Validation of Dynamic 3D MRI for Urodynamics Assessment Using an Anatomically Realistic In Vitro Model of the Bladder.

Lowery urinary tract symptoms (LUTS) affect a large majority of the aging population. 3D Dynamic MRI shows promise as a noninvasive diagnostic tool that can assess bladder anatomy and function (urodynamics) while overcoming challenges associated with current urodynamic assessment methods. However, validation of this technique remains an unmet need. In this study, an anatomically realistic, bladder-mimicking in vitro flow model was created and used to systematically benchmark 3D dynamic MRI performance using a highly controllable syringe pump. Time-resolved volumes of the synthetic bladder model were obtained during simulated filling and voiding events and used to calculate volumetric flowrate. During MRI acquisitions, pressure during each event was recorded and used to create PV loops for work assessment. Error between control and MRI-derived volume for voiding and filling events exhibited 3.36% and 4.66% differences, respectively. A slight increase in average error was observed for MRI-derived flowrate when compared to the control flowrate (4.90% and 7.67% for voiding and filling, respectively). Overall, average error in segmented volumes increased with decreasing volume flowrate. Pressure drops were observed during voiding. Pressure increased during filling. Enhanced validation of novel 3D MRI urodynamics is achieved by using high-resolution PIV for visualizing and quantifying velocity inside the bladder model, which is not currently possible with 3D Dynamic MRI.

Technical feasibility of uro-dynamic MRI study of voiding biomechanics: a pilot study.

INTRODUCTION: Dynamic volumetric MRI was used to non-invasively assess voiding biomechanics in a healthy male volunteer. METHODS: Using 3D Differential Subsampling with Cartesian Ordering (DISCO) Flex acquisition sequence, volumetric bladder images were obtained throughout the voiding effort. These were subsequently segmented using MIMICS. Segmented anatomical volumes were used to quantify total voided volume, post-void residual, volumetric displacement of urine over time, bladder neck angle, sphericity index, and prostatic urethral angle through the voiding effort. RESULTS: Bladder sphericity index correlated positively with flow rate. The greatest degree of bladder neck funneling correlated with the maximum urine flow rate. There was straightening of the prostatic urethral angle during voiding that also correlated positively with urine flow. CONCLUSION: This pilot study confirms the potential of dynamic MRI to provide non-invasive assessment of lower urinary tract anatomy and biomechanics during voiding.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to develop the novel analytical approach and to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Histologic inflammation and collagen content are not positively correlated in human BPH.

INTRODUCTION: Recent clinical studies have implicated prostate inflammation and fibrosis in the development of bladder outlet obstruction and lower urinary tract symptoms (LUTS). Studies utilizing rodent models, including work in our laboratory, have shown prostate fibrosis to occur as a consequence of inflammation. However, the relationship between collagen content and inflammation in human tissue samples obtained from surgical treatment of benign prostatic hypererplasia (BPH)/LUTS has not to our knowledge been previously examined. METHODS: Prostate tissue specimens from 53 patients (ages 47-88, mean 65.1) treated by open simple prostatectomy or transurethral resection of the prostate for BPH/LUTS were stained to quantitatively assess prostate inflammation and collagen content. Patients with prostate cancer present in greater than 5% of the surgical specimen were excluded. Prostate volume was determined from pelvic CT scan obtained within 2 years of surgery. RESULTS: Analysis of the data showed that inflammation was inversely correlated with collagen content (r = -0.28, p = 0.04). In men with prostates less than 75 cm3 inflammation increases and collagen content decreases with prostate volume (p = 0.002 and p = 0.03, respectively) while in men with prostate volume over 75 cm3 inflammation decreases and collagen content increases with prostate volume (p = 0.30 and p = 0.005, respectively). CONCLUSIONS: Our data do not support the assumed positive association of prostate inflammation with collagen content. Coordinated analysis of scatter plots of inflammation and collagen content with prostate volume revealed a subset of prostates with volumes >50 cm3 prostate characterized by intense inflammation and low collagen content and it is this subgroup that appears most responsible for the inverse correlation of inflammation and collagen.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

The role of the bladder diary in phenotyping men with LUTS.

AIMS: The aim of this study was to compare the clinical characteristics of men with lower urinary tract symptoms (LUTS) grouped by 24-h urine output determined from a bladder voiding diary. METHODS: An online database was queried to identify men who completed a 24-hour bladder diary (24HBD), and the Lower Urinary Tract Symptom Score (LUTSS) questionnaire from 2015 to 2019 using a mobile app. Data from the bladder diary and questionnaire were contemporaneously matched within a 2-week period. Additional data, including maximum uroflow (Qmax ) and postvoid residual urine (PVR), were obtained from the electronic medical record (EMR). The cohort was divided into three groups: normal, oliguria, and polyuria based on their 24-hour voided volume (24HVV). The LUTSS, 24HVV, maximum voided volume (MVV), maximum flow rate (Qmax ), and PVR were compared between those with oliguria and polyuria. RESULTS: A total of 327 men (mean age 62, SD: 19) completed the LUTSS questionnaire and contemporaneous 24HBD. Of these, 61% had a normal 24HVV, 13% had oliguria, and 26% had polyuria. A total of 147 patients from the study cohort had contemporaneous Qmax and PVR abstracted from the EMR. There was no difference in symptom severity, bother, or PVR among the three patient groups. However, several objective metrics were significantly correlated with urine output. Men with oliguria, as compared to men with polyuria were older (65 vs. 55 years) and had lower MVV (260 vs. 470 mL), fewer voids/24 h (8 vs. 13), and lower Qmax (8.5 vs. 18.3 mL/s). CONCLUSIONS: These observations suggest that men with oliguria or polyuria and LUTS constitute easily distinguished phenotypes that might require different diagnostic and therapeutic algorithms. Those with oliguria were older, and had lower MVVs and much lower uroflows, suggesting that they are more likely to have underlying disorders such as bladder outlet obstruction and detrusor underactivity or may be patients with overactive bladder who reduced fluid intake to improve symptoms.

A STAT5-Smad3 dyad regulates adipogenic plasticity of visceral adipose mesenchymal stromal cells during chronic inflammation.

Adipogenic differentiation of visceral adipose tissue-resident multipotent mesenchymal stromal cells (VA-MSC) into adipocytes is metabolically protective. Under chronic inflammatory stress, this neoadipogenesis process is suppressed by various pro-inflammatory cytokines and growth factors. However, the underlying mechanism(s) regulating VA-MSC plasticity remains largely unexplored. Using an adipogenic differentiation screen, we identified IFNγ and TGFß as key inhibitors of primary human VA-MSC differentiation. Further studies using human and mouse VA-MSCs and a chronic high-fat diet-fed murine model revealed that IFNγ/JAK2-activated STAT5 transcription factor is a central regulator of VA-MSC differentiation under chronic inflammatory conditions. Furthermore, our results indicate that under such conditions, IFNγ-activated STAT5 and TGFß-activated Smad3 physically interact via Smad4. This STAT5-Smad4-Smad3 complex plays a crucial role in preventing the early adipogenic commitment of VA-MSCs by suppressing key pro-adipogenic transcription factors, including CEBPδ, CEBPα, and PPARγ. Genetic or pharmacological disruption of IFNγ-TGFß synergy by inhibiting either STAT5 or Smad3 rescued adipogenesis under chronic inflammatory stress. Overall, our study delineates a central mechanism of MSC plasticity regulation by the convergence of multiple inflammatory signaling pathways.

E-cadherin deficiency promotes prostate macrophage inflammation and bladder overactivity in aged male mice.

Decreased E-cadherin immunostaining is frequently observed in benign prostatic hyperplasia (BPH) and was recently correlated with increased inflammation in aging prostate. Homozygous E-cadherin deletion in the murine prostate results in prostate inflammation and bladder overactivity at 6 months of age. However, this model is limited in that while E-cadherin is significantly reduced in BPH, it is not completely lost; BPH is also strongly associated with advanced age and is infrequent in young men. Here, we examined the functional consequences of aging in male mice with prostate luminal epithelial cell-specific E-cadherin heterozygosity. In control mice, aging alone resulted in an increase in prostate inflammation and changes in bladder voiding function indicative of bladder underactivity. At 24 months of age, mice with prostate-specific Cre-mediated heterozygous deletion of E-cadherin induced at 7 weeks of age developed additional prostatic defects, particularly increased macrophage inflammation and stromal proliferation, and bladder overactivity compared to age-matched control mice, which are similar to BPH/LUTS in that the phenotype is slow-progressing and age-dependent. These findings suggest that decreased E-cadherin may promote macrophage inflammation and fibrosis in the prostate and subsequent bladder overactivity in aging men, promoting the development and progression of BPH/LUTS.

Cluster analysis of men undergoing surgery for BPH/LUTS reveals prominent roles of both bladder outlet obstruction and diminished bladder contractility.

Lower urinary tract symptoms (LUTS) in aging men are commonly attributed to bladder outlet obstruction from benign prostatic hyperplasia (BPH) but BPH/LUTS often reflects a confluence of many factors. We performed a hierarchical cluster analysis using four objective patient characteristics (age, HTN, DM, and BMI), and five pre-operative urodynamic variables (volume at first uninhibited detrusor contraction, number of uninhibited contractions, Bladder Outlet Obstruction Index (BOOI), Bladder Contractility Index (BCI) and Bladder Power at Qmax) to identify meaningful subgroups within a cohort of 94 men undergoing surgery for BPH/LUTS. Two meaningful subgroups (clusters) were identified. Significant differences between the two clusters included Prostate Volume (95 vs 53 cc; p-value = 0.001), BOOI (mean 70 vs 49; p-value = 0.001), BCI (mean 129 vs 83; p-value <0.001), Power (689 vs 236; p-value <0.001), Qmax (8.3 vs 4.9 cc/sec; p-value <0.001) and post-void residual (106 vs 250 cc; p-value = 0.001). One cluster is distinguished by larger prostate volume, greater outlet resistance and better bladder contractility. The other is distinguished by smaller prostate volume, lower outlet resistance and worse bladder contractility. Remarkably, the second cluster exhibited greater impairment of urine flow and bladder emptying. Surgery improved flow and emptying for patients in both clusters. These findings reveal important roles for both outlet obstruction and diminished detrusor function in development of diminished urine flow and impaired bladder emptying in patients with BPH/LUTS.

Transrectal ultrasound guided prostate biopsy performed by supervised junior and senior residents is safe and does not result in inferior outcomes.

PURPOSE: To compare transrectal ultrasound guided prostate biopsy (TRUSBx) cancer detection and complication rates between residents at different levels of training and attending physicians at a single academic center. METHODS: We performed a retrospective review of consecutive series of 623 men undergoing TRUSBx from June 2014 to February 2017. The procedure was performed either by resident physicians under direct supervision by an attending physician or by an attending physician. In total, junior residents, senior residents and attending physicians performed 244, 212, and 167 biopsies, respectively. Prostate cancer detection, 30-day complications, and 30-day hospitalizations rates were the outcomes of interest. We performed multivariable logistic regression analysis to identify predictors of these outcomes and examined the hypothesis that TRUSBx performed by trainees would not be associated with inferior outcomes. RESULTS: There was no statistically significant difference in patient populations between the three groups when stratified by age, BMI, Charleston co-morbidity index, aspirin use, PSA level and palpable nodule on DRE. Prostate cancer was detected in 43.8% of the biopsies and there was no difference in detection rates (P = 0.53), Gleason score (P = 0.11), number of positive cores (P = 0.95), 30-day hospitalization (P = 0.86), and 30-day complication rates (P = 0.67) between TRUSBx performed by trainees and attending physicians. CONCLUSIONS: TRUSBx performed by residents and attending physicians yielded equivalent rates of cancer detection with no significant difference in 30-day complications or 30-day hospitalizations rates. There was no difference in outcomes between junior and senior residents suggesting that with adequate faculty supervision, it is safe for trainees at all levels to perform prostate biopsies.

Comprehensive non-invasive analysis of lower urinary tract anatomy using MRI.

PURPOSE: Anatomic changes that coincide with aging including benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) negatively impact quality of life. Use of MRI with its exquisite soft tissue contrast, full field-of-view capabilities, and lack of radiation is uniquely suited for quantifying specific lower urinary tract features and providing comprehensive measurements such as total bladder wall volume (BWV), bladder wall thickness (BWT), and prostate volume (PV). We present a technique for generating 3D anatomical renderings from MRI to perform quantitative analysis of lower urinary tract anatomy. METHODS: T2-weighted fast-spin echo MRI of the pelvis in 117 subjects (59F;58 M) aged 30-69 (49.5 ± 11.3) without known lower urinary tract symptoms was retrospectively segmented using Materialise software. Virtual 3D models were used to measure BWV, BWT, and PV. RESULTS: BWV increased significantly between the 30-39 and 60-69 year age group in women (p = 0.01), but not men (p = 0.32). BWV was higher in men than women aged 30-39 and 40-49 (p = 0.02, 0.05, respectively) ,but not 50-59 or 60-69 (p = 0.18, 0.16, respectively). BWT was thicker in men than women across all age groups. Regional differences in BWT were observed both between men and women and between opposing bladder wall halves (anterior/posterior, dome/base, left/right) within each sex in the 50-59 and 60-69 year groups. PV increased from the 30-39 to 60-69 year groups (p = 0.05). BWT was higher in subjects with enlarged prostates (> 40cm3) (p = 0.05). CONCLUSION: Virtual 3D MRI models of the lower urinary tract reliably quantify sex-specific and age-associated changes of the bladder wall and prostate.

A pilot study of bladder voiding with real-time MRI and computational fluid dynamics.

Lower urinary track symptoms (LUTS) affect many older adults. Multi-channel urodynamic studies provide information about bladder pressure and urinary flow but offer little insight into changes in bladder anatomy and detrusor muscle function. Here we present a novel method for real time MRI during bladder voiding. This was performed in a small cohort of healthy men and men with benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) to demonstrate proof of principle; The MRI urodynamic protocol was successfully implemented, and bladder wall displacement and urine flow dynamics were calculated. Displacement analysis on healthy controls showed the greatest bladder wall displacement in the dome of the bladder while men with BPH/LUTS exhibited decreased and asymmetric bladder wall motion. Computational fluid dynamics of voiding showed men with BPH/LUTS had larger recirculation regions in the bladder. This study demonstrates the feasibility of performing MRI voiding studies and their potential to provide new insight into lower urinary tract function in health and disease.

Second-harmonic generation microscopy analysis reveals proteoglycan decorin is necessary for proper collagen organization in prostate.

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn - / - ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to the SHG coherence length, and found more disordered fibril organization in the Dcn - / - . We have also used image analysis readouts based on entropy, multifractal dimension, and wavelet transforms to compare the collagen fibril/fiber architecture in the two models, where all these showed that the Dcn - / - prostate comprised smaller and more disorganized collagen structures. All these SHG metrics are consistent with decreased SHG phase matching in the Dcn - / - and are further consistent with ultrastructural analysis of collagen in this model in other tissues, which show a more random distribution of fibril sizes and their packing into fibers. As Dcn is a known tumor suppressor, this work forms the basis for future studies of collagen remodeling in both malignant and benign prostate disease.

Potency Analysis of Mesenchymal Stromal Cells Using a Phospho-STAT Matrix Loop Analytical Approach.

Potency assays for mesenchymal stromal cells (MSCs) need to be defined in advanced clinical trials. Here, we have developed an assay matrix approach that captures the signal transducer and activator of transcription (STAT) phosphorylation of MSCs upon stimulation with their combined secretome that arose with the interaction of activated peripheral blood mononuclear cells (PBMCs). Secretome of heat-inactivated (HI) MSCs cocultured with and without activated PBMCs was used as an internal reference. We have compared the short-term phosphorylation status of STAT1, STAT3, STAT4, STAT5, and STAT6 on MSCs derived from human bone marrow, adipose tissue, and umbilical cord using phosflow technology. Secretome of live MSCs cocultured with activated PBMCs downregulate STAT1 and STAT3 phosphorylation on MSCs, whereas the secretome of HI-MSCs or PBMCs do not. Thus, investigation of the combined secretome of MSC and PBMC interaction on MSCs determine the potency of MSCs as the generator and sensor of the secretome. Bone marrow, adipose, and umbilical cord MSCs are comparable in modulating STAT1 and STAT3 responses. Measurements of STAT1 and STAT3 phosphorylation on MSCs as responder cells correlate and predict allogeneic T-cell suppression. Our comparative phosphomatrix approach between live and reference HI-MSCs defines the potency of MSCs as both stimulators and responders as part of a robust platform for predictive potency analysis. Stem Cells 2019;37:1119-1125.

Reflex urine culture testing in an ambulatory urology clinic: Implications for antibiotic stewardship in urology.

OBJECTIVES: To evaluate the performance characteristics of urinalysis and urine microscopy parameters for predicting urine culture results and to implement a reflex urine culture program. METHODS: We reviewed the charts of all patients presenting to our clinic January-March 2013 and June-August 2014, excluding those who were catheter-dependent or with urinary diversions. We assessed the association of urinalysis and urine microscopy parameters on urine culture outcomes defining a positive urinalysis as nitrite-positive and/or the presence of ≥5 white blood cells per high-powered field with bacteria and a positive urine culture as ≥10 000 colony-forming units/mL excluding diphtheroids. We carried out logistic regression to assess for predictors of positive urine culture to inform implementation of a reflex urine culture program. RESULTS: A total of 2764 patients were evaluated. Logistic regression using urinalysis variables identified positive nitrites (odds ratio 18.6, P < 0.001) and large leukocyte esterase (odds ratio 41.8, P < 0.001) as the strongest predictors of positive urine culture. Logistic regression using urine microscopy variables identified >50 white blood cells per high-powered field (odds ratio 13.6, P < 0.001) and moderate/many bacteria (odds ratio 16.8, P < 0.001) as the strongest predictors of positive urine culture. We used our positive urinalysis definition to implement the reflex urine culture program and noted a 60% reduction in urine culture rates over the first 3 months of implementation. CONCLUSIONS: A urine positive for nitrites and/or ≥50 white blood cells per high powered field with bacteria seems to have a strong association with a positive urine culture and the best negative predictive value. A reflex urine culture program is an effective strategy to decrease the rates of unnecessary urine culture and their associated costs.

Urinary Metabolomic and Proteomic Analyses in a Mouse Model of Prostatic Inflammation.

Lower urinary tract symptoms (LUTS) are common among aging men. Since prostatic inflammation is one of its etiologies, it is plausible that urinary metabolite and protein biomarkers could be identified and used to diagnose inflammation-induced LUTS. We characterized the urine metabolome and proteome in a mouse model of bacterial-induced prostatic inflammation. Mass Spectrometry (MS)-based multi-omics analysis was employed to discover urinary protein and metabolite-based biomarkers. The investigation of isobaric dimethylated leucine (DiLeu) labeling on metabolites allowed metabolomics and proteomics analysis on the same liquid chromatography (LC)-MS platform. In total, 143 amine-containing metabolites and 1058 urinary proteins were identified and quantified (data are available via ProteomeXchange with identifier PXD018023); among them, 14 metabolites and 168 proteins were significantly changed by prostatic inflammation. Five metabolic pathways and four inflammation-related biological processes were potentially disrupted. By comparing our findings with urinary biomarkers identified in a mouse model of genetic-induced prostate inflammation and with those previously found to be associated with LUTS in older men, we identified creatine, haptoglobin, immunoglobulin kappa constant and polymeric Ig receptor as conserved biomarkers for prostatic inflammation associated with LUTS. These data suggest that these putative biomarkers could be used to identify men in which prostate inflammation is present and contributing to LUTS.

Effectiveness of a transrectal prostate needle biopsy protocol with risk-tailored antimicrobials in a veterans cohort.

PURPOSE: To prospectively implement a prostate biopsy protocol to identify high-risk patients for bleeding or infectious complications and use risk-tailored antimicrobials, patient education, and postbiopsy monitoring with the objective of reducing complications. MATERIALS AND METHODS: Overall, 637 consecutive patients from June 2014 to August 2016 underwent prostate biopsy at our Veterans Affairs hospital. In the protocol cohort, patients were screened before biopsy and prophylaxis was tailored (high risk = ceftriaxone; low risk = ciprofloxacin). Patients were also provided additional education about bleeding and monitored for up to 1-hour. We defined complications as any deviation from normal postbiopsy activities. Comparisons were made between preprotocol/postprotocol cohorts. Logistic regression was used to identify risk factors for admissions or complications. RESULTS: Median age was 67 years (IQR: 64-69, P = 0.29) in both groups (pre n = 334, post n = 303). Preprotocol, 99% patients received ciprofloxacin; postprotocol, 86% received ciprofloxacin and 14% received ceftriaxone (P<0.001). There were no deaths in either group. There were decreased 30-day complication and hospitalization rates in the postprotocol group (pre 15% vs. post 8.9%, P = 0.025; 3.3% vs. 1.0%, P = 0.048). Sepsis occurred in 2 patients preprotocol and no patients postprotocol. Postprotocol group was associated with decreased 30-day complications on multivariable logistic regression (OR = 0.58, 95% CI: 0.35-0.95, P = 0.031). CONCLUSIONS: A screening protocol before prostate biopsy is a targeted approach for selecting prophylactic antimicrobials and closer monitoring postbiopsy for bleeding. Our results suggest that the protocol has a favorable effect on complication and hospitalization rates.

Urosymphyseal Fistulas Resulting From Endoscopic Treatment of Radiation-induced Posterior Urethral Strictures.

OBJECTIVE: To describe the inciting events leading to urosymphyseal fistulas (UFs) and pubic osteomyelitis (PO) in patients who had radiation-induced urethral strictures. METHODS: We retrospectively reviewed patients who underwent simultaneous pubic debridement, simple cystectomy, and urinary diversion for refractory UF and PO from 2014 to 2016. We investigated inciting events leading to UF, as well as patient presenting symptoms, diagnosis, management, and outcomes. RESULTS: Five patients were identified over a 2-year period. All patients had a previous history of radiation for prostate cancer. The median age was 67 years. All patients developed UF and PO after endoscopic intervention for urethral stricture. The number of endoscopic interventions per patient for stricture ranged from 1 to 7, including serial dilation, balloon dilation, and urethrotomy. Sterile urine cultures were obtained before all endoscopic interventions. All patients had pelvic pain with ambulation and recurrent urinary tract infections at presentation. Patients were diagnosed using a combination of retrograde urethrography and magnetic resonance imaging. Simultaneous pubic debridement with simple cystectomy and diversion was used for management in all cases. One patient died postoperatively with the remainder recovering well without PO or fistula recurrence, with a median follow-up of 16 months. CONCLUSION: UF can occur as a complication of endoscopic treatment of posterior urethral stricture in patients with a history of radiation therapy for prostate cancer. This study demonstrates that UF and PO may develop even with minimally traumatic procedures and sterile urine. All patients treated for posterior stricture must be considered at risk of development of fistulas and osteomyelitis.