Frank Van der Aa

The Artificial Urinary Sphincter After a Quarter of a Century: A Critical Systematic Review of Its Use in Male Non-neurogenic Incontinence

CONTEXT The artificial urinary sphincter (AUS) has historically been considered the gold standard for the surgical management of non-neurogenic stress urinary incontinence (SUI) in men. As new surgical alternatives attempt to offer alternatives to treat male SUI, a contemporary assessment of the evidence supporting the use of AUS appears mandatory for clinical decision making. OBJECTIVE To conduct a critical systematic review of long-term outcomes after AUS implantation in male patients with non-neurogenic SUI. EVIDENCE ACQUISITION A literature search was conducted in PubMed/Medline and Embase databases using the keywords urinary incontinence and urinary sphincter, artificial and male, restricted to articles published in Dutch, English, French, and German between 1989 and 2011. Studies were included if they reported outcomes after AUS implantation in patients with non-neurogenic SUI with a minimum follow-up of 2 yr. Studies with heterogeneous populations were included if information about non-neurogenic patients was displayed separately. EVIDENCE SYNTHESIS Twelve reports were identified, gathering data about 623 patients. Only three studies were prospective. Continence, evaluated only by patient-reported pad use and various questionnaires, was achieved in 61-100% of cases (no pad or one pad per day). Dry rates (no pad) were only available in seven studies and varied from 4% to 86%. A pooled analysis showed that infection or erosion occurred in 8.5% of cases (3.3-27.8%), mechanical failure in 6.2% of cases (2.0-13.8%), and urethral atrophy in 7.9% (1.9-28.6%). Reoperation rate was 26.0% (14.8-44.8%). Patient satisfaction was evaluated in four studies with four different tools and seems to improve after AUS implantation. CONCLUSIONS Quality of evidence supporting the use of AUS in non-neurogenic male patients with SUI is low, based on heterogeneous data, low-quality studies, and mostly out-of-date efficacy outcome criteria. AUS outcomes need to be revisited to be compared with new surgical alternatives, all of which should be prospectively evaluated according to current evidence-based medicine standards.

Identification of telocytes in the upper lamina propria of the human urinary tract

The upper lamina propria (ULP) area of interstitial cells (IC) has been studied extensively in bladder, but is rather unexplored in the rest of the urinary tract. This cell layer is intriguing because of the localization directly underneath the urothelium, the intercellular contacts and the close relationship with nerve endings and capillaries. In this study, we examine the ULP layer of IC in human renal pelvis, ureter and urethra, and we make a comparison with ULP IC in bladder. Tissue was obtained from normal areas in nephrectomy, cystectomy and prostatectomy specimens, and processed for morphology, immunohistochemistry and electron microscopy. A morphological and immunohistochemical phenotype for the ULP IC was assessed and region‐dependent differences were looked for. The ULP IC in renal pelvis, ureter and urethra had a similar ultrastructural phenotype, which differed somehow from that of bladder IC, that is, thinner and longer cytoplasmic processes, no peripheral actin filaments and presence of dense core granules and microtubules. Together with their immunohistochemical profile, these features are most compatible with the phenotype of telocytes, a recently discovered group of stromal cells. Based on their global ultrastructural and immunohistochemical phenotype, ULP IC in human bladder should also be classified as telocytes. The most striking immunohistochemical finding was the variable expression of oestrogen receptor (ER) and progesterone receptor (PR). The functional relevance of ULP telocytes in the urinary tract remains to be elucidated, and ER and PR might therefore be promising pharmacological research targets.

Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie's disease.

BACKGROUND Peyronies disease (PD) is a connective tissue disorder of the tunica albuginea (TA). Currently, no gold standard has been developed for the treatment of the disease in its active phase. OBJECTIVE To test the effects of a local injection of adipose tissue-derived stem cells (ADSCs) in the active phase of a rat model of PD on the subsequent development of fibrosis and elastosis of the TA and underlying erectile tissue. DESIGN, SETTING, AND PARTICIPANTS A total of 27 male 12-wk-old Sprague-Dawley rats were divided in three equal groups and underwent injection of vehicle (sham), 0.5-μg [corrected] transforming growth factor (TGF)-β1 in a 50-μl vehicle in either a PD or a PD plus ADSC group in the dorsal aspect of the TA. INTERVENTION The sham and PD groups were treated 1 d after TGF-β1 injection with intralesional treatment of vehicle, and the PD plus ADSC group received 1 million human-labeled ADSCs in the 50-μl vehicle. Five weeks after treatment, six rats per group underwent erectile function measurement. Following euthanasia, penises were harvested for histology and Western blot. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The ratio of intracavernous pressure to mean arterial pressure (ICP/MAP) upon cavernous nerve stimulation, elastin, and collagen III protein expression and histomorphometric analysis of the penis. Statistical analysis was performed by analysis of variance followed by the Tukey-Kramer test for post hoc comparisons or the Mann-Whitney test when applicable. RESULTS AND LIMITATIONS Erectile function significantly improved after ADSC treatment (ICP/MAP 0.37 in PD vs 0.59 in PD plus ADSC at 5-V stimulation; p=0.03). PD animals developed areas of fibrosis and elastosis with a significant upregulation of collagen III and elastin protein expression. These fibrotic changes were prevented by ADSC treatment. CONCLUSIONS This study is the first to test stem cell therapy in an animal model of PD. Injection of ADSCs into the TA during the active phase of PD prevents the formation of fibrosis and elastosis in the TA and corpus cavernosum.

Long-term follow-up of sacral neuromodulation for lower urinary tract dysfunction.

To report our long‐term experience of sacral neuromodulation (SNM) for various lower urinary tract dysfunctions but with a focus on efficacy, safety, re‐interventions and degree of success.

Characterization of upper lamina propria interstitial cells in bladders from patients with neurogenic detrusor overactivity and bladder pain syndrome

The upper lamina propria (ULP) area of interstitial cells (IC) in bladder has been studied for more than a decade in several species including human beings. Nevertheless there is still lack of uniformity in terminology of this cell layer. The aim of the present study was to add new data to the morphological and immunohistochemical phenotype of these cells and to find out whether this phenotype is changed in bladders from patients with neurogenic detrusor overactivity (NDO) and bladder pain syndrome (BPS). Bladder tissue was obtained from a control group and from patients with NDO and BPS. Samples were processed for morphology, electron microscopy and immunohistochemistry. A morphological and immunohistochemical phenotype for the ULP IC was assessed and changes in this phenotype were looked for in samples from patients with NDO and BPS. The ULP IC were characterized ultrastructurally by the presence of actin filaments with densifications, many caveolae and abundant rough endoplasmic reticulum (RER); on immunohistochemistry ULP IC were immunoreactive for α‐sma, vimentin, CD10 and podoplanin and categorized as interstitial Cajal‐like cells (ICLC). In NDO and BPS bladders we found a phenotypical shift towards a fibroblastic phenotype which was even more pronounced in the NDO group. In both groups there was also an increased presence in ULP lymphocytes. The ULP area in the human bladder contains a population of ICLC with distinct ultrastructural morphology and immunohistochemical phenotype. Their unique α‐sma+/desmin–/CD34– phenotype allows studying this population in various bladder disorders. In bladders form patients with BPS and NDO, we observed these ULP ICLC to shift towards a fibroblast phenotype.

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned.

Multipotent Stromal Cell Therapy for Cavernous Nerve Injury-Induced Erectile Dysfunction

INTRODUCTION Erectile dysfunction (ED) following radical prostatectomy (RP) is a result of inadvertent damage to the cavernous nerves that run close to the prostate capsula. The mechanisms behind the development of post-RP ED are increasingly recognized and include cavernosal fibrosis and cavernosal smooth muscle apoptosis, resulting from cavernous nerve degeneration due to neuropraxia. In recent years, cell-based therapies have received increasing attention regarding their potential for recovery of erectile function following cavernous nerve injury (CNI). Multipotent stromal cells (MSCs) are an attractive cell source for this application based on their regenerative potential and their clinical applicability. AIM To review available evidence on the efficacy and mechanisms of action of MSC application for the treatment of ED, with an emphasis on ED following CNI. METHODS A nonsystematic review was conducted on the available English literature between 1966 and 2011 on the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar, and PubMed. RESULTS MSCs from both bone marrow and adipose tissue have shown beneficial effects in a variety of animal models for ED. While MSC application in chronic disease models such as diabetes, aging, and hyperlipidemia may result in cell engraftment and possibly MSC differentiation, this observation has not been made in the acute CNI rat model. In the latter setting, MSC effects seem to be established by cell recruitment toward the major pelvic ganglion and local paracrine interaction with the host neural tissue. CONCLUSIONS While the type of model may influence the mechanisms of action of this MSC-based therapy, MSCs generally display efficacy in various animal models for ED. Before translation to the clinic is established, various hurdles need to be overcome.

Metabolic Changes after Urinary Diversion

Urinary diversion is performed on a regular basis in urological practice. Surgeons tend to underestimate the metabolic effects of any type of diversion. From the patients perspective, diarrhea is the most bothersome complaint after urinary diversion. This might be accompanied by malabsorption syndromes, such as vitamin B12 deficiency. Electrolyte abnormalities can occur frequently such as hyperchloremic metabolic acidosis, or less frequently such as hypokalemia, hypocalcaemia, and hypomagnesaemia. Bone health is at risk in patients with urinary diversion. Some patients might benefit from vitamin D and calcium supplementation. Many patients are also subject to urinary calculus formation, both at the level of the upper urinary tract as in intestinal reservoirs. Urinary diversion can affect hepatic metabolism, certainly in the presence of urea-splitting bacteria. The kidney function has to be monitored prior to and lifelong after urinary diversion. Screening for reversible causes of renal deterioration is an integral part of the followup.

The use of sling vs sphincter in post‐prostatectomy urinary incontinence

The artificial urinary sphincter (AUS) is considered the ‘gold standard’ in post‐prostatectomy urinary incontinence. However, in recent years, male slings have gained much popularity due to the ease of surgery, good functional results and low complications rates. This review systematically shows the evidence for the different sling systems, describes the working mechanism, and compares their efficacy against that of the AUS. Furthermore subgroups of patients are defined who are not suited to undergo sling surgery.

Landmarks in erectile function recovery after radical prostatectomy.

The description of the nerve-sparing technique of radical prostatectomy by Walsh was one of the major breakthroughs in the surgical treatment of prostate cancer in the 20th century. However, despite this advance and consequent technological refinements to nerve-sparing surgery, a large proportion of men still suffer from erectile dysfunction (ED) as a complication of prostatectomy. A plethora of therapeutic approaches have been proposed to optimize erectile function recovery in these patients. Several preclinical and translational studies have shown benefits of therapies including PDE5 inhibitor (PDE5I) treatment, immunomodulation, neurotrophic factor administration, and regenerative techniques, such as stem cell therapy, in animal models. However, most of these approaches have either failed to translate to clinical use or have yet to be studied in human subjects. Penile rehabilitation with PDE5Is is currently the most commonly used clinical strategy, in spite of the absence of solid clinical evidence to support its use.