal or suboptimal cytoreduction), and response to chemotherapy. It was found that the combined determination of the level of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p circulating in blood plasma of patients with primary HGSOC tumors makes it possible to predict optimal cytoreduction with 80.1% sensitivity and 70% specificity (p = 0.022, TPR = 0.8, FPR = 0.3), as well as complete response to adjuvant chemotherapy with 77.8% sensitivity and 90.9% specificity (p = 0.001, TPR = 0.78, FPR = 0.09). After the additional verification of the obtained data in a larger HGSOC patient cohort, the combined quantification of these four miRNAs is proposed to be used as a criterion for selecting patients either for primary cytoreduction or neoadjuvant chemotherapy followed by interval cytoreduction.

Female urethral diverticulum is a fairly rare pathology, the frequency of which ranges from 0.02 to 6.00% of women worldwide. The stones inside urethra diverticulum even more rare. The most common reasons of urethral diverticula are frequent bladder catheterizations, labour trauma, infections. Clinically is may present with the dysuria, dyspareunia, dribble, urinary incontinence, vaginal discomfort. Voiding cystourethrography and cystourethroscopy are the most accurate methods of diagnosis for urethral diverticula. The presented article describes the clinical case in women with urethral diverticulum who complained on the vaginal discomfort, dyspareunia and presentation of the brown stones in vagina and underwent surgical excision of diverticulum with urethral reconstruction.

Aim. To analyze the literature data on modern approaches to morcellation of myomatous nodes in laparoscopic surgery and to highlight this area in a historical aspect. To form an idea of the main difficulties associated with morcellation, which contributed to and contribute to the improvement of the technique of this manipulation. Materials and methods. The review includes data from foreign articles published in the elibrary.ru and PubMed databases on this topic. Results. It describes both modern trends in the surgical treatment of patients with uterine myoma, and historical aspects of improving methods aimed at reducing risks, reducing the time of surgical intervention and improving its safety. Analyzed data on the use of electromorcellation, carried out both with the use of plastic containers, and without them. Conclusion. High requirements for surgical interventions contributed to the emergence of such a method of intracorporeal fragmentation of drugs, such as morcellation, which led to a significant reduction in the proportion of laparotomic operations in the treatment of patients with my uterus. The introduction of laparoscopy in the surgical treatment of uterine myoma allowed to achieve a fundamentally new high level of rehabilitation of patients. Removing removed drugs from the abdominal cavity is associated with a certain risk. Despite the significant number of proposed methods and devices for morcellation, they all require further improvement, since it is necessary to completely exclude contact of the myoma node tissue with abdominal organs in the extraction process. Currently, active research continues on ways to realize all the benefits of minimally invasive technologies in compliance with the rules of oncological safety.