Bladder Exstrophy-epispadias Complex Research Articles

Bladder exstrophy-epispadias complex and the role of methylenetetrahydrofolate reductase C677T polymorphism: A case control study.

Purpose:The Bladder Exstrophy-Epispadias Complex (BEEC) is the most serious form of midline abdominal malformation. The etiology of BEEC is unknown and is thought to be multifactorial. Methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T is strongly associated with other midline abnormalities such as neural tube defects. No proper case-control study existed comparing MTHFR polymorphism with BEEC. We sought to find an association with MTHFR polymorphism and patients with bladder exstrophy (BE).Materials and Methods:The design of the study was a case-control study, involving 50 children with BEEC and 50 normal healthy school children. Genetic analysis for MTHFR 677 polymorphism was carried out after DNA extraction and polymerase chain reaction amplification. Epidemiological analysis was done by using the birth defect questionnaire on parents of BEEC.Results:Forty-two classical BE, two cloacal exstrophies (CE), four epispadias, and two exstrophy variant patients were a part of this study. Severe variety of BE had a significant association with C667T MTHFR polymorphism as compared to the normal control population (P = 0.01).Conclusion:C677T MTHFR polymorphism has a strong association with severe variety (CE) of BEEC occurrence.

Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal.

Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [7–47]; median follow-up was 52 months [9–120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology.

Blasenaugmentation und -ersatz bei Kindern und Jugendlichen

In children and adolescents, the indication for continent urinary diversion or bladder augmentation is rare. Today, for most patients with a neurogenic bladder, conservative treatment (clean intermittent catheterization [CIC] and pharmacotherapy) is the method of choice, while for patients with bladder exstrophy-epispadias complex (BEEC), primary reconstruction is recommended. Only after failure of conservative treatment or primary reconstruction should bladder augmentation or urinary diversion be considered. Other rare indications include patients with malignant tumor involving the lower urinary tract (e. g., rhabdomyosarcoma). In patients with a hyperreflexive, small capacity, and/or low compliance bladder with a normal upper urinary tract, bladder augmentation (bowel segments/ureter) is an option. For those unable to perform CIC via the urethra, a continent cutaneous stoma should be offered. In patients with irreparable sphincter defects and normal renal function, a continent cutaneous diversion is an option and in those with a competent anal sphincter the rectosigmoid pouch can be offered. In this review, surgical options with their advantages and disadvantages are discussed.

Genetics of Bladder-Exstrophy-Epispadias Complex (BEEC): Systematic Elucidation of Mendelian and Multifactorial Phenotypes.

The Bladder-Exstrophy-Epispadias Complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and has a profound impact on continence, and on sexual and renal function. While previous reports of familial occurrence, in-creased recurrence among first-degree relatives, high concordance rates among monozygotic twins, and chromosomal aberra-tions were suggestive of causative genetic factors, the recent identification of copy number variations (CNVs), susceptibility regions and genes through the systematic application of array based analysis, candidate gene and genome-wide association studies (GWAS) provide strong evidence. These findings in human BEEC cohorts are underscored by the recent description of BEEC(-like) murine knock-out models. Here, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal uro-rectal development leading to the BEEC, demonstrating the importance of ISL1-pathway in human and mouse and propose SLC20A1 and CELSR3 as the first BEEC candidate genes, identified through systematic whole-exome sequencing (WES) in BEEC patients.

Bladder exstrophy-epispadias complex with adenocarcinoma in an adult patient: A case report.

The present case report presents the case of exstrophy-epispadias complex (EEC) with the widest separation of the symphysis pubis to date. A 33-year-old male was referred to hospital with previously unreconstructed EEC malformation. The diagnosis established was of EEC with separation of the symphysis pubis and left inguinal hernia with adenocarcinoma of the bladder. The patient underwent radical cystectomy plus an ileal conduit and an expanded local lymphadenectomy. Osteotomy was not performed, and instead the defect of the pelvis and abdominal wall was repaired using meshes and a lower abdominal island skin flap. At 1 year after surgery the patient recovered well, with no indications of mesh distortion or major complications.

Prospective study on the incidence of bladder/cloacal exstrophy and epispadias in Europe

On behalf of the European Society of Paediatric Urology (ESPU), a prospective study was designed with the aim of defining the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month period, and verifying the distribution of the exstrophy patients born during the study period among the different paediatric urology centres in Europe. The study was structured with a chief investigator and one national investigator for each country enrolled in the study. The national investigators nominated one local investigator for each European centre of paediatric surgery/paediatric urology and urology where the exstrophy complex could potentially be treated. The local investigators were responsible for reporting babies treated in their institutions for bladder/cloacal exstrophy and/or epispadias. During 2010, every 3 months, an electronic survey (Figure) was e-mailed to the local investigators asking them to report babies treated or referred for treatment during the previous 3 months. One-hundred and sixteen centres in 27 European counties were enrolled in the study. The overall response rate for the four online surveys was 79%. Two-hundred and thirty-eight babies were reported to be born with a condition within the bladder exstrophy epispadias complex (BEEC): 71 primary epispadias (66 males), 146 classic bladder exstrophy (97 males) of which two were female bladder exstrophy variant, and 21 cloacal exstrophy (17 males). Two of 67 (3%) male epispadias, 24/146 (16.4%) bladder exstrophy, and 6/21 (28%) cloacal exstrophy were antenatally diagnosed. Associated anomalies were reported in 2/71 (2.8%) epispadias patients, 8/146 (5.5%) bladder exstrophy patients, and 15/21 (71.4%) cloacal exstrophy patients. One-hundred and forty-seven (62%) of the 238 babies born in Europe with a condition within the exstrophy spectrum during 2010 were transferred from other institutions for treatment (36 male epispadias, 97 bladder exstrophy, and 14 cloacal exstrophy). Only 12 centres treated six or more exstrophy and or epispadias patients during the study period; 52 treated between one and five patients, of which 22 treated only one case in 12 months. This study provides a contemporary incidence of the BEEC in Europe. It demonstrates also that only a minority (19%) of the European centres involved in the treatment of exstrophy can be considered "high volume" exstrophy centres. There is a case for proposing a rationalisation of the treatment of this group of conditions in a small number of exstrophy units around Europe.

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.

Sexual function in adult patients with classic bladder exstrophy: A multicenter study

The bladder exstrophy-epispadias complex (BEEC) comprises a spectrum of congenital anomalies that represents the severe end of urorectal malformations, and has a profound impact on continence as well as sexual and renal functions. The relation between severity of BEEC and its associated functional impairments, on one hand, and the resulting restrictions in quality of life and potential psychopathology determine the patients' outcome. It is important for improving further outcome to identify BEEC-related sources of distress in the long term. Genital function and sexuality becomes an important issue for adolescent and adult BEEC individuals. Hence, the present study focused on sexual function and psychological adaption in patients with BEEC. In a multicenter study 52 patients (13 females, 39 males) with classic bladder exstrophy (BE) with their bladders in use were assessed by a self-developed questionnaire about sexual function, and psychosexual and psychosocial outcome. The patients were born between 1948 and 1994 (median age 31 years). Twelve of 13 (92%) females and 25 of 39 (64%) males with classic BE had answered the questions on sexual function. Of these, 50% females and 92% males answered that they masturbated. Females had sexual intercourse more frequently. Six (50%) females affirmed dyspareunia whereas only two (8%) males reported pain during erection. Eight (67%) females specified having orgasms. Eighteen (72%) males were able to ejaculate. Two males and none of the females lived in a committed partnership (Figure). Two (15%) females and 13 (33%) males answered all psychosocial questions. The majority of these patients had concerns about satisfactory sexuality and lasting, happy partnerships. A minority of patients of both sexes were willing to answer psychosocial questions. Sexual activity and relationships of many adult BE patients seems to be impaired. Not surprisingly, sexual activity and awareness were different in males and females even in a multi-organ anomaly. To date, one of the main goals of the medical treatment of BEEC/BE patients is to enable normal sexual life and fertility. However, only a few outcome studies have focused on these issues with contradicting results, most of them not using standardized outcome measures. In accordance with other studies, our female BE patients have dyspareunia and most of our male BE patients were able to ejaculate. But the question of normal force of ejaculation, ejaculated volume, or semen analysis remains unanswered. Despite partial confirmation of previous findings, there is inconsistency referring to the outcome measured by the available studies. This might in part be explained by the fact that, other than this study, most previous studies are the result of single-institution experience. Thus, selection bias in the patient sampling due to different a clinical collective in different hospitals may be the consequence. Furthermore, patients' honesty and self-reflection in answering difficult questions regarding their sexual and cosmetic impairments is questionable. In addition, studies include a wide range of age groups and are connected with this life period. Fears and condition-specific anxieties might change over time. Hence, the strengths of this study are the nationwide and treating physician-independent data acquisition as well as the large sample size of adult patients with a very rare congenital malformation. Unfortunately, more detailed analyses on sexual function and current psychosocial situation, for example correlation of data with clinical symptoms such as continence status, was not possible as data were mainly not answered by patients. To improve the quality of life of patients with BEEC/BE, treatment and follow-up should emphasize physical but also psychological care in these patients. Physicians should further re-evaluate their preconceptions and should take care of the patients throughout their lives.

Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.

Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.

Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P = 8.88 × 10(-5); follow-up: P = 0.0025; combined: 1.09 × 10(-6)) in a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the genital region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P = 0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify association of common variation with CBE.

Sub-urothelial polyp enucleation resection and urothelial auto-augmentation cystoplasty: a simple method for bladder exstrophy-epispadias complex reconstruction in bladder plate polyposis.

To report the results of a novel technique of sub-urothelial polyp enucleation resection (SUPER) and urothelial auto-augmentation cystoplasty (UAAC) in patients with bladder exstrophy and polyposis plate. Twenty-eight patients with bladder exstrophy covered by plate polyposis were referred for further management. From these, 12 patients had undergone SUPER, UAAC technique, and subsequent bladder closure. In this technique, the urothelium covering the polyps was utilized as tissue for auto-augmentation cystoplasty. Sixteen patients had been operated by simple polyps' excision and bladder closure. Biopsies of polyps were obtained in both groups at the time of closure for pathological evaluations. The bladder plate was measured pre-and post-bladder plate augmentation. The patients were evaluated every 3 months for 1 year and biannually thereafter for urinary continence and social dryness. Dry period of >3 h during the day with or without nocturnal incontinence was defined as social dryness. All patients experienced an uneventful postoperative period. No sign of metaplasia or dysplasia was observed in the histological and cystoscopy evaluations. These findings suggest that neither polyp recurrence nor bladder tumor development has occurred in any of the groups. The urinary continence improved significantly in the polyp's urothelial coverage augmentation cystoplasty technique (66.7%), while 31.3% of patients in simple closure technique achieved continence. Significantly higher mean bladder capacity was obtained in the augmentation group (190 ± 38 ml) and (119 ± 21 ml), respectively. Postoperative mild hydronephrosis and vesicoureteral reflux were significantly lower in auto-augmentation technique. The final clinical outcome of children with bladder exstrophy polyposis is promising. The combined SUPER and UAAC technique is feasible, safe and reproducible option for bladder exstrophy-epispadias complex (BEEC) patients with bladder plate polyposis. However, it will add one supplementary operation to the single or staged bladder reconstruction. These patients may warrant further surveillance with histopathological evaluations during the adult life.

Autologous Muscle Derived Cells for Treatment of Stress Urinary Incontinence in Women

We assess the 12-month safety and potential efficacy of autologous muscle derived cells for urinary sphincter repair (Cook MyoSite Incorporated, Pittsburgh, Pennsylvania) in women with stress urinary incontinence. Pooled data from 2 phase I/II studies with identical patient selection criteria and outcome measures were analyzed. Enrolled patients had stress urinary incontinence refractory to prior treatment and no symptom improvement during the last 6 months. Patients received intrasphincter injection of 10 (16), 50 (16), 100 (24) or 200×10(6) (24) autologous muscle derived cells for urinary sphincter repair, derived from biopsies of each patient's quadriceps femoris. The primary outcome measure was safety, determined by incidence and severity of adverse events. Potential efficacy was measured by changes in 3-day voiding diaries, 24-hour pad tests, and UDI-6 and IIQ-7 scores. A total of 80 patients underwent injection of autologous muscle derived cells for urinary sphincter repair, and 72 completed diaries and pad tests at 12-month followup. No adverse events attributed to autologous muscle derived cells for urinary sphincter repair were reported. Higher dose groups tended to have greater percentages of patients with at least a 50% reduction in stress leaks and pad weight at 12-month followup. All dose groups had statistically significant improvement in UDI-6 and IIQ-7 scores at 12-month followup compared to baseline. Autologous muscle derived cells for urinary sphincter repair at doses of 10, 50, 100 and 200×10(6) cells appears safe. Efficacy data suggest a potential dose response with a greater percentage of patients responsive to higher doses.

No TAP63 promoter mutation is detected in bladder exstrophy–epispadias complex patients

Background/PurposeBladder exstrophy–epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63−/− mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic ΔNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the ΔNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients. Methodsi) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data. Resultsi) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant. ConclusionOur data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only ΔNP63 promoter aberration is involved in BEEC pathogenesis.

Emotional and behavioral functioning in children with bladder exstrophy–epispadias complex: A developmental perspective

ObjectiveTo evaluate the emotional and behavioral functioning of children with bladder exstrophy–epispadias complex (BEEC), taking into account developmental and gender considerations. This study also sought to overcome methodological limitations of previous studies evaluating psychological well-being of children with BEEC. MethodsEighty-six children were consecutively evaluated using the parent report version of the Behavior Assessment System for Children during visits to a multidisciplinary urology clinic. ResultsResults indicated normative emotional and behavioral functioning across the sample. However, there was a significant effect of age, such that older children consistently had worse internalizing symptoms and adaptive functioning. Males tended to have more externalizing problems as they aged, and also tended to have lower levels of adaptive functioning but this was independent of age. The level of psychological impairment was unrelated to the specific type of BEEC, and was also unrelated to whether or not the patient had undergone continence surgery. ConclusionChildren with BEEC have a greater likelihood of experiencing a wide range of emotional and behavioral problems as they reach adolescence. These findings point to the need to prevent potential psychological distress by intervening with these children before they become clinically impaired.

Candidate gene association study implicates p63 in the etiology of nonsyndromic bladder‐exstrophy‐epispadias complex

Bladder-exstrophy-epispadias complex (BEEC) is a severe congenital anomaly that represents a spectrum of urological abnormalities where parts or all of the distal urinary tract fail to close during development. Multiple lines of evidence strongly suggested p63 as a plausible candidate gene. We conducted a candidate gene association study to further investigate the role of p63 in human BEEC. We conducted a family-based association study of p63 using 154 Caucasian patients with nonsyndromic BEEC and their unaffected parents. High throughput single nucleotide polymorphism (SNP) genotyping was carried out using Illumina's Golden Gate Assay for 109 selected tagging SNPs localized within p63 with a minor allele frequency > 0.01. Individual and haplotype SNP transmission disequilibrium tests were conducted using Plink and Haploview, respectively. We also examined parent-of-origin effects using paternal asymmetry tests implemented in FAMHAP (http://famhap.meb.uni-bonn.de/index.html). Nominally significant associations were identified between BEEC and six SNPs (rs17447782, rs1913720, rs6790167, rs9865857, rs1543969, rs4687100), and four haplotype blocks including or near these significant SNPs. Analysis of parent-of-origin effects showed significant results for seven SNPs (rs4118375, rs12696596, rs6779677, rs13091309, rs7642420, rs1913721, and rs1399774). None of these results remained significant after multiple testing correction. The altered transmission of p63 variants in nonsyndromic BEEC patients may be suggestive of its involvement in the disease etiology. Further and large multi-institutional collaborative studies are required to elucidate the role of p63 in nonsyndromic BEEC.

English

Bladder exstrophy-epispadias complex is a rare congenital anomaly. A higher occurrence in males compared to females is observed. It occurs due to failure of the abdominal wall closure during fetal development and results in protrusion of the posterior bladder wall through the lower abdominal wall. It involves a spectrum of anomalies of the lower abdominal wall, bladder, anterior bony pelvis and external genitalia. Here, we report a case of antenatal diagnosis of bladder exostrophy –epispadias complex in a seven months pregnant patient who came to us for routine antenatal sonography. On fetal MRI, our findings were confirmed. Patient was followed and normal vaginal delivery was done.

CNV Analysis in Monozygotic Twin Pairs Discordant for Urorectal Malformations

Early post-twinning mutational events can account for discordant phenotypes in monozygotic (MZ) twin pairs. Such mutational events may comprise genomic alterations of different sizes, ranging from single nucleotides to large copy-number variations (CNVs). Anorectal malformations (ARM) and the bladder exstrophy-epispadias complex (BEEC) represent the most severe end of the urorectal malformation spectrum. Recently, CNV studies in patients with sporadic ARM and the BEEC have identified de novo events that occur in specific chromosomal regions. We hypothesized that early arising, post-twinning CNVs might contribute to discordance in MZ twin pairs with ARM or the BEEC; knowledge of such CNVs might help to identify additional chromosomal regions involved in the development of these malformations. We investigated four discordant MZ twin pairs (three ARM and one BEEC) using molecular karyotyping arrays comprising 1,140,419 markers with a median marker spacing of 1.5 kb. Filtering the coding regions for possible disease-causing post-twinning de novo CNVs present only in the affected twin, but not in the unaffected twin or the parents, identified a total of 136 CNVs. These 136 CNVs were then filtered against publicly available databases and finally re-evaluated visually. No potentially causative CNV remained after applying these filter criteria. Our results suggest that post-twinning CNV events that affect coding regions of the genome did not contribute to the discordant phenotypes in MZ twin pairs that we investigated. Possible causes for the discordant phenotypes include changes in regulatory elements or smaller genetic changes within coding regions which may be detectable by whole-exome sequencing.

National Trends in Augmentation Cystoplasty in the 2000s and Factors Associated with Patient Outcomes

Augmentation cystoplasty is a major surgery performed by pediatric urologists. We evaluated national estimates of children undergoing augmentation cystoplasty in the United States for trends during the 2000s, and analyzed patient and hospital factors associated with outcomes. Patients who underwent augmentation cystoplasty registered in the 2000 to 2009 Kids' Inpatient Database were included. Estimates of total number of augmentation cystoplasties performed and patient and hospital characteristics were evaluated for trends. Hierarchical models were created to evaluate patient and hospital factors associated with length of stay, total hospital charges and odds of having a postoperative complication. An estimated 792 augmentation cystoplasties were performed in 2000, which decreased to 595 in 2009 (p = 0.02). Length of stay decreased from 10.5 days in 2000 to 9.2 days in 2009 (p = 0.04). A total of 1,622 augmentation cystoplasties were included in the hierarchical models and 30% of patients had a complication identified. Patient factors associated with increased length of stay and increased odds of any complication included bladder exstrophy-epispadias complex diagnosis and older age. Pediatric hospitals had 31% greater total hospital charges (95% CI 7-55). The estimated number of augmentation cystoplasties performed in children in the United States decreased by 25% in the 2000s, and mean length of stay decreased by 1 day. The cause of the decrease is multifactorial but could represent changing practice patterns in the United States. Of the patients 30% had a potential complication during hospitalization after augmentation cystoplasty. Older age and bladder exstrophy-epispadias complex diagnosis were associated with greater length of stay and increased odds of having any complication.

Term Newborn with Abdominal Wall Defect, Ambiguous Genitalia, and Respiratory Distress

Term newborn boy presents with abdominal wall defect, ambiguous genitalia, and respiratory distress (Fig 1). Figure 1. ### Prenatal History ### Birth History and Presentation ### Vital Signs ### Physical Examination ### Radiologic Findings Abdominal radiograph reveals widened symphysis pubis measuring 4.2 cm (normal: less than 1 cm) (Fig 2). Figure 2. ### Bladder Exstrophy Epispadias Complex (BEEC) Bladder exstrophy, or vesica ectopia, is a congenital malformation resulting in an everted bladder wall that is contiguous …

Lower urinary tract development and disease.

Congenital anomalies of the lower urinary tract (CALUT) are a family of birth defects of the ureter, the bladder, and the urethra. CALUT includes ureteral anomaliesc such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUVs). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease, and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, the bladder, and the urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, the bladder and the urethra and associated gene mutations are also presented. As we are entering the postgenomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families.