Complications in adulthood for patients with paediatric genitourinary reconstruction.

BACKGROUND: Caring for adults with prior paediatric genitourinary reconstruction remains a challenge for adult providers. Reconstructions typically have occurred decades before; surgical records are not always available and patients and families may be unable to convey procedures performed. Spina bifida (SB) patients are vulnerable to cognitive decline which may compound these challenges. Changes in patient body habitus and loss of function may contribute to problems with previous reconstructions. METHODS: This is a non-systematic review of the literature and represents expert opinion where data are non-existent. This review focuses on the evaluation and management of complications arising from genitourinary reconstruction in congenital neurogenic bladder patients. RESULTS: Common complications experienced by congenital neurogenic bladder patients include recurrent urinary tract infection, incontinence of catheterizable channel and urinary reservoir as well as malignancy as this population ages. Preservation of renal function and prevention of urinary tract infection while optimizing continence are essential guiding principles in the care of these patients. Many of the recommendations, however, are gleaned from available data in the adult spinal cord patient (a more commonly studied population) or the paediatric urologic literature due to limited studies in adult management of such patients. CONCLUSION: Close follow-up and vigilance is warranted to monitor for infectious, mechanical and malignant complications while optimizing preservation of the upper urinary tracts and patient quality of life.

Malignancy after Augmentation Enterocystoplasty: A Nationwide Study of Natural History, Prognosis and Oncogene Panel Analysis.

PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.

Female Pelvic Medicine & Reconstructive Surgery (FPMRS) challenges on behalf of the collaborative research in pelvic surgery consortium (CoRPS): managing complicated cases series 2: management of urinary incontinence in a neurogenic patient.

Discussion and management of incontinence in a patient with spina bifida by four international experts followed by a literature review.

Clinical outcomes of non-surgical management of detrusor leak point pressures above 40 cm water in adults with congenital neurogenic bladder.

AIMS: Neurogenic bladders (NGB) with detrusor leak point pressures >40 cm H2 O (dLPP > 40) have been associated with deterioration of renal function in children with myelomeningocele. For these children, careful pressure management preserves renal function. However, similar evidence is lacking in adult congenital urology (ACU) patients with NGB. We describe renal functional outcomes of non-surgical management of adults with dLPP > 40 or premicturition detrusor pressure (PMDP) >40 cm H2 O, consisting of close follow-up with urodynamic studies (UDS) and renal ultrasound (RUS), paired with adjustments to clean intermittent catheterization (CIC) frequency, anticholinergics, and addition of onabotulinumtoxinA toxin (BTX) injection. METHODS: We retrospectively reviewed the UDS of all patients at an ACU clinic from 2011 to 2016. Patients with dLPP/PMDP > 40 cm who elected for non-surgical management were included. We describe their management and renal functional outcomes. RESULTS: A total of 33/42 patients with dLPP/PMDP > 40 elected for non-surgical management. 28/33 (85%) were successfully managed without bladder augmentation or urinary diversion at follow-up of nearly 3 years. The median index dLPP/PMDP was 49 cm H2 O (IQR 44, 63) and final dLPP/PMDP was 28 (IQR 18, 43). There was a significant decrease in dLPP/PMDP and increase in bladder compliance between index and final UDS (P < 0.001). No patients advanced their CKD stage and 6/10 with baseline hydronephrosis had improvement or resolution of hydronephrosis with non-surgical management. CONCLUSIONS: A non-surgical protocol for ACU patients with NGB and dLPP/PMDP > 40, utilizing CIC, anticholinergics, and BTX is safe and effective when coupled with coordinated care and close follow-up.

Cystatin C as a marker of early renal insufficiency in children with congenital neuropathic bladder.

PURPOSE: Due to decreased muscle mass in children with congenital neuropathic bladder there may be significant inaccuracy when using the creatinine based estimated glomerular filtration rate. Cystatin C is highly sensitive and specific for measuring changes in the glomerular filtration rate in children and in patients with muscle wasting conditions. We hypothesized that a cystatin C calculated glomerular filtration rate would be more sensitive than the standard creatinine based modified Schwartz equation to detect renal insufficiency in children with congenital neuropathic bladder. MATERIALS AND METHODS: We prospectively identified children with congenital neuropathic bladder at a multidisciplinary spina bifida clinic who underwent serum creatinine and serum cystatin C testing. Clinical history and anthropomorphic variables at the time of laboratory testing were catalogued. The creatinine based glomerular filtration rate was estimated using the modified (bedside) Schwartz formula and the cystatin C based rate was calculated using the Zappitelli cystatin C formula. RESULTS: Dual estimated glomerular filtration rate calculation was done in 69 children at a total of 74 patient encounters. Absolute creatinine was within age range normal limits in each patient, including 1 with chronic kidney disease stage 3A. The median creatinine based estimated glomerular filtration rate was 123 ml per minute/1.73 m(2) (range 58 to 229). The median cystatin C based estimated rate was 103 ml per minute/1.73 m(2) (range 47 to 144) for an absolute median rate reduction of 15.4%. Using cystatin C estimates chronic kidney disease stage was upgraded from stage 1 to 2 in 13 patients (18.8%). CONCLUSIONS: In children with neuropathic bladder the cystatin C estimated glomerular filtration rate is a better screening test for early renal insufficiency that is not detected by creatinine based rate calculations. To our knowledge it remains to be determined whether the cystatin C estimated glomerular filtration rate can ultimately improve the clinical outcome in this population.

International Children's Continence Society's recommendations for initial diagnostic evaluation and follow-up in congenital neuropathic bladder and bowel dysfunction in children.

PURPOSE: The objective of this ICCS standardization document is to report the initial diagnostic evaluation and subsequent work-up of children with neuropathic bladder dysfunction. MATERIALS AND METHODS: Due to a paucity of level I or level II, "levels of evidence" publications, these recommendations are actually a compilation of best practices because they seem to be effective and reliable, although not with any control. RESULTS: Throughout the document, the emphasis is on promoting early, comprehensive evaluation of lower urinary tract function that is thorough but with a minimum of unnecessary testing. This includes what tests to order, when to order them and what to do with the results. Some of the recommendations may not be practical in various worldwide locations but the suggested testing should be considered the ideal approach to completely diagnosing and then promulgating treatments based on the full knowledge of the condition and its effect on urinary tract function. Once the findings are delineated, those lower urinary tract patterns of dysfunction that put the kidneys at risk for deterioration, that are barriers to attaining eventual continence, and that have long-term consequence to the lower urinary track can be obviated by specific management recommendations. The indications and timing of investigations to achieve these objectives are clearly defined in each diagnostic category and during follow-up. RECOMMENDATIONS: This document should be used as a basis for appropriate evaluation and timely surveillance of the various neuro-urologic conditions that affect children.

International Children's Continence Society's recommendations for therapeutic intervention in congenital neuropathic bladder and bowel dysfunction in children.

PURPOSE: We present a consensus view of members of the International Children's Continence Society on the therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. MATERIAL AND METHODS: Discussions were held by a group of pediatric urologists and gastroenterologists appointed by the board. The following draft review document was open to all the ICCS members via the ICCS web site. Feedback was considered by the core authors and by agreement, amendments were made as necessary. The final document is not a systematic literature review. It includes relevant research when available as well as expert opinion on the current understanding of therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. RESULTS: Guidelines on pharmalogical and surgical intervention are presented. First the multiple modalities for intervention that do not involve surgical reconstruction are summarized concerning pharmacological agents, medical devices, and neuromodulation. The non-surgical intervention is promoted before undertaking major surgery. Indicators for non-surgical treatments depend on issues related to intravesical pressure, upper urinary tract status, prevalence of urinary tract infections, and the degree of incontinence. The optimal age for treatment of incontinence is also addressed. This is followed by a survey of specific treatments such as anticholinergics, botulinum-A toxin, antibiotics, and catheters. Neuromodulation of the bladder via intravesical electrical stimulation, sacral nerve stimulation, transcutaneous stimulation, and biofeedback is scrutinized. Then follows surgical intervention, which should be tailored to each individual, based on careful consideration of urodynamic findings, medical history, age, and presence of other disability. Treatments mentioned are: urethral dilation, vesicostomy, bladder, augmentation, fascial sling, artificial urinary sphincters, and bladder neck reconstruction and are summarized with regards to success rates and complications. Finally, the treatment on neuropathic bowel dysfunction with rectal suppositories irrigation and transrectal stimulation are scrutinized.

Urodynamic evaluation of tethered cord syndrome including tight filum terminale: prolonged follow-up observation after intraspinal operation.

From pre- and postoperative urodynamic examinations of congenital neurogenic bladder caused by tethered cord syndrome including tight filum terminale, the results of intraspinal surgery on tethered cord syndrome are reported herein. As a result, urodynamic and electrophysiologic examinations are considered as excellent methods, which are safe and give objective findings, for diagnosis and prolonged observation of not only tethered cord syndrome but also congenital neurogenic bladder.

Congenital neuropathic bladder: practicalities and possibilities of conservational management.

Upper urinary tract and renal deterioration in the child with congenital neuropathy is due to high intravesical pressure associated with urinary retention. Preservation of kidney function often can be achieved when bladder emptying is improved by lowering the urethral resistance, when reflux is cured, and when infection is controlled. Since incontinence is most often of the overflow type, complete bladder evacuation can allow the child to remain dry for a socially acceptable period of time between voidings. Success depends greatly on the child's motivation and on his cooperation in a bladder training regimen. Diversion is sometimes unavoidable but should be considered only when conservational methods have failed.

Combined bladder augmentation and bladder neck suspension for neuropathic incontinence in girls.

We treated five girls with congenital neuropathic bladder, who had genuine stress incontinence combined with reduced detrusor compliance and/or detrusor hyperreflexia, by simultaneous Marshall-Marchetti-Krantz bladder-neck suspension and bladder augmentation using a sigmoid or ileocecal pouch. All are dry on 3 to 4 hourly intermittent self-catheterization and we suggest that this method represents a useful and much cheaper alternative to the artificial urinary sphincter.

[Pathology of the ureterovesical junction in neurogenic bladders in children and adolescents. A retrospective study of 119 patients]. / Pathologie de la jonction urétéro-vésicale dans les vessies neurologiques de l'enfant et de l'adolescent. Etude rétrospective de 119 patients.

Ureterovesical junction dysfunction in congenital or acquired neurogenic bladders represents a threat for the renal parenchyma. In order to evaluate the incidence, mechanisms of development and preventive and curative treatments proposed in diseases of the ureterovesical junction associated with neurogenic bladders, the files of 119 children were retrospectively evaluated. 68 patients suffered from congenital neurogenic bladder and 51 had an acquired neurogenic bladder. In the congenital neurogenic bladder group, vesico-ureteric reflux was observed in 22 cases (32%) and dilatation was observed in 18 cases (26.5%), while 21 patients had both dilatation and reflux. In the acquired neurogenic bladder group, reflux was observed in 8 cases (16%) and dilatation was observed in 3 cases (10%), one of whom had both reflux and dilatation. The predominant mechanism of decompensation of the ureterovesical junction in the two groups was a combination of low compliance and high peripheral resistance. In patients with abnormalities of the ureterovesical junction, the incidence of associated parenchymal lesions was similar (30%) whether neurogenic bladder was congenital or acquired. The disparities between these two comparable patient groups, the preventive and curative treatments proposed and their results are analysed in comparison with the data reported in the literature.

[Clinical studies on children with congenital neurogenic bladder treated during the past 10 years].

During the past 10 years, 22 children (13 males and 9 females) had been treated for congenital neurogenic bladder at our department. These cases were reviewed for urinary tract infection, urodynamics, vesicoureteral reflux and renal deterioration. Urinary tract infections were observed during the follow-up period in 12 of the 22 cases (54.6%). The incidence was 38.5% in males and 88.9% in females. Cystometric findings were arbitrarily divided into 3 types; hyperreflexic type, areflexic hypertonic type and areflexic hypotonic type. Of the 17 cases examined, 3 cases were of the hyperreflexic type, 6 cases the areflexic hypertonic type and 8 cases the areflexic hypotonic type. Urinary tract infections were not observed in 5 of the 8 cases categorized as the areflexic hypotonic type compared to one of the 9 cases of the hyperreflexic and areflexic hypertonic types together. UPP was examined in 13 cases. UP max values were lower than normal in the areflexic type cases, but were normal or higher in the hyperreflexic type cases. Vesicoureteral reflux was examined in 9 cases. Reflux was observed in 9 ureters of 6 patients. Renal deterioration was observed in 6 cases; 4 cases of hydronephrosis and 2 cases of pyelonephritis. Management of 22 cases consisted of ileal conduit (1 case), clean intermittent self-catheterization (2 cases) and Cred é maneuver and/or pharmacologic treatments (19 cases). The usefulness of clean intermittent self-catheterization and management for vesicoureteral reflux were discussed centering on 4 selected cases.

[Current trends in the treatment of malformative uropathies]. / Moderni orientamenti nel trattamento delle uropatie malformative.

Urinary tract malformations are common malformations. Surgical correction is very often required to normalize the urinary tract and to prevent renal function deterioration or to ameliorate a compromised renal function. The results of the surgical management have had a considerable improvement in the last decades. Three mechanisms worked at this regard: 1) the possibility of antenatal ultrasound diagnosis; 2) a better knowledge of the natural postnatal evolution; 3) the long-term results of the surgical treatment. Referring to literature's data and especially to a wide personal experience, the Author outlines the correct indications for surgery and the most effective surgical procedures in the management of the most important urinary tract malformations.

[Decisional criteria in the management of vesico-ureteral reflux in children with congenital neurogenic bladder]. / Critères décisionnels dans la prise en charge des reflux vésico-urétéraux chez l'enfant porteur d'une neurovessie congénitale.

OBJECTIVES: To determine, in the particular case of neurogenic bladder, the best criteria for selection and grading of the modalities available for the treatment of vesicoureteric reflux, which is often associated. METHODS: 194 patients with congenital neurogenic bladder, including 76 cases with vesicoureteric reflux were retrospectively reviewed. The various treatments applied, their results and their complications were reviewed. Conclusions are drawn and proposals are made for the optimal management of vesicoureteric reflux in the particular context of congenital neurogenic bladder. RESULTS: This series included 8 grade I, 28 grade II, 49 grade III and 23 grade IV and V. In more than 50% of cases, reflux was detected on during routine assessment of congenital neurogenic bladder, demonstrating the value of this assessment (25% of cases of reflux were detected before the age of one year). Management initially consisted of vesical drainage, often by intermittent catheterization, from the age of 2 to 3 years and antibiotic prophylaxis. This treatment was sufficient to correct reflux in 9 cases and to control it in 16 cases (no urinary tract infection, no deterioration of the upper tract). An elective anti-reflux operation was decided in 69 cases of VUR (1 grade I, 15 grade II, 38 grade III, 16 grade IV or V). Cohen's technique was performed in 3 cases and endoscopic injection of PTFE was performed in 3 cases. Most of these refluxing bladders were hypertonic and/or presented an abnormally high closing pressure. The operative criteria were: symptomatic reflux; persistent reflux; renal deterioration; non-compliance with treatment. Several complications were observed and are described. CONCLUSION: Vesicoureteric reflux in the context of congenital neurogenic bladder plays a major role in the deterioration of renal function. These forms of reflux usually occur in hypertonic bladders. Urodynamic studies appear essential before deciding treatment. Intermittent catheterization is able to control or even correct a certain number of these cases of reflux and should be introduced by the age of 2 or 3 years. When surgery is required, Cohen's operation is the easiest to perform, but is associated with an increased complication rate. Injection of PTFE or macroplastic could constitute a good indication.

Neuropathic bladder in the neonate.

The management of infants born with myelomeningocele depends on understanding how their bladder stores and empties urine. Storage at low pressure with effective emptying periodically throughout the day is the goal. Intervention is designed to impact on one or both of these processes so that infants can remain infection-free and at the same time allow for appropriate renal growth over time. Urodynamic evaluation plays an important role, so that neonates can be stratified according to their risk. Most patients require intermittent catheterization and pharmacotherapy to achieve these goals at some point in their lives.

Development of upper tract stones in patients with congenital neurogenic bladder.

OBJECTIVE: Patients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones. METHODS: We performed a 10-year retrospective case-control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann-Whitney U test. Multivariable logistic regression was performed. RESULTS: 52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel-urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel-urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015). CONCLUSION: Patients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population.

Single-center experience with botulinum toxin endoscopic detrusor injection for the treatment of congenital neuropathic bladder in children: effect of dose adjustment, multiple injections, and avoidance of reconstructive procedures.

OBJECTIVE: Since 2007, intra-detrusor OnabotulinumtoxinA (OnabotA) injections have been selectively offered at our institution for cases in which maximal anticholinergic therapy failed or was not tolerated. Herein we present our experience with this approach. MATERIALS AND METHODS: We prospectively obtained data on 17 patients who underwent OnabotA injections over a 4-year period. Demographic information, number of injections, and dose delivered were captured. Children were monitored with baseline and post-injection renal ultrasound, urodynamics, and assessed for side effects, satisfaction, and symptom improvement. RESULTS: Forty-three sessions were performed with injections given every ∼ 6 months. Mean patient age was 10.7 years (range, 3-17). Compared with baseline, after the first injection, mean bladder capacity adjusted for age and compliance improved by 27% (p = 0.039) and 45.2% (p = 0.041), respectively. After subsequent injections, these values increased to 35.7% (p = 0.043) and 55.1% (p = 0.091), respectively. Out of 13 symptomatic patients, ≥ 50% improvement was reported in ten (76.9%) and complete resolution in seven (53.8%). However, all three patients in whom the maximum dose of OnabotA was reduced from 300 to 200 units complained of recurrent symptoms. Fourteen children avoided surgical reconstruction as a second line of treatment. Overall patient/parental reported satisfaction rate was 70.6% (12/17). CONCLUSIONS: Intra-detrusor OnabotA injection is a promising intervention for management of neuropathic bladder in selected patients. Our data demonstrate improvement in symptoms and urodynamic parameters. Although an optimal dose has not been determined for children, we found optimal response with a maximum administration of OnabotA up to 300 units.

Renal function in children with congenital neurogenic bladder.

AIMS: Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. METHODS: We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. RESULTS: The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow-up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m²/min, and the final mean was 193.6 ± 93.6 mL/1.73 m²/min, p = 0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. CONCLUSIONS: Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management.

The effect of epigenetic therapy on congenital neurogenic bladders--a pilot study.

OBJECTIVES: To demonstrate that human smooth muscle cells derived from neurogenic bladders produce more collagen in vitro than smooth muscle cells derived from normal bladders, and that epigenetic therapy may normalize this increased collagen production. METHODS: Human smooth muscle cells from normal (n = 3) and neurogenic bladders (n = 3) were cultured in normal culture media and at different concentrations of the histone deacetylase inhibitors trichostatin A, valproic acid, and the DNA methylation inhibitor 5-azacytidine (5-aza). Collagen type I and III gene expression was measured using real-time quantitative reverse transcription-polymerase chain reaction after varying doses of drug exposure. Cell viability was measured using trypan blue. RESULTS: The smooth muscle cells from neurogenic bladders released significantly more collagen than the normal bladder cells (mean 4.1 vs 1.8 microg/mL in control media) when grown in normal conditions. Treatment with trichostatin A at 50 ng/mL decreased the collagen level in cells from neurogenic bladders to almost normal levels (2.1 microg/mL). In addition, valproic acid treatment decreased collagen types I and III gene expression relative to controls, with maximal effect at 300 mg/mL. These treatments had little effect on cell viability. CONCLUSIONS: Histone deacetylase inhibitors decreased collagen production of smooth muscle cells from neurogenic bladders in vitro. These agents may be a means of effectively preventing bladder fibrosis in patients with this condition.