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Background: Use of prophylactic antibiotics after stented hypospadias repair is very common, but most research has not identified any clinical benefits of this practice. Only one study has found that postoperative prophylaxis reduces symptomatic urinary tract infections (UTIs). Data from the same trial suggested that prophylaxis may also reduce urethroplasty complications. No studies on this subject have been placebo-controlled., Objective: We performed a randomized, double-blind, placebo-controlled study to evaluate the effect of postoperative prophylactic antibiotics on the incidence of infection or urethroplasty complications after stented repair of midshaft-to-distal hypospadias., Study Design: Boys were eligible for this multicenter trial if they had a primary, single-stage repair of mid-to-distal hypospadias with placement of an open-drainage urethral stent for an intended duration of 5-10 days. Participants were randomized in a double-blind fashion to receive oral trimethoprim-sulfamethoxazole or placebo twice daily for 10 days postoperatively. The primary outcome was a composite of symptomatic UTI, surgical site infection (SSI), and urethroplasty complications, including urethrocutaneous fistula, meatal stenosis, and dehiscence. Secondary outcomes included each component of the primary outcome as well as acute adverse drug reactions (ADRs) and C. difficile colitis., Results: Infection or urethroplasty complications occurred in 10 of 45 boys (22%) assigned to receive antibiotic prophylaxis as compared with 5 of 48 (10%) who received placebo (relative risk [RR], 2.1; 95% confidence interval [CI], 0.8 to 5.8; p = 0.16). There were no significant differences between groups in symptomatic UTIs, SSIs, or any urethroplasty complications. Mild ADRs occurred in 3 of 45 boys (7%) assigned to antibiotics as compared with 5 of 48 (10%) given placebo (RR, 0.6; 95% CI, 0.2 to 2.5; p = 0.72). There were no moderate-to-severe ADRs, and no patients developed C. difficile colitis., Conclusions: In this placebo-controlled trial of 93 patients, prophylactic antibiotics were not found to reduce infection or urethroplasty complications after stented mid-to-distal hypospadias repair. The study did not reach its desired sample size and was therefore underpowered to independently support a conclusion that prophylaxis is not beneficial. However, the result is consistent with most prior research on this subject., Gov Identifier: NCT02096159., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Complications after primary hypospadias repair often present late, that is, more than 1 year postoperatively. This has important implications for clinical practice and prospective research protocols. Follow-up regimen-or lack thereof-may contribute to delayed diagnosis of complications., Objective: To characterize and compare the follow-up regimens of patients with early and late-presenting urethroplasty complications after primary hypospadias repair, specifically noting the length of time between encounters during which complications emerged., Patients and Methods: Boys who underwent repair of urethroplasty complications after hypospadias surgery were identified, and retrospective chart reviews were performed. Late complications were defined by presentation more than 1 year after primary repair; all others were designated as early. We recorded the encounter at which each patient was first noted to have a complication, as well as the last encounter prior to this. Follow-up intervals during which complications emerged were determined. Comparisons of the type of primary repairs, complications, and follow-up regimens (prescribed as well as actual) were performed between patients with early and late complications., Results: A total of 51 patients underwent repair of 57 hypospadias complications. Eighteen patients (35%) had complications that presented late. Complications after a midshaft/distal hypospadias repair were more likely to present late than complications following a one- or two-stage proximal repair (59% vs. 31% vs. 6%, respectively; p = 0.003). The median interval between encounters during which late complications emerged was 24 months (IQR 16-43), compared with 1.2 (0.7-2.2) months for early-presenting complications (p < 0.001). Eleven of the 18 patients with late complications (61%) had not had an encounter beyond 3 months postoperatively prior to presentation of their complications; only four patients (8%) had a late complication that was unrecognized at a follow-up visit more than 6 months postoperatively (Figure). Patients with late complications had a greater discrepancy between prescribed and actual follow-up intervals, averaging 11 months (p = 0.001)., Conclusions: Late presentation of urethroplasty complications after hypospadias repair is relatively common. There is typically a lengthy follow-up interval during which late complications emerge. Many patients who presented with late complications had not previously been examined beyond the early postoperative period. Adherence to a more structured follow-up regimen that includes a visit outside of the early postoperative period (e.g. routine encounters at 6 months postoperatively) may facilitate earlier detection and reduce late presentation of complications, especially among patients with midshaft or distal primary repairs. Earlier diagnosis would allow secondary procedures to be completed sooner., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Recent studies have suggested that a smaller glans penis size may be associated with a higher likelihood of complications after hypospadias repair. Accurate identification of risk factors other than the well-understood variable of meatal location would allow development of better prognostic models and individualized risk stratification., Objective: To test the hypothesis that a smaller width of the glans penis predicts adverse outcomes after hypospadias surgery., Methods: Prospectively recorded clinical data were reviewed from a single-institution registry of primary hypospadias repairs performed between 2011 and 2014. Follow-up records were examined for occurrence of complications. Urethroplasty complications were defined to include meatal stenosis, dehiscence, urethrocutaneous fistula, urethral stricture, and/or urethral diverticulum. The subset of meatal stenosis and dehiscence were regarded as glanular complications. Regression analyses were performed to determine association between glans width and occurrence of complications. Because pre-operative androgen stimulation is known to increase glans penis size, separate subgroup analyses were included of patients with and without pre-operative use of testosterone cream., Results: A total of 159 patients met criteria for inclusion in the study cohort: 140 patients underwent a single-stage repair, while 19 patients had a two-stage repair. The median glans penis width was 15 mm (range 10-22). Eighty-four patients (53%) received testosterone cream pre-operatively and had a significantly wider glans penis than the 75 patients who did not (median 15.5 vs 14 mm; P < 0.001). Median clinical follow-up was 7 months (IQR 1-12), with a minimum time elapsed since surgery of 10 months at the time of chart review. Twenty-four patients (15%) had one or more urethroplasty complications, including 11 (7%) with glanular complications. Overall, there was no statistically significant association between glans width and urethroplasty complications (P = 0.26) or glanular complications (P = 0.90) (Summary Table). Subgroup analyses of patients with and without pre-operative testosterone also revealed no significant associations between glans width and complications., Conclusions: Glans penis width was not a risk factor for complications after hypospadias repair. This finding differs from the results of other recent studies and encourages further research into the value of measuring penile parameters in patients undergoing hypospadias repair., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: We characterize the use of pediatric open, laparoscopic and robot-assisted laparoscopic ureteral reimplantation in the United States from 2000 to 2012., Materials and Methods: We used the Kids' Inpatient Database to identify patients who underwent ureteral reimplantation for primary vesicoureteral reflux. Before 2009 laparoscopic ureteral reimplantion and robot-assisted laparoscopic ureteral reimplantation were referred to together as minimally invasive ureteral reimplantation. A detailed analysis of open vs robot-assisted laparoscopic ureteral reimplantation was performed for 2009 and 2012., Results: A total of 14,581 ureteral reimplantations were performed. The number of ureteral reimplantations yearly decreased by 14.3%. However, the proportion of minimally invasive ureteral reimplantations increased from 0.3% to 6.3%. A total of 125 robot-assisted laparoscopic ureteral reimplantations were performed in 2012 (81.2% of minimally invasive ureteral reimplantations), representing 5.1% of all ureteral reimplantations, compared to 3.8% in 2009. In 2009 and 2012 mean ± SD patient age was 5.7 ± 3.6 years for robot-assisted laparoscopic ureteral reimplantation and 4.3 ± 3.3 years for open reimplantation (p <0.0001). Mean ± SD length of hospitalization was 1.6 ± 1.3 days for robot-assisted laparoscopic ureteral reimplantation and 2.4 ± 2.6 for open reimplantation (p <0.0001). Median charges were $22,703 for open and $32,409 for robot-assisted laparoscopic ureteral reimplantation (p <0.0001). These relationships maintained significance on multivariate analyses. On multivariate analysis robot-assisted laparoscopic ureteral reimplantation use was associated with public insurance status (p = 0.04) and geographic region outside of the southern United States (p = 0.02). Only 50 of 456 hospitals used both approaches (open and robotic), and only 6 hospitals reported 5 or more robot-assisted laparoscopic ureteral reimplantations during 2012., Conclusions: Treatment of primary vesicoureteral reflux with ureteral reimplantation is decreasing. Robot-assisted laparoscopic ureteral reimplantation is becoming more prevalent but remains relatively uncommon. Length of stay is shorter for the robotic approach but the costs are higher. Nationally robot-assisted laparoscopic ureteral reimplantation appears to still be in the early phase of adoption and is clustered at a small number of hospitals., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Uroflowmetry with electromyography (uroflow-EMG) is commonly used for evaluation of lower urinary tract (LUT) function in children. Diagnostic criteria based largely on uroflow-EMG findings have previously been proposed for several conditions collectively termed non-neurogenic voiding disorders (NNVDs). These include dysfunctional voiding (DV), idiopathic detrusor overactivity disorder (IDOD), detrusor underutilization disorder (DUD), and primary bladder neck dysfunction (PBND). It is unknown whether practitioners with varying levels of training and experience can apply the diagnostic criteria for these conditions with a high level of consistency., Objective: To assess inter-rater agreement on diagnosis of NNVDs using uroflow-EMG studies., Study Design: Six raters performed post hoc evaluation of 84 uroflow-EMG studies and associated clinical data from children with symptoms of LUT dysfunction and no evidence of neurologic or anatomic abnormalities. Each rater was asked to categorize the uroflow-EMG studies as being consistent with DV, IDOD, DUD, PBND, or normal/unclassifiable. A consensus diagnosis was noted for studies on which at least four raters agreed. Inter-rater agreement was assessed via calculation of unweighted Fleiss' kappa statistics., Results: Overall inter-rater agreement on NNVD diagnoses was moderate (kappa 0.46, 95% CI 0.38-0.54). Agreement between individual raters ranged from 0.33 (fair) to 0.74 (substantial) (Figure). There was no consensus on diagnosis for 20 patients (24%)., Discussion: Several factors may contribute to inter-rater disagreement on diagnosis of NNVDs. These include instances where patients satisfy one criterion for a particular diagnosis while missing others - or have findings consistent with more than one diagnosis. Strategies to address this may involve simplifying the diagnostic criteria, developing a clear algorithm that prioritizes certain criteria, and/or allowing assignment of multiple diagnoses. Practitioners could also benefit from standardized education regarding the diagnostic criteria for NNVDs. Potential limitations of this analysis included the use of just one uroflow-EMG study per patient in almost all cases. Also, the raters had variable levels of previous experience using the diagnostic criteria for NNVDs, and it is possible that they were not always applied as originally intended. If this were the case, it would support development of a standardized education tool to facilitate practitioner understanding and application of the criteria., Conclusions: Uroflow-EMG has shown promise for improving clinical management of NNVDs associated with pediatric LUT dysfunction. However, inter-rater agreement on NNVD diagnoses using current criteria is suboptimal. Various mechanisms should be explored to improve consistency in practitioners' diagnosis of NNVDs., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

We report 4 pediatric cases of ureteropelvic junction obstruction involving delayed progression of initially mild postnatal hydronephrosis. All 4 children became symptomatic; however, 3 already had a substantial decrement of ipsilateral kidney function by the time of diagnosis. Two of these 3 patients had previous renal scintigraphy demonstrating normal differential function. We caution that counseling regarding hydronephrosis should emphasize the importance of prompt re-evaluation for any symptoms potentially referable to delayed presentation of ureteropelvic junction obstruction, irrespective of initial hydronephrosis grade. Future studies are needed to determine the optimal follow-up regimen for conservative management of hydronephrosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Regional anesthesia is often used in combination with general anesthesia for pediatric surgery, however, it is unknown if adjunctive regional blocks are beneficial to children undergoing urologic laparoscopic or robot-assisted laparoscopic (RAL) procedures., Objective: To compare perioperative outcomes in children with adjunctive caudal blocks, transversus abdominis plane (TAP) blocks, or no regional anesthesia for common RAL surgical procedures in pediatric urology., Study Design: Inclusion in this retrospective study was limited to children who underwent RAL renal or ureteral/bladder procedures and received a standardized regimen of scheduled intravenous ketorolac and oral acetaminophen for acute postoperative pain control, with opioids as needed (PRN). Perioperative outcomes were compared between patients with an adjunctive caudal block (n = 25), bilateral TAP blocks (n = 44), or no regional anesthesia (n = 51)., Results: Children with a preoperative caudal block received less intraoperative opioids than children with TAP blocks or no regional anesthesia (p < 0.001). This difference was observed both for renal procedures (p < 0.01) and ureteral/bladder procedures (p = 0.01). Patients with caudal blocks were also the least likely to require postoperative antiemetics (p = 0.03). There were no significant differences between groups in postoperative opioid use, maximum pain scores within 6 and 24 hours postoperatively, or length of hospital stay (LOS). No complications attributable to regional blocks were identified by chart review., Discussion: Use of adjunctive caudal blocks for pediatric RAL renal or ureteral/bladder surgical procedures may reduce need for alternate analgesic and/or anesthetic agents intraoperatively, as well as decrease postoperative nausea and vomiting. These findings may be related, since nausea and vomiting are common side effects of opioids and inhalational anesthetics. Consideration of the potential impact of caudal blocks on general anesthetic requirements is timely in light of concerns regarding the risk of anesthetic neurotoxicity in young patients. There was no evidence of improved postoperative pain control or shorter LOS for children who received regional anesthesia. It is unknown if regional blocks would have a greater impact in the absence of scheduled pain medications, which all patients in our study received. Limitations of this study include its retrospective nature and moderate sample size. Future randomized controlled trials are necessary to provide a more definitive understanding of regional anesthesia's role in minimizing pediatric surgical and anesthetic morbidity., Conclusion: Administration of caudal blocks should be considered for children of suitable age undergoing RAL surgery involving either the upper or lower urinary tract., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To demonstrate surgical reconstruction of a megameatus variant of hypospadias by using a modified, patient-specific approach., Methods: An 8-month-old male had a megameatus, which was discovered after newborn circumcision. In repair of megameatus, it is important to recognize the full extent to which the distal urethra is widened, in order to avoid inadvertent urethrotomy during mobilization of the glans wings and skin immediately proximal to the glans. In this case, a small wedge of tissue was excised from the ventral aspect of the urethra, and a midline relaxing incision of the urethral plate was made. Standard principles of hypospadias repair should be followed, with tension-free urethral tubularization, coverage of the neourethra with well-vascularized tissue, and adequate mobilization of the glans wings to allow midline reconstruction without compression of the underlying neourethra., Results: There were no perioperative or postoperative complications in this case. The urethral meatus was positioned near the tip of the glans penis, and there was no evidence of meatal stenosis or urethrocutaneous fistula at 5-months follow-up., Conclusion: Each case of megameatus is unique, and a variety of surgical techniques can be used in formulating an approach that achieves optimal cosmetic and functional outcomes., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To demonstrate a novel technique for robot-assisted laparoscopic excisional tailoring and reimplantation of a refluxing megaureter., Methods: A 9-year-old boy with dysfunctional elimination was found to have a refluxing megaureter and diminished ipsilateral renal function. Robotic ureteral reimplantation with excisional tailoring was performed using a three-port approach. Stay sutures were placed in the anterior aspect of the distal ureter and sequentially lifted to allow freehand excision of redundant ureter. The ureterovesical junction was left intact, and the ureter was repaired over a 6 Fr double-J stent. Detrusorotomy to create flaps for ureteral tunneling was performed with a carbon dioxide (CO2) laser., Results: The patient's vesicoureteral reflux was successfully corrected, and he is now asymptomatic., Conclusion: Specific technical modifications can facilitate robotic megaureter repair with intracorporeal excisional tailoring. The CO2 laser is advantageous for detrusorotomy., (Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Transurethral insertion of foreign bodies into the urinary bladder is uncommon in children. We report an 11-year-old boy who presented with hematuria and difficulty voiding secondary to numerous magnetic beads lodged in the urinary bladder and posterior urethra., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors.

Some murine retroviruses cause a spongiform neurodegenerative disease exhibiting pathology resembling that observed in transmissible spongiform encephalopathies. The neurovirulence of these "spongiogenic retroviruses" is determined by the sequence of their respective envelope proteins, although the mechanisms of neurotoxicity are not understood. We have studied a highly neurovirulent virus called FrCasE that causes a rapidly progressive form of this disease. Recently, transcriptional markers of endoplasmic reticulum (ER) stress were detected during the early preclinical period in the brains of FrCasE-infected mice. In contrast, ER stress was not observed in mice infected with an avirulent virus, F43, which carries a different envelope gene, suggesting a role for ER stress in disease pathogenesis. Here we have examined in NIH 3T3 cells the cause of this cellular stress response. The envelope protein of F43 bound BiP, a major ER chaperone, transiently and was processed normally through the secretory pathway. In contrast, the envelope protein of FrCasE bound to BiP for a prolonged period, was retained in the ER, and was degraded by the proteasome. Furthermore, engagement of the FrCasE envelope protein by ER quality control pathways resulted in decreased steady-state levels of this protein, relative to that of F43, both in NIH 3T3 cells and in the brains of infected mice. Thus, the ER stress induced by FrCasE appears to be initiated by inefficient folding of its viral envelope protein, suggesting that the neurodegenerative disease caused by this virus represents a protein misfolding disorder.