Surgery For Bladder Outlet Obstruction Research Articles

Development of the UroARC Surgical Calculator: A Novel Risk Calculator for Older Adults Undergoing Surgery for Bladder Outlet Obstruction.

Bladder outlet obstruction (BOO) is common in older adults. Many older adults who pursue surgery have additional vulnerabilities affecting surgical risk, including frailty. A clinical tool that builds on frailty to predict surgical outcomes for the spectrum of BOO procedures would be helpful to aid in surgical decision-making but does not currently exist. Medicare beneficiaries undergoing BOO surgery from 2014 to 2016 were identified and analyzed using the Medicare MedPAR, Outpatient, and Carrier files. Eight different BOO surgery categories were created. Baseline frailty was calculated for each beneficiary using the Claims-Based Frailty Index (CFI). All 93 variables in the CFI and the 17 variables in the Charlson Comorbidity Index were individually entered into stepwise logistic regression models to determine variables most highly predictive of complications. Similar and duplicative variables were combined into categories. Calibration curves and tests of model fit, including C statistics, Brier scores, and Spiegelhalter P values, were calculated to ensure the prognostic accuracy for postoperative complications. In total, 212,543 beneficiaries were identified. Approximately 42.5% were prefrail (0.15 ≤ CFI < 0.25), 8.7% were mildly frail (0.25 ≤ CFI < 0.35), and 1.2% were moderately-to-severely frail (CFI ≥0.35). Using stepwise logistic regression, 13 distinct prognostic variable categories were identified as the most reliable predictors of postoperative outcomes. Most models demonstrated excellent model discrimination and calibration with high C statistic and Spiegelhalter P values, respectively, and high accuracy with low Brier scores. Calibration curves for each outcome demonstrated excellent model fit. This novel risk assessment tool may help guide surgical prognostication among this vulnerable population.

Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction.

This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). Eighteen male Sprague-Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C-BOO groups received an equol-free diet, while the E-BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). Equol reduced BOO-induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C-BOO: 193 s, E-BOO: 438 s) and increased the micturition volume (C-BOO: 0.54 mL, E-BOO: 1.02 mL) compared to the C-BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C-BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.

Outcomes of Artificial Urinary Sphincter Implantation in Patients with Detrusor Underactivity and Postprostatectomy Incontinence.

There is insufficient evidence for postoperative outcomes of artificial urinary sphincter (AUS) implantation for postprostatectomy incontinence (PPI) with detrusor underactivity (DU). Thus, we assessed the impact of preoperative DU on the outcomes of AUS implantation for PPI. Medical records of men who underwent AUS implantation for PPI were reviewed. Patients who had bladder outlet obstruction surgery before radical prostatectomy or AUS-related complications that required revision of AUS within three months were excluded. Patients were divided into two groups based on the preoperative urodynamic study including pressure flow study, a DU group, and a non-DU group. DU was defined as a bladder contractility index less than 100. The primary outcome was postoperative postvoid residual urine volume (PVR). The secondary outcomes included maximum flow rate (Qmax), postoperative satisfaction, and international prostate symptom score (IPSS). A total of 78 patients with PPI were assessed. The DU group consisted of 55 patients (70.5%) and the non-DU group comprised 23 patients (29.5%). Qmax was lower in the DU group than in the non-DU group and PVR was higher in the DU group as per a urodynamic study before AUS implantation. There was no significant difference in postoperative PVR between the two groups, although the Qmax after AUS implantation was significantly lower in the DU group. While the DU group showed significant improvements in Qmax, PVR, IPSS total score, IPSS storage subscore, and IPSS quality of life (QoL) score after AUS implantation, the non-DU group showed postoperative improvement in IPSS QoL score. There was no clinically significant impact of preoperative DU on the outcome of AUS implantation for PPI; thus, surgery can be safely performed in patients with PPI and DU.

Incidental Prostate Cancer: A 23-Year Review Of A Tertiary Care Hospital.

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. The prevalence has been increasing with significant differences between regions. This study assesses the prevalence of incidental prostate cancer detected in specimens removed during bladder outlet obstruction operation. A retrospective analysis of the records of patients who had either endoscopic or open prostatectomy from January 1998 to December 2021 was conducted. The variables analysed were age, procedure, date of surgery, and Gleason score. A total of 2,842 patients underwent surgery on the prostate gland during the study period. Most of the patients, i.e. 2,733 (96.2%), were pathologically diagnosed with benign prostatic hyperplasia, while only 110 (3.9%) had prostate cancer. The frequency of incidental prostate cancer following surgery for bladder outlet obstruction has decreased over the last two decades at our centre, possibly because of an increase in PSA testing.

MP24-14 URORISK: A NOVEL SURGICAL RISK CALCULATOR FOR BLADDER OUTLET PROCEDURES IN OLDER ADULTS

You have accessJournal of UrologyCME1 Apr 2023MP24-14 URORISK: A NOVEL SURGICAL RISK CALCULATOR FOR BLADDER OUTLET PROCEDURES IN OLDER ADULTS Farnoosh Nik-Ahd, Shoujun Zhao, Lufan Wang, W. John Boscardin, and Anne M. Suskind Farnoosh Nik-AhdFarnoosh Nik-Ahd More articles by this author , Shoujun ZhaoShoujun Zhao More articles by this author , Lufan WangLufan Wang More articles by this author , W. John BoscardinW. John Boscardin More articles by this author , and Anne M. SuskindAnne M. Suskind More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003249.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder outlet obstruction (BOO) is common in older adults. As such, many who pursue surgery have additional vulnerabilities affecting surgical risk, including frailty and other comorbidities. No risk calculator for BOO surgery that factors in frailty exists. We developed the first risk calculator for BOO surgeries that includes components of frailty and comorbidity to predict the risk of common complications. METHODS: Medicare beneficiaries undergoing BOO surgery from 2014-2016 were examined using Medicare MedPAR, Outpatient, and Carrier files. Pre-procedure frailty was quantified for each subject using the 93-item Claims-Based Frailty Index (CFI). Each variable in the Charlson Comorbidity Index and CFI was extrapolated into stepwise logistic regression models to determine variables most predictive of surgical complications. The most prognostic variables were grouped into 13 categories. C-statistics, Brier scores, Spiegelhalter p values and model fit curves were calculated to assess model fit. RESULTS: A total of 212,543 subjects were included. BOO surgeries included transurethral resection of the prostate, GreenLight Laser Therapy, transurethral incision of the bladder neck, holmium laser enucleation of the prostate, transurethral microwave thermotherapy, transurethral incision of the prostate, UroLift, and transurethral needle ablation. Most subjects were white (88%), with CFI scores that were not frail (CFI<0.15, N=101,282, 48%) or pre-frail (0.15≤CFI<0.25, N=10,559, 39%). Variables most predictive of complications were congestive heart failure, primary malignancy, secondary or metastatic malignancy, pneumonia/influenza in the past year, neurodegenerative/neurologic diseases, dementia/psychiatric conditions and substance use, renal disease, chronic liver disease, anemias/platelets disorders, chronic lung disease, coronary artery disease, venous/lymphatic/thrombotic disorders, and stroke. Model fit for any complication within 30 days of surgery is shown (Figure). CONCLUSIONS: This is the first risk calculator for BOO surgery that includes predictors of frailty and comorbidity to individualize risk calculation among older adults. This serves as an effective and widely-applicable tool to help guide patient counseling and clinical decision-making. Source of Funding: NIH-NIA R01AG058616 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e323 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Farnoosh Nik-Ahd More articles by this author Shoujun Zhao More articles by this author Lufan Wang More articles by this author W. John Boscardin More articles by this author Anne M. Suskind More articles by this author Expand All Advertisement PDF downloadLoading ...

Treating overactive bladder symptoms after transurethral prostatic surgery for benign prostatic hyperplasia - Which medication to choose?

Overactive bladder (OAB) symptoms are often encountered in patients after transurethral resection of the prostate (TUR-P) or transurethral incision of the prostate (TUI-P) for benign prostatic obstruction (BPO). Either antimuscarinics or β-3 agonist has been found effective in relieving OAB symptoms. However, urologists usually do not prescribe such medication immediately after TUR-P or TUI-P to avoid an increase in postvoid residual and risk of urinary tract infection. If OAB medication can be used and adverse events (AEs) can be reduced to minimum, patients' quality of life after bladder outlet obstruction surgery could be improved. This study compared the safety and efficacy between solifenacin and mirabegron in men undergoing TUR-P or TUI-P. This prospective, randomized trial compared the safety and efficacy of OAB medication on the reduction in Urgency Severity Score (USS), OAB Symptoms Score (OABSS), International Prostate Symptom Score, and urgency urinary incontinence episodes in men with BPO undergoing surgical intervention. All patients could void smoothly after catheter removal and were randomly received daily solifenacin 5 mg, mirabegron 50 mg, or no interventions for 4 weeks. At 2 and 4 weeks postoperatively, participants' OAB symptoms and AEs were evaluated. A total of 57 men were enrolled in this study with a mean age of 70.8 ± 6.1 years. At 2 weeks postoperatively, USS (1.56 ± 1.72 vs. 2.39 ± 1.72 vs. 2.26 ± 1.73, P < 0.011) and OABSS (5.33 ± 3.65 vs. 7.67 ± 4.19 vs. 8.58 ± 4.31, P < 0.000) were significantly reduced in patients taking solifenacin, mirabegron, or control, respectively. Two patients in the solifenacin group developed urinary retention. However, the changes of variables at 4 weeks postoperatively were insignificant among the three groups. Solifenacin and mirabegron are two different drug classes both equally effective in treating immediate OAB symptoms after TUR-P or TUI-P. However, OAB symptoms could be relieved at 4 weeks without any medication. Considering AEs, β-3 agonist has a more favorable safety profile than antimuscarinics.

Detrusor Underactivity in Men with Bladder Outlet Obstruction.

Original articles concerning DU with BOO were identified through literature research from PubMed and EMBASE database. We selected 38 articles in our review, including those concerning pathophysiology, evaluation, treatment and predictors for a successful BOO surgery for DU. DU from BOO can result from several pathophysiological mechanisms. Although urodynamic study (UDS) is considered as a precise method to diagnose DU and BOO, there are some previous studies which proposed a non-invasive method to identify DU related to BOO. The treatment goal of DU is restoring bladder contractility using medication or surgery. Releasing outlet obstruction and resistance is the main strategy to restore bladder contractility when medication to directly increase bladder contractility has had limited efficacy. DU from BOO is poorly understood and is largely under-researched. The etiology and pathophysiology still need to be evaluated. Effective and safe medication to restore bladder contractility is also lacking. It remains valuable to perform further research to reveal the unknown aspects of DU.

High Intensity Focused Ultrasound Ablation for Prostate Cancer: Whole Versus Partial Gland Ablation.

We compared the clinical outcomes between whole-gland ablation (WGA) and partial gland ablation (PGA) using the high-intensity focused ultrasound (HIFU) technique for localized prostate cancer (PCa). We retrospectively investigated 206 patients who underwent WGA or PGA for localized PCa. Follow-up prostatic biopsy was performed 1 year postoperatively. We performed intergroup comparison of the postoperative functional and oncological outcomes and complication rates. In this study, 152 and 54 patients underwent PGA and WGA, respectively. The total operation time was significantly longer in the WGA than in the PGA group (107.5 minutes vs. 95.0 minutes, P=.004). Of the 86 patients who underwent postoperative prostate biopsy, no residual cancer was detected in 70.4% of the WGA and 72.9% of the PGA group. Incontinence-free survival was significantly shorter in the PGA than in the WGA group (P= .047); however, no significant intergroup difference was observed in erectile dysfunction-free survival (P= .317). The postoperative adverse event rate was significantly lower in the PGA than in the WGA group (37.5% vs. 66.7%, P=.023). Of the total patients investigated, 43 (20.9%) required additional endoscopic surgery for bladder outlet obstruction, and the additional endoscopic surgery rate was significantly higher in the WGA than in the PGA group (35.2% vs. 15.8%, P=.005). HIFU treatment was associated with acceptable oncological and fair functional outcomes in patients with localized PCa. Moreover, PGA was associated with significantly better clinical outcomes, including the faster recovery of urinary incontinence and adverse effects.

Bladder Decompensation in Patients with Benign Prostatic Hyperplasia: Causes, Complications, Rehabilitation

Background Despite the high efficiency of surgical methods in correction of bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia (BPH), a significant proportion of patients (up to 35%) remains after surgery with impaired contractile function of the bladder and lower urinary tract symptoms (LUTS). Both are consequences of structural and functional changes of the detrusor due to long-term exposure to obstructive factor. Today there is a lack of systematic reviews that provide a specialist with an integrative conception of pathological changes in the bladder wall caused by BPH associated prolonged BOO and evidence based methods of detrusor rehabilitation. The objective: systematization of modern conceptions about structural and functional changes in the bladder of patients with BPH caused by prolonged BOO, and methods of their correction. Materials and methods. An analytical review of the literature covering pathogenesis of bladder remodeling due to BPH associated long-term BOO and methods of bladder rehabilitation was performed. Literature sources were searched in PubMed, Google Scholar, Scopus and Web of Science databases by keywords. The search depth was 40 years. 74 relevant publications were selected for analysis. Results. Bladder remodeling due to obstructive factor is a complex staged process that involves all layers of the wall at the tissue, cellular and subcellular levels, affecting not only the executive structures (urothelium, smooth-muscle syncytium, fibrous connective tissue matrix), but also the system metabolism. Depending on the nature of the changes, there are 3 stages of this process: compensation, subcompensation and decompensation. In the compensatory stage, an increase of the load on the bladder leads to hypertrophy of smooth muscle fibers. At the same time, there is a reorganization of the vascular bed – neoangiogenesis, which should provide increased energy needs of muscles. In the stage of subcompensation, vicarious hypertrophy and neoangiogenesis cease. The most prominent disorders of the structure and function of the bladder are observed in the stage of decompensation. It includes a number of pathological processes: hypoxia, anaerobic metabolism, oxidative stress, inflammation, changes in the paracrine environment (increased levels of HIF-1α, vascular endothelial growth factor (VEGF) and angiopoietin-1). It is characterized by progressive loss of contractile function of the detrusor due to the death of smooth muscle cells and neurons, deterioration of viscoelastic characteristics of the bladder wall due to excessive collagen synthesis by fibroblasts, loss of barrier properties of the mucous membrane due to dystrophy. It was found that the severity of these pathological changes correlates with the severity of LUTS in patients who underwent surgery for BPH. The current arsenal of measures for bladder rehabilitation is quite diverse and includes periodic sterile catheterization, pharmacotherapy (cholinesterase inhibitors, antioxidants), physiotherapy (electrical stimulation, muscles training) and plastic surgery. However, there is still a lack of high-level studies to prove their effectiveness in patients who have undergone prostate surgery for BOO caused by BPH. Conclusions. Persistence of LUTS in patients who have undergone prostate surgery due to BOO may be caused by bladder decompensation. Long-term bladder decompensation due to prolonged exposure to obstructive factor is a complex process that includes decreased contractile activity, deterioration of the viscoelastic characteristics of the bladder, and impaired mucosal barrier function. Further research is needed to develop an effective bladder rehabilitation protocol.

UK national bladder outlet obstruction surgery snapshot audit.

To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK. A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery. There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively. There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Mucinous Adenocarcinoma of the Prostate Found Incidentally in Adenomectomy Specimen Complicated with Vesicocutaneous Fistulae

Primary mucinous tumors of the prostate gland are rare, including mucinous adenocarcinoma, prostatic adenocarcinoma with mucinous features, and mucinous adenocarcinoma of the prostatic urethra. In this report, we present a case of a locally advanced mucinous variant of prostatic ductal adenocarcinoma, found incidentally during pathology examination of an adenomectomy specimen, after bladder outlet obstruction surgery. Recent large studies indicated that mucinous adenocarcinoma of the prostate, treated by radical prostatectomy, is not more aggressive than ordinary nonmucinous prostatic adenocarcinoma. In our case, the rapid deterioration of our patient, the return of tumor in its initial size soon after surgery, in addition to its distal metastatic spread should be attributed not only to the mucinous variant of prostatic adenocarcinoma but also to the advanced stage during initial diagnosis and the noncompliance of the patient with the suggested treatment after surgery, omitting radiotherapy, and hormonal maneuvers.

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling.

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.

MP28-11 ANNEXIN A1 INHIBITS NLRP3 AND PREVENTS INFLAMMATION DURING BLADDER OUTLET OBSTRUCTION

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I (MP28)1 Apr 2020MP28-11 ANNEXIN A1 INHIBITS NLRP3 AND PREVENTS INFLAMMATION DURING BLADDER OUTLET OBSTRUCTION Shelby N. Harper*, Francis M. Hughes, Brent D. Nose, Michael Zheng, Huixia Jin, and J. Todd Purves Shelby N. Harper*Shelby N. Harper* More articles by this author , Francis M. HughesFrancis M. Hughes More articles by this author , Brent D. NoseBrent D. Nose More articles by this author , Michael ZhengMichael Zheng More articles by this author , Huixia JinHuixia Jin More articles by this author , and J. Todd PurvesJ. Todd Purves More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000867.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Inflammation is a delicate balance between activators and inhibitors. A pivotal activator of inflammation is the NLRP3 inflammasome, which our lab has shown to be a central mediator of bladder inflammation in response to bladder outlet obstruction (BOO). However, little is known about endogenous inhibitors of inflammation within the bladder. Studies in other tissues have found Annexin A1 (ANXA1) has profound anti-inflammatory properties mediated through its interaction with the formyl peptide receptors (FPRs). One study has noted the presence of ANXA1 within bladder urothelia, but it is currently unknown if ANXA1 may interact with NLRP3 and/or inhibit inflammation in this tissue. In this study, we explore ANXA1’s relationship with NLRP3 in bladder urothelia in vitro and its ability to attenuate inflammation during BOO in vivo. METHODS: Female rats (∼200 g) were used. In vitro, primary urothelium were plated (o/n, 96-well plate), then treated with Ac2-26 for 1 hour followed by 0.625 mM ATP for an additional hour before being assayed for caspase-1 activity. Controls were treated with 1.25 mM ATP for maximal caspase activation. In vivo, rats underwent BOO surgery via insertion of a transurethral catheter (1 mm o.d.), tying of silk suture around the urethra, and removing the catheter. Ac2-26 (an ANXA1 mimetic; 1 mg/kg/day, i.p.) or PBS was administered for 12 days. Immunohistochemistry, Evans blue (inflammation), and caspase-1 (inflammasome activity) assays were then performed. RESULTS: In vitro, Ac2-26 decreased ATP-stimulated caspase-1 activity in a dose dependent fashion (figure 1). In vivo, immunocytochemistry showed ANXA1, FPR1 and FPR2 were present in bladder urothelium, while Ac2-26 decreased BOO-induced inflammasome activation and inflammation (figure 2). CONCLUSIONS: ANXA1 is a functional antagonist of NLRP3 and can suppress inflammation during BOO suggesting it may be a useful pharmacologic target for inflammatory conditions in the bladder. Source of Funding: NIDDK: R01DK103534 (PI- Purves) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e424-e424 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shelby N. Harper* More articles by this author Francis M. Hughes More articles by this author Brent D. Nose More articles by this author Michael Zheng More articles by this author Huixia Jin More articles by this author J. Todd Purves More articles by this author Expand All Advertisement PDF downloadLoading ...

Transurethral prostate surgery as a preventive method against progression of chronic kidney disease in patients with urodynamically proven bladder outlet obstruction.

The present study was aimed to investigate (1) whether urodynamic factors are responsible for kidney damage in patients with bladder outlet obstruction (BOO) and (2) whether transurethral prostate surgery for BOO can alleviate the damage to the kidneys. This prospective observational study involved men aged 50-80years. Prostate size and urodynamic test were performed during screening period. Laboratory tests to measure the glomerular filtration rate, the urinary protein to creatinine ratio and dipstick urinalysis were performed before and 6months after the transurethral prostate surgery. Sixty-seven patients completed the laboratory study among a hundred enrolled patients with urodynamically proven BOO. Among the urodynamic parameters, only low bladder compliance (lower than 60mL/cmH2O) was associated with clinically significant proteinuria (p < 0.001). Transurethral prostate surgery significantly improved proteinuria (p = 0.007), especially in patients with low bladder compliance (p = 0.004), and subsequently decreased the risk grade of CKD progression (p < 0.001). Low bladder compliance in patients with BOO may be a risk factor for kidney damage. Transurethral prostate surgery to relieve BOO could be a preventive method against CKD progression in patients with low bladder compliance.

Development and validation of a clinical nomogram predicting bladder outlet obstruction via routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms.

We aimed to develop and validate a clinical nomogram predicting bladder outlet obstruction (BOO) solely using routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms (LUTS). A total of 750 eligible patients ≥50 years of age who had previously not responded (International Prostate Symptom Score [IPSS] improvement <4 points) to at least three different kinds of LUTS medications (including a-blocker) for the last 6 months were evaluated as subcohorts for nomogram development (n = 570) and for split-sample validation (n = 180). BOO was defined as Abrams–Griffiths number ≥40, or 20–39.9 with a slope of linear passive urethral resistance ratio >2 cmH2O ml−1 s−1. A stepwise multivariable logistic regression analysis was conducted to determine the predictors of BOO, and b-coefficients of the final model were selected to create a clinical nomogram. The final multivariable logistic regression model showed that age, IPSS, maximum urinary flow rate, postvoid residual volume, total prostate volume, and transitional zone index were significant for predicting BOO; these candidates were used to develop the final nomogram. The discrimination performance of the nomogram was 88.3% (95% CI: 82.7%–93.0%, P < 0.001), and the nomogram was reasonably well-fitted to the ideal line of the calibration plot. Independent split-sample validation revealed 80.9% (95% CI: 75.5%–84.4%, P < 0.001) accuracy. The proposed BOO nomogram based solely on routine clinical parameters was accurate and validated properly. This nomogram may be useful in determining further treatment, primarily focused on prostatic surgery for BOO, without impeding the detection of possible BOO in men with LUTS that is refractory to empirical medications.

Dietary macronutrients modulate hypertrophy and contractility of the detrusor in an experimental model of bladder obstruction

ObjectivesTo investigate the effects of various diets on structure and function of the bladder in both normal and obstructed bladders of male Wistar rats. MethodsSham-operated rats and rats with experimentally-induced bladder outlet obstruction (BOO) were fed with standard rats’ feed (control), High-carbohydrate (HCD), High-fat (HFD) and High-protein (HPD) diets. Feeding was continued for 4 weeks after BOO surgery. Bladder weight, detrusor contractility, Rho-Kinase (ROK) and Myosin Light Chain Kinase (MLCK) expressions were determined using standard methods. ResultsIn comparison with control, bladder weight was increased in HFD (164 ± 9 mg), BOO (437 ± 21 mg), HFD-BOO (523 ± 19 mg) and HPD-BOO (268 ± 18 mg). Detrusor contractility was reduced in BOO and HFD-BOO. The ROK- I and II expressions were high in HCD-BOO and low in HPD-BOO but ROK-I was also elevated in BOO. However, MLCK increased only in HCD-BOO. ConclusionThe results of the study reveal that diets with varying macronutrient compositions have variable effects on the bladder with and without obstruction. High-fat diets especially, affect detrusor morphology and function in both obstructed and unobstructed bladders.

Detrusor Underactivity and Bladder Outlet Procedures in Men

Detrusor underactivity (DU) is a common but poorly understood clinical problem. The diagnosis and treatment of DU are difficult and full of uncertainties. There are many overlaps between DU and bladder outlet obstruction (BOO) in clinical symptoms and managements. In this review, we discuss the relationship of clinical diagnosis and treatment between DU and BOO in men, especially the outcome of bladder outlet surgery in patients with DU. DU could be resulted from many different etiologies, including psychogenic, neurogenic, myogenic, and the reduced detrusor contractility after increasing muscle work against the increase of bladder outlet resistance. Current managements are usually focused on relieving voiding difficulty and prevent urine retention to avoid urinary tract infection and upper urinary tract deterioration. Since there is no suitable medical treatment to enhance bladder contractility, most of the researches focus on reducing bladder outlet resistance and treat BOO. Many recent studies have reported the therapeutic outcome of transurethral incision of the bladder neck, transurethral resection of the prostate and urethral sphincter botulinum toxin A injection. The current treatment options in DU are limited. Even if there are many clinical trials revealing good results in patients with DU after BOO surgery, the evidence that BOO surgeries benefit patients with DU are still controversial. The actual mechanism of detrusor function recovery after BOO surgery in men with DU has not been well elucidated. Nevertheless, a portion of men with DU can safely and effectively improve their voiding symptoms and voiding efficiency after BOO surgeries. Further research of the underlying pathophysiology between DU and BOO is mandatory.

Inhibitory effects of silodosin on the bladder mechanosensitive afferent activities and their relation with bladder myogenic contractions in male rats with bladder outlet obstruction.

We investigated the effects of silodosin, an α1A-adrenoceptor (AR) antagonist, on bladder function, especially on non-voiding contractions (NVCs), in a male rat model of bladder outlet obstruction (BOO) by evaluating cystometry (CMG) findings and bladder mechanosensitive single-unit afferent activities (SAAs), related with microcontractions, which may be similar with NVCs and to be of myogenic origin, in the rat model. BOO was created by partial ligation of the posterior urethra. At 4 days after surgery for BOO, an osmotic pump filled with silodosin (0.12 mg/kg/day) or its vehicle was subcutaneously implanted. At 10 days after surgery, CMG and SAAs measurements were taken under conscious and urethane-anesthetized conditions, respectively. The SAAs of Aδ- and C-fibers, which were identified by electrical stimulation of the pelvic nerve and by bladder distention, and intravesical pressure were recorded during constant bladder-filling with saline. Microcontractions were divided into three phases: "ascending," "descending," and "stationary." The silodosin-treated group showed a smaller number of NVCs in CMG measurements and lower SAAs of both Aδ- and C-fibers than the vehicle-treated group during bladder-filling. Moreover, in the vehicle-treated groups, the SAAs of both fibers for the ascending phase of microcontractions were significantly higher than those for the other two phases. On the contrary, no significant change was found between any of these three phases in the silodosin-treated group. The present results suggest that silodosin inhibits the SAAs of mechanosensitive Aδ- and C-fibers at least partly due to suppressing myogenic bladder contractions in male BOO rats.

Expression of cannabinoid 1 and, 2 receptors and the effects of cannabinoid 1 and, 2 receptor agonists on detrusor overactivity associated with bladder outlet obstruction in rats

BackgroundThis study investigated changes in the expression of cannabinoid (CB) receptors and the effects of CB1 and CB2 agonists on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO) in rats.MethodsMale Sprague Dawley rats were randomly assigned to four groups (n = 10) in each group. The control group comprised sham-operated rats. A animals in the BOO, CB1 agonist and CB2 agonist groups all underwent BOO surgery. Three weeks postoperatively, cystometrography (CMG) was performed on all rats. After confirming the presence of DO in the CB1 and CB2 agonist groups, a CB1 agonist (WIN 55,212–2) and a CB2 agonist (CB65) were instilled intravesically, and CMG was repeated. CMG parameters, including the contraction interval (CI) and contraction pressure (CP) were then analyzed. The bladders of rats in all four groups were excised following CMG. Immunofluorescence staining and Western blotting were performed to localize CB1 and CB2 and measure their expression levels in the urothelium and detrusor muscle.ResultsThe CI was significantly longer and the CP was significantly lower in the CB1 agonist group than in the BOO group. CI and CP in the CB2 agonist group showed the same results. CB1 receptor immunofluorescence staining signals and immunoreactive bands in Western blotting were increased in the BOO group compared with results in the control group. Similarly, results for the CB2 receptor were also increased in the BOO group, although this difference was not significant. The CMG parameters in the BOO group were significantly improved by the inhibitory effects of CB1 and CB2 agonists on BOO-associated DO. The expression of CB1 was significantly increased in the urothelium and detrusor muscle in BOO-associated DO, but no significant change in CB2 expression was observed.ConclusionsCB1 and CB2 receptors, especially CB1, play a role in the pathophysiology of BOO-associated DO, and could serve as therapeutic targets.