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Objective: To determine the rate of stone formation amongst patients of the exstrophy-epispadias complex with augmentation cystoplasty. We hypothesize that bowel segment choice influences the rate of stone formation after bladder augmentation and the rate of complications from bladder stone surgery., Methods: An IRB-approved institutional database of 1512 exstrophy-epispadias patients was reviewed retrospectively. Patients that had a history of bladder augmentation and were seen at our institution between 2003 and 2023 were included., Results: Out of 259 patients, bladder stones developed in 21.6% (56), of which the bowel segment used was colon in 147 patients and ileum in 100. Stones formed in 19% of colon augments compared to 29% ileal augments, however, this was not statistically significant (P = .07). The most common primary stone component was dahllite, followed by struvite for all augments (Table 1). The median time to stone treatment after augmentation was 4.14 years (0.75-31). Seventy-four percentage of patients had a recurrence that required a second surgery. The median time from first to second surgery and second to third surgery was 1.4 years and 2.22 years, respectively. Bladder stone surgery complications occurred in 14% of patients, vesicocutaneous fistula being the most common, and complications did not differ by augment type. Median follow-up after first stone intervention was 6.07 years (0-19.5)., Conclusion: The treatment of bladder stones in the exstrophy-epispadias complex remains challenging. Interventions to prevent recurrence are crucial as the majority of patients will require 2 or more stone surgeries in their lifetime., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest The author declares that there is no conflict of interest.

Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare.

Objective: To identify risk factors for stenosis and compare management strategies for stenosis etiology and to examine the efficacy of each approach. Patients with classic bladder exstrophy (CBE), a rare genitourinary malformation, may require construction of a continent urinary stoma (CUS) if incontinence persists. Stomal stenosis is a challenging complication as it is common, progressive, and recurrent., Methods: CBE patients who underwent CUS were retrospectively reviewed for risk factors for stenosis including stoma type, prior midline laparotomy number, and umbilicoplasty suture material. Stenosis etiology and management strategies were further reviewed., Results: A total of 260 CBE patients underwent CUS creation. Stenosis developed in 65 patients (25.0%) at a median interval of 1.9 years. Etiology included scar contracture (n = 41), keloid (n = 17), and hypertrophic scar (n = 7). Multifilament suture was the only variable associated with an increased risk of stenosis compared to monofilament suture (P = .009). Almost all patients required surgical intervention. Most scar contractures underwent stomal incision with success in 100%. Hypertrophic scars and keloids responded best to excision with local tissue rearrangement (66.7%). At last follow-up, all patients achieved success., Conclusion: Stomal stenosis is common and challenging for the reconstructive surgeon. Strategies to prevent and effectively manage this are greatly desired. Use of multifilament suture for the umbilicoplasty increased stenosis perhaps from a greater inflammatory response and scarring, while monofilament suture may reduce its incidence. Stomal incision for treating scar contractures, and excision with local tissue rearrangement for hypertrophic scars and keloids may improve successful primary surgical intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: To determine if the administration of standardized opioid disposal instructions with focused parental education improves proper disposal of leftover opioid medication among families of children undergoing ambulatory urologic surgery compared to routine postoperative instructions., Methods: A prospective, double-blinded, single-center randomized controlled trial was conducted in children 6-18 years undergoing ambulatory urology procedures between October 2021 and April 2023. Patients were randomized (1:1) to receive either the Food and Drug Administration (FDA) opioid disposal best practices worksheet plus nursing parental education or routine postoperative instructions alone. All patients were prescribed acetaminophen and ibuprofen and a per-protocol rescue opioid prescription. The primary outcome was rate of proper opioid disposal at 10-14 days post-procedure. Secondary outcomes included parents' postoperative pain measure (PPPM) scores, numerical pain scale (NPS) scores, and weight-based opioid utilization at 48 hours and 10-14 days., Results: We randomized 104 participants (53 intervention, 51 control) with 97% (101/104) complete follow-up data at 10-14 days. Patient demographics, procedural characteristics, and analgesia use were similar between groups. We observed no significant difference in proper opioid disposal rates between arms (31% intervention vs 18% control; estimated difference in proportion 13% [95% CI, -4%-29%]; P = .1). There were no increased odds of proper disposal of leftover opioid medication at 10-14 days with the intervention compared to the control (OR 2.0 [95% CI 0.8-5.1]; P = .1). We observed no differences in PPPM scores, NPS scores, or opioid utilization at 48 hours or 10-14 days., Conclusion: Providing formal opioid disposal instructions with parental education did not improve proper disposal of leftover opioid medication nor did it alter post-discharge opioid utilization after pediatric urologic surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare outcomes among patients undergoing first-time urethroplasty with buccal mucosa graft (BMG) who receive postoperative antibiotics vs those who do not., Methods: A retrospective cohort study was conducted using the TriNetX claims database between 2008-2022. Using CPT, ICD10, and LOINC codes, patients >18 years old undergoing primary urethroplasty with BMG who received an outpatient prescription for antibiotics between postoperative day 0-30 or did not were queried. Patients with positive preoperative urine culture or urinary tract infection (UTI) within 30days preoperatively were excluded. Surgical outcomes included 5-year revision rates and revision-free survival. Safety outcomes included new UTI within 30days, surgical site infection within 90days, or Clostridium difficile infection within 30days of urethroplasty., Results: We identified 884 patients (81% antibiotic cohort, 19% nonantibiotic cohort) that met inclusion criteria. Age at time of urethroplasty, suprapubic tube presence, and pre-existing medical comorbidities were comparable between cohorts (Table 1A). There was no difference in 5-year rates and revision-free survival for endoscopic revision (11.5% vs 9.5%, relative risk (RR) 1.2, 95% CI [0.7, 2.0], recurrence-free survival (RFS) log-rank P = .6), re-do urethroplasty (12.9% vs 13.7%, RR 0.9, 95% CI [0.6, 1.5], RFS log-rank P = .7), or all-cause revision (19.8% vs 17.7%, RR 1.1, 95% CI [0.8, 1.6], P = .5) between groups. Postoperative rates of UTI, surgical site infection, and C difficile infection were similar between groups., Conclusion: In this large retrospective cohort study of patients undergoing urethroplasty with BMG, we observed no significant benefit from use of postoperative antibiotics on long-term revision rates or perioperative infectious complications., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.

Background and Objective: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis., Methods: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy., Key Findings and Limitations: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d., Conclusions and Clinical Implications: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making., Patient Summary: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare clinically significant prostate cancer detection with TP-TBx utilizing software vs cognitive fusion. It is established that MRI prior to prostate biopsy improves detection of clinically significant cancer (csPCa, Grade Group ≥2). MRI/US fusion targeted biopsy via a transperineal approach (TP-TBx) is increasing in utilization due to the clean percutaneous approach that greatly reduces postbiopsy infection. However, the comparative effectiveness of formal software fusion over cognitive fusion remains under studied., Materials and Methods: We performed a retrospective multicenter study from June 2020 to July 2022 including age, race, prostate-specific antigen (PSA), prostate volume, PI-RADS, lesion size(s), number of cores sampled, indication (elevated PSA, prior negative, active surveillance) and anesthesia type. Surgeon preference determined use of cognitive (PrecisionPoint) vs software fusion techniques. Multivariable logistic regression determined factors associated with TP-TBx detection of csPCa., Results: We identified 490 patients (201 cognitive, 289 software fusion) who underwent TP-TBx. Patient age, PSA, number of targets, and PI-RADS were similar (all P > .05). Software fusion TP-TBx had 4 [95% confidence interval (CI) 3-5] more (estimated median difference) systematic cores sampled. csPCa was detected in 44% of all patients. In adjusted analysis, cognitive vs software fusion was similar in detection of csPCa (odds ratio 1.46, 95% CI 0.82-2.58)., Conclusion: Cognitive vs software fusion TP-TBx has similar csPCa detection, despite fewer systematic cores taken with cognitive fusion. The expense, additional time requirement, and similar outcomes of software fusion platforms confers higher value to cognitive TP-Bx., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To compare surgical outcomes among a cohort of eugonadal and hypogonadal patients undergoing primary urethroplasty (UP)., Methods: A retrospective cohort study was conducted using TriNetX between 2008-2023. Patients who were eugonadal and hypogonadal (symptoms plus testosterone <300 ng/dL) prior to UP were compared. A subgroup analysis of hypogonadal patients was performed to compare those with testosterone replacement therapy (TRT) vs TRT-naïve prior to UP. Propensity-score matching was used to adjust for differences in comorbidities. Outcomes were 5-year revision rates and revision-free survival for endoscopic revision and redo UP following primary UP., Results: We identified 12,556 eugonadal and 488 hypogonadal patients (153 TRT+, 335 TRT-) undergoing UP. Median age at UP and follow-up was 55years and 5years, respectively. After propensity-score matching, we compared 477 eugonadal and 477 hypogonadal patients. Hypogonadal patients had a statistically significantly higher 5-year redo UP rate (11% vs 6%, relative risk [RR] 1.5 [95%CI, 1.2-2.2]; P = .01) when compared to eugonadal patients however there was no difference in 5-year rates of endoscopic revision (11% vs 11%, RR 1.0 [95%CI, 0.7-1.5]; P = 1.0). We observed no difference in 5-year revision-free survival time for endoscopic revision or redo UP between groups. Hypogonadal patients treated with TRT had a significantly higher 5-year redo UP rate (15% vs 7%, RR 1.8 [95%CI, 1.1-3.3]; P = .02) compared to hypogonadal patients that were TRT-naïve prior to UP. There was no difference in rates of endoscopic revision (14% vs 10%, RR 1.3 [95%CI, 0.7-2.4]; P = .2) between subgroups., Conclusion: Pre-existing hypogonadism may modestly adversely affect surgical outcomes following primary UP based on data from a large, retrospective cohort study., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate trends in opioid prescribing rates following pediatric urologic surgery., Methods: We queried the TriNetX Research database for patients under age 18 who underwent one of seven common pediatric urology procedures. We identified the proportion of patients that received an oral opioid prescription within 5days of surgery. The primary analysis evaluated the trend in postoperative opioid prescriptions using 3-month intervals from January 2010 to December 2022. We performed an interrupted time series analysis assessing trends in opioid prescribing patterns both before and after the American Academy of Pediatrics challenge., Results: Of the 81,644 pediatric urology procedures, 29,595 (36.2%) received a postoperative opioid prescription, including 29.8% of circumcisions, 25.8% of hydrocelectomies, 39.6% of hypospadias repairs, 42.7% of pyeloplasties, 42.8% of ureteral reimplants. For all procedures we observed rising rates of opioid prescribing, increasing by 0.9% per 3-month interval prior to the challenge statement release from 2010 to 2018. We observed an overall significant decrease in opioid prescribing by 2.2% per 3-month interval following the challenge statement release. Additionally, since 2018, there was a significant decrease in opioid prescribing in all of the race, ethnicity, and age cohorts., Conclusion: Opioid prescribing following pediatric urology procedures has sharply decreased following the 2018 American Academy of Pediatrics challenge statement which underscores the value of cross-specialty quality improvement initiatives. Nonetheless, opioid prescribing remains high with potential racial or age disparities that warrant further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the risk of persistent opioid use following various urologic procedures in adolescents and young adults., Materials and Methods: The TriNetX LLC Diamond Network was queried for patients aged 13-21years who underwent pyeloplasty, hypospadias repair, inguinal hernia repair, inguinal orchiopexy, hydrocelectomy, or circumcision. Cohorts of patients prescribed and not prescribed postoperative opioids were created and propensity-matched for age, race/ethnicity, psychiatric diagnoses, and preoperative pain diagnoses. The primary outcome was new persistent opioid use, defined as new opioid use 3-9months after index procedure without another surgery requiring anesthesia during the postoperative timeframe., Results: Of 32,789 patients identified, 66.0% received a postoperative opioid prescription. After propensity score matching for each procedure, 18,416 patients were included: 197 for pyeloplasty, 469 for hypospadias repair, 1818 for inguinal hernia repair, 2664 for inguinal orchiopexy, 534 for hydrocelectomy, and 3526 for circumcision. Overall, 0.41% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 1.69% of patients who received postoperative opioids developed new persistent opioid use (P < .05). Patients prescribed postoperative opioids had statistically higher odds of developing new persistent opioid use for hypospadias repair (RR: 17.0; 95% CI: 2.27-127.2), inguinal orchiopexy (RR: 3.46; 95% CI: 1.87-6.4), inguinal hernia repair (RR: 2.18; 95% CI: 1.07-4.44), and circumcision (RR: 4.83; 95% CI: 2.60-8.98)., Conclusion: The use of postoperative opioids after urological procedures in adolescents and young adults is associated with a significant risk of developing new persistent opioid use., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ 2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To review the outcomes of classic bladder exstrophy (CBE) closure without the use of osteotomy or lower extremity/pelvic immobilization., Methods: A prospectively maintained institutional approved exstrophy-epispadias complex database of 1487 patients was reviewed for patients with CBE who had undergone closure without osteotomy nor immobilization. All patients were referred to the authors' institution for reconstruction later in life or for failed closure., Results: Of a total of 1016 CBE patients, 56 closure events were identified that met inclusion with a total of 47 unique patients. Thirty-eight closures were completed prior to 1990 (67.9%). Forty-five closure events developed eventual failure (45/56, 80.4%) (Table 1). Thirteen closure events were secondary closures (13/56, 23.2%). The primary closure failure rate was 83.7% (36/43) while the secondary closure failure rate was 69.2% (9/13). Failures were attributed to one or more of dehiscence, bladder prolapse, and vesicocutaneous fistula (25/45, 55.6%) (23/45, 51.1%) (6/45, 13.3%), respectively. Thirty-seven patients developed social continence (37/47, 78.7%), while only 8 patients developed spontaneous voided continence (7/47,17.0%) (Table 2). The most common methods of voiding were continent catheterizable channels (25/47, 53.2%) of which all were socially continent., Conclusion: These results illustrate the critical role osteotomy and postoperative immobilization can play in both primary and secondary exstrophy closure. While this is a historical case series, the authors believe that these results remain relevant to contemporary exstrophy surgeons., Competing Interests: Declaration of Competing Interest The authors have no financial or personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To determine whether radiological change on serial multiparametric magnetic resonance imaging scored using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) Scoring system predicts grade reclassification (GR) at surveillance biopsy in men on active surveillance (AS) with Grade Group 1 (GG1) prostate cancer (PCa)., Methods: We retrospectively reviewed records of 255 men with low-risk PCa on AS with magnetic resonance imaging (MRI)-informed diagnostic and confirmatory biopsies and studied the subset who had surveillance biopsies (n = 163) within 6months of an interval MRI., Results: We studied 309 PRECISE scores in 255 men. 14% demonstrated radiological progression (PRECISE 4-5) on interval MRI performed within 24months, compared to 34% of those whose interval MRI was performed at a >3-year interval (P = .002). 28% (46/163) of men undergoing surveillance biopsy experienced GR to ≥ GG2 PCa. There was no significant increase in the rate of GR with increasing PRECISE score (PRECISE 1-2: 24%, PRECISE 3: 23%, PRECISE 4-5: 38%; P = .11). There was a significant increase in the rate of GR with increasing PI-RADS score (P < .05). On multivariable analysis, a PI-RADS score of 4-5 was significantly associated with GR compared to men who had a highest PI-RADS ≤3 (OR=1.98 [95% CI: 1.45-3.09, P = .01])., Conclusion: In a low-risk AS cohort with limited follow-up, a patient's highest PI-RADS rather than their PRECISE score on interval MRI was predictive of GR on surveillance biopsy., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility., Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry., Design, Setting, and Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry., Outcome Measurements and Statistical Analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness., Results and Limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10 -4 )., Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry., Patient Summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients., Objective: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT)., Design, Setting, and Participants: A multicenter phase 1 trial was conducted at community and academic sites., Intervention: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only)., Outcome Measurements and Statistical Analysis: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates., Results and Limitations: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients., Conclusions: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches., Patient Summary: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To test the hypothesis that phenotypes in bladder exstrophy result from alterations in detrusor smooth muscle cell (SMC) gene expression., Methods: We generated primary human bladder smooth muscle cell lines from patients with classic bladder exstrophy (CBE) undergoing newborn closure (n = 6), delayed primary closure (n = 5), augmentation cystoplasty (n = 6), and non-CBE controls (n = 3). Gene expression profiles were then created using RNA sequencing and characterized using gene set enrichment analysis (GSEA)., Results: We identified 308 differentially expressed genes in bladder exstrophy SMC when compared to controls, including 223 upregulated and 85 downregulated genes. Bladder exstrophy muscle cell lines from newborn closure and primary delayed closures shared expression changes in 159 genes. GSEA analysis revealed increased expression in the inflammatory response and alteration of genes for genitourinary development in newborn and delayed closure SMC. However, these changes were absent in SMC from older exstrophy patients after closure., Conclusion: Bladder exstrophy SMC demonstrate gene expression changes in the inflammatory response and genitourinary development. However, gene expression profiles normalized in exstrophy SMC from older patients after closure, suggesting a normalization of exstrophy SMC over time. Our in vitro findings regarding the normalization of exstrophy SMC gene expression following bladder closure suggest that the development of poor detrusor compliance in bladder exstrophy has a complex multifactorial etiology. Taken together, our findings suggest that alterations in SMC gene expression may explain abnormalities in the exstrophy bladder seen prior to and immediately after closure and suggest that surgical closure may allow exstrophy SMC to normalize over time., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) is emerging to become a reference imaging tool for the staging and restaging of patients with prostate cancer for both clinical routine and trials. The prostate cancer molecular imaging standardized evaluation (PROMISE) criteria have been proposed as a framework for whole-body staging (molecular imaging TNM staging, denoted miTNM staging) to describe the prostate cancer disease extent on PSMA-PET., Objective: To create a comprehensive and integrated framework for PSMA-PET image interpretation and reporting., Evidence Acquisition: We propose the PROMISE V2 framework, which integrates an updated miTNM system, improved assessment of local disease, and a slightly modified PSMA-expression score for clinical routine. We have added a response monitoring framework defining qualitative and quantitative parameters to be recorded for a longitudinal assessment in clinical trials., Evidence Synthesis: We provide a comprehensive literature review on the current use of the PROMISE framework in clinical research and prospective trials. PROMISE variables demonstrate a clear association with survival. PSMA expression assessed by the PSMA-expression score was used in several trials, and a low PSMA-expression score is a negative prognosticator of overall survival after 177 Lu-PSMA radioligand therapy. The proposed imaging parameters recorded for response assessment in clinical trials can be utilized to determine response according to PSMA-PET progression (PPP) or Response Evaluation Criteria in PSMA-PET/Computed Tomography (RECIP) frameworks, but also future response criteria., Conclusions: PROMISE V2 offers standardized reporting of disease extent for clinical routine and research. Parameters recorded within clinical trials facilitate objective response assessment., Patient Summary: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) has become a standard imaging examination for prostate cancer. We propose a comprehensive framework for the analysis and reporting of PSMA-PET findings that will improve the communication between imaging experts and uro-oncologists., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer., Materials and Methods: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis., Results: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection., Conclusion: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To develop an imaging modality for the postoperative phalloplasty urethra. Despite high urologic complication rates after masculinizing genital surgery, existing methods for postsurgical evaluation after phalloplasty have drawbacks. Fluoroscopic studies like the retrograde urethrogram have limitations like user-dependence and need for meticulous positioning but also are inadequate for the evaluation of the anatomically complex postphalloplasty urethra. We developed a novel protocol utilizing CT urethrography with 3D reconstruction using cinematic rendering (3DUG) for neo-urethral imaging., Materials and Methods: Patients who underwent 3DUG after either phalloplasty, metoidioplasty, or prior to revision surgery were included. Low-dose imaging protocols were used to avoid any increases in radiation exposure. The first iteration of our protocol utilized retrograde contrast administration via the penile urethra, whereas the second iteration of our protocol utilized an antegrade technique with contrast instillation via the suprapubic catheter and a voiding scan. Imaging was initially obtained according to symptoms and then per protocol at 3 weeks after urethral lengthening., Results: Twenty-six patients were included in the series. Among postoperative phalloplasty patients imaged for symptoms, contrast extravasation/fistula was identified in 5 (63%), vaginal remnant in 3 (38%), and stricture in 2 (25%) compared to 5 (45%), 1 (9%), and zero respectively for patients imaged routinely. When intervention was required, operative findings correlated to anatomy on imaging., Conclusion: We present a new protocol for the use of 3D CT urethrography with cinematic rendering for neo-urethral reconstruction. This technique has the potential to improve surgical planning and surveillance of urologic complications in postphalloplasty patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the association of common sleep disorders with female sexual dysfunction., Materials and Methods: We conducted a cross-sectional analysis using the TriNetX Diamond Network. Adult women diagnosed with insomnia, obstructive sleep apnea, or circadian rhythm sleep disorder were assessed to determine the association with female sexual dysfunction, hypoactive sexual desire disorder, female orgasmic disorder, and female sexual arousal disorder. A propensity-score matched control cohort for age, race, ethnicity, tobacco use, outpatient service utilization, obesity, hyperlipidemia, diabetes mellitus, hypertensive disease, ischemic heart disease, and surgical procedures on the female genital system was generated, excluding those with any sleep disorders, sleep deprivation, or morbid obesity with alveolar hypoventilation. All cohorts excluded those with any antidepressant or antipsychotic prescriptions., Results: Our query yielded 1,317,491 women diagnosed with sleep apnea, 1,538,567 with insomnia, and 58,902 with circadian rhythm sleep disorder. Women with sleep apnea and insomnia had higher odds of hypoactive sexual desire disorder, female sexual arousal disorder, and female orgasmic disorder compared to matched controls. Women with sleep apnea, insomnia, or circadian rhythm sleep disorder all had a significantly higher odds of female sexual dysfunction compared to matched controls., Conclusion: In this large cross-sectional analysis, sleep disorders were strongly associated with female sexual dysfunction. It is thus crucial for providers to screen for poor sleep when conducting a thorough evaluation for sexual dysfunction in women to diagnose highly prevalent sleep disorders and improve overall health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To describe long-term outcomes and experience with the tunica vaginalis flap (TVF) as a tissue augment for complex epispadias repair., Methods: A prospectively maintained institutional database was reviewed for patients who underwent epispadias repair with TVF from 2010 to 2021. Evaluation of patient characteristics between those who developed dehiscence or UCF and those who did not was performed via Mann-Whitney U, Kruskal-Wallis, or Fisher's exact test, as appropriate., Results: A total of 47 male patients were identified, of whom, 1 (2.1%) had cloacal exstrophy, 38 (80.9%) had classic bladder exstrophy or a variant, and 8 (17.0%) had epispadias as their primary exstrophy-epispadias complex diagnosis. The median age at epispadias repair was 13 months (IQR 11 - 19). The overall rate of fistula or dehiscence development was 19.1% (9 patients), of whom, 7 developed urethrocutaneous fistulae, 1 dehiscence, and 1 both. Notably, 0 of the 5 patients who had undergone prior epispadias repair and 0 of the 8 patients with a diagnosis of isolated epispadias developed a UCF or dehiscence after repair with TVF. Differences in age at repair, primary EEC diagnosis, prior epispadias repair, pre-repair testosterone, fibrin sealant utilization, closure layers, stent removal time, and bladder capacity at repair were not statistically significant (P>.05) CONCLUSION: Our expanded evaluation indicates that utilization of the tunica vaginalis as an adjunct to epispadias repair may provide durable protection against fistula development in EEC patients who have undergone prior epispadias repair and in primary repair of patients with isolated epispadias., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine opioid use following Urological trauma. Increased opioid use is associated with inferior outcomes and risk of dependence, particularly in vulnerable populations. In contrast, multimodal analgesia following trauma allows decreased pain and readmission. Currently there is a paucity of data describing opioid usage following urological trauma. The purpose of this study was to assess utilization of opioids and multimodal pain regimens following urologic trauma., Methods: We retrospectively examined 116 patients hospitalized following urologic trauma from 2016-2021. Inpatient and discharge utilization of opioids, multimodal analgesia and length of stay were stratified by affected organ. Analyses were performed in STATA with p<0.05 reaching significance., Results: 116 patients were assessed; 84 (72.4%) required surgery. In the first 10 days, bladder injuries incurred higher mean and median OMEQ than other urological injuries. In nearly all groups, OMEQ prescribed at discharge is less than average inpatient OMEQ. Eighty-six (74.1%) patients received at least 2 different opioid medications while inpatient. Those with a history of opioid use received a significantly higher OMEQ dose per day (p<0.001). There were no significant differences between opioid prescribing patterns or average OMEQ dosages prescribed at discharge between those patients managed either surgically or non-operatively. Only 24 (20.7%) patients met the criteria for utilization of multimodal analgesia., Conclusion: Multimodal analgesia is severely underutilized following urological trauma. Combined with the development of opioid tolerance over long hospital stays, this creates an avenue for opioid misuse following discharge and provides an opportunity for improvement., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate racial, gender, and socioeconomic differences in the treatment of metastatic renal cell carcinoma (mRCC) and their impact on survival., Methods: Patients aged ≥18 years diagnosed with mRCC in the National Cancer Database (2004-2015) were analyzed. Multivariable logistic regression models were used to evaluate factors associated with systemic therapy and cytoreductive nephrectomy (CN) utilization. Cox proportional hazards regression models were used to evaluate overall survival., Results: In total, 31,989 patients with mRCC were identified with 30.2% receiving CN, 51.6% receiving systemic therapy, and 25.8% receiving no treatment. Females were at lower odds of receiving systemic therapy (OR 0.91, P <.01) and increased odds of no treatment (OR 1.14, P <.01). Non-Hispanic Black and Hispanic patients were at decreased odds of receiving CN (OR 0.75, P <.01 and OR 0.86, P = .01, respectively). Black patients were at decreased odds of receiving systemic therapy (OR 0.85, P <.01) and increased odds of no treatment (OR 1.41, P <.01). Adjusting for demographic and disease variables, Black patients were at increased risk of death (HR 1.06, P = .03), largely due to less use of systemic therapy and CN; survival differences disappeared after accounting for receipt of therapy (HR 0.99, P = .66)., Conclusion: There are racial, gender, and socioeconomic differences in the treatment of mRCC which are associated with a disparity in overall survival. Dismantling systemic barriers and improving access to care may lead to reduced disparities and improved outcomes for mRCC., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To quantify benign prostatic hyperplasia (BPH) patient preferences to promote guidelines-compliant, patient-centered care. Discordance between patient and urologist priorities for the treatment of BPH hinders patient-centered care. Physician assumptions regarding patient preferences lead to dissatisfied patients; a poor outcome in any quality of life surgery. American Urologic Association guidelines urge urologists to consider patient preferences when recommending a BPH treatment., Methods: In this cross-sectional, online survey study using researchmatch.org, participants were required to decide between theoretical BPH treatments in a balanced, choice-based conjoint analysis. The treatments had varying levels of four attributes: efficacy, recovery difficulty, risk of complications (Clavien-Dindo 2+), and risk of de novo ejaculatory dysfunction. Demographic information and International Prostate Symptom Score were collected and analyzed using comparative statistics. Each attribute was analyzed using a conditional logit model, and attribute importance (range in utility between attribute-levels) was calculated., Results: Out of 1235 recruited participants, 812 (66%) completed the study. Median International Prostate Symptom Score and age was 6 (IQR 3-12) and 56 (IQR 38-67), respectively. Complication risk was the most important attribute, followed by efficacy, recovery difficulty, and risk of ejaculatory dysfunction. In a subgroup analysis of age quartiles, participants age <38 and >67 held efficacy (31%) and complication risk (47%) to the highest relative importance, respectively., Conclusion: Males valued BPH treatments that minimize complication risks, while ejaculatory dysfunction was least impactful. Variation in results between age subgroups emphasizes the need for individualized care to maximize patient satisfaction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context: The incidental detection of localized renal masses has been rising steadily, but a significant proportion of these tumors are benign or indolent and, in most cases, do not require treatment. At the present time, a majority of patients with an incidentally detected renal tumor undergo treatment for the presumption of cancer, leading to a significant number of unnecessary surgical interventions that can result in complications including loss of renal function. Thus, there exists a clinical need for improved tools to aid in the pretreatment characterization of renal tumors to inform patient management., Objective: To systematically review the evidence on noninvasive, imaging-based tools for solid renal mass characterization., Evidence Acquisition: The MEDLINE database was systematically searched for relevant studies on novel imaging techniques and interpretative tools for the characterization of solid renal masses, published in the past 10 yr., Evidence Synthesis: Over the past decade, several novel imaging tools have offered promise for the improved characterization of indeterminate renal masses. Technologies of particular note include multiparametric magnetic resonance imaging of the kidney, molecular imaging with targeted radiopharmaceutical agents, and use of radiomics as well as artificial intelligence to enhance the interpretation of imaging studies. Among these, 99m Tc-sestamibi single photon emission computed tomography/computed tomography (CT) for the identification of benign renal oncocytomas and hybrid oncocytic chromophobe tumors, and positron emission tomography/CT imaging with radiolabeled girentuximab for the identification of clear cell renal cell carcinoma, are likely to be closest to implementation in clinical practice., Conclusions: A number of novel imaging tools stand poised to aid in the noninvasive characterization of indeterminate renal masses. In the future, these tools may aid in patient management by providing a comprehensive virtual biopsy, complete with information on tumor histology, underlying molecular abnormalities, and ultimately disease prognosis., Patient Summary: Not all renal tumors require treatment, as a significant proportion are either benign or have limited metastatic potential. Several innovative imaging tools have shown promise for their ability to improve the characterization of renal tumors and provide guidance in terms of patient management., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Metastatic cancer is lethal and patients who suffer bone metastases fare especially poorly. Bone-specific metastatic progression in prostate and breast cancers is a highly observed example of organ-specific metastasis, or organotropism. Though research has delineated the sequential steps of the metastatic cascade, the determinants of bone-specific metastasis have remained elusive for decades. Applying fundamental ecological principles to cancer biology models of metastasis provides novel insights into metastatic organotropism. We use critical concepts from foraging theory and movement ecology to propose that observed bone-specific metastasis is the result of habitat selection by foraging cancer cells. Furthermore, we posit that cancer cells can only perform habitat selection if and when they employ a reversible motile foraging strategy. Only a very small percentage of cells in a primary tumor harbor this ability. Therefore, our habitat selection model emphasizes the importance of identifying the rare subset of cancer cells that might exhibit habitat selection, ergo achieve bone-specific metastatic colonization., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10 -4 ), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10 -5 ; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10 -4 ; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry., (Copyright © 2022. Published by Elsevier B.V.)

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To propose EV-derived mRNA as a potential diagnostic biomarker detecting the presence of clear cell renal cell carcinoma (ccRCC). There is currently no kidney cancer specific screening or diagnostic technology. Therefore, one-third of kidney cancer diagnoses occur after the cancer has metastasized and is past curative measures MATERIALS AND METHODS: Urine, plasma, normal tumor adjacent tissue, and tumor tissue was collected from a limited population of ccRCC patients. Extracellular vesicle (EV) isolation was performed on each sample, followed by mRNA extraction from isolated EVs. NanoString nCounter technology was utilized to count the mRNA transcripts present in matched plasma, urine, tumor tissue, and normal tumor adjacent tissue samples., Results: 770 mRNA transcripts related to gene's affecting cancer's progression and metastasis processes were evaluated. Four EV derived mRNA transcripts (ALOX5, RBL2, VEGFA, TLK2) were found specific to urine and tumor tissue samples., Conclusion: Four candidate RCC-specific urine EV biomarkers were identified. However, due to the lack of a true negative control and urine collection techniques, further re-examination is necessary for validation. This study demonstrates the promise of defining disease-specific EV biomarkers in liquid biopsy patient samples., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether pandemic-related restrictions with video-based interviewing increased geographic clustering of urology applicants matching at a residency program near where they were raised or attended medical school., Materials and Methods: We utilized publicly available data from the urology match to compare dispersal patterns between applicants matching during the COVID-19 application cycle (2021) and those matching in the 5 prior application cycles (2016-2020). Variables included home state, undergraduate institution, medical school, and residency. Latitudes and longitudes were obtained for each institution and home state. The primary endpoint was distance (miles, as the most direct path) between medical school and residency program. We also assessed dispersal patterns by American Urological Association section., Results: Of the 1965 applicants matching to a urology program between 2016 and 2021, medical school was identified for 1956 (99.7%) applicants, undergraduate program for 1551 (79%) applicants, and home state for 1351 (69%) applicants. Comparing the COVID-19 application cycle to the 5 prior application cycles, there was no significant difference in the median distance between medical school and residency, undergraduate university and residency, or home state and residency. Similarly, there was no significant difference in the proportion of applicants matching at their home institution, matching from medical schools without a home urology program, matching from medical schools with a historically low volume of urology applicants (<1 matched applicant per year), or matching from a D.O., Conclusion: Virtual interviewing and the loss of in-person clinical rotations did not significantly alter dispersal patterns or hamper an applicant's ability to match at program outside their geographic region., (Copyright © 2021 Elsevier Inc. All rights reserved.)