Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

PROPOSED REVISION OF THE AMERICAN ASSOCIATION FOR SURGERY OF TRAUMA RENAL TRAUMA ORGAN INJURY SCALE: SECONDARY ANALYSIS OF THE MULTI-INSTITUTIONAL GENITOURINARY TRAUMA STUDY.

BACKGROUND: This study updates the American Association for Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention. METHODS: This was a secondary analysis of a multi-center retrospective study including patients with high grade renal trauma from 7 Level-1 trauma centers from 2013-2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells (PRBCs) transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the receiver-operator curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST organ injury scale. RESULTS: based on the 2018 OIS grading system, we included 549 patients with AAST Grade III-V injuries and CT scans (III: 52% (n = 284), IV: 45% (n = 249), and V: 3% (n = 16)). Among these patients, 89% experienced blunt injury (n = 491) and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC = 0.805, revised AUC = 0.883; p = 0.001) and number of units of PRBCs transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention. CONCLUSIONS: A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system. LEVEL OF EVIDENCE: II.

Sex Differences in Bladder Management, Symptoms, and Satisfaction After Spinal Cord Injury.

PURPOSE: We sought to characterize sex-stratified differences in bladder management and bladder symptoms and satisfaction after spinal cord injury. MATERIALS AND METHODS: This study was a prospective, cross-sectional, observational study; eligibility included: age ≥18 years and acquired spinal cord injury. Bladder management was grouped as (1) clean intermittent catheterization, (2) indwelling catheter, (3) surgery, and (4) voiding. Primary outcome was Neurogenic Bladder Symptom Score. Secondary outcomes were subdomains of the Neurogenic Bladder Symptom Score and bladder-related satisfaction. Multivariable regression was used in sex-stratified models to establish associations between participant characteristics and outcomes. RESULTS: A total of 1,479 participants enrolled in the study. Of the patients 843 (57%) were paraplegic and 585 (40%) were women. Median age and time from injury were 44.9 (IQR 34.3, 54.1) and 11 (IQR 5.1, 22.4) years. Women utilized clean intermittent catheterization at a lower rate (42.6% vs 56.5%) and surgery at a higher rate (22.6% vs 7.0%), especially catheterizable channel creation with or without augmentation cystoplasty (11.0% vs 1.9%). Women had worse measures of bladder symptoms and satisfaction across all outcomes. In adjusted analyses, women and men utilizing indwelling catheters had fewer associated overall symptoms (Neurogenic Bladder Symptom Score), less incontinence, and fewer storage and voiding symptoms. Surgery was associated with fewer bladder symptoms (Neurogenic Bladder Symptom Score) and less incontinence in women, and was also associated with better satisfaction in both sexes. CONCLUSIONS: There are significant sex-stratified differences in bladder management after spinal cord injury, which included a much higher use of surgery. Bladder symptoms and satisfaction are worse across all measurements in women. Women have a substantial associated benefit with surgery, while both sexes have fewer bladder symptoms with indwelling catheters compared to clean intermittent catheterization.

Clinical Validation of an Adult-acquired Buried Penis Classification System Based on Standardized Evaluation of the Penis, Abdomen, and Scrotum.

OBJECTIVE: To clinically validate a previously developed adult-acquired buried penis (AABP) classification system that is based on a standardized preoperative physical examination that subtypes patients by their penile skin/escutcheon complex (P), abdominal pannus (A), and scrotal skin (S). METHODS: The Trauma and Urologic Reconstruction Network of Surgeons (TURNS) database was used to create an AABP cohort. Patients were retrospectively classified using the previously described PAS classification system. The frequency of subtypes, surgical methods utilized for AABP repair, and correlations between PAS classification and surgery subtypes were analyzed. RESULTS: The final cohort consisted of 101 patients from 10 institutions. Interrater reliability between two reviewers was excellent (κ = 0.95). The most common subtypes were P2c (contributory escutcheon+insufficient penile skin; 27%) and P2a (contributory escutcheon+sufficient penile skin; 21%) for penile subtypes, A0 (no pannus; 41%) and A1 (noncontributory pannus; 39%) for abdominal subtypes, and S0 (normal scrotal skin with preserved scrotal sulcus; 71%) for scrotal subtypes. AABP repair procedures included escutcheonectomy (n = 59, 55%), scrotoplasty (n = 51, 48%), split-thickness skin grafting (n = 50, 47%), penile skin excision (n = 47, 44%) and panniculectomy (n = 7, 7%). P, A, and S subtypes were strongly associated with specific AABP surgical techniques. CONCLUSION: The PAS classification schema adequately describes AABP heterogeneity, is reproducible among observers, and correlates well with AABP surgery types. Future work will focus on how PAS subtypes affect both surgical and patient-centered outcomes.

A multicenter prospective cohort study of endoscopic urethral realignment versus suprapubic cystostomy after complete pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI. METHODS: Twenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction. RESULTS: There were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784). CONCLUSION: In this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.