Douglas W. Storm

A prospective study of risk factors for nephrolithiasis after Roux-en-Y gastric bypass surgery.

PURPOSE Roux-en-Y gastric bypass surgery has become an increasingly common form of weight management. Early retrospective reviews have suggested that new onset nephrolithiasis develops in some patients after undergoing Roux-en-Y gastric bypass. We present a prospective longitudinal study to assess risk factors for nephrolithiasis after Roux-en-Y gastric bypass. MATERIALS AND METHODS A total of 45 morbidly obese patients scheduled to undergo Roux-en-Y gastric bypass surgery were enrolled in this prospective study between November 2006 and November 2007. Exclusion criteria included history of nephrolithiasis or inflammatory bowel disease. Serum uric acid, parathyroid hormone, calcium, albumin, and creatinine and 24-hour urine collections were obtained within 6 months before Roux-en-Y gastric bypass, and at 6 to 12 months postoperatively. A Wilcoxon signed-rank test was used to compare preoperative and postoperative serum laboratory values and 24-hour urine values. McNemars test was used to determine if the percent of abnormal values underwent a statistically significant change after Roux-en-Y gastric bypass. For both statistical methods a p value was calculated for the change in each variable with p <0.05 considered statistically significant. RESULTS Statistically significant changes included increased urinary oxalate and calcium oxalate supersaturation, and decreased urinary citrate and total urinary volume postoperatively. A statistically significant percentage of patients exhibited decreased urinary calcium, while a statistically significant percentage of patients experienced increased urinary oxalate and calcium oxalate supersaturation. CONCLUSIONS Our prospective study demonstrated multiple factors that increase the relative risk of nephrolithiasis after Roux-en-Y gastric bypass. These changes may make stone formation after Roux-en-Y gastric bypass increasingly likely and pose an ongoing challenge in the realm of urology.

Initial experience with percutaneous selective embolization: A truly minimally invasive treatment of the adolescent varicocele with no risk of hydrocele development

OBJECTIVE Postoperative hydrocele development is a frustrating complication of varicocele surgical repair. To avoid this complication, we began to offer percutaneous embolization as a treatment option. We present our initial experience with this technique. METHODS A retrospective review of all patients who underwent percutaneous embolization and sclerotherapy of a varicocele at our institution was performed. RESULTS There were 27 patients with a mean age of 16 years (range 13-19 years). Indications included pain (48%), varicocele size (30%) and persistent testicular asymmetry (22%). Four patients had experienced failure of a previous surgical repair. Follow-up data were available for 21 patients (mean 9 months). The varicocele resolved in 19 patients (91%) with no evidence of hydrocele formation in any of the boys. There was resolution of pain in all patients for whom this was the indication for the procedure. In the two failures, access to the lower spermatic vein was not possible owing to the number and tortuosity of the vessels. CONCLUSIONS Percutaneous embolization and sclerotherapy represent a truly minimally invasive treatment with low morbidity, minimal pain and rapid recovery. In our early experience, since lymphatic channels are completely avoided, there appears to be no risk of hydrocele formation.

Robotic-assisted laparoscopic approach for posterior bladder neck dissection and placement of pediatric bladder neck sling: initial experience.

OBJECTIVES Bladder neck sling cystourethropexy is a common procedure used to correct intrinsic sphincter deficiency in children with spinal dyspharism. Various modifications of the procedure have been made but all involve circumferential dissection of the bladder neck and proximal urethra. The posterior dissection can be challenging and can result in injury to the rectum, urethra, or vagina. The posterior approach to the bladder neck as reported by Lottmann and later by de Badiola addresses these potential complications. Using these principles of the posterior approach, we performed a robotic-assisted laparoscopic placement of an acellular human dermal allograft bladder neck sling in 2 patients. We present our initial experience regarding this surgical technique. METHODS The diagnosis of intrinsic sphincter deficiency was established in 2 female patients, aged 9 and 10 years. Both patients had a neurogenic bladder secondary to spina bifida. Video urodynamics confirmed adequate bladder compliance and intrinsic sphincter deficiency. Robotic-assisted laparoscopic placement of a bladder neck sling was performed in both patients. RESULTS Both procedures were completed intracorporeally. The mean blood loss was 20 mL. The mean operative time was 189 minutes. No intraoperative or postoperative complications occurred. The mean hospital stay was 3 days (range 2-4). The follow-up ranged from 13 to 22 months. Postoperative studies revealed continued low-pressure, compliant bladders and stable upper tracts. At last follow-up, the 2 patients were using catheterization without difficulty and were continent. CONCLUSIONS The robotic-assisted laparoscopic approach to performing bladder neck dissection and placement of a bladder neck sling in children is technically feasible.

Bladder Volume at Onset of Vesicoureteral Reflux is an Independent Risk Factor for Breakthrough Febrile Urinary Tract Infection

PURPOSE Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. MATERIALS AND METHODS Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). RESULTS A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). CONCLUSIONS Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making.

Conservative management of a bleeding renal angiomyolipoma in pregnancy.

BACKGROUND: Bleeding angiomyolipomas in pregnancy are rare but may be devastating and potentially fatal. In previous cases, most of these lesions have been managed with urgent nephrectomy or embolization. Only one other case report describes treating these lesions through conservative management and vaginal delivery. CASE: A 32-year-old woman with known bilateral angiomyolipomas presented at 39 weeks of gestation with acute onset left flank pain. The ultrasound result was consistent with a bleeding angiomyolipoma. The patient was otherwise hemodynamically stable and was managed safely in a conservative outpatient approach that consisted of close clinic follow-up, serial hemoglobins, ultrasound studies, and vaginal delivery. CONCLUSION: Bleeding angiomyolipomas in pregnancy were managed successfully through conservative management and vaginal delivery.

In vitro analysis of the bactericidal activity of Escherichia coli Nissle 1917 against pediatric uropathogens.

PURPOSE The usefulness of prophylactic antibiotics to prevent recurrent urinary tract infections in children was recently questioned. Some groups have attempted to use probiotics, most commonly lactobacillus, to prevent recurrent infections by altering the intestinal bacterial reservoir with variable results. Mutaflor® is a possible alternative probiotic in which the active agent is Nissle 1917. Nissle 1917 is a commensal Escherichia coli strain that eradicates pathogenic bacteria from the gastrointestinal tract. Due to its ability to alter the intestinal biome we hypothesized that Mutaflor may have the potential to prevent recurrent urinary tract infections. Thus, we used an in vitro assay to analyze the effectiveness of Nissle 1917 for eradicating pediatric uropathogens. MATERIALS AND METHODS We established a collection of 43 bacterial pediatric uropathogens. With each isolate a microcin-type assay was performed to determine the effectiveness of Nissle 1917 on bacterial growth inhibition and competitive overgrowth. RESULTS Nissle 1917 adversely affected the growth of 34 of the 43 isolates (79%) isolates. It inhibited the growth of 21 isolates and overgrew 13. The percent of species adversely affected by Nissle 1917 was 40% for Pseudomonas, 50% for E. coli, Enterococcus and Staphylococcus, 100% for Klebsiella and Enterobacter, and 0% for Citrobacter and Serratia. CONCLUSIONS Nissle 1917, the active agent in Mutaflor, inhibited or out competed most bacterial isolates. These mechanisms could be used in vivo to eradicate uropathogens from the gastrointestinal tract. Further study is needed to determine whether Mutaflor can prevent recurrent urinary tract infections in children.

Relationship Among Bacterial Virulence, Bladder Dysfunction, Vesicoureteral Reflux and Patterns of Urinary Tract Infection in Children

PURPOSE We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation. MATERIALS AND METHODS E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology). RESULTS A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02). CONCLUSIONS In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies.

The Modern Metabolic Stone Evaluation in Children

OBJECTIVE To evaluate metabolic abnormalities in a contemporary pediatric population after their first stone episode. The incidence of pediatric nephrolithiasis is increasing and therefore the etiologies contributing to todays pediatric stone formation may also be changing. MATERIALS AND METHODS A retrospective review of all consecutive children presenting after their first kidney stone between 2000 and 2014 was performed. We compared demographic data, serum chemistry results, and 24-hour urine results and treatments. RESULTS One hundred thirteen children with a mean age of 11 years (5 months to 18 years) who presented with their first kidney stone episode between 2000 and 2014 were evaluated. Sixteen patients (14%) were found to have an underlying genetic or systemic disease. Overall, there was a low rate of serum chemistry abnormalities. The most common abnormalities found within the 24-hour urine evaluation included low urine volume (89%) and hypocitraturia (68%). Hypercalciuria occurred rarely (11%). CONCLUSION We identified a low rate of underlying genetic or systemic diseases contributing to modern pediatric stone presentation and an increased proportion of idiopathic stones. Our study differs from historical findings by identifying a low rate of hypercalciuria and a high rate of low urine volume and hypocitraturia, suggestive of changing metabolic abnormalities contributing to modern pediatric stone disease.

Utility of the distal ureteral diameter on VCUG for grading VUR

INTRODUCTION For children with VUR the grade of vesicoureteral reflux (VUR) remains one of the most predictive factors relative to outcome. However, the subjective nature of the currently accepted international reflux grading system (IRGS) leads to inter-observer variation. The potential of a direct measurement of the distal ureter on the voiding cystourethrogram (VCUG) normalized to the L1-L3 vertebral body distance (ureteral diameter ratio - UDR) to augment the ability of IRGS to predict the ultimate clinical outcome has previously been reported in a group of 79 children. OBJECTIVE The goal of this current review was to expand the previous review and analysis in order to assess the predictive ability of the UDR with respect to earlier clinical outcome and to compare this ability to the grade of VUR while controlling for other variables. STUDY DESIGN This retrospective review of the VCUG of 157 children with primary VUR included 124 girls and 33 boys with a mean age of 2.7 years (7 days-13.5 years). In addition to the UDR, other variables that were analyzed included: age, gender, VUR grade, laterality, history of febrile urinary tract infection (UTI) or multiple UTIs prior to diagnosis, and bladder-bowel dysfunction (BBD). Cox regression analysis was utilized and a generalized logit model for 2-year outcome was also fitted to compare the effect of UDR and VUR grade using Wald Chi-squared analysis. RESULTS The 2-year outcome after the VCUG was defined as: persistent VUR (47%), spontaneous VUR resolution (15%), or operative intervention (38%). Reasons for operative intervention included: breakthrough UTI (1/3), decreased relative renal function associated with renal scarring (1/3), and failure to resolve, along with parental preference (1/3). Increasing UDR was significantly associated with increased grade and a decreased chance of spontaneous resolution. It was unlikely for a child with Grade 4, 3, or 2 VUR to have spontaneous resolution if their UDR was above 0.25, 0.3, or 0.35, respectively. In addition, higher grades of VUR, older age, and bilateral VUR were significantly associated with failure to spontaneously resolve VUR. As seen in Figure, children with grades 2 and 3 VUR less than 2 years of age had a better chance of spontaneous resolution with a larger UDR than children 2 years of age or older. When adjusting for age, grade, laterality and multiple UTIs as covariates, each unit increase of UDR of 0.1 was significantly associated with either persistent VUR (OR = 1.73, 95% CI = 1.02-2.95, P = 0.043) or the need for surgical intervention (OR = 2.40, 95% CI = 1.39-4.17, P = 0.002) compared to spontaneous resolution. When testing the effect of UDR and grade of reflux in the same model, UDR was noted to have a larger effect on predicting failure to spontaneously resolve VUR than grade (Wald Chi-Squared 13.6; P = 0.001 vs 3.62; P = 0.46, respectively). DISCUSSION The UDR is a readily available objective measurement on the VCUG that has demonstrated ability to enhance the International Reflux Grading System. Limitations of the current review include operative intervention in 12% of the children for failure to improve or resolve VUR. This surgical intervention inhibits determination of spontaneous resolution rates. The findings in this study reflect those in a series of children from a single institution and, therefore, may be impacted by clinical practice bias and geographic variations. Subsequent multi-institutional studies could further define the potential of UDR as either an independent or additive predictive factor for grading VUR that will further permit individualized patient management. CONCLUSION In this single institution series, UDR was highly correlated with VUR grade; however, UDR proved more predictive of spontaneous resolution, persistence, or operative intervention than grade.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract

UNLABELLED Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production.