Altaf Mangera

Contemporary Management of Lower Urinary Tract Disease With Botulinum Toxin A: A Systematic Review of Botox (OnabotulinumtoxinA) and Dysport (AbobotulinumtoxinA)

CONTEXT The use of botulinum toxin A (BoNTA) in the treatment of lower urinary tract dysfunction has expanded in recent years and the off-licence usage list includes neurogenic detrusor overactivity (NDO), idiopathic detrusor overactivity (IDO), painful bladder syndrome (PBS), and lower urinary tract symptoms resulting from bladder outflow obstruction (BOO) or detrusor sphincter dyssynergia (DSD). There are two commonly used preparations of BoNTA: Botox (onabotulinumtoxinA) and Dysport (abobotulinumtoxinA). OBJECTIVE To compare the reported outcomes of onabotulinumtoxinA and abobotulinumtoxinA in the treatment of NDO, IDO, PBS, DSD, and BOO for adults and children. EVIDENCE ACQUISITION We performed a systematic review of the published literature on PubMed, Scopus, and Embase in the English language reporting on outcomes of both BoNTA preparations. Review articles and series with <10 cases were excluded. The articles were graded for level of evidence and conclusions drawn separately for data with higher-level evidence. EVIDENCE SYNTHESIS There is high-level evidence for the use of onabotulinumtoxinA and abobotulinumtoxinA in adults with NDO but only for abobotulinumtoxinA in children with NDO. Only onabotulinumtoxinA has level 1 evidence supporting its use in IDO, BOO, DSD, and PBS/interstitial cystitis. CONCLUSIONS We identified good-quality studies that evaluated onabotulinumtoxinA for all the indications described above in adults; such was not the case with abobotulinumtoxinA. Although this does not imply that onabotulinumtoxinA is more effective than abobotulinumtoxinA, it should be a consideration when counselling patients on the use of botulinum toxin in urologic applications. The two preparations should not be used interchangeably, either in terms of predicting outcome or in determining doses to be used.

A Systematic Review of Graft Augmentation Urethroplasty Techniques for the Treatment of Anterior Urethral Strictures

CONTEXT Reconstructive surgeons who perform urethroplasty have a variety of techniques in their armamentarium that may be used according to factors such as aetiology, stricture position, and length. No one technique is recommended. OBJECTIVE Our aim was to assess the reported outcomes of the various techniques for graft augmentation urethroplasty according to site of surgery. EVIDENCE ACQUISITION We performed an updated systematic review of the Medline literature from 1985 to date and classified the data according to the site of surgery and technique used. Data are also presented on the type of graft used and the follow-up methodology used by each centre. EVIDENCE SYNTHESIS More than 2000 anterior urethroplasty procedures have been described in the literature. When considering the bulbar urethra there is no significant difference between the average success rates of the dorsal and the ventral onlay procedures, 88.4% and 88.8% at 42.2 and 34.4 mo in 934 and 563 patients, respectively. The lateral onlay technique has only been described in six patients and has a reported success rate of 83% at 77 mo. The Asopa and Palminteri techniques have been described in 89 and 53 patients with a success rate of 86.7% and 90.1% at 28.9 and 21.9 mo, respectively. When considering penile strictures, the success rate of the two-stage penile technique is significantly better than the one-stage penile technique, 90.5% versus 75.7% as calculated for 129 and 432 patients, respectively, although the follow-up of one-stage procedures was longer at 32.8 mo compared with 22.2 mo. CONCLUSIONS There is no evidence in the literature of a difference between one-stage techniques for urethroplasty of the bulbar urethra. The two-stage technique has better reported outcomes than a one-stage approach for penile urethroplasty but has a shorter follow-up.

An Updated Systematic Review and Statistical Comparison of Standardised Mean Outcomes for the Use of Botulinum Toxin in the Management of Lower Urinary Tract Disorders

CONTEXT Botulinum toxin A (BoNTA) has received regulatory approval for use in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), but it remains unlicensed in other lower urinary tract symptoms (LUTS) indications such as nonneurogenic LUTS in men with benign prostatic enlargement (LUTS/BPE), bladder pain syndrome (BPS), and detrusor sphincter dyssynergia (DSD). OBJECTIVE To compare statistically the outcomes of high level of evidence (LE) studies with placebo using BoNTA for LUTS indications; NDO, OAB, LUTS/BPE, BPS and DSD. EVIDENCE ACQUISITION We conducted a systematic review of the published literature on PubMed, Scopus, and Embase reporting on BoNTA use in LUTS dysfunction. Statistical comparison was made between high LE studies with placebo and low LE studies. EVIDENCE SYNTHESIS In adult NDO, there are significantly greater improvements with BoNTA in daily incontinence and catheterisation episodes (-63% and -18%, respectively; p<0.01), and the urodynamic parameters of maximum cystometric capacity (MCC), reflex volume, and maximum detrusor pressure (MDP) (68%, 61%, and -42%, respectively; all p<0.01). In OAB, BoNTA leads to significant improvements in bladder diary parameters such as daily frequency (-29%), daily urgency (-38%), and daily incontinence (-59%) (all p<0.02). The urodynamic parameters of MCC and MDP improved by 58% (p=0.04) and -29% (p=0.002), respectively. The risk of urinary tract infection was significantly increased from placebo at 21% versus 7% (p<0.001), respectively; the risk of intermittent self-catherisation increased from 0% to 12% (p<0.001). Men with LUTS/BPE showed no significant improvements in International Prostate Symptom Score, maximum flow rate, or prostate volume. There were insufficient data for statistical analysis in DSD, BPS, and paediatric studies. Low LE studies were found to overestimate the effects of BoNTA in all indications, but differences from high LE studies were significant in only a few parameters. CONCLUSIONS BoNTA significantly improves all symptoms and urodynamic parameters in NDO and OAB. The effect of BoNTA in treating LUTS dysfunction appears to be overestimated in lower as opposed to higher LE studies.

Defining a Patient-Reported Outcome Measure for Urethral Stricture Surgery

BACKGROUND A systematic literature review did not identify a formally validated patient-reported outcome measure (PROM) for urethral stricture surgery. OBJECTIVE Devise a PROM for urethral stricture surgery and evaluate its psychometric properties in a pilot study to determine suitability for wider implementation. DESIGN, SETTING, AND PARTICIPANTS Constructs were identified from existing condition-specific and health-related quality of life (HRQoL) instruments. Men scheduled for urethroplasty were prospectively enrolled at five centres. INTERVENTION Participants self-completed the draft PROM before and 6 mo after surgery. MEASUREMENTS Question sets underwent psychometric assessment targeting criterion and content validity, test-retest reliability, internal consistency, acceptability, and responsiveness. RESULTS AND LIMITATIONS A total of 85 men completed the preoperative PROM, with 49 also completing the postoperative PROM at a median of 146 d; and 31 the preoperative PROM twice at a median interval of 22 d for test-retest analysis. Expert opinion and patient feedback supported content validity. Excellent correlation between voiding symptom scores and maximum flow rate (r = -0.75), supported by parallel improvements in EQ-5D visual analogue and time trade-off scores, established criterion validity. Test-retest intraclass correlation coefficients ranged from 0.83 to 0.91 for the total voiding score and 0.93 for the construct overall; Cronbachs α was 0.80, ranging from 0.76 to 0.80 with any one item deleted. Item-total correlations ranged from 0.44 to 0.63. These values surpassed our predefined thresholds for item inclusion. Significant improvements in condition-specific and HRQoL components following urethroplasty demonstrated responsiveness to change (p < 0.0001). Wider implementation and review of the PROM will be required to establish generalisability across different disease states and for more complex interventions. CONCLUSIONS This pilot study has defined a succinct, practical, and psychometrically robust PROM designed specifically to quantify changes in voiding symptoms and HRQoL following urethral stricture surgery.

Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair

To identify candidate materials which have sufficient potential to be taken forward for an in vivo tissue‐engineering approach to restoring the tissue structure of the pelvic floor in women with stress urinary incontinence (SUI) or pelvic organ prolapse (POP).

Are biomechanical properties predictive of the success of prostheses used in stress urinary incontinence and pelvic organ prolapse? A systematic review

Progressive weakness in pelvic floor tissues is extremely common and leads to the distressing problems of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). There has been extensive work on a vast array of materials spanning synthetics, autografts, allografts, and xenografts. Uniaxial testing of materials has been used to predict their success and rates of erosion. We aimed to compare the uniaxial properties of prostheses to native paravaginal tissue and correlate these to their success and erosion rates.

Developing a tissue engineered repair material for treatment of stress urinary incontinence and pelvic organ prolapse—which cell source?

Synthetic non‐absorbable meshes are widely used to augment surgical repair of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however, there is growing concern such meshes are associated with serious complications. This study compares the potential of two autologous cell sources for attachment and extra‐cellular matrix (ECM) production on a biodegradable scaffold to develop tissue engineered repair material (TERM).

Tissue engineering in urethral reconstruction--an update.

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty.

The placebo effect in overactive bladder syndrome

Overactive bladder syndrome (OAB) is a condition that involves urinary urgency and affected individuals are usually treated with behavioral therapy and antimuscarinic agents as first-line therapies. Existing evidence from clinical trial data suggests that a positive placebo effect occurs in patients receiving treatment for OAB. In our systematic Review of placebo-controlled, randomized trials in OAB, we show statistically significant improvements in three patient-reported outcomes—incontinence episodes per day, micturition episodes per day and mean micturition volume from baseline—after placebo in randomized studies for OAB. The findings could highlight the brains role in the pathophysiology of OAB or the role of additional bladder training conducted as part of OAB clinical trials. More research is needed to determine the underlying mechanisms of the placebo effect in OAB.

Management of anterior urethral stricture: an evidence-based approach

Purpose of review To provide a review of the latest evidence on the management of anterior urethral strictures. Recent findings A continuing role exists for urethrotomy or dilatation in the management of urethral strictures as first-line therapy in selected patients. In those patients with bulbar strictures who fail or are not suitable for these procedures, an anastomotic urethroplasty, and if not feasible a substitution urethroplasty using either a flap or oral mucosal graft either by a dorsal, lateral or ventral onlay approach should be considered. For penile strictures, a ventral onlay procedure using skin can be considered except in cases of lichen sclerosis when an onlay procedure utilizing oral mucosa provides the best results using either a one-stage or two-stage approach. Summary Various options exist for the management of anterior urethral stricture disease. The ‘reconstructive ladder’ has served to guide urologists over the years. The selection of the correct procedure should be patient-centred and based on the latest evidence.