["Epidemiology, diagnosis, treatment and follow-up of the bladder exstrophy-epispadias complex"]. / "The making of " ­ die neue S3-Leitlinie "Epidemiologie, Diagnostik, Therapie und Nachsorge des Blasenekstrophie-Epispadie Komplexes".

The development of the new S3 guideline "Epidemiology, diagnosis, treatment and follow-up of the bladder exstrophy-epispadias complex" was funded by the German Innovation Fund of the Federal Joint Committee (G-BA). Despite the relatively low level of evidence of the identified literature, a systematic approach and consistent evaluation of the literature enabled the formulation of a large number of evidence-based recommendations across a variety of topics. In addition, a patient guideline is under development in order to disseminate the guideline recommendations and to enhance self-management and understanding among patients and their relatives. A needs analysis had been carried out in order to adequately assess the topics that are most important for patients and relatives. Upon completion of the German guideline, an English translation in cooperation with the e­UROGEN network is planned.

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats.

BACKGROUND: The aim of the study was to demonstrate the efficacy of human muscle stem cells (MuSCs) isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model. METHODS: Colonies of pure human MuSCs were obtained from muscle biopsy specimens. Athymic rats were subjected to internal urethral sphincter damage by electrocauterization. Five days after injury, 2 × 105 muscle stem cells or medium as control were injected into the area of sphincter damage (n = 5 in each group). Peak bladder pressure and rise in pressure were chosen as outcome measures. To repeatedly obtain the necessary pressure values, telemetry sensors had been implanted into the rat bladders 10 days prior to injury. RESULTS: There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control (p = 0.007) 3 weeks after the cells had been injected. Only minimal histologic evidence of scarring was observed in treated rats. CONCLUSION: Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury. Translation into use in clinical settings is foreseeable.

A Prevalence Estimation of Exstrophy and Epispadias in Germany From Public Health Insurance Data.

Introduction: The prevalence of rare diseases is very important for health care research. According to the European Surveillance of Congenital Anomalies (EUROCAT) registers, the live prevalence for exstrophy and/or epispadias (grades 1-3) is reported with 1:23,255 (95% CI: 1:26,316; 1:20,000). A Europe-wide prevalence evaluation based on reports from excellence centers estimates a prevalence for exstrophies of 1:32,200 and for isolated epispadias of 1:96,800 in 2010. However, the frequency of exstrophy [International Statistical Classification of Diseases and Related Health Problems revision 10 (ICD-10): Q64.1] and epispadias (ICD-10: Q64.0) treated in different age groups in Germany remains unclear. Material and Method: Public health insurance data from 71 million people (approximately 87% of the population) were provided by the German Institute for Medical Documentation and Information (DIMDI) in accordance to the German Social Insurance Code for this research purpose. DIMDI analyzed the data source for the ICD diagnoses exstrophy and epispadias between 2009 and 2011. As provided data were robust over the years, averaged data are mentioned. Detailed subgroup analysis of small numbers was forbidden due to privacy protection. Results: Annually, 126 persons of all ages with epispadias and 244 with exstrophy are treated as inpatients. In the observed population, 34 infants (<1 year of age) with epispadias and 19 with exstrophy (58% male) are treated as outpatients each year. This corresponds to an estimated live prevalence of 1:11,000 (95% CI: 1:14,700; 1:8,400) for EEC (exstrophy-epispadias complex), more specifically a prevalence of 1:17,142 for epispadias and of 1:30,675 for exstrophy. The male-to-female ratio for exstrophy is 1.4:1 for infants and 1.6:1 for all minors. In children and adolescents, 349 epispadias and 393 exstrophies (up to the age of 17) are treated annually, whereas adults with exstrophy and even more with epispadias make comparatively less use of medical care. Conclusion: With the help of DIMDI data, the live prevalence of bladder exstrophy and epispadias in Germany could be estimated. The prevalence of epispadias was higher than in previous reports, in which milder epispadias phenotypes (grade 1 or 2) may not have been included. These analyses might enlighten knowledge about nationwide incidence and treatment numbers of rare diseases such as the EEC.

[Health care reality of selected pediatric urologic surgeries in Germany from 2006 to 2019]. / Versorgungswirklichkeit ausgewählter kinderurologischer Eingriffe in Deutschland von 2006 bis 2019.

BACKGROUND: The conservative and surgical treatment of children is a fundamental pillar of the urological specialist training program and represents one of the core competencies within urological healthcare. The loss of this expertise has been a reoccurring topic within urologic occupational policy. The aim of this study is to analyse actual case numbers and to compare the distribution and dynamics of pediatric urologic surgeries between the specialist departments of urology and pediatric surgery in Germany. MATERIALS AND METHODS: We defined the surgical treatments of maldecensus testis, hypospadias, and vesicoureteral reflux (VUR) as index interventions. Using the tool reimbursement.INFO (RI Innovation GmbH, Hürth, Germany) we analysed publicly available quality report data of German hospitals between 2006 and 2019. RESULTS: While orchidopexy was more commonly performed in the field of urology, the correction of hypospadias and the surgical treatment of VUR showed higher case numbers in the field of pediatric surgery. Proportionally, there was no relevant shift between urologic and pediatric surgical clinics for orchidopexy and surgical VUR therapy during the study period. For hypospadias corrections, the proportion of surgeries performed in pediatric surgical units is increasing (p < 0.0001). In pediatric surgery 84-93% of the analyzed procedures are performed in high-volume units, while this proportion is 56-73% in urology. In particular, a high proportion of VUR therapy in urology is performed as an occasional procedure (30% very low volume). CONCLUSIONS: The quality report data enable the compilation of case numbers and the analysis of the distribution between urology and pediatric surgery in Germany. Merely the correction of hypospadias has shown a relevant shift towards pediatric surgery. The causes and possible consequences for professional policy of this preliminary investigation are complex and require further analysis.

Improving Drinking and Micturition Habits in Preschool Children: An Educational Project.

INTRODUCTION: Children worldwide often do not drink enough. However, sufficient fluids are essential for physical and cognitive health. A regular and adequate supply of fluids also supports bladder maturation in the context of acquiring urinary continence. We investigated whether training preschool children and their caretakers improves drinking and micturition habits. METHODS: This field study in a pre-post design was conducted in 6 kindergartens in the district of Garmisch-Partenkirchen from October 2018 to February 2019. An intervention group (IG) received a 3-day training on drinking and micturition habits and was compared to a control group (CG) without any training. Caretakers (IG + CG) were instructed about drinking and voiding management, too. Behavioral changes were identified by questionnaires. To analyze the long-term effect, group interviews were performed with the IG 3 months after training. The training was evaluated on different levels. RESULTS: After training, the estimated total daily fluid intake in the IG (1,160 mL) significantly exceeded that of CG (830 mL) (p = 0.015). In the IG, fluid intake until 12:00 a.m. increased (p = 0.001), children took more time for voiding (p = 0.029), and urgency decreased (p = 0.008). Children (IG + CG) used leg support to enable pelvic floor relaxation more often both at home (p = 0.026) and in kindergarten (p = 0.047). Nocturnal enuresis was reduced by approximately 46% in the IG (p = 0.485). Group interviews in the IG showed a considerable learning effect. CONCLUSION: The present study could demonstrate an increased intake of fluids and significant changes in micturition behavior in the IG. So far, this is the first educational project in Germany addressing drinking and voiding management. Our results suggest that a training of preschool children and their caretakers is feasible and effective. Further nationwide research will be needed to confirm our results and assess the need for prevention in these areas.

SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

Treatment Strategies and Outcome of the Exstrophy-Epispadias Complex in Germany: Data From the German CURE-Net.

Introduction: To evaluate the impact of reconstructive strategies and post-operative management on short- and long-term surgical outcome and complications of classical bladder exstrophy (CBE) patients' comprehensive data of the multicenter German-wide Network for Congenital Uro-Rectal malformations (CURE-Net) were analyzed. Methods: Descriptive analyses were performed between 34 prospectively collected CBE patients born since 2009, median 3 months old [interquartile range (IQR), 2-4 months], and 113 cross-sectional patients, median 12 years old (IQR, 6-21 years). Results: The majority of included individuals were males (67%). Sixty-eight percent of the prospectively observed and 53% of the cross-sectional patients were reconstructed using a staged approach (p = 0.17). Although prospectively observed patients were operated on at a younger age, the post-operative management did not significantly change in the years before and after 2009. Solely, in prospectively observed patients, peridural catheters were used significantly more often (p = 0.017). Blood transfusions were significantly more frequent in males (p = 0.002). Only half of all CBE individuals underwent inguinal hernia repair. Cross-sectional patients after single-stage reconstructions showed more direct post-operative complications such as upper urinary tract dilatations (p = 0.0021) or urinary tract infections (p = 0.023), but not more frequent renal function impairment compared to patients after the staged approach (p = 0.42). Continence outcomes were not significantly different between the concepts (p = 0.51). Self-reported continence data showed that the majority of the included CBE patients was intermittent or continuous incontinent. Furthermore, subsequent consecutive augmentations and catheterizable stomata did not significantly differ between the two operative approaches. Urinary diversions were only reported after the staged concept. Conclusions: In this German multicenter study, a trend toward the staged concept was observed. While single-stage approaches tended to have initially more complications such as renal dilatation or urinary tract infections, additional surgery such as augmentations and stomata appeared to be similar after staged and single-stage reconstructions in the long term.

Guideline-adherence in the treatment of symptomatic urolithiasis in children and adolescents in southwestern Germany.

BACKGROUND: Approximately 1% of urolithiasis cases in Germany affect children. Interdisciplinary groups have agreed on national and international guidelines for children to recommend appropriate treatment pathways. The aim of this retrospective and preliminary study is to analyze whether adherence to current guidelines for pediatric stone disease in southwestern Germany is feasible. METHODS: During 2014 to 2017 24 children and adolescents (nine female, 15 male, median age 9.7 years), were treated for symptomatic urolithiasis in our institutions. We retrospectively collected clinical and operative courses. Clinical pathways were compared to previous guideline recommendations of the EAU 2014 and the German S2k guideline 2015. RESULTS: 17 of the 24 patients were treated according to guideline recommendations (71%). Non-adherency was based on parental decisions in two and technical/medical considerations in five cases. In 11 children (45.8%) secondary or adjunctive treatments were necessary, in three of the seven non-adherently treated (43%) and in eight of the 17 adherently treated children (47%). CONCLUSION: Our daily treatment approach seems to comply well with current pediatric stone guidelines. Nevertheless, guideline-non-adherent decision making emphasizes their strength and limitations, as specific clinical situations in children may require an individual treatment plan, as non-predictable conditions may occur.

[Bilateral reflux: contra "intravesical techniques"]. / Bilateraler Reflux ­ Kontra intravesikale Techniken.

In reflux surgery, decisions on surgical procedures can be made on an individual basis today. Almost all open surgical implantation techniques provide very good, sustainable results, and parents prefer less invasive techniques. Therefore, if intravesical techniques are used to correct bilateral reflux, it should be considered and discussed with the parents that these procedures are associated with increased invasiveness in terms of longer operation times, longer catheter dwell times, a longer inpatient stay and more complications such as macrohaematuria and bladder spams compared with extravesical techniques.

Classic bladder exstrophy and adenocarcinoma of the bladder: Methylome analysis provide no evidence for underlying disease-mechanisms of this association.

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of uro-rectal malformation spectrum involving aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). Long-term complications in CBE are malignancies of the bladder with 95% of them being adenocarcinomas. Since CBE and adenocarcinoma of the bladder are rare entities, their frequent co-occurrence suggests a common etiology. Recent studies suggest that promoter methylation of various genes play a crucial role during the phenotypical morphogenesis of adenocarcinomas of urinary bladder. To examine, whether epigenetic processes such as DNA methylation patterns are potentially associated with CBE, we performed Illumina 450 K methylation arrays in blood (n = 10) and tissue samples (n = 2) of CBE patients and healthy matched controls (n = 12). In our analysis, we found total lack of methylation in the blood and methylation differences were restricted to 10 CpG sites in the tissue samples. In comparison to other bladder anomalies, CBE tissue methylation profiles differ from those of adenocarcinoma, adenocarcinoma with CBE, urothelial carcinoma and urachal carcinoma. In this preliminary study, we did not provide any strong evidence of major DNA methylation alterations which would be suggestive for strong underlying epigenetic mechanism. However, larger studies are required to provide more robust statistical evidence to exclude smaller effects in the tissues.

Association Between Exstrophy-epispadias Complex And Congenital Anomalies: A German Multicenter Study.

OBJECTIVE: To further investigate associated anomalies in exstrophy-epispadias complex (EEC) patients congenital uro-rectal malformations network (CURE-Net) database was systematically screened. In literature the EEC comprises a spectrum of anomalies, mainly occurring "isolated" without additional congenital defects. Nevertheless, previous epidemiological studies indicated a higher association with renal, anorectal, and lower neurotubular anomalies, which may originate from the same developmental morphogenetic fields. MATERIALS AND METHODS: Seventy-three prospectively (born since 2009) and 162 cross-sectional recruited EEC patients (born 1948-2008) were analyzed. Associated anomalies were derived from patient's medical data as well as from a physical examination during a physician's interview, classified according to the international statistical classification of diseases and related health problems and grouped with the London Dysmorphology Database. Descriptive statistical analyses were performed. RESULTS: Majority of participants were male (68%) and expressed the classical bladder exstrophy phenotype (71%). Exstrophy variants occurred significantly more often in newborns (21%, P < .0001). Anomalies such as inguinal hernias, skeleton, and joint anomalies were equally present in both groups (P = .65 and P = .67). Heart defects were seen more often in newborns (6%) than in the cross-sectional group (1%; P = .033) and the general German population (1%). In total, 59% of the prospective and 48% of the cross-sectional patients had associated anomalies outside the spectrum (P = .16). CONCLUSION: Phenomenological multicenter data confirmed the dimension of associated anomalies inside and outside the EEC spectrum. The detected anomalies are either important in preparing for the primary reconstruction or later in long-term follow-up. Associated anomalies of EEC should be spotlighted during routine check-up in all EEC patients.

Needs Assessment in Care of Adults With Anorectal Malformations and Exstrophy-Epispadias Complex in Germany.

Introduction: Medical needs of adults with anorectal malformations (ARM) and the exstrophy-epispadias complex (EEC) are not fully understood. Therefore, the aim of the study was to evaluate how affected individuals get along with the current national medical care and what their medical or social long-term requirements are. Patients and Methods: Between 11/2014-07/2016 all adult members (≥18 years, ARM n = 113, EEC n = 126) of the German self-help organizations SoMA e.V. and Blasenekstrophie/Epispadie e.V. were contacted via email or post and asked to fill out an anonymous online questionnaire regarding medical requirements, treatment satisfaction, daily life impairment and expectations regarding physicians soft skills. The results were compared between both groups and male and female participants. Results: 56 participants with ARM (median age 26 years, IQR 19-38) and 52 participants with EEC (median age 31 years, IQR 22-37) filled in the questionnaire completely. Forty-five percent of the ARM and 67% of the EEC participants contacted an urologist. A general surgeon was visited by 23% of the ARM individuals, a peadiatric surgeon by 20%. Although 60% of the females with ARM and 82% of the females with EEC assessed gynecological counseling as helpful or neutral, a small subgroup of ARM females (n = 6, 16%; 70% non-isolated ARM or ARM with Hirschsprung disease and additional associated anomalies) were not satisfied. The majority of both groups reported no or only minor daily life impairment (p = 0.38). Professional knowledge, paying attention to patients' concerns, having empathy and taking enough time was important for over 90% of all participants. Thirty-eight percent of the ARM and 27% of the EEC individuals needed psychological support. Most medical consultations were judged to be helpful. Conclusion: Although adults with ARM and EEC being a self-help organization member and thus well informed and generally cope well, participants expressed their wish for expert counseling regarding family planning, reconstructive procedures, continence management, urological care and social welfare issues. Furthermore, specific expert consultations for gynecological issues in a subgroup of ARM females, mainly non-isolated, might be required. Actual needs of adults with rare conditions must be better clarified to improve medical care beyond childhood and adolescence.

Sexual Function and Quality of Life in Adult Male Individuals with Exstrophy-Epispadias Complex-a Survey of the German CURE-Network.

OBJECTIVE: To investigate sexual function and quality of life (QoL) in adult male individuals with exstrophy-epispadias complex (EEC). Data from the German Network for Congenital Urorectal Malformations (CURE-Net) were used. PATIENTS AND METHODS: Fifty-one male participants (≥18 years) recruited by CURE-Net between 2009 and 2012 were re-contacted per mail and asked to fill out 4 questionnaires including International Index of Erectile Function (IIEF-5), Cologne Assessment of Erectile Dysfunction (KEED), the Short-Form 36 (SF-36), and one self-designed questionnaire about their medical history, current health status, and sexual experience. The SF-36 results were compared with general German population. RESULTS: Nineteen male participants (37%) completed all questionnaires (median age 26 years, 84% classical bladder exstrophy). The majority (68%) was reconstructed in a staged or single-staged approach; further 32% had a primary urinary diversion. Seventy-four percent of the participants reported a certain degree of urinary incontinence. Mean IIEF-15 results showed mild to moderate or moderate impairment in all domains. The SF-36 results revealed no difference in the German population. Subgroup analysis showed statistically significant lower results in certain SF-36 domains with regard to incontinence, dissatisfaction with genital appearance, and antihypertensive drug intake. CONCLUSION: Although there is no difference in overall QoL comparing male individuals with EEC to the general German population, incontinence, dissatisfaction with genital appearance, and taking antihypertensive medication seem to have a considerable impact on QoL. Furthermore, mild to moderate erectile dysfunction and moderate intercourse satisfaction were confirmed, suggesting the need for further improvement in care for adult male individuals with EEC.

[Acute Flank Pain in Children and Adolescents]. / Akute Flankenschmerzen im Kindes- und Jugendalter.

Acute flank pain in children and adolescents is a clinically demanding symptom requiring profound diagnostic work-up. Thorough history taking, careful clinical examination as well as urine and laboratory tests in addition to ultrasound are required to guide towards the diagnosis. This article presents possible underlying conditions with specific diagnostic and therapeutic considerations.

Phimosis in a 10-yr-old Boy Without Urinary Infection-How to Inform Parents: Against Circumcision.

In a 10-yr-old boy with no abnormalities or symptoms other than nonretractability of the foreskin, the foreskin should be preserved. If treatment is needed, local corticoid application should be used as first-line therapy, as it gives excellent results in up to 90% of cases, before removing this sensitive part of the body.

Evaluation of sexual function in females with exstrophy-epispadias-complex: A survey of the multicenter German CURE-Net.

OBJECTIVE: Standardized knowledge about genital function in adult female individuals with exstrophy-epispadias complex (EEC) is scarce. The aim of this study was to investigate sexual function using the standardized Female Sexual Function Index (FSFI), and to assess the influence of bladder and vaginal reconstruction and the presence of incontinence on FSFI results. METHOD: Sixty-one females (aged ≥18 years) recruited by the German multicenter network for congenital uro-rectal malformations (CURE-Net) were asked to complete the FSFI and a self-designed semi-structured questionnaire assessing comprehensive medical data, gynecological, and psychosocial items. Twenty-one eligible females (34%) returned both questionnaires (mean ± standard deviation [SD] age of 26 ± 5.1 years). RESULTS: In 43% of participants, a staged or single-staged approach had been used for reconstruction, and these had their bladder in use. A primary or secondary urinary diversion (UD) after cystectomy had been performed in 38% of participants. Of the participants, 57% lived in a committed partnership, and 62% had sexual intercourse on a regular basis, with a further 19% experiencing pain or discomfort thereby. Introitus plasty was done in 43%. Mean total FSFI for all participants was 21.3 (SD 1.9). Most domain scores of patients after introitus plasty were similar compared with those without an operative vaginal approach, except for satisfaction (p = 0.057) and pain (p = 0.024). Comparing incontinent with continent patients, significant differences were found for desire (mean 4.6 vs. 3.5, p = 0.021), lubrication (mean 3.1 vs. 4.2, p = 0.049), and satisfaction (mean 1.6 vs. 3.6, p = 0.0065). In contrast pain was not significant between groups. CONCLUSIONS: Sexual activity rate in the present study was similar to that reported in the literature (81% vs. 89%), whereas dyspareunia rate was lower in our cohort (19% vs. 24%). The risk for sexual dysfunction seems to be lower in patients reconstructed with primary or secondary UD than patients with bladder in use. It is surprising that lubrification was better after UD than after bladder neck surgery. Incontinence and in some parts the history of an introitus plasty may play an additional role in development of sexual dysfunction in EEC. Although most of the female EEC patients lived in a committed partnership and had sexual intercourse, total FSFI values <26.55 clearly indicate a risk of sexual dysfunction. Although continence itself played a major role, females reconstructed with UD seem to have better sexual function. Further evaluation of sexual outcome and improvement of care for these patients is mandatory.

Cowper's syringocele: A rare differential diagnosis of infravesical obstruction in boys and young adults.

OBJECTIVE AND INTRODUCTION: Cowper's syringocele is a cystic dilation of the bulbourethral gland duct, initially defined by Maizels et al. in 1983. Although obstructive and non-obstructive types of this rare anomaly are described, clinical symptoms are highly unspecific. Therefore, we report 12 cases of children and young adults diagnosed with Cowper's syringocele to further clarify clinical course, comorbidity and treatment strategies. STUDY DESIGN: We retrospectively collected clinical data of 12 children and young adults from birth to 18.5 years (median 7.2 years) who had been treated in four different institutes during a period of 16 years. The primary specific diagnostic work-up consisted of ultrasound, cystourethrography, and cystoscopy. RESULTS: 3Older patients with a median age of 11.8 years clinically presented with obstructive voiding pattern or gross hematuria; infants with a median age of 0.6 years presented with febrile urinary tract infections (UTIs). After cystoscopic confirmation in all patients, endoscopic treatment was possible in nine; open surgical resection was necessary in three patients. Because of intrauterine megacystis and chronic renal failure, one boy underwent suprapubic diversion with a cystostomy soon after birth. Owing to urological comorbidity or later complications, additional procedures were necessary, for example, resection of minor urethral valves, prophylactic circumcision for UTI, endoscopic or open antireflux procedures, and occasionally complex bladder reconstructions in the long term. DISCUSSION: According to our data, the initial clinical symptoms of Cowper's syringocele were related to presenting age rather than the previously described type of syringocele according to Maizels et al. Infants presented with febrile UTIs; however, older boys and young adults had mainly voiding problems or nocturnal enuresis. Therefore, the clinical significance of the described syringocele types must be questioned. Eighty-three percent of our patients showed additional urological pathology such as vesicoureterorenal reflux, ureteropelvic junction obstruction, megaureter, or minor urethral valves. Thus, Cowper's syringocele hardly seems to be an isolated pathology. CONCLUSION: Although rare, Cowper's syringoceles should be considered in differential diagnosis of infravesical obstruction in boys and young adults. Diagnostics are usually justified by presenting symptoms such as UTI or urinary flow impairment, which seem to be age dependent. Despite modern diagnostic tools, diagnosis is usually made by cystourethrography and sometimes accidentally by cystoscopy. Considerable urological comorbidities and consecutive bladder dysfunction need long-term follow-up.

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.

Morphological and Functional Hip Long-Term Results after Exstrophy Repair.

Introduction Abnormalities of the bony pelvis in exstrophy-epispadias complex (EEC) and their possible relation to hip disease are well described. However, there is a lack of information about long-term orthopedic consequences and hip function in patients with EEC. Therefore, we investigated clinical and radiological results in an EEC patient cohort after long-term follow-up. Patients and Methods We conducted a cross-sectional study using standardized radiography, clinical investigation, and the Harris hip score. Seventeen postpuberty consecutive unselected EEC patients (3 female, 14 male; mean age 18.2 years) that presented to our clinic due to urological procedures or routine check-up from 2010 to 2011 were included. All had undergone symphysis approximation with a traction bandage without osteotomy in early childhood. Radiological analysis was conducted offline by two independent investigators. Results Radiological analysis showed a mean pubic diastasis of 5.1 cm (range 2.8-8.5 cm). Borderline hip dysplasia was present in four patients, one of them having had co-occurring developmental hip dysplasia in previous history. No severe dysplasia, subluxation, or luxation of the hip was found; however, one patient showed early hip arthrosis. Clinical examination revealed no relevant restriction of range of motion, although rotation and abduction were slightly altered in five patients. None of the EEC patients complained about pain or restriction in sports or daily activities. Harris hip score was perfect for all but one study participants. Conclusion Despite EEC-specific hip morphology, long-term hip function is not impaired in patients after symphyseal approximation without osteotomy in the newborn period. The symphysis diastasis after this procedure is comparable to available postosteotomy data. The large majority of EEC patients did not show dysplastic or degenerative hip disease. Functional hip score results confirmed reasonable age-related hip function in nearly all examined patients. However, postnatal ultrasound hip screening is recommended to prevent and adequately treat potential co-occurring developmental hip dysplasia.