Hillary L. Copp

Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children

PURPOSE The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to children with diagnosed reflux including those young or older than 1 year without evidence of bladder and bowel dysfunction and those older than 1 year with evidence of bladder and bowel dysfunction. From this evidence clinical practice guidelines were developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children with vesicoureteral reflux and a defined care program that permitted identification of cohort specific clinical outcomes. The reporting of meta-analysis of observational studies elaborated by the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) group was followed. The extracted data were analyzed and formulated into evidence-based recommendations. RESULTS A total of 2,028 articles were reviewed and data were extracted from 131 articles. Data from 17,972 patients were included in this analysis. This systematic meta-analysis identified increasing frequency of urinary tract infection, increasing grade of vesicoureteral reflux and presence of bladder and bowel dysfunction as unique risk factors for renal cortical scarring. The efficacy of continuous antibiotic prophylaxis could not be established with current data. However, its purported lack of efficacy, as reported in selected prospective clinical trials, also is unproven owing to significant limitations in these studies. Reflux resolution and endoscopic surgical success rates are dependent upon bladder and bowel dysfunction. The Panel then structured guidelines for clinical vesicoureteral reflux management based on the goals of minimizing the risk of acute infection and renal injury, while minimizing the morbidity of testing and management. These guidelines are specific to children based on age as well as the presence of bladder and bowel dysfunction. Recommendations for long-term followup based on risk level are also included. CONCLUSIONS Using a structured, formal meta-analytic technique with rigorous data selection, conditioning and quality assessment, we attempted to structure clinically relevant guidelines for managing vesicoureteral reflux in children. The lack of robust prospective randomized controlled trials limits the strength of these guidelines but they can serve to provide a framework for practice and set boundaries for safe and effective practice. As new data emerge, these guidelines will necessarily evolve.

Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis

PURPOSE The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. RESULTS In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same in males and females. Bilateral reflux prevalence is similar to unilateral reflux. Grade I-II reflux is estimated to be present in 16.7% and grade III-V reflux in 9.8% of screened patients. The estimate for renal cortical abnormalities overall is 19.3%, with 27.8% having renal damage in cohorts of symptomatic and asymptomatic children combined. In asymptomatic siblings only the rate of renal damage is 14.4%. There are presently no randomized, controlled trials of treated vs untreated screened siblings with vesicoureteral reflux to evaluate health outcomes as spontaneous resolution, decreased rates of urinary infection, pyelonephritis or renal scarring. In screened populations with prenatal hydronephrosis the prevalence of vesicoureteral reflux is 16.2%. Reflux in the contralateral nondilated kidney accounted for a mean of 25.2% of detected cases for a mean prevalence of 4.1%. In patients with a normal postnatal renal ultrasound the prevalence of reflux is 17%. The prenatal anteroposterior renal pelvic diameter was not predictive of reflux prevalence. A diameter of 4 mm is associated with a 10% to 20% prevalence of vesicoureteral reflux. The prevalence of reflux is statistically significantly greater in females (23%) than males (16%) (p=0.022). Reflux grade distribution is approximately a third each for grades I-II, III and IV-V. The estimate of renal damage in screened infants without infection is 21.8%. When stratified by reflux grade renal damage was estimated to be present in 6.2% grade I-III and 47.9% grade IV-V (p <0.0001). The risk of urinary tract infection in patients with and without prenatal hydronephrosis and vesicoureteral reflux could not be determined. The incidence of reported urinary tract infection in patients with reflux was 4.2%. CONCLUSIONS The meta-analysis provided meaningful information regarding screening for vesicoureteral reflux. However, the lack of randomized clinical trials for screened patients to assess clinical health outcomes has made evidence-based guideline recommendations difficult. Consequently, screening guidelines are based on present practice, risk assessment, meta-analysis results and Panel consensus.

Diagnostic Performance of Ultrasound in Nonpalpable Cryptorchidism: A Systematic Review and Meta-analysis

CONTEXT: Ultrasound is frequently obtained during the presurgical evaluation of boys with nonpalpable undescended testes, but its clinical utility is uncertain. OBJECTIVE: To determine the diagnostic performance of ultrasound in localizing nonpalpable testes in pediatric patients. METHODS: English-language articles were identified by searching Medline, Embase, and the Cochrane Library. We included studies of subjects younger than 18 years who had preoperative ultrasound evaluation for nonpalpable testes and whose testis position was determined by surgery. Data on testis location determined by ultrasound and surgery were extracted by 2 independent reviewers, from which ultrasound performance characteristics (true-positives, false-positives, false-negatives, and true-negatives) were derived. Meta-analysis of 12 studies (591 testes) was performed by using a random-effects regression model; composite estimates of sensitivity, specificity, and likelihood ratios were calculated. RESULTS: Ultrasound has a sensitivity of 45% (95% confidence interval [CI]: 29–61) and a specificity of 78% (95% CI: 43–94). The positive and negative likelihood ratios are 1.48 (95% CI: 0.54–4.03) and 0.79 (95% CI: 0.46–1.35), respectively. A positive ultrasound result increases and negative ultrasound result decreases the probability that a nonpalpable testis is located within the abdomen from 55% to 64% and 49%, respectively. Significant heterogeneity limited the precision of these estimates, which was attributable to variability in the reporting of selection criteria, ultrasound methodology, and differences in the proportion of intraabdominal testes. CONCLUSIONS: Ultrasound does not reliably localize nonpalpable testes and does not rule out an intraabdominal testis. Eliminating the use of ultrasound will not change management of nonpalpable cryptorchidism but will decrease health care expenditures.

Antibiotic Resistance Patterns of Outpatient Pediatric Urinary Tract Infections

PURPOSE We characterize the current national patterns of antibiotic resistance of outpatient pediatric urinary tract infection. MATERIALS AND METHODS We examined outpatient urinary isolates from patients younger than 18 years in 2009 using The Surveillance Network®, a database with antibiotic susceptibility results and patient demographic data from 195 United States hospitals. We determined the prevalence and antibiotic resistance patterns for the 6 most common uropathogens, ie Escherichia coli, Proteus mirabilis, Klebsiella, Enterobacter, Pseudomonas aeruginosa and Enterococcus. We compared differences in uropathogen prevalence between males and females using chi-square analysis. RESULTS We identified 25,418 outpatient urinary isolates. E. coli was the most common uropathogen overall but the prevalence of E. coli was higher among females (83%) than males (50%, p <0.001). Other common species among males were Enterococcus (17%), P. mirabilis (11%) and Klebsiella (10%). However, these uropathogens each accounted for 5% or less of female isolates (p <0.001). Resistance among E. coli was highest for trimethoprim-sulfamethoxazole (24%) but lower for nitrofurantoin (less than 1%) and cephalothin (15%). Compared to 2002 Surveillance Network data, E. coli resistance rates increased for trimethoprim-sulfamethoxazole (from 23% to 31% in males and from 20% to 23% in females) and ciprofloxacin (from 1% to 10% and from 0.6% to 4%, respectively). CONCLUSIONS E. coli remains the most common pediatric uropathogen. Although widely used, trimethoprim-sulfamethoxazole is a poor empirical choice for pediatric urinary tract infections in many areas due to high resistance rates. First-generation cephalosporins and nitrofurantoin are appropriate narrow-spectrum alternatives given their low resistance rates. Local antibiograms should be used to assist with empirical urinary tract infection treatment.

National Ambulatory Antibiotic Prescribing Patterns for Pediatric Urinary Tract Infection, 1998–2007

OBJECTIVE: The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs). METHODS: We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use. RESULTS: Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2–18.7, compared with children 13–17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6–8.5]), and temperature ≥100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0–8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection. CONCLUSIONS: Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower alternatives.

Diagnostic Imaging in Cryptorchidism: Utility, Indications, and Effectiveness

BACKGROUND Cryptorchidism (undescended testis) is the most common genitourinary anomaly in male infants. METHODS We reviewed the available literature on the diagnostic performance of ultrasound, computed tomography, and magnetic resonance imaging (MRI) in localizing undescended testes. RESULTS Ultrasound is the most heavily used imaging modality to evaluate undescended testes. Ultrasound has variable ability to detect palpable testes and has an estimated sensitivity and specificity of 45% and 78%, respectively, to accurately localize nonpalpable testes. Given the poor ability to localize nonpalpable testes, ultrasound has no role in the routine evaluation of boys with cryptorchidism. Magnetic resonance imaging has greater sensitivity and specificity but is expensive, not universally available, and often requires sedation for effective studies of pediatric patients. Diagnostic laparoscopy has nearly 100% sensitivity and specificity for localizing nonpalpable testes and allows for concurrent surgical correction. CONCLUSIONS Although diagnostic imaging does not have a role in the routine evaluation of boys with cryptorchidism, there are clinical scenarios in which imaging is necessary. Children with ambiguous genitalia or hypospadias and undescended testes should have ultrasound evaluation to detect the presence of müllerian structures.

Compliance With Antibiotic Prophylaxis in Children With Vesicoureteral Reflux: Results From a National Pharmacy Claims Database

PURPOSE Antibiotic prophylaxis is commonly used for medical management of vesicoureteral reflux. Little information exists on compliance with antibiotic prophylaxis in patients with vesicoureteral reflux. MATERIALS AND METHODS We queried the i3 Innovus (Ingenix) pharmacy claims 2002 to 2007 database for patients 18 years old or younger with vesicoureteral reflux (ICD-9 code 593.7 plus claim for cystogram) and analyzed those with at least 1 year of followup data. Criteria for management with antibiotic prophylaxis were 2 or more 30-day supplies of antibiotic prescriptions, or 4 or more 14-day supplies of prescriptions if the antibiotic was a penicillin or cephalosporin. Antibiotic prophylaxis compliance was determined using a medication possession ratio, an estimate of the proportion of time that patients have a prescribed drug available for use. Compliance was established as a medication possession ratio of 80% or greater, meaning coverage with antibiotic prophylaxis for 80% of the year or more. RESULTS Of 9,496 patients with vesicoureteral reflux 5,342 (56.3%) were treated with antibiotic prophylaxis. Most patients were female (81%) and 5 years old or younger (79%). Trimethoprims/sulfonamides were most commonly prescribed (62%) and antiseptics were next (24%). Of patients prescribed antibiotic prophylaxis 40% were compliant. Compliance was lower for 6 to 10-year-olds (OR 0.71, 95% CI 0.61-0.83) and 11 to 18-year-olds (OR 0.56, 95% CI 0.41-0.79) compared to younger children (5 years or less). Increased compliance was associated with 1 or more hospitalizations (OR 1.70, 95% CI 1.48-1.97) and 1 or more urologist visits (OR 1.41, 95% CI 1.25-1.58). CONCLUSIONS Among patients with vesicoureteral reflux who are prescribed prophylactic antibiotics 40% are compliant with treatment. Young age, frequent hospitalization and specialist visits are associated with compliance. This knowledge may help to develop effective interventions to improve compliance and underscores the importance of reporting compliance in clinical studies evaluating the usefulness of antibiotic prophylaxis in vesicoureteral reflux management.

Clinical Presentation and Urachal Remnant Pathology: Implications for Treatment

PURPOSE Symptomatic pediatric urachal remnants are frequently excised but to our knowledge it is unknown whether incidentally identified urachal remnants require removal. Urachal remnant excision in childhood is advocated to avoid future malignancy. Urachal anomalies that contain fibrostromal tissue without epithelium may have lower malignant potential and not require excision. In contrast, lesions with epithelium may have increased potential to undergo malignant transformation. We examined whether incidentally identified urachal remnants would be less likely to contain epithelial elements and not require removal. MATERIALS AND METHODS At our institution 29 patients underwent surgical excision of a urachal anomaly from 1999 to 2008. We retrospectively investigated the presentation mode, radiographic findings, associated genitourinary abnormalities, operative approach, tissue pathology, complications and followup in each patient. RESULTS The male-to-female ratio was 1.2:1. Patient presentation was incidental (5) or symptomatic (24). Symptomatic presentations included umbilical discharge without omphalitis in 13 cases, umbilical discharge with omphalitis in 7, omphalitis without umbilical discharge in 3 and urinary tract infection in 1. The epithelial types identified were transitional, gastrointestinal, squamous, metaplastic and mixed. Epithelium was present on pathological analysis in 3 of 5 patients who presented incidentally and in 17 of 24 who presented symptomatically. Statistical analysis showed no association between presentation mode and pathology (p = 0.63). Five patients 4 weeks to 2.5 months old had vesicoureteral reflux on voiding cystourethrogram for urachal remnant evaluation. CONCLUSIONS Analysis of 29 patients with urachal anomalies showed no association between incidental presentation and fibrostromal pathology. Patients presenting without symptoms were as likely to have epithelial elements in the urachal remnant as those presenting with symptoms. We could not define treatment recommendations for incidentally identified urachal remnants based on predicting the histopathological composition.

Prospective evaluation of the prognostic relevance of molecular staging for urothelial carcinoma

Nearly 50% of urothelial carcinoma patients with lymph node‐negative invasive cancers recur after radical surgery. In many cases, occult local or lymph node disease may be present but undetectable by current approaches. Reverse‐transcriptase polymerase chain reaction (RT‐PCR)‐detectable mRNA of Uroplakin II (UPII), a urothelial‐specific gene mRNA, was evaluated in perivesical and lymph node samples removed at radical surgery as a predictor of clinical recurrence.

Cumulative incidence of outcomes and urologic procedures after augmentation cystoplasty

OBJECTIVE Augmentation cystoplasty (AC) is a major surgery that can be associated with long-term morbidity. This study aimed to describe the cumulative incidence of outcomes and urologic procedures in a large cohort of children who underwent AC, identify significant sources of morbidity, and to evaluate baseline factors associated with outcomes of interest. METHODS Children≤18 years who underwent AC in the Pediatric Health Information System from 1999 to 2010 were included. All follow-up encounters up to June 2012 were included. Cumulative incidences for 15 outcomes and urologic procedures were calculated using non-informative censoring. Sensitivity analyses were performed to determine effect of censoring assumptions and including hospitals without complete datasets. As an exploratory analysis, baseline patient factors were evaluated for associations with outcomes and urologic procedures of interest using multivariable Cox proportional hazards models adjusted for clustering by hospital. RESULTS 2831 AC patients were identified. Based on cumulative incidence calculations and sensitivity analyses; the cumulative incidence ranges of outcomes and procedures at 1, 3, 5, and 10 years were calculated. Examples of 10-year cumulative incidence ranges are given for the following outcomes and procedures: bladder rupture (2.9-6.4%), small bowel obstruction (5.2-10.3%), bladder stones (13.3-36.0%), pyelonephritis (16.1-37.1%), cystolithopaxy (13.3-35.1%), and reaugmentation (5.2-13.4%). The development of chronic kidney disease was strongly associated with a diagnosis of lower urinary tract obstruction (HR 13.7; 95% CI 9.4-19.9). Bladder neck surgery and stoma creation at time of AC were associated with an increased hazard of bladder rupture (HR 1.9; 95% CI 1.1-3.3) and bladder stones (HR 1.4; 95% CI 1.1-1.8) respectively. CONCLUSIONS Outcomes of interest and urologic procedures after AC are common. Results from this large cohort can be used to counsel patients and families about expectations after AC. Pyelonephritis, chronic kidney disease, further reconstructive surgery, and calculus disease appear to cause significant morbidity. Collaborative efforts are needed to further reduce morbidity in this patient population.