Multi-Institutional Bladder Exstrophy Consortium After 8 Years: The Short- and Intermediate-Term Outcomes.

PURPOSE: Bladder exstrophy (BE) poses challenges both during the surgical repair and throughout follow-up. In 2013, a multi-institutional BE consortium was initiated, which included utilization of unified surgical principles for the complete primary repair of exstrophy (CPRE), real-time coaching, ongoing video capture and review of video footage, prospective data collection, and routine patient data analysis, with the goal of optimizing the surgical procedure to minimize devastating complications such as glans ischemia and bladder dehiscence while maximizing the rate of volitional voiding with continence and long-term protection of the upper tracts. This study reports on our short-term complications and intermediate-term continence outcomes. MATERIALS AND METHODS: A single prospective database for all patients undergoing surgery with a BE epispadias complex diagnosis at 3 institutions since February 2013 was used. For this study, data for children with a diagnosis of classic BE who underwent primary CPRE from February 2013 to February 2021 were collected. Data recorded included sex, age at CPRE, adjunct surgeries including ureteral reimplantations and hernia repairs at the time of CPRE, osteotomies, and immobilization techniques, and subsequent surgeries. Data on short-term postoperative outcomes, defined as those occurring within the first 90 days after surgery, were abstracted. In addition, intermediate-term outcomes were obtained for patients operated on between February 2013 and February 2017 to maintain a minimum follow-up of 4 years. Outcomes included upper tract dilation on renal and bladder ultrasound, presence of vesicoureteral reflux, cortical defects on nuclear scintigraphy, and continence status. Bladder emptying was assessed with respect to spontaneous voiding ability, need for clean intermittent catheterization, and duration of dry intervals. All operating room encounters that occurred subsequent to initial CPRE were recorded. RESULTS: CPRE was performed in 92 classic BE patients in the first 8 years of the collaboration (62 boys), including 46 (29 boys) during the first 4 years. In the complete cohort, the median (interquartile range) age at CPRE was 79 (50.3) days. Bilateral iliac osteotomies were performed in 89 (97%) patients (42 anterior and 47 posterior). Of those undergoing osteotomies 84 were immobilized in a spica cast (including the 3 patients who did not have an osteotomy), 6 in modified Bryant's traction, and 2 in external fixation with Buck's traction. Sixteen (17%) patients underwent bilateral ureteral reimplantations at the time of CPRE. Nineteen (21%) underwent hernia repair at the time of CPRE, 6 of which were associated with orchiopexy. Short-term complications within 90 days occurred in 31 (34%), and there were 13 subsequent surgeries within the first 90 days. Intermediate-term outcomes were available for 40 of the 46 patients, who have between 4 and 8 years of follow-up, at a median of 5.7 year old. Thirty-three patients void volitionally, with variable dry intervals. CONCLUSIONS: Cumulative efforts of prospective data collection have provided granular data for evaluation. Short-term outcomes demonstrate no devastating complications, that is, penile injury or bladder dehiscence, but there were other significant complications requiring further surgeries. Intermediate-term data show that boys in particular show encouraging spontaneous voiding and continence status post CPRE, while girls have required modification of the surgical technique over time to address concerns with urinary retention. Overall, 40% of children with at least 4 years of follow-up are voiding with dry intervals of > 1 hour.

Deep Learning of Videourodynamics to Classify Bladder Dysfunction Severity in Patients With Spina Bifida.

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

Retrograde urethrography in children: a decade of experience at a children's hospital.

BACKGROUND: Retrograde urethrography (RUG) is a radiologic procedure that optimizes imaging evaluation of the urethra, particularly in settings of difficulty with micturition or urethral injury. OBJECTIVE: To review our experience with RUG at a large pediatric radiology practice. MATERIALS AND METHODS: We conducted a retrospective review of medical records and fluoroscopic images of RUGs performed from January 2010 to December 2020. RESULTS: We identified 180 RUG exams (median frequency 17 exams per year), all in male children (median age 13 years). The most common indications were stricture (42%; n=76), postsurgical evaluation (34%; n=62) and trauma (16%; n=29). The most commonly used catheter was Foley (40%; n=72), with a median catheter size of 5 French (Fr) for infants younger than 1 year, 7 Fr for children ages 1-5 years and 8 Fr for children older than 5 years. About a third of the children (57; 32%) had combined voiding cystourethrography (VCUG)-RUG exams. Water-soluble contrast agent, either 17% or 43% Cysto-Conray, was used. Most RUG exams were normal (46%; n=83). The most common urethral pathology was stricture (30%; n=54), commonly involving a bulbar urethra (n=26). Urethral trauma was seen in 11 children (6%), 10 bulbar and 1 membranous. Most children with stricture were surgically treated (n=40; 74%), whereas most children with trauma were conservatively treated (n=8; 73%). The remaining diagnoses included diverticula, polyps, valves, fistulas and duplications, constituting <17% of our sample; most of these were surgically treated. Four exams (2%) were non-diagnostic. RUG showed 89% sensitivity and 97% specificity compared to cystourethroscopy/VCUG findings. Technical difficulties occurred in 14 (8%) children (e.g., pain or inappropriate catheter seal). CONCLUSION: Our experience indicates that when catheterization techniques are properly tailored, RUG provides a useful and successful radiologic method of evaluating the pediatric male urethra.

Quantifying Glans Width Changes in Response to Preoperative Androgen Stimulation in Patients Undergoing Hypospadias Repair.

PURPOSE: Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery. MATERIALS AND METHODS: Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated. RESULTS: A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p <0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p <0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p <0.001). A histogram plot revealed the distribution of GW change at surgery. CONCLUSIONS: In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.

Posterior Urethral Valves Outcomes Prediction (PUVOP): a machine learning tool to predict clinically relevant outcomes in boys with posterior urethral valves.

BACKGROUND: Early kidney and anatomic features may be predictive of future progression and need for additional procedures in patients with posterior urethral valve (PUV). The objective of this study was to use machine learning (ML) to predict clinically relevant outcomes in these patients. METHODS: Patients diagnosed with PUV with kidney function measurements at our institution between 2000 and 2020 were included. Pertinent clinical measures were abstracted, including estimated glomerular filtration rate (eGFR) at each visit, initial vesicoureteral reflux grade, and renal dysplasia at presentation. ML models were developed to predict clinically relevant outcomes: progression in CKD stage, initiation of kidney replacement therapy (KRT), and need for clean-intermittent catheterization (CIC). Model performance was assessed by concordance index (c-index) and the model was externally validated. RESULTS: A total of 103 patients were included with a median follow-up of 5.7 years. Of these patients, 26 (25%) had CKD progression, 18 (17%) required KRT, and 32 (31%) were prescribed CIC. Additionally, 22 patients were included for external validation. The ML model predicted CKD progression (c-index = 0.77; external C-index = 0.78), KRT (c-index = 0.95; external C-index = 0.89) and indicated CIC (c-index = 0.70; external C-index = 0.64), and all performed better than Cox proportional-hazards regression. The models have been packaged into a simple easy-to-use tool, available at https://share.streamlit.io/jcckwong/puvop/main/app.py CONCLUSION: ML-based approaches for predicting clinically relevant outcomes in PUV are feasible. Further validation is warranted, but this implementable model can act as a decision-making aid. A higher resolution version of the Graphical abstract is available as Supplementary information.

Total Motile Sperm Count in Adolescent Boys with Varicocele is Associated with Hormone Levels and Total Testicular Volume.

PURPOSE: The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. MATERIALS AND METHODS: We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. RESULTS: A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. CONCLUSIONS: Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.

Urine Proteomics: Evaluation of Different Sample Preparation Workflows for Quantitative, Reproducible, and Improved Depth of Analysis.

The growing field of urinary proteomics shows promise to expand the number of biomarkers for the diagnosis and prognosis of a number of human diseases. With the rapid developments in mass spectrometry methods for proteome quantification, there exists an opportunity for improved sample processing and separation workflows to make important contributions to urine proteomic analyses. Here we evaluate the performance of four sample preparation methods: MStern, PreOmics in-StageTip (iST), suspension-trapping (S-Trap), and conventional urea In-Solution trypsin hydrolysis for nondepleted urine samples. Data-dependent acquisition (DDA) mode on a QExactive HF mass spectrometer was used for single-shot label-free data acquisition. Our results demonstrate a high degree of reproducibility within each workflow. PreOmics iST yields the best digestion efficiency, whereas the S-Trap workflow gives the greatest number of peptide and protein identifications. Using the S-Trap method and starting with ∼0.5 mL, we identify ∼1500 protein groups and ∼17 700 peptides from DDA analysis with a single injection on the mass spectrometer.

Time to Complication Detection after Primary Pediatric Hypospadias Repair: A Large, Single Center, Retrospective Cohort Analysis.

PURPOSE: Controversy remains within the pediatric urology community regarding adequate duration of followup after hypospadias repair. Some have suggested that minimal long-term followup is necessary due to a low incidence of late complications. The objective of this study was to delineate time to complication detection for primary hypospadias repairs. MATERIALS AND METHODS: We queried our prospectively maintained hypospadias database and identified all patients undergoing primary hypospadias repair from June 2007 to June 2018. Patients were excluded if they had undergone primary repair elsewhere or did not have a followup visit. Complications were defined by the need for an additional unplanned surgical procedure. Kaplan-Meier analysis was performed to assess time to complication by degree of hypospadias. RESULTS: A total of 1,280 patients met inclusion criteria, of whom 976 (68.9%) underwent distal, 64 (4.9%) mid shaft and 240 (18.8%) proximal hypospadias repair. Complication rates were 10.7% (104 patients), 18.8% (12) and 53.8% (129, p<0.0001) for distal, mid shaft and proximal hypospadias repair, respectively. Only 47% of complications were detected within the first year postoperatively. Median time to complication for all repair types was 69.2 months (IQR 23 to 131.9), ie 83.1 months (IQR 42.0 to 131) for patients undergoing distal repair and 29.4 months (IQR 11.9 to 82.1) for patients undergoing proximal repair (p <0.001). CONCLUSIONS: In our large single institution series of pediatric patients undergoing hypospadias repair fewer than half of the complications presented within the first year postoperatively. Long-term followup is recommended for patients undergoing hypospadias repair to adequately detect and address complications.

Rater reliability of postnatal urinary tract dilation consensus classification.

BACKGROUND: A multidisciplinary urinary tract dilation (UTD) classification system was published in 2014 to standardize definitions and renal/bladder ultrasound image interpretation. OBJECTIVE: To evaluate intra- and inter-rater reliability of this system on postnatal RBUS. MATERIALS AND METHODS: Renal/bladder US of 60 infants (<12 months) with urinary tract dilation were anonymized, retrospectively reviewed and scored twice using the UTD classification system by a pediatric urologist and four pediatric radiologists. Exams included supine and prone images of each kidney. Raters recorded the anterior posterior renal pelvis diameter in each position; and when present calyceal dilation (central and peripheral), ureteral dilation, parenchymal and bladder abnormalities. A UTD score was given to each kidney based on these components. RESULTS: Intraclass correlation (ICC) of anterior posterior renal pelvis diameter measures was 0.99 (P<0.001). Intra-rater reliability for the anterior posterior renal pelvis diameter of each kidney was high, with ICC >0.95 (P<0.001). Inter-rater kappa values for UTD scores of both kidneys ranged from 0.60 to 0.77 (P <0.001). Intra-rater kappa values for UTD scores of both kidneys ranged from 0.74 to 0.92 (P <0.001). Of the six categories comprising the UTD score, discrepancy between raters was highest for interpretation of central and peripheral calyceal dilation. CONCLUSION: Present inter- and intra-rater reliability findings were similar to those previously reported for grading systems for urinary tract dilation. Across these studies, kappa values are generally lower than the 0.8 cut-off advocated for medical measures. Here, calyceal dilation commonly determined the kidney UTD score and was also the source of greatest discrepancy between raters. Improving consistency of calyceal dilation interpretation may improve UTD consensus score reliability.

Fetal anterior abdominal wall defects: prenatal imaging by magnetic resonance imaging.

Abdominal wall defects range from the mild umbilical cord hernia to the highly complex limb-body wall syndrome. The most common defects are gastroschisis and omphalocele, and the rarer ones include the exstrophy complex, pentalogy of Cantrell and limb-body wall syndrome. Although all have a common feature of viscera herniation through a defect in the anterior body wall, their imaging features and, more important, postnatal management, differ widely. Correct diagnosis of each entity is imperative in order to achieve appropriate and accurate prenatal counseling and postnatal management. In this paper, we discuss fetal abdominal wall defects and present diagnostic pearls to aid with diagnosis.

Intermediate-Term Followup of Proximal Hypospadias Repair Reveals High Complication Rate.

PURPOSE: Results following distal hypospadias repair are favorable. Grouping proximal and distal hypospadias repair artificially increases the perceived success rate of proximal hypospadias. We identified our complication rate of proximal hypospadias repair and hypothesized a higher complication rate for 1-stage repair. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive boys who underwent proximal hypospadias from 2007 to 2014. Proximal hypospadias was defined as a urethral meatus location at or more proximal than the penoscrotal junction after penile degloving. We further stratified boys into those with planned 1-stage vs 2-stage repair. Univariate and Cox regression analyses were performed to assess associations with covariates and compare time to the first complication, respectively. RESULTS: A total of 167 boys met study inclusion criteria. Median followup was 31.7 months for 1-stage repair in 86 patients and staged repair in 81. The overall complication rate was 56%. Complications developed in 53 of 86 1-stage (62%) vs 40 of 81 staged (49%) repairs (p = 0.11). The number of unplanned procedures per patient was higher in the 1-stage than in the staged group (0.99 vs 0.69, p = 0.06), as was the number of patients who had at least 2 complications (29 of 86 or 33% vs 13 of 81 or 16%, p = 0.03). Cox regression showed no difference in time to the first complication for staged compared to 1-stage repair (HR 0.77, 95% CI 0.43-1.39). CONCLUSIONS: Our 56% complication rate of proximal hypospadias warrants further long-term patient followup. More patients in the 1-stage group experienced at least 2 complications. However, when complications developed, they developed no differently in the 2 groups.

Gender differences in promotions and scholarly productivity in academic urology.

INTRODUCTION: The gender demographics within urology are changing as more women are entering the workforce. Since research productivity strongly influence career advancement, we aim to characterize gender differences in scholarly productivity and promotions in a cohort of graduated academic urologists. MATERIALS AND METHODS: Urologists who graduated between 2002 and 2008 from 34 residency programs affiliated with the top 50 urology hospitals as ranked in 2009 by U.S. News & World Report were followed longitudinally. Only urologists affiliated with an academic teaching hospital were included for analysis. RESULTS: A total of 543 residents graduated, 459 (84.5%) males and 84 (15.5%) females. Of these, 173 entered academia, 137 (79.2%) males and 36 (20.8%) females. Women had fewer publications compared to men (mean 19.3 versus 61.7, p = 0.001). Fewer women compared to men were promoted from assistant professor 11 (30.6%) versus 83 (60.6%), p = 0.005. Fewer women achieved associate professor 10 (27.8%) versus 67 (48.9%), p = 0.005 or professor ranks 1 (2.8%) versus 16 (11.7%), p = 0.005 respectively compared to men. In a multivariate logistic regression analysis, after controlling for the number of total publications and number of years since graduation, gender was not predictive of achieving promotion, OR = 0.81 (95% CI 0.31-2.13), p = 0.673. CONCLUSIONS: Women are underrepresented in senior faculty roles in urology. Scholarly productivity seems to play a major role in academic promotion within urology. With increasing women in academic urology, further studies are needed to explore predictors of promotion and how women can achieve higher leadership roles in the field.

Voiding Dysfunction: What Can Radiologists Tell Patients and Pediatric Urologists?

OBJECTIVE: Imaging children with dysfunctional voiding remains a challenge because 98% of these children have normal anatomy. Identifying the 1-2% of children who do have an anatomic basis for incontinence is important; this article focuses on how pediatric urologists use imaging for the evaluation of patients with this condition. CONCLUSION: Imaging a patient with dysfunctional voiding can provide findings that will allow an accurate diagnosis and lead to optimal management. The key for the pediatric urologist is using imaging studies judiciously because the diagnostic yield is low. If every patient with dysfunctional voiding who presents to the clinic undergoes imaging, there will be little gain. Understanding in which patients to try imaging sooner versus trying medical and behavioral management first is a function of experience.