Prevalence of urinary incontinence and other lower urinary tract symptoms in children in the Netherlands.

INTRODUCTION: The International Children's Continence Society (ICCS) defines urinary incontinence (UI) as 'involuntary leakage of urine' [1], a condition that can have a negative impact on a child's life. Although UI is common among children, the reported prevalences worldwide vary. Regarding children in the Netherlands, only a few studies report on the prevalence of UI and other lower urinary tract symptoms (LUTSs). OBJECTIVE: The aim was to investigate the prevalence of episodes of UI and other LUTSs along with associated 'risk factors' in children in the Netherlands. STUDY DESIGN: In a cross-sectional study, 240 children (8- to 17-year-olds) were included, who completed the Groningen Pediatric Defecation and Fecal Continence Questionnaire. UI was defined in accordance with the ICCS's definition of involuntary leakage of urine. To define a timeframe of episodes of UI, the situation during the past 6 months was specifically asked. The other LUTSs included were intermittency, straining, urinary tract infections, nocturia, and frequency. RESULTS: The prevalence of episodes of UI in the total group was 21.7%. Girls experienced UI significantly more often than boys (30.1% versus 14.2%, P = 0.003). Prevalence did not differ between the 8- to 12-year-olds and the 13- to 17-year-olds. The most prevalent form of UI was stress UI (8.8%). After excluding six children with a medical history that could influence bladder function, UI in 20.9% of the remaining 'healthy' children was found. Intermittency was experienced by 18.3% of the children, and 15% strained during micturition. Univariate analysis showed that the presence of straining, intermittency, nocturia, or fecal incontinence was significantly associated with UI. DISCUSSION: Of the children studied, episodes of UI occurred in 21.7%, and the condition did not decrease with age. It was found that UI is not limited to 'sick' children because it occurred in 20.9% of the 'healthy' subgroup. Although children with urge UI in daily practice were mainly seen, in this study, it was found that on average, stress UI was the most common form of UI among Dutch children. The prevalence of other LUTSs was also high, with intermittency and straining as the most frequent symptoms (18.3% and 15.0%, respectively). Intermittency and straining are significantly associated with UI, as are nightly nocturia and fecal incontinence. CONCLUSION: Episodes of UI and other LUTSs are common conditions among children in the Netherlands, even in the 'healthy' group. It is important that medical practitioners are aware of these phenomena, and they should be alert to the associated symptoms as they may be considered as 'risk factors'.

Expression and prognostic value of epidermal growth factor receptor, transforming growth factor-alpha, and c-erb B-2 in nephroblastoma.

BACKGROUND: Wilms tumor is one of the most common solid tumors in children. A transforming growth factor-alpha (TGF-alpha)/epidermal growth factor receptor (EGF-R) autocrine loop plays an important role in tumor growth. Abnormal expression of TGF-alpha, EGF-R and c-erb B-2 has been demonstrated in several human malignancies. METHODS: The immunohistochemical expression of TGF-alpha, EGF-R, and c-erb B-2 was studied in paraffin material of 62 clinical Wilms tumors. Patients had a mean follow-up of 5.7 years. RESULTS: Generally, TGF-alpha, EGF-R, and c-erb B-2 were expressed in tissue of the normal kidney and at variable levels in the three cell types of Wilms tumor, i.e., blastemal, epithelial, and stromal cells. Immunoreactive blastema cells were found in 48%, 44%, and 34% of tumors for TGF-alpha, EGF-R, and c-erb B-2, respectively. It was found that TGF-alpha, EGF-R, and c-erb B-2 blastemal and epithelial expression gradually increased from T1 to T3. The blastemal expression of TGF-alpha was statistically significantly correlated with clinicopathologic stages. Both univariate and multivariate analysis showed that blastemal TGF-alpha expression was indicative for clinical progression, but neither blastemal TGF-alpha, nor EGF-R or c-erb B-2 expression correlated with patients survival. Epithelial staining was of no prognostic value. The simultaneous expression of TGF-alpha/EGF-R was indicative for clinical progression at univariate level. CONCLUSIONS: Increased expression of TGF-alpha in the blastemal part of Wilms tumor correlated with tumor classification and clinical progression. These findings suggest that significant expression of TGF-alpha and EGF-R may play a role in promoting transformation and/or proliferation of Wilms tumor, perhaps by an autocrine mechanism. Therefore, their expression may be of value in identifying patients at high risk of tumor recurrence.

Neurogenic and non-neurogenic bladder dysfunction.

Children with a neurological defect have a clear cause for their bladder dysfunction; however, in neurologically normal children the cause of their incontinence is usually unclear. When no anatomical abnormalities seem to be present a functional problem is generally the cause. This type of incontinence is referred to as 'functional incontinence'. The different forms of bladder and sphincter dysfunction will be discussed and treatment modalities described. As the treatment modalities in children with neuropathic bladders focus on medical and especially surgical options, special attention is paid to new developments in surgical treatment. For those with functional incontinence treatment options are more variable and the new developments are described.

Cellular membrane associated mucins in artificial urine as mediators of crystal adhesion: an in vitro enterocystoplasty model.

PURPOSE: Cells are a major component of mucus in enterocystoplasties. We evaluate the role of secreted mucins on cells and cellular membranes as crystal adhesion and agglomeration mediators in artificial urine infected with Proteus mirabilis. MATERIALS AND METHODS: Five human intestinal cell lines, HT29, HT29-18N2, HT29-FU, HT29-MTX, Caco-2 and 1 ureter cell line, SV-HUC-1, were incubated for 3 hours in artificial urine with P. mirabilis (ATCC49565) in monolayer and scraped conditions. We isolated Triton X-100 soluble membrane proteins from cells to evaluate the effect of MUC2 and MUC 5AC as membrane associated proteins on crystal formation and crystal adherence. Scanning electron microscopy, light microscopy, Coulter Counter measurements and x-ray microanalysis were used to evaluate crystal formation. RESULTS: Brushite crystals were adhered to cellular surface sites rich in sulfur as crystal agglomerates. Smaller and more numerous crystals were observed in the presence of scraped cells. Crystal growth and agglomeration was inhibited by the presence of MUC 5AC, whereas MUC2 had the opposite effect. Both are present on cellular membranes and are rich in sulfur. Cellular invasion by bacteria occurred in all cell lines. CONCLUSIONS: Membrane associated cellular secretions such as MUC2 and 5AC are important crystal adhesion molecules on cells and have a clear effect on urease induced crystallization in vitro. MUC2 and MUC 5AC induce crystal adhesion and mucin type dependent effects on crystal agglomeration. The effects of MUC2 and MUC 5AC may explain the high incidence of bladder calculi in enterocystoplasties and emphasize the role of cellular surfaces in urine.

The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma.

Apoptotic cell death represents an important mechanism for the precise regulation of cell numbers in normal tissues. Various apoptosis-associated regulatory proteins, such as Bcl-2, Bax and Bcl-X, may contribute to the rate of apoptosis in neoplasia. The present study was performed to evaluate the prognostic value of these molecules in a group of 61 Wilms' tumours of chemotherapeutically pre-treated patients using an immunohistochemical approach. Generally, Bcl-2, Bax and for Bcl-X(S/L) were expressed in the blastemal and epithelial components of Wilms' tumour. Immunoreactive blastema cells were found in 53%, 41% and 38% of tumours for Bcl-2, Bax and for Bcl-X(S/L), respectively. An increased expression of Bcl-2 was observed in the blastemal component of increasing pathological stages. In contrast, a gradual decline of Bax expression was observed in the blastemal component of tumours with increasing pathological stages. Also blastemal Bcl-X(S/L) expression decreased with stage. Univariate analysis showed that blastemal Bcl-2 expression and the Bcl-2/Bax ratio were indicative for clinical progression, whereas epithelial staining was of no prognostic value. Multivariate analysis showed that blastemal Bcl-2 expression is an independent prognostic marker for clinical progression besides stage. These findings demonstrate that alterations of the Bcl-2/Bax balance may influence the clinical outcome of Wilms' tumour patients by deregulation of programmed cell death.

Measurement of urinary flow rate using ultrasound in young boys and infants.

PURPOSE: We present a technique for measuring urinary flow rates with ultrasound in male infants and children. MATERIALS AND METHODS: Urinary flow rate was measured simultaneously by an ultrasound probe placed around the base of the penis and by a funnel with a rotating disk at the bottom in 30 boys with a mean age of 6.7 years (range 4.5 to 10.5), and by ultrasound in 8 infants with a mean age of 10 months (range 1 to 28). Voided volume was measured with a graded cylinder or calculated from the weight change of diapers in infants. Ultrasound and rotating disk maximum flow rates were calculated. The ultrasound signal was calibrated by comparing the collected voided volume to the area under the curve for that void. The volume calculated from the rotating disk flow rate curve was also compared with the collected volume. RESULTS: Both methods yielded similar flow curves. However, ultrasound maximum flow rate significantly exceeded rotating disk maximum flow rate (13 +/- 6 ml. per second, range 5 to 22 versus 10 +/- 4 ml. per second, range 4 to 21, t test p <0.001). The underestimation of the flow rate by the rotating disk method may have been due to adherence of urine to the funnel wall. Rotating disk maximum flow rate was lower and voided volume was underestimated by up to 50% (average 15 +/- 2%) in 21 cases. Ultrasound maximum flow rate averaged 6 +/- 3 ml. per second (range 3 to 11.6 [oldest infant]) in the 8 infants. CONCLUSIONS: Urinary flow rates can be measured accurately using ultrasound in boys who produce small volumes and/or who are not toilet trained and also in infants. In future studies ultrasound will be applied to subsets of male infants with bladder dysfunction.

Etiological studies of severe or familial hypospadias.

PURPOSE: Hypospadias is a congenital anomaly occurring in 1250 to 1830 live male births, of which 20% involve a severe type. The recurrence risk in families is high. In the majority of cases the underlying etiology remains unknown, which hampers further management based on the specific requirements associated with a specific etiology. MATERIALS AND METHODS: In a single center study 63 unselected cases of severe hypospadias were studied for all presently known causes of hypospadias using clinical as well as molecular biological techniques. Also, 16 families with hypospadias were analyzed for possible androgen receptor gene mutations. RESULTS: In 31% of cases of severe hypospadias the underlying etiology was identified. Of these 31% of cases 17% were due to complex genetic syndromes, 9.5% were due to chromosomal anomalies, and 1 involved the vanishing testes syndrome, the androgen insensitivity syndrome and 5alpha-reductase type 2 deficiency, respectively. Based on hormone stimulation tests Leydig cell hypoplasia and disorders of testosterone biosynthesis were suspected in some patients but not confirmed by mutation analysis of the respective genes. Familial hypospadias was due to androgen insensitivity in only 1 family but no other etiologies were identified in this group. CONCLUSIONS: Using patient history, physical examination, karyotyping, hormonal evaluation, including human chorionic gonadotropin testing in prepubertal cases and additional biochemical and molecular genetic evaluation, an etiological diagnosis was made in 31% of cases of severe hypospadias. This diagnosis has implications for further patient treatment. In addition, familial hypospadias is rarely due to the androgen insensitivity syndrome.

Paediatric voiding dysfunction and enuresis.

Urinary incontinence and nocturnal enuresis are frequently encountered problems in children. In this review some aspects will be highlighted. Especially the different types of monosymptomatic nocturnal enuresis as well as some recent developments in children with dysfunctional voiding will be discussed.

Bladder calculi in augmentation cystoplasty in children.

OBJECTIVES: To determine the best preventive strategies for bladder calculi in children with an augmented bladder, the risk factors and prevention strategies for urolithiasis were evaluated. METHODS: The records of 89 patients following augmentation cystoplasty were reviewed to assess the results of augmentation cystoplasties and in particular the formation and prevention of calculi. RESULTS: The median follow-up was 4.9 years after augmentation. Most patients (71) had an ileocystoplasty. Bladder calculi occurred in 14 of the 89 patients (16%) and recurred in 4 patients. Girls had a higher incidence of urolithiasis. Other risk factors were cloacal malformations, vaginal reconstructions, anal atresia, clean intermittent catheterization problems and retention, bladder neck surgery, and symptomatic urinary tract infections. CONCLUSIONS: Subgroups with cloacal malformations, vaginal reconstructions, ureter reimplantation, and bladder neck surgery were identified that have an increased risk for stone formation and therefore warrant special care in the follow-up after augmentation. This care should include clear emphasis on the role of treating symptomatic urinary tract infections, especially in patients with cloacal malformations and vaginal reconstructions. Girls have a higher incidence of bladder calculi than boys.

Vesicoureteral reflux and videourodynamic studies: results of a prospective study.

OBJECTIVES: To study the influence of bladder instability on the conservative management and surgical treatment of children with vesicoureteral reflux (VUR), 102 children were included in a prospective study. METHODS: During a 5-year period all children suspected to have VUR underwent a videourodynamic study to determine VUR grade and bladder function. This resulted in a group of 36 boys and 66 girls who were followed up for well over 5 years. RESULTS: Bladder instability was found in 41 of 102 children (40%). The 102 children were either treated conservatively or surgically. Of the 77 children who were treated conservatively, bladder instability was found in 35 patients. In the conservatively treated group with bladder instability, reflux resolved in 57%; whereas in those with normal bladder function, reflux resolved in 67%. Of the 25 patients who were treated surgically, the operation was successful in 91%. Breakthrough infections occurred in 22 girls and 3 boys, including 14 of 41 patients with bladder instability (34%) and 11 of 61 patients with normal bladder function (18%). CONCLUSIONS: Bladder instability is a frequent finding and an important factor in the treatment of children with VUR. To determine if a patient has VUR and bladder instability a videourodynamic study has proved to be an easy and efficient diagnostic tool. When bladder instability is treated with anticholinergic medication, almost the same results can be expected from conservative treatment as from surgical treatment compared to children with a normal bladder function. Breakthrough urinary tract infections occur more often in girls and tend to occur more often in children with bladder instability.

Classification and treatment of functional incontinence in children.

Functional urinary incontinence in children may be caused by disturbances of the filling phase, the voiding phase or a combination of both. Detrusor overactivity may cause frequency and urgency, with or without urge incontinence. Girls present with symptoms of detrusor overactivity more often than boys, but sometimes other symptoms, e.g. urinary tract infections or constipation, prevail. Frequent contractions of the detrusor may cause the pelvic floor muscles to become overactive, resulting in staccato or fractionated voiding. When incontinence is the result of a voiding disorder the term 'dysfunctional voiding' is used. Bladder function in these children may be normal, but instability may be present. In children with a 'lazy' bladder, voiding occurs with no detrusor contractions, and postvoid residual volumes and overflow incontinence are the main characteristics. Diagnosis is based on the medical and voiding history, a physical examination, bladder diaries and uroflowmetry. The upper urinary tract should be evaluated in children with recurrent infections and dysfunctional voiding (reflux). Uroflowmetry can be combined with pelvic floor electromyography to detect overactivity of the pelvic floor muscles. Urodynamic studies are usually reserved for patients with dysfunctional voiding and those not responding to anticholinergic drugs. Treatment is usually a combination of 'standard therapy', behavioural therapy, bladder training, physiotherapy and medical treatment. The role of alpha-blockers needs to be evaluated further. Also, neuromodulation may have a place in treatment but the exact indications need to be defined. Clean intermittent self-catheterization is sometimes necessary in children with a lazy bladder and large residual volumes who do not respond to a more conservative approach. Future research needs to be directed towards improving understanding of the pathophysiology, epidemiology, classification and treatment modalities of functional incontinence in children.

Renal Doppler ultrasonography in children with equivocal obstructive uropathy: effect of intravenous normal saline fluid load and frusemide.

OBJECTIVE: To study the effect of hyperhydration with normal saline and frusemide on the renal resistive index (RI) in children with equivocal obstructive uropathy. PATIENTS AND METHODS: Twelve children (24 kidneys) with unilateral or bilateral hydronephrosis underwent isotopic diuretic renography and Doppler ultrasonography. All children had equivocal obstruction of the hydronephrotic kidneys with half-time drainage (T/2) values of 10-20 min. Doppler studies were carried out both at baseline and after the infusion of normal saline and frusemide. RESULTS: Of the 24 kidneys, five were normal and 19 were hydronephrotic; compared with normal kidneys, the hydronephrotic units had a significantly lower glomerular filtration rate (GFR) and longer T/2. At baseline, the mean RI values of normal and hydronephrotic kidneys were not significantly different (0.70, SD 0.03 and 0.71, SD 0.04, respectively). After the infusion of saline and frusemide, the mean RI of hydronephrotic kidneys (0.67, SD 0.07) was significantly (P = 0.01) higher than that of normal kidneys (0.60, SD 0.02), but the response of RI in hydronephrotic kidneys was variable. Based on the RI at baseline and after infusion, hydronephrotic kidneys could be categorized into three groups. Group 1 (n = 6) had an RI < 0.7 before and after infusion, group 2 (n = 6) had a baseline RI > 0.7 and < 0.7 after infusion, and in group 3 (n = 7) both RIs were > 0.7. Kidneys in group 3 had the lowest GFR and the highest T/2 values. Five of these seven hydronephrotic kidneys eventually had deteriorating GFRs requiring surgical correction; the GFR of the remaining hydronephrotic kidneys remained stable. CONCLUSION: In children with equivocal obstructive uropathy based on diuretic renography, the determination of RI before and after infusion of normal saline and frusemide could be helpful in distinguishing obstructed from non-obstructed kidneys.

Partial ureteral obstruction: role of renal resistive index in stages of obstruction and release.

OBJECTIVES: To study the changes in renal resistive index (RI) and renal function before and after release of different grades of partial unilateral ureteral obstructions. METHODS: Ten dogs were subjected to right partial ureteral obstruction. Grade 1 (mild) obstruction was applied to 5 dogs (group A) and grade 3 (moderate and severe) obstruction was applied to the other 5 dogs (group B). Obstruction was maintained for 8 weeks, followed by release of obstruction. All dogs were subjected to excretory urography, technetium-99m mercaptoacetyltriglycine diuretic renography with calculation of half-time drainage (T1/2), and bilateral renal Doppler ultrasonography before the start of the experiment, after 8 weeks of obstruction, and every 2 weeks during the 8 weeks after release of obstruction. RESULTS: In both groups, after induction of right ureteral obstruction, there was a dramatic decrease of effective renal plasma flow (ERPF), increase of RI, and increase of T1/2 of the right kidney. Relief of obstruction was associated with normalization of T1/2, reversal of RI, and recovery of ERPF to near basal values. No correlation was found between ERPF at the end of the recovery period and the functional parameters (T1/2, RI, or ERPF) of the obstructed kidney before release of obstruction. CONCLUSIONS: (1) Unilateral partial ureteral obstruction produces an elevation of RI and T1/2 and a fall in ERPF of the corresponding kidney. (2) After relief of function is regained with associated reversal of RI. (3) Functional parameters (T1/2, RI, or ERPF) of the obstructed kidney do not predict the recovery of ERPF after release of obstruction. (4) Rapid reversal of a previously elevated RI is an early indicator of recoverability of renal function after relief of ureteral obstruction.

Partial ureteral obstruction: effect of intravenous normal saline and furosemide upon the renal resistive index.

OBJECTIVE: To investigate the effect of intravenous normal saline fluid load, with and without furosemide, upon the renal resistive index (RI) of obstructed and nonobstructed kidneys. METHODS: Right partial ureteral obstruction was induced in 10 dogs. Grade 1 (mild) obstruction was performed in 5 dogs (group A), and grade 3 (severe) obstruction was carried out to the remaining 5 dogs (group B). Evaluation by Doppler ultrasonography was performed before induction of ureteral obstruction and by the end of the 8th week of obstruction. Every obstructed animal was subjected to bilateral renal Doppler ultrasonography 3 times in one setting: 1) before infusion of normal saline, 2) 30-60 minutes after intravenous infusion of normal saline (15 ml./kg.) given in a rate of 1 ml./kg./min. and 3) 10 minutes after admission of furosemide (1 mg./kg.). RESULTS: After induction of right partial ureteral obstruction, there was a significant increase of the RI of the right kidney and a significant decrease of the RI of the left kidney compared to baseline RI in both groups. Infusion of normal saline and administration of furosemide caused a further significant increase of the RI of the obstructed kidney and a further significant decrease of the RI in the nonobstructed kidney in both groups. CONCLUSION: In unilateral partial ureteral obstruction, addition of intravenous normal saline and furosemide cause the RI to increase in obstructed kidney and to decrease in nonobstructed kidney. Such a divergent response may be useful for the development of a pharmacologically challenged Doppler examination to diagnose better potentially obstructed kidneys.