Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies.

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

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.

Pain after midurethral sling; the underestimated role of mesh removal.

INTRODUCTION: The primary aim of this study was to evaluate the results of midurethral sling (MUS) removal in women who have pain as their single complication of MUS. MATERIAL AND METHODS: We performed a retrospective chart study supplemented with a cross sectional questionnaire. Women who underwent MUS removal for pain as the solitary reason for removal between 2004 and 2018 were included. Primary outcome was change in pain levels assessed by the visual analogue scale (VAS) pain score (range 0-10). Secondary outcome was the recurrence of stress urinary incontinence (SUI). RESULTS: Twenty-six of 31 patients returned the questionnaire. Median medical file follow-up was 12 months (range 2-66) and 25 months (range 5-104) regarding questionnaires. VAS pain score dropped from 7.8 (SD 1.9) at baseline to 4.5 (SD 3.2) at follow-up (p <.00). Seven (23%) patients were pain-free. Patients undergoing partial vaginal resection (n = 6) had a VAS pain score decrease of 4.7 (p = .02) versus 2.7 (p = .02) for complete vaginal removal (n = 14). Twenty-three (89%) patients experienced SUI at follow-up, whereof 10 (45%) reported (almost) no incidents of SUI. CONCLUSIONS: MUS removal is a viable and safe option with a significant drop in VAS pain score in patients with chronic pain after MUS placement. A post-operative increase of SUI and a possible renewed wish for SUI treatment have to be considered. This should not be a reason to refrain from information and/or referral for surgical removal.

Association between levator ani avulsion and urinary incontinence in women: A systematic review and meta-analysis.

BACKGROUND: Urinary incontinence is a bothersome symptom. Although the relationship between stress urinary incontinence (SUI) and vaginal delivery is established, the pathology underlying SUI after vaginal birth remains to be elucidated. OBJECTIVES: To determine whether levator ani muscle avulsion predisposes for SUI in women. SEARCH STRATEGY: Pubmed and Embase were searched for terms and their variations "levator ani muscle avulsion" and "urinary incontinence", from inception until 5 November 2019. SELECTION CRITERIA: Inclusion criterion: studies describing the relationship between urinary incontinence and levator ani muscle avulsion in women at least 1 year after delivery. Exclusion criterion: studies only analyzing the urethral sphincter or hiatus dimensions. DATA COLLECTION AND ANALYSIS: Odds ratios were used and if not available, were calculated as means of data synthesis, adjusted odds ratios if presented by the study, random-effects model to compute a pooled estimate. RESULTS: Seven studies were included, accounting for 2388 women. Comparing women with and without levator ani muscle avulsion, the overall odds ratio for SUI is 0.87 (95% confidence interval 0.56-1.34), and after adjustment for possible confounders was 0.72 (95% confidence interval 0.40-1.30). CONCLUSION: There is no relationship between levator ani muscle avulsion and SUI in women.

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.

Subject-Controlled, On-demand, Dorsal Genital Nerve Stimulation to Treat Urgency Urinary Incontinence; a Pilot.

OBJECTIVES: To evaluate the effect of subject-controlled, on-demand, dorsal genital nerve (DGN) stimulation on non-neurogenic urgency urinary incontinence (UUI) in a domestic setting. MATERIALS AND METHODS: Non-neurogenic patients >18 years with overactive bladder symptoms and UUI were included. Exclusion criteria were mainly stress urinary incontinence. Patients underwent 1 week of subject-controlled, on-demand, DGN stimulation, delivered by a percutaneously placed electrode near the DGN connected to an external stimulator (pulse-rate 20 Hz, pulse-width 300 µs). Patients activated the stimulator when feeling the urge to void and stimulated for 30 s. The amplitude was set at the highest tolerable level. A bladder diary including a severity score of the UUI episodes/void (scores: 0 = none, 1 = drops, 2 = dashes, 3 = soaks) and a padtest was kept 3 days prior to, during, and 3 days after the test period. The subjective improvement was also scored. RESULTS: Seven patients (4 males/3 females) were enrolled, the mean age was 55 years (range 23-73). Six completed the test week. In the remaining patient the electrode migrated and was removed. 5/6 finalized the complete bladder diary, 1/6 recorded only the heavy incontinence episodes (score = 3). 4/6 completed the padtest. In all patients who finalized the bladder diary the number of UUI episodes decreased, in 3/5 with ≥60%. The heavy incontinence episodes (score = 3) were resolved in 2/6 patients, and improved ≥80% in the other 4. The severity score of the UUI episodes/void was improved with ≥ 60% in 3/5 patients. The mean subjective improvement was 73%. CONCLUSION: This feasibility study indicates that subject-controlled, on-demand DGN stimulation using a percutaneously placed electrode is possible over a longer time period, in a home setting, with a positive effect on non-neurogenic overactive bladder symptoms with UUI. Although the placement is an easy procedure, it is difficult to fixate the electrode to keep it in the correct position. Improvements in hardware, like a better fixated electrode and an easy to control stimulator, are necessary to make SODGNS a treatment possibility in the future.

Dorsal genital nerve stimulation in patients with detrusor overactivity: a systematic review.

This study evaluates the outcome of trials to stimulate the dorsal genital nerve (DGN) in patients with lower urinary tract dysfunction. The aim of most studies was to suppress detrusor overactivity in patients with overactive bladder (OAB) syndrome by DGN stimulation. A literature search was performed using Pub Med, Web of Science, and Scopus databases (1980 to April 2012) for clinical trials of DGN stimulation in patients with detrusor overactivity. Seventeen studies were found in the literature. In the studies, different patterns of DGN stimulation were applied. The patterns were either continuous, conditional, or semi-conditional; on an acute or on a chronic basis. DGN stimulation lead to improvement of bladder capacity and reduction in urgency and/or incontinence episodes in many patients. The outcomes of conditional stimulation were comparable to continuous stimulation with respect to improvement of bladder capacity. The publications give evidence that DGN stimulation increases bladder capacity and suppresses involuntary detrusor contractions. Implantable DGN stimulation electrodes can open the way for more prolonged studies in larger patient groups to assess the effectiveness of chronic DGN stimulation in patients with OAB syndrome. Chronic DGN stimulation seems to be of value in the management of OAB syndrome.

Feasibility of noninvasive near-infrared spectroscopy to diagnose detrusor overactivity.

INTRODUCTION: Near-infrared spectroscopy (NIRS) is an optical technology able to detect the hemodynamic changes in biological tissues. Our objective was to determine the feasibility of applying NIRS in the noninvasive diagnosis of detrusor overactivity (DO). PATIENTS AND METHODS: Comparative analysis was performed on 39 involuntary detrusor contractions (IDC) from 23 filling cystometries with simultaneous noninvasive NIRS of the bladder in 14 patients with DO. Motion artifacts were checked for via surface EMG of the abdominal muscles. RESULTS: Thirty-nine IDC were obtained. The median amplitude of rise in detrusor pressure at DO was 48 cm H(2)O (range: 5-219). The median filling volume at DO was 148 ml (range: 9-531). NIRS curves demonstrated apparently significant deviations from baseline in 35 of 39 (90%) DO episodes. All onsets of NIRS deviations occurred within the time period of the IDC with a mean delay of 3 s (range: 0-9). CONCLUSION: NIRS can be a potential tool for the noninvasive diagnosis of DO.

Surgical access for electrical stimulation of the pudendal and dorsal genital nerves in the overactive bladder: a review.

PURPOSE: The anatomy of the pudendal nerve and its nerve branches, especially the dorsal nerve of the penis and clitoris (dorsal genital nerves), and the clinical application of electrical stimulation of these nerves in patients with overactive bladder syndrome and detrusor overactivity are reviewed. MATERIALS AND METHODS: A literature search was performed using the PubMed® database and reference lists of relevant studies to obtain articles concerning the anatomy as well as the electrical stimulation of the pudendal nerve and its nerve branches in patients with overactive bladder syndrome. RESULTS: According to the anatomy, electrical stimulation of the pudendal nerve and the dorsal genital nerves to suppress involuntary detrusor contractions is possible at several sites along their course from the sacral nerves to the penis or clitoris. The nerves are accessible by minimally invasive percutaneous methods. Stimulation of the pudendal nerve and dorsal genital nerves effectively increases bladder capacity, and inhibits involuntary detrusor contractions and overactive bladder symptoms. CONCLUSIONS: More clinically applied studies are recommended for stimulation of the dorsal genital nerves to assess its value and feasibility because most studies have been performed in an acute and experimental setting. The preferred type of electrode is not known, but if wire electrodes can be implanted and fixated well by a minimally invasive procedure, cuff electrodes are not necessary. Before deciding on continuous or conditional stimulation, chronic clinical studies are recommended because acute studies remain inconclusive. The feasibility of conditional stimulation depends on the availability of a reliable and clinically applicable detrusor activity sensor.

Quality of life in complete spinal cord injury patients with a Brindley bladder stimulator compared to a matched control group.

AIMS: To determine the effects on Quality of Life (QoL) of a Brindley procedure, which combines a sacral dorsal root rhizotomy to treat neurogenic detrusor overactivity with sacral anterior root stimulation to enable micturition, defecation, and penile erections in complete spinal cord injury (SCI) patients compared to a matched Control Group. METHODS: Cross-sectional study. The Qualiveen questionnaire, SF-36 questionnaire, and multiple choice questions about urinary continence and urinary tract infections were sent to 93 patients who had a Brindley stimulator implanted in the Netherlands and a matched Control Group of 70 complete SCI patients with neurogenic detrusor overactivity. Primary study outcomes were Specific Impact of Urinary Problems score and general QoL index of the Qualiveen. RESULTS: Response rates were 78% and 40% for patients with a Brindley stimulator and controls, respectively. Stimulators were still used for micturition in 46 (63%). These patients had a significant better Specific Impact of Urinary Problems score, general QoL index (Qualiveen), and continence rate, and less urinary tract infections compared to the Control Group. Patients also benefited of the rhizotomy with regard to QoL and continence rate if the stimulator was not used anymore. The subscales of the SF-36 had better scores for the patients who used their stimulator as compared to those who did not use the stimulator and compared to the Control Group. CONCLUSIONS: The Brindley stimulator for complete spinal cord injury patients improves Quality of Life, continence, and urinary tract infection rate compared to a matched Control Group.

Near-infrared spectroscopy: a novel, noninvasive, diagnostic method for detrusor overactivity in patients with overactive bladder symptoms--a preliminary and experimental study.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an optical technology. It detects the hemodynamic changes in tissues via noninvasive measurement of changes in the concentration of tissue chromophores such as oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb). Involuntary bladder contractions may cause changes detectable by NIRS. OBJECTIVE: To address the accuracy and reproducibility of NIRS to detect the hemodynamic effects of detrusor overactivity (DO). DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was carried out on 41 patients with overactive bladder symptoms. MEASUREMENTS: Forty-one patients underwent one or more filling cystometries with simultaneous NIRS of the bladder. The separated graphs representing both tests were presented to three urodynamicists on two occasions, 3 wk apart. The graphs showed curves with and without DO episodes with the bladder sensations marked. Thirteen of 47 graphs (28%) with DO and 16 of 58 graphs (28%) without DO were excluded due to motion artifacts. The urodynamicists marked pressure changes suggestive of DO on the cystometry curves. For NIRS curves they marked definite deviations from baseline. The sensitivity and specificity of NIRS for DO were determined. The inter- and intraobserver agreements were determined. RESULTS AND LIMITATIONS: Valid data from 33 of 41 patients (80%) were included in the analysis. The interobserver agreement to trace the effect of DO on NIRS curves was "substantial" (κ(f)>0.6). The sensitivity of the Hb(sum) (O(2)Hb+HHb) curves for DO was 62-97% with a specificity of 62-79% (area under the curve [AUC]: 0.80-0.82; p<0.001). O(2)Hb curves had 79-85% sensitivity and 82-91% specificity for DO (AUC: 0.80-0.85; p<0.001). The sensitivity and specificity of the HHb curves for DO were 71-82% and 77-82%, respectively (AUC: 0.73-0.84; p<0.001). These values represent the performance of NIRS in the data sample that is not contaminated with motion artifacts; they are not representative of a general clinical setting. CONCLUSION: NIRS is a potential noninvasive, reproducible, diagnostic method to detect DO.

Retraction of an intrathecal baclofen infusion catheter following suprapubic cystotomy: a case report.

INTRODUCTION: Intrathecal baclofen, administered via a Baclofen pump, is used for patients with spasticity. We report here a case of intrathecal catheter retraction following surgery. CASE REPORT: A male patient with adrenoleukodystrophy and a baclofen pump implant was admitted to the urology department with bladder stones. A transurethral cystolithotripsy and a suprapubic cystotomy were performed. Following surgery there was no adequate spasm control. Plain abdominal X-ray showed complete retraction of the catheter out of the intrathecal space. DISCUSSION: Intrathecal catheter retraction after surgery has been reported in a few cases. The retraction in this case did not seem to be due to the suprapubic cystotomy itself, but was more likely due to the positioning of the patient for cystoscopy and surgery, combined with possible loosening of the anchoring of the catheter. CONCLUSION: Specific attention should be paid to the positioning of patients before surgery in order to avoid intrathecal baclofen catheter withdrawal.