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.

Contemporary management and outcome of myelomeningocele: the Rotterdam experience.

OBJECTIVE: Myelomeningocele (MMC) is the most common form of spina bifida, with a lifelong impact on the quality of life for infants born with this condition. In recent decades, fetal surgery has evolved from an experimental therapy to standard of care for many centers in the world. In this study, the authors aimed to provide an overview of the current management and outcomes for infants with MMC managed at their institution. This then provides a center-specific historical cohort for comparison with future antenatal-treated MMC cases. METHODS: This is a retrospective, single-institution cohort study including all consecutive MMC cases between January 1, 2000, and June 1, 2018, at Erasmus MC. Outcome data included closure of the defect (location, timing, and surgical parameters), hydrocephalus management, Chiari malformation type II (CMTII) management, incidence of spinal cord tethering and outcome, motor outcomes, and continence. RESULTS: A total of 93 patients were included with predominantly lumbosacral lesions. Two patients died during follow-up. Hydrocephalus was present in 84%, with a 71% ventriculoperitoneal shunt reoperation rate. Surgery was performed in 12% for a tethered spinal cord at a mean age of 8 years. Decompression surgery was performed in 3 patients for CMTII. Special education in 63% was significantly associated with hydrocephalus (p < 0.015). Nineteen percent of patients were able to walk independently, and 47% were nonambulators. Social continence for urine was obtained in 75% of patients, 4% had fecal incontinence. CONCLUSIONS: This study provides an overview of current MMC outcomes at the authors' center and will serve as a historical cohort for comparison with future fetal surgery cases operated on at the center in the coming years. Apart from a relatively low surgical untethering rate, the authors' outcome data are comparable to those in the literature. Hydrocephalus is highly prevalent in postnatally treated MMC patients; in this study as in much of the literature, hydrocephalus is correlated with a low cognitive function. Fetal surgery for MMC halves the need for shunt treatment in a select group of MMC pregnancies, constituting a major indication for us to undergo the transition to a fetal surgery center. The fetal benefits of open antenatal surgery for MMC are well established, yet long-term data on especially tethered spinal cord are eagerly awaited.

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.

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.

Influence of sildenafil on blood oxygen saturation of the obstructed bladder.

BACKGROUND: Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction. METHODS: Thirty-two guinea pigs; sham operated (n = 8), sham operated + SC (n = 8), urethrally obstructed (n = 8) and urethrally obstructed + SC (n = 8) were studied during an 8 week period. BOS of the bladder wall was measured by differential path-length spectroscopy (DPS) before obstruction, at day 0, and at week 8. The bladder function was evaluated by urodynamic studies every week. RESULTS: Before surgery and after sham operation all study parameters were comparable. After sham operation, bladder function and BOS did not change. In the obstructed group the urodynamic parameters were deteriorated and BOS was decreased. In the group obstruction + SC, bladder compliance remained normal and overactivity occurred only sporadic. BOS remained unchanged compared to the sham group and was significantly higher compared to the obstruction group. CONCLUSIONS: In an obstructed bladder the loss of bladder function is accompanied by a significant decrease in BOS. Treatment of obstructed bladders with SC yields a situation of high saturation, high bladder compliance and almost no overactivity. Maintaining the microcirculation of the bladder wall might result in better bladder performance without significant loss of bladder function. Measurement of BOS and interventions focussing on tissue microcirculation may have a place in the evaluation / treatment of various bladder dysfunctions.

Laparoscopic transperitoneal pyeloplasty in children from age of 3 years: our clinical outcomes compared with open surgery.

OBJECTIVE: To report clinical outcomes for laparoscopic pyeloplasty (LP) in children compared with open pyeloplasty (OP) and literature findings. PATIENTS AND METHODS: In a prospective study, the outcomes of 57 consecutive transperitoneal LP in children from the age of 3 years were analyzed and compared with a matched historic control group of OP and with series of LP in the literature. Successful result was defined as resolution of symptoms, no conversion or re-operation, improved hydronephrosis, and/or improved renographic drainage. RESULTS: Mean operative time was 177 (SD 50.5)min in the LP group and 108 (SD 25.6)min in the OP group (p < 0.001). Mean hospital stay was 1.2 (SD 0.46) days in the LP and 6.7 (SD 1.2) days in the OP group. Improvement in renographic drainage was observed more often after LP than after OP (98% vs 83%; p = 0.010). A successful result was reported in 56 (98%) LP and 54 (95%) OP (p = 0.298) patients. Our LP series demonstrates a high success rate compared to literature data. CONCLUSIONS: Our LP has a similar success rate and more often improved renographic drainage in comparison to OP. Furthermore, our LP demonstrates a shorter hospital stay and favorable outcomes compared to the literature. We thus regard LP as standard treatment for repair of ureteropelvic junction obstruction in children from the age of 3 years.

Changes in bladder wall blood oxygen saturation in the overactive obstructed bladder.

PURPOSE: Several studies suggest that hypoxia of the bladder wall contributes to bladder dysfunction but the exact relation between bladder function and blood oxygen saturation, a surrogate marker for hypoxia, is not known. We determined bladder wall blood oxygen saturation in vivo in an animal model of bladder outlet obstruction to establish the exact relation between blood oxygen saturation and bladder function. MATERIALS AND METHODS: In 8 sham operated and 8 urethrally obstructed guinea pigs we measured blood oxygen saturation of the bladder wall by differential path length spectroscopy before surgery and 8 weeks postoperatively. Urodynamic investigations performed during the whole 8-week period provided data on bladder function. RESULTS: Before surgery and 8 weeks after sham surgery blood oxygen saturation in the bladder wall was between 88% and 95% during filling. It decreased during voiding and returned to greater than 90% within 30 seconds. Eight weeks after obstruction saturation was significantly lower than in the sham operated group during filling and voiding. The decrease was positively related to bladder pressure during filling and voiding, and was more pronounced when overactivity was present. Local bladder contractions occurred without a measurable increase in bladder pressure but were associated with a decrease in saturation. CONCLUSIONS: A normal bladder maintains a high oxygen saturation level during filling. Bladder obstruction compromises this ability, especially when it involves overactivity. Local bladder contractions without a measurable increase in bladder pressure were associated with a decrease in blood saturation.