Prevalence of high-risk bladder categorization with prenatal and postnatal myelomeningocele repair types.

INTRODUCTION: Urologic substudies of prenatal myelomeningocele (MMC) closure have focused primarily on continence without significant clinical benefit. Fetoscopic MMC repair (FMR) is a newer form of prenatal intervention and touts added benefits to the mother, but urological outcomes have yet to be analyzed. We set out to focus on bladder safety rather than continence and examined bladder outcomes with different prenatal MMC repairs (FMR and prenatal open [POMR]) and compared bladder-risk-categorization to traditional postnatal repair (PSTNR). METHODS: An IRB-approved retrospective analysis of all patients undergoing all forms of MMC repairs with inclusion and exclusion criteria based on the MOMS trial was performed. Bladder safety assessment required initial urodynamic studies (UDS), renal bladder ultrasound (RBUS), and/or voiding cystourethrogram (VCUG) within the 1st year of life. Follow-up analyses within the cohorts required follow-up studies within 18 months after initial evaluations. Outcomes assessed included bladder-risk-categorization based on the CDC UMPIRE study (high, intermediate, and safe), hydronephrosis (HN), and vesicoureteral reflux (VUR). A single reader evaluated each UDS. RESULTS: Initial UDS in 93 patients showed that the prevalence of high-risk bladders were 35% FMR versus 36% PSTNR and 60% POMR. Follow-up UDS showed only 8% of FMR were high-risk compared to 35% POMR and 36% PSTNR. Change from initial to follow-up bladder-risk-category did not reach significance (p = .0659); however, 10% PSTNR worsened to high-risk on follow-up, compared to none in either prenatal group. Subanalysis of follow-up UDS between the prenatal cohorts also was not significant (p = .055). Only 8% of FMR worsened or stayed high-risk compared to 35% with POMR (p = .1). HN was significantly different at initial and subsequent follow up between the groups with the least in the FMR group. CONCLUSIONS: Early outcome UDS analyses demonstrated lower incidence of high-risk bladders in FMR patients with a trend toward clinically significant improvement compared to POMR in regard to all evaluated metrics. Larger, prospective, confirmatory studies are needed to further evaluate the potential benefits on FMR on bladder safety and health.

Congenital Bladder Prolapse Through a Patent Urachus: Two Institutions' Experience.

We describe our experience in 2 institutions handling bladder prolapse through a patent urachus (PU), together with a brief review of published literature. Case 1: A term neonate with congenital prolapsed bladder via PU. Ultrasound at 21 weeks gestation revealed a male fetus with a large midline pelvic cyst communicating with the bladder which disappeared on subsequent 27 weeks ultrasound. Case 2: A term female neonate with congenital prolapsed bladder via PU with no prenatal diagnosis. In both cases the bladder closure was undertaken during the newborns' first days of life.

Identification of key microRNAs, transcription factors and genes associated with congenital obstructive nephropathy in a mouse model of megabladder.

OBJECTIVE: The present study aimed to investigate the molecular mechanism underlying congenital obstructive nephropathy (CON). METHODS: The microarray dataset GSE70879 was downloaded from the Gene Expression Omnibus, including 3 kidney samples of megabladder mice and 4 control kidneys. Using this dataset, differentially expressed miRNAs (DEMs) were identified between the kidney samples from megabladder mice and controls, followed by identification of the target genes for these DEMs and construction of a DEM and target gene interaction network. Additionally, the target genes were subjected to Gene Ontology and pathway enrichment analyses, and were used for construction of a protein-protein interaction (PPI) network. Finally, regulatory networks were constructed to analyze transcription factors for the key miRNAs. RESULTS: From 17 DEMs identified between kidney samples of megabladder mice and controls, 3 key miRNAs were screened, including mmu-miR-150-5p, mmu-miR-374b-5p and mmu-miR-126a-5p. The regulatory networks identified vascular endothelial growth factor A (Vegfa) as the common target gene of mmu-miR-150-5p and five transcription factors, including nuclear receptor subfamily 4, group A, member 2 (Nr4a2), Jun dimerisation protein 2 (Jdp2), Kruppel-like factor 6 (Klf6), Neurexophilin-3 (Nxph3) and RNA binding motif protein 17 (Rbm17). The gene encoding phosphatase and tensin homolog (Pten) was found to be co-regulated by mmu-miR-374b-5p and high mobility group protein A1 (Hmga1), whereas the kirsten rat sarcoma viral oncogene (Kras) was identified as a common target gene of mmu-miR-126a-5p and paired box 6 (Pax6). CONCLUSIONS: In summary, the above-listed key miRNAs, transcription factors and key genes may be involved in the development of CON.

Bladder augmentation in anuric/defunctioned microbladders and a novel antireflux mechanism for Mitrofanoff anastomosis to the ileal patch.

BACKGROUND/PURPOSE: Reconstruction of microbladders is a difficult surgical challenge: How can a neobladder be recreated when >90% of the new bladder is augmented patch, and how can a Mitrofanoff conduit be anastomosed when the native bladder is so tiny? This series describes microbladders secondary to anuria and/or diversion that required augmentation. This was done using a de-tubularized ileal segment, and because of the small size of the native bladder, Mitrofanoff anastomosis was performed to the bowel patch (using a novel "Keel Procedure"). METHODS: Our surgical experience in reconstruction of microbladders was reviewed: pre and post augmentation capacity, compliance and maximum detrusor pressure were compared. The success of the Mitrofanoff anti-reflux technique is described. Data are given as median (interquartile range) and compared by Wilcoxon paired rank test. RESULTS: 10 patients, median bladder capacity pre-op 10 (9-20) mls were reconstructed. The follow up time is 2.7years (2.2-4.2). Post-op bladder capacity increased 16-fold to 167 (114-281) mls, P<0.01. Compliance significantly improved from 1.7 (0.3-4.8) to 14.3 (4.1-66.3) mls/cmH2O, P<0.05. Maximum detrusor over-activity decreased from 27 (7-120) to 12.5 (8-26) cmH2O, (N.S. P=0.3). Videourodynamics confirmed a leak in 2 patients, leading to incorporation into the technique of a non-absorbable seromuscular suture to provide long-term robustness to the antireflux procedure. CONCLUSION: Bladder augmentation in microbladders is possible, and a functional Mitrofanoff procedure with a continent anti-reflux procedure can be created using the "Birmingham keel technique" implanting the Mitrofanoff into the augment patch, with 80% success (similar to published results for conventional anastomosis to native bladders). LEVEL OF EVIDENCE: Level IV.

Bladder agenesis, ectopic ureters and a multicystic dysplastic horseshoe kidney in one twin newborn with normal amniotic fluid index in utero.

A monochorionic-diamniotic twin baby presented with intrauterine growth restriction and anuria. The baby was found to have bladder agenesis, a pelvic dysplastic horseshoe kidney, vertebral anomalies, a ventricular septal defect and facial dysmorphisms. It was surprising to find no abnormalities in amniotic fluid indices prenatally, suggesting the possibility of urine output that declined as the pregnancy proceeded. Some degree of twin-to-twin transfusion of amniotic fluid was also possible, which could have rescued the oligohydramnios known to be associated with kidney and urinary tract abnormalities. It was also notable that there was no abnormality in respiratory function, especially since further investigations revealed close to no kidney function. The intrauterine growth restriction (IUGR) along with the multiple anomalies found made the baby unsuitable for dialysis and transplant, and the decision of transition to palliative care was made.

[Acute retention of urine secondary to a congenital diverticulum of the bladder]. / Rétention aiguë d'urine secondaire à un diverticule congénital bilatéral de la vessie.

Bladder diverticula in children are mostly congenital, frequently associated with vesicoureteral reflux. Their positive diagnosis is based primarily on retrograde urethrocystography. One complication of this condition is acute urinary retention. We report the case of a 4-month-old infant who presented acute retention of urine secondary to bilateral congenital bladder diverticulum and review the literature on this subject.

From gene discovery to new biological mechanisms: heparanases and congenital urinary bladder disease.

We present a scientific investigation into the pathogenesis of a urinary bladder disease. The disease in question is called urofacial syndrome (UFS), a congenital condition inherited in an autosomal recessive manner. UFS features incomplete urinary bladder emptying and vesicoureteric reflux, with a high risk of recurrent urosepsis and end-stage renal disease. The story starts from a human genomic perspective, then proceeds through experiments that seek to determine the roles of the implicated molecules in embryonic frogs and newborn mice. A future aim would be to use such biological knowledge to intelligently choose novel therapies for UFS. We focus on heparanase proteins and the peripheral nervous system, molecules and tissues that appear to be key players in the pathogenesis of UFS and therefore must also be critical for functional differentiation of healthy bladders. These considerations allow the envisioning of novel biological treatments, although the potential difficulties of targeting the developing bladder in vivo should not be underestimated.

HPSE2 mutations in urofacial syndrome, non-neurogenic neurogenic bladder and lower urinary tract dysfunction.

BACKGROUND: Urofacial syndrome (UFS) is characterised by congenital bladder dysfunction accompanied by a characteristic abnormal grimace upon smiling and crying. In recent years, biallelic mutations of HPSE2 and LRIG2 have been reported in UFS patients. Non-neurogenic neurogenic bladder (NNNB) has a bladder identical to UFS without typical facial features. The aim of this study was to analyse HPSE2 mutations in patients with UFS and NNNB or severe lower urinary tract dysfunction (LUTD) without abnormal facial expression. METHODS: Patients with UFS, NNNB and severe LUTD were enrolled in the study. We examined a total of 35 patients from 33 families. There were seven UFS patients from five different families, 21 patients with NNNB and seven with LUTD. HPSE2 gene mutation analysis was performed using the polymerase chain reaction protocol followed by Sanger sequencing in these patients. RESULTS: A twin pair with UFS was found to be homozygous for c.457C>T (p.Arg153*) mutation. No other pathogenetic variant was detected. CONCLUSION: HPSE2 mutations were found in one UFS family but not detected in patients with NNNB and severe LUTD. Considering the increasingly recognised cases of NNNB that were diagnosed in early childhood period, genetic factors appear to be responsible. Thus, further genetic studies are needed to discover novel associated gene variants in these bladder anomalies.

Her belly button is leaking: a case of patent urachus.

Patent urachus is one of the least commonly seen of the urachal anomalies. In this report, we present a case of a patent urachus in a15-day-old female who presented with leakage from the umbilical site. The purpose of this article is to discuss the embryology, clinical manifestations, diagnosis, and management of patent urachus.

[Lazy bladder syndrome: review of 126 cases]. / Mégavessie congénitale: analyse clinique et urodynamique de 126 cas.

PURPOSE: The lazy bladder syndrome (LBS) is characterized by an infrequent voiding, a large bladder capacity without neurological or urological disorders. In spite of being relatively common, there is little literature about it. The aim of our study was to compare the clinical features and urodynamic findings in asymptomatic or symptomatic patients with lazy bladder syndrome. PATIENTS AND METHODS: We reviewed the charts of 126 adult patients diagnosed with lazy bladder syndrome. Clinical and radiological features, urodynamic findings and therapeutic management were evaluated. With these data, we divided patients into 2 groups: asymptomatic and symptomatic patients. After, we performed a comparative analysis of the data. RESULTS: The incident of LBS was significantly higher in women (81%). Twenty-one patients were asymptomatic (17%), 105 patients were symptomatic (83%). The patients with symptomatic LBS were significantly older (54.3 years ± 14.7). Voiding dysfunction (53%) and urinary retention (27%) were the most common symptoms in symptomatic group. In the uroflowmetry test, maximum and mean uroflow were significantly higher in asymptomatic group (P=0.0074). Reduced bladder sensation revealed no difference in the 2 groups, but in the symptomatic group, detrusor has also a poor contractility (P=0.0001). Nineteen patients (18%) had uro-nephrological complications. CONCLUSION: LBS is certainly underestimated. Voiding dysfunction, urinary retention in infrequent voiders or uro-nephrological complication (urinary tract infection with fever, ureteral reflux…) should recall LBS diagnosis. The hypothesis of bladder structural failure or autonomic nervous system dysfunction may be discussed (suggested). LEVEL OF EVIDENCE: 5.

Genetics of human congenital urinary bladder disease.

Lower urinary tract and/or kidney malformations are collectively the most common cause of end-stage renal disease in children, and they are also likely to account for a major subset of young adults requiring renal replacement therapy. Advances have been made regarding the discovery of the genetic causes of human kidney malformations. Indeed, testing for mutations of key nephrogenesis genes is now feasible for patients seen in nephrology clinics. Unfortunately, less is known about defined genetic bases of human lower urinary tract anomalies. The focus of this review is the genetic bases of congenital structural and functional disorders of the urinary bladder. Three are highlighted. First, prune belly syndrome, where mutations of CHRM3, encoding an acetylcholine receptor, HNF1B, encoding a transcription factor, and ACTA2, encoding a cytoskeletal protein, have been reported. Second, the urofacial syndrome, where mutations of LRIG2 and HPSE2, encoding proteins localised in nerves invading the fetal bladder, have been defined. Finally, we review emerging evidence that bladder exstrophy may have genetic bases, including variants in the TP63 promoter. These genetic discoveries provide a new perspective on a group of otherwise poorly understood diseases.

The diagnostic value of MRI fistulogram and MRI distal colostogram in patients with anorectal malformations.

Contrast fistulogram (FG) and distal pressure colostogram (DPCG) are standard diagnostic methods for the assessment of anorectal malformations. Pelvic magnetic resonance imaging (MRI) earned a place among essential diagnostic methods in preoperative investigations after the Currarino syndrome and a high incidence of associated spinal dysraphism were described. The aim of our study was to evaluate the possibility of substituting FG and DPCG by a modified pelvic MRI, e.g. MRI fistulogram (MRI-FG) and MRI colostogram (MRI-DPCG). The prospective study involved 29 patients with anorectal malformations who underwent a modified pelvic MRI. The length and course of fistulas and rectum, and the presence of sacral anomalies were studied on MRI images and compared with images obtained by radiologic examinations. Modified MRI brought identical results as contrast studies in 25 patients when related to the fistula and rectum length and course. MRI was more accurate for the detection of sacral anomalies. MRI-FG was the only imaging method used in the four most recent patients. The results support the assumption that conventional contrast examinations for the assessment of anorectal malformations can be replaced by MRI, thus reducing the radiation dose.

Hutch bladder diverticula: a very uncommon entity in adults.

OBJECTIVE: We present the case of an adult patient diagnosed with Hutch diverticula after examination. Indications were of a type of congenital bladder diverticula very rare in children and unusual in adults, as very few cases in adults are addressed in the literature. METHODS: Intravenous Urography and Voiding Cystourethrogram (VCUG) were realized RESULTS: The intravenous urography revealed ureterohydronephrosis in the excretory phase that did not have repletion defects suggesting lithiasis at distal urethra. On the other hand, a narrowing of the urethra was observed at the point of bladder entry due to the presence of a juxtameatal bladder diverticulum. Next a retrograde cystography was performed which ruled out vesicourethral reflux and revealed that the diverticulum presented elevated residuals after urination. As a result of our patient's clinical characteristics and the absence of vesico-urethral reflux, we decided to perform an endoscopic surgical opening of the diverticula's neck. CONCLUSIONS Hutch paraurethral diverticula is an very uncommon entity, even in infancy. The Voiding Cystourethrogram (VCUG) is especially useful in diagnosing these patients. In symptomatic cases surgical correction of the diverticula is required.

Congenital bladder diverticulum causing acute urinary retention in an infant.

Congenital bladder diverticula (CBD) are unusual but not rare in childhood. Report of acute urinary retention due to congenital bladder diverticula are rarely found in the literature. Here we report a case of congenital bladder diverticulum with acute urinary retention in a ten months old male infant. Urinary tract infection and urinary retention are the most frequent presentation forms. In this case CBD produce urinary obstruction as a result of compression of the urethra which causes urinary retention. Voiding cystourethrogram revealed a large bladder diverticulum. Bladder diverticulum should be a differential diagnosis in male children, presenting with urinary retention, fever and an abdominal mass. Ultrasonography, voiding cystourethrogram & cystoscopy confirm the diagnosis and diverticulectomy was successfully done for the child.

Adult care of children from pediatric urology.

PURPOSE: In this article we highlight the difference, from established adult urology, in required approach to the care of adolescents and young adults presenting with the long-term consequences of the major congenital anomalies of the genitourinary tract. We review some abnormalities of the kidneys, progressive renal failure and disorders of bladder function from which general conclusions can be drawn. MATERIALS AND METHODS: The published literature was reviewed and augmented with material from our institutional databases. For renal function the CAKUT (congenital abnormalities of the kidney and urinary tract) database at University College London Hospitals was used, which includes 101 young adult patients with CAKUT in whom the urinary tract has not been diverted or augmented. For bladder function some data are from patient records at Boston Children's Hospital. RESULTS: Adolescents who grow up with the burden of a major congenital anomaly have an overwhelming desire to be normal. Many achieve high levels of education and occupy a wide range of employment scenarios. Babies born with damaged kidneys will usually experience improvement in renal function in the first 3 years of life. Approximately 50% of these cases will remain stable until puberty, after which half of them will experience deterioration. Any urologist who treats such patients needs to test for proteinuria as this is a significant indicator of such deterioration. In its absence, the urologist must have a reasonable strategy for seeking a urological cause. The most effective management for nephrological renal deterioration is with angiotensin converting enzyme inhibitors, which slow but do not prevent end stage renal failure. Renal deterioration is generally slower in these patients than in those with other forms of progressive renal disease. The bladder is damaged by obstruction or by functional abnormalities such as myelomeningocele. Every effort should be made to stabilize or reconstruct the bladder in childhood. A dysfunctional bladder is associated with or causes renal damage in utero, but continued dysfunction will cause further renal damage. Bladder function often changes in puberty, especially in boys with posterior urethral valves who may experience high pressure chronic retention. Dysfunction is managed with antimuscarinic drugs, clean intermittent self-catheterization and intestinal augmentation. Adult urologists must be able to manage the long-term problems associated with these treatments. CONCLUSIONS: Pediatric conditions requiring management in adolescence are rare but have major, lifelong implications. Their management requires a broad knowledge of pediatric and adult urology, and could well be a specialty in its own right. Therefore, adult urologists must remain aware of the conditions, the problems that they may encounter and the special management required for these patients to live normal lives.

Congenital bladder diverticulum presenting as bladder outlet obstruction in infants and children.

PURPOSE: Congenital primary bladder diverticulum is a rare cause of infra-vesical obstruction. We present a series of 12 cases who presented with urinary retention secondary to a large primary bladder diverticulum. The aim is to high light the diagnostic difficulties and management issues of congenital bladder diverticulae. METHODS: We reviewed the case sheets of 12 patients with congenital bladder diverticulae who presented as lower tract obstruction with or without infection at a tertiary care centre in the last 10 years. All patients had urine examinations (complete microscopic with culture), serum creatinine, ultrasonography, intravenous urogram, voiding cystourethrogram with or without cystoscopy. The cases were managed by extravesical mobilization of diverticulae, diverticulectomy, and ureteric re-implantation. All patients (aged 1-36 months, mean 16.8 months) presented with retention of urine but 4 of them had symptoms of fever, tachycardia, abdominal distension and vomiting. Serum creatinine was normal in 10 out of 12 cases, but was high in two. Urine cultures grew Escherichia coli in 5 cases. Ultrasonography showed moderate to severe hydronephrosis on the left side in 5 cases, on the right side in 4 cases and bilateral in 3 cases but diverticulae could be located in only 8 cases. Intravenous urogram revealed hydrouretero-nephrosis in 9 cases, a poor functioning kidney with hydrouretero-nephrosis in 3 cases and bilateral hydrouretero-nephrosis in 3 cases. A Voiding Cystourethrogram confirmed the diagnosis in all cases. Vesicoureteric reflux (Grade 4-5) into the ipsilateral ureter was seen in 9 children of which it was bilateral in three cases. RESULTS: All children underwent extravesical diverticulectomy with re-implantation of the ipsilateral ureter in 9 cases, bilateral in 3 cases. All had an uneventful recovery except for one who had a suprapubic leak which healed on conservative treatment. Postoperative ultrasonograms showed mild hydronephrosis in 2 cases and micturating cystourethrograms revealed a grade III V-U reflux in one case which was managed conservatively. Patients are maintaining a sterile urine culture after a follow up of 6-36 months. CONCLUSION: Primary bladder diverticulum should be kept as a differential diagnosis in cases of bladder outlet obstruction in infants and children. A carefully done voiding cystourethrogram is the hallmark of diagnosis. Good results can be achieved by diverticulectomy and primary definitive repair with ureteric re-implantation even in infants.