Long-term beneficial effects of mirabegron in pediatric patients with therapy-refractory neurogenic lower urinary tract dysfunction.

INTRODUCTION: Neurogenic lower urinary tract dysfunction (NLUTD) in children can cause renal failure and urinary incontinence if not treated sufficiently. Antimuscarinics (AM) and intradetrusor botulinum toxin injections (BoNT-A) with clean intermittent catheterization (CIC) are widely used treatment options for children with NLUTD. However, a considerable number will become refractory to these treatment options. This study aimed to evaluate the efficacy and long-term outcomes of mirabegron in children with NLUTD as an add-on and as a stand-alone treatment. MATERIAL AND METHODS: Patients under 18 years of age with NLUTD who were refractory to AM and/or BoNT-A and were treated with mirabegron 50 mg were retrospectively studied. Mirabegron was either used as monotherapy or in addition to AM and/or BoNT-A. Video-urodynamic studies (VUDSs) were performed before and after treatment with mirabegron. Changes in video-urodynamic parameters, the need for other NLUTD therapy during follow-up, patient-reported side effects, and urinary incontinence were outcomes of interest. RESULTS: A total of 34 patients with NLUTD were included. All patients were on CIC and the median age was 13.1 years (IQR 15.9-10.3). Median follow-up was 31.4 months (IQR 57.4-11.4). Bladder compliance improved by 89.9%, from 14.9 to 28.3 ml/cm H2O (p-value<0.001). Maximum cystometric capacity, end-filling detrusor pressure, volume at first detrusor overactivity, vesicoureteral reflux, and urinary incontinence significantly improved after mirabegron. The add-on therapy group showed more significant improvements in video-urodynamic outcomes compared to the monotherapy group. The median time of requiring other NLUTD therapy was 25.5 months (IQR 39.8-14.8). None of the included patients reported side effects. CONCLUSIONS: Mirabegron is an effective treatment for children with therapy-refractory NLUTD with an average efficacy of 2 years after which additional therapy is required. Despite the retrospective character of this study, our results confirm the beneficial effect of mirabegron in children with therapy-refractory NLUTD, in particular when mirabegron is used as add-on therapy in those with low-compliance bladders.

Neuro-Urology: Call for Universal, Resource-Independent Guidance.

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines.

Efficacy and Safety of Surgical Treatments for Neurogenic Stress Urinary Incontinence in Adults: A Systematic Review.

CONTEXT: Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI). OBJECTIVE: To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management. EVIDENCE ACQUISITION: A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively. CONCLUSIONS: The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques. PATIENT SUMMARY: Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.

Two-year safety and efficacy outcomes for the treatment of overactive bladder using a long-lived rechargeable sacral neuromodulation system.

AIMS: Sacral neuromodulation (SNM) therapy for overactive bladder (OAB) has proven long-term safety and efficacy. Historically, the only commercially available SNM device was nonrechargeable requiring replacement surgery due to battery depletion. The Axonics System is the first rechargeable SNM device and is qualified to last a minimum of 15 years in the body. The study objective was to evaluate the safety and efficacy of this rechargeable SNM system. This study reports 2-year outcomes. METHODS: A total of 51 subjects were implanted with the Axonics System in a single nonstaged procedure. Subjects had OAB, confirmed on a 3-day voiding diary (≥8 voids/day and/or ≥2 incontinence episodes over 72 hours). Test Responders were defined as subjects that were responders at 1 month postimplant. The efficacy analysis included therapy responder rates, change in the quality of life, and subject satisfaction reported in Test Responders (n = 30) and all implanted subjects (n = 37) that completed the follow-up visits. Adverse events (AEs) are reported in all implanted subjects. RESULTS: At 2 years, 90% of the Test Responders continued to respond to the therapy based on voiding diary criteria. Satisfaction with therapy was reported by 93% of subjects and 86% found their charging experience acceptable. Of the urinary incontinence Test Responders, 88% continued to be responders at 2 years, and 28% were completely dry. There were no unanticipated (AEs) or serious device-related AEs. CONCLUSIONS: The Axonics System® provides sustained clinically meaningful improvements in OAB subjects at 2 years. There were no serious device-related AEs. Subjects reported continued satisfaction with their therapy.

Treatment of Urinary Urgency Incontinence Using a Rechargeable SNM System: 6-Month Results of the ARTISAN-SNM Study.

PURPOSE: Sacral neuromodulation is a guideline recommended treatment of urinary dysfunction and fecal incontinence in patients in whom conservative treatments have failed. Historically sacral neuromodulation has been delivered using a nonrechargeable device with an average life span of 4.4 years. Surgery is required to replace the implanted neurostimulator due to battery depletion. Implantation of a long-lived implanted neurostimulator can eliminate the need for replacement surgeries, potentially reducing patient surgical risks and health care costs. The Axonics r-SNM System™ is a miniaturized, rechargeable sacral neuromodulation system designed to deliver therapy for at least 15 years. The ARTISAN-SNM (Axonics® Sacral Neuromodulation System for Urinary Urgency Incontinence Treatment) study is a pivotal study using rechargeable sacral neuromodulation therapy to treat urinary urgency incontinence. Six-month results are presented. MATERIALS AND METHODS: A total of 129 eligible patients with urinary urgency incontinence were treated. All participants were implanted with a tined lead and the rechargeable sacral neuromodulation system in a nonstaged procedure. Efficacy data were collected using a 3-day bladder diary, the validated ICIQ-OABqol (International Consultation on Incontinence Questionnaire Overactive Bladder quality of life) questionnaire and a participant satisfaction questionnaire. Therapy responders were identified as participants with a 50% or greater reduction in urinary urgency incontinence episodes compared to baseline. We performed an as-treated analysis in all implanted participants. RESULTS: At 6 months 90% of participants were therapy responders. The mean ± SE number of urinary urgency incontinence episodes per day was reduced from 5.6 ± 0.3 at baseline to 1.3 ± 0.2. Participants experienced a clinically meaningful 34-point improvement on the ICIQ-OABqol questionnaire. There were no serious device related adverse events. CONCLUSIONS: The Axonics r-SNM System is safe and effective with 90% of participants experiencing clinically and statistically significant improvements in urinary urgency incontinence symptoms.

Long-term results of continent catheterizable urinary channels in adults with non-neurogenic or neurogenic lower urinary tract dysfunction.

Objectives: To evaluate the long-term results after the construction of a Continent Catheterizable Urinary Conduit (CCUC) in adults. Methods: This study retrospectively reviewed the charts of 41 adults from two tertiary centers who received a CCUC. The demographics, underlying diseases, indications for a CCUC and outcomes such as the reoperation rate and the occurrence of complications were extracted. The patient reported outcome was measured with the Patient Global Impression of Improvement (PGI-I) scale and four additional questions about continence, leakage and stomal problems. Results: Twenty-nine patients were women. The median age at surgery was 32 years, with a median follow-up of 52 months. Twenty-six patients had a neurogenic bladder. The reoperation rate was 48.8%, with a median of 10.5 months after constructing the CCUC. Superficial stomal stenosis was the most common registered complication (20 times) and stoma revision was the most often performed reoperation (12 times). Twenty-four patients completed the PGI-I; the mean improvement rating was 2 (=much better). Conclusion: The construction of a CCUC in adults is associated with a high complication and reoperation rate. The high reoperation rate is in accordance with the sparse literature. Despite this, patients reported 'much better' on the PGI-I.

Surgical Management of Anatomic Bladder Outlet Obstruction in Males with Neurogenic Bladder Dysfunction: A Systematic Review.

CONTEXT: Surgical treatment of anatomic bladder outlet obstruction (BOO) may be indicated in males with neurogenic bladder dysfunction. A bothersome complication after surgery is urinary incontinence. OBJECTIVE: To identify the optimal practice in the surgical treatment of anatomic BOO in males with neurogenic bladder dysfunction, due to multiple sclerosis, Parkinson disease, spinal cord injury (SCI), spina bifida, or cerebrovascular accident (CVA). EVIDENCE ACQUISITION: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Medline, Embase, Cochrane controlled trial databases, Web of Science, and Google Scholar were searched for publications until January 2017. EVIDENCE SYNTHESIS: A total of 930 abstracts were screened. Eight studies were included. The types of anatomic BOO discussed were benign prostate obstruction, urethral stricture, and bladder neck sclerosis. The identified surgical treatments were transurethral resection of the prostate (TURP) in patients with Parkinson, CVA or SCI, endoscopic treatment of urethral stricture by laser ablation or urethrotomy (mainly in SCI patients), and bladder neck resection (BNR) in SCI patients. The outcome of TURP may be highly variable, and includes persistent or de novo urinary incontinence, regained normal micturition control, and urinary continence. Good results were seen in BNR and endoscopic urethrotomy studies. Laser ablation and cold knife urethrotomy resulted in restarting intermittent catheterization or adequate voiding. Overall, a high risk of bias was found. CONCLUSIONS: This systematic review provides an overview of the current literature on the outcome of several surgical approaches of different types of anatomic BOO in males with neurogenic bladder dysfunction. Identifying the optimal practice was impossible due to limited availability of high-quality studies. PATIENT SUMMARY: The outcome of several surgical approaches in males with neurogenic bladder dysfunction with benign prostate obstruction, urethral stricture, or bladder neck sclerosis is overviewed. The optimal practice could not be identified.

Outcome and complications of adjustable continence therapy (ProACT™) after radical prostatectomy: 10 years' experience in 143 patients.

AIMS: To evaluate our outcomes of the adjustable continence balloons ProACT™ for the treatment of male stress urinary incontinence after radical prostatectomy. METHODS: Between May 2007-August 2016 the ProACT™ was implanted in 143 patients without a history of radiotherapy. Endpoints were patient-reported changes in pad counts and complications. Treatment was considered successful if no pad or just one "security" pad per day sufficed, and improved if daily pad use was reduced by ≥50%. RESULTS: Incontinence before implantation was mild in 36 (25%), moderate in 57 (40%), and severe in 50 (35%) patients. Complications within 30 days were classified by the Clavien-Dindo classification; eight (5.6%) grade I, three (2.1%) grade II, three (2.1%) grade IIIb, and 129 (90.2%) patients had no complication. Revision was done in 43 (30%) patients. The IPSS quality of life item improved significantly from 5.0 (IQR 4.0-5.0) preoperative to 2.0 (IQR 1.0-4.0) and 1.0 (IQR 0.0-3.0) 6 and 12 months after implantation, respectively. After a median follow up of 56 months (range 28 to 79, n = 112), 72 (64%) patients were improved, including 51 (45%) patients were successful. Daily pad use decreased from 3.0 to 1.0 (67% reduction). The median outcome on the Patient Global Impression of Improvement scale was "much better," and 97 (87%) patients perceived improvement. CONCLUSIONS: The minimally invasive ProACT™ device showed a clear beneficial continence outcome in patients with stress urinary incontinence after radical prostatectomy. The majority of the patients were satisfied and perceived improvement ≥50% on daily pad use on the long term.

Continent catheterizable tubes/stomas in adult neuro-urological patients: A systematic review.

AIMS: To systematically review all available evidence on the effectiveness and complications of continent cutaneous stoma or tube (CCS/T) to treat bladder-emptying difficulties in adult neuro-urological patients. METHODS: The search strategy and studies selection were performed on Medline, Embase, and Cochrane using the PICOS method according to the PRISMA statement (CRD42015019212; http://www.crd.york.ac.uk/PROSPERO). RESULTS: After screening 3,634 abstracts, 11 studies (all retrospective, enrolling 213 patients) were included in a narrative synthesis. Mean follow-up ranged from 21.6 months to 8.7 years (median: 36 months, IQR 28.5-44). At last follow-up, the ability to catheterize rate was ≥84% (except in one study: 58.3%) and the continence rate at stoma was >75%. Data comparing health-related quality-of-life before and after surgery were not available in any study. Overall, 85/213 postoperative events required reoperation: 7 events (7 patients) occurring ≤3 months postoperatively, 22 events (16 patients) >3 months, and 56 events (55 patients) for which the time after surgery was not specified. Sixty additional complications (60 patients) were reported but did not require surgical treatment. Tube stenosis occurred in 4-32% of the cases (median: 14%, IQR 9-24). Complications related to concomitant procedures (augmentation cystoplasty, pouch) included neovesicocutaneous fistulae, bladder stones, and bladder perforations. Risk of bias and confounding was high in all studies. CONCLUSIONS: CCS/T appears to be an effective treatment option in adult neuro-urological patients unable to perform intermittent self-catheterization through the urethra. However, the complication rate is meaningful and the quality of evidence is low, especially in terms of long-term outcomes including the impact on the quality-of-life.

Long-term effectiveness and complication rates of bladder augmentation in patients with neurogenic bladder dysfunction: A systematic review.

AIMS: To systematically evaluate effectiveness and safety of bladder augmentation for adult neuro-urological patients. METHODS: The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement was followed for review of publications. The Medline, Embase, and Cochrane controlled trial databases and clinicaltrial.gov were searched until January 2015. No limitations were placed on date or language. Non-original articles, conference abstracts, and publications involving children and animals were excluded. Risk-of-bias and confounder assessment was performed. RESULTS: A total of 20 studies including 511 patients were eligible for inclusion. The level of evidence for the included studies was low, most level 4 studies with only one level 3 study. The data were narratively synthesized. Across all studies high risk-of bias and confounding was found. Primary outcomes were assessed in 16 of the 20 studies and showed improved quality of life and anatomical changes as well as stable renal function. The secondary outcomes were reported in 17 of the 20 studies and urodynamic parameters and continence all demonstrated improvement after bladder reconstruction. Long-term complications continued up to 10 years post-operatively, including bowel dysfunction in 15% of the patients, stone formation in 10%, five bladder perforations and one bladder cancer. CONCLUSIONS: Available studies are not plentiful and of relatively poor quality, appropriately designed prospective studies are urgently needed. Despite this, bladder augmentation appears to be a highly effective procedure at protecting the upper urinary tract and improving quality of life. However, it is associated with relatively high morbidity in both the short and long term.

20 years experience with appendicovesicostomy in paediatric patients: Complications and their re-interventions.

AIMS: To evaluate the long-term outcome of appendicovesicostomies and to present the frequency and timing of complications needing re-intervention. METHODS: In this retrospective study we included patients in whom an appendicovesicostomy was created at our institution between 1993 and 2011. Patients with a follow-up less than 1 year were excluded. Patient characteristics and conduit-related complications requiring re-intervention were collected. RESULTS: One hundred and twenty-eight patients were included with mean age at initial surgery of 10.1 ± 3.9 years. Two thirds of the children had underlying neurogenic disease. The mean follow-up was 10.1 ± 4.8 years. All but one patient continued to use the catheterizable channel. Re-intervention for conduit-related complications was necessary in 32.0% of the patients. A second, third, and fourth re-intervention was required in respectively 10.9%, 2.3%, and 1.6%. The commonest complications were cutaneous/fascial stenosis in 14.8%, stenosis at conduit-bladder level in 9.4%, and stomal incontinence in 6.3% of the patients. The most performed re-interventions were stoma revision (in 16.4% of the patients), conduit revision (10.2%), and dilatation of a stenotic tract (4.7%). 63.3% of the re-interventions was superficial and/or endoscopic. The peak incidence of re-interventions was in the 1st year after conduit construction and decreased yearly. CONCLUSIONS: Our study gives an overview of patients and their conduits developing from prepubertal children to young adults. During a mean follow-up of 10.1 years, roughly one third of the patients needed a re-intervention. We conclude that an appendicovesicostomy is an effective and durable treatment for whom transurethral clean intermittent catheterization is not feasible. Neurourol. Urodynam. 36:1325-1329, 2017. © 2016 Wiley Periodicals, Inc.

Maximum Urethral Closure Pressure Increases After Successful Adjustable Continence Therapy (ProACT) for Stress Urinary Incontinence After Radical Prostatectomy.

OBJECTIVE: To evaluate changes of the urethral pressure profile (UPP) after implantation of adjustable continence therapy (ProACT), a minimally invasive procedure in which 2 volume-adjustable balloons are placed periurethrally for treatment of male stress urinary incontinence. The working mechanism of the ProACT to achieve continence has not been fully understood. We hypothesized that successful treatment with ProACT improves urinary continence by inducing a significant increase in static urethral pressure. MATERIALS AND METHODS: We included patients who underwent UPP before and after ProACT implantation. UPPs were initially performed with the Brown-Wickham water perfusion method and later with the T-DOC Air-Charged catheter method. Pre- and postoperative UPPs and International Prostate Symptom Scores were evaluated. UPP measurements of successfully (no or 1 precautionary pad per day) and unsuccessfully treated patients were compared. RESULTS: Twenty-seven patients were included in the study; 23 patients were successfully and 4 patients were unsuccessfully treated. Maximum urethral closure pressure (MUCP) increased significantly from median 58.0 to 79.0 cmH2O in the successfully treated group (P = .001). Within the subgroup of unsuccessfully treated patients, MUCP did not change significantly (P = .715). The change in MUCP was statistically significantly different between the successful and unsuccessful group (P = .034). Total score of the International Prostate Symptom Scores did not change significantly after ProACT implantation (P = .097). CONCLUSION: Successful treatment with ProACT is associated with a significant increase of MUCP. This implies that increased static urethral pressure contributes to the working mechanism of the ProACT device to achieve continence.

Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well-designed randomised controlled trials are needed to make definitive conclusions. PATIENT SUMMARY: Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Simplified scoring of the Actionable 8-item screening questionnaire for neurogenic bladder overactivity in multiple sclerosis: a comparative analysis of test performance at different cut-off points.

BACKGROUND: The Actionable questionnaire is an 8-item tool to screen patients with multiple sclerosis (MS) for neurogenic bladder problems, identifying those patients who might benefit from urological referral and bladder-specific treatment. The original scoring yields a total score of 0 to 24 with cut-off point 6. A simplified scoring, yielding a total score of 0 to 8 with cut-off point 3, has been developed in urogynaecological patients, but has not been investigated in MS. METHODS: One-hundred-and-forty-one MS patients completed the Actionable on two occasions. We compared the test performance of the simplified scoring with cut-off point 3 with that of cut-off point 2, using the original scoring with cut-off point 6 as a gold standard. The following measures were calculated: True Positives (TP), True Negatives (TN), False Positives (FP), False Negatives (FN), Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and Accuracy. The associations between positive test result and urological treatment, and bladder-specific drug treatment were calculated. RESULTS: For cut-off point 3 the outcomes (Test 1, Test 2) were: TP 43.26 %, 40.88 %; TN 29.79 %, 32.85 %; FP 0.00 %, 0.00 %; FN 26.95 %, 26.28 %; Sensitivity 0.62, 0.61; Specificity 1.00, 1.00; PPV 1.00, 1.00; NPV 0.53, 0.55; Accuracy 0.73, 0.74; and for cut-off point 2: TP 59.57 %, 59.85 %; TN 26.95 %, 31.39 %; FP 2.84 %, 1.46 %; FN 10.63 %, 7.30 %; Sensitivity 0.85, 0.89; Specificity 0.90, 0.96; PPV 0.95, 0.98; NPV 0.72, 0.81; Accuracy 0.87, 0.91. Cut-off 3 completely prevented FP outcomes, but wrongly classified 26 % of the patients as negative (FN). Cut-off 2 reduced the FN to 7-10 %, with low FP values (2.84-1.46 %). With cut-off 2, the percentage of patients screened positive was higher in the Progressive group (75.00 %) than in the Relapsing Remitting group (56.25 %) (P = 0.0331), which was not the case with cut-off 3. Only a positive test according to the original scoring was associated with both urological treatment (P = 0.0119) and bladder-specific medication (P = 0.0328). CONCLUSIONS: Our findings suggest that in MS patients the simplified Actionable scoring is more accurate with cut-off point 2 than with cut-off point 3, especially by substantially reducing FN outcomes; and that in MS the original Actionable scoring seems preferable.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY: Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Surgical management of functional bladder outlet obstruction in adults with neurogenic bladder dysfunction.

BACKGROUND: The most common type of functional bladder outlet obstruction in patients with neurogenic bladder is detrusor-sphincter dyssynergia (DSD). The lack of co-ordination between the bladder and the external urethral sphincter muscle (EUS) in DSD can result in poor bladder emptying and high bladder pressures, which may eventually lead to progressive renal damage. OBJECTIVES: To assess the effectiveness of different surgical therapies for the treatment of functional bladder outlet obstruction (i.e. DSD) in adults with neurogenic bladder dysfunction. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, and handsearching of journals and conference proceedings (searched 20 February 2014), and the reference lists of relevant articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing a surgical treatment of DSD in adults suffering from neurogenic bladder dysfunction, with no treatment, placebo, non-surgical treatment, or other surgical treatment, alone or in combination. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included five trials (total of 199 participants, average age of 40 years). The neurological diseases causing DSD were traumatic spinal cord injury (SCI), multiple sclerosis (MS), or congenital malformations.One trial compared placement of sphincteric stent prosthesis with sphincterotomy. For urodynamic measurements, results for postvoid residual urine volume (PVR) and cystometric bladder capacity were inconclusive and consistent with benefit of either sphincteric stent prosthesis or sphincterotomy at three, six, 12, and 24 months. Results for maximum detrusor pressure (Pdet.max) were also inconclusive at three, six, and 12 months; however, after two years, the Pdet.max after sphincterotomy was lower than after stent placement (mean difference (MD) -30 cmH2O, 95% confidence interval (CI) 8.99 to 51.01).Four trials considered botulinum A toxin (BTX-A) injection in the EUS, either alone or in combination with other treatments. The comparators included oral baclofen, oral alpha blocker, lidocaine, and placebo. The BTX-A trials all differed in protocols, and therefore we did not undertake meta-analysis. A single 100 units transperineal BTX-A injection (Botox®) in patients with MS resulted in higher voided urine volumes (MD 69 mL, 95% CI 11.87 to 126.13), lower pre-micturition detrusor pressure (MD -10 cmH2O, 95% CI -17.62 to -2.38), and lower Pdet.max (MD -14 cmH2O, 95% CI -25.32 to -2.68) after 30 days, compared to placebo injection. Results for PVR using catheterisation, basal detrusor pressure, maximal bladder capacity, maximal urinary flow, bladder compliance at functional bladder capacity, maximal urethral pressure, and closure urethral pressure at 30 days were inconclusive and consistent with benefit of either BTX-A injection or placebo injections. In participants with SCI, treatment with 200 units of Chinese manufactured BTX-A injected at eight different sites resulted in better bladder compliance (MD 7.5 mL/cmH2O, 95% CI -10.74 to -4.26) than participants who received the same injections with the addition of oral baclofen. Results for maximum uroflow rate, maximal cystometric capacity, and volume per voiding were inconclusive and consistent with benefit of either BTX-A injection or BTX-A injection with the addition of oral baclofen. However, the poor quality of reporting in this trial caused us to question the relevance of bladder compliance as an adequate outcome measure.In participants with DSD due to traumatic SCI, MS, or congenital malformation, the results for PVRs after one day were inconclusive and consistent with benefit of either a single 100 units transperineal BTX-A (Botox®) injection or lidocaine injection. However, after seven and 30 days of BTX-A injection, PVRs were lower (MD -163 and -158 mL, 95% CI -308.65 to -17.35 and 95% CI -277.57 to -39.03, respectively) compared to participants who received lidocaine injections. Results at one month for Pdet.max on voiding, EUS activity in electromyography, and maximal urethral pressure were inconclusive and consistent with benefit of either BTX-A or lidocaine injections.Finally, one small trial consisting of five men with SCI compared weekly BTX-A injections with normal saline as placebo. The placebo had no effect on DSD in the two participants allocated to the placebo treatment. Their urodynamic parameters were unchanged from baseline values until subsequent injections with BTX-A once a week for three weeks. These subsequent injections resulted in similar responses to those of the three participants who were allocated to the BTX-A treatment. Unfortunately, the report presented no data on placebo treatment.Only the trial that compared sphincterotomy with stent placement reported outcome measures renal function and urologic complications related to DSD. Results for renal function at 12 and 24 months, and urologic complications related to DSD at three, six, 12, and 24 months were inconclusive and consistent with benefit of either sphincteric stent prosthesis or sphincterotomy.Adverse effects reported were haematuria due to the cystoscopic injection and muscle weakness, of which the latter may be related to the BTX-A dose used.All trials had some methodological shortcomings, so insufficient information was available to permit judgement of risk of bias. At least half of the trials had an unclear risk of selection bias and reporting bias. One trial had a high risk of attrition bias, and another trial had a high risk of reporting bias. AUTHORS' CONCLUSIONS: Results from small studies with a high risk of bias have identified evidence of limited quality that intraurethral BTX-A injections improve some urodynamic measures after 30 days in the treatment of functional bladder outlet obstruction in adults with neurogenic bladder dysfunction. The necessity of reinjection of BTX-A is a significant drawback; a sphincterotomy might therefore be a more effective treatment option for lowering bladder pressure in the long-term.However, because of the limited availability of eligible trials, this review was unable to provide robust evidence in favour of any of the surgical treatment options. More RCTs are needed, measuring improvement on quality of life, and on other types of surgical treatment options for DSD since these are lacking. Future RCTs assessing the effectiveness of BTX-A injections also need to address the uncertainty about the optimal dose and mode of injection for this specific type of urological condition.

Urodynamic effects of volume-adjustable balloons for treatment of postprostatectomy urinary incontinence.

OBJECTIVE: To evaluate the urodynamic changes in patients treated with Adjustable Continence Therapy for men (ProACT) for postprostatectomy incontinence and to explore the clinical and urodynamic preimplantation parameters as predictors of clinical outcome. MATERIALS AND METHODS: Patients underwent urodynamic studies before and after ProACT implantation. ProACT was considered successful if patients used none or 1 dry precautionary pad and nonsuccessful if the patient reported ≥1 wet pad/d. The pre- and postimplantation assessments were retrospectively compared within and between the success and nonsuccess groups. Multivariate logistic regression analysis was performed to investigate the association between the preimplantation variables and the clinical outcomes of ProACT implantation. RESULTS: A total of 49 patients were included, 37 with successful and 12 with nonsuccessful clinical outcome. Postimplantation urodynamic studies were performed a median of 9 months after ProACT implantation. In the successfully treated patients, maximum free flow rate, bladder contractility index, maximum of bladder contractility parameter W, and bladder voiding efficiency were significantly lower after implantation. The detrusor pressure at maximum flow rate, postvoid residual urine volume, and bladder outlet obstruction index were significantly higher. A longer duration of urinary incontinence, the use of >5 pads daily, and a smaller cystometric bladder capacity were all independently associated with nonsuccessful clinical outcome after ProACT implantation. CONCLUSION: ProACT implantation with successful clinical outcome resulted in greater urethral resistance during voiding and reduced bladder contraction strength. A longer duration of incontinence, the use of >5 pads daily, and a smaller cystometric bladder capacity were independent predictors of unsuccessful clinical outcomes, suggesting ProACT implantation should be considered sooner, rather than later, after conservative treatment of postprostatectomy incontinence has failed.

Sacral neuromodulation as treatment for refractory idiopathic urge urinary incontinence: 5-year results of a longitudinal study in 60 women.

PURPOSE: We evaluated the results of sacral neuromodulation after 5-year followup in women with refractory idiopathic urge urinary incontinence. MATERIALS AND METHODS: A neuromodulation system with an original (nontined) lead was implanted by open surgery after a positive percutaneous nerve evaluation in 60 women from 1990 to 2004. Voiding incontinence diary parameters were used to evaluate efficacy. Success was defined as at least a 50% decrease in the number of incontinence episodes or pads used daily. Safety was also evaluated. RESULTS: The success rate gradually decreased from 52 patients (87%) at 1 month to 37 (62%) at 5 years. Complete continence persisted in 15% of patients. The system was still used by 80% of patients at 5 years. In 32 patients a total of 57 adverse events occurred, which were not severe (Clavien grade I and IIIb in 61% and 39%, respectively). CONCLUSIONS: Sacral neuromodulation appears to be a safe technique for refractory idiopathic urge urinary incontinence in women. The success rate gradually decreased to 62% after 5 years with 15% of patients completely continent.

Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence.

OBJECTIVE: To assess the effect of intra-sphincteric injections of bone marrow mesenchymal stromal cells (MSCs) on Valsalva leak point pressure (VLPP) changes in an animal model of stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats underwent bilateral pudendal nerve section to induce SUI. Six rats were SUI controls, 6 received periurethral injection of Plasma-Lyte (SUI placebo control) and 12 were given periurethral injection of PKH26-labeled MSCs. Four weeks after injection, conscious cystometry was undertaken in animals and VLPP recorded. All groups were sacrificed, and frozen urethra sections were submitted to pathology and immunohistochemistry assessment. RESULTS: Rat MSCs were positive for the cell surface antigens CD44, CD73, CD90, and RT1A, and negative for CD31, CD45, and RT1B, confirming their stem cell phenotype. In vitro, differentiated MSCs expressed α-smooth muscle actin (SMA) and desmin, markers of smooth and striated muscles in vivo. Immunohistochemistry of rat urethras revealed PKH26-labeled MSCs in situ and at the injection site. LPP was significantly improved in animals injected with MSCs. Mean LPP was 24.28 ± 1.47 cmH(2) O in rats implanted with MSCs and 16.21 ± 1.26 cmH(2) O in SUI controls (P<0.001). Atrophic urethras with implanted MSCs were positively stained for myosin heavy chain and desmin. CONCLUSION: Rat MSCs have the ability to differentiate and skew their phenotype towards smooth and striated muscles, as demonstrated by SMA up-regulation and desmin expression. Periurethral injection of MSCs in an animal model of SUI restored the damaged external urethral sphincter and significantly improved VLPP.

Effect of antiepileptic agent, levetiracetam, on urodynamic parameters and neurogenic bladder overactivity in chronically paraplegic rats.

OBJECTIVES: To investigate the effects of different levetiracetam (LEV) doses on urodynamic parameters in an animal model of neurogenic detrusor overactivity (NDO). METHODS: A total of 54 female rats were studied. Of the 54 rats, 6 served as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic control and treatment groups were further subdivided (n = 6), and cystometry was performed at 3 and 4 weeks after SCT, respectively. RESULTS: All paraplegic controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/- 0.2/min. The contraction amplitude and bladder capacity were not significantly different. After 1 week of LEV treatment, these urodynamic parameters improved significantly in a dose-dependent manner, and the changes were more striking at 2 weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/- 0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01). The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P = .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P = .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002). CONCLUSIONS: The results of our study have shown that LEV is an effective treatment of NDO after SCT in rats. It might prove to be a novel, alternative therapeutic approach to NDO. The follow-up of these experimental results with a clinical trial is warranted.