The transvaginal mesh class action: a tertiary teaching hospital experience of all mid-urethral sling procedures performed between 1999 and 2017.

INTRODUCTION AND HYPOTHESIS: Class action against Ethicon (J&J), manufacturer of transvaginal mesh devices, including mid-urethral slings (MUS), was brought to the Federal Court of Australia in 2016 by Shine Lawyers. As a result, subpoenas to all hospitals and networks were received, which overrode patient privacy concerns. This medical record search allowed a complete audit and communication with patients to offer clinical review. This enabled a review of complications, readmission and re-operation for women who underwent a MUS for stress urinary incontinence. METHODS: A cohort study of women who underwent MUS treatment for stress urinary incontinence (SUI) at a single tertiary teaching hospital between 1999 and 2017 was carried out. The main outcome measures were the rate of readmission and re-operation following MUS procedures. These include voiding dysfunction managed by sling loosening or sling division, mesh pain or exposure managed by mesh removal and reoperation for recurrent stress urinary incontinence. RESULTS: Between 1999 and 2017, a total of 1,462 women were identified as having a MUS; of these, 1,195 (81.7%) had full patient records available. Voiding dysfunction requiring surgical intervention with sling loosening or division was 3%, excision for mesh exposure was 2%, and partial or complete excision for pain was 1% at a median of 10 years from index surgery. The reoperation rate for recurrent stress urinary incontinence was 3%. CONCLUSION(S): This audit of all MUS procedures performed at a tertiary centre confirms an overall low rate of readmission for complications and recurrent SUI surgery; this justifies its continued availability with appropriate informed consent.

Three-year patient-reported outcomes of single-incision versus transobturator slings for female stress urinary incontinence are equivalent.

INTRODUCTION AND HYPOTHESIS: Patient-reported outcome measures (PROMs) are important for understanding the success of surgery for stress urinary incontinence, as patient perception of success does not always correlate with physician perception of success. We report PROMS after single-incision slings (SIS) and transobturator mid-urethral slings (TMUS). METHODS: This was a planned outcome analysis of secondary endpoints in a study in which the primary aim was to compare efficiency and safety using a non-inferiority design (results reported previously). In this analysis of quality of life (QOL), validated PROMs were collected at baseline, 6, 12, 18, 24, and 36 months to quantify incontinence severity (Incontinence Severity Index), symptom bother (Urogenital Distress Inventory), disease-specific QOL impact (Urinary Impact Questionnaire), and generic QOL impact (PGI-I; not applicable at baseline). PROMs were analyzed within treatment groups as well as between groups. Propensity score methods were used to adjust for baseline differences between groups. RESULTS: A total of 281 subjects underwent the study procedure (141 SIS, 140 TMUS). Baseline characteristics were balanced after propensity score stratification. Participants had significant improvement in incontinence severity, disease-specific symptom bother, and QOL impact. Improvements persisted through the study and PROMs were similar between treatment groups in all assessment at 36 months CONCLUSIONS: Following SIS and TMUS, patients with stress urinary incontinence had significant improvement in PROMs including Urogenital Distress Inventory, Incontinence Severity Index, and Urinary Impact Questionnaire at 36 months, indicating disease-specific QOL improvement. Patients have a more positive impression of change in stress urinary incontinence symptoms at each follow-up visit, indicating generic QOL improvement.

International Urogynecology consultation chapter 2 committee 3: the clinical evaluation of pelvic organ prolapse including investigations into associated morbidity/pelvic floor dysfunction.

INTRODUCTION AND HYPOTHESIS: This manuscript from Chapter 2 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) reviews the literature involving the clinical evaluation of a patient with POP and associated bladder and bowel dysfunction. METHODS: An international group of 11 clinicians performed a search of the literature using pre-specified search MESH terms in PubMed and Embase databases (January 2000 to August 2020). Publications were eliminated if not relevant to the clinical evaluation of patients or did not include clear definitions of POP. The titles and abstracts were reviewed using the Covidence database to determine whether they met the inclusion criteria. The manuscripts were reviewed for suitability using the Specialist Unit for Review Evidence checklists. The data from full-text manuscripts were extracted and then reviewed. RESULTS: The search strategy found 11,242 abstracts, of which 220 articles were used to inform this narrative review. The main themes of this manuscript were the clinical examination, and the evaluation of comorbid conditions including the urinary tract (LUTS), gastrointestinal tract (GIT), pain, and sexual function. The physical examination of patients with pelvic organ prolapse (POP) should include a reproducible method of describing and quantifying the degree of POP and only the Pelvic Organ Quantification (POP-Q) system or the Simplified Pelvic Organ Prolapse Quantification (S-POP) system have enough reproducibility to be recommended. POP examination should be done with an empty bladder and patients can be supine but should be upright if the prolapse cannot be reproduced. No other parameters of the examination aid in describing and quantifying POP. Post-void residual urine volume >100 ml is commonly used to assess for voiding difficulty. Prolapse reduction can be used to predict the possibility of postoperative persistence of voiding difficulty. There is no benefit of urodynamic testing for assessment of detrusor overactivity as it does not change the management. In women with POP and stress urinary incontinence (SUI), the cough stress test should be performed with a bladder volume of at least 200 ml and with the prolapse reduced either with a speculum or by a pessary. The urodynamic assessment only changes management when SUI and voiding dysfunction co-exist. Demonstration of preoperative occult SUI has a positive predictive value for de novo SUI of 40% but most useful is its absence, which has a negative predictive value of 91%. The routine addition of radiographic or physiological testing of the GIT currently has no additional value for a physical examination. In subjects with GIT symptoms further radiological but not physiological testing appears to aid in diagnosing enteroceles, sigmoidoceles, and intussusception, but there are no data on how this affects outcomes. There were no articles in the search on the evaluation of the co-morbid conditions of pain or sexual dysfunction in women with POP. CONCLUSIONS: The clinical pelvic examination remains the central tool for evaluation of POP and a system such as the POP-Q or S-POP should be used to describe and quantify. The value of investigation for urinary tract dysfunction was discussed and findings presented. The routine addition of GI radiographic or physiological testing is currently not recommended. There are no data on the role of the routine assessment of pain or sexual function, and this area needs more study. Imaging studies alone cannot replace clinical examination for the assessment of POP.

CO2 surgical laser for treatment of stress urinary incontinence in women: a randomized controlled trial.

BACKGROUND: Stress urinary incontinence is a common condition that can be treated conservatively and/or surgically. Given the risks of surgery, developing effective nonsurgical treatment options would be beneficial. Some studies have suggested that laser therapy may improve or cure stress urinary incontinence. However, there is a lack of sham-controlled randomized controlled trials to judge treatment efficacy. OBJECTIVE: This study aimed to compare the effects of CO2 vaginal laser vs sham therapy for treating stress urinary incontinence. STUDY DESIGN: This was a multicenter, participant-blinded, sham-controlled, parallel group (1:1) superiority randomized controlled trial performed in outpatient clinics in 2 hospitals. We included women aged 18 to 80 years with objective and subjective stress urinary incontinence. Participants had undertaken or declined supervised pelvic floor muscle training. Intervention was performed using a CO2 fractionated vaginal laser. Participants underwent 3 treatments, 4 weeks apart, with increasing energy and density settings. Sham treatment was performed using an identical technique with a deactivated pedal. The primary outcome was the subjective stress urinary incontinence rate (proportion with leak with cough, sneeze, or laughter) at 3 months after completion of treatment. Secondary outcomes included objective stress urinary incontinence, change in the disease-specific patient-reported outcomes, health-related quality of life, and adverse effects. Categorical outcomes were compared using the chi square test and continuous outcomes using analysis of covariance, adjusting for the baseline score. RESULTS: There were 52 participants who received laser and 49 who received sham treatment. One participant in each group withdrew from the study before the endpoint, and 2 participants in the laser group did not participate in the follow-up visits. Participant mean age was 53 (34-79) years. Mean body mass index was 26.1 (18.1-49.6); 90% were vaginally parous. At 3 months, there was no difference between the sham and active treatment arm in subjective stress urinary incontinence (46 [96%] vs 48 [98%]; relative risk, 0.98 [95% confidence interval, 0.91-1.05]; P=.55) or in objective stress urinary incontinence (37 [80%] vs 33 [80%]; relative risk, 0.99 [95% confidence interval, 0.81-1.23]; P=.995). Patient-reported outcomes and health-related quality of life were also comparable between the groups. Vaginal bleeding occurred in 3 participants after laser and 1 participant after sham treatment. Pain during treatment did not differ between laser and sham treatment. CONCLUSION: We were unable to show an improvement in stress urinary incontinence after CO2 vaginal laser therapy compared with sham treatment.

Vaginal pressure sensor measurement during maximal voluntary pelvic floor contraction correlates with vaginal birth and pelvic organ prolapse-A pilot study.

AIMS: To measure the force applied along the anterior and posterior vaginal walls in a cohort of 46 patients measured by a fiber-optic pressure sensor and determine if this correlates with vaginal parity and pelvic organ prolapse (POP). METHODS: An intravaginal fiber-optic sensor measured pressure at nine locations along the anterior and posterior vaginal walls during a maximal voluntary pelvic floor muscle contraction (MVC). An automated probe dilation cycle measured the tissue resistance incorporating the vagina and surrounding anatomy. MVC and resting tissue resistance (RTR) were assessed between subjects grouped by the number of vaginal births and prolapse stage. RESULTS: A previous vaginal birth was associated with a significant threefold decrease in the overall anterior pressure measurement during MVC. Decreased anterior pressure measurements were observed at Sensors 1 and 3 (distal vagina) and, posteriorly at Sensors 4-6 (midvagina). Women with Stage 2 posterior prolapse exhibited a decreased MVC pressure in the midvagina than those with Stage 0/1. In this pilot study, there was no difference in the vaginal wall RTR according to previous vaginal birth or stage of prolapse. CONCLUSION: This pilot study found that a decrease in vaginal pressure measured during MVC is associated with vaginal birth and with posterior POP. Greater sample size is required to assess the role of resting tissue pressure measurement.

Outcomes following sacrocolpopexy using ultralight and lightweight mesh.

INTRODUCTION AND HYPOTHESIS: This study reports the long-term anatomic and subjective outcomes following sacrocolpopexy based on mesh weight and provides device-specific data. METHODS: This cohort study compared ultra-lightweight (≤ 20 g/m2) with lightweight mesh (≥ 25 g/m2). The primary outcome was composite failure defined as at least one of ≥ stage 2 apical prolapse, anterior or posterior vaginal wall beyond hymen, complaint of bulge or retreatment. Effect measure estimates were calculated as the incidence rate ratio of composite failure comparing the use of ultra-light with lightweight mesh. Crude and adjusted incidence rate ratios (IRRs) were obtained using uni- and multivariable Poisson regression models. RESULTS: Of 358 women who met inclusion criteria, 220 (61%) agreed to attend for review; 95 (43%) had ultra-lightweight mesh and 125 (57%) had lightweight mesh including UpsylonTM. Median follow-up for ultra-light and lightweight mesh was 36 (IQR 22-42) and 63 (IQR 48-87) months, respectively (p < 0.001). Accounting for differences in follow-up time, there was no significant difference in composite failure between ultra-light and lightweight mesh groups (IRR 1.47, 95% CI 0.83-2.52, p = 0.15). This persisted after adjustment for age, body mass index, parity, smoking and presence of advanced prolapse prior to surgery (IRR 1.52, 95% CI 0.94-2.47, p = 0.087). Mesh exposure for both groups was mostly asymptomatic, and the rate was 7% for the ultra-light group and 8% in the lightweight group. Overall, repeat surgery for recurrent apical prolapse and mesh exposure occurred in 4% and 2%, respectively. CONCLUSIONS: Ultra-lightweight mesh appears to have similar incidence rate of failure compared to lightweight mesh. UpsylonTM mesh has a similar low rate of recurrent apical prolapse and mesh exposure.

Female Sexual Function following Sling Surgery: A Prospective Parallel Cohort, Multi-Center Study of the Solyx™ Single Incision Sling System versus the Obtryx™ II Sling System.

PURPOSE: Limited data exist regarding sexual function after single incision sling (SIS) surgery. We compared sexual function 36 months postoperatively between patients undergoing SIS and transobturator sling (TMUS) for treatment of stress urinary incontinence. MATERIALS AND METHODS: Assessment of sexual function was a planned secondary objective of this prospective, multi-center study that enrolled women to Solyx SIS or Obtryx II TMUS. The primary study aim was to compare efficacy and safety using non-inferiority design at 36 months. Patient-reported outcomes of sexual function were assessed at baseline and 6, 12, 18, 24 and 36 months using Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Changes in sexual function were analyzed within and between groups. Outcomes for patients requiring surgical retreatment were determined. RESULTS: Baseline characteristics were balanced using propensity score stratification (N=141 SIS, N=140 TMUS). Groups were similar in age, body mass index and concomitant surgery performed. Average length of followup was 30 months. Baseline sexual activity was similar (123/141 SIS, 114/140 TMUS, p=0.18). Severity of urinary incontinence did not correlate with baseline sexual activity. Mean PISQ-12 scores increased significantly from baseline to 36 months for both groups, indicating better sexual function at each visit. There were no significant differences in PISQ-12 scores between groups except at 36 months, where the difference was small (-2.5, 95% CI [-4.7, 0.2]). Among patients undergoing surgical retreatment (9/281, 3%), improvement in sexual function was maintained. De novo dyspareunia was rare following both treatments (SIS 1/141, TMUS 0/140, p=1.00). CONCLUSIONS: Patients have significant improvement in sexual function after SIS and TMUS. De novo sexual pain is low after sling surgery.

Efficacy of Clorpactin in refractory bladder pain syndrome/interstitial cystitis: a randomized controlled trial.

INTRODUCTION: Clorpactin is an antibacterial agent with limited evidence for its use as instillation therapy in patients with bladder pain syndrome/interstitial cystitis (BPS/IC). This was a multi-centre, single-blinded randomized controlled trial to investigate whether Clorpactin instillation results in symptom improvement in patients with refractory BPS/IC. METHODS: Fifty women with refractory BPS/IC were randomized to undergo cystoscopy/hydrodistension (25) or instillation of Clorpactin 0.4% solution (25) under general anaesthesia. Primary outcome was based on Global Response Assessment (GRA) at 3 months; secondary outcomes were based on O'Leary Sant Symptom (OLSI) and Problem (OLPI) questionnaire scores, visual analogue scale (VAS) score for pain and bladder diary parameters. RESULTS: Complete follow-up data were available on 22 in the hydrodistension group and 16 in the Clorpactin group. GRA improvement was 4.5% for hydrodistension and 56% for Clorpactin (p = 0.001) at 3 months. Reduction in mean total scores for OLSI (14.1 to 9.1; p = 0.004) and OLPI (12.6 to 7.4; p = 0.001) was seen in the Clorpactin group only. VAS pain scores were reduced in the Clorpactin group only (7.4 to 3.3; p < 0.001). Post-treatment VAS pain scores did not differ between groups although 6/25 (24%) women in the Clorpactin group required admission for pain compared to 1/25 (4%) in the hydrodistension group. CONCLUSIONS: Clorpactin treatment results in significant improvement in BPS/IC symptoms, bother and pain based on the GRA, OLSI/OLPI and VAS pain scores at 3 months post-treatment compared to cystoscopy/hydrodistension. These conclusions are limited by the high loss to follow-up in both groups.

Prospective study of a single-incision sling versus a transobturator sling in women with stress urinary incontinence: 3-year results.

BACKGROUND: Long-term safety and efficacy data on use of single-incision slings in stress urinary incontinence are limited. OBJECTIVE: To determine whether the single-incision sling Solyx (Boston Scientific, Marlborough, MA) is noninferior to the transobturator sling Obtryx II (Boston Scientific) in efficacy and safety for treatment of stress urinary incontinence. This 522 post-market surveillance study has been designed in response to a Food and Drug Administration request to evaluate improvement in stress urinary incontinence at 36 months following single-incision sling compared with baseline, as well as provide an assessment of mesh-related complications and subject-reported outcomes, relative to the transobturator sling control. STUDY DESIGN: This prospective, nonrandomized, parallel cohort, multicenter postapproval study enrolled subjects to receive single-incision sling or transobturator sling. Study sites were assigned to a cohort group based on documented competency with the cohort device. Patient follow-up was 36 months to compare efficacy and adverse events for noninferiority. Inclusion criteria included stress predominant urinary incontinence, a positive cough stress test, and post-void residual ≤150 cc. Participants were ineligible if they had undergone previous stress urinary incontinence surgery or had a previous mesh complication. Primary endpoint was treatment success defined by composite negative cough stress test and subjective improvement in stress urinary incontinence using Patient Global Impression of Improvement at 36 months. Secondary endpoints included adverse events and indications for retreatment. Noninferiority margins of 15% and 10% were prespecified for the primary efficacy and safety endpoints. Data analysis was performed using intent-to-treat and per-protocol methods. Due to the observational nature of the study, a propensity score methodology was applied to account for differences in patient and surgeon characteristics between treatment groups. The study design and variables to be included in the propensity score model were reviewed and approved by Food and Drug Administration reviewers before outcome analyses were performed. RESULTS: No evidence of imbalance in baseline characteristics was observed between groups after propensity score stratification in the 281 subjects. EBL (72.3±92 vs 73.1±63.9 mL, P=.786), time to spontaneous void (1.1±2 vs 0.8±2.8 days, P=.998), and time to discharge (0.7±0.7 vs 0.6±0.6 days, P=.524) were similar between groups. At 36 months, treatment success was 90.4% in the single-incision sling group and 88.9% in the transobturator sling group (P=.93). At 36 months, mesh-related complications were similar between groups (mesh exposure: 2.8% vs 5.0%, P=.38). Serious adverse events including pain during intercourse (0.7% vs 0%, P=1.00), pelvic pain (0.7% vs 0%, P=1.00), and urinary retention (2.8% vs 4.3%, P=.54) were similar between groups. CONCLUSION: Single-incision sling was not inferior to transobturator sling for long-term treatment success of stress urinary incontinence. The rates of serious adverse events were acceptably low and similar between groups.

Effect of investigative laparoscopy on bladder pain syndrome: a prospective cohort trial.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain is a debilitating condition, and establishing both an etiology and a successful management plan is challenging. Bladder pain syndrome (BPS) is one such etiology, with some studies reporting a prevalence of up to 50% in women with chronic pelvic pain (Van De Merwe et al. Eur Urol 53: 60-67, 2008; Cervigni and Natale Int J Urol 21: 85-88, 2014). This study aimed to assess the impact that investigative laparoscopy with treatment of endometriosis has on bladder pain syndrome in women with and without endometriosis. METHODS: A prospective cohort study was conducted with participants recruited from a tertiary gynecology unit and the private rooms of participating gynecologists. Women included were those scheduled for laparoscopy for investigation of pelvic pain of > 6 months, aged 18-40 years. Each patient completed a preoperative questionnaire, and a standardized study operative report was used to collect laparoscopy findings. Any endometriosis found was treated with excisional surgery. Patients were then reviewed with the same questionnaire at 3, 6 and 12 months post-surgery. RESULTS: A total of 150 patients were included in the trial. Seventy-five percent of patients (n = 112/150) were diagnosed with endometriosis. Of them, 43% (n = 48/112) also had BPS. The overall BPS rate was 43% (n = 64/150). At 12 months, there was a significant reduction in overall pain and pelvic pain in all groups. Of the women with BPS, there was no difference in symptom score reduction between those with endometriosis treated and those without endometriosis. BPS resolved in 42% of women 12 months post-laparoscopy, regardless of whether endometriosis was diagnosed and treated or not. Of the women without BPS preoperatively, 14% developed de novo BPS at 12 months, regardless of whether endometriosis was diagnosed and treated or not. CONCLUSION: Our findings show that BPS improves in the 12 months after investigative laparoscopy and treatment of endometriosis for chronic pelvic pain, regardless of presence or absence of endometriosis.

Hysterectomy with uterosacral suspension or Uphold™ hysteropexy in women with apical prolapse: a parallel cohort study.

INTRODUCTION AND HYPOTHESIS: The aim was to compare objective and subjective cure rates between Uphold™ hysteropexy (HP) and vaginal hysterectomy (VH) with uterosacral suspension. METHODS: A sample size of 49 in each arm would be required to detect a clinical difference of 20% between the groups. Owing to delayed recruitment, this originally planned randomised controlled trial was changed to a patient preference study after randomising initial 6 participants. Women with symptomatic stage ≥2 uterine descent wishing a surgical solution were included. Routine follow-up was scheduled at 6 weeks, 6 months, 12 months, and annually thereafter. Primary outcome was absence of stage ≥2 apical prolapse. Secondary outcomes included a composite cure of no leading edge beyond the hymen, absence of bulge symptoms and no retreatment; patient-reported outcomes were based on quality-of-life questionnaires (PFDI-20, PFIQ-7, PISQ-12, PGI-I, EQ5D and a health score). RESULTS: We recruited 50 patients undergoing VH between 2011 and 2013 and 51 patients undergoing HP between 2011 and 2016. Participants were followed up for a median of 25 months (23-96). Five women from the VH (10%) and 7 from the HP (14%) group were lost to follow-up. Combined anatomical and symptomatic outcomes were available for 41 (82%) VH and 39 (76%) in the HP group. There was no difference in objective apical outcomes; the incidence of stage 2 prolapse was 0% in the VH group and 2% in HP group (p = 0.50). We found no difference in the composite cure rate (78% VH vs 85% HP, 0.45) between the groups. There was no significant difference in surgical complications (p = 0.33), assessed using Clavien-Dindo classification. There was a 2% surgery rate for mesh exposure in the HP group. CONCLUSIONS: Uphold™ uterine suspension and VH appear to have similar objective and subjective cure at 25 months, with no significant difference in surgical complications.

Blended Nanostructured Degradable Mesh with Endometrial Mesenchymal Stem Cells Promotes Tissue Integration and Anti-Inflammatory Response in Vivo for Pelvic Floor Application.

The current urogynecological clinical meshes trigger unfavorable foreign body response which leads to graft failure in the long term. To overcome the present challenge, we applied a tissue engineering strategy using endometrial SUSD2+ mesenchymal stem cells (eMSCs) with high regenerative properties. This study delves deeper into foreign body response to SUSD2+ eMSC based degradable PLACL/gelatin nanofiber meshes using a mouse model targeted at understanding immunomodulation and mesh integration in the long term. Delivery of cells with nanofiber mesh provides a unique topography that enables entrapment of therapeutic cells for up to 6 weeks that promotes substantial cellular infiltration of host anti-inflammatory macrophages. As a result, degradation rate and tissue integration are highly impacted by eMSCs, revealing an unexpected level of implant integration over 6 weeks in vivo. From a clinical perspective, such immunomodulation may aid in overcoming the current challenges and provide an alternative to an unmet women's urogynecological health need.

The impact of pelvic organ prolapse and/or continence surgery on pelvic floor muscle function in women: A systematic review.

AIMS: To systematically review the evidence for the effect of pelvic organ prolapse (POP) and/or continence surgery on pelvic floor muscle (PFM) morphometry and function in women, and to investigate whether a relationship exists between PFM measures and clinician-reported objective pelvic floor outcomes postoperatively. METHODS: Six electronic databases were searched until March 2018. Studies were included if they examined the effect of POP and/or continence surgery on the PFM in women, and reported pre- and postoperative data. Methodological quality was assessed using a modified Downs and Black checklist. Three meta-analyses were planned based on postoperative follow-up time. RESULTS: Twenty-one studies met the inclusion criteria. Varied surgical interventions and 33 different PFM measures were represented. The methodological quality of included studies varied considerably. The 0 to 6 weeks postoperative meta-analysis showed no statistically significant change in PFM function (SMD = 0.04; 95% confidence interval [CI] = -0.26 to 0.33). This was consistent at 3 and 6 or more months (SMD = 1.13; 0.35 95% CI = -0.34 to 2.60, - 0.42 to 1.12 respectively). None of the included studies investigated the relationship between PFM measures and clinician-reported objective outcomes postoperatively. CONCLUSIONS: This review did not show a clear effect of POP and/or continence surgery on PFM morphometry or function in women and was unable to show a relationship with outcomes such as objective prolapse score and urodynamic findings. This could be because surgery does not measurably impact on the PFM or due to the poor quality and heterogeneity of studies. Future well-designed research is needed to specifically investigate change in the PFM following surgery.

A fiber-optic sensor-based device for the measurement of vaginal integrity in women.

AIMS: Pelvic floor disorders (PFDs) in women are a major public health concern. Current clinical methods for assessing PFDs are either subjective or confounded by interference from intra-abdominal pressure (IAP). This study introduces an intravaginal probe that can determine distributed vaginal pressure during voluntary exercises and measures the degree of vaginal tissue support independent of IAP fluctuations. METHODS: An intravaginal probe was fabricated with 18 independent fiber-optic pressure transducers positioned along its upper and lower blades. Continuous pressure measurement along the anterior and posterior vaginal walls during the automated expansion of the probe enabled the resistance of the tissue to be evaluated as a function of displacement, in a manner reflecting the elastic modulus of the tissue. After validation in a simulated vaginal phantom, in vivo measurements were conducted in the relaxed state and during a series of voluntary exercises to gauge the utility of the device in women. RESULTS: The probe reliably detected variations in the composition of sub-surface material in the vaginal phantom. During in-vivo measurements the probe detected distributed tissue elasticity in the absence of IAP change. In addition, the distribution of pressure along both anterior and posterior vaginal walls during cough, Valsalva and pelvic floor contraction was clearly resolved with a large variation observed between subjects. CONCLUSIONS: Our data highlight the potential for the probe to assess the integrity of the vagina wall and support structures as an integrated functional unit. Further in vivo trials are needed to correlate data with clinical findings to assist in the assessment of PFDs.

Development, implementation and evaluation of an advanced practice in continence and women's health physiotherapy model of care.

BACKGROUND: With public health facing workforce shortages, increasing costs and increasing demands, innovative patient pathways are vital to meet patient needs. Advanced practice physiotherapy roles are well established in emergency departments and musculoskeletal/orthopaedic services and have begun to emerge in other clinical areas. AIMS: In 2014, the Royal Women's Hospital, Monash Health and Barwon Health received a Victorian Department of Health and Human Services (DHHS) Workforce Innovation grant to develop and implement an advanced practice in continence and women's health physiotherapy assessment model of care. MATERIAL AND METHODS: A new model of care was developed with an advanced practice physiotherapy-led assessment clinic integrated into the triage and assessment process of gynaecology, urogynaecology and urology clinics in major public health centres. A clinical competency and credentialing pathway and toolkit were developed to support training and development of advanced practice skills for senior physiotherapists in this clinical area. The initial assessment of the new model of care was undertaken by DHHS and Price-Waterhouse Coopers, including access to care, cost of assessment and safety. RESULTS: An advanced practice continence and women's health physiotherapy assessment clinic was implemented safely and contributed to improved access to care as assessed by reduced waiting lists and waiting times for assessment, with high levels of patient satisfaction and no adverse events. CONCLUSION: Advanced practice continence and women's health physiotherapy clinics can contribute to streamlined, cost-efficient triage and assessment processes for patients with urological or gynaecological issues attending tertiary medical clinics.

Video of the laparoscopic repair of a vesico-uterine fistula.

AIM: Vesico-uterine fistulas (VUFs) are rare in modern gynecological practice. We aim to demonstrate with a video the surgical techniques involved in laparoscopic repair of a vesico-uterine fistula (Youssef's syndrome). METHODS: A 37-year-old woman, para 2 and otherwise healthy, was referred to the Urogynaecology Unit 4 months following a vaginal birth after a previous cesarean, with ongoing pink-colored vaginal watery discharge. Cystoscopy and hysteroscopy confirmed the findings of a well-granulated fistulous tract connecting the base of the bladder and anterior uterine wall just above the level of the internal os. She underwent an uncomplicated laparoscopic repair of VUF. RESULTS: She has remained asymptomatic with resumption of normal menses and no clinical evidence of fistula recurrence at 6-week and 6-month post-operative reviews. CONCLUSION: This video demonstrates the surgical techniques involved in the laparoscopic repair of a VUF, a rare case in modern gynecological practice where there are few surgical videos demonstrating techniques.

RCT of vaginal extraperitoneal uterosacral ligament suspension (VEULS) with anterior mesh versus sacrocolpopexy: 4-year outcome.

INTRODUCTION AND HYPOTHESIS: This study assessed the safety and efficacy of vaginal extraperitoneal uterosacral ligament suspension (VEULS) with anterior overlay mesh versus sacrocolpopexy (SCP) for posthysterectomy vault prolapse. METHODS: This was a multicenter randomized trial of women with posthysterectomy vault prolapse stage >2 according to the Pelvic Organ Prolapse Quantification (POP-Q) system. Primary outcome was a composite of no vaginal bulge symptoms, no anatomical recurrence in the anterior or apical compartment at or beyond the hymenal ring, and no surgical retreatment for prolapse 12 months postsurgery. Secondary outcomes were peri- and postoperative complications, changes in prolapse, and urogenital and sexual symptoms at 12, 24, and 48 months based on the Pelvic Floor Distress Inventory (PFDI)-20. RESULTS: Between 2006 and 2011, 82 eligible women were randomized: 39 received VEULS and 43 received SCP. Primary composite outcome at 12 months for success was 41% for VEULS and 65% for SCP [odds ratio (OR 2.68, p = 0.03)]. Perioperative complications were more common in the SCP group. C-point was higher for SCP (-6.0 VEULS vs -8.0 SCP, p = 0.005) and total vaginal length (TVL) was longer for SCP (8.0 VEULS vs 9.0 SCP, p = 0.05). Cumulative mesh exposure rate at 4 years was similar between the uterosacral [4/39 (10.3%)] and sacrocolpopexy [4/43 (9.3%)] groups, bearing in mind that not all patients were examined at 4 years. Subjective outcomes derived from three domains of the PFDI-20 were similar at 12, 24, 48 months. Postoperative Pelvic Organ Prolapse Distress Inventory (POPDI) score improved similarly for both groups at all timepoints, with the minimally important difference of at least 21 reached for both groups. CONCLUSIONS: Composite outcome of success was better for SCP at 12 months, but subjective outcomes for prolapse at all timepoints over 4 years for VEULS and SCP were not significantly different.

N-cadherin identifies human endometrial epithelial progenitor cells by in vitro stem cell assays.

STUDY QUESTION: Is there a specific surface marker that identifies human endometrial epithelial progenitor cells with adult stem cell activity using in vitro assays? SUMMARY ANSWER: N-cadherin isolates clonogenic, self-renewing human endometrial epithelial progenitor cells with high proliferative potential that differentiate into cytokeratin+ gland-like structures in vitro and identifies their location in some cells of gland profiles predominantly in basalis endometrium adjacent to the myometrium. WHAT IS KNOWN ALREADY: Human endometrium contains a small population of clonogenic, self-renewing epithelial cells with high proliferative potential that differentiate into large gland-like structures, but their identity and location is unknown. Stage-specific embryonic antigen-1 (SSEA-1) distinguishes the epithelium of basalis from functionalis and is a marker of human post-menopausal (Post-M) endometrial epithelium. STUDY DESIGN, SIZE, DURATION: Prospective observational study of endometrial epithelial cells obtained from hysterectomy samples taken from 50 pre-menopausal (Pre-M) and 24 Post-M women, of which 4 were from women who had taken daily estradiol valerate 2 mg/day for 8 weeks prior. PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene profiling was used to identify differentially expressed surface markers between fresh EpCAM (Epithelial Cell Adhesion Molecule)-magnetic bead-selected basalis-like epithelial cells from Post-M endometrium compared with predominantly functionalis epithelial cells from Pre-M endometrium and validated by qRT-PCR. In vitro clonogenicity and self-renewal assays were used to assess the stem/progenitor cell properties of magnetic bead-sorted N-cadherin+ and N-cadherin- epithelial cells. The cellular identity, location and phenotype of N-cadherin+ cells was assessed by dual colour immunofluorescence and confocal microscopy for cytokeratin, proliferative status (Ki-67), ERα, SSEA-1, SOX9 and epithelial mesenchymal transition (EMT) markers on full thickness human endometrium. MAIN RESULTS AND THE ROLE OF CHANCE: CDH2 (N-cadherin gene) was one of 11 surface molecules highly expressed in Post-M compared to Pre-M endometrial epithelial cells. N-cadherin+ cells comprise a median 16.7% (n = 8) and 20.2% (n = 5) of Pre-M endometrial epithelial cells by flow cytometry and magnetic bead sorting, respectively. N-cadherin+ epithelial cells from Pre-M endometrium were more clonogenic than N-cadherin- cells (n = 12, P = 0.003), underwent more population doublings (n = 7), showed greater capacity for serial cloning (n = 7) and differentiated into cytokeratin+ gland-like organoids. N-cadherin immunolocalised to the lateral and apical membrane of epithelial cells in the bases of glands in the basalis of Pre-M endometrium and Post-M gland profiles, co-expressing cytokeratin, ERα but not SSEA-1 or SOX9, which localized on gland profiles proximal to N-cadherin+ cells. N-cadherin+ cells were quiescent (Ki-67-) in the basalis and in Post-M endometrial glands and co-localized with EMT markers vimentin and E-cadherin. LARGE SCALE DATA: The raw and processed data files from the gene microarray have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus data set with accession number GSE35221. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study in human endometrium only using in vitro stem cell assays. The differential ability of N-cadherin+ and N-cadherin-cells to generate endometrial glands in vivo was not determined. A small number of uterine tissues analysed contained adenomyosis for which N-cadherin has been implicated in epithelial-EMT. WIDER IMPLICATIONS OF THE FINDINGS: A new marker enriching for human endometrial epithelial progenitor cells identifies a different and potentially more primitive cell population than SSEA-1, suggesting a potential hierarchy of epithelial differentiation in the basalis. Using N-cadherin as a marker, the molecular and cellular characteristics of epithelial progenitor cells and their role in endometrial proliferative disorders including endometriosis, adenomyosis and thin dysfunctional endometrium can be investigated. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Cancer Council Victoria grant 491079 (C.E.G.) and Australian National Health and Medical Research Council grants 1021127 (C.E.G.), 1085435 (C.E.G., J.A.D.), 145780 and 288713 (C.N.S.), RD Wright Career Development Award 465121 (C.E.G.), Senior Research Fellowship 1042298 (C.E.G.), the Victorian Government's Operational Infrastructure Support and an Australian Postgraduate Award (HPTN), and China Council Scholarship (L.X.). The authors have nothing to declare.

Long-term outcomes of intravesical dimethyl sulfoxide/heparin/hydrocortisone therapy for interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: For decades, intravesical dimethyl sulfoxide (DMSO) cocktail therapy has been used for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), but little is known about its long-term efficacy. We aimed to assess the long-term efficacy of intravesical DMSO/heparin/hydrocortisone/bupivacaine therapy in patients with IC/BPS. METHODS: Patients with IC/BPS from our institutions who underwent this therapy with >2 years follow-up were surveyed with O'Leary-Sant interstitial cystitis symptom and problem index questionnaires before and after therapy. Chart reviews and telephone surveys were then conducted to determine their posttherapy course. RESULTS: Of 68 eligible women, 55 (80.0%) with a median follow-up of 60 months (range 24-142) were surveyed. Their mean age at therapy onset was 44.8 years and their mean body mass index was 26.2 kg/m2. There were statistically significant improvements in O'Leary-Sant and pain scores of 23-47% at both 6 weeks and the end of the follow-up period. At the end of the follow-up period, 19 of the 55 women (34.5%) were cured (requiring no further treatment) and 12 (21.8%) were significantly improved (requiring only ongoing oral medication). Univariate and multivariate analyses showed that DMSO treatment failure was more likely in patients with pretreatment day-time urinary frequency more than 15 episodes per day (OR 1.41), nocturia more than two episodes per night (OR 2.47), maximum bladder diary voided volume <200 ml (OR 1.39) and bladder capacity under anaesthesia <500 ml (OR 1.6). CONCLUSIONS: At a median follow-up of 60 months, intravesical DMSO cocktail therapy appeared moderately effective for the treatment of IC/BPS. Treatment failure was more frequent in patients with pretreatment symptoms of reduced bladder capacity.

Vaginal wall weakness in parous ewes: a potential preclinical model of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Ewes develop pelvic organ prolapse (POP) and may be a suitable model for preclinical studies evaluating cell-based therapies for POP. The aim of this study was to establish a clinical score of vaginal weakness and to compare POP Quantification System (POP-Q) values in conscious nulliparous and parous ewes and determine whether ewes are a suitable POP model. METHODS: Ewes (n = 114) were examined while conscious, without sedation, and standing in a V conveyer by adapting the human POP-Q measurement. Ovine POP was defined as descent to the introitus from POP-Q points Aa 3 cm above the introitus on the anterior wall, Ap 3 cm above the introitus on the posterior wall, or increased Ba anterior wall descent above the urethra (≥0). A test-retest showed good inter- and intrarater reliability. RESULTS: There was no evidence of tissue mobility at Aa, Ap, Ba (all -3 cm) in nulliparous ewes (n = 14). In contrast, multiparous ewes had a median of -1 and interquartile range (IQR) (-2 to 0) for Aa, [0 (-1 to 0)] for Ap and [0 (-2.75 to 0)] for Ba (n = 33; P < 0.0001 in comparison with nulliparous) ewes. Ovine vaginal displacement was seen in 50.9 % of parous ewes and was strongly associated with parity (P = 0.003). CONCLUSIONS: A modified POP-Q in conscious ewes was established showing that the vaginal wall of parous animals has similar regions of weakness as do women and may be similarly related to parity. Ewes appear to be a representative preclinical model of human vaginal prolapse.