Nadir I. Osman

The Underactive Bladder: A New Clinical Concept?

UNLABELLED Detrusor underactivity (DU) is an increasingly recognised cause of lower urinary tract symptoms in both men and women. There has been a lack of research into all aspects of this dysfunction, and as yet, no effective treatments exist. DU can be diagnosed at present only on the basis of an invasive urodynamic study. An international consensus group met at the International Consultation on Incontinence-Research Society and International Continence Society annual meetings in 2014 to consider the feasibility of developing a working definition of a symptom complex associated with DU. Drawing an analogy to detrusor overactivity (urodynamic diagnosis) and overactive bladder (symptom complex), the aim of this process is to help identify affected patients and facilitate further clinical and epidemiological research. PATIENT SUMMARY Bladder underactivity is an underresearched but important cause of urinary symptoms in men and women. In this paper, an international expert group presents a working definition for the symptoms that characterise bladder underactivity, with the aim of facilitating further research in this area.

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).

Fowler's syndrome[mdash]a cause of unexplained urinary retention in young women?

Urinary retention in women is an uncommon and poorly understood condition. In 1986, Fowler and colleagues described a syndrome in young women with unexplained urinary retention associated with polycystic ovary syndrome. The underlying abnormality was a poorly relaxing external urethral sphincter that when studied using concentric needle electromyography showed a distinct abnormal pattern suggesting direct spread of impulses between muscle fibres. These findings were subsequently reproduced by other researchers and in larger patient cohorts, but remain the subject of much debate. A poorly relaxing sphincter is thought to cause increased urethral afferent activity, which inhibits bladder afferent signalling leading to poor bladder sensation and detrusor underactivity. Most studies of Fowlers syndrome are limited due to small cohorts with no control group and a lack of videourodynamic data. Whether Fowlers syndrome represents a distinct cause of urinary retention or results from a maladaptive behaviour and is similar to dysfunctional voiding is unclear. Application of sacral neuromodulation in patients diagnosed with Fowlers syndrome can restore normal voiding, in the absence of any effective pharmacotherapy or surgical treatment.

Silodosin: a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia

Introduction: Silodosin is a new uroselective alpha-blocker with high pharmacological selectivity for the 1A adrenoceptor. It is an effective and well-tolerated treatment in men with lower urinary tract symptoms (LUTS), due to presumed bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH). The efficacy of silodosin is at least equivalent to existing selective alpha-1 antagonists such as tamsulosin. A beneficial consequence of its high selectivity is improved cardiovascular safety and failure to interact with other therapies such as anti-hypertensives and phosphodiesterase type-5 inhibitors. Areas covered: This paper discusses the mechanism of action, uroselectivity and clinical efficacy/tolerability of Silodosin. Additionally, drug interactions and urodynamic effects are reviewed with a focus on ejaculatory dysfunction. Expert opinion: Silodosin is a rapidly efficacious and safe agent in the treatment of LUTS/BPH in men. A lack of clinically important cardiovascular side effects makes it of potential use in the elderly. There is a higher risk of ejaculatory dysfunction, which may lead to discontinuation in younger men. The availability of generic counterparts may make this compound less marketable in countries with social healthcare systems.

Contemporary concepts in the aetiopathogenesis of detrusor underactivity

Detrusor underactivity (DUA) is a poorly understood, yet common, bladder dysfunction, referred to as underactive bladder, which is observed in both men and women undergoing urodynamic studies. Despite its prevalence, no effective therapeutic approaches exist for DUA. Exactly how the contractile function of the detrusor muscle changes with ageing is unclear. Data from physiological studies in animal and human bladders are contradictory, as are the results of the limited number of clinical studies assessing changes in urodynamic parameters with ageing. The prevalence of DUA in different patient groups suggests that multiple aetiologies are involved in DUA pathogenesis. Traditional concepts focused on either efferent innervation or myogenic dysfunction. By contrast, contemporary views emphasize the importance of the neural control mechanisms, particularly the afferent system, which can fail to potentiate detrusor contraction, leading to premature termination of the voiding reflex. In conclusion, the contemporary understanding of the aetiology and pathophysiology of DUA is limited. Further elucidation of the underlying mechanisms is needed to enable the development of new and effective treatment approaches.

A Systematic Review of Surgical Techniques Used in the Treatment of Female Urethral Stricture

CONTEXT Female urethral stricture (FUS) is a rare and challenging clinical entity. Several new surgical techniques have been described for the treatment of FUS, although with the limited number of reports, there is no consensus on best management. OBJECTIVE We evaluated the evidence for surgical interventions reported for treating FUS. EVIDENCE ACQUISITION We performed a systematic review of the PubMed and Scopus databases, classifying the results by surgical technique and type of graft in the case of graft augmentation urethroplasty. EVIDENCE SYNTHESIS A total of 221 patients have been reported on with outcome measures after intervention for FUS. The mean age of women was 51.8 yr of age (range: 22-91). All studies were retrospective case series. There was no consistent definition of FUS nor unified diagnostic criteria. Most studies used a combination of diagnostic tests. Where aetiology was defined, idiopathic and iatrogenic stricture were the two most common causes. Ninety-eight patients underwent prior intervention for FUS, mostly urethral dilatation or urethrotomy. Success was defined as the lack of need for further intervention. Urethral dilatation, assessed in 107 patients, had a mean success rate of 47% at a mean follow-up of 43 mo. Fifty-eight patients had vaginal or labial flap augmentation, with a mean success rate of 91% at 32.1 mo of mean follow-up. Vaginal or labial graft augmentation had a mean success rate of 80% in 25 patients at a mean follow-up of 22 mo. Oral mucosal augmentation, performed in 32 patients, had a mean success rate of 94% at 15 mo of mean follow-up. No instances of de novo stress incontinence were reported. CONCLUSION The techniques of urethroplasty all have a higher mean success rate (80-94%) than urethral dilatation (<50%), although with shorter mean follow-up. Urethroplasty in experienced hands appears to be a feasible option in women who have failed urethral dilatation, although there is a lack of high-level evidence to recommend one technique over another.

Biomaterials for Pelvic Floor Reconstructive Surgery: How Can We Do Better?

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.

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.

Tissue engineered buccal mucosa for urethroplasty: Progress and future directions

PURPOSE Autologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material. RESULTS Few clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis. CONCLUSIONS Tissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.

Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits.

PURPOSE Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation. MATERIALS AND METHODS Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days. RESULTS At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling. CONCLUSIONS Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials.