Urologic manifestations of hypotonia, ataxia, and delayed development syndrome (HADDS), a rare neurodevelopmental disorder.

INTRODUCTION: Early B-cell factor 3 (EBF3) is a transcription factor involved in neuronal differentiation and maturation. Pathogenic variants are associated with hypotonia, ataxia, and delayed development syndrome (HADDS) (MIM#617330). Urologic manifestations are common and may have implications regarding long term renal function. OBJECTIVE: To review all known patients with pathogenic variants of the EBF3 gene resulting in HADDS with urologic manifestations. We hypothesize a high rate of bladder dysfunction secondary to the EBF3 variant's impact on relaxation of the urinary sphincter leading to detrusor sphincter dyssynergia (DSD). METHODS: The PubMed database was queried for publications of the EBF3 mutation between January 2017 and January 2023. Search terms were "EBF3 mutation OR HADDS AND urology OR phenotype". Retrospective analysis of HADDS patients cared for in our institution was performed. Demographic and clinical information was collected. RESULTS: We identified 52 patients (33F:19M) through literature (28F:18M) and retrospective review (5F:1M). There was a high prevalence of genitourinary physical exam abnormalities, history of urinary tract infection, vesicoureteral reflux (VUR), and diagnosis of neurogenic bladder. Within the literature review cohort, 67% had a urologic diagnosis. Females were disproportionately affected with urologic manifestations. In our cohort, four of six children were diagnosed with VUR and severe voiding dysfunction consistent with neurogenic bladder (67%). These children were managed with a vesicostomy. Five children had bowel dysfunction requiring therapy. Urodynamics suggested a high prevalence of external sphincter dyssynergia. Less severe forms of DSD were felt to be implicated in the abnormal voiding parameters in children who presented later in life based on non-invasive flow studies. DISCUSSION: There is significant variability in the phenotypic presentation of patients with HADDS. While EBF3 plays a clear role in neurodevelopment, it also impacts muscle development and may impact muscle relaxation. The location of the genetic variant may impact the degree of DSD, with more severe forms leading to earlier presentations. Initial work-up should include a renal ultrasound (RUS) and post void residual (PVR). Consideration can be given to obtaining a VCUG, DMSA scan or urodynamic studies. Yearly screening should be pursued with an RUS and PVR in those with an initial unremarkable work-up given the variable timing and severity of presentation. CONCLUSION: Urologic manifestations of HADDS include high rates of bladder dysfunction secondary to DSD, vesicoureteral reflux, urinary tract infection, and cryptorchidism. These patients are at risk of renal deterioration if urinary abnormalities are not properly diagnosed and managed.

Testicular relapse of acute lymphoblastic leukemia.

Contemporary chemotherapy regimens have led to improved survival and decreased incidence of testicular relapse for pediatric patients with acute lymphoblastic leukemia (ALL). Local therapies to the testes, such as radiotherapy and orchiectomy, are often not necessary given that high-dose chemotherapy agents can overcome the relative blood-testis barrier. However, urologists should be aware of clinical scenarios involving ALL which still warrant testicular biopsy to guide management. Here, we present a case of a 12-year-old boy with high-risk pre-B cell ALL presenting with a testicular relapse and a clinical presentation overlapping with non-infectious epididymo-orchitis.

Ureteral stent extraction strings in children: Stratifying the risk of post operative urinary tract infection.

INTRODUCTION: Ureteral stents facilitate recovery and avoid external drains in pediatric ureteral reconstruction. Extraction strings avoid the need for a secondary cystoscopy and anesthetic. Due to concerns regarding febrile UTIs in children with extraction strings, we retrospectively assessed the relative risk of UTI in children with extraction strings. OBJECTIVE: Our hypothesis was that stents with extraction strings do not increase the risk of UTI after pediatric ureteral reconstruction. METHODS: Records of all children undergoing pyeloplasty and ureteroureterostomy (UU) from 2014 to 2021 were reviewed. The incidences of UTI, fever, and hospitalization were recorded. RESULTS: 245 patients mean age 6.4 years (163M:82F) underwent pyeloplasty (n = 221) or UU (n = 24). 42% (n = 103) received prophylaxis. Of these, 15% developed UTI versus 5% of those not receiving prophylaxis (p < 0.05). 42 females had prior history of UTI, compared to 20 males (p < 0.05). 49 patients had an extraction string. Stents with extraction strings were removed on average 0.6 months post-op while others underwent cystoscopic removal on average 1.26 months post-op (p < 0.05). 9 (18.4%) required hospitalization for febrile UTI while the stent with extraction string was in place, while only 13 (6.6%) of those without extraction string did (p < 0.02). Of the 9 children with a febrile UTI in the extraction string group, 6 had history of prior UTI (46.1%), compared to only 3 (8.3%) without a prior UTI (p < 0.05). With no prior UTI, there was no difference in UTI risk between those with (3, 8.3%) and without (8, 6.4%) extraction string (p = 0.71). Females with prior UTI and extraction string were more likely to develop UTI than those with prior UTI and no extraction string (p = 0.01). There were not enough males with history of UTI to analyze alone. There were 5 (10%) stent dislodgements in the extraction string group, 2 required further intervention with cystoscopy or percutaneous drainage. DISCUSSION: Extraction strings provide the assurance of drainage while avoiding the need for a second general anesthetic procedure. There is not an increased risk of UTI with extraction string in those without prior history of UTI, but we no longer routinely leave extraction strings if there is history of UTI. CONCLUSION: Children, particularly females, with prior history of UTI have a significantly increased risk of febrile UTIs associated with the use of extraction strings. Prophylaxis does not seem to reduce this risk. Patients with no prior UTI had no higher risk of UTI with extraction string use for pyeloplasty or UU.

Clinical utility and interrater reliability of video urodynamics in children with isolated fibrolipoma of filum terminale.

INTRODUCTION: Children with an isolated fibrolipoma of filum terminale (IFFT) but otherwise normal spinal cord are often evaluated with video urodynamics (VUDS). VUDS interpretation is subjective and can be difficult in young children. These patients may undergo detethering surgery if there is concern for current or future symptomatic tethered cord. OBJECTIVE: We hypothesized that VUDS in children with IFFT would have limited clinical utility regarding decision for or against detethering surgery and VUDS interpretation would have poor interrater reliability. METHODS: Patients with IFFT who underwent VUDS for from 2009 to 2021 were retrospectively reviewed to evaluate clinical utility of VUDS. 6 pediatric urologists who were blinded to patient clinical characteristics reviewed the VUDS. Gwet's first order agreement coefficient (AC1) with 95% CI was used to assess interrater reliability. RESULTS: 47 patients (24F:23M) were identified. Median age at initial evaluation was 2.8yrs (IQR:1.5-6.8). 24 (51%) patients underwent detethering surgery (Table). VUDS at initial evaluation were interpreted by treating urologist as normal in 4 (8%), reassuring for normal in 39 (81%), or concerning for abnormal in 4 (9%). Based on neurosurgery clinic and operative notes for the 47 patients, VUDS made no change in management in 37 patients (79%), prompted detethering in 3 (6%), was given as reason for observation in 7 (15%), and was normal or reassuring for normal but not documented as a reason for observation in 16 (34%) (Table). Interrater reliability for VUDS interpretation had fair agreement (AC1 = 0.27) for overall categorization of VUDS and EMG interpretation (AC1 = 0.34). Moderate agreement was seen for detrusor overactivity interpretation (AC1 = 0.54) and bladder neck appearance (AC1 = 0.46). DISCUSSION: In our cohort, 90% of patients had a normal or reassuring for normal interpretation of VUDS. VUDS interpretation affected clinical course in a minority of patients. There was fair interrater reliability for overall VUDS interpretation and therefore clinical course regarding detethering surgery could vary depending upon interpreting urologist. This fair interrater variability appeared to be related to variability in EMG, bladder neck appearance, and detrusor overactivity interpretation. CONCLUSION: VUDS affected clinical management in about 20% of our cohort and supported the choice for observation in around 50% of patients. This suggests VUDS does have clinical utility in pediatric patients with IFFT. The overall VUDS interpretation had fair interrater reliability. This suggest VUDS interpretation has limitations in determining normal versus abnormal bladder function in children with IFFT. Neurosurgeons and urologists should be aware of VUDS limitations in this patient population.

Management of adolescent varicocele.

Varicocele is defined as an abnormal dilation and tortuosity of the internal spermatic veins found within the pampiniform plexus. It is a common finding in adolescents and adult men alike, however its diagnosis in the adolescent population poses different dilemmas in regard to indications for treatment than in adults. Failed Paternity is a clear-cut indication for repair in adult men attempting to father children. In adolescents, the physicians, family and patients must consider potential for future fertility problems which may or may not actually become of concern. Assessing the degree of negative effect of the varicocele on an adolescent's testicular health can also be difficult as teenagers typically are not asked to provide semen for analysis and thus surrogate markers for testicular health such as testicular size differentials must be used. Treatment options for the adolescent varicocele are similar to options in adult populations. While risks and benefits of various techniques can be considered, the gold standard for varicocele repair in adolescents has not been clearly defined. We aim to discuss diagnosis of varicocele, considerations for initiating treatment of varicocele in the adolescent, and techniques for management.

Complications following Staged Hypospadias Repair Using Transposed Preputial Skin Flaps.

PURPOSE: Proximal hypospadias repair using a staged approach is a complex reconstructive operation with the potential for significant complications requiring repeat surgery. We report outcomes of staged hypospadias repair using transposed preputial skin flaps and factors predictive of postoperative complications. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent staged proximal hypospadias repair using transposed preputial skin flaps between 2002 and 2013. Patient demographics, operative details, complications, reoperations and factors predictive of complications were reviewed. RESULTS: A total of 56 patients were identified with a mean age of 14.1 months (median 14.3) at first stage. Mean followup was 38.6 months (median 34.1). Complications requiring additional unplanned operation(s) were observed in 38 patients (68%), including fistulas in 32 (57%), diverticula in 8 (14%), meatal stenosis in 5 (9%), urethral stricture in 8 (14%) and glans dehiscence in 3 (5%). In addition, redo first stage repair was performed in 4 patients (7%). Since some patients had more than 1 complication, the total number of complications is greater than the number of patients undergoing a redo operation. On univariate analyses the use of small intestinal submucosa was significantly associated with an increased risk of fistula (91% vs 49%, p = 0.02) and urethral diverticulum (64% vs 24%, p = 0.04). Incision of the tunica albuginea of the corpora was associated with an increased likelihood of fistula (77% vs 44%, p = 0.03). Finally, patients with glans dehiscence were significantly younger at first stage (5.8 vs 14.8 months, p = 0.01). CONCLUSIONS: The reoperation rate for complications in children undergoing staged hypospadias repair using transposed preputial skin flaps is higher than previously reported.

Pediatric Medical Device Consortia: A Novel Pathway for Pediatric Device Development for Pediatric Urologists and Other Pediatric Specialists.

INTRODUCTION: A great need currently exists for medical devices designed specifically for children. This gap is most likely a result of economic, clinical and regulatory challenges as well as a lack of established mechanisms for joining pediatric device ideas with qualified individuals/programs and industry partners. We describe our experience with forming a pediatric medical device consortium that originated from the pediatric urology division and the technology transfer office of a university affiliated children's hospital. METHODS: We reviewed the developmental history of a pediatric medical device consortium at a university affiliated children's hospital from March 2011 to June 2013 with emphasis on the organizational aspects of the consortium. RESULTS: A pediatric medical device consortium was formed with the assistance of university seed funding to encourage faculty collaboration across multiple campuses. The consortium continued its progress as a resource for pediatric device projects to become a Food and Drug Administration supported pediatric device consortium in 2013. This allows the consortium to expand its activities through the P50 PDC Grant Program. CONCLUSIONS: Pediatric urologists can have a major role in organizing pediatric device consortia. Consortia can combine academic centers with the local business, investment, higher education and philanthropic communities to rapidly advance pediatric medical device projects. Novel approaches are necessary for pediatric device projects to overcome current barriers to commercialization, including an extended stay in the academic setting.

Outcomes of endoscopic incision for the treatment of ureterocele in children at a single institution.

PURPOSE: We assessed outcomes in children with ureterocele after transurethral incision at our institution between 2001 and 2014, focusing on end points of vesicoureteral reflux, improvement of hydronephrosis and need for second surgery. MATERIALS AND METHODS: We performed chart reviews of 83 patients, collecting information including age at transurethral incision, gender, renal anatomy, ureterocele location, indication for transurethral incision, and preincision and postincision vesicoureteral reflux and hydronephrosis status. Patients were divided into those with single system and duplex system ureteroceles, and intravesical and extravesical location for analysis. Statistical evaluations were performed with the Wilcoxon rank test and Fisher exact test. RESULTS: Transurethral incision was performed at a mean age of 34.2 months in patients with single system ureterocele and 8.9 months in those with duplex system ureterocele (p <0.0001). Cure rates (improvement of hydronephrosis and absence of vesicoureteral reflux) were 55.6% in patients with single system ureterocele and 14.9% in those with duplex system ureterocele (p = 0.0031). Rates of de novo reflux into the ureterocele moiety were 27.8% for patients with single system ureterocele and 56.2% for those with duplex system ureterocele (p = 0.0773). Patients with single system ureterocele required significantly fewer second surgeries (3.8%) than those with duplex system ureterocele (73.7%, p <0.0001). CONCLUSIONS: Patients with single system ureterocele may benefit from endoscopic incision. Transurethral incision was definitive in all such patients except 1 in our study. Although most patients with duplex system ureterocele will need a second operation, transurethral incision remains of value in this population in instances of sepsis or bladder outlet obstruction, or to facilitate planned reconstruction when the child is older.

Changing stone composition profile of children with nephrolithiasis.

OBJECTIVE: To determine if this trend toward calcium phosphate stone formation exists in children. METHODS: This is a retrospective study of medical records of 179 children managed at our medical center from 1992-2010 for whom stone analysis and other pertinent laboratory data were available. A comparison of patients managed from 1992-2000 (P1) and 2001-2010 (P2) was undertaken. Statistical analysis included nonparametric tests. RESULTS: There were no significant differences in the mean age of the 2 cohorts. During both periods, boys comprised a significantly higher proportion during the first decade of life, whereas girls comprised a significantly higher proportion during the second decade. A higher percentage of patients had calcium oxalate (CaOx) stones in P1 compared to P2 (60% vs 47%, P = .0019). There was a significant increase in the percentage of patients having calcium phosphate stones in P2 compared to P1 (27% vs 18.5%, P = .008). Twenty-seven patients had recurrent stones. A comparison of the compositions of the first and last stones of patients within this group demonstrated an increasing proportion of brushite stones (3.7% vs 11.1%, P = .04). Twenty-four hour urine testing results were similar for those with CaOx and calcium phosphate stones. CONCLUSION: An increasing proportion of children have calcium phosphate calculi. Brushite stones are more prevalent in children with recurrent stone events. The impetus of these shifts is not readily apparent.

Robotic assisted ureteral reimplantation: current status.

The da Vinci robot is being used for an increasing variety of reconstructive procedures. Robotic-assisted laparoscopic ureteral reconstruction is now performed routinely, and has been shown to have similar efficacy and safety profiles to open surgery in various studies. In this article, we focus on use of the robot to aid in distal ureteral reconstruction in the adult and pediatric population. Indications reviewed will include benign and malignant conditions. The appropriate pre-operative evaluation, the set-up of the operating room and patient positioning, the described techniques for ureteral reimplantation, and the appropriate post-operative care and follow-up will all be discussed. Literature for the past 10 years has been reviewed, and emphasis given to most recent publications and those describing novel approaches to using the robot for distal ureteral reconstruction.

Bladder tissue engineering.

The bladder can lose the ability to store and empty effectively as a result of numerous conditions. When conservative methods to maximize patient safety and quality of life fail, surgical reconstruction of the bladder is usually considered. Augmentation cystoplasty can be performed with the use of the small bowel, large bowel, or less often, stomach. An alternative approach, tissue engineering, identifies the body's own potential for regeneration and supports this propensity with appropriate raw materials and growth factors so that the body's original structure and function may be restored. Tissue engineering can involve the use of a scaffold or matrix alone or of cell-seeded matrices. Harvesting cells and culturing them has become an important tool in tissue engineering. Multiple possibilities for sources of cells have been investigated, including stem cells and differentiated cells from organs other than the bladder; however, to date, autologous bladder cells remain the gold standard for culture and seeding.