Michael Garcia-Roig

Vesicoureteral Reflux Index: 2-Institution Analysis and Validation

PURPOSEnThe vesicoureteral reflux index is a novel tool designed to predict spontaneous reflux resolution in infants younger than 2 years. We performed a multi-institutional validation study to confirm the discriminatory power of the vesicoureteral reflux index to predict the vesicoureteral reflux resolution rate in young children.nnnMATERIALS AND METHODSnWe identified patients diagnosed with primary vesicoureteral reflux before age 24 months who had 2 or more voiding cystourethrograms available. Demographics, vesicoureteral reflux grade and timing, ureteral anomalies and radiographic outcomes were evaluated. The C-index was estimated for time to event model assessment.nnnRESULTSnA total of 219 girls and 150 boys met study inclusion criteria. Mean ± SD age at diagnosis was 4.7 ± 4.9 months. Of the patients 101 (27.4%) had early to mid filling, 214 (58%) had late filling and 54 (14.6%) had voiding only vesicoureteral reflux. High grade reflux was present in 87 patients (23.6%) and ureteral anomalies were observed in 50 (13.6%). A vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater showed an improvement/resolution rate of 88.2%, 77.3%, 62.3%, 32.1% and 14.3%, respectively. On time to event analysis children with filling phase vesicoureteral reflux (p <0.001), grade 4-5 reflux (p <0.001) and ureteral anomalies (p = 0.003) had significantly longer median time to resolution. Median time to spontaneous resolution was 12.6, 12.7, 15.1, 25.6 and 31 months or greater for a vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater, respectively (C-index 0.305, 95% CI 0.252-0.357). During the study period 65 patients (17.6%) underwent surgical intervention.nnnCONCLUSIONSnThe vesicoureteral reflux index is a simple tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in patients diagnosed at younger than 2 years. The index provides valuable prognostic information, facilitating individualized patient care.

Surgical Scar Location Preference for Pediatric Kidney and Pelvic Surgery: A Crowdsourced Survey

Purpose: The benefits of minimally invasive surgery in pediatric urology, such as reduced length of hospital stay and postoperative pain, are less predictable compared to findings in the adult literature. We evaluated the choices that adult patients make for themselves and their children regarding scar location. Materials and Methods: We surveyed the preference for scar location/size based on surgery for bladder and kidney procedures with additional questions assessing the impact of a hidden incision, length of hospital stay and pain. The survey was posted to Amazon® Mechanical Turk®. Results: We analyzed a total of 954 completed surveys. Surgical history was reported in 660 surveys (69%) with scar bother reported in 357 (54.2%). For pelvic surgery the initial choice was a Pfannenstiel incision for 434 respondents (45.5%), laparoscopy port incisions for 392 (41.1%) and no preference for incision location for 126 (13.2%). When incisions were illustrated relative to undergarments, 718 respondents (75.3%) chose Pfannenstiel. For kidney surgery 567 respondents (59.4%) initially chose the dorsal lumbotomy incision, 170 (17.8%) chose a flank incision, 105 (11.0%) chose laparoscopy ports and 110 (11.5%) had no preference. Respondents were told that minimally invasive surgery might result in less pain/length of hospital stay and were asked to restate the incision choice. For pelvic surgery 232 of 434 respondents (53.5%) who had chosen Pfannenstiel and 282 of 394 (71.6%) who had chosen laparoscopy remained consistent (p <0.001). For kidney surgery 96 respondents (56.5%) who chose a flank incision, 322 (56.8%) who chose dorsal lumbotomy and 68 (64.2%) who chose laparoscopy remained consistent (p = 0.349). Agreement between the incision choice by respondent as a child and for a child was 82% (&kgr; = 0.69) for pelvic surgery and 84.6% (&kgr; = 0.75) for kidney surgery. Conclusions: The smallest incision is not always the patient preferred incision, particularly in childhood when pain, length of hospital stay and blood loss may be equivocal among approaches. Discussion of surgical treatment options should include scar length, location and relationship to undergarments.

The dilemma of adolescent varicocele

Adolescent varicocele is associated with ipsilateral testicular hypotrophy and the concern for future infertility. A testicular size discrepancy greater than 15–20xa0% between left and right testicle is an indication for treatment to allow catch-up growth in the hope of preventing a future decline in fertility. Some authors advocate for a period of watchful waiting, as normal testicular growth may occur asymmetrically. We review the current literature to highlight some controversies and challenges in management.

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets

Background:Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.Methods:Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules – HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models.Results:In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial–mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression.Conclusions:This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

Prospective multicenter study on robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV): Outcomes and complications

BACKGROUNDnRobot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) is a minimally invasive alternative to open surgery. We have previously reported retrospective outcomes from our study group, and herein provide an updated prospective analysis with a focus on success rate, surgical technique, and complications among surgeons who have overcome the initial learning curve.nnnOBJECTIVEnTo assess the safety and efficacy of RALUR-EV in children, among experienced surgeons.nnnDESIGN AND METHODSnWe reviewed our prospective database of children undergoing RALUR-EV by pediatric urologists at eight academic centers from 2015 to 2017. Radiographic success was defined as absence of vesicoureteral reflux (VUR) on postoperative voiding cystourethrogram. Complications were graded using the Clavien scale. Univariate regression analysis was performed to assess for association among various patient and technical factors and radiographic failure.nnnRESULTSnIn total, 143 patients were treated with RALUR-EV for primary VUR (87 unilateral, 56 bilateral; 199 ureters). The majority of ureters (73.4%) had grade III or higher VUR preoperatively. Radiographic resolution was present in 93.8% of ureters, as shown in the summary table. Ureteral complications occurred in five ureters (2.5%) with mean follow-up of 7.4 months (SD 4.0). Transient urinary retention occurred in four patients following bilateral procedure (7.1%) and in no patients after unilateral. On univariate analysis, there were no patient or technical factors associated with increased odds of radiographic failure.nnnDISCUSSIONnWe report a radiographic success rate of 93.8% overall, and 94.1% among children with grades III-V VUR. In contemporary series, alternate management options such as endoscopic injection and open UR have reported radiographic success rates of 90% and 93.5% respectively. We were unable to identify specific patient or technical factors that influenced outcomes, although immeasurable factors such as tissue handling and intraoperative decision-making could not be assessed. Ureteral complications requiring operative intervention were rare and occurred with the same incidence reported in a large open series. Limitations include lack of long-term follow-up and absence of radiographic follow-up on a subset of patients.nnnCONCLUSIONSnRadiographic resolution of VUR following RALUR is on par with contemporary open series, and the incidence of ureteral complications is low. RALUR should be considered as one of several viable options for management of VUR in children.

Detailed evaluation of the upper urinary tract in patients with prune belly syndrome using magnetic resonance urography

INTRODUCTIONnMagnetic resonance urography (MRU) has proven to be useful in the setting of complex urologic anatomy. Prune belly syndrome (PBS) patients are known to have malformed and highly variable urinary tract anatomy due to significant dilation and renal dysplasia.nnnOBJECTIVEnTo further characterize the renal and ureteral anatomy and renal function in patients with PBS via MRU.nnnSTUDY DESIGNnChildren with PBS undergoing MRU (2006-2011) were identified. Studies were performed to evaluate severe hydronephrosis in all patients. Demographics, previous imaging, and MRU findings were collected. A single radiologist reviewed all studies.nnnRESULTSnMRU was performed on 13 boys, with a median age of 29.3 months (IQR 6-97). Two patients underwent >1 study for ureteropelvic junction obstruction (UPJ obstruction) and calyceal diverticulum with a solitary kidney, respectively. Hydroureteronephrosis (HUN) was identified in 12 boys (92%), while one (8%) did not have ureteral dilation. All patients demonstrated morphologic abnormalities beyond HUN as follows: five (38%) renal dysplasia; five (38%) scarring; four (31%) calyceal diverticula; and three (23%) thickened bladder. The median renal transit time (RTT) was 6 min (IQR 3.5-10.5), and >8 min (range 8.5-35) in six patients; one patient was ultimately diagnosed with obstruction. The mean serum creatinine was 0.5 ± 0.3 mg/dl. This summary figure is a coronal excretory phase T1 MRU image demonstrating absence of well-defined calyces and a 5-cm calyceal diverticulum (white arrow).nnnDISCUSSIONnThis study reports significant anatomic and functional findings on MRU that were not readily apparent when using standard imaging for children with PBS. The high-resolution images and functional data obtained with MRU allowed for visualization of calyceal diverticula and abnormal renal pelvic anatomy not previously described in PBS. In addition, renal dysplasia could be identified with MRU, which is badly characterized in the PBS population outside of renal biopsy studies. Potential limitations of the study included its nature as a small retrospective case series, which limited the ability to compare imaging modalities. Imaging modalities were based on individual clinical needs; therefore, comparison with diuretic renal scintigraphy was limited.nnnCONCLUSIONnMRU provided anatomic and functional details of the urinary tract in children with PBS that allowed for characterization of new renal anatomic abnormalities, including the incidence of calyceal diverticula and renal dysplasia, which have not been previously described. While renal scarring, dysplasia and calyceal diverticula were easily discerned on MRU in ten patients, their clinical significance requires longer follow-up in a larger patient population.

Urinary tract infection in the setting of vesicoureteral reflux

Vesicoureteral reflux (VUR) is the most common underlying etiology responsible for febrile urinary tract infections (UTIs) or pyelonephritis in children. Along with the morbidity of pyelonephritis, long-term sequelae of recurrent renal infections include renal scarring, proteinuria, and hypertension. Treatment is directed toward the prevention of recurrent infection through use of continuous antibiotic prophylaxis during a period of observation for spontaneous resolution or by surgical correction. In children, bowel and bladder dysfunction (BBD) plays a significant role in the occurrence of UTI and the rate of VUR resolution. Effective treatment of BBD leads to higher rates of spontaneous resolution and decreased risk of UTI.

National Trends in the Management of Primary Vesicoureteral Reflux in Children

Purpose In September 2011 the AAP (American Academy of Pediatrics) released updated guidelines for the evaluation of children 2 to 24 months old with a febrile urinary tract infection. We documented the impact of the guideline on diagnosis and surgical management of vesicoureteral reflux at U.S. children’s hospitals. We hypothesized that voiding cystourethrogram studies and the vesicoureteral reflux treatment rate decreased concurrent with the national guideline release. Materials and Methods The Pediatric Health Information System was queried for children (younger than 18 years) with primary vesicoureteral reflux and their antireflux surgical history from January 2004 to June 2015. Voiding cystourethrogram orders were recorded. Interrupted time series analysis quantified trends surrounding several seminal vesicoureteral reflux publications (2007) and guideline publication (2011). Results A total of 43,341 voiding cystourethrogram encounters (male 23,946 [55.3%]) were identified for patients at a median age of 3 months (IQR 1–20). For all children monthly voiding cystourethrogram orders increased (+1.0 to +1.6 encounters per month, p <0.034) to September 2011, then sharply declined by 106 encounters per month from September to October 2011 (p <0.001) then did not change significantly (p=0.096, R2=0.79). For those children 2 to 24 months old with a urinary tract infection (3,379 records; male 1,384 [41.0%], median age 4 months [IQR 3–7]) voiding cystourethrograms gradually increased from January 2007 to September 2011 (+0.1 encounters per month, p=0.036), then similarly decreased by 21 encounters per month from September to October 2011 (p <0.001), then did not change significantly (p=0.064, R2=0.78). Overall 28,484 procedures for primary vesicoureteral reflux were identified (male 5,950 [20.9%], median age 4.8 years [IQR 2.5–7.2]). Total surgical procedures did not change significantly until October 2011, then declined (‐1.5 procedures per month, p <0.001, R2=0.66). Conclusions The number of voiding cystourethrograms ordered nationally in all children and those with a urinary tract infection decreased sharply with the 2011 AAP urinary tract infection guideline release and did not change thereafter. A steady decline in procedures for primary vesicoureteral reflux occurred after October 2011.

Vesicoureteral Reflux Index: Predicting Primary Vesicoureteral Reflux Resolution in Children Diagnosed after Age 24 Months

Purpose: The Vesicoureteral Reflux Index is a validated tool that reliably predicts spontaneous resolution of reflux or at least 2 grades of improvement for patients diagnosed before age 24 months. We evaluated the Vesicoureteral Reflux Index in children older than 2 years. Materials and Methods: Patients younger than 18 years who were diagnosed with primary vesicoureteral reflux after age 24 months and had undergone 2 or more voiding cystourethrograms were identified. Disease severity was scored using the Vesicoureteral Reflux Index, a 6‐point scale based on gender, reflux grade, ureteral abnormalities and reflux timing. Proportional subdistribution hazard models for competing risks identified variables associated with resolution/improvement at different time points. Results: A total of 21 males and 250 females met inclusion criteria. Mean ± SD age was 4.0 ± 2.1 years and patients had a median vesicoureteral reflux grade of 2. The Vesicoureteral Reflux Index score improved by 1 point in 1 patient (100%), 2 points in 25 (67.6%), 3 points in 48 (37%), 4 points in 18 (21.4%) and 5 to 6 points in 4 (18.2%). Female gender (p = 0.005) and vesicoureteral reflux timing (late filling, p = 0.002; early/mid filling, p <0.001) independently predicted nonresolution. Median resolution time based on Vesicoureteral Reflux Index score was 2 months or less in 15.6% of patients (95% CI 11.0–13.8), 3 months in 34.7% (95% CI 25.4–44.1), 4 months in 55.9% (95% CI 40.1 to infinity) and 5 months or more in 30.3% (95% CI 29.5 to infinity). High grade (IV or V) reflux was not associated with resolution at any point. Ureteral abnormalities were associated with lack of resolution in the first 12 to 18 months (HR 0.29, 95% CI 0.29–0.80) but not in later followup. Vesicoureteral Reflux Index scores of 3, 4 and 5 were significantly associated with lack of resolution/improvement compared to scores of 2 or less (p = 0.031). Conclusions: The Vesicoureteral Reflux Index reliably predicts primary vesicoureteral reflux improvement/resolution in children diagnosed after age 24 months. Spontaneous resolution/improvement is less likely as Vesicoureteral Reflux Index score and time from diagnosis increase.

Delayed upper tract drainage on voiding cystourethrogram may not be associated with increased risk of urinary tract infection in children with vesicoureteral reflux.

INTRODUCTIONnUrinary stasis in the setting of obstruction provides an opportunistic environment for bacterial multiplication and is a well-established risk factor for UTI. Vesicoureteral reflux (VUR) with delayed upper tract drainage (UTD) on VCUG has been reported to correlate with increased UTI risk. We sought to determine whether delayed UTD can be reliably classified, and whether it correlates with UTI incidence, VCUG, or endoscopic findings.nnnMETHODSnChildren undergoing endoscopic surgery for primary VUR (2009-2012) were identified. VUR grade, timing, and laterality were abstracted. Demographics, hydrodistention (HD) grade, reported febrile and culture-proven UTI were assessed. UTD on VCUG was graded on post-void images as 1xa0=xa0partial/complete UTD or 2xa0=xa0no/increased UTD. Inter-observer agreement was calculated. Patients were excluded for incomplete imaging or inability to void during VCUG.nnnRESULTSnThe cohort included 128 patients (10M, 118F), mean age 4.1 ± 2.1 years. Mean age at diagnosis was 2.8xa0±xa02.8 years. Mean maximum VUR grade was 3xa0±xa00.9: 1 (7.8%), 2 (20.3%), 3 (43%), 4 (25.8%), 5 (3.1%). UTD occurred inxa045xa0(35%), and no drainage in 83 (65%) patients. Agreement coefficient between graders was 0.596 (pxa0<xa00.0001). Cultures were available in 100 patients (70 positive). Patients experienced a mean of 2xa0±xa01.2 parent-reported fUTIs and 1.2xa0±xa01.2 culture-proven UTIs from birth to surgery. UTI rate did not differ by UTD status for parent or culture-proven UTI (Table). On multivariate analysis, no patient characteristic was a significant predictor of UTI based on drainage status. Children diagnosed with VUR before 1 year of age had a higher verified UTI rate (pxa0<xa00.001). However, drainage was not a significant predictor of UTI rate and when testing the interaction of drainage and age.nnnCONCLUSIONnWe sought to determine whether UTD was an accurate predictor of UTI risk to maximize available prognostic information from a single VCUG. Delayed UTD was not a predictor of infection in our patients, nor was it associated with previously described UTI risk factors, such as VUR timing or grade, and voiding dysfunction. Limitations included the retrospective nature of the study in patients undergoing endoscopic VUR treatment, and possible inaccurate UTI reports from parents and pediatricians. UTD can be reliably scored using a binary system with high inter-observer correlation. Our data call into question the previous finding that children with poor UTD are at increased risk of recurrent UTI. Delayed UTD is also not associated with higher HD, or VUR grade compared with those with more prompt UTD.