Clinical and Urodynamic Predictors for Failure of Medical Management with Alpha Blockers in PBNO: A Retrospective Cohort Analysis.

OBJECTIVE: To evaluate the clinical and urodynamic variables that may predict the failure of alpha-blockers in primary bladder neck obstruction (PBNO) patients. Alpha-blockers are useful as a treatment option in patients with PBNO. Nonresponders need to undergo bladder neck incision (BNI). Little is known about the predictive factors determining the success of treatment. MATERIALS AND METHODS: This was a retrospective study, spanning over a period of 8 years. PBNO was diagnosed in the presence of a bladder outlet obstruction index (BOOI) >40 with video-urodynamic evidence of obstruction at the bladder neck. The patients were initially managed with alpha-blockers (alfuzosin and tamsulosin) for 3-6 months, and BNI contemplated when pharmacotherapy failed. The patients with upper tract changes managed with upfront BNI or clean intermittent catheterization were excluded. The data for the international prostate symptom score (IPSS), uroflowmetry, urodynamic studies, and ultrasonography of pre and post-treatment periods were reviewed. Treatment outcomes were defined as complete response (>50% improvement in Qmax and IPSS score) and partial response (30%-50% improvement in Qmax and IPSS score) at 3 or 6 months. RESULTS: Ninety-nine patients were analyzed. 21 patients underwent BNI for the failure of medical management and 31 for recurrence of symptoms at a mean follow-up of 18.8 ± 3.5 months (12-70 months). Independent predictors of failure of pharmacotherapy with alpha-blockers were age (P = .021), Pdet@Qmax (P = .015), and BOOI (P = .019). CONCLUSION: Alpha-blockers are more likely to fail in PBNO in younger patients generating higher voiding pressures and BOOI > 60.

Intradetrusor OnabotulinumtoxinA Injections at the Time of Holmium Laser Enucleation of the Prostate for Men with Severe Storage Symptoms.

Introduction: Intradetrusor onabotulinumtoxinA (OTA) injection is a well-established treatment option for refractory overactive bladder; however, its use at the time of holmium laser enucleation of the prostate (HoLEP) for men with bladder outlet obstruction (BOO) and severe storage symptoms has not been previously reported. Materials and Methods: We retrospectively identified men with BOO and severe storage symptoms who underwent treatment with 200 U of intradetrusor OTA (Botox®) at the time of HoLEP. Patients were propensity score matched to a cohort of HoLEP-only patients based on age, Michigan Incontinence Symptom Index (M-ISI) score, preoperative urinary retention, urge incontinence, and prostate size. Perioperative, postoperative, and patient-reported outcomes were examined between groups. Results: We identified 82 men who underwent HoLEP, including 41 patients in the OTA group and 41 patients in the control group. There was no difference in operative times (59 minutes OTA vs 55 minutes control, p = 0.2), rates of same-day trial of void (TOV) (92% OTA vs 94% control, p = 0.7), or rates of same-day discharge (88% OTA vs 85% control, p = 0.6) between groups. There was no difference in temporary postoperative urinary retention (7% OTA vs 2% control, p = 0.3) between groups. Patients who received OTA injections had a significant reduction in their incontinence scores at 3-month follow-up (M-ISI -8, interquartile range [IQR]: -13 to 0, p < 0.001), whereas control patients did not (M-ISI -5, IQR: -8 to -1, p = 0.2). There was no difference in rates of 90-day complications between groups (OTA 10% vs control 5%, p = 0.7). Conclusions: Intradetrusor OTA at the time of HoLEP is safe and is associated with improved urinary incontinence scores and AUA Symptom Score. Rates of same-day discharge and same-day TOV after HoLEP were not affected by OTA. These findings support the role of OTA as an adjunct to surgical intervention in men with incontinence in the presence of BOO.

Anti-fibrotic effect of tocotrienols for bladder dysfunction due to partial bladder outlet obstruction.

PURPOSE: To investigate potential beneficial effects of tocotrienols which have been suggested to inhibit hypoxia-inducible factor (HIF) pathway, on partial bladder outlet obstruction (PBOO)-induced bladder pathology. MATERIALS AND METHODS: PBOO was surgically created in juvenile male mice. Sham-operated mice were used as controls. Animals received daily oral administration of either tocotrienols (T3) or soybean oil (SBO, vehicle) from day 0 to 13 post-surgery. Bladder function was examined in vivo by void spot assay. At 2 weeks post-surgery, the bladders were subjected to physiological evaluation of detrusor contractility in vitro using bladder strips, histology by H&E staining and collagen imaging, and gene expression analyses by quantitative PCR. RESULTS: A significant increase in the number of small voids was observed after 1 week of PBOO compared to the control groups. At 2 weeks post-surgery, PBOO+SBO mice showed a further increase in the number of small voids, which was not observed in PBOO+T3 group. PBOO-induced decrease in detrusor contractility was similar between two treatments. PBOO induced bladder hypertrophy to the same degree in both SBO and T3 treatment groups, however, fibrosis in the bladder was significantly less prominent in the T3 group than the SBO group following PBOO (1.8- vs. 3.0-fold increase in collagen content compared to the control). Enhanced levels of HIF target genes in the bladders were observed in PBOO+SBO group, but not in PBOO+T3 group compared to the control. CONCLUSIONS: Oral tocotrienol treatment reduced the progression of urinary frequency and bladder fibrosis by suppressing HIF pathways triggered by PBOO.

Intravesical Injection of Botulinum Toxin Type A in Men without Bladder Outlet Obstruction and Post-Deobstructive Prostate Surgery.

PURPOSE: A significant proportion of men without bladder outlet obstruction (BOO) have been reported to have overactive bladders (OAB). This article aimed to review the specific group of reports on the use of botulinum toxin type A (BTX-A) injections into the bladder wall. MATERIALS AND METHODS: Original articles reporting men with small prostates without BOO were identified through a literature search using the PubMed and EMBASE databases. Finally, we included 18 articles that reviewed the efficacy and adverse effects of BTX-A injections in men. RESULTS: Of the 18 articles screened, 13 demonstrated the therapeutic efficacy and adverse effects of BTX-A injections in men. Three studies compared BTX-A injection response between patients without prior prostate surgery and those undergoing prior prostate surgery, including transurethral resection of the prostate and radical prostatectomy (RP). Patients with prior RP experienced better efficacy and had a low risk of side effects. Two studies focused on patients who had undergone prior surgery for stress urinary incontinence, including male sling and artificial urethral sphincter surgery. The BTX-A injection was a safe and effective procedure for this specific group. OAB in men was found to have a different pathophysiology mechanism from that in female patients, which may decrease the efficacy of BTX-A injection in men. However, patients with small prostates and low prostate-specific antigen levels demonstrated better efficacy and tolerability after BTX-A injection. CONCLUSIONS: Although intravesical injection of BTX-A was a good option for controlling refractory OAB in men, the evidence-based guidelines are still limited. Further research is necessary to better understand the role of BTX-A injections on various aspects and histories. Therefore, treating patients using strategies tailored to their individual conditions is important.

Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage-Myofibroblast Transition in Bladder Remodeling.

Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO-induced remodeling is aimed. Four single-strand DNAs are self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-ß1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-ß1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling.

The bladder contractility and bladder outlet obstruction indices in adult women. Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of the bladder contractility index (BCI), bladder outlet obstruction index (BOOI), and the related evidence. This manuscript deals with adult women and follows a previous manuscript reporting on adult men. METHODS: Twenty-nine experts were invited to answer the two-round survey including three foundation questions and 12 survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in women. RESULTS: Eighteen experts participated in the survey with 100% completion. Consensus was noted with regard to 2 of 12 questions, both in the negative. The experts had a consensus that BOOI was neither accurate nor useful and a similar negative trend was noted with regard to BCI. However, there was support, short of consensus, for the utility on an index of bladder contractility and bladder outflow obstruction. Systematic search yielded eight publications pertaining to stress urinary incontinence (n = 6), pelvic organ prolapse (n = 1), and intra-sphincteric botulinum toxin (n = 1). CONCLUSIONS: Experts had significant concerns with regard to the use of the male BCI and BOOI in adult women despite a general recognition of the need for numerical indices of contractility and obstruction. Systematic search showed a striking lack of evidence in this regard.

The bladder contractility and bladder outlet obstruction indices in adult men: Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of Bladder Contractility Index (BCI) and Bladder Outlet Obstruction Index (BOOI) and the related evidence. METHODS: Twenty-eight experts were invited to answer the two-round survey including three foundation questions and 15 survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in men. RESULTS: Nineteen experts participated in the survey with 100% completion. Consensus was noted with regard to 6 of 19 questions. Experts strongly agreed with utility of quantifying bladder contractility and bladder outflow obstruction with near unanimity regarding the latter. There was consensus that BCI and BOOI were accurate, that BCI was clinically useful, and for defining severe bladder outflow obstruction as BOOI > 80. Systematic search yielded 69 publications (BCI 45; BOOI 50). Most studies examined the indices as a continuous variable or by standard cutoffs (BCI 100, 150; BOOI 20, 40). CONCLUSION: There is general agreement among experts on need for indices to quantify bladder contractility and bladder outflow obstruction as well as with regard to accuracy and utility of BCI and BOOI indices. Few studies have examined the discriminant power of existing cutoffs or explored new ones. This is an extraordinary knowledge gap in the field of urology.

Outcomes of bladder neck botulinum toxin injection for female primary bladder neck obstruction-does subjective improvement correlate with an objective assessment?

INTRODUCTION AND HYPOTHESIS: Common options for management of primary bladder neck obstruction (PBNO) in women include medications and surgical treatment. Less invasive treatment such as bladder neck botulinum toxin injection can be an alternate therapy in patients with failed conservative management. In this study, we describe the subjective and objective outcomes, patient satisfaction, and willingness for repeat treatment with bladder neck botulinum toxin injection in females with PBNO. METHODS: A retrospective analysis of ten female PBNO patients managed with bladder neck botulinum toxin injection was performed. Subjective parameters were quantified with symptom assessment, International Prostate Symptom Score (IPSS), and Quality of life (QoL) score. Objective parameters were assessed with maximum flow rate (Qmax) in uroflowmetry and postvoid residual (PVR). RESULTS: The mean pre-treatment IPSS, QoL score, Qmax, PVR was 24.2 ± 5.0, 4.8 ± 0.63, 5.73 ± 3.18 ml/s, and 210 ± 66 ml, respectively. Seven of the ten patients subjectively improved (IPSS 12.9 ± 9.6, QoL2.9 ± 1.6, p < 0.05). Three patients improved objectively (mean Qmax 17.3 ± 2.7 ml/s, PVR 42.7 ± 7.5 ml, p < 0.05). Three patients accepted repeat botulinum toxin injection. Three patients who showed no improvement underwent bladder neck incision with resolution of symptoms. CONCLUSION: Botulinum toxin can be an intermediary therapy in female patients with PBNO who want a minimally invasive procedure.

Inhibitory effects of vibegron, a ß3-adrenoceptor agonist, on the myogenic contractile and mechanosensitive afferent activities in an obstructed rat bladder.

To determine the role of ß3-adrenoceptor agonists on bladder sensory facilitation related to bladder myogenic contractile activities in bladder hyperactivity, we investigated the effects of vibegron, a ß3-adrenoceptor agonist, on the bladder and sensory function by evaluating cystometry and mechanosensitive single-unit afferent activities (SAAs), respectively, in a male rat model of bladder outlet obstruction (BOO). BOO was created by partial ligation of the urethra. Ten days after the surgical procedure, cystometric and SAA measurements were taken under two distinct conditions: a conscious-restrained condition, in which the bladder was constantly filled with saline, and a urethane-anesthetized condition involving an isovolumetric process with saline. For each measurement, vibegron (3 mg/kg) or its vehicle was administered intravenously after the data were reproducibly stable. In addition, the expression of ß3-adrenoceptor and substance P (SP), a sensory neuropeptide, in the bladder was further evaluated following immunohistochemical procedures. Number of non-voiding contractions (NVCs) in cystometry was decreased after vibegron-administration, which was a significant change from vehicle group. Number of microcontractions and SAAs of Aδ- and C-fibers were significantly decreased by vibegron-administration. Furthermore, ß3-adrenocepor and SP were co-expressed in the suburothelium layer of the bladder. These findings indicated that vibegron showed inhibitory effects on NVCs and microcontractions of the bladder, and SAAs of the Aδ- and C-fibers in BOO rats. The study suggested that vibegron can partly inhibit the mechanosensitive afferent transduction via Aδ- and C-fibers by suppressing bladder myogenic contractile activities in the rat bladder hyperactivity associated with BOO.

Co-administration of sodium hydrosulfide and tadalafil modulates hypoxia and oxidative stress on bladder dysfunction in a rat model of bladder outlet obstruction.

PURPOSE: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. MATERIALS AND METHODS: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. RESULTS: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCL(p<0.001), carbachol(p<0.01), electrical field stimulation(p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine ß-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. CONCLUSIONS: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.

Sodium butyrate ameliorates erectile dysfunction through fibrosis in a rat model of partial bladder outlet obstruction.

BACKGROUND: In different animal models, a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) reduced inflammation, oxidative stress and fibrosis which were involved in the pathogenesis of erectile dysfunction (ED), but whether NaBu could improve ED in an experimental animal model of benign prostate hyperplasia (BPH) was not known. OBJECTIVE: To investigate the preventive effect of NaBu on ED in a partial bladder outlet obstruction (PBOO) rat model. MATERIALS AND METHODS: PBOO was induced by partial urethral obstruction. NaBu (20 mg/kg/day) was administered orally to rats for 6 weeks after creation of PBOO. In vivo erectile responses, in vitro relaxation and contraction responses in cavernosal tissue were measured. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to determine the gene and protein expression. Inflammation, fibrosis, and localization of proteins were evaluated using histological techniques. HDAC activity and tumor necrosis factor (TNF)-α levels were measured in penile tissues. RESULTS: NaBu improved decreased intracavernosal pressure/mean arterial pressure, nitrergic and endothelium-dependent relaxation responses, and contractile responses to phenylephrine and electrical field stimulation in the PBOO group without affecting increased bladder weight. Increased endothelial nitric oxide synthase (eNOS), transforming growth factor (TGF)-ß1, and nuclear factor kappa B (NF-κB) gene levels in PBOO group were ameliorated by NaBu treatment. The administration of NaBu to PBOO rats significantly increased neuronal NOS (nNOS) and decreased TGF-ß1 protein expression. The nuclear/cytosolic ratio of NF-κB demonstrated a decrease in PBOO and all treatment groups compared to control. A significant increase in the nuclear-to-cytoplasmic ratio of nuclear factor erythroid 2-related factor 2 (Nrf2) after PBOO was reduced by the treatment. Both eNOS and inducible NOS (iNOS) protein expression, together with TNF-α levels did not differ in the penile tissue of all groups. In histological analysis, increased TGF-ß1 protein expression and fibrosis, as well as decreased nNOS protein in PBOO, were reversed by the treatment. NaBu did not normalize moderate inflammation in obstructed rats. An increase in the HDAC activity in PBOO was significantly suppressed by NaBu. DISCUSSION: Inhibition of the HDAC activity by NaBu in penile tissue could ameliorate fibrosis-associated changes induced by PBOO. CONCLUSION: NaBu promotes recovery of erectile function, and also significantly prevents penile fibrosis and normalizes TGF-ß1 and nNOS protein expression in a rat model of PBOO. The HDAC pathway may present a promising target to prevent ED in patients with BPH.

Effect of videourodynamic subtypes on treatment outcomes of female dysfunctional voiding.

INTRODUCTION AND HYPOTHESIS: Dysfunctional voiding (DV) is not uncommon in women and is typically challenging to treat. This study retrospectively investigated the long-term treatment outcomes of DV women with different videourodynamics (VUDS) characteristics. METHODS: Data of women with VUDS-proven DV (n = 302) were retrospectively analyzed. All patients at first received biofeedback pelvic floor muscle training and medications; urethral sphincter botulinum toxin A injection was administered after treatment failure. Long-term follow-up outcomes were graded by global response assessment (GRA) and objective responses of decrease of detrusor pressure (Pdet), increase in maximum flow rate (Qmax) and voiding efficiency (VE). The treatment outcomes were investigated among different VUDS subgroups. RESULTS: Of 302 women, 165 (54.6%) had mid-urethral DV, 117 (38.7%) had distal urethral DV, and 20 (6.6%) had both bladder neck dysfunction (BND) and mid-urethral DV. A total of 170 (56.3%) patients were available for follow-up VUDS after treatment. Pdet was decreased in all three subgroups, but increase in Qmax and VE was only noted in the BND plus DV subgroup. Overall, 120 (70.6%) patients showed improvement (GRA ≥ 1), including 14 with BND plus DV (93.3%), 50 with mid-urethral DV (60.8%) and 56 with distal urethral DV (77.8%) (p = 0.044). All three subgroups showed significant reduction in bladder outlet obstruction index after treatment, with BND plus DV subgroup showing the greatest reduction. CONCLUSIONS: Women with DV have different VUDS characteristics resulting from different pathophysiological mechanisms and treatment results. The VUDS characteristics may help predict treatment outcomes of female DV.

Outcomes of a complementary and alternative medicine based on vitamins, herbal products, and amino acid as a first line treatment in idiopathic overactive bladder syndrome in men and women without bladder outlet obstruction.

OBJECTIVE: To evaluate the efficacy and tolerability of a complementary and alternative medicine (CAM) called Kubiker (Naturmed, Montegranaro, FM, Italy), consisting of vitamins (C and D), herbal products (cucurbita maxima, capsicum annum, polygonum cuspidatum), and amino acid L-Glutamine, as first line treatment of (OAB). MATERIALS AND METHODS: According to institutional protocols, data on patients addressing to a tertiary referral centre for OAB symptoms were recorded. OAB was evaluated through validated questionnaires including ICIQ-SF, USS, and OAB-q-SF. Patients with previous antimuscarinic or ß3 agonist treatment, neurological disease or pathologies which may mimic OAB, including infections, were excluded. Only unobstructed patients were considered and were given CAM twice daily for 12 weeks. After treatment, symptoms were re-evaluated repeating previous questionnaires and PGI-I was given to evaluate perceived improvement. RESULTS: A total of 41 patients were evaluated and 35 respected inclusion criteria and were enrolled. All subjects had a full compliance and adherence with CAM medication intake. The median patient's age was 65 (56-73). Male were 8 (22.9%) while females were 27 (77.1%). Median baseline OAB-q SF and ICIQ-SF scores were 18 (15-25) and 9 (6-13), respectively. After treatment, 85.7% patients had a clinical benefit, with a significant reduction of OAB symptoms, also according to USS (p < 0.01). The median OAB-q SF and ICIQ-SF scores were 10 (7-15) and 6 (0-8) (p < 0.01). CAM was successful with an improvement in subjective patient's satisfaction, with a median PGI-I score of 2 (1-3). Patients (men and women) who still had UUI after 3 months CAM medication were eight (22.8%), and among them, those who did not refer any therapeutic benefit were five (14.3%). CONCLUSIONS: According to our study, CAM may be useful medication for a first line treatment of uncomplicated idiopathic OAB cases, providing a nonnegligible effects on symptoms. However, further studies are mandatory to draw definitive conclusions.

Serum/glucocorticoid-regulated kinase 1-targeted transient receptor potential oxalate subtype 1 regulates bladder smooth muscle cell proliferation due to bladder outlet obstruction in mice via activated T cell nuclear factor transcription factor 2.

Bladder outlet obstruction (BOO) is a type of chronic disease that is mainly caused by benign prostatic hyperplasia. Previous studies discovered the involvements of both serum/glucocorticoid-regulated kinase 1 (SGK1) and activated T cell nuclear factor transcription factor 2 (NFAT2) in the proliferation of smooth muscle cells after BOO. However, the relationship between these two molecules is yet to be explored. Thus, this study explored the specific mechanism of the SGK1-NFAT2 signaling pathway in mouse BOO-mediated bladder smooth muscle cell proliferation in vivo and in vitro. In vivo experiments were performed by suturing 1/2 of the external urethra of female BALB/C mice to cause BOO for 2 weeks. In vitro, mouse bladder smooth muscle cells (MBSMCs) were treated with dexamethasone (Dex) or dexamethasone + SB705498 for 12 h and were transfected with SGK1 siRNA for 48 h. The expression and distribution of SGK1, transient receptor potential oxalate subtype 1 (TRPV1), NFAT2, and proliferating cell nuclear antigen (PCNA) were measured by Western blotting, polymerase chain reaction, and immunohistochemistry. The relationship between SGK1 and TRPV1 was analyzed by coimmunoprecipitation. The proliferation of MBSMCs was examined by 5-ethynyl-2'-deoxyuridine and cell counting kit 8 assays. Bladder weight, smooth muscle thickness, and collagen deposition in mice after 2 weeks of BOO were examined. Bladder weight, smooth muscle thickness, the collagen deposition ratio, and the expression of SGK1, TRPV1, NFAT2, and PCNA were significantly increased in mice after 2 weeks of BOO. Compared with the control, 10 µM Dex promoted the expression of these four molecules and the proliferation of MBSMCs. After inhibiting TRPV1, only the expression of SGK1 was not affected, and the proliferation of MBSMCs was inhibited. After silencing SGK1, the expression of these four molecules and the proliferation of MBSMCs decreased. Coimmunoprecipitation suggested that SGK1 acted directly on TRPV1. In this study, SGK1 targeted TRPV1 to regulate the proliferation of MBSMCs mediated by BOO in mice through NFAT2 and then affected the process of bladder remodeling after BOO. This finding may provide a strategy for BOO drug target screening.

Benefits and Harms of Conservative, Pharmacological, and Surgical Management Options for Women with Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel.

CONTEXT: While the management of bladder outlet obstruction (BOO) in men has been a topic of several systematic reviews and meta-analyses, no such evidence base exists for female BOO. OBJECTIVE: The aim of this systematic review was to evaluate the benefits and harms of therapeutic interventions for the management of BOO in women. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The study protocol was registered with PROSPERO (CRD42020183839). A systematic literature search was performed and updated by a research librarian in May 2021. The study population consisted of adult female patients diagnosed with BOO, who underwent treatment. EVIDENCE SYNTHESIS: Out of 6344 records, we identified 33 studies enrolling 1222 participants, of which only six randomized controlled trials (RCTs) were found. One placebo-controlled crossover randomized trial assessed the role of baclofen in 60 female patients with dysfunctional voiding. The trial met its primary endpoint with a significantly greater decrease in the number of voids per day in the baclofen group (-5.53 vs -2.70; p = 0.001). The adverse events were mild and comparable in both groups (25% vs 20%). One placebo-controlled crossover randomized trial assessed the role of sildenafil in 20 women with Fowler's syndrome. There were significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR), but with no statistically significant difference when compared with placebo. In a large RCT including 197 female patients with functional BOO, the alpha-blocker alfuzosin significantly improved IPSS, Qmax, and PVR compared with baseline, but the differences were not statistically significant compared with the placebo group. Several small single-arm prospective series reported improvement of BOO-related symptoms and voiding parameters with urethroplasty, sling revision, urethral dilation, vaginal pessary, and pelvic organ prolapse repair. CONCLUSIONS: Evidence to support the use of conservative, pharmacological, and surgical treatments for BOO is scarce. PATIENT SUMMARY: According to the present systematic review of the literature, evidence to support the use of conservative, pharmacological, and surgical treatments for either anatomical or functional bladder outlet obstruction is scarce.

Preliminary results of a randomized crossover clinical trial comparing a new electromagnetic and vibrating device and alpha-blocker agents in patients affected by bladder outlet obstruction secondary to benign prostatic hyperplasia.

To the Editor, Benign Prostatic Hyperplasia (BPH) is one of the main causes of patients seeking urological counselling in Western countries. It has been estimated that nearly 70 percent of United States men between the ages of 60 and 69 years, and nearly 80 percent of men ≥ 70 years, have some degree of BPH [...].

Therapeutic Effects of Urethral Sphincter Botulinum Toxin A Injection on Dysfunctional Voiding with Different Videourodynamic Characteristics in Non-Neurogenic Women.

Although female dysfunctional voiding (DV) is common in urological practice, it is difficult to treat. This study evaluated the therapeutic efficacy of urethral botulinum toxin A (BoNT-A) on non-neurogenic female DV. Based on the videourodynamic study (VUDS), the DV was classified into three subgroups according to the obstructive site. A successful treatment outcome was defined as an improvement of voiding efficiency by 10% and reported global response assessment by ≥1. The study compared therapeutic efficacy, baseline urodynamic parameters, and changes in urodynamic parameters between the treatment success and failure groups and among three DV subgroups. Predictive factors for successful treatment were also investigated. A total of 81 women with DV were categorized into three groups: 55 (67.9%) had mid-urethral DV, 19 (23.5%) had distal urethral DV, and 7 (8.6%) had combined BN dysfunction and mid-urethral DV after BN transurethral incision. The treatment outcome was successful for 55 (67.9%) patients and failed for 26 (32.1%). Successfully treated patients had a significant decrease of detrusor pressure, post-void residual volume, and bladder outlet obstruction index, as well as an increase in voiding efficiency at follow-up versus the treatment failure group. The logistic regression of urodynamic parameters and clinical variables revealed that a greater volume of first sensation of filling predicts a successful BoNT-A treatment outcome (p = 0.047). The urethral BoNT-A injection is effective in treating non-neurogenic women with DV, with a success rate of 67.9%. The videourodynamic characteristics of DV may differ among patients but does not affect the treatment outcome.

Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction.

Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial BOO (pBOO), we found that rats treated with metformin showed lower baseline pressures with a reduced inflammatory reaction in the early phase (2 wk) after pBOO. The NLR family pyrin domain containing 3 inflammasome pathway was inhibited in pBOO rat bladders with treatment of metformin in the early phase. Metformin reduced the activity of NLR family pyrin domain containing 3 in primary urothelial cells. In the chronic phase (9 wk after pBOO), metformin treatment ameliorated bladder fibrosis and improved the reduced compliance. Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-wk pBOO rat bladders. Autophagy was inhibited with upregulation of profibrotic proteins in primary fibroblasts from chronic pBOO bladders, which could be restored by administration of metformin. The antifibrotic effects of metformin on fibroblasts were diminished after silencing of AMP-activated protein kinase or light chain 3B. In summary, this study elucidates that oral administration of metformin relieves inflammation in the bladder during the early phase of pBOO. Long-term oral administration of metformin can prevent functional and histological changes in the pBOO rat bladder. The current study suggests that metformin might be used to prevent the development of bladder dysfunction secondary to BOO.NEW & NOTEWORTHY The present study in a rat model showed that oral administration of metformin alleviated inflammation following partial bladder outlet obstruction in the early phase and ameliorated bladder fibrosis as well as bladder dysfunction by long-term treatment. Our study indicated that metformin is a potential drug to inhibit bladder remodeling and alleviate bladder dysfunction. Clinical trials are needed to validate the effect of metformin on the bladder dysfunction and bladder fibrosis in the future.

Prescribing patterns for medical treatment of suspected prostatic obstruction: a longitudinal register-based study of the Scottish Health and Social Care Open Data.

BACKGROUND: The diagnosis of lower urinary tract symptoms related to suspected bladder outflow obstruction from benign prostate hyperplasia/enlargement in men is increasing. This is leading to high demand on healthcare services; however, there is limited knowledge of differences in pharmacotherapy prescribing for this condition based on geography. OBJECTIVE: To investigate potential variation in drug prescribing for suspected bladder outflow obstruction in Scotland, based on analysis of publicly available data, to identify trends and inform future prescribing. STUDY DESIGN: A longitudinal register-based data study of prescribing and patient data publicly available from Scottish registries. All information is available as monthly aggregates at the level of single general practices. SETTING AND PARTICIPANTS: 903 (97%) general practices in Scotland, over a 50-month period (October 2015 to November 2019). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analysed numbers of daily doses of drugs for suspected bladder outflow obstruction prescribed per month using a Bayesian Poisson regression analysis, incorporating random effects to account for spatial and temporal elements. RESULTS: Prescriptions for suspected bladder outflow obstruction medications increased during the observation period (overall average rate of change 1.24±0.28, ranging from 0.893 in Orkney to 1.95 in Lanarkshire). While some determinants of health inequality regarding prescribing practices across health boards are consistent with those known from the literature, other inequalities remain unexplained after accounting for practice-specific and patient-specific characteristics such as deprivation and rurality. CONCLUSIONS: Inequalities in prescribing for suspected bladder outflow obstruction medications exist in Scotland, partially ascribable to accepted sociodemographic and geographic factors.

The effect of testosterone replacement therapy on bladder functions, histology, apoptosis, and Rho-kinase expression in bladder outlet obstruction and hypogonadism rat model

Background/aim: The effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models. Materials and methods: 30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared. Results: BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO group (P < 0.01), BOO + orchiectomy led ROCK-2 increase. The testosterone treatment failed to reverse the up-regulation of ROCK-2 induced by orchiectomy although it tended to lower ROCK-2 level. Compared to sham group (P = 0.002), changes in maximal bladder capacity and leak point pressure were higher (P = 0.026, P = 0.001), and bladder compliance was lower in BOO group. Also, the apoptosis index was different between the two groups (P = 0.380). Smooth muscle/collagen ratio was higher in BOO + orchiectomy + T group than in BOO + orchiectomy group (P = 0.010). Conclusions: The research draws attention to alternating treatment approaches in case of the presence of hypogonadism and BOO.