Rien J.M. Nijman

EAU Guidelines on Vesicoureteral Reflux in Children

CONTEXT Primary vesicoureteral reflux (VUR) is a common congenital urinary tract abnormality in children. There is considerable controversy regarding its management. Preservation of kidney function is the main goal of treatment, which necessitates identification of patients requiring early intervention. OBJECTIVE To present a management approach for VUR based on early risk assessment. EVIDENCE ACQUISITION A literature search was performed and the data reviewed. From selected papers, data were extracted and analyzed with a focus on risk stratification. The authors recognize that there are limited high-level data on which to base unequivocal recommendations, necessitating a revisiting of this topic in the years to come. EVIDENCE SYNTHESIS There is no consensus on the optimal management of VUR or on its diagnostic procedures, treatment options, or most effective timing of treatment. By defining risk factors (family history, gender, laterality, age at presentation, presenting symptoms, VUR grade, duplication, and other voiding dysfunctions), early stratification should allow identification of patients at high potential risk of renal scarring and urinary tract infections (UTIs). Imaging is the basis for diagnosis and further management. Standard imaging tests comprise renal and bladder ultrasonography, voiding cystourethrography, and nuclear renal scanning. There is a well-documented link with lower urinary tract dysfunction (LUTD); patients with LUTD and febrile UTI are likely to present with VUR. Diagnosis can be confirmed through a video urodynamic study combined with a urodynamic investigation. Early screening of the siblings and offspring of reflux patients seems indicated. Conservative therapy includes watchful waiting, intermittent or continuous antibiotic prophylaxis, and bladder rehabilitation in patients with LUTD. The goal of the conservative approach is prevention of febrile UTI, since VUR will not damage the kidney when it is free of infection. Interventional therapies include injection of bulking agents and ureteral reimplantation. Reimplantation can be performed using a number of different surgical approaches, with a recent focus on minimally invasive techniques. CONCLUSIONS While it is important to avoid overtreatment, finding a balance between cases with clinically insignificant VUR and cases that require immediate intervention should be the guiding principle in the management of children presenting with VUR.

In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer.

PurposeProstate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [11C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [11C]choline uptake and the cell proliferation in human prostate cancer.MethodsProstate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [11C]choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen. ResultsProstate cancer showed Ki-67 staining and high uptake of [11C]choline. Statistical analysis showed no significant correlation between [11C]choline uptake and Ki-67 staining (R=0.23; P=0.34). No significant relationships were found between the uptake of [11C]choline (SUV) and either preoperative PSA (R=0.14; P=0.55) or Gleason sum score (R=0.28; P=0.25).ConclusionIn vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [11C]choline in prostate cancer.

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using 11C-Choline Positron Emission Tomography

PURPOSE An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of (11)C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). METHODS AND MATERIALS Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq (11)C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. RESULTS None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for (11)C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. CONCLUSIONS (11)C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.

Urinary tract infections in children: EAU/ESPU guidelines

CONTEXT In 30% of children with urinary tract anomalies, urinary tract infection (UTI) can be the first sign. Failure to identify patients at risk can result in damage to the upper urinary tract. OBJECTIVE To provide recommendations for the diagnosis, treatment, and imaging of children presenting with UTI. EVIDENCE ACQUISITION The recommendations were developed after a review of the literature and a search of PubMed and Embase. A consensus decision was adopted when evidence was low. EVIDENCE SYNTHESIS UTIs are classified according to site, episode, symptoms, and complicating factors. For acute treatment, site and severity are the most important. Urine sampling by suprapubic aspiration or catheterisation has a low contamination rate and confirms UTI. Using a plastic bag to collect urine, a UTI can only be excluded if the dipstick is negative for both leukocyte esterase and nitrite or microscopic analysis is negative for both pyuria and bacteriuria. A clean voided midstream urine sample after cleaning the external genitalia has good diagnostic accuracy in toilet-trained children. In children with febrile UTI, antibiotic treatment should be initiated as soon as possible to eradicate infection, prevent bacteraemia, improve outcome, and reduce the likelihood of renal involvement. Ultrasound of the urinary tract is advised to exclude obstructive uropathy. Depending on sex, age, and clinical presentation, vesicoureteral reflux should be excluded. Antibacterial prophylaxis is beneficial. In toilet-trained children, bladder and bowel dysfunction needs to be excluded. CONCLUSIONS The level of evidence is high for the diagnosis of UTI and treatment in children but not for imaging to identify patients at risk for upper urinary tract damage. PATIENT SUMMARY In these guidelines, we looked at the diagnosis, treatment, and imaging of children with urinary tract infection. There are strong recommendations on diagnosis and treatment; we also advise exclusion of obstructive uropathy within 24h and later vesicoureteral reflux, if indicated.

The relevance of urodynamic studies for urge syndrome and dysfunctional voiding: A multicenter controlled trial in children

PURPOSE The objective of this study was to compare prospectively, in urge syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns, to assess changes in urodynamic patterns after treatment, and to correlate urodynamic patterns and parameters with treatment outcome. MATERIALS AND METHODS In the European Bladder Dysfunction Study 97 children with clinically diagnosed urge syndrome received standard treatment, to which was randomly added placebo, oxybutynin or bladder training with online feedback. In a separate branch 105 children with clinically diagnosed dysfunctional voiding were randomly allocated to standard treatment or standard treatment plus pelvic floor training with online feedback. In all children urodynamic studies were performed before and immediately after treatment. RESULTS In urge syndrome detrusor overactivity was present in 33% of cases before and 27% after treatment (of which 65% were de novo). Detrusor overactivity did not correlate with treatment outcome. In dysfunctional voiding increased pelvic floor activity during voiding, which was present in 67% of cases before and 56% after treatment (of which 45% were de novo), did not correlate with treatment outcome. In urge syndrome as well as in dysfunctional voiding neither maximum detrusor pressure during voiding, cystometric bladder capacity, bladder compliance nor free flow patterns correlated with treatment outcome. CONCLUSIONS Neither detrusor overactivity nor increased pelvic floor activity during voiding correlated with treatment outcome. Standard treatment could be the first choice in urge syndrome as well as in dysfunctional voiding, reserving urodynamic studies for patients in whom this first approach fails.

Expression and Prognostic Value of Epidermal Growth Factor Receptor, Transforming Growth Factor-, and c-erb B-2 in Nephroblastoma

Wilms tumor is one of the most common solid tumors in children. A transforming growth factor‐α (TGF‐α)/epidermal growth factor receptor (EGF‐R) autocrine loop plays an important role in tumor growth. Abnormal expression of TGF‐α, EGF‐R and c‐erb B‐2 has been demonstrated in several human malignancies.

Pediatric UrologyThe Relevance of Urodynamic Studies for Urge Syndrome and Dysfunctional Voiding: A Multicenter Controlled Trial in Children

PURPOSE The objective of this study was to compare prospectively, in urge syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns, to assess changes in urodynamic patterns after treatment, and to correlate urodynamic patterns and parameters with treatment outcome. MATERIALS AND METHODS In the European Bladder Dysfunction Study 97 children with clinically diagnosed urge syndrome received standard treatment, to which was randomly added placebo, oxybutynin or bladder training with online feedback. In a separate branch 105 children with clinically diagnosed dysfunctional voiding were randomly allocated to standard treatment or standard treatment plus pelvic floor training with online feedback. In all children urodynamic studies were performed before and immediately after treatment. RESULTS In urge syndrome detrusor overactivity was present in 33% of cases before and 27% after treatment (of which 65% were de novo). Detrusor overactivity did not correlate with treatment outcome. In dysfunctional voiding increased pelvic floor activity during voiding, which was present in 67% of cases before and 56% after treatment (of which 45% were de novo), did not correlate with treatment outcome. In urge syndrome as well as in dysfunctional voiding neither maximum detrusor pressure during voiding, cystometric bladder capacity, bladder compliance nor free flow patterns correlated with treatment outcome. CONCLUSIONS Neither detrusor overactivity nor increased pelvic floor activity during voiding correlated with treatment outcome. Standard treatment could be the first choice in urge syndrome as well as in dysfunctional voiding, reserving urodynamic studies for patients in whom this first approach fails.

Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence

Functional urinary incontinence causes considerable morbidity in 8.4% of school‐age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi‐center controlled trial was designed, the European Bladder Dysfunction Study.

International Children's Continence Society standardization report on urodynamic studies of the lower urinary tract in children

The objective of this document created by the ICCS standardization subcommittee is to provide a uniform guideline on measurement, quality control and documentation of urodynamic studies in children.

A unique 970kb microdeletion in 9q33.3, including the NR5A1 gene in a 46,XY female

We report on a female patient with XY sex reversal with clitoromegaly, neonatal male testosterone and AMH levels, and a normal urine steroid profile. Array CGH revealed a de novo microdeletion of chromosome 9q33.3, including the NR5A1 gene. NR5A1 encodes for the steroidogenic factor-1 (SF-1) and heterozygous mutations in this gene were recently identified as an important cause of XY sex reversal. However, a deletion of NR5A1 has only been reported once. Patients with a mutation in NR5A1, have severe underandrogenisation with mild testicular dysgenesis. Müllerian structures may be present, while postnatal testosterone levels may be normal. This points towards a predominantly early embryonic effect of low, local, androgen levels, with or without reduced AMH levels. We recommend not only NR5A1 mutation screening, but also copy number analysis in patients with 46,XY sex reversal of unknown cause, even in the absence of dysmorphisms or congenital abnormalities.