Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy.

Bladder exstrophy is a rare congenital malformation leaving the urinary bladder open in the midline of the abdomen at birth. There is a clear genetic background with chromosome aberrations, but so far, no consistent findings apart from 22q11-duplications detected in about 2%-3% of all patients. Some genes are implicated like the LZTR1, ISL1, CELSR3, and the WNT3 genes, but most are not explained molecularly. We have performed chromosomal microarray analysis on a cohort of 140 persons born with bladder exstrophy to look for submicroscopic chromosomal deletions and duplications. Pathogenic or possibly pathogenic microdeletions or duplications were found in 16 patients (11.4%) and further 9 with unknown significance. Two findings were in regions linked to known syndromes, two findings involved the same gene (MCC), and all other findings were unique. A closer analysis suggests a few gene networks that are involved in the pathogenesis of bladder exstrophy; the WNT-signaling pathway, the chromosome 22q11 region, the RIT2 and POU families, and involvement of the Golgi apparatus. Bladder exstrophy is a rare malformation and is reported to be associated with several chromosome aberrations. Our data suggest involvement of some specific molecular pathways.

Masculinizing surgery in disorders/differences of sex development: clinician- and participant-evaluated appearance and function.

OBJECTIVES: To report the long-term follow-up outcomes of masculinizing surgery in disorders/differences of sex development (DSD), including both physicians' and patients' perspectives on appearance and functional outcome, including sexuality. PATIENTS AND METHODS: In total, 1040 adolescents (age ≥16 years) and adults with a DSD took part in this multicentre cross-sectional clinical study in six European countries in 2014/2015. Of those, 150 living in other than the female gender had some kind of masculinizing surgery: hypospadias repair, orchidopexy, breast reduction and/or gonadectomy. The study protocol included medical data collection, an optional genital examination, and patient-reported outcomes including satisfaction with appearance and current sexual functioning. RESULTS: Diagnoses included partial and mixed gonadal dysgenesis (45,XO/46,XY; n = 38), Klinefelter syndrome/46,XX males (n = 57), and various 46,XY DSDs (n = 42; e.g. partial androgen insensitivity syndrome, severe hypospadias) and 13 with other diagnoses. Of the participants, 84 underwent hypospadias surgery, 86 orchidopexy, 52 gonadectomy and 32 breast reduction (combinations possible). Physicians evaluated anatomical appearance at genital examination as poor in approximately 11% of patients. After hypospadias surgery, 38% of participants reported that they were (very) dissatisfied with anatomical appearance and 20% with function. The physician and patient evaluations were moderately correlated (r = 0.43). CONCLUSION: The majority of participants were neutral to satisfied with the appearance and function in the long-term after masculinizing surgery. Given the initial severe phenotype and a risk of unsatisfactory results after masculinizing surgery in DSD, treatment should be handled by experienced multidisciplinary teams in order to optimize the postoperative results.

Health-related quality of life among children, adolescents, and adults with bladder exstrophy-epispadias complex: a systematic review of the literature and recommendations for future research.

PURPOSE: Bladder exstrophy-epispadias complex (BEEC) is a rare spectrum of genitourinary malformations. Children risk long-term urinary and genital dysfunctions. To achieve a comprehensive understanding, this study aimed to review the literature on generic and disease-specific health-related quality of life (HRQOL) in BEEC patients, and methodologies used. METHODS: A literature search was conducted in Pubmed/CINAHL/Embase/PsycINFO/Cochrane, from inception to May 2018. A meta-analysis of HRQOL in BEEC patients compared to healthy references was performed. RESULTS: Twenty-one articles (published 1994-2018), describing HRQOL of children and adolescents (n = 5) and adults only (n = 5), or integrated age populations (n = 11), were identified (median sample size 24, loss to follow-up 43%, response rate 84%). Overall HRQOL was reduced in BEEC patients compared to healthy references in 4/4 studies. Impaired physical or general health in BEEC patients has been described in 9 articles, diminished mental health in 11, restricted social health in 10, and sexual health/functioning or body perception impairments in 13 articles. Urinary incontinence was the most common factor related to worse HRQOL (12 studies). In six studies, HRQOL was better than healthy norms. In eligible studies (n = 5), the pooled estimate of the effect of BEEC indicated worse HRQOL for children and adults (0 > effect sizes < 0.5). Thirty-six HRQOL assessments were used, none developed and validated for BEEC. CONCLUSIONS: HRQOL in BEEC patients may be negatively impacted, particularly considering mental and social HRQOL. Sexual health/functioning or body perception impairments may be present in adolescents and adults. However, HRQOL is heterogeneously assessed and subsequent findings are differently reported. Additional research is warranted and can be improved.

Psychiatric symptoms in men with hypospadias - preliminary results of a cross-sectional cohort study.

AIM: Population studies have shown an increased risk of neurodevelopmental disorders in males born with the congenital condition hypospadias, where the opening of the urethra is on the underside of the penis. We investigated overall psychiatric morbidity in cases and matched controls. METHODS: This study compared 167 men born with hypospadias from 1959 to 1994 in Stockholm or Gothenburg in Sweden using hospital registers. They were compared with controls from the Swedish population registry, who were contacted by regular mail and students who were recruited by local advertisements. The total sample had a mean age of 33.5 years (range: 19-54). They completed self-rating scales for depressive, anxiety and obsessive-compulsive symptoms and symptoms of attention deficit hyperactivity disorder. In addition, 33 cases and 47 controls underwent psychiatric morbidity interviews that covered the 17 most common psychiatric diagnoses. RESULTS: A fifth (21%) of both the cases and controls reported current or previous psychiatric symptoms. There were no significant differences in self-rated depression, anxiety or obsessive-compulsive disorder symptoms between the patients and controls or between the different phenotype groups. The distribution was not significantly affected by the severity of hypospadias. CONCLUSION: Psychiatric morbidity was no higher in men with hypospadias than population-based controls.

Psychosocial and Sexual Outcomes in Adolescents following Surgery for Proximal Hypospadias in Childhood.

PURPOSE: We evaluated psychosocial outcomes, psychosexual development and sexual function in adolescents who had undergone surgery for proximal hypospadias. We hypothesized that these outcomes would be impaired compared to peers. MATERIALS AND METHODS: We identified 55 males age 14 years or older who underwent surgery for penoscrotal to perineal (intraoperatively defined) hypospadias between 1996 and 2005. A total of 33 patients with a median age of 17.5 years (range 14 to 25) answered a Web based questionnaire with self-constructed questions, completed the validated Psychological General Well-Being Index, Body-Esteem Scale for Adolescents and Adults and Penile Perception Score, and underwent clinical evaluation. A total of 31 patients with distal hypospadias (median age 19 years, range 14 to 35) and 25 age matched healthy men (17.5 years, range 14 to 25) served as controls. RESULTS: Interest in sex, age at sexarche and satisfaction with sexual experiences were comparable between patients and controls. Three patients with proximal hypospadias (10%) and 1 control (4%) reported occasional erectile problems. Three patients with proximal hypospadias (11%), 1 patient with distal hypospadias (3%) and 1 control (4%) affirmed anejaculation. There were no differences in results between validated questionnaires. Patients with proximal hypospadias were more dissatisfied with penile length (39%) compared to controls (12%, p = 0.049). Concerning physical contact, 10 patients (38%) expressed uncertainty. Extra support in school was more frequent among patients with proximal hypospadias (p = 0.024 vs distal hypospadias, p = 0.068 vs control group). CONCLUSIONS: Despite concerns regarding penile length, sexual experiences were comparable to those of other adolescents, although more than a third of patients with proximal hypospadias demonstrated uncertainty on questions relating to desire for physical contact. Specialized tutoring in school was more common in patients with proximal hypospadias. Continuous followup throughout childhood allowing extra time for age adequate information and support is warranted.

WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish.

Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1:30,000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT-pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild-type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G>A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT-pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC.

Normalized Urinary Flow at Puberty after Tubularized Incised Plate Urethroplasty for Hypospadias in Childhood.

PURPOSE: An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood. MATERIALS AND METHODS: A total of 126 boys underwent tubularized incised plate urethroplasty for distal penile to mid shaft hypospadias at Queen Silvia Children's Hospital in Gothenburg between 1999 and 2003. Of the patients 48 were toilet trained at surgery. We report on 40 patients who had data available at 2 and 12 months postoperatively, 7 years postoperatively and at puberty (median age 15.0 years, range 13.7 to 17.1). Of the patients 31 had distal and 9 had mid penile hypospadias. Clinical examination, urinary medical history, uroflowmetry and ultrasound measuring residual urine were performed. Maximum urinary flow was correlated to age and voided volume, using Miskolc nomograms for comparison of percentiles. RESULTS: At 1 year postoperatively 15 boys (37.5%) had normal urinary flow (above 25th percentile), compared to 16 (40%) at 7 years and 38 (95%) at puberty (p <0.0001). Improvement was significant in patients with distal (p <0.0001) and mid penile hypospadias (p = 0.008), as well as in patients who did (p = 0.0078) and did not undergo intervention (p <0.0001). During followup 5 patients underwent meatotomy due to obstructive symptoms and 4 underwent dilation. Three of these 9 patients had lichen sclerosus. CONCLUSIONS: There is great potential for normalization of urinary flow at puberty for boys with hypospadias treated with tubularized incised plate urethroplasty. Unless symptoms occur, a conservative approach seems preferable.

Long-term followup of men born with hypospadias: urological and cosmetic results.

PURPOSE: We present data on long-term functional and cosmetic results after hypospadias surgery. MATERIALS AND METHODS: Males older than 18 years with hypospadias treated in Sweden were asked to participate in the study, as well as age matched controls and circumcised men. All participants answered questionnaires, and a subgroup was examined during an outpatient visit. Relationships with outcome were analyzed using analysis of variance and regression analysis. RESULTS: A total of 167 patients with a mean age of 34 years and 169 controls with a mean age of 33 years answered the questionnaire. Of the patients 63% had distal, 24% mid and 13% proximal hypospadias. A total of 46 patients and 49 controls presented for physical examination. Patients were significantly less satisfied with the penile cosmetic outcome regarding all parameters of the Penile Perception Score. There was a difference in penile length between patients and controls (mean 9.7 vs 11.6 cm, p <0.001). More patients than controls reported voiding dysfunction symptoms (p = 0.003). Patients had a lower maximum urinary flow rate than controls (p = 0.001). These differences were most prominent between patients with proximal hypospadias and controls. CONCLUSIONS: Men operated on for hypospadias were less satisfied with the cosmetic result than controls, and had a shorter penile length. Patients presented with more symptoms of voiding dysfunction and displayed a lower maximum urinary flow rate. Patients with proximal hypospadias were more affected than those with milder hypospadias. Our results indicate that patients with hypospadias can be subgrouped and that those with severe phenotypes should be followed more closely during childhood as well as later in adulthood.

Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region.

BACKGROUND: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. METHODS: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. RESULTS: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes. CONCLUSION: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation.

A qualitative content analysis of the experience of hypospadias care: The importance of owning your own narrative.

Objectives: There is a lack of studies on men's individual experiences of living with hypospadias. We aimed to explore the personal experiences of having hypospadias in relation to healthcare and surgery. Subjects and methods: Purposive sampling was used to include men (aged 18 and over) with hypospadias representing different phenotypes (from distal to proximal) and ages in order to maximise the variation and richness of our data. Seventeen informants, aged 20-49, were included in the study. In-depth semi-structured interviews were conducted between 2019 and 2021. Inductive qualitative content analysis was used to analyse the data. Results: We identified three categories: (1) Having surgery, which comprised the decision to operate, the experience of having surgery, and the outcomes of surgery; (2) Going to the doctor, which focused on follow-up care, re-entering care in adolescence or adulthood, and the experience of healthcare interactions; (3) Being informed, both about hypospadias in general, as well as about your specific body and medical history. There was overall a large variation in experiences. The latent theme across the data was the importance of owning your own narrative. Conclusion: The experience of men with hypospadias in healthcare is complex and varied, highlighting the difficulty of fully standardised care. Based on our results, we suggest that follow-up should be offered in adolescence, and that ways of accessing care for late onset complications be made clear. We further suggest clearer consideration for the psychological and sexual aspects of hypospadias. Consent and integrity in all aspects and all ages of hypospadias care should be adapted to the maturity of the individual. Access to trustworthy information is key, both directly from educated healthcare staff and if possible, from websites or patient-led forums. Healthcare can play a key role in providing the growing individual with tools to understand and address concerns that may develop relating to their hypospadias through life, giving them ownership over their own narrative.

Bowel Control, Bladder Function, and Quality of Life in Children with Cloacal Malformations.

INTRODUCTION: Long-term outcomes of cloacal malformations remain unclear. We evaluated postoperative bowel control, bladder function and quality of life in patients under 18 years of age with cloaca. MATERIALS AND METHODS: This was a multi-center cross-sectional observational study accomplished by the Nordic Pediatric Surgery Research Consortium. Patients with a cloacal malformation, 4-17 years of age, were eligible. Data including patient characteristics, surgical procedures, and complications were retrieved from case records. Established questionnaires with normative control values evaluating bowel function, bladder function, and health-related quality of life (HRQoL) were sent to the patients and their caregivers. The study was approved by the participating center's Ethics Review Authorities. RESULTS: Twenty-six (67%) of 39 eligible patients with median age 9.5 (range, 4-17) years responded. Twenty-one (81%) patients had a common channel ≤3 cm. Imaging confirmed sacral anomalies in 11 patients and spinal cord abnormalities in nine. Excluding patients with stoma (n = 5), median bowel function score was 12 [7-19], and 5 patients (20%) reported a bowel function score ≥17, approaching normal bowel control level. Bowel management increased proportion of socially continent school-aged children to 52%. Six (23%) patients had a permanent urinary diversion or used clean intermittent catheterization (CIC), while majority (70%) of the remaining patients were urinary continent. The reported HRQoL was comparable to healthy Swedish children. CONCLUSION: Whilst well-preserved spontaneous bowel control was rare, a majority of patients were dry for urine without any additional procedures. Few patients experienced social problems or negative impact on HRQoL due to bladder or bowel dysfunction. LEVEL OF EVIDENCE: Level IV.

How the First Year of COVID-19 Affected Elective Pediatric Urology Patients: A Longitudinal Study Based on Waiting Lists and Surveys From 10 European Centers.

Introduction: COVID-19 impacted healthcare systems worldwide, and elective surgical activity was brought to a minimum. Although children were not primarily affected by the disease, pediatric urology was halted by clinical closedown and staff allocation. We aimed to document how these prioritizations affected waiting lists, and to investigate how European centers dealt with the challenge of these logistical and financial prioritizations. Materials and Methods: This was a 1-year prospective study, starting March 2020. Participants were surveyed at 3-month intervals about waiting lists for several common procedures as well as OR capacity and funding. Further, centers retrospectively reported on surgical and outpatient activity rates during 2019-2021. Waiting list tendencies were evaluated in relation to study baseline. Results: A marked decrease in surgical and outpatient activity was seen in the spring of 2020. Some included pediatric urology centers were able to increase their budget (15%) and staff working hours (20%) during part of the study period. Still, at the end of the study, the centers had increased the total number of patients on waiting lists with 11%, whereas the average days on waiting lists had accumulated with 73%, yielding a total of 6,102 accumulated waiting days in the study population. Centers with decreased resources had markedly negative effects on waiting lists. Conclusions: Correlations between COVID-19 derived burdening of healthcare systems and the availability of pediatric urology greatly depends on the prioritizations made at individual centers. Ongoing monitoring of these correlations is warranted to safely avoid unnecessary negative impact on the pediatric population.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Genetic Counseling for Bladder Exstrophy-Epispadias Complex.

Bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum and has profound impact on continence, sexual, and renal function. Treatment of BEEC is primarily surgical, and the main goals are safe closure of the abdominal wall, urinary continence while preserving renal function, and adequate cosmetic and functional genital reconstruction. Psychosocial and psychosexual outcomes and adequate health-related quality of life depend on long-term multidisciplinary care. The overall outcome is now considered very positive and affected individuals usually lead self-determined and independent lives with the desire to start their own families later in life. Certainty about the risk of recurrence and the provision of information about the current state of knowledge about the identified genetic causes with high penetrance will have an impact on family planning for healthy parents with an affected child and for affected individuals themselves. This review addresses this information and presents the current state of knowledge.

Role of Genetic Counseling for Patients with Hypospadias and Their Families.

Congenital malformations often have a genetic background associated with a recurrence risk and may be part of a syndrome. Therefore, for children with a congenital malformation, the parents should be offered genetic counseling, and the child should also be offered the same when they reach adulthood. Hypospadias is a common malformation in boys that arises during genital development in weeks 8 to 16. This results in an underdevelopment of the ventral aspect of the penis with a misplacement of the urethral opening somewhere along the penis, scrotum, or in the perineum and with different degrees of penile curvature. The cause can be monogenic, but generally it is regarded as a complex disorder caused by both genetic and environmental factors. Severe hypospadias and familial cases should be genetically investigated, as for other forms of disorders of sex development, according to current guidelines with sequencing of relevant genes. Hypospadias associated with another independent malformation may be part of a syndrome and should be investigated. Fortunately, boys born with milder hypospadias generally have a good outcome and thus the clinical value of finding a disease-causing mutation appears to be limited especially in light of the present cost of genetic analysis. However, all men born with hypospadias should be advised on the recurrence risk and risk for reduced fertility.

[On micropenis, diagnosis and differential diagnoses]. / Mikropenis och liknande tillstånd ­ kunskap sparar mycket oro.

The term inconspicuous penis in children covers both micropenis with a penile length less than 2.5 SD for age and other conditions with a normal length of corpora, but when the penis looks smaller due to other diagnoses. Micropenis in a newborn is a serious condition that needs immediate attention by a paediatric endocrinologist. The boy should have a continuous support until adulthood. Other conditions that resembles micropenis are for example buried or webbed penis that only affects the skin or the adherence of the skin to the penile body, so that penis looks smaller even though the corpora are of normal length. Such conditions are treated and often operated by pediatric urologists. A proper clinical examination distinguishes between these diagnoses and gives a possibility to direct the child to the proper treatment without unnecessary concern for the parents.

The Swedish reflux trial in children: II. Vesicoureteral reflux outcome.

PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection. MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle. RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years. CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

The Swedish reflux trial in children: v. Bladder dysfunction.

PURPOSE: We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grades III and IV, and related improved dilating reflux, renal damage and recurrent urinary tract infection to dysfunction. MATERIALS AND METHODS: A total of 203 children between ages 1 to less than 2 years with reflux grades III and IV were recruited into this open, randomized, controlled, multicenter study. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup. Lower urinary tract function was investigated by noninvasive methods, at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured questionnaire and post-void residual flow measurement in 161. RESULTS: At study entry 20% of patients had lower urinary tract dysfunction, characterized by high bladder capacity and increased post-void residual urine. At 2 years there was dysfunction in 34% of patients. Subdivision into groups characteristic of children after toilet training revealed that 9% had isolated overactive bladder and 24% had voiding phase dysfunction. There was a negative correlation between dysfunction at 2 years and improved dilating reflux (p = 0.002). Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years (p = 0.001). Recurrent urinary tract infections were seen in 33% of children with and in 20% without dysfunction (p = 0.084). CONCLUSIONS: After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction, mainly voiding phase problems. Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome.

The Swedish reflux trial in children: I. Study design and study population characteristics.

PURPOSE: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. MATERIALS AND METHODS: Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. RESULTS: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. CONCLUSIONS: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

Health-Related Quality of Life in Patients with the Bladder Exstrophy-Epispadias Complex and Relationship to Incontinence and Sexual Factors: A Review of the Recent Literature.

The bladder exstrophy-epispadia complex (BEEC) includes malformations with midline closing defects of the lower abdomen and external genitalia. Long-term consequences with urinary incontinence and sexual dysfunction, in spite of multiple surgical interventions, are common and expected to affect the patient's health-related quality of life (HRQOL). The extent and the predictive factors are, however, not known. New patient-reported outcome research is emerging, but valid and reliable condition-specific HRQOL are still missing. The aim of this review is to summarize and discuss the latest published reports (2015-2019) on HRQOL in patients with the BEEC and its relationship to incontinence and sexual factors.