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Postoperative adhesions represent a major medical challenge and are associated with serious health and economic consequences. 4DryField ® PH (PlantTec Medical GmbH, Lueneburg, Germany) is a starch-based medical device designed both to prevent adhesions and for hemostasis. This paper explores methods to successfully apply it in gynecological surgery, leveraging the authors' extensive clinical experience. We provide detailed insights into best practices that benefit most patients with conditions such as endometriosis, along with practical tips and guidance on optimizing application and dosage. Our real-world clinical experience across various indications, supported by published data, demonstrates significant patient benefits: reduced adhesion formation, better recovery, less pain, and improved fertility. Patient acceptance and satisfaction are notably high. The device can be applied to surgical wounds as a powder for hemostasis and transformed into a gel in situ or as a premixed gel when adhesion prevention is prioritized. Specific advantages for each method are demonstrated by case studies. When used correctly, 4DryField PH is safe and effective, especially for larger wound areas with a high risk of reoperation and adhesion formation and when pregnancy is desired. It offers great versatility due to its use as either in situ gel or premixed gel with different viscosities. Despite some remaining gaps in clinical evidence and ongoing studies, our personal clinical experience suggests significant benefits with minimal risks. Therefore, we have no concerns regarding the broad use of 4DryField PH in gynecology and other surgical disciplines. Future research should focus on patient-reported outcomes and health economic benefits to support reimbursement efforts.

Endometriosis patients face a significant economic burden. In addition to the directly attributable costs of the diagnosis and therapy of endometriosis, such as drug treatment and multimodal pain therapy, various indirect follow-up costs can be expected, e.g., due to incapacity for work and reduced work performance. As already reported in previous publications, endometriosis is associated with considerable costs for the health care system and society as well as for the affected women and their families. In order to measure the extent of the costs associated with endometriosis patients, 250 patients with an average age of 32.80 years were recruited via social media and interviewed about their self-financed costs as part of an online survey. The assessed direct costs comprise inpatient treatments, outpatient or pain therapy, fertility treatments, hormone therapies, prescribed and privately paid medications and aids, other therapeutic procedures, and directly attributable travel costs for endometriosis treatments. This resulted in an average cost of € 2059.55 per year. Indirect costs were calculated based on loss of income, day-to-day support, care costs, costs due to follow-up illnesses and other costs. On average, the indirect costs were € 2174.25. The average costs resulting from the survey totalled € 4233.81 per year with a standard deviation of € 8240.31. An increase of out-of-pocket costs can be assumed. This may result from an improved range of services for alternative treatment methods and an increased awareness of the need for personal investment in health. However, further health economic studies are needed to validate the results., Competing Interests: Conflict of Interest All authors declare the following: Payment/services info: The Endo Health GmbH (formerly UG) received funding from the European Regional Development Fund (ERDF) from the state of Saxony, Germany. Financial relationships: Nadine Rohloff declares employment and stock/stock options from Endo Health GmbH. CEO, Shareholder. Nadine Rohloff and Nicole R Heinze declare personal fees from DGE (German Nutrition Society). Nicole R Heinze and Teres Götz declare employment from Endo Health GmbH. Consulting fees. Intellectual property info: The Endo-App is a medical device and a registered trademark. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The treatment of endometriosis and adenomyosis requires a complex, multidisciplinary approach. Some centres have established multidisciplinary teams (MDT) and regular meetings. There are currently no international data or recommendations., Objectives: To examine existing MDT meetings and define consensus recommendations to support implementation and conduct., Materials and Methods: Online questionnaires were sent through the European Endometriosis League (EEL) based on a Delphi protocol. After a literature review and assessment of existing MDT meetings, essential aspects for consensus statements were identified. The consensus statements were evaluated using a 5-point Likert scale with the possibility to modify them. Results were analysed between rounds and reported to the respondents. Consensus, defined as ≥70% agreement, concluded the Delphi process when achieved in the majority of statements., Main Outcome Measures: Prevalence and type of existing MDT meetings and recommendations., Results: In round 1, 69 respondents participated, with 49.3% (34) having an MDT meeting at their institutions, of which 97% are multidisciplinary. 50 % meet once a month and 64.7% indicated that less than 25% of their patients are discussed. Throughout the three rounds, 47 respondents from 21 countries participated. During the process, 82 statements were defined, with an agreement of 92.7% on the statements., Conclusions: This study assessed existing MDT meetings for endometriosis and adenomyosis and developed recommendations for their implementation and conduct. The consensus group supports the strengths of MDT meetings, highlighting their role in offering guideline-based, multidisciplinary, and personalised care., What Is New?: This study presents the first international data and recommendations on MDT meetings for endometriosis and adenomyosis.

Introduction: Endometriosis can significantly impair the quality of life of those affected. Multimodal self-help measures are recommended but are often difficult to access. Smartphone apps have been shown to improve the quality of life for other conditions with chronic pain. The aim of this study was to examine the impact of the Endo-App (Endo Health GmbH, Chemnitz, Germany) on both disease-related quality of life and symptoms of endometriosis affecting it., Methods: In the present randomized, controlled pilot study, the impact of utilizing the Endo-App on the quality of life among a sample of 122 women affected by endometriosis is assessed. To measure the changes over a 12-week period, the study incorporates the validated Endometriosis Health Profile (EHP-5 and EHP-30) questionnaire from Oxford University, among other assessment tools., Results: The use of the Endo-App leads to significant changes in the following areas after 12 weeks compared to the control group: pain disability, pain self-efficacy, fatigue, depressive symptoms, and Endometriosis Health Profile scores. The EHP-5 score from T0 to T12 is reduced by -16.76 (p-value of the Mann-Whitney U test (p U ) = 0.008), and the EHP-30 score by -15.48 (p U = 0.004). The results remain significant in sensitivity analyses. The effect size of Cohen's d was in the medium range., Conclusion: In summary, the Endo-App improves both physical and psychological symptoms and the patient's self-efficacy. The Endo-App contributes to improving endometriosis care in Germany and enables women suffering from endometriosis to significantly increase their quality of life., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the State Chamber of Physicians of Saxony, Germany issued approval EK-BR-113/21-1. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The Endo Health GmbH (formerly UG) received funding from the European Regional Development Fund (ERDF) from the state of Saxony, Germany. Financial relationships: Nadine Rohloff declare(s) employment and stock/stock options from Endo Health GmbH. CEO, Shareholder. Sebastian D Schäfer declare(s) non-financial support from Adboard AGE, Adboard EEL, Adboard SEF, WES Ambassador, Board AGEM. Nadine Rohloff declare(s) personal fees from DGE (German Nutrition Society). Reimbursement for lectures. Nicole R Heinze declare(s) employment from Medical School Hannover. Employment since 03/2024. Sebastian D Schäfer declare(s) Support for attending meetings and/or travel from Theramex. Teresa Götz, Sarah S Kortekamp, Nicole R Heinze, Charlotte Weber declare(s) employment from Endo Health GmbH. Sebastian D Schäfer declare(s) personal fees from Roche. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. Sebastian D Schäfer declare(s) personal fees from Endo Health GmbH, Gedeon Richter GmbH, Baxter Medical GmbH, PlantTec Medical GmbH. Participation on a Data Safety Monitoring Board or Advisory Board, Consulting fees. Sebastian D Schäfer declare(s) personal fees from Eisai Pharma. Consulting fees . Intellectual property info: The Endo-App is a medical device and a registered trademark. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rohloff et al.)

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part focuses on intrauterine devices and sterilization. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. This summary presents recommendations and statements about intrauterine devices and female and male sterilization., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline./Die Interessenkonflikte der Autor*innen sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Aim This official guideline was published and coordinated by the DGGG, OEGGG and SGGG with the involvement of other medical societies. The aim was to provide a consensus-based overview of non-hormonal forms of contraception based on an evaluation of the relevant literature. The first part of these summarized statements and recommendations presents natural family planning methods such as lactational amenorrhea, barrier methods and coitus interruptus. The second part will focus on intrauterine devices and sterilization methods. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, OEGGG and SGGG using a structured consensus process. Recommendations The guideline provides recommendations on the indications for, safety of use, benefits, and limitations of the different methods as well as recommendations on providing advice and other aspects of non-hormonal contraception. Natural family planning methods, lactational amenorrhea, barrier methods and coitus interruptus are discussed., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline./Die Interessenkonflikte der Autor*innen sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Purpose: Endometriosis can significantly impair the quality of life of those affected. Multimodal self-help measures are recommended but often difficult to access. Smartphone apps have been shown to improve the quality of life for other conditions with chronic pain. The aim of this study was to examine whether there is evidence of beneficial effects of the smartphone app "Endo-App ® " and whether a multicenter randomized controlled trial should be planned to substantiate these effects., Methods: In a sample of N = 106 women affected by endometriosis the present study determined the influence of the use of Endo-App ® on their quality of life. Among others, the validated questionnaire Endometriosis Health Profile from Oxford University was used for this purpose., Results: The use of Endo-App ® lead to a highly significant improvement in quality of life already after 2 weeks. A statistically significant change was found for nine out of ten measured variables of quality of life. A series of further analyses validated that the measured positive effects were not due to other confounding factors., Conclusion: In summary, the results indicate that the quality of life of women with endometriosis improved by the digital self-management tool Endo-App ® . More studies are needed to further explore the influence of the app on quality of life and as confirmatory evidence of beneficial effects. For this purpose, a randomized controlled trial should be conducted over a longer period of time., Trial Registration: This trial is registered at clinicaltrials.gov under the registration number NCT05528601 on August 18, 2022. It was retrospectively registered., (© 2024. The Author(s).)

Ferroptosis, an iron-dependent form of non-apoptotic cell death, plays a pivotal role in various diseases and is gaining considerable attention in the realm of endometriosis. Considering the classical pathomechanism theories, we hypothesized that ferroptosis, potentially driven by increased iron content at ectopic sites, may contribute to the progression of endometriosis. This retrospective case-control study provides a comprehensive immunohistochemical assessment of the expression and tissue distribution of established ferroptosis markers: GPX4, ACSL4, and TfR1 in endometriosis patients. The case group consisted of 38 women with laparoscopically and histologically confirmed endometriosis and the control group consisted of 18 women with other gynecological conditions. Our study revealed a significant downregulation of GPX4 in stromal cells of endometriosis patients ( M = 59.7% ± 42.4 versus 90.0% ± 17.5 in the control group, t (54) = -2.90, p = 0.005). This finding aligned with slightly, but not significantly, higher iron levels detected in the blood of endometriosis patients, using hemoglobin as an indirect predictor (Hb 12.8 (12.2-13.5) g/dL versus 12.5 (12.2-13.4) g/dL in the control group; t (54) = -0.897, p = 0.374). Interestingly, there was no concurrent upregulation of TfR1 ( M = 0.7 ± 1.2 versus 0.2 ± 0.4 for EM, t (54) = 2.552, p = 0.014), responsible for iron uptake into cells. Our empirical findings provide support for the involvement of ferroptosis in the context of endometriosis. However, variances in expression patterns within stromal and epithelial cellular subsets call for further in-depth investigations.

Objective: Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis., Methods: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed., Results: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs., Conclusions: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Ovarian cancer (OC) is the eighth cancer both in prevalence and mortality in women and represents the deadliest female reproductive cancer. Due to generally vague symptoms, OC is frequently diagnosed only at a late and advanced stage, resulting in high mortality. The tumor extracellular matrix and cellular matrix receptors play a key role in the pathogenesis of tumor progression. Syndecans are a family of four transmembrane heparan sulfate proteoglycans (PG), including syndecan-1, -2, -3, and -4, which are dysregulated in a myriad of cancers, including OC. Many clinicopathological studies suggest that these proteins are promising diagnostic and prognostic biomarkers for OC. Furthermore, functions of the syndecan family in the regulation of cellular processes make it an interesting pharmacological target for anticancer therapies.

Introduction: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries., Material and Methods: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared., Results: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (r Spearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups., Conclusions: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

The stem cell marker and RNA-binding protein Musashi-1 is overexpressed in endometriosis. Musashi-1-siRNA knockdown in Ishikawa cells altered the expression of stem cell related genes, such as OCT-4. To investigate the role of both human Musashi homologues (MSI-1 and MSI-2) in the pathogenesis of endometriosis, immortalized endometriotic 12-Z cells and primary endometriotic stroma cells were treated with Musashi-1- and Musashi-2-siRNA. Subsequently, the impact on cell proliferation, cell apoptosis, cell necrosis, spheroid formation, stem cell phenotype and the Notch signaling pathway was studied in vitro. Using the ENDOMET Turku Endometriosis database, the gene expression of stem cell markers and Notch signaling pathway constituents were analyzed according to localization of the endometriosis lesions. The database analysis demonstrated that expression of Musashi and Notch pathway-related genes are dysregulated in patients with endometriosis. Musashi-1/2-double-knockdown increased apoptosis and necrosis and reduced stem cell gene expression, cell proliferation, and the formation of spheroids. Musashi silencing increased the expression of the anti-proliferation mediator p21. Our findings suggest the therapeutic potential of targeting the Musashi-Notch axis. We conclude that the Musashi genes have an impact on Notch signaling and the pathogenesis of endometriosis through the downregulation of proliferation, stemness characteristics and the upregulation of apoptosis, necrosis and of the cell cycle regulator p21.

The present article summarises the recommendations for the handling, histopathological workup, diagnostics and reporting in surgical pathology of biopsies and resection specimens in patients with the clinical diagnosis of endometriosis. In addition to practical aspects of pathology, the guidelines also take into account the clinical requirements for histopathology for the optimal diagnosis and therapy of the patients.Based on the definition of endometriosis of the corpus uteri (adenomyosis uteri) most commonly used in the pathological literature, this was defined in the guidelines as the detection of the endometriosis focus in the myometrium at a distance from the endomyometrial border of a medium-sized visual field (100× magnification), which in metric units corresponds to around 2.5 mm. In bowel resection specimens, the status of the resection margins had to be documented within the histopathological report.Also mentioned are the requirements for the reporting of carcinomas associated with endometriosis, including the immunohistochemical evaluation of steroid hormone receptors and mismatch repair proteins., (© 2021. The Author(s).)

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interests of the authors are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithelial endometriotic (12Z) and co-culture (1:1 St-T1b:12Z) spheroids to mimic the architecture of endometrium, and either collagen I or Matrigel to model ectopic locations. Stromal spheroids, but not single cells, assumed coordinated directional migration followed by matrix remodeling of collagen I on day 5 or 7, resembling ectopic lesions. While generally a higher area fold increase of spheroids occurred on collagen I compared to Matrigel, directional migration was not observed in co-culture or in 12Z cells. The fold increase in area on collagen I was significantly reduced by MMP inhibition in stromal but not 12Z cells. Inhibiting ROCK signalling responsible for actomyosin contraction increased the fold increase of area and metabolic activity compared to untreated controls on Matrigel. The number of protrusions emanating from 12Z spheroids on Matrigel was decreased by microRNA miR-200b and increased by miR-145. This study demonstrates that spheroid assay is a promising pre-clinical tool that can be used to evaluate small molecule drugs and microRNA-based therapeutics for endometriosis.

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates Rho-associated protein kinase 2 ( ROCK2 ), cofilin 2 ( CFL2) , Ras-related C3 botulinum toxin substrate 1 ( RAC1 ), neural Wiskott-Aldrich syndrome protein ( WASL ), and integrin α-V ( ITGAV ). qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL . On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters, and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

Introduction: Stem cells mediate cyclic regeneration of the endometrium. The upregulated expression of receptors and modulators of the notch signaling pathway in endometriosis suggests an involvement in the pathogenetic process. Here, we investigated the effects of notch pathway inhibition by a γ-secretase inhibitor (GSI) on stemness-associated properties of the epithelial endometriotic cell line 12Z and of primary endometriotic stroma cells., Material and Methods: 12Z cells and primary endometriotic stroma cells of 7 patients were treated with or without GSI, and analyzed for changes in gene expression by TaqMan low-density arrays, quantitative PCR, and flow cytometry. The functional impact of GSI treatment was studied by MTT assay, cell cycle analysis, colony formation assay, annexin V apoptosis assay, and aldehyde dehydrogenase activity assays., Results: In 12Z cells, GSI treatment reduced aldehyde dehydrogenase activity and colony formation, and induced a shift to the G2/M phase of the cell cycle. Cell viability was decreased and apoptosis was increased in both cell models. GSI further induced transcriptional downregulation of the stemness-associated factors leukemia inhibitory factor receptor (LIFR), sex-determining region Y (SRY)- box 2, interferon-induced transmembrane protein 1, and hes-related family bHLH transcription factor with YRPW motif 1, in 12Z cells and in primary cell cultures. Downregulation of LIFR expression by GSI was confirmed at the protein level by flow cytometry., Conclusions: Our in vitro data suggest that application of GSI may be a worthwhile approach in the treatment of endometriosis that warrants further investigation., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Strain elastography (SE) is a new technique of parametric imaging that allows quantification of the elasticity of tissue. The aim of our study was to determine if the elasticity of para-urethral tissue correlates with urethral mobility and urinary incontinence (UI). Ninety-nine unselected women were investigated with SE. They were given a standardized interview about UI, and SE raw data for the para-urethral tissue were acquired in a sagittal standard urethra-symphysis view while being stimulated by a coughing fit. We placed one region of interest (ROI A) in the tissue between the urethra and vagina at midlevel of the urethra bordering the urethral wall. The second ROI (ROI B) was set at the level of the os urethra internum in the tissue of the bladder neck in one line to ROI A. We measured elasticity in both ROIs with TDI-Q (Tissue Doppler Imaging-Quantification Software) and calculated the ratio between ROI A and ROI B (A/B). Mobility of the urethra was quantified by measuring the angle between a line parallel to the urethra and a line parallel to the bladder neck during stress and rest. SE analysis was feasible in all cases. A/B was found to be correlated with the incidence of urethral mobility (p < 0.001). The incidence of UI was associated with an increase in urethral mobility (p = 0.04). No correlation between UI and A/B could be shown (p = 0.24). We observed a correlation between urethral mobility and elasticity of the para-urethral tissue. In case of increasing urethral mobility, the para-urethral tissue close to the bladder neck seems to be more elastic, and the patients reported about more symptoms of UI. No noticeable correlation between UI and urethral elasticity was shown. SE may be a useful technique for direct quantification of tissue elasticity and assessment of pelvic floor biomechanics., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate normal uterine tissue with special regard to age and the presence of uterine fibroids and adenomyosis with transvaginal elastography., Materials and Methods: In a prospective study elastographic data of the uterus were obtained in 206 unselected women with transvaginal ultrasound. Women who presented without any uterine pathology in ultrasonography were included in a control group, women with uterine fibroids in a uterine fibroid group, and women with adenomyosis in an adenomyosis group. In the control group strain values were measured at two regions of interest (ROIs) placed one upon the other in the anterior inferior uterine segment during a cycle of compression. The maximum strain ratio (ROI1 / ROI2) was stored as the "age index". In all groups strain values were measured at two ROIs placed side by side in a uterine fibroid (uterine fibroid group) or adenomyosis (adenomyosis group) or healthy homogeneous tissue (control group) and adjacent healthy tissue. Maximum strain ratios (ROI3 / ROI4) were stored as the "lesion index"., Results: The "age index" was significantly negatively correlated with the age of the women (r = -0.49, p < 0.001). The median "lesion indices" were significantly (p < 0.001) different between the uterine fibroid, adenomyosis and control groups. Median "lesion indices" were 2.65, 0.44 and 1.19, respectively., Conclusion: The "age index" shows that normal uterine tissue has a certain age-dependent stiffness that increases with age. The "lesion index" allows for the assessment of the presence of a uterine fibroid or adenomyosis and helps to differentiate between both focal findings. Thus the use of elastography in addition to conventional ultrasound could help to diagnose uterine focal lesions and may be useful in preoperative planning., (© Georg Thieme Verlag KG Stuttgart · New York.)

Endometriosis is characterized by growth of endometrial tissue at ectopic locations. Down-regulation of microRNA miR-200b is observed in endometriosis and malignant disease, driving tumour cells towards an invasive state by enhancing epithelial-to-mesenchymal transition (EMT). miR-200b up-regulation may inhibit EMT and invasive growth in endometriosis. To study its functional impact on the immortalized endometriotic cell line 12Z, the stromal cell line ST-T1b, and primary endometriotic stroma cells, a transient transfection approach with microRNA precursors was employed. Expression of bioinformatically predicted targets of miR-200b was analysed by qPCR. The cellular phenotype was monitored by Matrigel invasion assays, digital-holographic video microscopy and flow cytometry. qPCR revealed significant down-regulation of ZEB1 (P < 0.05) and ZEB2 (P < 0.01) and an increase in E-cadherin (P < 0.01). miR-200b overexpression decreased invasiveness (P < 0.0001) and cell motility (P < 0.05). In contrast, cell proliferation (P < 0.0001) and the stemness-associated side population phenotype (P < 0.01) were enhanced following miR-200b transfection. These properties were possibly due to up-regulation of the pluripotency-associated transcription factor KLF4 (P < 0.05) and require attention when considering therapeutic strategies. In conclusion, up-regulation of miR-200b reverts EMT, emerging as a potential therapeutic approach to inhibit endometriotic cell motility and invasiveness., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Endometriosis is associated with severe pelvic pain and reduced fertility. Recently, it has been linked to a dysregulation of microRNAs (miRNAs), which are post-transcriptional regulators of gene expression. The functional effect of dysregulated miR-142-3p expression in endometrial stroma cells was investigated. An increased expression of miR-142-3p resulted in a significantly reduced expression of steroid sulfatase and interleukin-6-coreceptor gp130 as well as reduced interleukin-6-mediated activation of the STAT3-pathway, suggesting an effect of miR-142-3p both on steroid hormone- and cytokine-mediated signalling events. At the functional level, miR-142-3p overexpression significantly reduced cell viability (P ≤ 0.01). miR-142-3p regulation emerges as a future therapeutic strategy for endometriosis., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the presence of a lesion indicative of endometriosis with transvaginal elastography., Materials and Methods: Transvaginal ultrasound and clinical examination were carried out in 48 women with clinical symptoms indicative of endometriosis. In 31 cases strain values were measured at two regions of interest (ROIs) in the Douglas's cul-de-sac during a cycle of compression and decompression with a vaginal probe., Results: A significant difference was found for the ratio of the ROI measuring points in the Douglas' cul-de-sacs of women with a palpable nodule in examination compared to women without a palpable nodule (p = 0.002)., Conclusion: The ratio of strain values between two ROIs in the Douglas' s cul-de-sac is associated with the presence of an endometriotic lesion. In the future, these findings could allow for a more detailed pre-surgical evaluation and possibly serve as a novel diagnostic tool for predicting deep infiltrating endometriosis., (© Georg Thieme Verlag KG Stuttgart · New York.)