Foci Of Endometriosis Research Articles

Morphology of endometrial inflammatory changes in foci of endometriosis and adenomyosis

The high prevalence of endometriosis, its impact on menstrual and reproductive functions, obstetric complications, and the quality of life of women in the reproductive age determines the urgency of the problem.The objective: to assess the prevalence of inflammatory changes in foci of heterotopic endometrium in patients with endometriosis and adenomyosis.Materials and methods. 92 women of reproductive age – from 21 to 46 years old – who applied for surgical treatment for symptomatic adenomyosis (47 women – 1st group) and ovarian endometriosis (45 patients – 2nd group), and 30 practically healthy women of the same age (control group) were examined.Histological examination of adenomyosis and ovarian endometriosis biopsies was performed using a light microscope at magnifications of 40 and 100. For immunohistochemical examination, primary and secondary antibodies were used to determine CD34, CD68, and CD138 markers.Results. In patients with adenomyosis and ovarian endometriosis the following concomitant gynecological pathologies as uterine fibroids, endometrial hyperplasia, chronic endometritis, chronic abnormal uterine bleeding, the frequency of which is significantly higher in adenomyosis, were diagnosed. This may indicate the pathogenetic role of chronic inflammation in the development of these pathological conditions.In patients with adenomyosis the positive expression of CD68 in the epithelial component of heterotopias was determined in 8 (17.0±5.6%) women, and in 4 (8.9±4.2%) women with ovarian endometriosis, which indicated a low phagocytic activity. During the assessment of CD34 expression in vessel walls and the stromal component of endometrioid heterotopias, a positive reaction was determined in 16 (34.0±6.9%) patients with adenomyosis and in 10 (22.2±6.2%) patients with ovarian endometriosis, which reflects the processes of neoangiogenesis and the activity of the pathological process.Positive expression of CD138 in endometrioid heterotopias prevailed in the group of patients with adenomyosis – 12 (25.5±6.4%) cases versus 4 (8.9±4.2%) cases in the group of patients with ovarian endometriosis (p<0.05). This confirmed the histological results and clinical data regarding the presence of chronic endometritis and isthmocele.Conclusions. The identified inflammatory changes, weak phagocytic activity and signs of neoangiogenesis in foci of heterotopic endometrium are more significant in patients with adenomyosis, which is confirmed by clinical and morphological data.

Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level

Current therapeutics of endometriosis focus on hormonal disruption of endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types in EcE is important for targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve metabolic pathways in paired samples of EuE and EcE from women with confirmed endometriosis. We detect nine major cell types in both EuE and EcE. Metabolic pathways are most differentially regulated in perivascular, stromal, and endothelial cells, with the highest changes in AMPK signaling, HIF-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis. We identify transcriptomic co-activation of glycolytic and oxidative metabolism in perivascular and stromal cells of EcE, indicating a critical role of metabolic reprogramming in maintaining endometriotic lesion growth. Perivascular cells, involved in endometrial stroma repair and angiogenesis, may be potential targets for non-hormonal treatment of endometriosis.

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

BackgroundEndometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging.MethodsGene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment.ResultsGene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm.ConclusionOverall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.

The #Enzian classification for ultrasound diagnosis of endometriosis: description and explanation of the classification using our own clinical cases

An extensive deep infiltrating endometriosis usually requires complex and time-consuming surgical treatment, often with multidisciplinary surgery teams forming. The goal of ultrasound is to find and describe in detail, if possible, all endometriosis lesions at the preoperative stage. A structured classification is needed for a detailed description of all foci of pelvic and extrapelvic endometriosis that would be understandable to both the radiologists and the gynecological surgeon. The current version of the #Enzian classification was designed by an international team of scientists from 11 countries with vast experience in the diagnosis and treatment of endometriosis. This classification is based on a description of the location of endometriosis lesions, the depth of invasion into the pelvic organs and tissues, as well as the presence of invasion into adjacent abdominal organs and disruption of their functions. The classification provides continuity between preoperative imaging and surgical assessment of the severity of endometriosis. In this article, we tried to describe and comment in detail on the ultrasound version of this classification, illustrated by our own clinical cases. Using the #Enzian classification provides clinicians with a common “language” to describe endometriosis in a comprehensive and easily reproducible manner. The authors of this article have been using the #Enzian classification in their work for more than 2 years. Based on our existing experience, we consider the #Enzian classification not only convenient and useful, but also meets all the requirements of both a diagnostician and a surgeon.

International Endometrial Tumor Analysis (IETA) descriptors in the diagnosis of chronic endometritis

Objective: to compare the terms, definitions and measurement methods developed by the IETA group with the ultrasound criteria of chronic endometritis (CE) used in Russia.Material and methods. A retrospective cohort study of 158 reproductive age women with clinical and laboratory diagnosis of CE was carried out. Sonographic examination was performed in the early or middle proliferative phase (cycle day 4–10 days) with the use of Affiniti70 ultrasound system (Philips, the Netherlands) with a multifrequency 3D endocavitary probe. Uterine corpus volume, endometrial thickness and volume were measured, followed by percentage endometrial/uterine volume ratio calculation, the so-called adjusted endometrial volume. Qualitative analysis of grayscale imaging included assessment of endometrial structure and echogenicity; closure or separation of the endometrial layers; contour of endometrial midline; the presence of acoustic artifacts, such as reverberation in the presence of gas or liquid in the uterine cavity, described by a number of authors. Relevant IETA descriptions were searched when assessing all qualitative CE features. In parallel, a qualitative score analysis proposed by the IETA group was carried out.Timely preoperative diagnosis of endometrioic cyst (endometrioma), as well as deep endometriosis remains relevant. The aim of the study was to assess the diagnostic value of ultrasound in patients with endometriomas and assess the combination of them with other foci of external genital endometriosis. The study based on retrospective analysis of a date of 95 patients with ultrasound signs of ovarian endometriomas, who underwent examination in MedicoProfi LLC – Borisov Medical and Diagnostic Clinic (Krasnoyarsk) during the period from January 2019 to October 2023. All of patients underwent surgery , followed by morphological evaluation. In the vast majority of cases, it was possible to detect a combination of endometriomas with one or more foci of deep endometriosis. Superficial peritoneal endometriosis and adhesions were found on surgery in all cases when endometriomas appeared isolated on ultrasound. The results of the study showed: endometriomas combined with deep endometriosis in 96.8% of cases. Thus, ultrasound detection of endometrioma is a very reliable sign of deep endometriosis presence. The “kissing ovaries” symptom in bilateral endometriomas can be considered as an absolutely reliable sign of the uterosacral ligaments endometriosis with specificity of 100% and positive predictive value of 100%. The presence of the “kissing ovaries” sign should be depicted in the conclusion of the ultrasound protocol, since it highly suggestive to obliteration of the pouch of Douglas and involvement of adjacent organs (fallopian tubes, intestines, ureters, etc.) in the endometrioid infiltrates, which is extremely important for the surgery planning, as well as in patients with infertility. There is an obvious need to introduce the extended pelvic ultrasound protocol to the diagnostic algorithm for patients with suspected endometriosis, which will more accurately describe the disease extension.Results. The comparative analysis of endometrium description in CE indicates a similar measurement technique for endometrial and intrauterine lesions thickness, both proposed by the IETA group and used in our country. Most of the IETA descriptors for qualitative ultrasound findings may be used in CE diagnosis. However, there are no some significant ultrasound features for identifying the inflammation, such as marked and partially or completely thickened midline, as well as gas focuses within the endometrium or in the uterine cavity, in IETA description.Conclusion. Terminology standardization allows compare the results and perform multicenter studies followed by meta-analysis for the diagnosis of chronic endometritis, if researchers use the similar descriptors.

Ultrasound image of ovarian endometrioma as an indicator of external genital endometriosis

Timely preoperative diagnosis of endometrioic cyst (endometrioma), as well as deep endometriosis remains relevant. The aim of the study was to assess the diagnostic value of ultrasound in patients with endometriomas and assess the combination of them with other foci of external genital endometriosis. The study based on retrospective analysis of a date of 95 patients with ultrasound signs of ovarian endometriomas, who underwent examination in MedicoProfi LLC – Borisov Medical and Diagnostic Clinic (Krasnoyarsk) during the period from January 2019 to October 2023. All of patients underwent surgery , followed by morphological evaluation. In the vast majority of cases, it was possible to detect a combination of endometriomas with one or more foci of deep endometriosis. Superficial peritoneal endometriosis and adhesions were found on surgery in all cases when endometriomas appeared isolated on ultrasound. The results of the study showed: endometriomas combined with deep endometriosis in 96.8% of cases. Thus, ultrasound detection of endometrioma is a very reliable sign of deep endometriosis presence. The “kissing ovaries” symptom in bilateral endometriomas can be considered as an absolutely reliable sign of the uterosacral ligaments endometriosis with specificity of 100% and positive predictive value of 100%. The presence of the “kissing ovaries” sign should be depicted in the conclusion of the ultrasound protocol, since it highly suggestive to obliteration of the pouch of Douglas and involvement of adjacent organs (fallopian tubes, intestines, ureters, etc.) in the endometrioid infiltrates, which is extremely important for the surgery planning, as well as in patients with infertility. There is an obvious need to introduce the extended pelvic ultrasound protocol to the diagnostic algorithm for patients with suspected endometriosis, which will more accurately describe the disease extension.

Non-invasive diagnostics of endometriosis based on plasma miRNA expression

Aim. To develop a method for noninvasive diagnosis of external genital endometriosis based on plasma microRNA concentrations.Materials and Methods. 80 women of reproductive age who were admitted to the gynecological department for routine laparoscopy were retrospectively examined, according to the results of which and histological examination, the patients were divided into 2 groups: the main group — 54 patients with laparoscopically and histologically confirmed external genital endometriosis (EGE); the control group — 26 patients without EGE. Before laparoscopy, a blood sample was taken from all patients for a molecular-biological study of the expression of 10 microRNAs: miR-183, miR-125b, miR-126, miR-16, miR-15a, miR-200a, miR-20a, miR-21, miR-222 and miR-29b. Identification of the studied and normalizing RNAs (U6 RNA and 103a microRNA) was performed according to the method of Chen et al. The presented values of the expression of the studied microRNAs are given in the form of 2-ΔCt. The expression ratio is given in the form of 2-ΔCt (main)/2-ΔCt (control), if the expression in the group of patients with endometriosis exceeded that in the control group, and in the form of 2-ΔCt (control)/2-ΔCt (main), if vice versa.Results. Comparison of the expression of 10 mi-croRNAs between the two groups revealed statistically significant differences only in miR-183: its expression in patients with EGE was statistically 1.5 times higher than that in women of the control group (p=0.017).We have not detected a difference in the expression of mir-200a, while according to other researchers, representatives of the mir-200 family are among the most frequent whose expression changes with endometriosis. MIR-16 expression also did not differ statistically among the patients we examined, whereas a group of American colleagues revealed its increase in patients with endometriosis and with endometriosis-associated ovarian tumors. We found no difference in mir-21 expression. The results of other researchers are contradictory: some found its increase in endometrioid cysts compared with eutopic endometrium, an increase in the epithelium of the fallopian tubes with their endometriosis compared with unaffected; others did not reveal a difference between the eutopic endometrium of endometriosis patients and healthy women, but showed a decrease in expression in peritoneal foci and foci of deep infiltrative endometriosis compared with eutopic endometrium.The expression of mir-222 was reduced in the patients we examined with endometriosis, which goes against the existing ideas about the pro-oncogenic role of this microRNA. An increase in its expression in cancer of the stomach, bladder, liver, lungs, breast, endometrium, ovaries is described. At the same time, the oncosuppressive effect of mir-222 is also known in prostate cancer, squamous cell carcinoma of the oral cavity.Conclusion. Taking into account the revealed statistically significant difference in microRNA expression by ROC analysis, we determined their effectiveness and specificity in the diagnosis of EGE. Of course, further studies with a large contingent of patients are needed to confirm the diagnostic value of these biomarkers. In addition, our study did not allow us to establish a statistical difference in microRNA expression in patients with impaired fertility. But it is the test that makes it possible to differentiate female infertility — associated with endometriosis and without it, as a rule, tubal-peritoneal genesis — that will become a key tool in the personalized management of patients with infertility.In our work, the distribution of patients by stages of EGE turned out to be uneven (there were no women with stage I at all) and it was not possible to establish a statistical difference in microRNA expression depending on the "length of service" of the disease.

A Rare Case of Endometriosis in Urinary Bladder

Endometriosis with involvement of urinary tract is a rare occurrence. It is a chronic condition with presence of endometrial tissue outside uterine cavity. Most likely location is peritoneal surface of pelvis. We present a case of 32 year old female presenting with pelvic pain. On sonography bladder mass was detected. Transurethral resection of bladder mass revealed foci of endometriosis with mild inflammation in stroma. The diagnosis relies on identification of atleast two of the three components: endometrial glands, endometrial stromal cells or recent or old haemorrhage. Endometriosis with minimal stroma should be differentiated from invasive adenocarcinoma of the bladder. This case reports demonstrates that endometriosis in bladder although rare should always be ruled out by proper histological examination and save patient from unnecessary overtreatment.

Targeting c-MYC: a potential non-hormonal therapeutic approach for endometriosis treatment

Endometriosis is a benign gynecological disease in which eutopic endometrial tissue composed of glands and stroma grow within the pelvic cavity. The disease affects females of reproductive age and is characterized by pelvic pain, infertility and reduced quality of life. The majority of pharmacologic treatment modalities for endometriosis focus on suppression of estradiol production and/or action; an approach associated with adverse side effects. c-MYC is elevated in eutopic endometrium and endometriotic lesion tissue in patients with endometriosis and the disease shares many similar pathological characteristics with that of endometrial carcinoma. While targeting of c-MYC with Omomyc has recently gained substantial interest in the field of cancer research, there has been no recent attempt to evaluate the potential utility in targeting c-MYC for endometriosis treatment. The following perspective article compares the similarities between endometriosis and endometrial cancer and presents preliminary data suggesting that targeting c-MYC with Omomyc reduces endometriotic cell proliferation and viability in vitro. Future application of targeting c-MYC in endometriosis treatment and potential pros and cons are then discussed.

Microvesicles released from ectopic endometrial foci as a potential biomarker of endometriosis.

Angiogenesis is engaged in endometriosis. It is regulated by regulatory factors and cytokines, transported in microvesicles. The purpose was to investigate the presence of MVs with vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) in peripheral blood and peritoneal fluid of women operated on for endometrioma or teratoma Material and methods:Microvesicles (MVs) were determined in blood samples and peritoneal fluid samples collected from women aged 20-60 years operated on for endometriosis (test group) and teratoma (control group). The final investigations were performed on 47 patients, who qualified for the study based on the meticulous inclusion criteria. MVs were analyzed by flow cytometry (FACS) using annexin V, antibodies for molecules characteristic of cells from endometriosis foci (keratin 18 (K18), CD105, CD146), and antibodies for intraepithelial vascular growth factor VEGF and metalloproteinase-9 (MMP-9). The sample was double "reading" using flow cytometry (FACSCantoII). Cytometry analysis confirmed MVs' presence in plasma and peritoneal fluid collected from patients with both endometriosis and teratomas. A statistically significant higher level of AnnexinV (+) MVs were observed in plasma samples of endometriosis patients. In the control group, there was a higher percentage of double-positive VEGF (+)/MMP-9 (+) and single MMP-9 (+) positive MVs in the serum. In the peritoneal fluid higher frequency of double-positive VEGF (+)/MMP-9 (+) MVs were found in the control group. However, the amount of VEGF (+) / MMP-9 (+) MVs object did not enable to differentiate between the test and control groups. The study was the first, in which MVs were confirmed in plasma and peritoneal fluid in benign adnexa tumors. Microvesicles are present in peripheral blood and peritoneal fluid samples collected from patients with endometriosis and teratomas. Microvesicles with proangiogenic factors (VEGF and MMP-9) are more abundant in blood and peritoneal fluid samples from patients with teratomas.

A method for isolating and culturing ectopic epithelial and stromal cells to study human adenomyosis.

Although adenomyosis is a common and benign gynecological disease, the specific pathogenesis of this condition is yet to be fully elucidated. It is difficult to culture primary cells of the ectopic endometrial epithelia and stroma from human adenomyosis lesions. Most of the previous of studies on adenomyosis were based on primary eutopic endometrium cells. However, as yet, no efficient protocols have been developed for the isolation, culture or purification of primary ectopic epithelial and stromal cells from human adenomyosis lesions. Therefore, the present study aimed to develop an efficient protocol for the isolation and culture of primary ectopic epithelial and stromal cells from human adenomyosis lesions. In the present study, we aimed to obtain ectopic endometrium tissue from human adenomyosis foci and use a simple and operable type I collagenase digestion method for primary culture. Cells were isolated by sterile cell strainer filtration and flow cytometry was performed to identify, purify, and evaluate the viability of isolated ectopic endometrial cells. Using our method, we successfully isolated and cultured highly purified and active ectopic endometrial epithelial and stromal cells from human adenomyosis foci. Ep-CAM was expressed in ectopic epithelial cells of human adenomyosis with a purity of 93.74% and a viability of 80.58%. In addition, CD10 were robustly expressed by ectopic stromal cells in human adenomyosis. Cellular purity and viability were determined to be 96.37 and 93.49%, respectively. Our method provides a new experimental model for studying the molecular pathogenesis of human adenomyosis.

Endometriosis as an Uncommon Cause of Intestinal Obstruction-A Comprehensive Literature Review.

The prevalence of intestinal endometriosis has been estimated to be between 3% and 37% of all endometriosis cases. Cases of intestinal occlusion due to endometriosis foci on the small bowel and on the large bowel are even rarer, with a reported prevalence of 0.1-0.7%. The aim of this literature review was to summarize the available published evidence on the diagnosis, characteristics, and management of intestinal occlusion due to endometriosis. The search on PubMed retrieved 295 records, of which 158 were rejected following a review of the title and abstract. After reviewing the full text, 97 studies met the Population, Intervention, Comparator, Outcomes, and Study (PICOS) criteria and were included in the analysis. The total number of patients with bowel occlusion due to endometriosis included in the studies was 107. The occlusive endometrial foci were localized on the ileum in 38.3% of the cases, on the rectosigmoid in 34.5% of the cases, at the ileocecal junction and the appendix in 14.9% of the cases, and at the rectum in 10.2% of the cases. Only one case reported large bowel obstruction by endometriosis of the hepatic flexure of the colon extending to the transverse colon (0.9%), and in one case the obstruction was caused by an omental giant endometrioid cyst compressing the intestines. We identified six cases of postmenopausal females with acute bowel obstruction due to endometriosis. Malignant degeneration of endometriosis was also identified as a cause of intestinal occlusion. The mechanisms of obstruction include the presence of a mass in the lumen of the intestine or in the wall of the intestine, extrinsic compression, adhesions, or intussusception.

Management of Perineal Epidermoid Cyst in a 20-year-old Female

Epidermoid cysts are cutaneous or subcutaneous masses caused by the implantation of epidermal elements into the dermis. This case report presented an epidermal cyst of the perineum clinically mimicking endometriosis in a female patient. A 20-year-old virgo female patient was admitted to our clinic with complaints of severe pain, especially in the right leg, and postmenstrual bleeding for three years. In the transrectal ultrasound, a 54*39 mm cystic lesion with dense internal echo was detected in the medial neighborhood of the pelvic floor right obturator internus muscle. Since the cystic lesion detected in the contrast-enhanced pelvic MRI was evaluated as an epidermoid cyst and no significant endometrioma or endometriosis focus was detected, an operation was planned. Surgical excision should be performed not only for symptom relief and diagnosis but also to exclude rare malignancy. However, it is vital to master the pelvic and perineal anatomy along with careful surgery.

Fibrosis as a key link in the morphogenesis of extragenital endometriosis

The clinical of extragenital endometriosis is variable and depends on the localization, while the leading manifestation is a pronounced pain syndrome, which in some cases can simulate various surgical pathologies. Materials and methods: A morphological and IHC study was performed in 82 cases of extragenital endometriosis of various localization. Research results: An IHC study showed positive expression of -SMA in fibrosis foci around and between endometriosis foci. The expression area of TGF-1 was different for the cytogenic stroma and the perifocally located connective tissue. Conclusions: Fibrosis is an integral component of the morphogenesis of endometrioid heterotopias, while the degree of its severity depends on the duration of the existence of endometriosis foci. Severe pain syndrome is probably associated with deformation of organs and tissues, compression of nerve endings due to fibrosis processes.

ПРОБЛЕМА НЕВЫНАШИВАНИЯ БЕРЕМЕННОСТИ ПРИ АДЕНОМИОЗЕ: ПУТИ РЕШЕНИЯ

The purpose of this study is to substantiate the possibility of successful therapy of miscarriage with adenomyosis based on the study of a clinical case (the patient has a history of 7 unsuccessful IVF attempts). The analysis of this clinical case revealed that despite the presence of clinical signs of endometriosis, in particular, adenomyosis, such as copious, prolonged, painful menstruation with menarche, the absence of pregnancy for 12 months, provided regular sexual activity without the use of contraception by a married couple, unsuccessful IVF attempts in the anamnesis, the diagnosis of adenomyosis was made untimely. Although one of the signs of this disease may be the absence of spontaneous spontaneous pregnancy, despite regular ovulation, patency of the fallopian tubes and a normal spermogram in the partner, as was the case in this case. It is necessary to pay attention to the possibility of this pathology as a cause of infertility in infertile women. At the same time, each unsuccessful IVF attempt can also increase the likelihood of miscarriage, according to research. The adenomyosis revealed in this case apparently caused infertility . The treatment prescribed according to the current clinical recommendations, using progestogens in a continuous mode, in particular, dienogest at a dosage of 2 mg, showed a good result. It is important to take into account that the timing of drug administration and the time of its withdrawal are strictly individual, based on clinical criteria. In this case, as a criterion for drug withdrawal, the achievement of uniformity of the endometrium during ultrasound of the pelvic organs was used, which served as confirmation of the effective suppression of foci of endometriosis in the myometrium. To achieve this result, it took 15 months of hormone therapy with dienogest. The subsequent course of pregnancy was favorable and ended with the birth of a healthy full-term baby. This could also indicate the readiness of both the myometrium and the endometrium for fetal gestation and the normal course of pregnancy. This clinical case demonstrates the effectiveness of using dienogest at a dosage of 2 mg, prescribed with an individual selection of the duration of the course of therapy, in patients with adenomyosis in order to restore reproductive function.

Enhanced expression of certain biomarkers as a predictive factor for malignant transformation of atypic lesions in ovarian endometriosis

BackgroundPatients with ovarian endometriosis (OE) are known to have a 2.5-fold increase in the risk of malignant neoplasms. OE is polymorphic condition histologically subdivided on two forms: “without atypia” and “with atypia”. First form is considered benign, while second one is precursor of ovarian malignant transformation. AimAssess of the morphological and immunohistochemical characteristics indicative of the risk of malignant neoplastic transformation of OE atypical lesions. Materials and methodsSeventy-eight fragments of ovarian tissue (resected regarding ovarian endometrioid cists) were studied histologically for determination of cystic ovarian endometriosis foci with and without atypia. Thirty-five histological slides with OE and 8 slides with adenocarcinomas of different types were studied immunohistochemically. Monoclonal antibodies to Ki-67, Всl-2, р53 proteins and polyclonal antibodies to HNF-1β were used. Results were evaluated by means of Histological score (H-score) method. ResultsThirty-five foci of cystic OE without atypia and 32 foci with epithelial atypia were observed. In foci with epithelial atypia, the expression of Ki-67, Bcl-2 and HNF-1β was significantly higher relatively to the foci without atypia, while expression of р53 was the same in foci with and without atypia. From 4 subtypes of studied ovarian adenocarcinomas the expression of HNF-1β was only observed in clear cell adenocarcinoma. ConclusionEnhanced expression of biomarkers Ki-67, Bcl-2 and HNF-1β in cystic OE with atypia indicates on the risk of malignant transformation of lesions with atypia. Using of these biomarkers can be useful for differential diagnostics of OE with and without atypia and for decision about surgical treatment.

Comparing inpatient management of chronic pelvic pain flares before and after the COVID-19 pandemic.

Patients with chronic pelvic pain (CPP) may experience pain exacerbations requiring hospital admissions. Due to the effects of backlogged elective surgeries and outpatient gynaecology appointments resulting from the COVID-19 pandemic, we hypothesised that there would be an increased number of women admitted with CPP flares. We conducted a retrospective review of all acute gynaecology admissions at the Royal Infirmary of Edinburgh from July to December 2018 (pre-COVID) and 2021 (post-COVID lockdown). We collected information on the proportion of emergency admissions due to CPP, inpatient investigations and subsequent management. Average total indicative hospital inpatient costs for women with CPP were calculated using NHS National Cost Collection data guidance. There was no significant difference in the number of emergency admissions due to pelvic pain before (153/507) and after (160/461) the COVID-19 pandemic. As high as 33 and 31% had a background history of CPP, respectively. Across both timepoints, investigations in women with CPP had low diagnostic yield: <25% had abnormal imaging findings and 0% had positive vaginal swab cultures. Women with CPP received significantly more inpatient morphine, pain team reviews and were more likely to be discharged with strong opioids. Total yearly inpatient costs were £170,104 and £179,156 in 2018 and 2021, respectively. Overall, emergency admission rates for managing CPP flares was similar before and after the COVID-19 pandemic. Inpatient resource use for women with CPP remains high, investigations have low diagnostic yield and frequent instigation of opiates on discharge may risk dependence. Improved community care of CPP is needed to reduce emergency gynaecology resource utilisation. Existing treatments for chronic pelvic pain (CPP) and endometriosis focus on surgery or hormone medication, but these are often ineffective or associated with unacceptable side-effects. As a result, women continue to experience chronic pain and often have 'flares' of worsening pain that may lead to hospital admission. The COVID-19 pandemic resulted in backlogged gynaecology clinics and surgeries. The aim of this study was to compare the management of emergency pelvic pain admissions for women with CPP before and after COVID-19. We also aimed to better understand their in-hospital management and estimate their hospital length of stay costs. We did not find an increase in CPP patients admitted for pelvic pain flares after the COVID-19 lockdown. Women with CPP often undergo multiple hospital tests and are often prescribed with strong pain medications which can cause long-term problems. Efforts are needed to improve long-term pain management for women with CPP.

Malignant endometriosis-associated ovarian and extraovarian neoplasia (review of literature)

Malignant transformation of endometrioid heterotopias develops in 0.7-2.5 % of cases; 75 % of cases have an ovarian localisation and 25 % an extraovarian one. As it has been suggested that malignant endometriosis-associated neoplasia (MEAN) is developed in foci of atypical endometriosis. The review describes the mechanisms of carcinogenesis, the clinical and morphological features of the disease, and the principles of therapy. MEAN usually occur in younger women, are detected at stages I-II, and are mostly represented by clear cell and endometrioid carcinomas, but rare histological types have also been described. CTNNB1, PTEN, PIK3CA and ARID1A mutations are often detected in MEAN. The treatment of MEAN is not standardised, there are no prospective randomized trials assessing treatment. Patients with ovarian MEAN receive therapy similar to epithelial ovarian cancer. Patients with extraovarian localisation represent a subgroup that of patients that may require a personalised approach.

Oxidative phosphorylation inhibitors inhibit proliferation of endometriosis cells.

Developing novel therapies to cure and manage endometriosis is a major unmet need that will benefit over 180 million women worldwide. Results from the current study suggest that inhibitors of oxidative phosphorylation may serve as novel agents for the treatment of endometriosis. Current therapeutic strategies for endometriosis focus on symptom management and are not curative. Here, we provide evidence supporting the inhibition of oxidative phosphorylation (OXPHOS) as a novel treatment strategy for endometriosis. Additionally, we report an organotypic organ-on-a-chip luminal model for endometriosis. The OXPHOS inhibitors, curcumin, plumbagin, and the FDA-approved anti-malarial agent, atovaquone, were tested against the endometriosis cell line, 12Z, in conventional as well as the new organotypic model. The results suggest that all three compounds inhibit proliferation and cause cell death of the endometriotic cells by inhibiting OXPHOS and causing an increase in intracellular oxygen radicals. The oxidative stress mediated by curcumin, plumbagin, and atovaquone causes DNA double-strand breaks as indicated by the elevation of phospho-γH2Ax. Mitochondrial energetics shows a significant decrease in oxygen consumption in 12Z cells. These experiments also highlight differences in the mechanism of action as curcumin and plumbagin inhibit complex I whereas atovaquone blocks complexes I, II, and III. Real-time assessment of cells in the lumen model showed inhibition of migration in response to the test compounds. Additionally, using two-photon lifetime imaging, we demonstrate that the 12Z cells in the lumen show decreased redox ratio (NAD(P)H/FAD) and lower fluorescence lifetime of NAD(P)H in the treated cells confirming major metabolic changes in response to inhibition of mitochondrial electron transport. The robust chemotoxic responses observed with atovaquone suggest that this anti-malarial agent may be repurposed for the effective treatment of endometriosis.

The prospects of cell therapy for endometriosis.

Endometriosis is a chronic inflammatory estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the physiological region. Despite the fact that this disease is common, laparoscopic surgery is currently the gold standard in the treatment of endometriosis. In this regard, it is necessary to develop new effective methods of minimally invasive therapy for endometriosis. One of the promising areas in the treatment of endometriosis is cell therapy. Cellular therapy is a vast branch of therapeutic methods with various agents. Potential cell therapies for endometriosis may be based on the principle of targeting aspects of the pathogenesis of the disease: suppression of estrogen receptor activity, angiogenesis, fibrosis, and a decrease in the content of stem cells in endometriosis foci. In addition, immune cells such as NK cells and macrophages may be promising agents for cell therapy of endometriosis. Standing apart in the methods of cell therapy is the replacement therapy of endometriosis. Thus, many studies in the field of the pathogenesis of endometriosis can shed light not only on the causes of the disease and may contribute to the development of new methods for personalized cell therapy of endometriosis.