Randomized trial of prophylactic antibiotics vs. placebo after midshaft-to-distal hypospadias repair: the PROPHY Study.

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.

Early vs. late-presenting urethroplasty complications after hypospadias repair: A retrospective analysis of patient follow-up.

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.

Use of Pediatric Open, Laparoscopic and Robot-Assisted Laparoscopic Ureteral Reimplantation in the United States: 2000 to 2012.

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.

Delayed Presentation of Ureteropelvic Junction Obstruction and Loss of Renal Function After Initially Mild (SFU Grade 1-2) Hydronephrosis.

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.

Robot-assisted laparoscopic ureteral reimplantation with excisional tailoring for refluxing megaureter.

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.

Endoscopic management of transurethrally inserted magnetic beads.

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.

CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer.

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.

Endoplasmic reticulum (ER) stress induced by a neurovirulent mouse retrovirus is associated with prolonged BiP binding and retention of a viral protein in the ER.

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.