Development of the human ovary: Fetal through pubertal ovarian morphology, folliculogenesis and expression of cellular differentiation markers.

A definition of normal human fetal and early postnatal ovarian development is critical to the ability to accurately diagnose the presence or absence of functional ovarian tissue in clinical specimens. Through assembling an extensive histologic and immunohistochemical developmental ontogeny of human ovarian specimens from 8 weeks of gestation through 16 years of postnatal, we present a comprehensive immunohistochemical mapping of normal protein expression patterns in the early fetal through post-pubertal human ovary and detail a specific expression-based definition of the early stages of follicular development. Normal fetal and postnatal ovarian tissue is defined by the presence of follicular structures and characteristic immunohistochemical staining patterns, including granulosa cells expressing Forkhead Box Protein L2 (FOXL2). However, the current standard array of immunohistochemical markers poorly defines ovarian stromal tissue, and additional work is needed to identify new markers to advance our ability to accurately identify ovarian stromal components in gonadal specimens from patients with disorders of sexual differentiation.

Feasibility of Awake Intravesical Botulinum Toxin Injection in Pediatric Neurogenic Bladder.

PURPOSE: Cystoscopic injection of botulinum neurotoxin (BoNT) is typically performed under general anesthesia in pediatric patients with neurogenic bladder, accumulating anesthetic exposures and operating room costs. As most of these patients already tolerate clean intermittent catheterization (CIC), it has become our practice to offer a trial of awake injection. We report our initial experience here. We hypothesized that higher sensory level, female sex and absence of mental health issues or cognitive delay might predict successful first awake injection and decreased operative times. MATERIALS AND METHODS: Surgical records from 2 academic hospitals from 2018-2020 were reviewed. Generalized linear models were fit to determine predictors of success and procedural length. RESULTS: Trial of awake injection was offered to 22 patients. Eighteen patients (8 female, 10 male, 4-20 years old) elected to proceed. All 18 patients were managed with CIC at baseline, 14 had anxiety or behavioral issues, 10 had cognitive delay and 7 had sensory level below S2. Two patients (11%) required conversion to general anesthesia and one of these subsequently opted for a repeat awake injection trial. Fifteen of the 18 patients (83%) had or planned subsequent injections awake. Of the remaining, 1 proceeded to bladder augment, 1 is considering ileovesicostomy and 1 requested subsequent injections under anesthesia. No intraoperative complications occurred. CONCLUSIONS: Awake BoNT injection is feasible in pediatric patients with neurogenic bladder managed with CIC, even in the setting of intact sensation, well-managed mental health issues or cognitive delay, thereby increasing the viability of BoNT as an early tool in the management of neurogenic bladder.

Active surveillance for intermediate-risk prostate cancer: yes, but for whom?

PURPOSE OF REVIEW: Active surveillance is becoming more widely accepted as an initial management option for carefully selected men with favorable intermediate-risk prostate cancer (PCa). As prospective active surveillance cohorts mature sufficiently to begin evaluating longer-term outcomes, consensus on more precise evidence-based guidelines is needed to identify the patient cohorts who may be safely managed with active surveillance and what the ideal surveillance protocol entails. RECENT FINDINGS: Long-term outcomes updates have suggested a trend toward worse 15-year survival outcomes for intermediate-risk patients on active surveillance compared with definitive treatment, but 'intermediate-risk' is a broad category and there is a subset of favorable intermediate-risk patients for whom survival outcomes remain equivalent. Promising updates to current risk stratification include consideration of genomic classifiers, advanced imaging and more nuanced interpretation of biopsy results. SUMMARY: Despite widespread acknowledgement of the pitfalls of overtreatment in clinically localized PCa, utilization of active surveillance in the intermediate-risk population remains marginal, in part due to the absence of easily interpretable consensus recommendations. As more long-term outcomes data become available for this subgroup, the field is now poised to refine the definition of favorable intermediate-risk patients for whom active surveillance is a safe, evidence-based first-line management option.

Case of Urethral Hypoplasia in Prune Belly Syndrome Successfully Managed With Vesicoamniotic Shunts and a Progressive Augmentation by Dilation Urethra Anterior Procedure.

Urethral atresia is a rare but clinically significant cause of congenital lower urinary tract obstruction. Initial management options include urinary diversion until definitive urethral reconstruction or progressive urethral dilation. Given the overall rarity of the condition, there are no evidence-based guidelines for the immediate and long-term management of urethral atresia, and clinical practice varies widely. We present an illustrative case managed with progressive urethral dilation alongside urinary diversion to highlight key factors in shared clinical decision making. Ultimately, pooled multi-institutional long-term outcomes data are needed to better guide practice for these patients and their families.

Prenatal Presentation of a Covered Cloacal Exstrophy Variant; Early Diagnostic Challenges Within the Broad Spectrum of the Exstrophy-Epispadias Complex.

There is a broad range of variant phenotypes that can occur within the bladder exstrophy and epispadias complex spectrum. Accurate prenatal detection helps prepare families and to coordinate subspecialty resources. Here, we present the case of a patient with prenatally diagnosed patient with covered cloacal exstrophy variant along with four additional cases illustrating the nonlinear spectrum from isolated epispadias to cloacal exstrophy. Given the rarity of these variants overall and of each subtype within the spectrum, there is a need for long-term multi-institutional outcomes data to improve detection, characterization, and prognostication for these patients.

Think before you pop: Outcomes of non-operative management of ureteroceles.

INTRODUCTION/BACKGROUND: Ureteroceles are often diagnosed antenatally and incidentally and treated in a minimally invasive fashion with endoscopic puncture. Recent literature suggests that observation, or non-operative management, is an effective and viable management option in select patients with ureteroceles and certain radiologic findings, however there is no consensus on how to best select patients for non-operative management. OBJECTIVE: To 1) determine if pediatric ureteroceles managed non-operatively require less or sooner secondary surgical intervention than those managed with up-front incision, 2) describe characteristics of success and failure in pediatric ureteroceles managed non-operatively, and 3) identify risk factors associated with receiving intervention and time to intervention. RESULTS: Of 287 ureteroceles, 65 (23%) were managed non-operatively and underwent secondary surgical intervention less frequently (9% vs. 34%, P < 0.01) and later (median age 40 vs. 20 months) than those managed with puncture. Successful non-operative management was associated with fewer comorbidities, smaller ureterocele size, absence of vesicoureteral reflux (VUR) and high-grade VUR, single collecting system, lesser degree of hydronephrosis, ipsilateral MCDK and intravesical location. For all ureteroceles, high-grade VUR, duplex system, and female sex were associated with shorter time to secondary intervention (intervention after initial management). DISCUSSION: In the largest retrospective review of ureterocele management, smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis were factors that increased the efficacy of non-operative management of select pediatric ureteroceles. Furthermore, time to event analysis showed that non-operative management did not predispose patients to sooner secondary intervention (Figure). Lack of a standardized protocol for ureterocele management is a limitation of this single institution retrospective study as it introduces selection bias to the results, however few patients with low risk characteristics underwent puncture and no high risk patients were observed. CONCLUSION: Smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis are factors that may increase the efficacy of non-operative management of select pediatric ureteroceles, which may delay or avoid secondary surgical intervention.

Revisiting the utility of prenatal ultrasound in the routine workup of first febrile UTI: A systematic review and meta-analysis of the negative predictive value of prenatal ultrasound for identification of urinary tract abnormalities after first febrile urinary tract infection in children.

CONTEXT: The current EAU/ESPU and recently retired AAP pediatric UTI guidelines recommend renal bladder ultrasound after first febrile UTI in children to screen for structural abnormalities, regardless of findings on prenatal ultrasound. OBJECTIVE: Test the hypothesis that a normal prenatal ultrasound could rule out urinary tract abnormality on post-UTI ultrasound. DATA SOURCES: Medline, Embase, Cochrane Library. STUDY SELECTION: Studies including pediatric patients with first febrile UTI who had both prenatal and post-UTI ultrasound. DATA EXTRACTION: Anatomical abnormalities detected by prenatal and post-UTI ultrasound as reported per individual study criteria were extracted. Meta-analyses of 9 studies (2981 patients) were performed using a random-effects model and composite estimates of the negative predictive value (NPV) of prenatal ultrasound were calculated. RESULTS: Overall summary NPV of prenatal ultrasound for all pediatric patients was 77%, with heterogeneity score (I2) 97.9%. Summary NPV of prenatal ultrasound for all patients under two years of age was similar at 75%, with I2 98.2% For the 4 studies to which we could apply a more stringent definition of abnormality, summary NPV was 85% and I2 97.5% for prediction of moderate post-UTI ultrasound abnormalities and summary NPV was 93% and I2 90.4% for severe abnormalities. DISCUSSION: While we calculated an 85% NPV for a normal prenatal ultrasound to rule out significant postnatal abnormality as defined within individual studies, substantial heterogeneity amongst publications limited the precision of our estimates. This highlights the need for more rigorous investigations with attention to timing of ultrasound and the application of clinically meaningful definitions for abnormal prenatal and post-UTI studies. This may allow judicious use of prenatal ultrasound to guide clinical management for children with first febrile UTI and minimize redundant imaging with potential for false positive results. Until then, the current guidelines are justified based on the limited and heterogenous data from the currently available published studies.

How Often Does Magnetic Resonance Imaging Detect Prostate Cancer Missed by Transrectal Ultrasound?

BACKGROUND: Lesion-targeted prostate biopsy based on multiparametric magnetic resonance imaging (mpMRI) has been shown to be superior to systematic transrectal ultrasound (TRUS) biopsy (SBx) alone in men at risk for prostate cancer (PCa). However, the incremental benefit of MRI-targeted biopsy (MBx) beyond SBx with ultrasound-targeted biopsy (UBx) is less clear. OBJECTIVE: We performed a three-way comparison of UBx versus MBx versus SBx for PCa detection. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center cohort study was conducted on consecutive patients with PCa suspicion or low-risk PCa on active surveillance (AS). All men had at least one lesion (Prostate Imaging Reporting and Data System [PI-RADS] ≥3) on pre-biopsy mpMRI. UBx, MBx, and SBx were performed during the same encounter, and the urologists were blinded to MRI results and targeting until both SBx and UBx were completed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The ability of each biopsy type to identify the highest grade group (GG) was determined, and UBx and MBx were compared using a paired t test. RESULTS AND LIMITATIONS: We prospectively enrolled 201 consecutive men undergoing targeted prostate biopsy: 72 (36%) were biopsy-naïve, 34 (17%) had a prior negative SBx, and 95 (47%) were on AS. Median age and prostate-specific antigen were 66 yr (interquartile range [IQR] 62-71) and 6.8 ng/ml (IQR 4.9-9.8), respectively. Suspicious hypoechoic lesions were reported on TRUS in 69%. Among the 169 men with PCa, SBx detected the highest GG or was equivalent to UBx/MBx in 136 (80%) men. UBx detected the highest GG or was equivalent to MBx in 19 (11%) men, and MBx alone detected the highest GG in 14 (8%) men. There was no significant difference between UBx and MBx in direct comparison (p = 0.08). Limitations include that patients were not randomized, our population was heterogeneous, and TRUS expertise at a tertiary care academic center might not reflect routine practice. CONCLUSIONS: In the setting of high expertise and experience with both ultrasound and MRI, MBx offers only a modest benefit over SBx and UBx. PATIENT SUMMARY: At a highly experienced academic medical center, we examined the detection rates of prostate cancer among men undergoing prostate biopsy using three techniques: transrectal ultrasound lesion-targeted biopsy, magnetic resonance imaging-targeted biopsy, and systematic biopsy. We identified a few more cases of aggressive prostate cancer with magnetic resonance imaging-targeted biopsy, but a large majority was found by ultrasound alone.