DIRAS3 regulates autophagy in an endometriosis epithelial cell line.

RESEARCH QUESTION: What is the role of DIRAS3 in endometriosis pathogenesis? DESIGN: Prospective patient cohort study combined with experiments in the 12Z human endometriosis epithelial cell line model to determine the role of DIRAS3 in endometriosis. Endometrium and endometriosis lesion samples were collected from premenopausal women from 24 control and 40 endometriosis patients by laparoscopic surgery. The role of DIRAS3 in endometriosis was assessed by siRNA knockdown in 12Z cells followed by proliferation, apoptosis, invasion and autophagy assays. Autophagy was induced by serum starvation and the levels of autophagy determined by assessing changes in the expression levels and localization of autophagy marker proteins, such as LC3. RESULTS: DIRAS3 mRNA showed a large increase in expression in ectopic endometriosis lesions compared with endometrium from control patients, with expression largely localized to the epithelium. DIRAS3 knockdown in 12Z endometriosis epithelial cells caused a significant reduction in the number of proliferating cells (1.6-fold, adjusted P = 0.0007) and increased apoptosis (AnnexinV/7AAD double-positive cells +48%, P = 0.01), indicating an effect on cell proliferation. Induction of autophagy by serum starvation caused significant upregulation in DIRAS3 expression after 24 h (mRNA +2.4-fold [adjusted P = 0.017], protein +8.1-fold (adjusted P = 0.029), reduced LC3I/LC3II ratio (-2.2-fold, adjusted P = 0.044) and an increase in the number of double positive LC3/DIRAS3 puncta (+2.3-fold, P = 0.02). Knockdown of DIRAS3 in serum-starved cells led to a reduction in autophagy, indicated by an overall decrease in LC3 expression and significant increase in LC3I/LC3II ratio. CONCLUSIONS: DIRAS3 is highly upregulated in endometriosis lesions. Studies in an endometriosis epithelial cell line indicate that DIRAS3 facilitates cell survival in this context by inducing autophagy.

Fertility preserving management of ovarian torsion.

OBJECTIVE: To analyze characteristics of acute and chronic ovarian torsion, review treatment recommendations, and present possible surgical techniques for fertility preservation in young women. DESIGN: Literature review and demonstration of perioperative management of ovarian torsion using radiologic images and intraoperative video footage. Ovarian torsion is mostly mentioned in context of gynecologic emergencies, where acute ovarian torsion with arterial obstruction leads to ovarian ischemia and necrosis. However, ovarian torsion can also occur as a partial or intermittent torsion with venous and lymphatic obstruction, followed by ovarian swelling. In both cases, surgical management of ovarian torsion commonly includes oophorectomy, although leading guidelines recommend preservation of the ovary. We here aimed to raise awareness for the clinical features of ovarian torsion and demonstrate adequate perioperative management, thereby avoiding surgical overtreatment in young women. SETTING: Medical University of Vienna, Department of Obstetrics and Gynecology. PATIENT(S): We present a case of acute ovarian torsion with a consequently ischemic ovary as well as a case of chronic ovarian torsion with related massive ovarian edema. The patients included in this video gave consent for publication of the video and posting of the video online, including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.), and other applicable sites. INTERVENTION(S): Laparoscopic management with detorsion of the torquated ovaries, cystectomy on an ischemic ovary and oophoropexy to the pelvic side wall and utero-ovarian ligament to prevent recurrence. MAIN OUTCOME MEASURES: Postoperative relief of pain and normalization of ovarian size and morphology on ultrasound imaging. RESULTS: The current cases show successful conservative surgical management of ovarian torsion, hence preserving hormonal function and fertility in young women. CONCLUSION: Although it is recommended to preserve fertility in young women affected by ovarian torsion, surgical overtreatment by means of oophorectomy is still common in clinical routine. Increasing awareness for the clinical characteristics of acute and chronic ovarian torsion, as well as for the importance of preservation of the ovary, is crucial. We therefore believe that ovarian torsion and its surgical management deserve increased attention in the future.

Does the Use of the "Proseek® Multiplex Inflammation I Panel" Demonstrate a Difference in Local and Systemic Immune Responses in Endometriosis Patients with or without Deep-Infiltrating Lesions?

Endometriotic lesions are able to infiltrate surrounding tissue. This is made possible partly by an altered local and systemic immune response that helps achieve neoangiogenesis, cell proliferation and immune escape. Deep-infiltrating endometriosis (DIE) differs from other subtypes through the invasion of its lesions over 5 mm into affected tissue. Despite the invasive nature of these lesions and the wider range of symptoms they can trigger, DIE is described as a stable disease. This elicits the need for a better understanding of the underlying pathogenesis. We used the "Proseek® Multiplex Inflammation I Panel" in order to simultaneously detect 92 inflammatory proteins in plasma and peritoneal fluid (PF) of controls and patients with endometriosis, as well as in particular patients with DIE, in order to gain a better insight into the systemically and locally involved immune response. Extracellular newly identified receptor for advanced gycation end-products binding protein (EN-RAGE), C-C motif Chemokine ligand 23 (CCL23), Eukaryotic translation initiation factor 4-binding protein 1 (4E-BP1) and human glial cell-line derived neurotrophic factor (hGDNF) were significantly increased in plasma of endometriosis patients compared to controls, whereas Hepatocyte Growth factor (HGF) and TNF-related apoptosis inducing ligand (TRAIL) were decreased. In PF of endometriosis patients, we found Interleukin 18 (IL-18) to be decreased, yet Interleukin 8 (IL-8) and Interleukin 6 (IL-6) to be increased. TNF-related activation-induced cytokine (TRANCE) and C-C motif Chemokine ligand 11 (CCL11) were significantly decreased in plasma, whereas C-C motif Chemokine ligand 23 (CCL23), Stem Cell Factor (SCF) and C-X-C motif chemokine 5 (CXCL5) were significantly increased in PF of patients with DIE compared to endometriosis patients without DIE. Although DIE lesions are characterized by increased angiogenetic and pro-inflammatory properties, our current study seems to support the theory that the systemic immune system does not play a major role in the pathogenesis of these lesions.

Perioperative Techniques for the Use of Botulinum Toxin in Overactive Bladder: Results of a Multinational Online Survey of Urogynecologists in Germany, Austria, and Switzerland.

INTRODUCTION AND HYPOTHESIS: Botulinum toxin (BoNT) is a widely used treatment for overactive bladder (OAB). Despite its common use, no standardized treatment regimen exists so far. The aim of this survey was to evaluate the variation in perioperative treatment strategies among members of the German-speaking urogynecologic societies. MATERIALS AND METHODS: A clinical practice online survey was carried out between May 2021 and May 2022, and all members of the German, Swiss, and Austrian urogynecologic societies were invited to participate. Participants were grouped in two ways. First, they were grouped into (1) urogynecologists with board certification and (2) non-board-certified general obstetricians and gynecologists (OBGYNs). Second, we set a cut-off at 20 transurethral BoNT procedures per year to differentiate between (1) high- and (2) low-volume surgeons. RESULTS: One hundred and six completed questionnaires were received. Our results demonstrated that BoNT is mostly used as a third-line treatment (93%, n = 98/106), while high-volume surgeons used it significantly more often as a first/second-line treatment (21% vs. 6%, p = 0.029). Large variations existed in the use of perioperative antibiotics, preferred sites of injection, the number of injections, and the timing of the measurement of the postvoid residual volume (PVRV). Forty percent of participants did not offer outpatient treatment to patients. Local anesthesia (LA) was mostly used by board-certified urogynecologists (49% vs. 10%, p < 0.001) and high-volume surgeons (58% vs. 27%, p = 0.002). Injections into the trigone were also more often performed by board-certified urogynecologists and high-volume surgeons (22% vs. 3% (p = 0.023) and 35% vs. 6% (p < 0.001), respectively). PVRV was controlled between weeks 1 and 4 by only 54% of participants (n = 57/106). Clean intermittent self-catheterization (CISC) was infrequently taught (26%). CONCLUSIONS: Our survey confirmed that BoNT is widely used by urogynecologists in the three German-speaking countries, but practice patterns vary widely, and no standardized method could be detected, despite interviewing urogynecologic experts. These results clearly demonstrate that there is a need for studies to define standardized treatment strategies for the best perioperative and surgical approach regarding the use of BoNT in patients with OAB.

The human placenta shapes the phenotype of decidual macrophages.

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.

The latest advances in the pharmacological management of endometriosis.

INTRODUCTION: Endometriosis is a benign disease, characterized by a wide range of symptoms and different degrees of severity, which is why therapy should be individually adapted to the patient's needs. Over the years, a lot of research has gone into finding new therapeutic approaches for this enigmatic disease. AREAS COVERED: This review presents the latest advances in pharmacological management of endometriosis and is solely focused on studies published from 2010 to 2021. EXPERT OPINION: Clinicians and researchers are constantly searching for new therapeutic strategies for endometriosis patients. As there are well-established treatments, however, any new medication should fulfill at least one of the three criteria: increased efficacy, comparable efficacy but a better safety profile, or treatments that have a lack of accompanying contraceptive effects that are seen in most endometriosis treatments. While some new substances show promising results, further studies are needed to demonstrate the fulfillment of one of the above-mentioned criteria.

MLLT11 Regulates Endometrial Stroma Cell Adhesion, Proliferation and Survival in Ectopic Lesions of Women with Advanced Endometriosis.

MLLT11 is a gene implicated in cell differentiation and the development and progression of human cancers, but whose role in the pathogenesis of endometriosis is still unknown. Using quantitative RT-PCR and immunohistochemistry, we analyzed 37 women with and 33 women without endometriosis for differences in MLLT11 expression. We found that MLLT11 is reduced in the ectopic stroma cells of women with advanced stage endometriosis compared to women without endometriosis. MLLT11 knockdown in control stroma cells resulted in the downregulation of their proliferation accompanied by G1 cell arrest and an increase in the expression of p21 and p27. Furthermore, the knockdown of MLLT11 was associated with increased apoptosis resistance to camptothecin associated with changes in BCL2/BAX signaling. Finally, MLLT11 siRNA knockdown in the control primary stroma cells led to an increase in cell adhesion associated with the transcriptional activation of ACTA2 and TGFB2. We found that the cellular phenotype of MLLT11 knockdown cells resembled the phenotype of the primary endometriosis stroma cells of the lesion, where the levels of MLLT11 are significantly reduced compared to the eutopic stroma cells of women without the disease. Overall, our results indicate that MLLT11 may be a new clinically relevant player in the pathogenesis of endometriosis.

Vaginal transisthmic myomectomy: a step by step video tutorial.

OBJECTIVE: To provide a video tutorial on vaginal transisthmic myomectomy in women with large submucosal fibroids. DESIGN: Stepwise demonstration of the technique, with a narrated video footage. SETTING: Submucosal fibroids protrude into the uterine cavity and can cause numerous symptoms, including abnormal uterine bleeding, dysmenorrhea, subfertility, and obstetric complications. Over the last decades, hysteroscopic resection has become the preferred surgical approach for submucosal fibroids because it provides significant advantages regarding perioperative morbidity and postoperative recovery time when compared with laparotomy or laparoscopy with complete transection of the uterine wall. However, in large or multiple fibroids, longer surgery durations of hysteroscopic resection can lead to higher complication rates and incomplete resection. In some cases, hysteroscopic resection might even be impossible to perform. Furthermore, in many regions, special equipment for hysteroscopic myomectomy might not be available. Herein, we present a minimally invasive surgical alternative for approaching submucosal fibroids. PATIENT(S): A 26-year-old woman presenting with hypermenorrhea and dysmenorrhea (on a numeric rating scale from 0-10) caused by a recurrent International Federation of Gynaecology and Obstetrics (FIGO) type 0 fibroid measuring 5 cm in diameter. INTERVENTION(S): Vaginal transisthmic myomectomy performed with a longitudinal transection of the uterine cervix and isthmus, morcellation of the fibroid with a scalpel, and multilayer reconstruction. MAIN OUTCOME MEASURE(S): Vaginal transisthmic myomectomy is a fast and relatively simple, minimally invasive surgical technique suitable for large or multiple FIGO 0 and some FIGO 1 fibroids, necessitating the use of only basic surgical equipment. RESULT(S): Vaginal transisthmic myomectomy provides an additional minimally invasive surgical approach for submucosal fibroids. CONCLUSION(S): This surgical option for selected patients may help prevent complications resulting from prolonged hysteroscopic surgery, repeated hysteroscopic procedures owing to incomplete resection, and the morbidity of transabdominal approaches for myomectomy. With this video, we aim to expedite the clinical learning curve of this technique, which should be investigated on a broader scale in the future.

Hsa-mir-135a Shows Potential as A Putative Diagnostic Biomarker in Saliva and Plasma for Endometriosis.

Endometriosis is a chronic disease characterized by the implantation and proliferation of endometrial tissue outside of the uterine cavity. The nonspecific nature of the symptoms and the lack of sensitive, noninvasive diagnostic methods often lead to a significant delay in diagnosis, highlighting the need for diagnostic biomarkers. The correlation of circulating miRNAs with altered inflammatory signals seen in patients with endometriosis has raised the possibility that miRNAs can serve as biomarkers for the disease. In our study, we analyzed miRNA expression in saliva of women with and without endometriosis using a FireFly custom multiplex circulating miRNA assay. This focused panel included 28 human miRNAs, 25 of which have been previously found to be differentially expressed either in plasma, serum, and/or blood of women with endometriosis, compared to controls. We found that hsa-mir-135a was expressed significantly higher in the saliva of women with endometriosis, independent of disease stage and menstrual cycle phase. We confirmed that hsa-mir-135a also showed significantly elevated expression in the plasma of endometriosis patients. This indicates that hsa-mir-135a is a putative noninvasive biomarker of endometriosis in both saliva and plasma, but further validation studies are required to assess its clinical value as a biomarker.

Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Local estrogen therapy (LET) has beneficial effects on genitourinary atrophy; however it is currently unclear if LET improves sexual function in postmenopausal women with pelvic organ prolapse (POP). AIM: To evaluate if LET vs placebo results in an improved sexual function in postmenopausal women with symptomatic POP. METHODS: We performed a secondary analysis of sexual outcomes of a previous randomized controlled trial comparing LET and placebo in 120 postmenopausal women (60/group) with symptomatic POP stage ≥3 and planned prolapse surgery. Women were randomly assigned to receive local estrogen or placebo cream 6 weeks preoperatively. The effect of therapy vs placebo was assessed with ANOVA with interaction effect of time*group and a multivariable linear regression model was built to assess the impact of different variables on sexual function before therapy. OUTCOMES: We evaluated the sexual function score in sexually active women of our study population using the German Pelvic Floor Questionnaire at recruitment time and again after 6 weeks of treatment. RESULTS: Among 120 randomized women, 66 sexually active women remained for final analysis. There was no significant difference in the change of the sexual function score over time between the treatment groups (difference in changes in score from baseline to 6 weeks for Estrogen group vs control group was -0.110 with 95% CI -0.364 to 0.144) Multivariable analysis showed that no independent risk factor for unsatisfying sexual function score could be identified. CLINICAL IMPLICATIONS: Based on our results, LET has no beneficial effect on sexual function in postmenopausal women with POP. STRENGTHS AND LIMITATIONS: Main strength of our study lies in the study design and in the use of a condition- specific questionnaire. As this is a secondary analysis, this study may be insufficiently powered to identify differences in sexual data between groups. CONCLUSION: LET had no impact on female sexuality in postmenopausal women with POP. Marschalek M-L, Bodner K, Kimberger O, et al. Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial. J Sex Med 2022;19:1124-1130.

Myomectomy for a large uterine fibroid via mini-laparotomy: a step-by-step video tutorial.

OBJECTIVE: To provide a video tutorial on myomectomy via mini-laparotomy in women with large uterine fibroids. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Uterine fibroids represent the most common benign gynecologic disease, and myomectomy is a frequent reproductive surgery aiming to preserve or improve fertility. Abdominal and laparoscopic myomectomy are common treatments, but over the last decades, laparoscopy has become the preferred surgical approach because it provides significant advantages, such as shorter recovery time and a lower overall risk of complications. However, removal of large fibroids by laparoscopy is often technically challenging or even impossible. PATIENT(S): A 29-year-old woman presenting with urinary frequency and lower abdominal pressure due to a 14-cm diameter FIGO type 4 uterine fibroid in the anterior uterine wall. INTERVENTION(S): Myomectomy via mini-laparotomy using a 4-cm transverse skin incision and morcellation with a scalpel using an atraumatic circular self-retaining wound retractor. MAIN OUTCOME MEASURE(S): Mini-laparotomy represents a safe and simple approach combining the benefits of laparoscopy, such as reduced postoperative pain, reduced morbidity, and shorter hospitalization time, and the benefits of laparotomy, such as shorter duration of surgery, cost-effectiveness, and no need for advanced laparoscopic skills. RESULT(S): Mini-laparotomy can provide preferable cosmesis compared with alternative approaches. CONCLUSION(S): Mini-laparotomy represents an alternative minimally-invasive approach for large uterine fibroids, resulting in good overall outcome and no need for special surgical skills or equipment including power-morcellators. With this video, we aim to expedite the clinical learning curve of this technique and believe that selected patients desiring fertility could benefit from its application on a broader scale in the future.

Comparison of a practice-based versus theory-based training program for conducting vacuum-assisted deliveries: a randomized-controlled trial.

PURPOSE: Vacuum-assisted deliveries (VAD) are complex procedures that require training and experience to be performed proficiently. We aimed to evaluate if a more resource intensive practice-based training program for conducting VAD is more efficient compared to a purely theory-based training program, with respect to immediate training effects and persistence of skills 4-8 weeks after the initial training. METHODS: In this randomized-controlled study conducted in maternity staff, participants performed a simulated low-cavity non-rotational vacuum delivery before (baseline test) and immediately after the training (first post-training test) as well as 4-8 weeks thereafter (second post-training test). The study's primary endpoint was to compare training effectiveness between the two study groups using a validated objective structured assessment of technical skills (OSATS) rating scale. RESULTS: Sixty-two participants were randomized to either the theory-based group (n = 31) or the practice-based group (n = 31). Total global and specific OSATS scores, as well as distance of cup application to the flexion point improved significantly from baseline test to the first post-training test in both groups (pall < 0.007). Skill deterioration after 4-8 weeks was only found in the theory-based group, whereas skills remained stable in the practice-based group. CONCLUSION: A practice-based training program for conducting VAD results in comparable immediate improvement of skills compared to a theory-based training program, but the retention of skills 4-8 weeks after training is superior in a practice-based program. Future studies need to evaluate, whether VAD simulation training improves maternal and neonatal outcome after VAD.

The Role of Long Non-Coding RNAs in Endometriosis.

Endometriosis is a chronic gynecological disorder affecting the quality of life and fertility of many women around the world. Heterogeneous and non-specific symptoms may lead to a delay in diagnosis, with treatment options limited to surgery and hormonal therapy. Hence, there is a need to better understand the pathogenesis of the disease to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation but remain relatively under investigated in endometriosis. Mutational and transcriptomic studies have implicated lncRNAs in the pathogenesis of endometriosis. Single-nucleotide polymorphisms (SNPs) in lncRNAs or their regulatory regions have been associated with endometriosis. Genome-wide transcriptomic studies have identified lncRNAs that show deregulated expression in endometriosis, some of which have been subjected to further experiments, which support a role in endometriosis. Mechanistic studies indicate that lncRNAs may regulate genes involved in endometriosis by acting as a molecular sponge for miRNAs, by directly targeting regulatory elements via interactions with chromatin or transcription factors or by affecting signaling pathways. Future studies should concentrate on determining the role of uncharacterized lncRNAs revealed by endometriosis transcriptome studies and the relevance of lncRNAs implicated in the disease by in vitro and animal model studies.

Temporal trends in obstetric anal sphincter injury from the first vaginal delivery in Austria, Canada, Norway, and Sweden.

INTRODUCTION: Obstetric anal sphincter injuries (OASI) are severe complications that can cause considerable short- and long-term morbidity. Austria, Canada, Norway, and Sweden have similar socio-economic characteristics, and all four countries have access to national birth registers. In this study, we hypothesized that the incidence of OASI should be very similar for different obstetric scenarios in these four countries. Therefore, the aim was to compare the incidence of OASI in these four countries in primiparous women, with spontaneous or instrumental delivery (vacuum or forceps), and in women with a first vaginal birth after cesarean section (VBAC). MATERIAL AND METHODS: Aggregated data on 1 933 930 vaginally delivered primiparous women and women with VBAC were retrieved from the birth registers gathered in Austria, Canada, Norway, and Sweden. The annual rate of OASI (ICD-10 codes O70.2-O70.3) was presented as the percentage of women with a spontaneous delivery, vacuum or forceps delivery, and a VBAC during the period 2004-2016. RESULTS: The incidence of OASI varied considerably between countries and over time. Canada and Sweden had the highest rates, and Austria and Norway the lowest. In Norway, the rate of OASI decreased consistently for all types of deliveries after introducing a perineal protection program in 2004 (p < 0.001). During vacuum delivery, the incidence of OASI varied between countries from 4.1% to 15.5% across the study period. In Canada and Norway, the rate of OASI after a forceps delivery was similar in 2004 at ~20% and with differing trajectories to 24.3% (ß 0.49) and 6.2% (ß -1.15) (trend, all p < 0.001) in 2016. CONCLUSIONS: This comparative register study suggests that there may be considerable potential for lowering the incidence of OASI. The perineal protection program implemented by Norway has been successful. Each country should critically, without prejudice, analyze their current clinical practices and rate of OASI and consider the best preventive strategy.

LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.

Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.

Surgical Assessment of Tissue Quality during Pelvic Organ Prolapse Repair in Postmenopausal Women Pre-Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial.

The aim of this prospective randomized, double-masked, placebo-controlled, multicenter study was to analyze the surgeon's individual assessment of tissue quality during pelvic floor surgery in postmenopausal women pre-treated with local estrogen therapy (LET) or placebo cream. Secondary outcomes included intraoperative and early postoperative course of the two study groups. Surgeons, blinded to patient's preoperative treatment, completed an 8-item questionnaire after each prolapse surgery to assess tissue quality as well as surgical conditions. Our hypothesis was that there is no significant difference in individual surgical assessment of tissue quality between local estrogen or placebo pre-treatment. Multivariate logistic regression analysis was performed to identify independent risk factors for intra- or early postoperative complications. Out of 120 randomized women, 103 (86%) remained for final analysis. Surgeons assessed the tissue quality similarity in cases with or without LET, representing no statistically significant differences concerning tissue perfusion, tissue atrophy, tissue consistency, difficulty of dissection and regular pelvic anatomy. Regarding pre-treatment, the rating of the surgeon correlated significantly with LET (r = 0.043), meaning a correct assumption of the surgeon. Operative time, intraoperative blood loss, occurrence of intraoperative complications, total length of stay, frequent use of analgesics and rate of readmission did not significantly differ between LET and placebo pre-treatment. The rate of defined postoperative complications and use of antibiotics was significantly more frequent in patients without LET (p = 0.045 and p = 0.003). Tissue quality was similarly assessed in cases with or without local estrogen pre-treatment, but it seems that LET prior to prolapse surgery may improve vaginal health as well as tissue-healing processes, protecting these patients from early postoperative complications.

Wide Variation in Post-Void Residual Management after Urogynecologic Surgery: A Survey of Urogynecologists' Practices.

To date there is no standardized regimen or evidence-based practical guideline concerning post-void residual (PVR) measurement after urogynecologic surgeries. This survey aimed to evaluate current practice patterns and the approach taken among urogynecologists surrounding PVR measurement. An online survey was sent to members of several urogynecologic societies assessing pre- and postoperative management of patients undergoing urogynecologic surgery. A total of 204 urogynecologists from 21 countries participated in the survey. The vast majority of urogynecologists perform some kind of voiding trial to assess voiding function postoperatively. The cut-off values to perform catheterization, the methods of measurement, and the number of successfully passed voiding showed strong differences. Only 34.4% of the respondents consider routine PVR measurement after urogynecologic surgery to be evidence-based. PVR measurement after urogynecologic surgeries is widely performed and if pathological, it almost always provokes invasive treatment. However, there is a wide variation of implemented strategies, methods, and cut-off values. Scientific societies are challenged to devise a standardized regimen based on evidence for the management of urinary retention after urogynecologic surgery.

Predictors of Persistent Postsurgical Pain After Hysterectomy-A Prospective Cohort Study.

STUDY OBJECTIVE: To determine sociodemographic, surgical, and psychologic risk factors, including pain sensitivity, for persistent postsurgical pain (PPSP) after hysterectomy. DESIGN: A prospective cohort study. SETTING: Canadian academic medical center. PATIENTS: Patients (N = 200) who underwent hysterectomy (vaginal, laparoscopic, robotic, or open) between 2013 and 2014. INTERVENTIONS: Participants completed preoperative questionnaires assessing baseline pain scores and psychologic factors, including the Pain Sensitivity Questionnaire, Brief Pain Inventory Interference Items, the Beck Depression Inventory, the Numeric Rating Scale (NRS), and the Pain Catastrophizing Scale. Pain was recorded 1 and 24 hours postoperatively using the NRS. Patients were reassessed at 6 weeks postoperatively and completed the Brief Pain Inventory Interference Items, Patient Global Impression of Change, and the NRS. Patients who reported pain at 6 weeks were reassessed at 12 weeks using the above-mentioned questionnaires. MEASUREMENTS AND MAIN RESULTS: Of 200 study participants, 58 (32%) met the definition for PPSP (NRS ≥ 1 at 12 weeks), and 11 (6.1%) met the definition for moderate to severe postsurgical pain (NRS ≥ 4 at 12 weeks). Risk factors for PPSP included baseline pain scores, depression, pain catastrophizing, uterine mass, open surgical approach, acute postoperative pain, history of chronic pain, and having a hysterectomy due to pain. Multivariate regression analysis revealed that depression, pain catastrophizing, open surgical approach, and acute postoperative pain at 1 hour represent independent predictors of PPSP. Pain sensitivity was not associated with PPSP but was associated with acute and severe acute (NRS≥4) pain at 24 hours. CONCLUSION: Patients at risk for PPSP after hysterectomy can be identified preoperatively using validated questionnaires. This information can be used to guide targeted perioperative interventions to mitigate their risk.

The effectiveness of surgical procedures to prevent post-hysterectomy pelvic organ prolapse: a systematic review of the literature.

INTRODUCTION AND HYPOTHESIS: Hysterectomy is one of the most commonly performed gynecological surgical procedures. One of the long-term risks associated with hysterectomy is the occurrence of pelvic organ prolapse (POP). To prevent post-hysterectomy POP, several suspension procedures are routinely performed at the time of hysterectomy. We performed a systematic review of published data in order to define the most effective surgical procedures for the prevention of post-hysterectomy POP. METHODS: We performed a systematic review of the literature by searching PubMed, the Cochrane Library, EMBASE, Ovid MEDLINE, and clinicaltrials.gov up to 24 May 2020. The search strategy included the keywords hysterectomy, post-hysterectomy, prolapse, colposuspension, culdoplasty, McCall, and combinations thereof. The inclusion criterion was a surgical procedure at the time of hysterectomy to prevent de novo POP. The outcome was incidence of post-hysterectomy POP. RESULTS: Six out of 553 retrieved studies met the methodological criteria for complete analysis. In this review, 719 women aged over 18 years were included. Only 2 studies were designed as prospective trials; however, only 1 compared women undergoing a procedure at the time of hysterectomy with controls. The prevalence of post-hysterectomy prolapse varied from 0% to 39%. CONCLUSION: A systematic review of published literature suggests that performing variations of McCall culdoplasty at the time of hysterectomy might be the most effective prophylactic surgical procedure for preventing post-hysterectomy pelvic organ prolapse.