Surgery for female urethral stricture.

BACKGROUND: Female urethral stricture (FUS) is a rare entity that causes great morbidity and suffering in those affected. As the available scientific data is sparce, there are no formal guidelines or standard of care for this disease. METHODS: This is a narrative review of the surgical management for female urethral stricture. The literature review was performed on PubMed. Articles were limited to English, but there was no limitation in terms of date. RESULTS: Management of FUS is divided between endoscopic and open surgical repair. Urethral dilation with or without urethrectomy can be offered as a first-line treatment. However, the rate of success of this procedure remains inferior to open surgical repair, and its efficacy decreases with the number of previous dilations. For distal urethral strictures, distal urethrectomy and advancement meatoplasty may be considered. Vaginal flaps are readily available, easy to harvest, well-vascularized, and allow for a dorsal or ventral orientation urethroplasty. The results of this procedure are promising, but most studies are small and retrospective. Labia flaps are easily accessible, wet, hairless, and elastic. The main limitations with the use of vaginal or labial tissues are co-existing conditions such as lichen sclerosis or vaginal atrophy, which may affect future results. Vaginal and labial graft urethroplasty can be used when it is not possible to mobilize an adequate flap. Stricture-free rates of this technique are variable. In cases of more severe stricture, an augmentation urethroplasty using buccal mucosa graft may be necessary. The techniques used in FUS replicate those for male urethral strictures, where both ventral and dorsal approaches can be utilized. CONCLUSIONS: Although there is growing interest in the field, the optimal management of FUS remains to be determined.

Bladder outlet obstruction in women: Scope of the problem and differential diagnosis.

INTRODUCTION: The prevalence, formal definition, and diagnostic criteria of bladder outlet obstruction in owmen have not been clearly defined. METHODS: This is a literature review of the definition of BOO in women, its prevalence, as well as its differential diagnosis. RESULTS: The main causes of BOO in women are divided into functional and anatomic conditions. Functional etiologies include detrusor external sphincter dyssynergia, dysfunctional voiding, Fowler's syndrome, and primary bladder neck obstruction. Anatomic causes can be further divided into extrinsinc and intrinsic conditions. Intrinsic etiologies include urethral stricture and urethral diverticula, whereas extrinsic causes comprise pelvic organ prolapse, post anti-incontinence surgery, and Skene's gland cyst or abscess. CONCLUSIONS: There are multiple etiologies to BOO in women, and this condition is most probably underdiagnosed, owing to a lack of consensus for a standard definition.

Voiding efficiency in children is significantly impaired by the presence of the urethral catheter during pressure-flow studies.

BACKGROUND: Little is known about the effect of catheterization during pressure-flow studies (PFS) on voiding efficiency in children. Our objective was to determine the effect of urethral catheterization on Qmax and flow index (FI) during PFS compared to the free flow of uroflowmetry (UF). METHODS: We retrospectively reviewed 63 consecutive children who underwent UF and PFS at our center on the same day (2019-2022). Voiding data was available for 46 patients. Patients first underwent a UF with full bladder, then PFS after urethral catheter insertion. Patients with urethral pathologies (n = 6), on clean intermittent catheterization (CIC) (n = 2) and with major comorbidities (n = 2) were excluded. Indications for UF/PFS were LUTS, recurrent UTIs, incontinence or neurosurgical pre-operative evaluation. Data was collected from the UF and the PFS and compared using paired t-test. The idealized Qmax and flow index (FI) were calculated for UF and PFS using the formulas described by Franco et al.: Male Qmax = 11.26 + 0.0701(TBC [total bladder capacity]) - 0.0000513(TBC); Female Qmax = 10.723 + 0.073(TBC) - 0.0000423(TBC), FI = Actual Qmax/Expected Qmax (Franco and et al., 2016; Franco et al., 2018; Franco and et al., 2016). RESULTS: Median age was 7 years old (IQR 5-11). Twenty-one (40%) patients were male and 32 (60%) patients were female. Of the 53 patients, 3 boys and 4 girls (n = 7; 13%) were unable to void with the catheter in place during PFS but able to void after its removal. Of the remaining 46 cases, the Qmax during PFS was 5 mL/s slower than the Qmax recorded on the UF without catheter, representing a decrease of 29% (12.3 vs 17.3 mL/s; p < 0.0001). The impact of urethral catheter during PFS was more important in males vs females (Qmax decreased by 7.7 vs 3.3 mL/s, or 45 vs 19%). The mean FI during PFS was 44%, which was a 30% reduction compared to the 74% FI obtained with UF (p < 0.00001). In males, the FI decreased by 37% on PFS, whereas it decreased 26% in females, similar to the Qmax decrease. CONCLUSIONS: Voiding efficiency, as assessed by Qmax and FI, is decreased during PFS compared to uroflow studies. Our data documents for the first time the impact of urethral catheterization on pediatric voiding efficiency. Abnormal flow rates and elevated PVRs should be used to guide patient management only if obtained by uroflow. Prospective validation comparing free flow with PFS studies will help characterize the impact of urethral catheter relative to bladder pathology, age, gender and catheter size used.

Sodium-Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study.

OBJECTIVE: To determine whether sodium-glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events. RESEARCH DESIGN AND METHODS: We conducted a multisite, population-based, new-user, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum's de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% CIs of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models. RESULTS: SGLT2 inhibitor (n = 453,560) and GLP-1RA (n = 375,997) users had a median follow-up ranging from 1.5 to 2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer compared with GLP-1RAs (HR 0.90, 95% CI 0.81-1.00). Similarly, when compared with DPP-4 inhibitors (n = 853,186), SGLT2 inhibitors (n = 347,059) were not associated with an increased risk of bladder cancer (HR 0.99, 95% CI 0.91-1.09) over a median follow-up ranging from 1.6 to 2.6 years. Results were consistent across sensitivity analyses. CONCLUSIONS: Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer compared with GLP-1RAs or DPP-4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence.

Adaptation to partial urethral obstruction in healthy aging LOU rats and the role of nerve growth factor signaling pathway in the bladder.

AIM: Aging is associated with poor ability to adapt to stress and abnormal nerve growth factor (NGF) profile. Lower urinary tract symptoms frequently disturb the quality of life of the aging population with no optimal treatment for both genders. The aim of the study was to compare the bladder response to bladder outflow obstruction in young and old LOU rats, a model of healthy aging that does not develop insulin resistance, and its relation to proNGF/NGF imbalance. METHODS: 6- and 36-month-old female LOU rats were subjected to partial bladder urethral obstruction (PUO) for 2 weeks. Morphometric parameters (body and bladder weight) and glycemia were evaluated. Cystometry was carried out to measure functional parameters followed by ex vivo assessment of muscle strip contractile characteristics. Tissue proteins were examined by immunoblotting and morphology was examined by microscopy. RESULTS: Body weight and glycaemia were not affected by surgery. PUO increases significantly bladder weight with increased thickness and fibrosis of the bladder wall as revealed by histological examination in both age groups. Cystometry showed that old PUO rats had a significant reduction in the intercontraction interval and the bladder capacity, a pattern opposite to young rats with PUO. Contractile properties of bladder strip were not affected by age or PUO. On the molecular level, the old rats had lower abundance of the mature NGF relative to proNGF, with signs of p75NTR activation suggested by the higher expression of TNF-α and JNK phosphorylation in the bladder tissue. CONCLUSION: Bladder adaptation to PUO occurs only in young LOU rats to maintain efficient bladder contractility. Old LOU rats display proNGF/NGF imbalance and the associated p75NTR activation. This can further induce tissue damage and degeneration through activation of JNK pathway and release of TNF-α which in turn interferes with the necessary bladder adaptation.

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder.

The extracellular matrix of the bladder consists mostly of type I and III collagen, which are required during loading. During bladder injury, there is an accumulation of collagen that impairs bladder function. Little is known about the genes that regulate production of collagens in the bladder. We demonstrate that the transcription factor Odd-skipped related 1 (Osr1) is expressed in the bladder mesenchyme and epithelium at the onset of development. As development proceeds, Osr1 is mainly expressed in mesenchymal progenitors and their derivatives. We hypothesized that Osr1 regulates mesenchymal cell differentiation and production of collagens in the bladder. To test this hypothesis, we examined newborn and adult mice heterozygous for Osr1, Osr1+/-. The bladders of newborn Osr1+/- mice had a decrease in collagen I by western blot analysis and a global decrease in collagens using Sirius red staining. There was also a decrease in the cellularity of the lamina propria, where most collagen is synthesized. This was not due to decreased proliferation or increased apoptosis in this cell population. Surprisingly, the bladders of adult Osr1+/- mice had an increase in collagen that was associated with abnormal bladder function; they also had a decrease in bladder capacity and voided more frequently. The results suggest that Osr1 is important for the differentiation of mesenchymal cells that give rise to collagen-producing cells.

Is Early Surgical Treatment for Benign Prostatic Hyperplasia Preferable to Prolonged Medical Therapy: Pros and Cons.

Background and objectives: Treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) has shifted over the last decades, with medical therapy becoming the primary treatment modality while surgery is being reserved mostly to patients who are not responding to medical treatment or presenting with complications from BPH. Here, we aim to explore the evidence supporting or not early surgical treatment of BPH as opposed to prolonged medical therapy course. Materials and Methods: The debate was presented with a "pro and con" structure. The "pro" side supported the early surgical management of BPH. The "con" side successively refuted the "pro" side arguments. Results: The "pro" side highlighted the superior efficacy and cost-effectiveness of surgery over medical treatment for BPH, as well as the possibility of worse postoperative outcomes for delayed surgical treatment. The "con" side considered that medical therapy is efficient in well selected patients and can avoid the serious risks inherent to surgical treatment of BPH including important sexual side effects. Conclusions: Randomized clinical trials comparing the outcomes for prolonged medical therapy versus early surgical treatment could determine which approach is more beneficial in the long-term in context of the aging population. Until then, both approaches have their advantages and patients should be involve in the treatment decision.

Multicentered Assessment of Clinical Outcomes and Factors Associated With Failure of the Adjustable TransObturator Male System (ATOMS).

OBJECTIVE: To assess postoperative outcomes from the Adjustable TransObturator Male System (ATOMS) and identify factors influencing failure to achieve continence. PATIENTS AND METHODS: A multicentered analysis was performed on all patients treated for postprostatectomy incontinence using the third-generation ATOMS at 9 Canadian tertiary referral centers. The primary outcome was continence (defined as requiring ≤1 pad postoperatively for patients requiring ≥2 pads preoperatively and 0 pads for those requiring 1 pad preoperatively). Secondary outcomes included improvement (>50% change in pad use), patient satisfaction, explantation, and postoperative complications. RESULTS: Two hundred and eighty nine patients with a mean age of 68.9 years were analyzed. Pre-operatively mean pad per day use was 4.2 (1-12), 31.5% of patients reported severe incontinence (≥5 pads/day), 33.9% had concurrent radiotherapy and 19.4% had failed previous incontinence surgery. Overall continence rate was 73.3% (n = 212) at a mean follow-up of 19.6 months. More than eighty nine percent (89.3%) (n = 258) of patients experienced >50% improvement, 84.4% (n = 244) of patients were satisfied with the results of surgery. More than seven percent (7.9%) (n = 23) required device explantation. On multivariate Cox regression analysis, concurrent radiotherapy (hazard ratio [H.R.] 2.3, P < .001), diabetes (H.R. 2.2, P = .007) and increased pre-operative pad usage (H.R. 1.1, P = .02) were each associated with failure to achieve continence, while patient age (P = .60), obesity (P = .08), prior urethral stenosis (P = .56), and prior incontinence surgery (P = .13) were not. Radiation therapy was also associated with device explantation (H.R. 2.7, P = .02). CONCLUSION: ATOMS is a safe and efficacious for treatment of postprostatectomy incontinence. However, patients with prior radiation, increased pre-operative pad use, or diabetes are less likely to achieve continence.

Receptor GPR91 contributes to voiding function and detrusor relaxation mediated by succinate.

AIM: Succinate activates the receptor GPR91 identified in the bladder. The present study aims to unravel the mechanisms of bladder relaxation by succinate and how the receptor is involved in structural and functional changes of the bladder. METHODS: Physiological recordings of bladder function were carried out by cystometry and organ bath from C57BL/6 mice, homozygous GPR91-/- mice, and Sprague-Dawley (SD) rats. GPR91 expression was confirmed by polymerase chain reaction and tissue morphology was examined by light (Masson trichrome) and fluorescence microscopy. Nitric oxide (NO) and ATP secretion were measured. RESULTS: Bladders of GPR91 KO mice had a greater mass to body weight ratio with a thicker bladder wall compared to C57BL/6 mice. They also displayed increased basal and maximal bladder pressures, and decreased intercontraction intervals, bladder capacity, micturition volume, and compliance. During cystometry, bladders of SD rats and C57BL/6 mice instilled with succinate (10 mM) showed signs of relaxation while bladders of GPR91 KO mice were unresponsive. Similarly, in organ bath, succinate relaxed bladder strips preincubated with carbachol, except GPR91 KO ones. Relaxation was stronger in the presence of urothelium and independent of NO synthesis. Bladder strips from all mice groups showed similar responses to KCl, carbachol, and electrical stimulation. In vitro, succinate increased NO secretion in urothelial cell culture of both C57BL6 and GPR91 KO mice while ATP secretion was potently decreased by succinate in C57BL6 culture only. CONCLUSION: Succinate through GPR91 is essential to bladder structure and contraction. GPR91 relaxes the detrusor partially by decreasing urothelial ATP secretion.

Antagonism of proNGF or its receptor p75NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction.

AIMS/HYPOTHESIS: Although 80% of diabetic patients will suffer from voiding difficulties and urinary symptoms, defined as diabetic voiding dysfunction (DVD), therapeutic targets and treatment options are limited. We hypothesise that the blockade of the pro-nerve growth factor (NGF)/p75 neurotrophin receptor (p75NTR) axis by an anti-proNGF monoclonal antibody or by a small molecule p75NTR antagonist (THX-B) can restore bladder remodelling (represented by bladder weight) in an animal model of DVD. Secondary outcomes of the study include improvements in bladder compliance, contractility and morphology, as well as in voiding behaviour, proNGF/NGF balance and TNF-α expression. METHODS: In a streptozotocin-induced mouse model of diabetes, diabetic mice received either a blocking anti-proNGF monoclonal antibody or a p75NTR antagonist small molecule as weekly systemic injections for 4 weeks. Animals were tested at baseline (at 2 weeks of diabetes induction), and after 2 and 4 weeks of treatment. Outcomes measured were voiding function with voiding spot assays and cystometry. Bladders were assessed by histological, contractility and protein expression assays. RESULTS: Diabetic mice showed features of DVD as early as 2 weeks after diabetes diagnosis (baseline) presented by hypertrophy, reduced contractility and abnormal cystometric parameters. Following treatment initiation, a twofold increase (p < 0.05) in untreated diabetic mouse bladder weight and thickness compared with non-diabetic controls was observed, and this change was reversed by p75NTR antagonism (37% reduction in bladder weight compared with untreated diabetic mice [95% CI 14%, 60%]) after 4 weeks of treatment. However, blocking proNGF did not help to reverse bladder hypertrophy. While diabetic mice had significantly worse cystometric parameters and contractile responses than non-diabetic controls, proNGF antagonism normalised bladder compliance (0.007 [Q1-Q3; 0.006-0.009] vs 0.015 [Q1-Q3; 0.014-0.029] ml/cmH2O in untreated diabetic mice, representing 62% reduction [95% CI 8%, 110%], p < 0.05) and contractility to KCl, carbachol and electrical field stimulation (p < 0.05 compared with the diabetic group) after 2 weeks of treatment. These effects were not observed after 4 weeks of treatment with proNGF antagonist. p75NTR antagonism did not show important improvements in cystometric parameters after 2 weeks of treatment. Slightly improved bladder compliance (0.01 [Q1-Q3; 0.009-0.012] vs 0.013 [Q1-Q3; 0.011-0.016] ml/cmH2O for untreated diabetic mice) was seen in the p75NTR antagonist-treated group after 4 weeks of treatment with significantly stabilised contractile responses to KCl, carbachol and electric field stimulation (p < 0.05 for each) compared with diabetic mice. Bladder dysfunction observed in diabetic mice was associated with a significant increase in bladder proNGF/NGF ratio (3.1 [±1.2] vs 0.26 [±0.04] ng/pg in control group, p < 0.05 at week 2 of treatment) and TNF-α (p < 0.05). The proNGF/NGF ratio was partially reduced (about 60% reduction) with both treatments (1.03 [±0.6] ng/pg for proNGF antibody-treated group and 1.4 [±0.76] ng/pg for p75NTR blocker-treated group after 2 weeks of treatment), concomitant with a significant decrease in the bladder levels of TNF-α (p < 0.05), despite persistent hyperglycaemia. CONCLUSIONS/INTERPRETATION: Our findings indicate that blockade of proNGF and the p75NTR receptor in diabetes can impede the development and progression of DVD. The reported improvements in morphological and functional features in our DVD model validates the proNGF/p75NTR axis as a potential therapeutic target in this pathology. Graphical abstract.

Best practices for cystometric evaluation of lower urinary tract function in muriform rodents.

AIMS: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. METHODS: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. RESULTS: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. CONCLUSIONS: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Short-term evaluation of the adjustable bulbourethral male sling for post-prostatectomy urinary incontinence.

OBJECTIVE: The Argus perineal sling is a minimally invasive surgical option to treat post-prostatectomy stress urinary incontinence (PPSUI). This study retrospectively evaluated the short-term clinical outcomes with the Argus sling for PPSUI management and determined the effects of potential preoperative parameters on intraoperative retrograde leak point pressure (RLPP). METHODS: In this retrospective review of 16 men with various degrees of stress incontinence after prostatic surgery who underwent Argus sling, PPSUI was evaluated by pad usage, urodynamics, 24-hour pad weight, and validated questionnaires. Findings before and a minimum of 6 months after sling placement were compared. "Cure" was defined as no pad usage or the use of 1 pad for security; "improvement" was defined as a reduction in daily pad use by >50%. RESULTS: After a mean (±SD) follow-up of 9.75 ± 3.51 months, 62.5% of patients were cured, 18.75% were improved, and 18.75% were still incontinent. Preoperative 24-hour pad weight was positively correlated with RLPP (P = .0121, r = 0.6286). Mean RLPP was 37.93 ± 3.45 cmH2 O. During follow-up, 44% of men had transient perineal or scrotal pain managed conservatively. Sling explantation, reported in 3 of 16 patients, was associated with urethral erosion or previous radiation therapy. CONCLUSION: The Argus male sling can lead to satisfactory results in carefully selected patients. Increased stress urinary incontinence severity based on 24-hour pad weight required higher RLPP to achieve continence. Favorable satisfaction variables and quality of life scores are affected by appropriate intraoperative tensioning pressure.

Beta-3 Adrenoceptor Signaling Pathways in Urothelial and Smooth Muscle Cells in the Presence of Succinate.

Succinate, an intermediate metabolite of the Krebs cycle, can alter the metabolomics response to certain drugs and controls an array of molecular responses in the urothelium through activation of its receptor, G-protein coupled receptor 91 (GPR91). Mirabegron, a ß3-adrenergic receptor (ß3-AR) agonist used to treat overactive bladder syndrome (OAB), increases intracellular cAMP in the detrusor smooth muscle cells (SMC), leading to relaxation. We have previously shown that succinate inhibits forskolin-stimulated cAMP production in urothelium. To determine whether succinate interferes with mirabegron-mediated bladder relaxation, we examined their individual and synergistic effect in urothelial-cell and SMC signaling. We first confirmed ß3-AR involvement in the mirabegron response by quantifying receptor abundance by immunoblotting in cultured urothelial cells and SMC and cellular localization by immunohistochemistry in rat bladder tissue. Mirabegron increased cAMP levels in SMC but not in urothelial cells, an increase that was inhibited by succinate, suggesting that it impairs cAMP-mediated bladder relaxation by mirabegron. Succinate and mirabegron increased inducible nitric oxide synthesis and nitric oxide secretion only in urothelial cells, suggesting that its release can indirectly induces SMC relaxation. Succinate exposure decreased the expression of ß3-AR protein in whole bladder in vivo and in SMC in vitro, indicating that this metabolite may lead to impaired pharmacodynamics of the bladder. Together, our results demonstrate that increased levels of succinate in settings of metabolic stress (e.g., the metabolic syndrome) may lead to impaired mirabegron and ß3-AR interaction, inhibition of cAMP production, and ultimately requiring mirabegron dose adjustment for its treatment of OAB related to these conditions.

Bladder overdistension with polyuria in a hypertensive rat model.

AIMS: Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. MATERIALS AND METHODS: Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. RESULTS: Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. CONCLUSIONS: Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology.

Succinate decreases bladder function in a rat model associated with metabolic syndrome.

AIMS: Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function. MATERIALS AND METHODS: Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks. Conscious cystometry was performed at the end of this period. Bladders were collected and used for contractility studies and morphological assessment. Two-way ANOVA was performed to compare between the two strains and student t-tests to compare treatment groups within each strain. RESULTS: Compared to SD rats, Dahl rats showed signs of bladder dysfunction. Succinate treatment led to higher urinary succinate levels and lower bladder capacities compared to saline-treated animals. In SD rats, this was associated with higher collagen content, lower GPR91 expression and an altered bladder nerve profile in the bladder. In succinate-treated Dahl rats, detrusor contractility was reduced and associated with decreased cholinergic innervation and increased collagen content. CONCLUSIONS: It is suggested that succinate negatively affects bladder function via effects through its receptor, GPR91, and that its effects are enhanced in the presence of metabolic disturbance. These findings contribute to our understanding of the pathophysiology of bladder dysfunction, specifically in a metabolic syndrome setting.

Lumbar to sacral root rerouting to restore bladder function in a feline spinal cord injury model: Urodynamic and retrograde nerve tracing results from a pilot study.

AIMS: Lumbar to sacral rerouting surgery can potentially allow voiding via a skin-central nervous system-bladder reflex pathway. Here, we assessed if this surgery was effective in treating neurogenic bladder dysfunction/sphincter in felines. METHODS: Eight cats underwent spinal cord transection (SCT) at thoracic level 10/11. Unilateral L7 to S1 ventral root anastomosis was performed 1 month later in six cats. Two cats served as transection-only controls. Electrical and manual stimulation of L6-S1 dermatomes, and urodynamics were performed at 3, 5, 7, and 9/10 months post transection. At 9/10 months, cats were also evaluated by direct electrophysiological testing of anastomosed roots with urodynamics, then tissue collection and examination of the root anastomosis site and lumbosacral cord ventral horns for cells retrogradely labeled from tracer dye injected 2 weeks earlier into the bladder wall. RESULTS: At 9/10 months, four of six rerouted cats exhibited increased detrusor pressure provoked by cutaneous stimulation, one cat bilaterally. Two cats presented with a voiding stream after ipsilateral cutaneous stimulation at 7 and 9 months. All six rerouted animals showed regrowth of axons from the L7 ventral horn to the bladder, although some aberrant axonal regrowth was also observed. CONCLUSION: L7 to S1 ventral root rerouting below the level of SCT showed successful axonal regrowth to the bladder from the L7 spinal cord segment in all rerouted animals, and induced increased detrusor pressure response to cutaneous stimulation in a subset. This feasibility study paves the way for future animal studies for bladder reinnervation.

Radiation Exposure During Videourodynamics: Establishing Risk Factors.

OBJECTIVES: The use of fluoroscopy during urodynamics can be helpful in the evaluation of patients with lower urinary tract dysfunction. However, fluoroscopy introduces the potential hazards of ionizing radiation, including malignancy. In this study we analyzed the data for radiation exposure during videourodynamic study (VUDS) at our center; we have also tried to establish the factors associated with increased exposure to radiation during VUDS. METHODS: We reviewed all VUDS from August 2010 to May 2011. Patients were included if they were ≥18 years old and had data recorded on total radiation exposure (radcm2 ). Age, sex, body mass index, fluoroscopy time, diagnosis, and urodynamic findings were recorded. Multivariate linear regression analysis was used to identify independent risk factors that influenced increased radiation exposure. RESULTS: A total of 203 videourodynamic studies were assessed in 106 female and 97 male patients with a mean age of 64.3 and body mass index of 26.8. The average fluoroscopy time was 100.2 sec and exposure was 560.9 radcm2 . The most common indication for videourodynamics was incontinence, 40.9%. On multivariate linear regression analysis body mass index, vesico-ureteral reflux, sex, number of fill cycles, and larger capacity were independent predictors of increased radiation exposure. CONCLUSIONS: We have shown that increased radiation exposure as measure with Dose Area Product during VUDS was significantly associated with larger BMI, female gender, larger bladder capacity, presence of VUR, junior operator, and higher number of fill cycles. Further studies are now underway to attempt to reduce exposure based on these findings.

Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer.

BACKGROUND: The use of androgen deprivation therapy in prostate cancer may be associated with an increased risk of anemia, but the evidence remains limited. This study aimed to determine if androgen deprivation is associated with increased risk of anemia in patients newly diagnosed with prostate cancer. METHODS: This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 10,364 men newly diagnosed with nonmetastatic prostate cancer between 1 April 1998 and 30 September 2015. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for anemia (hemoglobin <130 g/L) associated with current and past use of androgen deprivation therapy, compared with nonuse. RESULTS: There were 3,651 incident anemia events during 31,574 person-years of follow-up (rate: 11.6/100 person-years). Current androgen deprivation therapy use was associated with a nearly three-fold increased hazard of anemia, compared with nonuse (23.5 vs. 5.9 per 100 person-years, respectively; HR: 2.90, 95% CI: 2.67, 3.16). The HR was elevated in the first 6 months of use (HR: 2.20, 95% CI: 1.95, 2.48) and continued to be elevated with longer durations of use. Past androgen deprivation therapy use was associated with a lower estimate (HR: 1.27, 95% CI: 1.12, 1.43), which returned closer to the null ≥25 months after treatment discontinuation (HR: 0.95, 95% CI: 0.79, 1.15). CONCLUSIONS: The use of androgen deprivation therapy is associated with increased risk of anemia, which reverses upon treatment discontinuation.

Prospective evaluation of anxiety, pain, and embarrassment associated with cystoscopy and urodynamic testing in clinical practice.

INTRODUCTION: We sought to prospectively assess anxiety, pain, and embarrassment associated with diagnostic cystoscopy and multi-channel urodynamic study (UDS). METHODS: All consecutive patients undergoing diagnostic cystoscopy or UDS in our department over a period of nine months were asked to participate. Two anonymous auto-administered questionnaires were specifically designed to collect basic epidemiological data, document medical history, and assess the quality of information provided, along with prevalence and level (0-10 numerical visual analog rating scale) of anxiety, pain, and embarrassment experienced before and/or during the procedures. Statistical analysis was carried out to identify underlying factors that could have influenced patients' experience and ascertain potential correlations between anxiety, pain, and embarrassment. RESULTS: 101 and 185 patients were respectively evaluated immediately after cystoscopy and UDS. Multivariate analysis repeatedly showed statistical correlations between anxiety, pain, and embarrassment, with regard to prevalence and level of intensity in both cystoscopy and UDS populations. Males and young patients were more likely to present anxiety, pain, or embarrassment during cystoscopy and UDS. Interestingly, patients who reported having received complete information before cystoscopy were significantly more likely to experience anxiety (62.6% vs. 20.0%; p=0.009). CONCLUSIONS: The present study demonstrated the major impact of gender and age on patients' experience. Interestingly, information provided before cystoscopy was reported to have a negative impact on patients' perception of anxiety; this could be partly prevented by optimizing the way information is provided to patients.