Randomized Controlled Trial Comparing Open Simple Prostatectomy or Prostate Artery Embolization in Large Prostates: Clinical and Urodynamic Assessment - PoPAE Study.

OBJECTIVE: To evaluate the effects of Prostate artery embolization (PAE) and open simple prostatectomy (OP) on lower urinary tract symptoms and urodynamic parameters in subjects with prostate size >80cc³. METHODS: PoPAE study (OP or PAE) was a randomized, open-label controlled trial performed between January 2020 and May 2022. Subjects with large prostates (>80cc³), urodynamic parameters meeting obstruction criteria (Bladder Outlet Obstruction Index-BOOI>40), and good detrusor function (Bladder contractility index>100) were included. The primary and co-primary endpoints were the variation in peak flow rate on uroflowmetry (Qmax) and BOOI. The secondary endpoints were the IPSS and ultrasonographic changes. RESULTS: Twenty three and 25 subjects underwent PAE and OP were evaluated, respectively. At baseline, the 2 groups have shown similar clinical, radiological, laboratory, and urodynamic parameters. After 6 months, Qmax improved 8,3 ± 4.17 mL/sec in PAE and 15.1 ± 8.04 mL/sec in OP (mean difference 6.78 in favor of PE; P = .012 [CI -9.00 to -3.00]). After treatment, 88% of those men underwent OP were classified as unobstructed or equivocal (BOOi<40). On the other hand, 70% of subjects underwent PAE remained obstructed (BOOI>40) and none of them shifted to unobstructed status (BOOI<20). It was observed a similar reduction in IPSS and PVR in both groups. CONCLUSION: PAE was inferior to conventional surgery for releasing BOO and improving peak urinary flow in large prostates. Nevertheless, PAE was able to improve symptoms and PVR, and might be an alternative method in selected patients.

Management of the Devastated Bladder Outlet after Prostate CANCER Treatment.

PURPOSE OF REVIEW: Devastating complications of the bladder outlet resulting from prostate cancer treatments are relatively uncommon. However, the combination of the high incidence of prostate cancer and patient longevity after treatment have raised awareness of adverse outcomes deteriorating patients' quality of life. This narrative review discusses the diagnostic work-up and management options for bladder outlet obstruction resulting from prostate cancer treatments, including those that require urinary diversion. RECENT FINDINGS: The devastated bladder outlet can be a consequence of the treatment of benign conditions, but more frequently from complications of pelvic cancer treatments. Regardless of etiology, the initial treatment ladder involves endoluminal options such as dilation and direct vision internal urethrotomy, with or without intralesional injection of anti-fibrotic agents. If these conservative strategies fail, surgical reconstruction should be considered. Although surgical reconstruction provides the best prospect of durable success, reconstructive procedures are also associated with serious complications. In the worst circumstances, such as prior radiotherapy, failed reconstruction, devastated bladder outlet with end-stage bladders, or patient's severe comorbidities, reconstruction may neither be realistic nor justified. Urinary diversion with or without cystectomy may be the best option for these patients. Thorough patient counseling before treatment selection is of utmost importance. Outcomes and repercussions on quality of life vary extensively with management options. Meticulous preoperative diagnostic evaluation is paramount in selecting the right treatment strategy for each individual patient. The risk of bladder outlet obstruction, and its severest form, devastated bladder outlet, after treatment of prostate cancer is not negligible, especially following radiation. Management includes endoluminal treatment, open or robot-assisted laparoscopic reconstruction, and urinary diversion in the worst circumstances, with varying success rates.

The effect of pelvic floor muscle training in women with functional bladder outlet obstruction.

INTRODUCTION AND HYPOTHESIS: Female voiding dysfunction is often due to bladder outlet obstruction (BOO). We investigated pelvic floor muscle training (PFMT) effectiveness in women with functional BOO. METHODS: This is a prospective study recruiting 63 women functionally obstructed, over 18yo, maximum flow rate (Qmax) less than 12 ml/sec, naïve of voiding treatment. Exclusion criteria were anatomical BOO, neurological condition, pelvic intervention, psychiatric or anticholinergic medication, diabetes mellitus and affected upper urinary tract. At baseline, women underwent uroflow, post void residual (PVR) measurement, cystoscopy, cystogram and urodynamic study (UDS) with pelvic electromyography (EMG). Blaivas-Groutz nomogram has been used to define obstruction. After diagnosis, patients underwent six-month PFMT. Re-evaluation was offered four weeks after end of treatment. Data were analyzed with SPSSv22.0. RESULTS: 63 women were recruited and 48 finally included. At baseline, 20 reported 3 urinary tract infections (UTIs) during last year, and 12 had one episode of urine retention. Median Qmax was 7.5 ml/sec and median PVR 110 ml. 40 women were obstructed. 16 (40%) had mild, 16 (40%) moderate and 8 (20%) severe obstruction. All subjects had an overactive pelvic floor on EMG. Obstructed women were re-evaluated. Median Qmax was 8.5 ml/sec, close to baseline (p = 0.16). Median PVR was 65 ml, reduced to baseline (p = 0.02). 33 (82.5%) remained obstructed, 22 (66.67%) with mild, 8 (24.24%) moderate and 3 (9.09%) severe obstruction. 7 (17.5%) were non-obstructed. 4 patients reported one UTI episode with no cases of retention. CONCLUSIONS: A 6 month PFMT reduced UTIs and PVR in women with functional BOO. Additionally, most patients had a de-escalation to milder obstruction.

Role of human adipose-derived stem cells (hADSC) on TGF-ß1, type I collagen, and fibrosis degree in bladder obstruction model of Wistar rats.

INTRODUCTION: Bladder outlet obstruction (BOO) was caused by a series of histological and biochemical changes in the bladder wall, through the inflammation process in the bladder wall, hypertrophy and fibrosis. ADSC has an important role in bladder regeneration. METHODS AND MATERIALS: This study was an experimental randomized study using male Wistar rats which were monitored at 2 and 4 weeks to determine the effect of ADSC therapy on TGF-ß1 type I collagen, and degree of fibrosis. RESULT: Rats were divided into 5 groups. In the week 2 BOO group, 1 sample included in the category of moderate fibrosis, 1 sample that was given ADSC with mild fibrosis category, 3 samples included in severe fibrosis category, 3 samples that were given ADSC included in the category of moderate fibrosis. The concentration of TGF-ß1 in the hADSC therapy group was significantly lower than the control group at the 2nd and 4th week of monitoring (p2 = 0.048, p4 = 0.048), and also with more type I collagen on 2nd and the 4th week (p2 = 0.048, p4 = 0.048). CONCLUSION: ADSC therapy can reduce the concentration of TGF-ß1, type I collagen, and degree of fibrosis in the male Wistar BOO model.

Human amniotic fluid stem cells can alleviate detrusor dysfunction caused by bladder outlet obstruction in rats.

The present study examined whether bladder detrusor dysfunction due to partial bladder outlet obstruction (pBOO) could be improved after the treatment of human amniotic fluid stem cells (hAFSCs). 72 female rats were grouped into sham operation, pBOO, and pBOO with hAFSCs treatment (pBOO + hAFSCs) for in vitro and in vivo studies. Bladder weight, bladder wall thickness, the ratio of collagen to smooth muscle and the levels of positive CD11b/c and HIS48 cells was significantly increased after pBOO but improved after hAFSCs treatment. Cystometries showed impaired bladder function after pBOO. Protein and mRNA levels of hypoxia inducible factor-1α, CCL2, interleukin-1ß, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), α-smooth muscle actin, collagen I and collagen III were increased at 2 and/or 6 weeks, but proteins and mRNA expressions of protein gene product 9.5 were decreased at 2 and 6 weeks after pBOO. These abnormalities were improved after hAFSCs treatment. The expressions of TGF-ß1 and CTGF in cultured detrusor cells of pBOO rats were increased but were improved after hAFSCs treatment. The present results showed hAFSCs treatment could improve bladder detrusor dysfunction in pBOO rats, which may be related to the reduction of inflammatory and pro-fibrotic markers in detrusor muscle cells.

Human Urine-Derived Stem Cells Improve Partial Bladder Outlet Obstruction in Rats: Preliminary Data and microRNA-mRNA Expression Profile.

Partial bladder outlet obstruction (pBOO) often results in bladder tissue inflammation and remodeling. As human urine-derived stem cells (USCs) have demonstrated therapeutic benefits, we used a rat model to investigate the effect of USCs on bladder function and explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing. Eighteen rats were assigned to a sham surgery group, pBOO group, and pBOO+USC group (six biweekly treatments). Routine urodynamic monitoring, analysis of detrusor muscle strips, and pathophysiology assessments were conducted. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis. After USC treatment, elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity were found. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs was reversed by USC treatment. Two large nodes (miR-142 and miR-9a) were identified in the miRNA-gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions. This is the first study to demonstrate the protective effect of USCs on bladder function and remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.

Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder.

BACKGROUND: Underactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder. METHODS: Male Sprague-Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies. RESULTS: We observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue. CONCLUSIONS: Ad-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB.

European Association of Urology Guidelines on the Management of Female Non-neurogenic Lower Urinary Tract Symptoms. Part 2: Underactive Bladder, Bladder Outlet Obstruction, and Nocturia.

CONTEXT: Female lower urinary tract symptoms (LUTS) are a common presentation in urological practice. Thus far, only a limited number of female LUTS conditions have been included in the European Association of Urology (EAU) guidelines compendium. The new non-neurogenic female LUTS guidelines expand the remit to include these symptoms and conditions. OBJECTIVE: To summarise the management of underactive bladder (UAB), bladder outlet obstruction (BOO), and nocturia in females. EVIDENCE ACQUISITION: The literature search was updated in September 2021 and evidence synthesis was conducted using modified GRADE approach as outlined for all EAU guidelines. A new systematic review on BOO was carried out by the panel for purposes of this guideline. EVIDENCE SYNTHESIS: The important considerations for informing guideline recommendations are presented, along with a summary of all the guideline recommendations. CONCLUSIONS: Non-neurogenic female LUTS are an important presentation of urological dysfunction. Initial evaluation, diagnosis, and management should be carried out in a structured and logical fashion on the basis of the best available evidence. This guideline serves to present this evidence to practising urologists and other health care providers in an easily accessible and digestible format. PATIENT SUMMARY: This report summarises the main recommendations from the European Association of Urology guideline on symptoms and diseases of the female lower urinary tract (bladder and urethra) not associated with neurological disease. We cover recommendations related to the treatment of underactive bladder, obstruction of the bladder outlet, and nighttime urination.

[Female voiding dysfunction: Clean intermittent catheterization is not the only option]. / Troubles de la vidange vésicale chez la femme : l'autosondage n'est pas la seule solution.

Female voiding dysfunction exists but are largely underdiagnosed, especially in France. They can result from two different mechanisms: detrusor underactivity or bladder outlet obstruction, with very different pathophysiology and therapeutic management. There are many different therapeutic options, including surgical treatments, to offer as alternative to clean intermittent catheterization which are often burdensome for patients. Seeking voiding dysfunction in female patients with lower urinary tract symptoms and searching for their etiology to tackle it could lead to a paradigm change in these women: from standardized treatment to individualized treatment. In their practice, nurses can detect warning symptoms suspect of voiding dysfunction, and have thus a role to play in the improvement of patients' screening, education other healthcare providers, and management of female voiding dysfunction.

Inhibition of DNA methylation during chronic obstructive bladder disease (COBD) improves function, pathology and expression.

Partial bladder outlet obstruction due to prostate hyperplasia or posterior urethral valves, is a widespread cause of urinary dysfunction, patient discomfort and also responsible for immense health care costs. Even after removal or relief of obstruction, the functional and pathologic aspects of obstruction remain as a chronic obstructive bladder disease (COBD). Epigenetic changes, such as DNA methylation, contribute to the persistent character of many chronic diseases, and may be altered in COBD. We tested whether candidate genes and pathways and the pathophysiology of COBD were affected by a hypomethylating agent, decitabine (DAC). COBD was created in female Sprague-Dawley rats by surgical ligation of the urethra for 6 weeks, followed by removal of the suture. Sham ligations were performed by passing the suture behind the urethra. After removal of the obstruction or sham removal, animals were randomized to DAC treatment (1 mg/kg/3-times/week intraperitoneally) or vehicle (normal saline). Bladder function was non-invasively tested using metabolic cages, both one day prior to de-obstruction at 6 weeks and prior to sacrifice at 10 weeks. Residual volume and bladder mass were measured for each bladder. Bladders were examined by immunostaining as well as qPCR. The effects of DNA methyltransferase (DNMT)-3A knockout or overexpression on smooth muscle cell (SMC) function and phenotype were also examined in bladder SMC and ex vivo culture. Residual volumes of the DAC treated group were not significantly different from the NS group. Compared to COBD NS, COBD DAC treatment helped preserve micturition volume with a significant recovery of the voiding efficiency (ratio of the maximum voided volume/maximum bladder capacity) by one third (Fig. 1, p > 0.05). Brain-derived neurotrophic factor (BDNF) variants 1 and 5 were upregulated by COBD and significantly reduced by DAC treatment. Deposition of collagen in the COBD bladder was reduced by DAC, but gross hypertrophy remained. In bladder SMC, DNMT3A overexpression led to a loss of contractile function and phenotype. In bladders, persistently altered by COBD, inhibition of DNA-methylation enhances functional recovery, unlike treatment during partial obstruction, which exacerbates obstructive pathology. The underlying mechanisms may relate to the gene expression changes in BDNF and their effects on signaling in the bladder.

Partial inhibition of activin receptor-like kinase 4 alleviates bladder fibrosis caused by bladder outlet obstruction.

The bladder undergoes profound structural alterations after bladder outlet obstruction (BOO), characterized by hypertrophy of the bladder wall and accumulation of extracellular matrix (ECM). Transforming growth factor-ß (TGF-ß) has been found to promote fibrosis of the bladder induced by partial bladder outlet obstruction (pBOO). Activin receptor-like kinase 4 (ALK4) is a downstream receptor of the TGF-ß superfamily. However, the role of the ALK4-Smad2/3 pathway in the pathogenesis of bladder fibrosis caused by pBOO remains unknown. This study focused on learning the role of ALK4 in the process of bladder fibrosis caused by pBOO. The pBOO mice models showed that ALK4 expression was found to upregulate in the wild-type bladder 6 weeks after pBOO compared to control group. Then, mice with heterozygous knockout of the ALK4 gene (ALK4+/-) were generated. Histological analysis and Western blot (WB) results showed significant suppression of collagen expression in the bladders of ALK4+/- mice after pBOO compared with WT mice. WB also showed that ALK4+/- mice demonstrated significant suppression of phosphorylated Smad2/3 (p-Smad2/3) expression in the bladder 6 weeks after pBOO but not of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase or protein 38 (p-ERK, p-JNK, p-P38) expression. This effect might have occurred through partial inactivation of the Smad2/3 signaling pathway. In vitro, ALK4 overexpression promoted collagen production in cultured BSMCs and activated the Smad2/3 signaling pathway. Taken together, our results demonstrated that ALK4 insufficiency alleviated bladder fibrosis in a mouse model of pBOO partly by suppressing Smad2/3 activity.

The Postural Tachycardia Syndrome (PoTS) Bladder-Urodynamic Findings.

OBJECTIVE: To evaluate the urodynamics (UDS) of patients with postural tachycardia syndrome (PoTS). METHODS: Patients with a confirmed diagnosis of PoTS referred by the department of neuro-cardiology to the neuro-urology were identified and their UDS were retrospectively reviewed. RESULTS: In total, 50 patients (47 = 94.0% female) with confirmed PoTS and available UDS were identified. Mean age of females and males was 32.4 and 28.2 years, P = .15. Intermittent self-catheterisation was being used by 15/47 (31.9%) females at assessment. Detrusor overactivity was observed in 6 females (12.8%) (all at end fill and associated with urgency). In total, 14 (29.8%) females had no sensation of filling. No patients had an "unsafe" bladder. In total, 15/47 (31.9%) of women were unable to void with UDS catheters. Straining was reported in 22/35 (68.8%) of females. The female bladder outflow obstruction index = PDetQmax - 2.2(Qmax) was over 5 in 10/28 (35.7%) and over 18 in 5 (17.9%). The bladder contractility index = PDetQmax + 5Qmax was under 100 in 18/28 (28.6%) women. CONCLUSION: The UDS of patients with "PoTS bladder" often demonstrate a poorly sensate but stable and safe bladder with functional obstruction and impaired bladder contractility that may necessitate straining or intermittent self-catheterisation.

Update on the Management of Urological Problems Following Kidney Transplantation.

Urological problems in kidney transplant recipients are not limited only to posttransplantation urological complications. These problems are a cause of significant patient mortality and morbidity that have wide-ranging effects on graft survival throughout the entire life of the graft. Ultimately, the transplant comprises a major portion of the urinary system; therefore, the transplant team should be prepared for foreseeable and unforeseeable urological problems in the short and long terms. These mainly include postoperative urological complications (urine leakage, ureteral stenosis, and vesicoureteral reflux), bladder outlet obstruction, and graft urolithiasis. In recent years, significant advances have been made in the management of urological complications, especially due to advances in endourologic interventions. The aim of this review is to summarize the management of urological problems after kidney transplantation in the context of the current literature.

Intralesional steroid injection combined with bladder neck incision is efficacious in the treatment of recurrent bladder neck contracture.

OBJECTIVES: Bladder neck contracture (BNC) is a well-recognized complication following radical prostatectomy (RP). This problem may recur after failing initial endoscopic management. This study evaluated the efficacy of intralesional steroid injection combined with bladder neck incision (BNI) for recurrent BNC following RP. METHODS: Between November 2011 and March 2018, data from all men who underwent BNI and intralesional steroid injection for recurrent BNC from a single regional center were collected. BNC was diagnosed endoscopically and identified as recurrent if having previously failed endoscopic management with BNI alone. Follow up was initially performed at 3 months with an International Prostate Symptom Score and urinary flow rate. Patients were noted to be recurrence-free when discharged from follow up or after having undergone a continence procedure indicating stability of the contracture. RESULTS: Thirty patients underwent BNI and intralesional steroid injection for recurrent BNC over the study period. All patients had received prior endoscopic incision of BNC without lasting success. Seventy percent (21/30) of patients were recurrence-free post-procedure, and this increased to 83.3% (25/30) after a repeat procedure in four patients. All five patients who had previous salvage radiotherapy had their recurrent BNC successfully managed with one BNI and intralesional steroid injection. The mean follow up was 33.4 months (range 7-75). There were no adverse events recorded. CONCLUSIONS: BNI combined with injection of intralesional steroids is a simple, cost-effective intervention which requires no specialist equipment/skills outside the realm of a general urologist. It is safe and has an excellent success rate.

Fetal bladder outflow obstruction: Interventions, outcomes and management uncertainties.

Fetal lower urinary tract obstruction (LUTO) is classically based on prenatal ultrasound identification of a dilated/ thick-walled bladder, bilateral hydronephrosis, dilated ureters and a dilated posterior urethra (also known as the "keyhole sign") in a male fetus. Although the most common underlying diagnosis is posterior urethral valves, the prenatal appearance may be similar with urethral atresia or stenosis, the Prune-Belly Syndrome, or even a cloacal anomaly in a female. These conditions form part of the Congenital Anomalies of Kidney and Urinary Tract (CAKUT) spectrum, which is the commonest cause of end-stage renal disease in children. Although it is difficult to predict postnatal renal function from the prenatal appearance, studies have recently identified predictive features (based on ultrasound findings and fetal biochemistry), and established staging systems to assist with counselling, and, where indicated, patient selection for in-utero intervention. Current in-utero therapy includes amnio-infusion, vesico-amniotic shunting, and fetal cystoscopy with valve ablation or urethral stenting. Postnatal survival and renal functional outcomes, complications and management uncertainties are described, highlighting areas of future development.

PRImary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study).

INTRODUCTION: Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. METHODS AND ANALYSIS: PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. ETHICS AND DISSEMINATION: Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN10327305.