Ranjiv Mathews

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.

An Analysis of Clinical Outcomes Using Color Doppler Testicular Ultrasound for Testicular Torsion

Objectives. To delineate the clinical outcomes of color Doppler ultrasound (US) in the equivocal torsion patient. Methods. From 1992 to 1997, 130 patients (<23 years old) from 2 institutions underwent US imaging using a 7.5-mHz linear transducer to evaluate an acute scrotum equivocal, or of low suspicion, for torsion. The US reports and hospital charts of these patients were retrospectively reviewed. Results. After clinical and radiologic evaluation, torsion was excluded in 110 patients without surgical exploration. In 3 patients, intermittent testicular torsion was diagnosed and in 17 patients, emergent exploration was performed for US diagnosis of testicular torsion. Twenty-five patients (22.7%) were subsequently lost to follow-up. Follow-up of 85 patients with US negative for torsion (mean length of follow-up = 466.9 days) revealed no testicular atrophy in 83. Two patients underwent delayed orchiectomy/contralateral orchiopexy for missed testicular torsion. Of 17 patients with US positive for torsion, 9 underwent orchiectomy for a necrotic torsed testis, 7 viable torsed testes were found, and 1 torsed appendix testis was found. Therefore, color Doppler US for the equivocal acute scrotum yielded a 1% false-positive rate, sensitivity of 88.9%, and specificity of 98.8%. Conclusion. When faced with ruling out testicular torsion, it is necessary to integrate the multiple pieces of patient data, knowing that each piece of data may have inaccuracies. With this in mind, this analysis of outcomes verifies that color Doppler US is an excellent adjunctive study in the clinically real situation in which the clinical evaluation is equivocal or low suspicion.

Anomalies of the inferior vena cava and renal veins: embryologic and surgical considerations.

Anomalies of the inferior vena cava and renal veins occur infrequently but if unidentified can lead to significant morbidity during surgical exploration. An understanding of the embryologic development of the vena cava and its tributaries is necessary to understand the genesis of these sometimes complex anomalies and their accompanying anatomic variants. Newer radiologic modalities in the form of spiral computed tomography (CT) and three-dimensional reconstruction of spiral CT allow clear definition of the anatomy of these anomalies. Variations in the embryologic evolution of the vena cava dictate the different venous anomalies that may be encountered in the retroperitoneum. Additionally, the utility of newer radiologic modalities in the identification of these anomalies is discussed.

Urogynaecological and obstetric issues in women with the exstrophy‐epispadias complex

The authors from Copenhagen write about their 15‐year consistent strategy in the treatment of antenatally suspected PUJ obstruction. The group deals with this controversial subject in some detail, and they outline data which they feel are helpful for urologists giving advice to parents about the advisability of having the condition treated by operative or conservative means.

Clinical and molecular characterization of the bladder exstrophy‐epispadias complex: analysis of 232 families

Authors from John Hopkins University School of Medicine in Baltimore present their study into the identifying genetic and non‐genetic factors contributing to the risk of bladder exstrophy‐epispadias complex. They found it to occur most commonly as an isolated sporadic birth defect, and found no evidence of a single‐gene effect or a common environmental factor.

CLOACAL EXSTROPHY-IMPROVING THE QUALITY OF LIFE: THE JOHNS HOPKINS EXPERIENCE

PURPOSE Exstrophy of the cloaca is a multisystem anomaly involving the gastrointestinal, nervous, musculoskeletal and genitourinary tracts which should be managed with a multidisciplinary approach. Improvement in management has led to survival for the majority of infants, and the focus has shifted to improvement in quality of life. The experience with management of cloacal exstrophy at a large center is evaluated. MATERIALS AND METHODS Demographic data as well as functional results of management of the multiple anomalies in 37 patients with cloacal exstrophy were evaluated. Surgical reconstruction was aimed at providing the best functional and cosmetic results. RESULTS Average patient age at review was 13.6 years. Most patients (32 of 37) had undergone an initial attempt at bladder closure from birth to greater than 24 months of age. Colostomy was performed when possible and if initial ileostomy was performed, the bowel was augmented later with the hindgut segment. When the hindgut segment was not used for bowel reconstruction, it was preserved for bladder augmentation or genital reconstruction. While urinary continence was achievable in many children, it was usually after augmentation and/or continent diversion. CONCLUSIONS Improvements in perinatal management have increased survival in cloacal exstrophy. Therefore, the focus of reconstruction has shifted to reduction in the numbers of incontinent stomas, assistance with ambulation and improved cosmesis. All of these goals are achievable using a multidisciplinary approach to the management of this complex anomaly.

The RIVUR Trial: Profile and Baseline Clinical Associations of Children With Vesicoureteral Reflux

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is diagnosed in ∼30% to 40% of children who have imaging studies after urinary tract infections (UTIs). Our goal is to characterize children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and to compare our study cohort with those from previously published studies. METHODS: RIVUR investigators from 19 pediatric sites in the United States recruited 607 children with grade I through IV VUR. Children were enrolled after a first or second UTI. This cross-sectional report of baseline data includes extensive clinical, parental report, and imaging study results. RESULTS: RIVUR recruited 607 children (558 girls, 49 boys) with grade I (11%), II (42%), III (38%), or IV (8%) reflux. The median age was 12 months, and most children (91%) were enrolled after their first UTI. The UTI leading to enrollment was both febrile and symptomatic for 323 children, febrile only in 197 children, and symptomatic only in 86. Renal involvement at baseline as documented by a 99mTc dimercaptosuccinic acid scan was uncommon with cortical defects identified in 89 (15%) children. Bladder and bowel dysfunction was identified in 71 (56%) of 126 toilet-trained subjects assessed. CONCLUSIONS: RIVUR is the largest prospective, randomized trial for children with primary VUR to date, comparing prophylaxis with placebo. The study sample comprises patients from 19 pediatric clinical sites in the United States, whose demographic and clinical characteristics may differ from those of children enrolled in previous trials from other countries.

Factors That Influence Parental Decisions to Participate in Clinical Research: Consenters vs Nonconsenters

IMPORTANCE A childs health, positive perceptions of the research team and consent process, and altruistic motives play significant roles in the decision-making process for parents who consent for their child to enroll in clinical research. This study identified that nonconsenting parents were better educated, had private insurance, showed lower levels of altruism, and less understanding of study design. OBJECTIVE To determine the factors associated with parental consent for their childs participation in a randomized, placebo-controlled trial. DESIGN Cross-sectional survey conducted from July 2008 to May 2011. The survey was an ancillary study to the Randomized Intervention for Children with VesicoUreteral Reflux Study. SETTING Seven childrens hospitals participating in a randomized trial evaluating management of children with vesicoureteral reflux. PARTICIPANTS Parents asked to provide consent for their childs participation in the randomized trial were invited to complete an anonymous online survey about factors influencing their decision. A total of 120 of the 271 (44%) invited completed the survey; 58 of 125 (46%) who had provided consent and 62 of 144 (43%) who had declined consent completed the survey. MAIN OUTCOMES AND MEASURES A 60-question survey examining child, parent, and study characteristics; parental perception of the study; understanding of the design; external influences; and decision-making process. RESULTS Having graduated from college and private health insurance were associated with a lower likelihood of providing consent. Parents who perceived the trial as having a low degree of risk, resulting in greater benefit to their child and other children, causing little interference with standard care, or exhibiting potential for enhanced care, or who perceived the researcher as professional were significantly more likely to consent to participate. Higher levels of understanding of the randomization process, blinding, and right to withdraw were significantly positively associated with consent to participate. CONCLUSIONS AND RELEVANCE Parents who declined consent had a relatively higher socioeconomic status, had more anxiety about their decision, and found it harder to make their decision compared with consenting parents, who had higher levels of trust and altruism, perceived the potential for enhanced care, reflected better understanding of randomization, and exhibited low decisional uncertainty. Consideration of the factors included in the conceptual model should enhance the quality of the informed consent process and improve participation in pediatric clinical trials.

NEURAL INNERVATION OF THE NEWBORN EXSTROPHIC BLADDER: AN IMMUNOHISTOCHEMICAL STUDY

PURPOSE Continence in bladder exstrophy is not always easy to attain. Some patients have a small noncontractile bladder while in others an adequate capacity bladder may not contract normally. Innervation of the detrusor determines its ability to contract. The exstrophic bladder during organogenesis does not store urine. Therefore, its requirements for contraction are limited and its innervation would potentially reflect this difference in function. The availability of specific immunostains allows better differentiation of the neural elements in tissue specimens. Our study focuses on myelinated nerves innervating the newborn exstrophic detrusor. MATERIALS AND METHODS Biopsies were obtained from the anterior wall of 10 newborn exstrophic bladders at the time of initial closure and compared to 10 newborn controls. Patient age at bladder closure ranged from 1 to 90 days (mean 22). Specimens were formalin fixed and paraffin embedded. Then 4 micro. thick sections were stained with S100, an immunostain that stains neural crest elements including Schwanns elements (myelinated nerve fibers). The entire tissue section was examined. Microscopic fields were sequentially examined with a morphometric system comprising a microscope, video camera and personal computer with a video frame grabber. The output image was displayed on a second monitor and the nerves in each field and numbers of fields in each section were counted. To be considered, fields had to have greater than 75% tissue coverage. The average number of nerves per field was compared between the exstrophic bladders and normal controls. RESULTS The average number of myelinated nerves per field in the newborn exstrophic bladders (0.13 per field) was significantly reduced compared to normal controls (1.25 per field) and statistically significant (p<0.001). This reduction in nerve fibers appeared to be due to lack of smaller fibers with preservation of larger fibers. There was no difference in innervation in cases closed at birth compared to those closed after month 1 of life. CONCLUSIONS The newborn exstrophic bladder has fewer myelinated nerve fibers than normal controls primarily due to reduction in the smaller fibers which may represent a maturational delay in the development of the exstrophic bladder. Another possible explanation may be degeneration of the fibers due to lack of bladder contraction but no indication of nerve degeneration was evident in our study. Followup studies of patients at various stages of reconstruction will determine the evolution of neural innervation in the exstrophic bladder.

Versatility of the adult psoas hitch ureteral reimplantation

PURPOSE The psoas hitch ureteral reimplant has been described in the literature as an excellent method to restore ureterovesical continuity in patients with ureteral defects of various etiologies. However, long-term data on the durability of this procedure are lacking. We retrospectively reviewed patients who underwent ureteral reconstruction using the psoas hitch reimplantation to determine long-term efficacy. MATERIALS AND METHODS Ureteral reimplantation in the adult is frequently performed in the setting of ureteral tissue loss secondary to resection or injury. The psoas hitch reimplantation is a simple, versatile technique that avoids the inclusion of intestinal segments and can be used in most patients requiring reimplantation. Indications for surgery and the long-term followup were examined in 20 patients undergoing reimplantation using the psoas hitch. RESULTS The indications for ureteral reconstruction included surgical injury in 13 cases, recurrent pyelonephritis with reflux in 1, obstruction secondary to cancer in 2, trauma in 1, retroperitoneal fibrosis in 1 and ureteral stricture in 2. At followup of 1 to 14 years (mean 6) 17 patients have not required further intervention for urological problems and have retained normal renal function. In the 2 patients with cancer ileal conduit was performed later and in 1 flank pain persisted despite negative urological evaluation. CONCLUSIONS Psoas hitch ureteral reimplantation can be used successfully for bridging various ureteral defects in difficult clinical situations. Adequate renal and bladder mobilization will allow reconstruction despite long ureteral defects.