Can Lymph Node Involvement in Unilateral Wilms Tumor be Predicted by Preoperatively known Data in Combination with Intraoperative Findings?

OBJECTIVE: This study aimed to identify parameters that allow the estimation of tumor-infiltrated lymph nodes (LN) after pretreatment for unilateral Wilms tumor (WT). SUMMARY BACKGROUND DATA: Complete tumor resection with removal of regional LN is always necessary. Positive LNs require local irradiation influencing benefits in case of NSS in long-term follow-up. Clinical and tumor-related data available at the time of surgery in combination with intraoperative findings (IAF) were used to estimate the LN status during surgery. METHODS: Altogether, 2115 patients with unilateral WT were prospectively enrolled in SIOP-93-01 / GPOH and SIOP-2001 / GPOH over a period of 30 years (1993-2023). LN infiltration by tumor was calculated for age, sex, metastases at diagnosis, tumor volume (TV), TV shrinkage, and intraoperative findings (IAF) using logistic regression models. RESULTS: Age ≥48 months (P<0.001, OR 2.17, CI 1.57 - 3.00), TV at diagnosis ≥300 (P<0.001, OR 3.72, CI 2.37 - 5.85), metastasis at diagnosis (P<0.001, OR 6.21, CI 4.47 - 8.62) and IAF (>1: P<0.001, OR 3.54, CI 2.13 - 5.88) correlated with positive LNs. TV shrinkage was not predictive of positive LN. Three flow charts were developed based on age, TV at diagnosis, metastasis, and IAF. These flowcharts defined risks between 0% and 41.5% for LN infiltration by tumor. CONCLUSIONS: The combination of age, TV at diagnosis, and metastasis with IAF allows the estimation of the frequency of positive LNs, which may help surgeons deciding about NSS.

Surgical Factors Influencing Local Relapse and Outcome in the Treatment of Unilateral Nephroblastoma.

OBJECTIVE: This study aims to identify factors associated with the occurrence of local relapse (LR) after treatment for unilateral nephroblastoma. BACKGROUND: Despite the fact that LR is rare (~5%) its adverse impact on the need for relapse treatment and outcome (40%-80% overall survival) cannot be neglected. Identifying the causative factors may improve initial treatment to achieve better local control. METHODS: Altogether 2386 patients with unilateral nephroblastoma prospectively enrolled over a period of 32 years (1989-2020) by the German Society for Pediatric Oncology and Hematology (SIOP-9/GPOH, SIOP-93-01/GPOH and SIOP-2001/GPOH) were retrospectively analyzed. Hazard ratios (HR) of LR were calculated for sex, age, size, local staging, histology, type of removal, rupture, lymph node (LN) removal using univariate and multivariate Cox models. RESULTS: Age >48 months, tumor volume >500 mL, histology and LN extent of removal were identified as significant risk factors for LR [HR: 1.68, P =0.018, confidence interval (CI): 1.09-2.58; HR: 1.84, P =0.015, CI: 1.13-3.00; HR: 3.19, P <0.001, CI: 2.03-5.00; HR: 2.26, P =0.002, CI: 1.36-3.576]. LR occur significantly more often in Stage I and II, even if no LN are removed. The risk of metastases is significantly increased after local recurrence (HR: 11.5, P <0.001, CI: 7.11-18.60). LR is associated with a subsequent 18.79-fold increased risk of death (HR: 18.79, P <0.001, CI: 2.07-5.28). CONCLUSIONS: Several factors are responsible for the occurrence of LR. Surgical ones, like LN sampling allow further reduction of LR and consequently a better outcome of patients with unilateral nephroblastoma.

Bladder cancer in patients with neurogenic bladder disorder: a comparative study of different etiologies.

PURPOSE: The objective of this study was to conduct a comparative study of different etiologies of neurogenic bladder disorders (NBDs) in patients with bladder cancer (BC) regarding patient- and tumor-related parameters and their oncological outcome. METHODS: Out of 98 patients with bladder tumors and neurogenic disease, 23 patients with BC and NBDs from Jan 1, 2010, to Dec 31, 2020, were included. The different etiologies of NBDs were merged in three groups based on the level of the nervous system (NS)-lesion: (i) central (n = 6), (ii) spinal cord (n = 10), and (iii) peripheral lesions (n = 7). RESULTS: Patients with lesions at the spinal cord level were younger at the time of BC diagnosis compared to patients with central or peripheral NS lesions (54 vs. 68 vs. 78 years, p = 0.0219). However, the latency to malignant transformation was more than twice as long (33 vs. 15 years, p = 0.0108). Most tumors were muscle-invasive or locally advanced BCs (62%) and presented lymph node metastases (55%), resulting in a poor mean overall survival of 30.9 ± 3.6 months. No significant differences regarding histopathology, tumor stage, and oncological outcome could be observed between the groups. CONCLUSION: Patients with NBDs have a poor prognosis regardless of their etiology or the level of NS lesion. Patients with spinal cord lesions, including congenital NBDs, appear to develop BC at a young age, but compared to other etiologies latency from NBD to BC is longer.

Bladder cancer in patients with spina bifida: a serious risk.

PURPOSE: After bladder augmentation (BA) using bowel segments, it is known that there is a risk for secondary malignancies. It remains unclear whether this also applies to spina bifida (SB) patients without BA. The aim of this study was to analyze the frequency of bladder cancer (BC) in SB at a single tertiary institution and assess the patients' oncologic outcome. METHODS: Patients with SB and BC treated from January 2016 until March 2020 were included and corresponding data were collected retrospectively. Endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Among 132 adult patients with SB, four with a median age of 34.5 years (IQR 31.5-36.8, range 31-37) had a BC. None of the patients had undergone BA. Most common symptoms included recurrent urinary tract infections (UTI) (75%) and hydronephrosis (75%). At the time of the diagnosis, tumors were locally advanced (≥ T3) and lymph-node positive in all cases. All patients underwent radical cystectomy with adjuvant chemotherapy in two out of four cases. Histology showed squamous cell carcinomas (SCC) or at least a squamous cell component in all patients. The median PFS was 5.9 months (IQR 5.1-124.5) and the median OS was 8.7 months (IQR 6.3-125.5). CONCLUSIONS: SCC in SB can appear at a young age and is usually diagnosed in an advanced tumor stage with poor prognosis despite radical surgical resection. Patients with SB without BA with clinical symptoms, new onset of hematuria, and/or upper tract dilatation should receive a cystoscopy ± further imaging.

Challenges in pediatric urologic practice: a lifelong view.

The role of the pediatric urologic surgeon does not end with initial reconstructive surgery. Many of the congenital anomalies encountered require multiple staged operations while others may not involve further surgery but require a life-long follow-up and often revisions. Management of most of these disorders must extend into and through adolescence before transitioning these patients to adult colleagues. The primary goal of management of all congenital uropathies is protection and/or reversal of renal insult. For posterior urethral valves, in particular, avoidance of end-stage renal failure may not be possible in severe cases due to the congenital nephropathy but usually can be prolonged. Likewise, prevention or minimization of urinary tract infections is important for overall health and eventual renal function. Attainment of urinary continence is an important goal for most with a proven positive impact on quality of life; however, measures to achieve that goal can require significant efforts for those with neuropathic bladder dysfunction, obstructive uropathies, and bladder exstrophy. A particular challenge is maximizing future self-esteem, sexual function, and reproductive potential for those with genital anomalies such as hypospadias, the bladder exstrophy epispadias complex, prune belly syndrome, and Mullerian anomalies. Few endeavors are rewarding as working with children and their families throughout childhood and adolescence to help them attain these goals, and modern advances have enhanced our ability to get them to adulthood in better physical and mental health than ever before.

Pregnancy following urinary tract reconstruction using bowel segments: a review of published literature.

PURPOSE: To provide a literature review of the urological and obstetric outcomes during and after pregnancy following urinary diversion using bowel segments. METHODS: A systematic literature research by specific keywords was performed in February 2017. Relevant articles were assessed and available parameters such as, e.g., number of included patients, indication for and type of urinary diversion, birth mode and complications during and after pregnancy were evaluated. RESULTS: We found 61 relevant articles published between 1961 and 2017. Overall, data of 282 females carrying 330 babies within 395 pregnancies were listed. Birth was via vaginal delivery in 132 cases, while 183 females delivered via elective or emergency cesarean. The main urological complications during pregnancy were urinary tract infections, pyelonephritis and dilatation of the upper urinary tract. In total, 155 episodes of pyelonephritis (39.2%) were reported, but no major or persisting complications occurred. CONCLUSION: After urinary diversion, pregnancy is possible without major complications. Due to an increased risk of pyelonephritis and dilatation of the upper urinary tract requiring intervention, these pregnancies should be considered high risk. Vaginal delivery as well as delivery by cesarean is feasible, but should be carried out in centers of expertise with urological stand-by.

Practical recommendations of the EAU-ESPU guidelines committee for monosymptomatic enuresis-Bedwetting.

BACKGROUND AND AIMS: The objective of this update of the EAU-ESPU guidelines recommendations for nocturnal enuresis was to review the recent published literature of studies, reviews, guidelines regarding the etiology, diagnosis and treatment options of nocturnal enuresis and transform the information into a practical recommendation strategy for the general practitioner, pediatrician, pediatric urologist and urologist. MATERIAL AND METHODS: Since 2012 a monthly literature search using Scopus® was performed and the relevant literature was reviewed and prospectively registered on the European Urology bedwetting enuresis resource center (http://bedwetting.europeanurology.com/). In addition, guideline papers and statements of the European Society for Paediatric Urology (ESPU), the European Association of Urology (EAU), the National Institute for Health and Care Excellence (NICE) and the International Children Continence Society (ICCS) were used to update the knowledge and evidence resulting in this practical recommendation strategy. Recommendations have been discussed and agreed within the working group of the EAU-ESPU guidelines committee members. RESULTS: The recommendations focus to place the child and his family in a control position. Pragmatic analysis is made of the bedwetting problem by collecting voiding and drinking habits during the day, measuring nighttime urine production and identification of possible risk factors such as high-volume evening drinking, nighttime overactive bladder, behavioral or psychological problems or sleep disordered breathing. A questionnaire will help to identify those risk factors. CONCLUSION: Motivation of the child is important for success. Continuous involvement of the child and the family in the treatment will improve treatment compliance, success and patient satisfaction.

EAU/ESPU guidelines on the management of neurogenic bladder in children and adolescent part II operative management.

BACKGROUND: Treatment in children and adolescents with a neurogenic bladder is primarily conservative with the goal of preserving the upper urinary tract combined with a good reservoir function of the bladder. However, sometimes-even in childhood-conservative management does not prevent the development of a low-compliant bladder or overactive detrusor. MATERIAL & METHODS: After a systematic literature review covering the period 2000-2017, the ESPU/EUAU guideline for neurogenic bladder underwent an update. RESULTS: In these patients, surgical interventions such as botulinum toxin A injections into the detrusor muscle, bladder augmentation, and even urinary diversion may become necessary to preserve the function of the upper (and lower) urinary tracts. The creation of a continent catheterizable channel should be offered to patients with difficulties performing transurethral clean intermittent catheterization. However, a revision rate of up to 50% needs to be considered. With increasing age continence of urine and stool becomes progressively more important. In patients with persistent weak bladder outlets, complete continence can be achieved only by surgical interventions creating a higher resistance/obstruction at the level of the bladder outlet with a success rate of up to 80%. In some patients, bladder neck closure and the creation of a continent catheterizable stoma is an option. CONCLUSION: In all these patients close follow-up is mandatory to detect surgical complications and metabolic consequences early.

EAU/ESPU guidelines on the management of neurogenic bladder in children and adolescent part I diagnostics and conservative treatment.

BACKGROUND: In childhood, the most common reason for a neurogenic bladder is related to spinal dysraphism, mostly myelodysplasia. AIMS: Herein, we present the EAU/ESPU guidelines in respect to the diagnostics, timetable for investigations and conservative management including clean intermittent catheterization (CIC). MATERIAL AND METHODS: After a systematic literature review covering the period 2000 to 2017, the ESPU/EUAU guideline for neurogenic bladder underwent an update. RESULTS: The EAU/ESPU guideline panel advocates a proactive approach. In newborns with spina bifida, CIC should be started as soon as possible after birth. In those with intrauterine closure of the defect, urodynamic studies are recommended be performed before the patient leaves the hospital. In those with closure after birth urodynamics should be done within the next 3 months. Anticholinergic medication (oxybutynin is the only well-investigated drug in this age group-dosage 0.2-0.4 mg/kg weight per day) should be applied, if the urodynamic study confirmed detrusor overactivity. Close follow-up including ultrasound, bladder diary, urinalysis, and urodynamics are necessary within the first 6 years and after that the time intervals can be prolonged, depending on the individual risk and clinical course. In all other children with the suspicion of a neurogenic bladder due to various reasons as tethered cord, inflammation, tumors, trauma, or other reasons as well as those with anorectal malformations, urodynamics-preferable video-urodynamics, should be carried out as soon as there is a suspicion of a neurogenic bladder and conservative treatment should be started soon after confirmation of the diagnosis of neurogenic bladder. With conservative treatment the upper urinary tract is preserved in up to 90%, urinary tract infections are common, but not severe, complications of CIC are quite rare and continence can be achieved at adolescence in up to 80% without further treatment. DISCUSSION AND CONCLUSIONS: The transition into adulthood is a complicated time for both patients, their caregivers and doctors, as the patient wants to become independent from caregivers and treatment compliance is reduced. Also, transition to adult clinics for patients with neurogenic bladders is often not well-established.

EAU-ESPU guidelines recommendations for daytime lower urinary tract conditions in children.

The objective is to review the literature related to lower urinary tract (LUT) conditions in children to conceptualize general practice guidelines for the general practitioner, pediatrician, pediatric urologist, and urologist. PubMed was searched for the last 15-year literature by the committee. All articles in peer-review journal-related LUT conditions (343) have been retrieved and 76 have been reviewed extensively. Prospective trials were few and the level of evidence was low. Most of the recommendations have been done by committee consensus after extensive discussion of literature reports. History taking is an integral part of evaluation assessing day- and nighttime urine and bowel control, urgency, and frequency symptoms. Exclusion of any neurogenic and organic cause is essential. Uroflowmetry and residual urine determination are recommended in all patients to evaluate bladder emptying. Urodynamic studies are reserved for refractory or complicated cases. Urotherapy that aims to educate the child and family about bladder and bowel function and guides them to achieve normal voiding and bowel habits should initially be employed in all cases except those who have urinary tract infections (UTI) and constipation. Specific medical treatment is added in the case of refractory overactive bladder symptoms and recurrent UTIs.Conclusion: Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.What is Known:• Symptoms of the lower urinary tract may have significant social consequences and sometimes clinical morbidities like urinary tract infections and vesicoureteral reflux. In many children, however, there is no such obvious cause for the incontinence, and they are referred to as having functional bladder problems.What is New:• This review aims to construct a practical recommendation strategy for the general practitioner, pediatrician, pediatric urologist, and urologist for LUTS in children. Producing recommendations for managing LUTS in children based on high-quality studies is not possible. LUTS in children should be evaluated in a multimodal way by minimal invasive diagnostic procedures. Urotherapy is the mainstay of treatment and specific medical treatment is added in refractory cases.

Are EAU/ESPU pediatric urology guideline recommendations on neurogenic bladder well received by the patients? Results of a survey on awareness in spina bifida patients and caregivers.

AIMS: The Paediatric Urology Guidelines Panel reports initial experience with patient involvement in spina bifida patient groups to gather information on their awareness of the guidelines and reflection of guideline recommendations. METHODS: The survey was delivered to spina bifida patients/parents via the national society groups in Turkey, Germany, and The Netherlands. Questions included demographic features, medical status, awareness, and agreement on the recommendations given in the guidelines and future expectations. RESULTS: A total of 291 patients from 3 countries responded to the survey. Mean age was 13.9 ± 12.2 years, male/female ratio 138/151, 75% of all surveys were completed by the caregivers. The medication was taken by 78% of patients (64% anticholinergics). Complete dryness rates for urine and stool were 24% and 47%, respectively. The agreement rates on the recommendations regarding urodynamics, intermittent catheterization, anticholinergics drug use, bowel management, and life-long follow-up were 97%, 82%, 91%, 77%, and 98%, respectively. Only 8% of responders were aware of the European Association of Urology/European Society for Pediatric Urology guidelines. The priorities of patients for future expectations were as the following: quality of life (QoL), surgical techniques, development of new medications and sexuality/fertility issues. Male spina bifida patients preferred new medications and sex/fertility issues more, whereas females favored QoL issues improvement more. CONCLUSIONS: Although the native language of the involved patients was different from English, awareness of guidelines was 8%. The general approval of the recommendations given in the guidelines is quite high. The national society groups showed a great interest to get involved in the creation of the guidelines to improve health care for spina bifida patients.

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.

Prospective analysis of long-term renal function in survivors of childhood Wilms tumor.

BACKGROUND: Considering the improved outcome, a better understanding of the late effects in Wilms tumor survivors (WT-S) is needed. This study was aimed at evaluating renal function and determining the prevalence of clinical and subclinical renal dysfunction in a cohort of WT-S using a multimodal diagnostic approach. METHODS: Thirty-seven WT-S were included in this prospective cross-sectional single center study. To evaluate renal function, glomerular filtration rate (GFR) and urinary protein excretion were assessed. Additionally, kidney sonomorphology and blood pressure were analyzed. RESULTS: All examined WT-S (mean age 28.7 years, mean follow-up 24.8 years) had been treated with a combination of surgery and chemotherapy; 59.5% had received adjuvant radiotherapy. Impaired glomerular renal function was detected in a considerable proportion of WT-S, with age-adjusted cystatin-based GFR estimation below age norm in 55.9%. A lower cystatin-based estimated GFR (eGFR) correlated with longer follow-up time and higher irradiation dose. In 5 patients (13.5%) albuminuria was identified. Analysis of sonomorphology detected compensatory contralateral renal hypertrophy in 83.3% of WT-S. Chronic kidney disease (CKD) ≥ stage II was present in 55.9% of WT-S. Blood pressure measurements revealed arterial hypertension in 15 (40.5%) WT-S (newly diagnosed n=10). In 24.3% both CKD ≥ stage II and arterial hypertension were determined. CONCLUSION: Even though WT-S are believed to carry a low risk for end-stage renal disease, in this study, a remarkable number of WT-S presented with previously unidentified subclinical signs of renal function impairment and secondary morbidity. Therefore, it is important to continue regular follow-up, especially after transition into adulthood.

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.

Sexual Function and Fertility of Women with Classic Bladder Exstrophy and Continent Urinary Diversion.

PURPOSE: We evaluated the outcome in female patients with classic bladder exstrophy and continent urinary diversion for sexual function and fertility. MATERIALS AND METHODS: We reviewed the medical records of female exstrophy patients who underwent continent urinary diversion in our department between 1969 and 2014. Patients were invited for followup examination and asked to complete questionnaires relating to sexual function, social integration and maternity. RESULTS: Of 38 eligible patients 29 (response rate 76%) with a followup of 22.3 years were included in study. Primary continent urinary diversion was done in 62% of patients and 38% underwent secondary continent urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the Female Sexual Function Index was only little affected in all domains except desire. Mean total Female Sexual Function Index score was 28.4 of a possible 36. Of the women 31% were classified as at risk for sexual dysfunction, 72% had a stable relationship, 41% were married and 31% had completed higher education. The incidence of pelvic organ prolapse requiring surgical repair was 38%. A total of 16 healthy children were conceived by 12 patients. The pregnancy rate after primary continent urinary diversion was higher than after secondary diversion. CONCLUSIONS: The sexuality and fertility of female patients with exstrophy after continent urinary diversion appears to be comparable with those in previously reported series of patients in whom the bladder was preserved. Management of sexual function, gynecologic pathologies and fertility should be an active part of long-term followup.

Sexual Function, Social Integration and Paternity of Males with Classic Bladder Exstrophy following Urinary Diversion.

PURPOSE: We evaluated patients with classic bladder exstrophy and a history of urinary diversion for sexual function, social integration and paternity. MATERIALS AND METHODS: We reviewed the medical records of males older than 18 years with exstrophy who had undergone urinary diversion at our department between 1969 and 2014. Patients were invited for structured followup examinations and were asked to complete questionnaires relating to sexual function, social integration and paternity. RESULTS: Of 79 eligible patients 39 (49%) with a mean followup of 23.8 years (range 2 to 45) were included in the study. Of the patients 41% had undergone primary urinary diversion and 59% had undergone secondary urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the International Index of Erectile Function was negatively affected in all domains, with mild to moderate dysfunction in 90% of patients. Of the patients 73% had a stable relationship and 32% were married. A high level of education had been achieved by 77% of patients. Sperm quality was poor (oligoasthenoteratozoospermia) in 71% of patients. Among the patients 11 had fathered a total of 16 healthy children. CONCLUSIONS: Despite multiple reconstructive procedures of the genitourinary tract, including removal of the exstrophic bladder and subsequent urinary diversion, sexuality and paternity in this subset of patients was comparable to reported series of men in whom the bladder had been preserved. Evaluation of sexual function and fertility should be part of long-term followup, and treatment should be offered if indicated. Currently staged concepts of exstrophy repair should be applied to improve the cosmetic and functional outcomes of the genitourinary tract in patients with exstrophy.

CNV analysis in 169 patients with bladder exstrophy-epispadias complex.

BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. METHODS: To detect further CNVs, array analysis was performed in 169 BEEC patients. Prior to inclusion, 22q11.21 duplications were excluded using multiplex ligation-dependent probe amplification. RESULTS: Following the application of stringent filter criteria, seven rare CNVs were identified: n = 4, not present in 1307 in-house controls; n = 3, frequency of <0.002 in controls. These CNVs ranged from 1 to 6.08 Mb in size. To identify smaller CNVs, relaxed filter criteria used in the detection of previously reported BEEC associated chromosomal regions were applied. This resulted in the identification of six additional rare CNVs: n = 4, not present in 1307 in-house controls; n = 2, frequency <0.0008 in controls. These CNVs ranged from 0.03-0.08 Mb in size. For 10 of these 13 CNVs, confirmation and segregation analyses were performed (5 of maternal origin; 5 of paternal origin). Interestingly, one female with classic bladder extrophy carried a 1.18 Mb duplication of 22q11.1, a chromosomal region that is associated with cat eye syndrome. CONCLUSIONS: A number of rare CNVs were identified in BEEC patients, and these represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial BEEC phenotypes.

Efficacy, safety, and tolerability of intravesically administered 0.1% oxybutynin hydrochloride solution in adult patients with neurogenic bladder: A randomized, prospective, controlled multi-center trial.

AIMS: To verify the efficacy, safety and tolerability of intravesical administration of 0.1% oxybutynin hydrochloride compared to its oral administration for treatment of neurogenic detrusor overactivity (NDO) in a randomized, prospective, controlled, open-label, multi-center trial in 35 adult patients. METHODS: NDO was confirmed within the previous 24 months by urodynamic studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin hydrochloride orally three times per day for a period of 28 days. Primary efficacy criterion was the change in the maximum bladder capacity between the beginning of the study and after 4 weeks as assessed by UDS. Adverse drug reactions (ADR) were collected and an evaluation of anticholinergic effects was conducted. RESULTS: The increase in maximum bladder capacity was 117 ml with intravesical application (P = 0.0002) versus 18 ml with the oral application (P = 0.51). The difference was statistically significant (P = 0.0086). ADR were reported by 10 (55.6%) of patients with intravesical administration, and by 14 (82.4%) of patients with oral administration. Significant differences in favor of the intravesical application were observed in ADR affecting vision (1/10 vs. 9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14), and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were reported. CONCLUSIONS: This study demonstrates the efficacy and safety of intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect to the increase in maximum bladder capacity. Neurourol. Urodynam. 35:582-588, 2016. © 2015 Wiley Periodicals, Inc.

Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma.

Although neuro- and nephroblastoma are common solid tumors in children, the simultaneous occurrence is very rare and is often associated with syndromes. Here, we present a unique case of synchronous occurrence of neuro- and nephroblastoma in an infant with no signs of congenital anomalies or a syndrome. We performed genetic testing for possible candidate genes as underlying mutation using the next-generation sequencing (NGS) approach to target 94 genes and 284 single-nucleotide polymorphisms (SNPs) involved in cancer. We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T→C) in the anaplastic lymphoma kinase (ALK) gene and one novel heterozygous rearrangement Q418Hfs(*)11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene FANCD2 leading to a truncated protein. Besides, several SNPs associated with the occurrence of neuroblastoma and/or nephroblastoma or multiple primary tumors were identified. The next-generation sequencing approach might in the future be useful not only in understanding tumor etiology but also in recognizing new genetic markers and targets for future personalized therapy.

Presentation, Management and Long-Term Outcome of Ureteropelvic Junction Obstruction in Duplex Kidneys.

PURPOSE: Ureteropelvic junction obstruction in association with a duplex collecting system is a rare but challenging upper urinary tract pathology. We report our 21-year experience with this anomaly in terms of presentation, diagnostic evaluation and management. MATERIALS AND METHODS: We retrospectively identified all patients with ureteropelvic junction obstruction in a duplex collecting system between 1991 and 2012. We reviewed each case for presenting symptoms, anatomy and management. Median followup was 10.8 years (range 2 to 22). RESULTS: Ureteropelvic junction obstruction in duplex kidneys was diagnosed in 21 patients. Ten patients presented with clinical symptoms such as flank pain and urinary tract infection but 11 were asymptomatic. Six patients were diagnosed by prenatal ultrasound. The lower pole and the upper pole were affected in 22 and 3 renal units, respectively. Bilateral ureteropelvic junction obstruction was found in 4 cases. Duplication was complete in 5 patients, incomplete in 11 and undetermined in 5. Surgery was performed in 14 patients, including pyelopyelostomy or ureteropyelostomy in 7, dismembered pyeloplasty in 6 and heminephrectomy in 1. Reintervention was required in 1 case. Conservative treatment was adopted in 7 patients with clinically insignificant obstruction and unimpaired renal function. In all of these patients upper urinary tract dilatation gradually improved during 3 years. CONCLUSIONS: Ureteropelvic junction obstruction in a duplex kidney is a rare but challenging anomaly that requires careful evaluation. Treatment should be individualized according to clinical presentation (symptomatic/asymptomatic), anatomy (lower/upper pole), duplication type (complete/incomplete) and obstruction with time (severity/development) on dynamic renogram.