Safety and Efficacy Report for the Use of Poly-4-Hydroxybutyrate as a Retropubic Mid-Urethral Sling (MUS) for Stress Urinary Incontinence: A Prospective 24 Months Follow-Up of New Poly-4-Hydroxybutyrate TephaFlex SUI Bioresorbable MUS.

STUDY OBJECTIVE: To investigate the feasibility and safety of the retropubic mid-urethral sling (MUS) procedure with a resorbable mesh implant made of poly-4-hydroxybutyrate (P4HB). DESIGN: A prospective clinical cohort study with 24 months follow-up. SETTING: A tertiary academic hospital. PATIENTS: Seventeen women with moderate to severe stress urinary incontinence (SUI). INTERVENTIONS: A retropubic MUS procedure with P4HB sling. MEASUREMENTS AND MAIN RESULTS: Seventeen women underwent an uncomplicated MUS procedure with a new sling made of resorbable P4HB. Following safety criteria, there has been no need to stop the study before 24 months' end point. Three serious adverse events were reported during follow-up: (1) inability to void urine after 1 week postsurgery, (2) a hysterectomy and bilateral oophorectomy performed due to a precancerous endometrial lesion at 16 months after initial MUS procedure and (3) exposed mesh with a part of device sheath left behind. These participants underwent an uncomplicated reintervention with no additional and/or permanent harm. Reinterventions because of failure of cure contained 3 second MUS procedures and one admission of urethral bulking agent. Seventy-six percent and 47 percent of patients were objectively cured of SUI at 12 and 24 months, respectively. CONCLUSIONS: Preliminary evidence suggests that a sling made of P4HB can be safely used for MUS procedures and could be an alternative for permanent polypropylene slings in patients that prefer the use of nonpermanent material.

Cost-effectiveness of urethral bulking polydimethylsiloxane-Urolastic® compared with mid-urethral sling surgery for stress urinary incontinence: A two-arm cohort study.

OBJECTIVE: To investigate the cost-effectiveness of urethral bulking polydimethylsiloxane-Urolastic® (PDMS-U) compared with mid-urethral sling (MUS) surgery for stress urinary incontinence (SUI) at 1-year follow-up. DESIGN: Prospective, two-arm cohort study with 2-year follow-up. SETTING: International multicentre. POPULATION: Women with moderate to severe SUI. MAIN OUTCOME MEASURES: Primary outcome was subjective cure (Patient Global Impression of Improvement). SECONDARY OUTCOMES: objective cure (negative cough stress test), Urogenital Distress Inventory (UDI-6), complications and re-interventions. Cost-effectiveness outcomes: total costs, quality-adjusted life year (QALY) using IIQ7-scores (Incontinence Impact Questionnaire) and EQ-5D-5L, incremental cost-effectiveness ratio (ICER) and monetary benefit (adjusted for baseline confounders). RESULTS: In all, 131 PDMS-U and 153 MUS surgery patients were treated. Subjective cure rates for MUS surgery and PDMS-U were, respectively: 101/112 (90%) versus 40/87 (46%), adjusted odds ratio (aOR; for age, body mass index [BMI], severity, type of urinary incontinence and previous SUI procedure) was 4.9. Objective cure rates for MUS surgery and PDMS-U were respectively: 98/109 (90%) versus 58/92 (63%), aOR 5.4. Average total costs for PDMS-U and MUS surgery were €3567 and €6688. ICER for MUS surgery cost €15 598 per IIQ QALY and €37 408 per EQ-5D-5L QALY. With a willingness to pay (WTP) of €25 000, MUS has a 84% chance of being cost-effective using IIQ, whereas PDMS-U has a 99% chance of being cost-effective using EQ-5D-5L. CONCLUSION: MUS surgery is more cost-effective in realising improved disease-specific quality of life (QoL), while PDMS-U is more cost-effective in realising improved generic QoL.

The effect of CO2 laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause.

BACKGROUND: Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. OBJECTIVE: To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. DESIGN, SETTING, AND PARTICIPANTS: An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. INTERVENTIONS: Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. RESULTS AND LIMITATIONS: Compared to OVX-only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p < 0.01), and higher focal depth (60 (IQR 60-80) vs. 80 (IQR 80-80) p < 0.05). CO2 laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. CONCLUSIONS: In a large animal model for GSM, CO2 laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO2 laser therapy should not be adopted into widespread practice for treating GSM.

Predictors of outcomes in patients with repeat surgery for obstetric fistula: a retrospective review.

INTRODUCTION AND HYPOTHESIS: Predictors of surgical outcomes in patients with an obstetric fistula who have been operated before should be identified in order to guide surgical strategy and optimize counseling of the patient. METHODS: This retrospective study is aimed at identifying predictors of outcomes for repeat surgery in 346 patients who had been operated on before for an obstetrics fistula at the Fistula Care Center (FCC) in Lilongwe, Malawi. Repeat cases were only undertaken by advanced and expert surgeons. The primary outcome was successful anatomical closure, based on a negative postoperative dye test. The secondary outcomes involved urinary continence, based on a patient-reported questionnaire and an objective 1-h pad weight test. Logistic regression models were used to test the predictors for statistical significance. RESULTS: Successful fistula closure was achieved in 288 (83%) patients and continence was achieved in 185 (64%) patients after the first repeat attempt at the FCC. Lack of urethral involvement (Goh classification: proximity to the urethra) was shown to be a good predictor of the outcomes: fistula closure and subjective and objective continence. CONCLUSIONS: Absence of urethral involvement is an independent predictor for successful outcomes in repeat surgery for obstetric fistulas. Even in the hands of an expert surgeon, the risk of another failure in achieving anatomical closure or subjective or objective continence is between 4 and 5 times higher than when the urethra is not involved.

Transvaginal Mesh-related Complications and the Potential Role of Bacterial Colonization: An Exploratory Observational Study.

STUDY OBJECTIVE: This study aimed to investigate the potential role of transvaginal mesh bacterial colonization in the development of mesh-related complications (MRCs). DESIGN: An observational and exploratory study. SETTING: Tertiary referral center (Amsterdam UMC, location AMC, Amsterdam, The Netherlands). PATIëNTS: 49 patients indicated for mesh removal and 20 women of whom vaginal tissue was retrieved during prolapse surgery as a reference cohort. INTERVENTIONS: collection of mesh-tissue complex (patient cohort) or vaginal tissue (reference cohort) MEASUREMENTS AND MAIN RESULTS: Homogenized samples were used for quantitative microbiological culture. Inflammation and fibrosis were semiquantitatively histologically scored; Gram staining and fluorescence in situ hybridization were used to detect bacteria and bacterial biofilms. Of the 49 patients, 44 samples (90%) were culture positive, with a higher diversity of species and more Gram-negative bacteria and polymicrobial cultures in the MRC cohort than the reference cohort, with mostly staphylococci, streptococci, Actinomyces spp., Cutibacterium acnes, and Escherichia coli. Patients with clinical signs of infection or exposure had the highest bacterial counts. Histology demonstrated moderate to severe inflammation in most samples. Gram staining showed bacteria in 57% of culture-positive samples, and in selected samples, fluorescence in situ hybridization illustrated a polymicrobial biofilm. CONCLUSION: In this study, we observed distinct differences in bacterial numbers and species between patients with MRCs and a reference cohort. Bacteria were observed at the mesh-tissue interface in a biofilm. These results strongly support the potential role of bacterial mesh colonization in the development of MRCs.

The Microcirculation of Vaginal Tissue in Women with Obstetric Vesicovaginal Fistula and Short-Term Effects of Surgical Repair on Microvascular Parameters.

OBJECTIVES: The objective of the study was to better understand the extent of the ischemic trauma and the effects of surgical repair on the vaginal microcirculation in patients with obstetric vesicovaginal fistula (VVF). DESIGN: In this observational study, we evaluated the vaginal microvasculature surrounding VVF using handheld vital microscopy (HVM) before, during, and 2 weeks after surgical VVF repair. PARTICIPANTS: Seventeen women undergoing VVF repair were included in this study. SETTING: The study was conducted in the Fistula Care Centre in Lilongwe, Malawi. METHODS: We used HVM with incident dark-field imaging to non-invasively visualize the microvasculature of the vaginal tissue surrounding fistulas. The primary outcome was the presence of microvascular flow. Secondary outcomes included angioarchitecture, fistula closure (postoperative dye test), and urinary continence (pad weight test). RESULTS: Microvascular flow was present before, during, and after surgical repair in, respectively, 83.8%, 83.9%, and 93.4% of obtained image sequences. The angioarchitecture was normal in 75.8% of the image sequences before surgery, 69.4% at fistula closure, and 89.1% two weeks after VVF repair. Fourteen (82.4%) patients had a closed fistula after surgical repair. LIMITATIONS: The study was limited by the lack of a control group and the relatively small sample size. CONCLUSION: Although the vaginal microcirculation in women with VVF is compromised, extensive ischemic damage is not observed in the tissue surrounding fistulas. This suggests significant regenerative capacity of the vaginal vasculature in young women, or less extensive ischemic damage than presumed. Following surgical repair, we observed improvement of microcirculatory flow and angioarchitecture, suggesting that surgery is a good option for patients with obstetric VVF.

Sexual Function Following Treatment for Stress Urinary Incontinence With Bulk Injection Therapy and Mid-Urethral Sling Surgery.

BACKGROUND: Peri-urethral bulking injections (PBI) gain popularity for the treatment of stress urinary incontinence (SUI), but - in contrast to mid-urethral sling (MUS) surgery - little is known about its impact on sexual function. METHODS: This was a secondary analysis of a prospective cohort study that included patients with moderate to severe SUI undergoing either MUS surgery or PBI with polydimethylsiloxane Urolastic (PDMS-U). The validated Dutch and English version of the 'Pelvic Organ Prolapse and/or Urinary Incontinence Sexual Function Questionnaire - IUGA Revised' (PISQ-IR) was used to assess sexual function at baseline, at 6 and 12 months of follow-up. For between-group analysis, differences in baseline characteristics were corrected using multivariate analysis of covariance. OUTCOMES: The primary outcome was the PISQ-IR single summary score of sexually active (SA) women following both procedures, calculated by mean calculation. Secondary outcomes were the PISQ-IR subscale scores of SA and non-sexually active (NSA) women, the proportions of sexual activity and subjective improvement ('Patient Global Impression of Improvement' (PGI-I)). RESULTS: A total of 259 women (MUS: n = 146, PBI: n = 113) were included in this study. The PISQ-IR single summary score of SA women improved following both interventions (in the MUS group from 3.2 to 3.4 and in the PBI group from 3.0 to 3.3 after 12 months). After correcting for differences in baseline characteristics, the PISQ-IR summary score at 6 and 12 months was similar for both treatment groups. For SA women, condition-specific and condition-impact subscale scores significantly improved following both procedures. CLINICAL IMPLICATIONS: In treating SUI, PBI is inferior to MUS surgery. However, there is a need for less invasive strategies, especially for women who are unfit for surgery or have contraindications. Sexual function improves after PBI using PDMS-U, which is relevant for the counselling of women with SUI about available treatment options. STRENGTHS & LIMITATIONS: Strength: until this study, there was a lack of knowledge about the effects of PBI on sexual function. LIMITATION: there may be indication bias as we did not perform a randomized controlled trial. CONCLUSION: PBI using PMDS-U and MUS surgery for the treatment of SUI improve sexual function equally in SA women, mainly by decreasing the condition's impact on sexual activity and quality. Latul YP, Casteleijn FM, Zwolsman SE, et al. Sexual Function Following Treatment for Stress Urinary Incontinence With Bulk Injection Therapy and Mid-Urethral Sling Surgery. J Sex Med 2022;19:1116-1123.

Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery.

BACKGROUND: Female pelvic organ prolapse (POP) has a negative effect on female sexual functioning and with an increasing life expectancy female sexual dysfunction caused by POP will be an arising global issue. AIM: Improvement in female sexual functioning, measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA-Revised (PISQ-IR), 24-months after pessary or surgery, for both sexually active (SA) and sexually inactive women (NSA) presenting with POP. METHODS: A multicenter prospective comparative cohort study was conducted in 22 Dutch hospitals. Women referred with moderate to severe POP symptoms and POP stage ≥ 2 were included and chose either pessary therapy or surgical intervention. The PISQ-IR was filled in at baseline and 24-months, the delta of change was calculated and compared between both groups. Multivariate linear regression was performed to adjust for potential confounding factors in the association between the summary score of the PISQ-IR and therapy. OUTCOMES: Change in PISQ-IR between pessary and surgical intervention. RESULTS: The delta of change at 24-months was calculated for 198 women in the pessary group and 129 women in the surgery group. SA women in the surgery group reported statistically significant more improvement on the condition-specific (-0.19 95%CI -0.35; -0.03, P = .02), and condition-impact (-0.48 95%CI -0.69; -0.28, P < .001) domains as well as on the summary score (-0.15 95%CI -0.23; -0.08, P < .001) as compared to the pessary group. No significant differences between pessary and surgery were found on the domains for NSA women. After controlling for potential baseline confounders, surgery still had a statistically significant effect on the summary score (B = 0.08; 95%CI interval 0.007-0.15, P = .03). Women having surgery had 2.62 times higher odds of changing from NSA to SA than pessary therapy. CLINICAL IMPLICATIONS: SA women who clearly express that POP-related symptoms limit their sexual functioning should be counseled that surgery results in a more remarkable improvement. STRENGTHS & LIMITATIONS: Our strengths include the large sample size, long-term follow-up, the use of the PISQ-IR as a validated outcome tool evaluating both SA and NSA women, and this study reflects real-life clinical practice that enhances the external validity of the findings. A limitation of our study is the considerable proportion of non-responders at 24-months follow-up. CONCLUSION: Sexual function in SA women with POP is superior in case surgery is performed as compared to pessary therapy. van der Vaart LR, Vollebregt A, Pruijssers B, et al. Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery. J Sex Med 2022;19:270-279.

Surgical management of pudendal nerve entrapment after sacrospinous ligament fixation.

OBJECTIVE: To analyse the efficacy of sacrospinous ligament (SSL) suture removal on the reduction of pain symptoms in the case of suspected pudendal nerve entrapment after sacrospinous ligament fixation (SSLF). DESIGN: Retrospective cohort study. SETTING: Tertiary referral centre, the Netherlands. POPULATION: A cohort of 21 women having their SSLF sutures removed because of SSLF-related pain symptoms. METHODS: Clinical record review. MAIN OUTCOME MEASURES: The primary outcome was reduction of pain after SSL suture removal. Secondary outcome measures were time interval between suture placement and suture removal, complete suture removal, adverse events and recurrence of pelvic organ prolapse (POP). RESULTS: A total of 21 women underwent SSL suture removal for severe and/or persistent pain, which was confirmed on clinical examination: 95% of the women (20/21) reported pain reduction after suture removal, and 57% reported complete pain relief. The time interval between suture placement and suture removal was at a median of 414 days (range 8-1855 days). Sutures could be completely removed in 86% of cases (18/21). One woman had excessive blood loss (520 ml) without blood transfusion. At 6-8 weeks after surgery, 10% of the women (2/21) had renewed symptomatic POP, stage ≥ 2, for which additional POP surgery was indicated. CONCLUSIONS: When performed by an experienced clinician, SSL suture removal is feasible and efficacious, with low morbidity. In addition, the risk of recurrent POP in the short term appeared to be low. TWEETABLE ABSTRACT: The surgical removal of sacrospinous ligament sutures is safe and efficacious for pain relief, even remote from initial placement.

Follow-up of obstetric fistula repair using Singapore fasciocutaneous flap and/or gracilis muscle flap.

AIMS: To report on the follow-up of obstetric fistula repair using vascularized surgical flaps, namely the Singapore fasciocutaneous flap, the gracilis muscle flap, or a combination of both. METHODS: This cross-sectional study reports on the follow-up of 60 patients after fistula repair with a vascularized surgical flap at the Fistula Care Center in Lilongwe, Malawi. The primary outcome was fistula closure based on patients' self-reported continence grade. Secondary outcomes were urinary incontinence based on a 1-h pad-weight test, quality of life based on the Incontinence Quality of Life (I-QOL) questionnaire, surgical complications, and the indication for additional surgery after repair. RESULTS: Successful closure was achieved in 62% of cases and full continence was achieved in 12% of cases. Incontinence based on a 1-h pad weight test improved between surgery and follow-up. QOL scores based on the I-QOL were low but patients indicated moderate to great improvement in quality of life. Twenty-two (37%) patients experienced surgical complication, mostly minor wound breakdowns. No major complications were reported. Six (10%) patients were indicated for additional surgery during follow-up. CONCLUSION: The relative safety of the surgical procedures is shown in the findings of this study, including no reports on major complications during follow-up. Vascularized flaps should be considered in complex fistula cases, especially in repeat cases and before considering urinary diversion as a last resort.

The effects of oestrogen on vaginal wound healing: A systematic review and meta-analysis.

AIMS: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes. METHODS: A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated. RESULTS: Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-ß1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant. CONCLUSIONS: Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.

Validation of an ovine vesicovaginal fistula model.

INTRODUCTION AND HYPOTHESIS: A representative, large animal model of vesicovaginal fistulas is needed for the training of surgeons and for the development of new surgical techniques and materials for obstetric fistula repair. METHODS: The safety, feasibility, and reproducibility of vesicovaginal fistula creation were studied in 4 adult female sheep. A 1-cm fistula was created between the vagina and the bladder through a transvaginal approach. The defect was allowed to heal for 8 weeks and the animals were then euthanized. The primary outcome was the fistula patency. Secondary outcomes were fistula size, urogenital dimensions, urodynamic evaluation, histology (inflammation, vascularization, collagen deposition) and biomechanical characteristics of the fistula edge (stress at break, maximum elongation, and stiffness). RESULTS: The transvaginal creation of a vesicovaginal fistula was safe. All animals survived the surgical procedure and follow-up period, without complications. Three of the four animals demonstrated a patent vesicovaginal fistula after 8 weeks. Baseline data are provided of the urogenital dimensions and the urodynamic, histological, and biomechanical characteristics of the model. CONCLUSIONS: The ewe is a safe, feasible, and reproducible model for vesicovaginal fistulas. The model can help to study new techniques and materials to boost surgical innovation for vesicovaginal fistula repair.

Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse: A Randomized Clinical Trial.

Importance: Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase. Objective: To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse. Design, Setting, and Participants: The PEOPLE project was a noninferiority randomized clinical trial conducted in 21 participating hospitals in the Netherlands. A total of 1605 women with symptomatic stage 2 or greater pelvic organ prolapse were requested to participate between March 2015 through November 2019; 440 gave informed consent. Final 24-month follow-up ended at June 30, 2022. Interventions: Two hundred eighteen participants were randomized to receive pessary treatment and 222 to surgery. Main Outcomes and Measures: The primary outcome was subjective patient-reported improvement at 24 months, measured with the Patient Global Impression of Improvement scale, a 7-point Likert scale ranging from very much better to very much worse. This scale was dichotomized as successful, defined as much better or very much better, vs nonsuccessful treatment. The noninferiority margin was set at 10 percentage points risk difference. Data of crossover between therapies and adverse events were captured. Results: Among 440 patients who were randomized (mean [SD] age, 64.7 [9.29] years), 173 (79.3%) in the pessary group and 162 (73.3%) in the surgery group completed the trial at 24 months. In the population, analyzed as randomized, subjective improvement was reported by 132 of 173 (76.3%) in the pessary group vs 132 of 162 (81.5%) in the surgery group (risk difference, -6.1% [1-sided 95% CI, -12.7 to ∞]; P value for noninferiority, .16). The per-protocol analysis showed a similar result for subjective improvement with 52 of 74 (70.3%) in the pessary group vs 125 of 150 (83.3%) in the surgery group (risk difference, -13.1% [1-sided 95% CI, -23.0 to ∞]; P value for noninferiority, .69). Crossover from pessary to surgery occurred among 118 of 218 (54.1%) participants. The most common adverse event among pessary users was discomfort (42.7%) vs urinary tract infection (9%) following surgery. Conclusions and Relevance: Among patients with symptomatic pelvic organ prolapse, an initial strategy of pessary therapy, compared with surgery, did not meet criteria for noninferiority with regard to patient-reported improvement at 24 months. Interpretation is limited by loss to follow-up and the large amount of participant crossover from pessary therapy to surgery. Trial Registration: Netherlands Trial Register Identifier: NTR4883.

Embryology, anatomy, physiology and pathophysiology of the peritoneum and the peritoneal vasculature.

The peritoneum is a large serous membrane with both epithelial and mesenchymal features, and is essential for maintaining an intra-abdominal homeostatic equilibrium. The peritoneum plays a central role in the pathogenesis of a number of disorders. Pathological processes affecting the peritoneum such as inflammation and carcinomatosis can have serious clinical consequences, but the pathophysiology of these conditions is poorly understood. Understanding peritoneal embryology, anatomy and physiology is crucial to comprehend pathophysiological mechanisms and to devise a new focus for research. The vascular response to pathological processes appears to be of considerable importance, since the peritoneal vasculature plays a pivotal role in most associated diseases. Therefore, this review summarizes currently available literature with special emphasis on the development, anatomy and function of the peritoneal vasculature. Pathological processes are described to illustrate physiological and pathophysiological characteristics of the peritoneum.

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging.

AIM: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. METHODS: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). RESULTS: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2-38.2 cpll/mm2). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm2 (95% CI 11.2-13.77 mm/mm2), mean PVD was 12.2 (95% CI 11.0-13.5 mm/mm2), MFI was 3 and PPV was 100%. CONCLUSIONS: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer.

Animal experimental research assessing urogynecologic surgical mesh implants: Outcome measures describing the host response, a systematic review and meta-analysis.

AIM: Before the introduction of new biomaterials for prolapse surgery, animal studies on the host response are required. Unfortunately, large variation in study design hampers obtaining an overview of the safety and efficacy, and translation to clinical practice. Our aim is to systematically review the literature on all outcome measures describing the host response in animal studies assessing the biocompatibility of urogynecologic surgical mesh implants for prolapse surgery. Furthermore, by meta-analysis, we aim to assess the effect of implantation and compare this to control animals receiving sham surgery or native tissue repair. METHODS: We performed a systematic search from inception to August 2020. Since this is an explorative study we included original, controlled, and noncontrolled animal studies describing any host response to the implant. Quantitative outcome measures reported ≥10 times in ≥2 articles were eligible for meta-analysis. RESULTS: Fifty articles were included in the qualitative synthesis and 36 articles were eligible for meta-analysis. In total, 154 outcome measures were defined and classified into (1) histomorphology, (2) biomechanics and, (3) macroscopic morphology. Animals with vaginal implants demonstrated significantly increased M1 and M2 macrophages, MMP-2, neovascularization, TNF-α, and stiffness, and lower vaginal contractility compared to control animals. CONCLUSION: The host response significantly differs in animals after vaginal mesh implantation compared to control animals, both pro- and anti-inflammatory. However, we observed a paucity in the uniformity of reported outcomes. For future animal studies, we propose the development of a core outcome set, which ideally predicts the host response in women.

Efficacy of surgical revision of mesh complications in prolapse and urinary incontinence surgery.

INTRODUCTION AND HYPOTHESIS: Women with mesh-related complications in prolapse (POP) and stress-urinary incontinence (SUI) surgery may benefit from operative mesh resection to alleviate symptoms. We hypothesized that mesh resection would alleviate symptoms and aimed to evaluate risks and benefits in these women. METHODS: We carried out a cross-sectional study. Primary outcome was improvement specified as better, unchanged or worsened symptoms after mesh revision surgery. Secondary outcomes were health-related quality of life (HrQol) scores of validated questionnaires, surgical characteristics and physical findings at follow-up visits. Descriptive data were reported with mean and medians. Associations were calculated with Spearman correlation coefficient and chi-square test to determine statistical differences between groups. RESULTS: Fifty-nine women who underwent mesh revision surgery between 2009 and 2016 were included. After a median follow-up of 1.7 (IQR: 1.1-2.4) years, 44 women (75%) reported improvement of symptoms. No significant surgical or patient characteristics were identified that could differentiate which patients did or did not experience cure or complications.A trend was observed to better HrQol scores in women who reported overall improvement after mesh revision surgery. Seventeen (29%) women needed a subsequent operation after mesh removal. CONCLUSIONS: This cross-sectional study shows that mesh revision surgery alleviates symptoms in 75% of women with mesh-related complications. Type of revision surgery and individual characteristics did not seem to matter to the individual chance of cure or complications. These data can facilitate the counseling of women considering mesh revision surgery.

Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial.

BACKGROUND: Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. METHODS: The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. DISCUSSION: This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853 . EudraCT: 2017-003144-21; registered: 24-07-2017.

The vaginal microcirculation after prolapse surgery.

AIMS: Oxygen plays a crucial role in wound healing after prolapse surgery. Trauma to the vaginal vasculature might limit the delivery of oxygen to the surgical wound, which may negatively affect wound healing and regeneration of connective tissue. This possibly increases the future risk of recurrence. We aimed to determine the effects of vaginal prolapse surgery on the microcirculation of the vaginal wall. METHODS: We evaluated the vaginal microcirculation in healthy participants without known vascular disease undergoing anterior and/or posterior colporrhaphy. We used incident dark-field imaging for in vivo assessment before and after (1 day, 2 weeks, and 6 weeks) surgery. We studied perfusion (microvascular flow index [MFI]), angioarchitecture (morphology/layout of microvessels) and capillary density. RESULTS: Ten women were included. Interindividual differences were observed 1 day postoperatively with regard to perfusion and angioarchitecture. Microvascular flow at the surgical site was absent or significantly reduced in some participants, whereas normal microvascular flow was observed in others (MFI range 0-3). Perfusion and angioarchitecture had been restored in all participants after 6 weeks (MFI range 2-3), regardless of the extent of vascular trauma 1 day postoperatively. CONCLUSIONS: The difference in the extent of vascular trauma between women undergoing seemingly identical surgical procedures suggests that some individuals are more susceptible to vascular trauma than others. Delivery of oxygen to the wound and subsequent wound healing may be compromised in these cases, which could be related to the development of anatomical recurrence. Future studies should investigate whether there is a relationship between the vaginal microvasculature and the recurrence of prolapse.

Patients' satisfaction and safety of bulk injection therapy Urolastic for treatment of stress urinary incontinence: A cross-sectional study.

AIMS: Primary outcome was to evaluate patients' satisfaction after being treated with bulk injection therapy polydimethylsiloxane Urolastic (PDMS-U) for stress urinary incontinence (SUI). Secondary outcomes were: subjective cure, objective cure, severity of SUI symptoms, complications, reintervention rate, and disease-specific quality of life. Furthermore, to determine if outcomes worsened during time-after-treatment (time-frames: 0-12, 13-24, and ≥25 months). METHODS: In a cross-sectional design, patients treated with PDMS-U were recruited for hospital revisit. The primary outcome, patients' satisfaction, was assessed by the surgical satisfaction questionnaire. Subjective cure, objective cure, and severity of symptoms were assessed by the patients global impression of improvement, standardized cough stress test, and Sandvik severity scale, respectively. Medical charts and face-to-face interviews were used to determine complications and reinterventions. RESULTS: About 110 patients participated, 87 revisited the hospital. Median follow-up was 25 months (interquartile range: 14;35 months). Patients' satisfaction rate was 51%. Subjective and objective cure were respectively 46% and 47%. Most prevalent complications were: urinary retention (22%), pain (15%), and dyspareunia (15%). Exposure and erosion occurred in 7% and 5%, respectively. Reintervention rate of reinjection and excision of bulk material was 6% and 18.0%, respectively. Objective cure significantly worsened during time-after-treatment (P = < .05). CONCLUSIONS: About half of the patients being treated with PDMS-U were satisfied and subjectively cured 2 years after treatment, although the majority still experienced symptoms of SUI. Most complications were mild and transient, however, in 18% excision of bulk material was indicated for severe or persistent complications such as pain, exposure, or erosion.