Caudal anesthesia is not associated with post-operative complications following distal hypospadias repair.

INTRODUCTION: The use of caudal anesthesia at the time of hypospadias repair remains controversial as some prior studies have reported increased postoperative complication rates associated with caudal nerve block. However, these results have been called into question due to confounding factors and heterogeneous study groups. OBJECTIVE: Given the importance of identifying true risk factors associated with increased hypospadias complication rate, we examined our experience with caudal anesthesia limiting our analysis to distal repairs. We hypothesized that caudal anesthesia would not be associated with increased postoperative complications. STUDY DESIGN: We retrospectively reviewed our institutional hypospadias database from June 2007 to January 2021. All boys who underwent single-stage distal hypospadias repair with either caudal or penile block with minimum 1 month follow up were included. Records were reviewed to determine the type of local anesthesia, type of hypospadias repair, all complications, and time to complication. Association between any complication and local anesthesia type was evaluated by univariate and multivariate logistic regression analysis controlling for age at surgery and type of repair. A sub-analysis was performed for complications occurring ≤30 days. RESULTS: Overall, 1008 boys, 832 (82.5%) who received caudal and 176 (17.5%) penile block, were included. Median age at surgery was 8.1 months and median follow up was 13 months. Overall complication rate was 16.4% with 13.8% of patients requiring repeat operation. Median time to complication was 10.59 months and was significantly shorter in the caudal group (8.45 vs. 25.2 months). Caudal anesthesia was associated with higher likelihood of complication on univariate analysis; however, this was not true on multivariate analysis when controlling for age and type of repair. Caudal anesthesia was not associated with increased likelihood of complication within 30 days. DISCUSSION: Since the association between caudal anesthesia and hypospadias complications was first suggested, several studies have tried to answer this question with variable results. Our findings add to the evidence that there is no association between caudal anesthesia and increased hypospadias complications in either the short or long term. The major strengths of our study are a large, homogenous study population, robust follow up and inclusion of data from 14 surgeons over 14 years. Limitations include the study's retrospective nature as well as lack of standardized follow up protocol throughout the study period. CONCLUSIONS: After controlling for possible confounders, caudal nerve block was not associated with increased risk of postoperative complications following distal hypospadias repair.

Does ketorolac administration at the time of hypospadias surgery increase unplanned encounters in the immediate postoperative period?

INTRODUCTION & OBJECTIVE: The opioid crisis has raised concerns for long-term sequela of routine administration of opioids to patients, particularly in the pediatric population. Nonsteroidal anti-inflammatory drug use is limited in hypospadias surgery due to concerns for post-operative bleeding, particularly with ketorolac. We hypothesize that ketorolac administration at the time of hypospadias repair is not associated with increased bleeding or immediate adverse events. METHODS: A retrospective single institution study included all patients undergoing hypospadias surgery from 2018 to 2021. Outcomes measured include peri-operative ketorolac administration, opioid prescriptions, and unplanned encounters (i.e., emergency department or office visits). Comparative statistics using non-parametric and binary/categorical tests and a logistic regression were performed. RESULTS: 1044 patients were included, among whom there were 562 distal, 278 proximal and 204 hypospadias complication repairs. Ketorolac was administered to 396 (37.9%) patients and its utilization increased during the study period [Summary Figure]. Patients receiving ketorolac were older (p = 0.002) and were prescribed opioids less often after surgery (2.0% vs 5.2%, p = 0.009). There was no difference in unplanned encounters across repair types (p = 0.1). Multivariate logistic regression showed ketorolac use was not associated with an increased likelihood of an unplanned encounter. DISCUSSION: The use of NSAIDs post-operatively has traditionally been limited due to concerns about bleeding risks, however the present study displayed no significant increases in unplanned patient encounters either in the ED or outpatient clinic after ketorolac administration. Our study has several limitations including its retrospective and single-institutional design, difficulties of pain assessment in pediatric population, and possibility of under estimation of unplanned encounters due to limited access to patients' records outside of our institution. CONCLUSIONS: The use of ketorolac is not associated with an increase in unplanned encounters in children undergoing hypospadias repair. It should be considered a safe agent for perioperative analgesia to decrease opioid utilization. Further studies will evaluate long-term surgical outcomes in children receiving ketorolac after hypospadias repair.

Thoracic spinal arachnoid cyst in a pediatric patient presenting with isolated bladder and bowel incontinence.

Spinal arachnoid cysts (SAC) are uncommon benign spinal cord lesions, particularly in children, that can result in a variety of neurologic symptoms, including neurogenic bladder. Here we present the case of a 7-year-old female with new onset, isolated urinary and stool incontinence who was found to have a T4-T7 SAC. Though this was initially believed to be an incidental imaging finding, after thorough work-up and persistence of her symptoms despite conservative measures she underwent neurosurgical intervention with complete resolution of incontinence. SAC represents a very rare but potentially reversible cause of neurogenic bladder that the urologist should be aware of.

Incidence and resolution of de novo hydronephrosis after pediatric robot-assisted laparoscopic extravesical ureteral reimplantation for primary vesicoureteral reflux.

INTRODUCTION: With the advent of robot-assisted laparoscopic ureteral reimplantation (RALUR) for primary vesicoureteral reflux (VUR), understanding and minimizing its complications continues to be critical. Incidence of de novo hydronephrosis after RALUR could be indicative of an outcome that needs further study or could be a benign transient finding. OBJECTIVE: In the present study, we hypothesized that the incidence of de novo hydronephrosis after RALUR is low and resolves spontaneously. METHODS: An IRB-approved prospective single-institutional registry was utilized to identify all patients undergoing RALUR via an extravesical approach from 2012 to 2020. Patients with primary VUR and minimal (Grade I SFU) or no hydronephrosis prior to surgery were included. Patients who had other associated pathology or underwent concomitant procedures were excluded. Preoperative characteristics including VUR and hydronephrosis grades as well as post-operative clinical details and hydronephrosis grades were aggregated and analyzed. RESULTS: 86/172 (50%) patients (133 ureters), with median reflux grade of 3 (IQR: G2, G3) met the inclusion criteria. Patients underwent RALUR at a median age of 5.7 years (IQR: 3.4, 8.7) with median 36.2 months (IQR: 19.6, 63.6) follow-up. Renal ultrasound at 4-6 weeks post-op showed de novo hydronephrosis in 18 (13.5%) ureters; the complete resolution was seen in 13 ureters (72%) at a median of 4.5 months from surgery. Among the 5 with non-resolved hydronephrosis (SFU G2:4, G3:1), 2 patients (3 ureters) underwent subsequent interventions. DISCUSSION: The present study evaluating the natural history of de novo hydronephrosis after RALUR-EV performed for primary VUR, is to our knowledge the largest cohort of patients undergoing RALUR that this has been studied in. In our cohort, the incidence of de novo hydronephrosis after RALUR was 13.5%, similar to rates reported in two OUR cohorts, and significantly lower than reported incidence rates of 22-26% in several OUR cohorts, and 30% in a RALUR cohort. In the present cohort, hydronephrosis resolved spontaneously in more than 72% of cases. The median time from surgery until resolution of hydronephrosis was 4.5 (1.6, 10.5) months, which is shorter in comparison to the average time to resolution of 7.6 months, reported by Kim et al. in an earlier study. CONCLUSIONS: De novo hydronephrosis after RALUR can be followed with serial renal ultrasounds. The majority of de novo hydronephrosis post-RALUR is transient and resolves spontaneously within a year of surgery with a very low re-intervention rate.

Intrascrotal Lipoblastoma: A Rare Cause of Paratesticular Mass in a Pediatric Patient.

There is a broad differential diagnosis for a pre-pubertal child presenting with a scrotal mass including both benign and malignant etiologies. Lipoblastomas are rare benign neoplasms originating from fat cells that occur most commonly on the trunk or extremities of young children. There have been less than 20 cases of scrotal lipoblastomas reported in the literature, with the majority occurring in children less than 3 years of age. Here we present a unique case of an 18-month male presenting with a paratesticular mass found to be a lipoblastoma on final pathology.

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.

Expanding the Use of Nephron-Sparing Surgery for Wilms Tumor.

Radical nephrectomy combined with contemporary chemotherapeutic and radiation therapy protocols has drastically improved outcomes for children with Wilms tumor. Patients with bilateral disease and a syndrome predisposing to tumor development have necessitated the use of nephron-sparing surgery in select cases. Success in managing these patients has increased the indication for partial nephrectomy, although current guidelines for unilateral Wilms tumor are limited. Given that children are being cured with increasing success, recent focus has shifted to long-term health outcomes in addition to tumor treatment. Specifically, renal function has an impact on long-term cardiovascular health and events. Adult outcomes with partial nephrectomy provide a guideline for a paradigm shift in the management of children with Wilms tumor, particularly with advances in imaging and adjuvant therapy. The data are limited for children undergoing partial nephrectomy for unilateral Wilms tumor and outcomes for larger tumors will need to be studied closely in future trials. Increased utilization of neoadjuvant chemotherapy could further expand the number of patients eligible for partial nephrectomy.

Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor's contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.

Post-operative complications following masculinizing genitoplasty in moderate to severe genital atypia: results from a multicenter, observational prospective cohort study.

INTRODUCTION: Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of Mϋllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. METHODS: This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children's hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3-6 in those with a 46, XY or 45,X/46, XY chromosome complement, age <3 years with no previous genitoplasty; patients were included independent of whether genitoplasty was performed. Cosmesis was graded according to a 4-point Likert scale and complications per the Clavian-Dindo classification. RESULTS: Of the 31 participants, 30 underwent hypospadias repair and 1 patient did not undergo a genitoplasty procedure. The majority of participants (22) received a staged hypospadias repair. Seventeen complications were identified in 12 of the 31 children (41%) at 12 months of follow up. Glans dehiscence and urethrocutaneous fistula were the most common complications. Orchiopexy was performed in 14 (44%) and streak gonads were removed in 4 (13%) participants. Both parents and surgeons reported improved cosmesis after surgery when compared to baseline. CONCLUSION: Genitoplasty was chosen by parents for the majority of children eligible for study. No single surgical approach for masculinizing moderate to severe genital ambiguity in young patients with 46, XY or 45,X/46, XY DSD was adopted by all surgeons. Complications occurred in 41% of those who underwent genitoplasty for severe hypospadias. Overall, appearance of the genitals, as determined by parents and surgeons, improved following genitoplasty. Outcomes of early genitoplasty are needed to guide families when making decisions about such procedures for their young children.

The following 3 cases were presented at the 2020 virtual PUOWG conferenceLate Presentation of Wilms Tumor in a Patient with Hemihypertrophy after Normal Screening.

An identifiable genetic malformation or predisposition syndrome is present in 18% of Wilms tumor cases. Given this, children with conditions associated with a greater than 1% risk of developing Wilms tumor are recommended to have regular surveillance imaging with renal ultrasound until age 7. Seven years is the recommended screening duration because 95% of cases will occur by this age. We present a case of a child with isolated hemihypertrophy, associated with 5% risk of Wilms tumor, who presented with a tumor after the recommended screening, at age 9, brining into question the age cutoffs currently used.

A functional long-term 2D serum-free human hepatic in vitro system for drug evaluation.

Human in vitro hepatic models generate faster drug toxicity data with higher human predictability compared to animal models. However, for long-term studies, current models require the use of serum and 3D architecture, limiting their utility. Maintaining a functional long-term human in vitro hepatic culture that avoids complex structures and serum would improve the value of such systems for preclinical studies. This would also enable a more straightforward integration with current multi-organ devices to study human systemic toxicity to generate an alternative model to chronic animal evaluations. A human primary hepatocyte culture system was characterized for 28 days in 2D and serum-free defined conditions. Under the studied conditions, human primary hepatocytes maintained their characteristic morphology, hepatic markers and functions for 28 days. The acute and chronic administration of known drugs validated the sensitivity of the system for drug testing. This human 2D model represents a realistic system to evaluate hepatic function for long-term drug studies, without the need of animal serum, confounding variable in most models, and with less complexity and resultant cost compared to most 3D models. The defined culture conditions can easily be integrated into complex multi-organ in vitro models for studying systemic effects driven by the liver function for long-term evaluations.

Utilization of Robot-assisted Surgery for the Treatment of Primary Obstructed Megaureters in Children.

OBJECTIVE: To describe the technical aspects of robot assisted laparoscopic ureteral reimplantation (RALUR) for the management of primary obstructive megaureter (POM) and report initial outcomes, safety, and feasibility of the procedure. METHODS: Using an IRB- approved robotic surgery registry, we performed a retrospective chart review of patients undergoing RALUR for POM between April 2009 and May 2019. RESULTS: A total of 18 patients underwent RALUR using a modified Lich-Gregoir technique for management of POM and 7 (38.9%) of these underwent intracorporeal ureteral tapering at the time of surgery. At median follow up of 27.5 (IQR 11-50) months, no patient required reoperation for recurrent obstruction and all patients had improvement in hydronephrosis postoperatively. 30-day complications were low with 1 Grade I, 2 Grade II and 1 Grade III Clavien-Dindo complication. The most common issue postoperatively was febrile urinary tract infection, occurring in 6 patients (33.3%), at an average of 3.2 months after surgery. Increased operative time was the only significant difference between the tapered verses nontapered group. CONCLUSION: We present the largest series of RALUR for POM to date. Based upon our initial experience with this technique we believe it is technically feasible and reproducible with good outcomes and low complication rates. Future studies are needed to track long-term outcomes and better understand indications for and the utility of ureteral tapering as well as how to minimize febrile UTIs postoperatively. Additional follow up is needed to determine the efficacy of RALUR as compared to open ureteral reimplantation for POM.

Does contrast-enhanced ultrasound have a role in evaluation and management of pediatric renal trauma? A preliminary experience.

BACKGROUND: To report our initial experience using intravenous contrast-enhanced ultrasound (CEUS) in pediatric renal trauma with the potential for substantial radiation reduction. METHODS: A retrospective review of all patients who underwent intravenous CEUS at our institution between May 2015 and January 2018 for the suspicion of blunt renal trauma. CEUS was obtained either as an immediate or short-term comparison to contrast-enhanced computed tomography (CECT), or in outpatient follow-up. RESULTS: CEUS was performed on 7 patients (9 kidneys) with age range 2 months to 16 years old. CEUS was utilized as a comparison to CECT in 4 of 7 patients for initial evaluation, clinical change, or short-term follow-up. CEUS alone was used in one patient with low suspicion for renal injury. In the remaining two patients, CEUS was obtained as a follow-up study weeks after the initial CECT, following conservative management. All patients with confirmed renal injury by CECT (n = 5) underwent a follow-up CEUS at 1-2 months. CONCLUSIONS: In an era of conservative management for renal trauma in which operative intervention is dictated more often by the clinical course than radiographic findings, it is reasonable to consider alternative imaging methods such as CEUS in stable patients to decrease radiation exposure. LEVEL OF EVIDENCE RATING: IV.

Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics.

A pumpless, reconfigurable, multi-organ-on-a-chip system containing recirculating serum-free medium can be used to predict preclinical on-target efficacy, metabolic conversion, and measurement of off-target toxicity of drugs using functional biological microelectromechanical systems. In the first configuration of the system, primary human hepatocytes were cultured with two cancer-derived human bone marrow cell lines for antileukemia drug analysis in which diclofenac and imatinib demonstrated a cytostatic effect on bone marrow cancer proliferation. Liver viability was not affected by imatinib; however, diclofenac reduced liver viability by 30%. The second configuration housed a multidrug-resistant vulva cancer line, a non-multidrug-resistant breast cancer line, primary hepatocytes, and induced pluripotent stem cell-derived cardiomyocytes. Tamoxifen reduced viability of the breast cancer cells only after metabolite generation but did not affect the vulva cancer cells except when coadministered with verapamil, a permeability glycoprotein inhibitor. Both tamoxifen alone and coadministration with verapamil produced off-target cardiac effects as indicated by a reduction of contractile force, beat frequency, and conduction velocity but did not affect viability. These systems demonstrate the utility of a human cell-based in vitro culture system to evaluate both on-target efficacy and off-target toxicity for parent drugs and their metabolites; these systems can augment and reduce the use of animals and increase the efficiency of drug evaluations in preclinical studies.

The Robot-Assisted Extravesical Anti-reflux Surgery: How We Overcame the Learning Curve.

Management of vesicoureteral reflux (VUR) has evolved over the past several decades, with a trend toward a decrease in surgical management. In spite of this, ureteral reimplantation remains a commonly performed procedure by pediatric urologists in selected cases. Although the basic tenets of the ureteral reimplant procedure remain the same, the extra- vs. intravesical approach, and the traditional open vs. minimally invasive approach remain the primary options to correct reflux. Considering the advantages conferred by the robotic surgery platform, many leading centers have preferentially adopted robot-assisted laparoscopic extravesical anti-reflux surgery, or in common surgical parlance, the robot-assisted laparoscopic ureteral reimplantation (RALUR), over pure laparoscopic or open approaches. Predicated on our experience of performing over 170 cases of RALUR, we have made technical modifications which we posit reduce the morbidity of the procedure while offering acceptable outcomes. This review highlights the evolution and establishment of RALUR as a standardization of care in the surgical management of VUR at our institution. In particular, we emphasize the technical nuances and specific challenges encountered through the learning curve in hopes of facilitating this process for others.

Case Report: Nephron-sparing Surgery in a Patient With Bilateral Multifocal Wilms Tumor.

We present a case of bilateral multifocal Wilms tumor in a nonsyndromic 12-month-old male. Our management approach included 12 weeks of preoperative chemotherapy for maximal tumor shrinkage and, despite the central location of the tumors, successful staged bilateral nephron-sparing surgery. We advocate for a broader application of nephron-sparing surgery in Wilms tumor cases with the goal of preserving renal function without compromising oncologic outcomes.