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Bladder volume at the onset of vesicoureteral reflux (VUR) is an important prognostic indicator of spontaneous resolution and the risk of pyelonephritis. We aim to determine whether pediatric urologists and pediatric radiologists can accurately estimate the timing of reflux by examining voiding cystourethrogram (VCUG) images without prior knowledge of the instilled contrast volume. Total bladder volume and the volume at the time of reflux were collected from VCUG reports to determine the volume at the onset of VUR. Thirty-nine patients were sorted into three groups: early-/mid-filling reflux, late-filling and voiding only. Thirty-nine images were shown to three pediatric urologists and two pediatric radiologists in a blinded fashion and they were then asked to estimate VUR timing based on the above categories. A weighted kappa statistic was calculated to assess rater agreement with the gold standard volume-based report of VUR timing. The mean patient age at VCUG was 3.1±2.9 months, the median VUR was grade 3, and 20 patients were female. Overall agreement among all five raters was moderate (k=0.43, 95% confidence interval [CI] 0.36–0.50). Individual agreement between rater and gold standard was slight to moderate with kappa values ranging from 0.13 to 0.43. Pediatric radiologists and urologists are unable to accurately and reliably characterize VUR timing on fluoroscopic VCUG. These findings support the recently published American Academy of Pediatrics protocol recommending the routine recording of bladder volume at the onset of VUR as a standard component of all VCUGs to assist in a more accurate assessment of the likelihood of resolution and risk of recurrent urinary tract infections.

Summary Introduction Vesicoureteral reflux is a common pediatric urologic condition that often has several reasonable treatment options depending on condition severity. In order to choose the best treatment for their child, parents are expected to make judgements that weigh attributes such as treatment cost, effectiveness, and complication rate. Prior research has shown that factors such as treating hospital and surgeon also influence patient treatment choice. Objectives This study evaluates parental preferences for reflux treatment using profile case best-worst scaling, an emerging technique in both urologic and health care preference estimation. The study also uses latent class analysis (LCA) to identify parental sub-classes with different preferences. Study design Data were collected from a community sample of parents via a multimedia best-worst scaling survey instrument published to Amazon's Mechanical Turk online community. After extensive review of the literature, reflux attributes and attribute levels were selected to correspond with available treatments. The profile case best-worst scaling exercise elicited preferences for granular attributes of reflux treatments. Data were analyzed using multinomial logistic regression and class analysis to distinguish preference heterogeneity. Probability scaled values (PSVs) reflected the order of desirability of the attributes. Attribute preference importance was rescaled into dollar units for comparison as well. Results We analyzed data for 248 respondents. The highest treatment effectiveness was more desirable than all other leveled treatment attributes (PSV 17.8, all p Discussion In this community-based sample, high treatment effectiveness and low complication rate were the most desirable treatment attributes to parents, though parents likely have heterogenous treatment preference structures. Shared parent-physician decision-making that incorporates parental preferences will likely allow more effective, targeted decision-making in the future. Summary Table 1 . Profile Case Best Worst Scaling Attribute Level Logit 95% CI∗∗ PSV∗∗∗ Effectiveness 53 percent −2.639 (-2.831, −2.447) 0.39 77 percent −0.178 (-0.372, 0.016) 3.76 88 percent 1.378 (1.190, 1.566) 10.52 97 percent 3.274 (3.053, 3.495) 17.76 Societal Cost $1343 0.380 (0.181, 0.579) 5.77 $6365 −1.046 (-1.247, −0.846) 1.77 $7059 −1.265 (-1.464, −1.067) 1.45 $9556 −1.800 (-1.994, −1.605) 0.87 All complication rate 1.538 (1.346, 1.730) 11.32 4 percent 0.215 (0.015, 0.415) 5.12 10 percent −1.446 (-1.640, −1.252) 1.22 13 percent −1.720 (-1.914, 1.525) 0.94 Length of hospital stay No visit to hospital 0.421 (0.218, 0.623) 5.94 Same day outpatient hospitalization 0.585 (0.386, 0.783) 6.65 1 day (overnight, home next day) −0.496 (-0.699, −0.293) 2.88 2 days −1.010 (-1.212, −0.807) 1.83 Doctor recommends Yes 1.078 (0.909, 1.248) 9.00 No −1.856 (-2.027, −1.685) 0.83 Cosmetic appearance and Invasiveness No scar and no invasive procedure N/A∗ N/A 4.34 No scar and endoscopic intervention with anesthesia −0.042 (-0.251, 0.167) 4.20 MIS with anesthesia and small scars −0.807 (-1.014, −0.600) 2.20 Open surgery with anesthesia and large scar −1.427 (-1.623, −1.227) 1.24 Profile case MNL model constructed using leveled attributes. ∗ Reference coefficient for MNL. ∗∗95% CI - 95% confidence interval. ∗∗∗PSV – probability scaled value.

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241). Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2–4-fold) and miR-192 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors ( Conclusions: The interconnected discovery–validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients. Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464–72. ©2018 AACR.

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.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).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, p0.034) to September 2011, then sharply declined by 106 encounters per month from September to October 2011 (p0.001) then did not change significantly (p=0.096, RThe 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.

Circumcision is one of the most common urologic procedures performed at pediatric ambulatory centers. Emerging data on the short- and long-term effects of perioperative opioid administration has highlighted the importance of an opioid-free anesthetic regimen. We sought to evaluate the effectiveness of an opioid-free anesthetic in pediatric circumcision and its correlation with ambulatory surgery center efficiency. Patients, 3 years of age and younger, who underwent circumcision or circumcision revision by two surgeons pre and post introduction of an opioid-free anesthetic fast-track regimen at an outpatient surgical center were included. There were 100 patients included in this analysis, with 50 patients in each cohort. On univariate analysis, fast-tracking was associated with a decrease in median combined in-room and post-anesthesia care unit times (102.5 vs. 129.0 min, p-value &lt, 0.001). This difference continued after multivariable analysis with an adjusted median combined in-room and post-anesthesia care unit time difference of −15.6 min (95% CI −34.2 to −12.7 min, p-value 0.018). In addition, the fast-track cohort received less intraoperative morphine equivalents without an increase in post-operative analgesic administration or change in postoperative questionnaire score. This demonstrates that opioid-free anesthesia may be used effectively in pediatric circumcision while also allowing for significant time savings for surgical centers.

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.

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%) chos...

INTRODUCTION AND OBJECTIVES:Vesicoureteral reflux (VUR) is a common cause of febrile urinary tract infections (fUTI) in children. The 2011 AAP UTI guidelines recommended a VCUG after the second fUT...

To compare health-related quality of life (HRQoL) in children with prune-belly syndrome (PBS) and their caregivers to healthy controls, as children and adolescents with PBS face numerous potential physical and psychosocial challenges.Study participants completed the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL) 4.0 generic core scales (children) or Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) (caregivers) in an online, anonymous format. The PedsQL 4.0 is a 23-item, age-adjusted, validated questionnaire that assesses physical, emotional, social, and school functioning in pediatric patients. The Q-LES-Q-SF is a validated, self-report measure that assesses various areas of daily functioning in adults.PedsQL 4.0 was completed by 32 children with PBS. Individual physical (66.3 ± 20 vs 84.4 ± 17.3; P.0001), emotional (68.4 ± 23.4 vs 80.9 ± 19.6; P.01), social (63.1 ± 21.3 vs 87.4 ± 17.2; P .0001), and school (53 ± 21.7 vs 78.6 ± 20.5; P.0001) functioning scales were all significantly lower than in healthy children. Nineteen caregivers completed the Q-LES-Q-SF. Caregivers had a mean raw score of 54.8 ± 9.6, which was significantly lower (P = .02) than the comparative healthy adult cohort (59.8 ± 11.3).PBS profoundly impacts HRQoL in children, negatively affecting physical, emotional, social, and school functioning. Caregivers of PBS patients also report an overall lower quality of life, highlighting the challenges that families with chronically ill children often face.

Summary Introduction and Objective: Health literacy is defined as the ability to obtain, integrate, and appraise health-related knowledge. It is known to correlate with disparities in clinical outcomes in adults with chronic disease. Patients with spina bifida represent a potentially vulnerable cohort as they often have multiple comorbidities. The authors aimed to characterize health literacy in adolescent patients with spina bifida and their caregivers. Study design The Newest Vital Sign (NVS), a validated assessment of health literacy and numeracy, was administered to patients (aged ≥10 years) and caregivers in outpatient pediatric urology and multidisciplinary spina bifida clinics. Subjects not fluent in English or Spanish and those with cognitive delay were excluded. Survey responses and demographic information were analyzed and compared between the spina bifida and control groups. Results Three hundred eleven caregivers (caregivers for patients with spina bifida: 185, caregivers for the controls: 126) and 84 adolescents (those with spina bifida: 46, controls: 38) completed the NVS. Although there was no difference in health literacy between caregivers (p = 0.98), adolescents with spina bifida demonstrated lower NVS scores (spina bifida 1 [0–3] vs. control 2 [2–4]; p = 0.02) (Figure). Health literacy of patients with spina bifida and controls increased with age (p = 0.002). Adjusting for age and gender, the odds of having limited literacy were 5.5 times higher in patients with spina bifida than in the controls (p = 0.004). Inadequate caregiver health literacy was associated with a lower education level (p Discussion Spina bifida is among the most complex birth defects compatible with life and affects a multitude of systems. Although it is well established that limited health literacy in adults with chronic disease is associated with adverse outcomes, there are considerably fewer data in the pediatric population. The authors found that caregivers of patients with spina bifida exhibited health literacy and numeracy comparable with parents in the control group, despite lower education levels. In contrast, adolescents with spina bifida demonstrated poorer health literacy than the controls. Multidisciplinary care is necessary, given the medical complexity of spina bifida; therefore, impaired understanding of adults’ own needs may pose a barrier to successful transition to their care and subsequent outcomes. Conclusions The majority of surveyed caregivers for patients with spina bifida exhibited adequate health literacy, especially those with some college education; however inadequate health literacy was more likely among adolescents with spina bifida when compared with the controls. Screening for health literacy may be useful to assess readiness for transition to more independent self-care among patients with spina bifida. Download : Download high-res image (106KB) Download : Download full-size image Summary Figure . Comparison of health literacy between adolescents (P = 0.02).

Objective To quantitatively evaluate parental preferences for the various treatments for vesicoureteral reflux using crowd-sourced best-worst scaling, a novel technique in urologic preference estimation. Methods Preference data were collected from a community sample of parents via 2 best-worst scaling survey instruments published to Amazon's Mechanical Turk online community. Attributes and attribute levels were selected following extensive review of the reflux literature. Respondents completed an object case best-worst scaling exercise to prioritize general aspects of reflux treatments and multiprofile case best-worst scaling to elicit their preferences for the specific differences in reflux treatments. Data were analyzed using multinomial logistic regression. Results from the object-case provided probability scaled values (PSV) that reflected the order of importance of attributes. Results We analyzed data for 248 and 228 respondents for object and multiprofile case BWS, respectively. When prioritizing general aspects of reflux treatment, effectiveness (PSV = 20.37), risk of future urinary tract infection (PSV = 14.85), and complication rate (PSV = 14.55) were most important to parents. Societal cost (PSV = 1.41), length of hospitalization (PSV = 1.09), and cosmesis (PSV = 0.91) were least important. Parents perceived no difference in preference for the cosmetic outcome of open vs minimally invasive surgery (P = .791). Bundling attribute preference weights, parents in our study would choose open surgery 74.9% of the time. Conclusion High treatment effectiveness was the most important and preferred attribute to parents. Alternatively, cost and cosmesis were among the least important. Our findings serve to inform shared parent-physician decision-making for vesicoureteral reflux.

Management of vesicoureteral reflux may involve a period of observation while the patient is on continuous antibiotic prophylaxis while awaiting spontaneous resolution. There are several indications for surgical correction that include non-resolution after a period of observation, parent preference, or breakthrough infections while on antibiotic prophylaxis, just to name a few. Endoscopic injection for correction of vesicoureteral reflux is an effective, minimally invasive method of treatment. Successful treatment is dependent on surgical technique, with a success rate of 77 to 94% with the double hydrodistension implantation technique (HIT) and uniform endpoints of injection. We aim to describe the double HIT technique for endoscopic injection along with tips and tricks for a successful result. This review contains 10 figures, 5 tables and 26 references Keywords: Vesicoureteral reflux, minimally invasive, febile urinary tract infection, voiding cystourethrogram, deflux, dextranomer/hyaluronic acid, children, cystoscopy, pyelonephritis, endoscopy

Summary Background Robot-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. Objective To assess the safety and efficacy of RALUR-EV in children, among experienced surgeons. Design and methods We 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. Results In 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. Discussion We 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. Conclusions Radiographic 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. Summary Table . Outcomes, overall and by preoperative vesicoureteral reflux (VUR) grade Radiographic resolution by preoperative VUR grade n a (%) I 15/16 (93.8) II 24/26 (92.1) III 49/52 (92.4) IV 38/41 (92.7) V 10/10 (100.0) Overall 136/145 (93.8) a Number of ureters without VUR present/number of ureters studied with voiding cystourethrogram or radionuclide cystogram.

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.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.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, p0.001) 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).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.

Renal cell carcinoma with tumor thrombus of the inferior vena cava presents a special surgical challenge. The use of surgical techniques derived from the field of transplantation surgery have previously been shown to enable optimal control of inferior vena cava, allowing for the extirpation of most tumors via a transabdominal approach without the need for venovenous or cardiopulmonary bypass. In this report, we provide a stepwise description of the transplantation techniques employed at the University of Miami/Jackson Memorial Hospital for the resection of renal cell carcinoma with intracaval tumor. In addition, we review the results of centers that have utilized these surgical maneuvers.

UNLABELLED What's known on the subject? and What does the study add? The surgical implications of renal cell carcinoma with coexisting bland and tumour thrombi of the inferior vena cava is not well described. In this study we review our experience managing these tumours. On multivariate analysis, we found that the presence of bland thrombus was associated with an increased need for surgical interruption of the inferior vena cava. OBJECTIVE • To study the role of interruption of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) and associated bland and tumour thrombi. METHODS • We reviewed 129 consecutive patients with the preoperative diagnosis of RCC with tumour thrombus who underwent radical nephrectomy and tumour thrombectomy in one academic institution between May 1997 and February 2011. RESULTS • Percentages of patients with levels I, II, III and IV tumour thrombus were 29%, 13%, 48% and 9%, respectively. • The perioperative mortality rate was 2.3%. There were 29 (22%) perioperative complications recorded. • In all, 19 patients underwent surgical interruption of the IVC by ligation or segmental resection, including one level II, 14 level III and four level IV thrombi. • A total of 15 patients (12%) had bland thrombus associated with the tumour thrombus; four of these underwent intraoperative IVC filter placement and eight underwent surgical IVC interruption. • Advanced level of tumour thrombus was the only significant factor predicting association of bland thrombus (odds ratio [OR]= 2.09, 95% confidence interval [CI]: 1.082-4.037, P= 0.028). • On multivariate analysis, level of thrombus (OR = 3.1, 95% CI: 1.30-7.74, P= 0.011) and association of bland thrombus (OR = 9.07, 95% CI: 2.42-34.01, P= 0.001) were significant factors for IVC interruption. CONCLUSIONS • Surgical interruption of the IVC is a feasible option in selected patients with chronic IVC obstruction. Association of bland thrombus with tumour thrombus should alert the surgical team to the potential for a challenging surgery. • Precise preoperative imaging to assess the degree of venous obstruction and to help with differentiation between bland and tumour thrombus is key to achieving a surgical outcome with minimal morbidity.

Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens.Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis.Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers.Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

Objective To describe a modified open surgical technique for the resection of renal cell carcinoma with level I or II tumor thrombus. Method In our modified technique, the renal artery is ligated early and the tumor thrombus is secured ahead of kidney mobilization by either milking into the renal vein or with extirpation from the inferior vena cava. We retrospectively studied patients who were managed with this technique. Results Between September 2006 and June 2010, 20 patients with a median age of 65 years underwent surgery for renal cell carcinoma with level I (n = 15) or II (n = 5) tumor thrombus using the modified technique. Median blood loss was 275 mL with 75% of patients requiring at least 1 transfused unit of blood. No case was complicated by an intraoperative tumor embolism. Following surgery, patients stayed a median of 5 days in the hospital and none experienced a perioperative complication. Conclusion The described surgical technique allows for the safe and effective resection of renal cell carcinoma with level I or II tumor thrombus. This technique enables vascular control of the inferior vena cava with a minimal risk of tumor embolization.

Summary Introduction Urinary 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. Methods Children 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 1 = partial/complete UTD or 2 = no/increased UTD. Inter-observer agreement was calculated. Patients were excluded for incomplete imaging or inability to void during VCUG. Results The cohort included 128 patients (10M, 118F), mean age 4.1 ± 2.1 years. Mean age at diagnosis was 2.8 ± 2.8 years. Mean maximum VUR grade was 3 ± 0.9: 1 (7.8%), 2 (20.3%), 3 (43%), 4 (25.8%), 5 (3.1%). UTD occurred in 45 (35%), and no drainage in 83 (65%) patients. Agreement coefficient between graders was 0.596 (p Conclusion We 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. Table . Urinary tract infection rate/year by parent reported and positive culture UTI versus upper tract drainage on voiding cystourethrogram according to binary drainage scoring system. Urinary tract infection vs. upper tract drainage p-value N Mean (SD) Median (mad) UTI rate/year by parent reported UTI Complete upper tract contrast drainage or less than filling 45 0.66 (0.53) 0.47 (0.28) 0.71 Unchanged upper tract contrast or more than filling 83 0.7 (0.5) 0.62 (0.33) UTI rate/year by positive culture Complete upper tract contrast drainage or less than filling 24 0.746 (0.657) 0.47 0.1664 Unchanged upper tract contrast or more than filling 49 0.538 (0.410) 0.441

BACKGROUND: Molecular profiling of renal cell carcinomas (RCCs) may improve the distinction between oncocytoma and malignant RCC subtypes and aid in early detection of metastasis. The hyaluronic acid (HA) family includes HA synthases (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL-P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor growth and metastasis. The authors evaluated the expression of HA family members in kidney specimens. METHODS: By using quantitative polymerase chain reaction, mRNA levels of 12 HA family members were measured in tumor specimens obtained from 86 consecutive patients undergoing nephrectomy; 80 of them also provided normal specimens. Mean and median follow-up were 15.2 ± 8.8 and 13.8 months. RCC specimens included clear cell RCC: 65; papillary: 10; chromophobe: 5; oncocytoma: 6; metastasis positive: 17. RESULTS: Median HAS1, CD44s, and RHAMM transcript levels were elevated 3- to 25-fold in clear cell RCC and papillary and chromophobe tumors when compared with normal tissues. HYAL-4, CD44s, and RHAMM levels were elevated 4- to 12-fold in clear cell RCC and papillary tumors when compared with oncocytomas; only HYAL-4 levels distinguished between chromophobe and oncocytoma (P = .009). CD44s and RHAMM levels were significantly higher in tumors

The 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.We 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.A 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 (p0.001), grade 4-5 reflux (p0.001) 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.The 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.

Adolescent varicocele is associated with ipsilateral testicular hypotrophy and the concern for future infertility. A testicular size discrepancy greater than 15–20 % 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.

In this month’s edition of European Urology, Chromecki and coworkers report on a retrospective series of 2492 patients, pooled from 16 centers, who underwent nephroureterectomy (NU) for the treatment of upper tract urothelial carcinoma (UTUC) [1]. A multivariate analysis of patients with organ-confined UTUC treated by NU showed cancerspecific mortality and progression-free survival to be significantly influenced by age, pathologic stage, lymphovascular invasion, and tumor multifocality. We applaud the authors because this study is the largest of its kind to identify risk factors for UTUC progression and cancerspecific mortality. This information improves our ability to risk-stratify patients with UTUC. In a similar study of 656 patients, Ouzzane et al. [2] identified age, pathologic stage, lymph node metastasis, tumor location, and tumor multifocality as predictors of cancer-specific mortality. Combined, these findings aid in discussions of disease prognosis and may guide management decisions. Despite these advances in our ability to identify patients most at risk of metastasis from UTUC, few strides have been made in the last 30 yr toward improving patient survival. How might we improve our ability to diagnose and manage patients with UTUC beyond the technical improvements of ureteroscopy and

Renal cell carcinoma (RCC) is largely diagnosed incidentally on imaging taken for unrelated reasons. The management of localized lesions is primarily extirpative with excellent results. Treatment of advanced RCC has evolved over recent years with the use of targeted therapies such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and antibody-mediated therapies. The treatment response to these targeted therapies is highly variable, with no clear clinical method of identifying patients who will benefit from or not tolerate therapy. The field of molecular markers has evolved significantly in the last decade, with a multitude of markers identified that predict treatment response and drug toxicity. The following review critically evaluates those molecular markers that have been assessed for their utility in predicting treatment response in patients with advanced/metastatic renal cell carcinoma (mRCC). Identifying the ideal treatment for these patients will improve responses to therapy, minimize morbidity, and save significant healthcare dollars.

No consensus exists regarding the most effective procedure for neovagina formation. We describe our experience with modified single Monti tube colovaginoplasty in pediatric patients with disorders of sexual differentiation.Six patients were retrospectively identified who underwent primary sigmoid vaginoplasty with a modified single Monti tube between 2009 and 2012. Data were collected from patient charts. The procedure is performed by isolating an 8 to 10 cm segment of distal sigmoid colon or proximal rectum, which is detubularized along the anterior mesentery, folded and retubularized longitudinally, leaving the mesentery in a cephalad position. A channel is dissected in the pelvis to accommodate the neovagina.Mean patient age was 12.7 years (range 6 to 17). The primary diagnosis was androgen insensitivity in 3 cases (50%), and Mayer-Rokitansky syndrome, partial androgen insensitivity and persistent cloaca in 1 each (16.7%). Chromosomal analysis revealed 46XY in 4 patients (66.7%). Median followup was 7.9 months (range 3 to 41). One patient who engages in vaginal intercourse reported satisfactory vaginal length without discomfort. In 1 patient an anastomotic stricture developed, which was managed by buccal mucosal grafting.Modified single Monti tube sigmoid vaginoplasty is a safe, effective technique for neovagina formation in pediatric patients with disorders of sexual differentiation. Compared to other existing methods, our technique allows for the use of shorter bowel segments with decreased tension of the vascular pedicle.

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.

Summary Introduction Magnetic 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. Objective To further characterize the renal and ureteral anatomy and renal function in patients with PBS via MRU. Study design Children 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. Results MRU 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). Discussion This 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. Conclusion MRU 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. Download : Download high-res image (56KB) Download : Download full-size image Figure .

To describe the frequency and severity of atherosclerosis contained within the non-neoplastic tissue of partial nephrectomy (PN) specimens. Archived open PN specimens were evaluated for histological evidence of atherosclerosis. Clinically significant atherosclerosis was defined as arterial luminal narrowing of >25 % due to fibrointimal thickening. Histological findings were correlated with clinical data including history of major medical comorbidities and preoperative statin use. The study cohort was comprised of 114 patients (71 men and 43 women). The mean age at the time of surgery was 59.3 years, and 69 (60.5 %) patients had a history of at least one major medical comorbidity including hypertension (54.5 %), diabetes (16.7 %) and coronary artery disease (12.3 %). Clinically significant atherosclerosis was observed in 29 (25.4 %) patients. These individuals were older (p = 0.001), and three times more likely to have greater than one major medical comorbidity (p = 0.002). In addition, only 17 (58.6 %) were prescribed a statin at the time of surgery. Atherosclerosis is frequently observed in the non-neoplastic tissue of PN specimens. Patients found to have atherosclerosis can potentially benefit from intensive lifestyle modification and medical therapy with lipid-lowering medications. These measures would likely have the greatest clinical impact on those patients without an existing history of major medical comorbidities.

INTRODUCTION AND OBJECTIVES: Elevated Hyaluronic Acid (HA) levels are a molecular determinant of bladder cancer (BCa) metastasis. Furthermore, HA, HYAL-1 hyaluronidase and HA-synthesizing enzymes are potential markers for BCa diagnosis and predicting prognosis. 4-Methylumbelliferone (4-MU) is an orally bioavailable dietary supplement that inhibits HA synthesis. Epithelial mesenchymal transition (EMT) is the hallmark of invasion and metastasis, in which cancer cells acquire an invasive phenotype. Since HA promotes tumor metastasis, we evaluated the antitumor effects of 4-MU in vitro and in vivo and examined whether 4-MU can reverse the EMT by inhibiting HA synthesis. METHODS: Quantitative PCR was used to measure mRNA expression of EMT genes ( ;-catenin, Twist, and Snail) in 66 bladder tissue specimens (27 normal; 39 tumor); follow-up: 26 4.3 months; median 20 months. The effect of 4-MU (0.2 – 0.6 mM) on cell proliferation, apoptosis, intracellular signaling, and the expression of HA receptors and EMT genes were examined in BCa cell lines, 253J-Lung and HT1376. Effect of 4-MU on tumor growth was analyzed in subcutaneous xenografts. RESULTS: Among the EMT genes, both Snail and Twist were differentially expressed in BCa tissues when compared to normal bladder (P 0.001). Furthermore, Twist expression significantly correlated with metastasis ( : 0.25 0.15, : 0.12 0.14; P 0.028). -catenin expression negatively correlated with survival (chi square 4.3, p 0.038). 4-MU inhibited proliferation and induced apoptosis in the BCa cells. Following a 48 h exposure at the IC50 for HA synthesis (0.4 mM), 4-MU inhibited proliferation by 61% and increased apoptosis by 73%. 4-MU induced caspase-8, -9 and -3 activation and up-regulation of Fas and FADD. 4-MU downregulated the expression of HA-receptors CD44, RHAMM, EMT promoters ;-catenin, Snail and Twist by 4-10-fold, but increased the expression of E-cadherin by 2-fold, suggesting EMT-reversal. In xenograft studies, 4-MU significantly decreased tumor growth ( 3-fold) when treatment was started either on the day of tumor cell injection or after tumors became palpable. No weight loss or serum or organ toxicity was observed in treated mice. Tumors showed reduced microvessel density ( 3-fold) and HA expression but increased TURNEL positive cells. CONCLUSIONS: This is the first study that shows inhibition of HA synthesis by an orally bioavailable, non-toxic supplement that potentially reverses EMT and has potent anti-tumor activity.

In an effort to preserve renal function, nephron-sparing approaches such as partial nephrectomy are now routinely performed for the treatment of small renal masses (SRMs). To date, several groups have studied the utility of examining the renal parenchyma contained beyond the tumor margin of partial nephrectomy specimens for histopathologic evidence of non-neoplastic disease processes. The diagnosis of progressive renal disease through the study of this tissue allows for early medical intervention with possible further preservation of renal function. In this review, we discuss the management of SRMs with an emphasis on the emerging role of evaluating tumor specimens for non-neoplastic pathologic abnormalities. We believe that the thorough study of tissue contained beyond the tumor margin of partial nephrectomy specimens is the next step in preserving renal function and improving survival for patients with SRMs.

OMNEX (Ethicon, Inc.; Somerville, NJ) is a cyanoacrylate-based synthetic surgical sealant. To date, the use of OMNEX has only been described in a limited number of vascular surgery procedures. We present the cases of two patients who underwent successful extracorporeal renal artery aneurysm repair with the aid of OMNEX sealant. This report is the first evidence to suggest the utility of OMNEX in renovascular surgery.

disease using this model with an 87.8% accuracy. We hypothesize that in this era of incidentalomas, tumor size has lost its predictive ability to differentiate benign vs. malignant lesions. We believe that classification trees are easier to use in the clinical setting when compared with logistic regression models as they mimic the clinician’s thought process. This classification tree will be validated with an external dataset.

This study aimed to identify non-neoplastic pathologic changes in partial nephrectomy specimens of patients without a known history of medical comorbidities. Routine analysis of this tissue may allow the clinician to identify subclinical renal disease.We retrospectively reviewed our database of patients who underwent open partial nephrectomy for a small renal mass. Non-neoplastic tissue of partial nephrectomy specimens of patients without a known history of chronic kidney disease, diabetes mellitus, hypertension, or coronary artery disease was evaluated for glomerular, interstitial, and vascular pathologic changes.A rim of non-neoplastic tissue was adequate for pathologic evaluation in 91.8% of specimens. A total of 45 patients were studied with a median age of 52.0 years. Atherosclerosis was the most commonly identified pathologic finding in 9 (20%) patients, followed by mesangial expansion and interstitial fibrosis, each found in 8 (17.8%) patients. Linear regression found interstitial fibrosis to be the only pathologic lesion associated with preoperative serum creatinine (coefficient = 0.697, P = 0.001). Male gender was also associated with a higher preoperative creatinine (coefficient = 0.270, P = 0.034). Postoperative serum creatinine was not associated with any of the examined lesions.Current surgical techniques provide adequate non-neoplastic tissue for pathologic evaluation. We observed a striking degree of pathologic disease in patients without a known history of medical comorbidities. Routine inspection of the non-neoplastic parenchyma of partial nephrectomy specimens should be performed as it can alert the clinician to presence subclinical renal disease allowing for medical intervention.