Surgical techniques in substitution urethroplasty using buccal mucosa for the treatment of anterior urethral strictures

OBJECTIVES: Since the resurgence in the use of buccal mucosa (BM) in substitution urethroplasty in the late 1980s and early 1990s, there has been controversy as to which surgical technique is the most appropriate for its application. METHODS: The authors performed an updated literature review. Several centres have published widely on this topic, and the points considered include the use BM in dorsal onlay grafts, ventral onlay grafts, and tubularised grafts and the role of two-stage procedures. RESULTS: In experienced hands, the outcomes of both dorsal onlay grafts and ventral onlay grafts in bulbar urethroplasty are similar. The dorsal onlay technique is, however, possibly less dependent on surgical expertise and therefore more suitable for surgeons new to the practice of urethroplasty. The complications associated with ventral onlay techniques can be minimised by meticulous surgical technique, but in series with longer follow-up, complications still tend to be more prevalent. In penile urethroplasty, two-stage dorsal onlay of BM (after complete excision of the scarred urethra) still provides the best results, although in certain circumstances a one-stage dorsal onlay procedure is possible. In general, ventral onlay of BM and tube graft procedures in the management of penile strictures are associated with much higher rates of recurrence and should therefore be avoided. CONCLUSIONS: In experienced hands the results of the ventral and dorsal onlay of BM for bulbar urethroplasty are equivalent. Two-stage procedures are preferable in the penile urethra, except under certain circumstances when a one-stage dorsal onlay is feasible

The aging bladder insights from animal models

Alterations in bladder function with aging are very common and are very likely to represent an increasing healthcare problem in the years to come with the general aging of the population. In this review the authors describe the prevalence of lower urinary tract symptoms (LUTS) and comment upon potential mechanisms which may be responsible for the increasing prevalence of lower LUTS with increasing age, based on laboratory studies. It is clear that there is a complex interplay between the various components of the neural innervation structure of the bladder in leading to changes with age, which are likely to underpin the LUTS which are seen in the aging bladder

Delayed repair of pelvic fracture urethral injuries: Preoperative decision-making.

Pelvic fracture urethral injuries comprise one of the most challenging reconstructive procedures in urology. The obliterated or stenosed urethra can usually be effectively repaired by an end-to-end anastomosis (bulbomembranous anastomosis). To achieve this, a progression of surgical steps can be used to make a tension-free anastomosis. Before undertaking surgery it is important to comprehensively assess the patient to define their anatomical defects, in particular the site of the stenosis, the length of the distraction injury and the integrity of the bladder neck, and thus guide preoperative decision-making. Contemporary reports suggest that most pelvic fracture urethral distraction defects (PFUDD) can be adequately managed by a perineal approach. Nevertheless it is essential that all surgeons treating these injuries are familiar with the whole spectrum of operative steps that are necessary to repair PFUDD

Overcoming scarring in the urethra: Challenges for tissue engineering.

Urethral stricture disease is increasingly common occurring in about 1% of males over the age of 55. The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis. An increase in collagen is associated with the loss of the normal vasculature of the normal urethra. The actual incidence differs based on worldwide populations, geography, and income. The stricture aetiology, location, length and patient's age and comorbidity are important in deciding the course of treatment. In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures, review current treatment regimens, and present the challenges of using tissue-engineered buccal mucosa (TEBM) to repair scarring of the urethra. In asking this question we are also mindful that recurrent fibrosis occurs in other tissues-how can we learn from these other pathologies

Could Reduced Fluid Intake Cause the Placebo Effect Seen in Overactive Bladder Clinical Trials? Analysis of a Large Solifenacin Integrated Database

Objective To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from “treatment” continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). Materials and Methods We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. Results Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. Conclusion Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms

Acute In Vivo Response to an Alternative Implant for Urogynecology

Purpose. To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Methods. A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. Results. Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. Conclusions. The acute in vivo response to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues

The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials

Purpose To understand how improvements in the symptoms of overactive bladder (OAB) seen with the b3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect. Methods In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (C50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (B8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination. Results Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy. Conclusions The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit

Onset of action of the beta 3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder

Purpose Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1–2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a b3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies. Methods This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV). Results A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated. Conclusions The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB

European Association of Urology. Position statement on screening for prostate cancer

n/