Current position of neuromodulation for bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Despite established effectiveness in overactive bladder and nonobstructive retention, neuromodulation's application in interstitial cystitis/bladder pain syndrome (IC/BPS) remains a topic of ongoing research. The purpose of this article is to review recent developments in neuromodulation as treatment of IC/BPS offering guidance for healthcare practitioners dealing with IC/BPS cases. RECENT FINDINGS: Recent research underlines the promising role of sacral, tibial and pudendal neuromodulation in management of IC/BPS symptoms. Studies reveal encouraging outcomes, particularly in alleviating urgency and frequency symptoms. However, while urgency and frequency symptoms tend to improve, comprehensive pain relief remains a challenge. Percutaneous tibial nerve stimulation (PTNS) and transcutaneous tibial nerve stimulation (TTNS) stand out due to their minimal invasive nature. Existing literature points to the need for larger prospective studies with extended follow-up periods to validate the efficacy and sustainability of neuromodulation. SUMMARY: Neuromodulation is a promising treatment modality for refractory IC/BPS. Due to the minimal invasive nature, they should be tried before rigorous surgery. However, the limited quantity of available data and the variability in pain relief outcomes necessitate cautious interpretation. The review emphasizes the need for further research.

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 functioning and the complication rate of extreme long existing urinary diversions.

PURPOSE OF REVIEW: This review is timely and relevant because many patients live many years with urinary diversions. Knowledge about the long term outcome with respect to function and complications are important for patient counseling and for the manner to follow-up patients. This study was performed to investigate the functioning of urinary diversions constructed > 25 years earlier. RECENT FINDINGS: Most studies have a relatively shorter follow-up, mainly focussing on short term postoperative complications. Focussing on the long term, urinary tract infections (UTI) including pyelonephritis are common. Mild kidney function deterioration is described. SUMMARY: Retrospective study (2018-2019); 43 patients with regular follow-up at the Radboud University Medical Centre Nijmegen the Netherlands. Ileal conduit (n = 19) and ureterosigmoidostomy (n = 11) are the most common diversion types for reasons such as: bladder exstrophy (n = 15), urinary incontinence (n = 9) and malignancy (n = 8). This series with a median follow-up of 40 years, shows it is possible to live and cope with a urinary diversion for a very long time. Ureterosigmoidostomies give relatively good results. Ileal conduits are functioning properly with acceptable complication rates. 95% suffers from chronic UTI's. Kidney function deterioration was mild. Diversions for benign reasons have more complex complications compared to diversion constructed for malignant reasons. VIDEO ABSTRACT: http://links.lww.com/COU/A32.

Urodynamic Effects of Prostatic Urethral Lift Procedure for Male Voiding Lower Urinary Tract Symptoms.

Aims: Primary objective is to investigate whether prostatic urethral lift (PUL) results in an improvement of urodynamic parameters that define bladder outlet obstruction (urethral resistance algorithm [urethral resistance factor (URA)], Schäfer grade, detrusor pressure at maximum flow [PdetQmax], and detrusor pressure at bladder opening [PdetOpen]). Materials and Methods: Twenty patients (main inclusion criteria: ≥50 years of age, benign prostatic obstruction (BPO), international prostate symptom score (IPSS) ≥13, prostate volume ≤60 mL, and no middle prostate lobe) were enrolled in the study and a PUL was performed. Patients underwent urodynamic investigation and filled out the IPSS and quality of life (QoL) before and after PUL. A paired t-test was used to analyze the results. Results: The mean age was 68 years (range 55-79), mean prostate volume (TRUS) was 45 mL (range 20-59), and mean prostate-specific antigen was 2.0 µg/L (0.2-4.4). IPSS of the 16 patients reduced significantly (from 22.20 to 14.47, p = 0.000). Qmax during pressure flow study improved significantly (from 4.5 to 7.2 mL/s, p = 0.001), no significant difference was found in Qmax during free uroflowmetry. There was no significant difference found in postvoiding residual. URA decreased significantly post-treatment (from 52 to 37 cmH2O, p = 0.000). The Schäfer obstruction plot decreased significantly (from 3.5 to 2.6, p = 0.022). Seven patients underwent Greenlight Laser Vaporization of the prostate after the PUL attributable to unsatisfactory results. Conclusions: PUL has desobstructive effects, but they seem clinically modest. The procedure improves urodynamic parameters as well as QoL in males with lower urinary tract symptoms based on BPO. However, the mechanism how PUL leads to a remarkable symptom relief remains unclear and cannot be explained by the desobstructive mechanisms we observed.

Patient-reported outcomes and health-related quality of life after urinary diversions.

PURPOSE OF REVIEW: To study the recent literature on health-related quality of life (HRQOL) in patients after radical cystectomy followed by urinary diversion. RECENT FINDINGS: General consensus regarding, which urinary diversion is superior in terms of HRQOL has not been reached. Although there is an increase in studies favoring the orthotopic neobladder, overall quality of these studies is poor. Other studies suggest that HRQOL outcomes in different types of urinary diversions is similar and that other factors, such as age, comorbidities and sex are more important instead. Patient choice, in consultation with the treating surgeon should be the determinant of which urinary diversion is performed. Furthermore, sexual function can play an important role in HRQOL. However, practice shows that counselling on the option of sexual-preserving techniques is still not implemented in routine clinical practice. Furthermore, studies regarding differences in HRQOL after urinary diversion between male and female individuals are lacking. SUMMARY: Thorough preoperative counselling on the different types of urinary diversion and options for sexual-preserving techniques decreases decision regret and increases HRQOL in patients after radical cystectomy.

Results of the York Mason Procedure with and without Concomitant Graciloplasty to Treat Iatrogenic Rectourethral Fistulas.

BACKGROUND: Rectourethral fistulas (RUFs) are rare but devastating complications after surgery or radiation therapy to the urethra, prostate, or rectum. RUF repair is challenging, especially in irradiated patients. OBJECTIVE: To evaluate the efficacy of the York Mason (YM) procedure with or without concomitant gracilis muscle interposition (graciloplasty) for RUF repair. DESIGN, SETTING, AND PARTICIPANTS: Records of patients with an iatrogenic RUF who underwent the YM procedure between 2008 and 2018 in two university hospitals were reviewed. Data on etiology, diagnostic and operative procedures, urinary and fecal diversion, and postoperative follow-up were collected. INTERVENTION: Twenty-eight patients underwent 33 YM procedures. Concomitant graciloplasty was performed in four (14%) primary repairs and two (7%) repairs for recurrent RUFs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was successful RUF repair, defined as absence of symptoms and no leakage on control urethrocystography. The secondary endpoint was colostomy reversal rate. RESULTS AND LIMITATIONS: Median follow-up was 24 mo. Ten patients (36%) were irradiated previously. The ultimate success rate was 75% after a maximum of three YM procedures. Success rates were 89% and 50% in patients with nonirradiated and irradiated fistulas, respectively. In irradiated patients, the success rates of the first YM procedure with and without graciloplasty were 100% and 29%, respectively. In recurrent cases, concomitant graciloplasty did not result in better outcomes. Colostomy reversal was possible in 15 patients after successful repair. In all patients, fecal continence was intact and no anal stenosis was reported. Limitations of the study include small sample size and the retrospective design. CONCLUSIONS: Combination of the YM procedure with graciloplasty resulted in higher success rates of RUF repair in patients with irradiated fistulas. Fecal continence was preserved, and colostomy reversal is feasible. PATIENT SUMMARY: We analyzed the outcomes, complications, and colostomy reversal rate of the York Mason procedure for the repair of rectourethral fistulas (RUFs). We found that concomitant graciloplasty increases success rates in case of prior radiation therapy. Colostomy reversal is feasible after RUF repair.

De-implementation of urodynamics in The Netherlands after the VALUE/VUSIS-2 results: a nationwide survey.

INTRODUCTION AND HYPOTHESIS: We aimed to estimate the level of de-implementation of preoperative routine urodynamics (UDS) before stress urinary incontinence (SUI) surgery in The Netherlands and to analyze facilitators and barriers. Routine UDS was performed by 37% of the medical specialists in 2010. We hypothesized that the recommendations from the recent Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) and Value of Urodynamic Evaluation (ValUE) studies would have been followed by a reduction of routine UDS. METHODS: A national survey was performed among all Dutch gynecologists and urologists dealing with SUI in daily practice. The questionnaire contained two parts: (1) respondents' characteristics and their actual care concerning preoperative UDS, and (2) facilitators and barriers. RESULTS: The response rate was 41% (127/308). Of the respondents, 93% (n = 118) did not perform routine UDS in the preoperative workup for women in this group. Professional characteristics associated with not following the recommendations were profession urologist, academic hospital, and a lower number of midurethral sling (MUS) placed yearly. Facilitators to follow the recommendation not to perform routine UDS were adequate design of the VUSIS-II study and outcome and recommendations from the studies. Barriers not to follow the recommendation were believe in the additional value of UDS, especially the pressure transmission ratio, and the presence of detrusor overactivity. CONCLUSION: According to respondents to this questionnaire, VUSIS-II and ValUE study results are well implemented in The Netherlands. The vast majority of respondents replied as not performing routine preoperative UDS in women with primary, uncomplicated (predominant) SUI. Therefore, there is no need for a further de-implementation strategy.

Complications of Urethral Bulking Agents for Stress Urinary Incontinence: An Extensive Review Including Case Reports.

OBJECTIVES: Stress urinary incontinence in women is a common problem that significantly impacts quality of life. Periurethral injection of urethral bulking agents (UBAs) is a simple, noninvasive, and cost-effective treatment. However, complications associated with UBA are often underappreciated. Objective of this review was to get a complete overview of all published complications of UBA. METHODS: An extensive search of the scientific literature was conducted to quantitatively summarize the complications and their treatments of 8 UBAs. A total of 117 articles (original articles and case reports) were included in the final analysis. Complication incidence, treatment incidence, and follow-up time were extracted when mentioned. Statistical analysis of complication incidence of each UBA was calculated if possible. RESULTS: A total of 2095 complications in 6462 treated patients were reported in 79 studies. Sixty-seven (3%) were considered serious implying operative correction (Clavien grade III); of these, 46 (69%) required incision and drainage, and 21 (31%) required a more invasive procedure. In 38 case reports and small case series, 49 patients were treated for 110 complications. Of these 110 complications, 41 (37%) can be classified as Clavien grade III. CONCLUSIONS: This extensive review shows that various UBAs have different complication rates, with certain UBAs being more prone to serious complications. Based on available publications, most UBAs have a good safety profile, with low complication rates. However, although the majority of UBA complications are transient and require no or noninvasive treatment, serious complications may require invasive intervention and treatment.

A New Implanted Posterior Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome: 3-Month Results of a Novel Therapy at a Single Center.

PURPOSE: This study was designed to investigate the safety and performance of a new implantable system for tibial nerve stimulation for overactive bladder symptoms. MATERIALS AND METHODS: A battery-free stimulation device for tibial nerve stimulation (BlueWind Medical, Herzliya, Israel) was implanted in 15 patients. Safety and efficacy assessments were done at 3 months after activation with a 3-day bladder diary, a 24-hour pad test and 2 quality of life questionnaires. RESULTS: Two males and 13 females were enrolled in the study. Mean age was 54 years (range 19 to 72). Five of 15 patients were previously treated with percutaneous tibial nerve stimulation and 12 experienced urgency urinary incontinence. Median operative time was 34 minutes. At 3 months of followup a significant change was seen in 24-hour frequency from a mean ± SD of 11.8 ± 3.5 to 8.1 ± 2.0 times per day (p = 0.002), the number of severe urinary urgency episodes from 6.5 ± 5.1 to 2.0 ± 2.1 times per day (p = 0.002), the number of severe incontinence episodes from 2.8 ± 5.2 to 0.3 ± 0.4 episodes per day (p = 0.017), urinary loss per day from 243 ± 388 to 39 ± 55 gm (p = 0.038) and improvement in quality of life. After implantation, 3 patients received prolonged antibiotic treatment and 3 received pain medication for 1 week. In 1 patient the device was explanted due to pain and swelling suspicious for infection, although tissue cultures did not reveal a bacterial infection. CONCLUSIONS: This novel posterior tibial nerve stimulator is safe and easy to implant with good clinical results.

TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in urinary bladder afferent neural pathways was investigated using spinal c-fos measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice underwent noxious bladder distention and treatment with either intravesical instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin (RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice underwent paraformaldehyde perfusion for rapid fixation and L6-S1 spinal cord sections were removed followed by immunohistochemical staining for c-fos. A number of c-fos expressing neurons in the dorsal horns of L6-S1 spinal cord transections were quantified. Groups were compared using univariate ANOVA. Even with the absence of bladder inflammation on H&E, the TRPV4 -/- mice still have a significant twofold higher c-fos expression (n = 39, SD 2) after noxious bladder distention compared to wild type mice (n = 20, SD 3). A twofold increase in c-fos expression was observed after LPS treatment in wild types (n = 42, SD 5), but no increase was seen in TRPV4 -/- mice (n = 42, SD 2). After desensitization of primary afferent C-nerve fibers with RTX, c-fos expression in TRPV4-/- mice decreased significantly (threefold) (n = 12, SD 4). Results imply that TRPV4 channels are important for bladder afferent signaling. TRPV4 -/- mice bladders generate more noxious sensory output, which is predominantly mediated through TRPV1 expressing high threshold nerve fibers. This study reveals TRPV1 related adaptive changes in afferent pathways of the TRPV4 -/- mouse. We propose that this effect is caused by a congenital impairment of low threshold nerves that mediate normal bladder filling sensations.

Results of primary versus recurrent surgery to treat stress urinary incontinence in women.

INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in patients who had undergone primary or recurrent (secondary) surgery for stress urinary incontinence (SUI). METHODS: A retrospective cohort study that included patients who underwent surgery to treat SUI in a tertiary referral center was carried out. All patients had, predominantly, SUI. Exclusion criteria were patients with a neurogenic bladder or a neobladder and patients without postoperative follow-up (FU). The primary objective was to assess the success rate, defined as cured SUI or improved SUI at six weeks and at the latest available moment of FU. The secondary objective was to assess complications. RESULTS: A total of 541 women with SUI underwent surgery for SUI between 2002 and 2010. After exclusion of 102 patients a total of 242 patients with primary SUI and 197 patients with recurrent SUI were identified. The success rate at first FU was 89 %. At last FU (median 205 days) the success rate was 83 % (P < 0.01). There were no significant differences in success rate between primary and recurrent surgery at first FU. The overall success rate of primary surgery was 86 %; for recurrent surgery it was 79 %. During surgery, 27 bladder injuries occurred (6.2 %), with no significant difference between the two groups. At last FU, 11 patients (2.6 %) had persistent residual volume, necessitating prolonged clean intermittent self-catheterization. CONCLUSIONS: The results of recurrent surgery to treat recurrent or persistent SUI are still good in experienced hands and do not significantly differ from results of primary surgery. The complication rates are comparable to those of primary surgery.

Detrusor overactivity does not predict bothersome storage symptoms after photoselective vaporization of the prostate with lithium triborate laser.

OBJECTIVE: To find out if detrusor overactivity (DO) is a predictor of moderate or severe storage lower urinary tract symptoms (LUTS) persisting 6 months after photoselective vaporization of the prostate (PVP). MATERIALS AND METHODS: Patients with bladder outlet obstruction proved by urodynamics who underwent PVP with the lithium triborate laser were followed for 6 months with the International Prostate Symptom Score (IPSS) questionnaire. Moderate-to-severe storage LUTS were defined as IPSS storage domain score >8 and/or a score for an IPSS question on urgency >3. Predictive values of DO, IPSS domains, urgency, prostate volume, bladder outlet obstruction grade, and energy used were tested by logistic regression analysis. RESULTS: Seventy-six men at the age of 66.4 ± 6.8 years underwent PVP, including 36 (47.4%) with DO. Incidence of moderate or severe storage LUTS was decreasing from 60.5% to 48.7% at week 6 and 11.8% at month 6 postoperatively. At a univariate analysis, urgency score and storage domain score were significantly associated with bothersome storage LUTS at month 6. Multivariate analysis confirmed predictive value of preoperative urgency having an odds ratio of 5.7 (95% confidence interval, 1.41-23.16; P = .014). DO was not associated with the defined outcome. CONCLUSION: In our group, DO was not useful in predicting persistent storage symptoms after PVP. Patients with severe preoperative urgency should be informed about a risk of such outcome.

An update of the interstitial cell compartment in the normal human bladder.

AIMS: Interstitial cells, also called myofibroblasts, most probably play a major role in the pathogenesis of the overactive bladder. However, no specific phenotypic marker has been identified. We investigated whether N-cadherin could play a role as a discriminatory marker for interstitial cells in the human bladder. METHODS: Bladder biopsies (n = 16) were collected from macroscopically nonpathological locations during cystectomy which was performed because of bladder cancer. Tissue was analyzed for expression of N-cadherin. N-cadherin+ cells were phenotyped using antibodies against PGP9.5, smoothelin, vimentin, and C-kit. Findings were related to bladder tissue histology and ultrastructure of myofibroblastic cells. RESULTS: N-cadherin+/vimentin+ cells with branched cell bodies were found in the lamina propria and detrusor layer. They were closely associated with neurons and showed no colocalization of PGP9.5 or smoothelin. A second type of N-cadherin+ cells was found at the boundary of detrusor bundles and in the lamina propria. These cells colocalization C-kit. We assumed that N-cadherin+/vimentin+ cells are similar to the ultrastructurally defined myofibroblasts. CONCLUSIONS: N-cadherin can play a role as a discriminatory marker for interstitial cells in the human bladder, as the interstitial compartment of the human bladder houses a population of cells from mesenchymal origin, immunopositive for N-cadherin, vimentin, and C-kit.

EAU policy on live surgery events.

CONTEXT: Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest. OBJECTIVE: To provide a European Association of Urology (EAU) policy on LSEs to regulate their organisation during urologic meetings. EVIDENCE ACQUISITION: The project was carried out in phases: a systematic literature review generating key questions, surveys sent to Live Surgery Panel members, and Internet- and panel-based consensus finding using the Delphi process to agree on and formulate a policy. EVIDENCE SYNTHESIS: The EAU will endorse LSEs, provided that the EAU Code of Conduct for live surgery and all organisational requirements are followed. Outcome data must be submitted to an EAU Web-based registry and complications reported using the revised Martin criteria. Regular audits will take place to evaluate compliance as well as the educational role of live surgery. CONCLUSIONS: This policy represents the consensus view of an expert panel established to advise the EAU. The EAU recognises the educational role of live surgery and endorses live case demonstration at urologic meetings that are conducted within a clearly defined regulatory framework. The overriding principle is that patient safety must take priority over all other considerations in the conduct of live surgery. PATIENT SUMMARY: Controversy exists regarding the true educational value of live surgical demonstrations on patients at surgical meetings. An EAU committee of experts developed a policy on how best to conduct live surgery at urologic meetings. The key principle is to ensure safety for every patient, including a code of conduct and checklist for live surgery, specific rules for how the surgery is organised and performed, and how each patient's results are reported to the EAU. For detailed information, please visit www.uroweb.org.

Value of urodynamics before stress urinary incontinence surgery: a randomized controlled trial.

OBJECTIVE: To estimate whether a strategy of immediate surgery was noninferior to a strategy based on discordant urodynamic findings followed by individually tailored therapy in women with stress urinary incontinence (SUI). METHODS: A multicenter diagnostic cohort study with an embedded noninferiority randomized controlled trial was conducted in six academic and 24 nonacademic Dutch hospitals. Women with predominant SUI eligible for surgical treatment based on clinical assessment were included between January 2009 and November 2010. All patients underwent urodynamics. In patients in whom urodynamics were discordant with clinical assessment, participants were randomly allocated to receive either immediate surgery or individually tailored therapy based on urodynamics. The primary outcome was clinical improvement assessed by the Urogenital Distress Inventory 12 months after baseline. Analysis was by intention to treat; a difference in mean improvement of 5 points or less was considered noninferior. RESULTS: Five hundred seventy-eight women with SUI were studied, of whom 268 (46%) had discordant findings. One hundred twenty-six patients gave informed consent for randomization and were allocated to receive immediate surgery (n=64) or individually tailored therapy (n=62). The mean improvement measured with the Urogenital Distress Inventory after 1 year was 44 points (±24) in the group receiving immediate surgery and 39 (±25) points in the group receiving individually tailored treatment. The difference in mean improvement was 5 points in favor of the group receiving immediate surgery (95% confidence interval -∞ to 5). There were no differences with respect to cure or complication rate. CONCLUSION: In women with uncomplicated SUI, an immediate midurethral sling operation is not inferior to individually tailored treatment based on urodynamic findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00814749. LEVEL OF EVIDENCE: I.

The distribution and function of chondroitin sulfate and other sulfated glycosaminoglycans in the human bladder and their contribution to the protective bladder barrier.

PURPOSE: Glycosaminoglycan replenishment therapies are commonly applied to treat bladder inflammatory conditions such as bladder pain syndrome/interstitial cystitis. Although there is evidence that these therapies are clinically effective, much is still unknown about the location and function of different types of glycosaminoglycans in the bladder. We investigated the location of sulfated glycosaminoglycans in the bladder and evaluated their contribution to the urothelial barrier. MATERIALS AND METHODS: The location of different glycosaminoglycans (heparan sulfate, chondroitin sulfate and dermatan sulfate) in human and porcine bladders was investigated with immunofluorescence staining and isolating glycosaminoglycans using selective urothelial sampling techniques. Barrier function was evaluated with transepithelial electrical resistance measurements (Ω.cm(2)) on primary porcine urothelial cell cultures. The contribution of different glycosaminoglycans to the bladder barrier was investigated with specific glycosaminoglycan digesting enzymes and protamine. RESULTS: High glycosaminoglycan concentrations are located around the urothelial basal membrane and at the urothelial luminal surface. After removing the glycosaminoglycan layer, urothelial permeability increased. Natural recovery of the glycosaminoglycan layer takes less than 24 hours. Chondroitin sulfate was the only sulfated glycosaminoglycan that was located on the urothelial luminal surface and that contributed to urothelial barrier function. CONCLUSIONS: This study reveals an important role for chondroitin sulfate in bladder barrier function. Therapies aiming at restoring the luminal glycosaminoglycan layer in pathological conditions such as bladder pain syndrome/interstitial cystitis are based on a sound principle.

The value of preoperative urodynamics according to gynecologists and urologists with special interest in stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to assess variations in practice in the use of preoperative urodynamics in women with stress urinary incontinence (SUI). METHODS: We performed an E-survey among all Dutch gynecologists and urologists who have SUI as focus in daily practice. The questions concerned the common policy and preferred policy. Descriptive statistics were used. RESULTS: Of the 260 targeted specialists, 163 (63%) responded. We found that 37% of the respondents performed standard preoperative urodynamics; in the preferred practice, this would reduce to only 18%. Eighty percent indicated they would operate a patient with a positive stress test without urodynamic SUI, whereas 21% would do this also in case the clinical stress test was negative. Only 9% of the respondents indicated they adapted the choice of the type of sling based on urethral pressure profilometry parameters. CONCLUSIONS: Urodynamics are not routinely performed, and outcomes hardly influence the choice of treatment.

The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study.

PURPOSE: TRPV4 (transient receptor potential vanilloid 4 channel) is a nonselective cation channel involved in different sensory functions that was recently implicated in bladder mechanosensation. We investigated the cellular site of TRPV4 in bladder urothelium and explored a molecular connection between TRPV4 and urothelial adherence junctions. MATERIALS AND METHODS: We obtained healthy tissues sections from cystectomy in humans due to cancer in 3 and noncancerous conditions in 2. Besides human biopsies tissues from 7 normal and 7 TRPV4-/-mice, and the urothelial cell line RT4 were also used. Experiments were done with polyclonal antibody against TRPV4 (against the N-terminus of rat TRPV4). A molecular connection between TRPV4 and different adherence junction components was investigated using immunofluorescence, Western blot and immunoprecipitation. RESULTS: Results revealed TRPV4 on urothelial cell membranes near adherence junctions. Results were comparable in the urothelial cell line, human bladders and mouse bladders. Subsequent immunoprecipitation experiments established a molecular connection of TRPV4 to α-catenin, an integral part of the adherence junction that catenates E-cadherin to the actin-microfilament network. CONCLUSIONS: Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.