Risk of re-operation after outpatient distal hypospadias repair in a large, multistate cohort.

BACKGROUND: Repair of distal hypospadias is one of the most common pediatric urology procedures in the US. However, the risk of postsurgical complications has been reported primarily from single-institution and tertiary center studies, with short duration of patient follow-up. OBJECTIVE: The aim of the study was to examine the incidence of re-operation and risk factors for re-operation following outpatient distal hypospadias repair in a large, representative sample of US children. METHODS: A retrospective cohort study of patients aged 0-18 years undergoing single-stage distal hypospadias repair was conducted. Data were obtained from the State Ambulatory Surgery and Services Databases of 9 participating states. Patients who underwent outpatient surgery in 2008-2013 were identified using Current Procedural Terminology (CPT) codes. Patients with records suggesting prior surgery for hypospadias (CPT) were excluded, as were patients who underwent the initial repair <2 years before the end of state data availability. Return outpatient surgery visits across institutions within each of the 9 states were tracked to identify re-operations after the single-stage repair, using CPT codes for surgical treatment of hypospadias complications in 2008-2015. Time-to-event analyses were used to estimate the probability (risk) of re-operation over time and to examine whether patient and institutional characteristics were predictive of re-operation (age, race/ethnicity, health insurance, facility ownership, and institutional volume of hypospadias repair). RESULTS: A total of 4673 children treated across 148 institutions were included. The median follow-up time was 4.1 years (range: 2-7.9). Most patients were <1 year of age at the time of initial repair (53%). The risk of re-operation was 2.6% (95% confidence interval [CI]: 2.1-3.0%) at 1 year and 6.7% (95% CI: 6.0-7.5%) at 5 years after initial repair (Figure). Approximately 13% of re-operation patients had the re-operation at a different institution. None of the patient or institutional factors examined was a significant predictor of the risk of re-operation. DISCUSSION: In this population-based cohort, the estimated 5-year risk of re-operation following single-stage distal hypospadias repair was 6.7% (95% CI: 6.0-7.5). Most re-operations occurred after the first year, informing long-term expectations about postoperative complications. This study was limited by a lack of data on severity of hypospadias and surgeon characteristics and the inability to track re-operations outside of the state in which the original repair was performed. CONCLUSION: Approximately 7% of children undergoing distal hypospadias repair undergo a re-operation within 5 years. None of the factors studied were predictive of re-operations.

Trends in surgical management of multicystic dysplastic kidney at USA children's hospitals.

INTRODUCTION AND OBJECTIVE: Multicystic dysplastic kidney (MCDK) is a congenital renal cystic disease often incidentally diagnosed in children. Historically, children with MCDK underwent early nephrectomy because of concerns for the development of hypertension or malignancy. Over the last decade, management recommendations have not supported routine early surgical removal of MCDK. The study authors sought to determine the current trends in the use of nephrectomy for MCDK in US children's hospitals because national practice patterns have not been investigated. METHODS: A population-based retrospective cohort study using the Pediatric Health Information System (PHIS) was conducted. The study population was comprised of patients aged 0-18 years with a diagnosis of MCDK (International Classification of Diseases-9th revision, code 753.19) admitted to the inpatient department of the study hospital between January 2006 and September 2015. Patients with additional renal anomalies including polycystic kidney, medullary cystic kidney, and medullary sponge kidney were excluded, as were patients treated in a hospital that did not contribute data to the PHIS continuously throughout the study period. Trends in the annual proportion of nephrectomies performed were analyzed among admissions in the study population, along with patient clinical and demographic information. RESULTS: A total of 3792 MCDK admissions, in 34 hospitals, were included in the study. Overall, 569 nephrectomies were performed during the study period. The proportion of nephrectomy decreased annually by 9.2% on average, from 22.1% in 2006 to 7.3% in the first 3 quarters of 2015. No significant trends were observed in the annual number of overall MCDK admissions or patient age at procedure among patients who had a nephrectomy. Among nephrectomies, 84.2% were open and 15.8% were minimally invasive procedures (laparoscopic non-robotic, 10% and robotic, 5.8%). The proportion of minimally invasive nephrectomies increased annually by 13.7%, from 8% in 2006 to 29% in 2015. DISCUSSION: Trends in the use of nephrectomy for MCDK at a national level have not been previously reported. This study is limited by the use of inpatient discharge data, which did not allow estimating the true rate of nephrectomy in patients born with MCDK. CONCLUSIONS: During the study period, there has been a decrease in the use of nephrectomy for MCDK in pediatric hospitals, along with a concurrent increase in utilization of minimally invasive techniques to perform nephrectomies. These results suggest that in general, urologists at freestanding children's hospitals are heeding recommendations for observation and against routine early surgical removal of these kidneys; although trends in the use of nephrectomy varied between hospitals, there is room for continued improvement in following these recommendations.

Benefits of spinal anesthesia for urologic surgery in the youngest of patients.

INTRODUCTION: Increasing concerns regarding potential negative effects of early use of inhalational and intravenous anesthetics on neurocognitive development have led to a growing interest in alternative forms of anesthesia in infants. The study institution's outcomes with spinal anesthesia (SA) for urologic surgery in infants aged less than 90 days are reported and their outcomes with a matched cohort of patients who underwent general anesthesia (GA) are compared. METHODS: This is a retrospective single-center analysis. Patients aged less than 90 days who underwent SA for four urologic surgeries (inguinal hernia repair, scrotal exploration, posterior urethral valve ablation, and ureterocele puncture) were identified from the study institution's SA database. An age- and procedure-matched control cohort was identified from a list of patients who underwent the aforementioned four procedures under GA since 2013. Outcomes of interest included success rate of SA, complications from spinal placement, narcotic use, need for supplemental medications and oxygen, and length of hospital stay. RESULTS: Forty patients were identified; 20 in the SA and 20 in the GA group. Mean patient age was 54 (standard deviation, 35) days. There were no significant differences between the groups in age, gender, weight, history of prematurity, or presence of comorbidities. Eighty percent of SA patients had successful SA; reasons for conversion to GA included failure of spinal needle placement (75%) and agitation during operative procedure (25%). Ninety-six percent of patients who received GA (primarily or converted) had an endotracheal tube (ETT) placed. No patient in the SA group had a complication from spinal needle placement. Patients in the SA group were less likely to receive narcotics during the operative procedure (P = 0.001) and also had a lower mean morphine equivalent dose/kilogram (P = 0.002). Patients in the SA group were also less likely to receive any supplemental medications during the operative procedure (P = 0.001), particularly intravenous corticosteroids (P < 0.001). There were no significant differences in the length of hospital stay. CONCLUSIONS: The use of SA has clear advantages for this medically vulnerable population. For the majority of patients, it obviates the need for ETT placement and airway management and avoids the potential negative effects of GA on neurocognitive development. It also decreases the use of narcotics and other supplemental medications. In scenarios in which the benefit of surgery must be weighed against the risk of GA, such as neonatal torsion, SA may allow a paradigm shift in the timing of surgery.

Urinary antimicrobial peptides: Potential novel biomarkers of obstructive uropathy.

INTRODUCTION: Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, there is mounting evidence to support their expression in noninfectious injury, with unclear meaning as to their function. It is possible that AMPs represent urothelial injury. Urinary tract obstruction is known to alter the urothelium; however, AMPs have not been evaluated for expression in this noninfectious injury. OBJECTIVE: A pilot study to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with nonobstructed controls. STUDY DESIGN: Bladder urine was collected from consenting/assenting pediatric patients with UPJO at intervention. Control bladder urines were obtained from age-matched and sex-matched healthy children without known obstruction or infection. Enzyme-linked immunosorbent assays were run for the following AMPs: ß defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5); and normalized to urine creatinine. Results were analyzed with Student's t-test or Mann-Whitney U test, when appropriate, and receiver operating characteristic curves. A P-value of <0.05 was considered significant. RESULTS: Thirty bladder urine samples were obtained from children with UPJO at the time of decompressive intervention. Mean patient age was 4.7 years (range 0.3-18.4); 20 (67%) patients were male. Fifteen bladder urine samples were obtained from age-matched and sex-matched controls. Urinary AMP levels were significantly higher in UPJO patients than controls for BD-1 (P = 0.015), NGAL (P < 0.001), LL-37 (P < 0.001), and HIP/PAP (P = 0.046). Optimal threshold values of these AMPs were determined, with each demonstrating significant odds ratios of predicting urinary obstruction. DISCUSSION: Certain urinary AMPs are altered even in noninfectious urinary tract pathology. This represents a novel induction of AMP expression, as the current study is the first to report elevations in BD-1 and HIP/PAP in urinary tract obstruction. This suggests other roles for these AMPs outside of their antimicrobial properties, and likely is a reflection of the urothelial and tubular stress resulting from obstructive uropathy. CONCLUSIONS: Induction of AMPs BD-1, NGAL, LL-37, and HIP/PAP was found to occur in urinary tract obstruction. Further evaluation of AMP expression as a biomarker of uroepithelial injury outside of infection is indicated.

The modified Ulaanbaatar procedure: Reduced complications and enhanced cosmetic outcome for the most severe cases of hypospadias.

INTRODUCTION/OBJECTIVE: Proximal hypospadias is one of the most challenging conditions that pediatric urologists have to deal with. Many procedures have been devised over the years, but nothing has been proven to be the best option. Although there have been some attempts at correcting severe hypospadias in one procedure, most have advocated a staged approach. The classic approach - laying penile skin or a graft within a split glans followed by glanuloplasty at the second stage - by definition requires two operations on the glans. In the Ulaanbaatar procedure the distal glanular urethra is constructed at the first stage, allowing for a single glans procedure and thus potentially better cosmetic outcomes. The present study discusses experience with the Ulaanbaatar procedure for severe hypospadias. STUDY DESIGN: The study retrospectively reviewed every child who underwent both stages of this procedure at the present institution. It reviewed age, associated diagnoses, surgical technique and outcomes. SURGICAL TECHNIQUE: The first stage was analogous to a classic first-stage procedure with regard to division of the urethral plate and correction of penile curvature. However, an island flap of preputial skin was mobilized and tubularized to create the glanular urethra. No attempt was made to bridge the native meatus and this reconstructed urethra, and the remaining penile skin was placed between the two. The second stage was performed 6 months later by tubularizing the penile skin between the two meatuses. RESULTS: The series consisted of 34 boys. Mean age at surgery was 18.3 months (range 6-118). Nineteen underwent evaluation for genital ambiguity at birth (56%). Thirty (88%) received pre-operative testosterone or human chorionic gonadotropin (HCG). After urethral plate transection, persistent curvature was addressed during the first stage, with dorsal plication in 12 (35%), urethral plate transection alone in six (18%) or ventral grafting with small intestinal submucosa in 16 (47%). Twenty-three boys (67%) had the neourethra tunneled through the glans, and 11 (33%) had the glans split followed by glanuloplasty. Average time between the two stages was 7 months (range 4.0-13.9). Four patients (12%) developed urethral diverticula that required repair. One developed recurrent epididymitis related to an abnormal ejaculatory duct (no stricture) and underwent vasectomy. No patient developed a fistula. Mean length of follow-up was 15.2 months (range 0.3-55.5). DISCUSSION: This modification of the classic staged hypospadias repair may allow for better cosmetic outcome, since the majority of boys required no formal glanuloplasty. There were reduced complications, perhaps because the urethral defect acted like a controlled fistula, allowing for better tissue healing prior to final urethral reconstruction.

Ureteroureterostomy irrespective of ureteral size or upper pole function: a single center experience.

OBJECTIVE: Although ureteroureterostomy (UU) is an established procedure for the treatment of duplex anomalies, there may be a reluctance to apply this approach to patients with poor upper pole function and/or marked degrees of ureteral dilation. METHODS: An institutional review board (IRB)-approved retrospective analysis of all patients undergoing UU between 2006 and present was performed. All patients underwent an end-to-side anastomosis with a double-J stent left in the lower pole ureter. Laparoscopic repairs were done 'high' and open repairs were done 'low'. If the upper pole ureter remained massively dilated after transection, the ureter was partially closed to reduce the length of the anastomosis. Data collected included demographics, diagnosis, surgical interventions, imaging studies and outcomes. RESULTS: A total of 41 patients (43 renal units) were identified. There were 35 females and six males with an average age at surgery of 2.3 years (range 55 days to 15.9 years) and an average follow up of 2.8 years. Diagnosis included ureterocele (17), ectopic duplex ureter (25) and ureteral triplication (1). Thirty-six patients underwent UU only and five underwent UU with simultaneous lower pole reimplantation. Twelve of the 41 patients (29%) underwent laparoscopic repair. Twelve of the 43 renal units (28%) required ureteral tapering, of which three were performed laparoscopically. Preoperative median upper pole function was 17% (0-35%). Six patients had no measurable function and ten had < 15%. No patient developed lower pole hydronephrosis in the follow-up period. There were two complications: one patient was found to have a post-operative ureterovesical junction (UVJ) stricture and the second had an anastomotic stricture. CONCLUSION: Ureteroureterostomy is a safe and effective technique for the reconstruction of duplex anomalies, even with a massively dilated and poorly functioning upper pole moiety. With no identifiable negative effect on the lower pole system, the concept of automatically removing 'dysplastic' upper pole segments can be challenged.

Synthetic peptide derived from alpha-fetoprotein inhibits growth of human breast cancer: investigation of the pharmacophore and synthesis optimization.

Asynthetic peptide that inhibits the growth of estrogen receptor positive (ER+) human breast cancers, growing as xenografts in mice, has been reported. The cyclic 9-mer peptide, cyclo[EMTOVNOGQ], is derived from alpha-fetoprotein (AFP), a safe, naturally occurring human protein produced during pregnancy, which itself has anti-estrogenic and anti-breast cancer activity. To determine the pharmacophore of the peptide, a series of analogs was prepared using solid-phase peptide synthesis. Analogs were screened in a 1-day bioassay, which assessed their ability to inhibit the estrogen-stimulated growth of uterus in immature mice. Deletion of glutamic acid, Glu1, abolished activity of the peptide, but glutamine (Gln) or asparagine (Asn) could be substituted for Glu1 without loss of activity. Methionine (Met2) was replaced with lysine (Lys) or tyrosine (Tyr) with retention of activity. Substitution of Lys for Met2 in the cyclic molecule resulted in a compound with activity comparable with the Met2-containing cyclic molecule, but with a greater than twofold increase in purity and corresponding increase in yield. This Lys analog demonstrated anti-breast cancer activity equivalent to that of the original Met-containing peptide. Therefore, Met2 is not essential for biologic activity and substitution of Lys is synthetically advantageous. Threonine (Thr3) is a nonessential site, and can be substituted with serine (Ser), valine (Val), or alanine (Ala) without significant loss of activity. Hydroxyproline (Hyp), substituted in place of the naturally occurring prolines (Pro4, Pro7), allowed retention of activity and increased stability of the peptide during storage. Replacement of the first Pro (Pro4) with Ser maintains the activity of the peptide, but substitution of Ser for the second Pro (Pro7) abolishes the activity of the peptide. This suggests that the imino acid at residue 7 is important for conformation of the peptide, and the backbone atoms are part of the pharmacophore, but Pro4 is not essential. Valine (Val5) can be substituted only with branched-chain amino acids (isoleucine, leucine or Thr); replacement by d-valine or Ala resulted in loss of biologic activity. Thus, for this site, the bulky branched side chain is essential. Asparagine (Asn6) is essential for activity. Substitution with Gln or aspartic acid (Asp), resulted in reduction of biologic activity. Removal of glycine (Gly8) resulted in a loss of activity but nonconservative substitutions can be made at this site without a loss of activity indicating that it is not part of the pharmacophore. Cyclization of the peptide is facilitated by addition of Gln9, but this residue does not occur in AFP nor is it necessary for activity. Gln9 can be replaced with Asn, resulting in a molecule with similar activity. These data indicate that the pharmacophore of the peptide includes side chains of Val5 and Asn6 and backbone atoms contributed by Thr3, Val5, Asn6, Hyp7 and Gly8. Met2 and Gln9 can be modified or replaced. Glu1 can be replaced with charged amino acids, and is not likely to be part of the binding site of the peptide. The results of this study provide information that will be helpful in the rational modification of cyclo[EMTOVNOGQ] to yield peptide analogs and peptidomimetics with advantages in synthesis, pharmacologic properties, and biologic activity.