Saul P. Greenfield

Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial

OBJECTIVES. There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux. METHODS. One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans. RESULTS. The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis. CONCLUSIONS. Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.

Endoscopic Therapy for Vesicoureteral Reflux: A Meta-Analysis. I. Reflux Resolution and Urinary Tract Infection

PURPOSE Current American Urological Association treatment guidelines for vesicoureteral reflux do not include any recommendations pertaining to endoscopic therapy (subureteral injection of bulking agent). We performed a meta-analysis of the existing literature pertaining to endoscopic treatment to allow comparison with reports of open surgical correction. MATERIALS AND METHODS We searched all peer reviewed articles published through 2003 pertaining to endoscopic treatment of vesicoureteral reflux. A total of 63 articles were double reviewed by 9 pediatric urologists, and the data were tabulated on data retrieval sheets. A mixed effects logistic regression model was used to obtain overall estimates of event probabilities (eg reflux resolution, ureteral obstruction) together with their 95% confidence intervals. Individual study estimates were obtained with overall estimate and observation characteristics using empirical Bayes calculations. Differences between or among specific groups were assessed using the F-test. RESULTS The database included 5,527 patients and 8,101 renal units. Following 1 treatment the reflux resolution rate (by ureter) for grades I and II reflux was 78.5%, grade III 72%, grade IV 63% and grade V 51%. If the first injection was unsuccessful, the second treatment had a success rate of 68%, and the third treatment 34%. The aggregate success rate with 1 or more injections was 85%. The success rate was significantly lower for duplicated (50%) vs single systems (73%), and neuropathic (62%) vs normal bladders (74%). The success rate was similar among children and adults. Following a previous failed open reimplantation endoscopic treatment was successful in 65% of patients. After endoscopic treatment with variable followup pyelonephritis developed in 0.75% of patients and cystitis in 6%. There were few reports of renal scarring following treatment. CONCLUSIONS Endoscopic treatment provides a high rate of success in children with reflux that decreases with increasing grade, although multiple treatments may be necessary. Future reports of endoscopic therapy should include rates of urinary tract infection and renal scarring.

The Use of Intravesical Oxybutynin Chloride in Children with Neurogenic Bladder

Intravesical oxybutynin chloride was administered to 10 children with neurogenic bladder (myelomeningocele in 9 and imperforate anus in 1) and urinary incontinence refractory to regimens of intermittent catheterization and oral anticholinergic medication. Therapy consisted of instillation of 5 mg. crushed oxybutynin chloride in 10 cc sterile saline twice daily. Of the children 5 (50%) became completely dry day and night, 3 (30%) achieved daytime continence alone, and 2 did not improve clinically and remained in diapers. Urodynamic study revealed increases in bladder capacity up to 335% over baseline and decreases of maximum filling pressures to 63%. No local or systemic side effects were noted. Surgical bladder augmentation was avoided in those who clinically responded to this therapy.

Sibling Reflux: A Dual Center Retrospective Study

PURPOSE Siblings of index patients with vesicoureteral reflux are known to have an increased incidence of reflux. Previous reports may be biased due to significantly more female siblings undergoing screening. In addition, it has been suggested that screening is unnecessary in older children. MATERIALS AND METHODS We retrospectively reviewed the records of probands with vesicoureteral reflux. A total of 422 families comprising 622 siblings was identified at our centers from 1985 to 1994. Of the 255 boys and 277 girls newborn to 16 years old (mean age 6.2 years) 85% were evaluated. Almost 43% of the probands (225) were older than 7 years. RESULTS Vesicoureteral reflux was noted in 144 siblings (52 boys and 92 girls, 27%). The majority had low grade reflux but in 111 (77%) maximum reflux grade was II or III. Reflux nephropathy was demonstrated on a nuclear renal scan in 18 of the 132 tested siblings (13.6%). In all of these children reflux was grades II to IV and 27% were older than 10 years. CONCLUSIONS When vesicoureteral reflux is discovered, all siblings should be considered for screening. The evaluation of older siblings remains controversial, since they comprise only a small fraction of all siblings with reflux but may have a significant portion of reflux nephropathy. There was a 27% overall incidence with a 33% rate in girls. The incidence of reflux in siblings decreased after age 7 years but reflux nephropathy was identified even in the older children.

Two-stage repair for severe hypospadias

In 39 patients a 2-stage modified Belt-Fuqua repair was performed for severe hypospadias and chordee. Patient age at initial surgery averaged 2 years and stage 2 was done 7 months later. Testosterone was given before stage 1 to 22 patients (56%) and before both stages to 13 (33%). Of 5 patients with intersex 2 had mixed gonadal dysgenesis, 1 was a true hermaphrodite and 2 were 46 XX male subjects. The preoperative meatal location was subglanular in 9 cases, mid shaft in 8, proximal shaft in 2, penoscrotal in 15 and perineal in 5. Those with subglanular meatus had hypoplastic distal urethras and severe chordee. A dorsal Nesbit procedure for chordee correction was done in 24 cases (62%). Neourethral length ranged from 3 to 7 cm. (average 4 cm.) and average followup was 16 months. Neourethral diverticula developed in 8 cases (21%) and they were repaired uneventfully an average of 7 months (range 2 to 24) after stage 2. Minor urethral strictures (3 distal and 4 proximal) were treated with a single visual internal urethrotomy and there was 1 (2.5%) urethrocutaneous fistula. All children had excellent cosmetic and functional outcomes. A staged approach allows for cosmetic reconstruction of the glans and mucosal collar during stage 1 and offers 2 opportunities to augment penile size with testosterone. Bladder or buccal mucosal grafts are avoided since the prepuce is always adequate. There are no hypospadias deformities, penile shaft torsion or asymmetry. Fistula formation is minimal and strictures are minor. The 2-stage repair remains a safe, reliable alternative for boys with severe hypospadias.

Experience With Vesicoureteral Reflux in Children: Clinical Characteristics

PURPOSE We reviewed our 9-year experience with a large population of children with vesicoureteral reflux who were evaluated and treated according to contemporary concepts. MATERIALS AND METHODS From 1985 to 1993 we followed 288 boys and 752 girls with vesicoureteral reflux. If surgery was not performed, patients were on antibiotic prophylaxis and evaluation was done every 18 months with contrast voiding cystography and radionuclide renal imaging. Urine cultures were obtained every 4 months. Two negative voiding cystourethrograms 1 year apart were required to discontinue prophylaxis. RESULTS The major reasons for initial evaluation were urinary tract infection in 560 children (54%), voiding dysfunction without urinary tract infection in 156 (15%), sibling surveys in 122 (12%) and prenatal hydronephrosis in 23 (2%). In 150 kidneys (10%) in 132 children scarring at presentation was grade 0 in 10 (7%), I in 18 (12%), II in 27 (18%), III in 30 (20%), IV in 48 (32%) and V in 17 (11%). Of these 132 patients 17 presented at ages less than 1 year (13%), 29 at ages 1 to 3 (22%), 50 at ages 4 to 6 (38%), 24 at ages 7 to 9 (18%) and 12 at ages greater than 10 (9%). No new scars were seen in children on prophylaxis without breakthrough infection. After 1 negative voiding cystourethrogram reflux was noted again in 27% of the cases. Breakthrough infections developed in 62 children of whom a third were older than 7 years. Reimplantation in 205 children (20%) was performed for grade IV to V reflux (101), breakthrough infection (62), advanced age (18), large periureteral diverticulum (12) and noncompliance (3). Five boys and 57 girls (30% of all children) had urinary tract infections after successful reimplantation. CONCLUSIONS Almost half of the children with vesicoureteral reflux have no history of culture proved urinary tract infection. Scarring may be associated with any reflux grade and it may be initially diagnosed at any age. Only half of the scars are noted with higher grades of reflux (IV and V). Continuous prophylaxis prevents new scarring. Breakthrough infections are rare but they can occur at ages greater than 7 years. Two consecutive negative cystograms are necessary before discontinuing prophylaxis. Children should be monitored after reimplantation for recurrent urinary tract infection.

Vesicoureteral reflux: practical aspects of evaluation and management

Abstract. The efficacy of both medical and surgical therapy for vesicoureteral reflux (VUR) has been well established. Controversy remains, however, regarding who should be evaluated for the presence of VUR, who should undergo corrective surgery, who should be treated medically and for how long. Medical treatment requires many years of continuous antibiotic prophylaxis, so compliance with therapy is essential. Many children are lost to follow-up, however, and remain untreated after a medical regimen is started. This large number of untreated children raises issues of the appropriateness of blanket therapeutic recommendations for all children with VUR and challenges the clinician to devise more effective treatment strategies.

Experience with Varicoceles in Children and Young Adults

PURPOSE Varicocele ligation in children and adolescents has been advocated for left testicular growth arrest. We report our experience with this population as well as the results of the microscopic inguinal technique. MATERIALS AND METHODS Between 1994 and 1999, 184 children and young adults presented with unilateral left varicoceles. At presentation 171 patients were asymptomatic and 13 had pain. Testicular measurement was assessed with calipers in 158 cases and ultrasound in 26. Surgery was performed using a microscopic inguinal technique in 58 patients and loupes in 16 of those who presented with left testicular growth arrest initially or who had growth arrest while under observation. Only one child underwent surgery for pain alone. RESULTS Patient age at presentation ranged from 5 to 22 years, and 70% presented between the ages of 12 and 16 years. Of the 13 patients with pain ages ranged from 13 to 22 years and 6 (46%) also had left testicular growth arrest. Initially, 109 (60%) boys were found not to have left testicular growth arrest and were followed, while 56 (30%) with left testicular growth arrest (ages 9 to 22 years) underwent surgery and 19 were lost to followup. Left testicular growth arrest developed in 17 (15%) of the followed group (ages 11 to 17 years) after 6 to 41 months (average 22) of observation and they underwent surgery. Postoperatively, varicocele disappeared in 66 (89%) patients and it was smaller in 8, in whom 8 loupes were used in 2 and the microscope was used in 6. Of the 36 patients who returned for postoperative measurement 30 (83%) had catch-up growth, while 6 did not. No hydroceles were noted. CONCLUSIONS Varicoceles can be found in boys as young as 5 years and left testicular growth arrest as early as 9 years. As left testicular growth arrest can develop if not present initially, these boys must be followed with serial testicular measurements before and after puberty until late adolescence. Microscopic inguinal ligation results in complete resolution of the varicocele in almost 90% of patients with no complicating hydroceles. Left testicular catch-up growth can be expected in more than 80% of patients at any age.

TOILET HABITS OF CHILDREN EVALUATED FOR URINARY TRACT INFECTION

The toilet habits of 77 girls and 24 boys who were evaluated after having a urinary tract infection were examined prospectively. Children with known urological conditions that can predispose to urinary tract infections were excluded. A voiding cystourethrogram and renal ultrasound were performed, and a diary of toilet habits was obtained for all patients. Six children were lost to followup. Of the remaining 95 children imaging studies were negative in 60 (negative imaging group) and positive in 35 (positive imaging group). Only 10% of the negative imaging group were without constipation or abnormal voiding compared to 60% of the positive imaging group (p = 0.0001). Toilet habits can affect the development of urinary tract infections. Our data suggest that the evaluation of urinary tract infection should include an inquiry into these habits. Among children with negative imaging studies there may be functional problems that promote the development of urinary tract infections.

Expanded Followup of Intravesical Oxybutynin Chloride Use in Children with Neurogenic Bladder

PURPOSE We evaluated the long-term results of intravesical oxybutynin chloride use in children with neurogenic bladders who could not tolerate or whose conditions were refractory to oral therapy. MATERIALS AND METHODS We reviewed our experience with 28 children (myelomeningocele in 27 and imperforate anus in 1) who presented with urinary incontinence and/or elevated bladder pressures refractory to intermittent catheterization and oral anticholinergic medication. Intravesical oxybutynin was administered to each child by instillation of 5 mg. crushed oxybutynin chloride in 10 cc sterile saline 2 times daily during catheterization. RESULTS Seven patients (25%) could not tolerate intravesical oxybutynin secondary to anticholinergic side effects. The remaining 21 children have been followed on intravesical oxybutynin for a mean of 35 months (range 3 to 67). Of these 21 children 12 (57%) became completely dry day and night, 5 (24%) achieved daytime continence between catheterizations and 4 (19%) remained clinically unchanged with 2 in diapers. On urodynamics these 21 patients had increased bladder capacity of up to 1,150% (mean 237%, p < 0.0001) and decreased mean maximum filling pressures of -31% (p = 0.002). CONCLUSIONS Although a number of patients continued to have anticholinergic side effects, a majority had significant improvement in urodynamic parameters and continence. The response appears to be durable, and it spares many of these children from undergoing bladder augmentation.