Barbara Kortmann

Urotherapy in children: quantitative measurements of daytime urinary incontinence before and after treatment according to the new definitions of the International Children's Continence Society

OBJECTIVE To assess the effectiveness of urotherapy in children with lower urinary tract dysfunction, according to the new definitions of the International Childrens Continence Society. MATERIAL AND METHODS We performed a retrospective review of 122 children (aged 8.8 ± 2.0 years) treated in an outpatient program for lower urinary tract dysfunction. Exclusion criteria included all neurologic abnormalities. In 98 children (80%) daytime urinary incontinence was a predominant symptom. Therapy consisted of an individually adapted drinking and voiding schedule, pelvic floor relaxation, instructions on toilet behavior, biofeedback uroflowmetry and if necessary recommendations for regulation of defecation. Before and at the end of training, patients were evaluated for number and severity of daytime wet accidents per week, using a scoring system to grade the severity of incontinence. Secondary measurements of accompanying voiding symptoms were performed. RESULTS Of the 90 children with daytime urinary incontinence for whom sufficient objective data were collected, 42% became completely dry during the daytime and 36% showed a 50% or greater level of response. Secondary measurements showed a significant reduction in daily voiding frequency (mean 7.0 ± .3, P<0.0001) and mean post-void residual (P<0.003), and an improvement in flow pattern (P<0.05). CONCLUSIONS Urotherapy is successful for the treatment of daytime urinary incontinence in children. Additional benefit was evident in improvement of accompanying voiding symptoms. A combination of the definitions of the International Childrens Continence Society and a scoring system to grade severity improved the evaluation method. Further research into long-term efficacy will be performed.

Tissue Engineered Tubular Construct for Urinary Diversion in a Preclinical Porcine Model

PURPOSE The ileal conduit has been considered the gold standard urinary diversion for patients with bladder cancer and pediatric patients. Complications are mainly related to the use of gastrointestinal tissue. Tissue engineering may be the technical platform on which to develop alternatives to gastrointestinal tissue. We developed a collagen-polymer conduit and evaluated its applicability for urinary diversion in pigs. MATERIALS AND METHODS Tubular constructs 12 cm long and 15 mm in diameter were prepared from bovine type I collagen and Vypro® II synthetic polymer mesh. Characterized tubes were sterilized, seeded with and without primary porcine bladder urothelial cells, and implanted as an incontinent urostomy using the right ureter in 10 female Landrace pigs. At 1 month the newly formed tissue structure was functionally and microscopically evaluated by loopogram and immunohistochemistry, respectively. RESULTS The survival rate was 80% with 1 related and 1 unrelated death. By 1 month the collagen was resorbed and a retroperitoneal tunnel had formed that withstood 40 cm H(2)O water pressure. In 5 cases the tunnel functioned as a urostomy. Histological analysis revealed a moderate immune response, neovascularization and urothelial cells in the construct lumen. The polymer mesh provoked fibroblast deposition and tissue contraction. No major differences were observed between cellular and acellular constructs. CONCLUSIONS After implanting the tubular constructs a retroperitoneal tunnel was formed that functioned as a urinary conduit in most cases. Improved large tubular scaffolds may generate alternatives to gastrointestinal tissue for urinary diversion.

Needs of children with a chronic bladder in preparation for transfer to adult care

OBJECTIVE Transfers to adult care can be problematic, resulting in postponement due to the protective nature of pediatric care and patient dependency. It is unknown whether these findings apply specifically to urology patients. Our department is taking part in a national general transition project. In this light, our aim was to investigate the specific needs of adolescent urologic patients, regarding their independence and transition. PATIENTS AND METHODS 80 patients, born in 1975-1998, with a chronic bladder condition received a questionnaire. They were divided into pre- and post-transfer groups. Parents (n = 7) of post-transfer patients formed a third group. Questionnaires were based on those used in the national transition study, supplemented with urological questions. Pre-transfer patients were asked about their level of independence, what subjects were discussed during consultations, and their expectations and wishes regarding transfer. Post-transfer patients and parents were asked for their opinions on the transfer process. RESULTS 73% (n = 58) responded (55 pre-transfer and 3 post-transfer patients plus parents). It appeared that the confidence built-up with the pediatric urologist impeded the transfer. An adequate level of disease-related knowledge was reported. Relationships, sexuality and fertility were hardly talked about (respectively n = 17, 16 and 18). Parents played an important role, which patients appreciated, confirming their dependency. Despite the 49% (n = 27) who stated they can arrange their urological care themselves, 44% (n = 24) felt ill-prepared for transfer. CONCLUSION Although overall self-perceived knowledge is sufficient, the trust in and personal relationship with the pediatric urologist formed the greatest obstruction to successful transition. These findings have been used to improve support during transition by creating a transition protocol.

Long-Term Outcomes in Males with Disorders of Sex Development

PURPOSE Indications that the prenatal action of testosterone in the brain is an important determinant of gender development and improved reconstructive techniques have caused a shift in male gender assignments in patients with 46XY disorders of sex development. We report long-term outcome data on psychosexual development and sexual function of these individuals in a cross-sectional study. MATERIALS AND METHODS Physical status of 14 men with a mean age of 25 years with disorders of sex development was assessed by structured interview and physical examination. Psychosexual outcome was evaluated by questionnaires and compared to a control group of 46 healthy, age matched men. RESULTS A total of 13 men underwent 1 to 6 (mean 2) genital surgeries. Mean age at first surgery was 2.7 years. Mean penile length was 6.6 cm. All men reported erections and were able to experience orgasms. Ejaculatory dysfunction was reported by 7 men. Mean penile length was 7.9 cm in patients who were able to achieve penetrative intercourse and 4.9 cm in those who were not. Meatus was glanular in 5 patients, coronal in 7 and at the distal shaft in 1. Compared to controls, men with disorders of sex development were less satisfied with the appearance of the penis and scrotum but not with total body image. These patients reported decreased sexual desire and activities. CONCLUSIONS Outcome in this group of men with disorders of sex development was poor regarding penile length, ejaculation, satisfaction with external genitalia and frequency of sexual activity. Other aspects, such as overall body image and psychosexual functioning, showed no difference from controls.

Tissue engineering of diseased bladder using a collagen scaffold in a bladder exstrophy model

To compare the regenerative capacity of diseased bladder in a large animal model of bladder exstrophy with regeneration in healthy bladder using a highly porous collagen scaffold.

Treatment response of an outpatient training for children with enuresis in a tertiary health care setting

PURPOSE To evaluate treatment effectiveness for children with enuresis, according to the definitions of the International Childrens Continence Society (ICCS, 2006). MATERIAL AND METHODS Children ≥6 years of age followed a 4-month outpatient treatment consisted of a visit during which history regarding enuresis was taken, causes were explained and therapeutic tips & tricks were discussed. All children received a booklet about enuresis and were trained with an alarm and/or pharmacological therapy. At baseline, 4, 10 and 16 months, the number of wet nights during the previous 28 days and the use of medication were assessed. Success of treatment was determined using ICCS definitions of treatment outcome. RESULTS 66 children with enuresis were included (48 boys/18 girls) in this retrospective study. Mean age: 11(± 2.6) years. 91%(n = 60) of the children had non-monosymptomatic enuresis. Results at 4 months: 46% full, 15% good, 21% partial response (n = 66). At 10 months: 55% full, 4% good, 29% partial response (n = 49). At 16 months: 53% full, 6% good, 25% partial response (n = 34). Overall, use of pharmacological therapy showed a decline in time. CONCLUSION According to the ICCS definitions, outpatient treatment for enuresis shows a good overall treatment response, and these results can be used to compare with other studies in the future.

Discrepant results of serum creatinine and cystatin C as a clue to urine leakage after renal transplantation.

REFERENCES 1. Langnas AN, Marujo W, Stratta RJ, et al. Vascular complications after orthoptic liver transplantation. Am J Surg 1991; 161: 76. 2. Chalasani N, Kahi C, Francois F, et al. Model for end-stage liver disease (MELD) for predicting mortality in patients with acute variceal bleeding. Hepatology 2002; 35: 1282. 3. Rattner D, Ellman L, Warshaw A. Portal vein thrombosis after elective splenectomy: An underappreciated, potentially lethal syndrome. Arch Surg 1993; 128: 565. 4. Valeri A, Venneri F, Presenti L, et al. Portal vein thrombosis: A rare complication of laparoscopic splenectomy. Surg Endosc 1998; 12: 1173. 5. Poplansky MR, Kaufman JA, Geller SC, et al. Mesenteric venous thrombosis treated with urokinase via the superior mesenteric artery. Gastroenterology 1996; 110: 1633. 6. Ryu R, Lin TC, Kumpe D, et al. Percutaneous mesenteric venous thrombectomy and thrombolysis: Successful treatment followed by liver transplantation. Liver Transpl Surg 1998; 4: 222. 7. Ciccarelli O, Goffette P, et al. Transjugular intrahepatic portosystemic shunt approach and local thrombolysis for treatment of early post transplant portal vein thrombosis. Transplantation 2001; 72: 159. 8. Bilbao JI, Arias M, Herrero JI, et al. Percutaneous transhepatic treatment of a posttransplant portal vein thrombosis and a pre-existing spontaneous splenorenal shunt. Cardiovasc Intervent Radiol 1995; 18: 323. 9. Blum U, Haag K, Rössle M, et al. Noncavernomatous portal vein thrombosis in hepatic cirrhosis: Treatment with transjugular intrahepatic portosystemic shunt and local thrombolysis. Radiology 1995; 195: 153. 10. Olliff SP, Pain JA, Karani JB, et al. Percutaneous transhepatic dilatation of late portal vein stenosis following orthoptic liver transplantation. J Intervent Radiol 1991; 6: 29.

Bladder regeneration using multiple scaffolds with growth factors in a bladder

INTRODUCTION Tissue engineering may become an alternative to current bladder augmentation techniques. Large scaffolds are needed for clinically significant augmentation, but can result in fibrosis and graft shrinkage. The purpose of this study was to investigate the use of multiple scaffolds instead of one large scaffold, to enhance bladder tissue regeneration and bladder capacity. Second, acellular collagen, collagen-heparin, and collagen-heparin scaffolds with growth factors (GFs) were used and the biological activity of the different scaffolds was compared in a large animal model. MATERIALS AND METHODS Scaffolds were made of bovine type I collagen with or without heparin (Ø = 3.2 cm). Collagen-heparin scaffolds were loaded with GFs, vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and heparin-binding epidermal growth factor (HB-EGF). Three identical scaffolds prepared from collagen (COL-group), collagen with heparin (COLHEP-group), or collagen-heparin with growth factors (COLHEPGF-group) were implanted in one porcine bladder. The outcome was compared with sham-operated animals (Sham-group), in which no scaffold was used. Urodynamic evaluation was performed before surgery and 3 months after bladder reconstruction, together with histological evaluation. RESULTS Survival rate was 92%, 12 animals completed the study, 3 of every group, 1 animal developed peritonitis due to urine leakage and was sacrificed. The regenerated area was largest in the COLHEP-group, and least in the COL-group (p = 0.002). Histological evaluation revealed a normal urothelial layer and good angiogenesis in all groups, and comparable ingrowth of smooth muscle cells. Urodynamics showed no statistically significant differences in bladder capacity and compliance between groups. Bladder capacity and compliance was very high in this animal model, which made it impossible to study the increase due to augmentation. CONCLUSIONS Implantation of multiple collagen-heparin scaffolds in one bladder is feasible in a porcine model, resulting in tissue almost indistinguishable from native tissue involving all cell layers of the bladder. Collagen scaffolds with heparin incorporated resulted in a larger area of regenerated tissue. To reach clinically significant augmentation, multiple larger collagen-heparin scaffolds, with or without GFs, need to be tested to study the largest possible diameter of scaffold and number of used scaffolds still resulting in well-vascularized tissue.

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by the stent was observed in four out of seven animals. These results indicated that blind stent placement was not possible in goats. In four new goats, clinical protocols were followed using X-ray and iodinated contrast fluids to visualize the kidney and stent during stent placement. With this adaptation the stents were successfully placed in the kidneys of these four new goats with minimal additional effort. It is likely that other groups in other fields ran into similar problems that could have been avoided by following clinical protocols. Therefore, we would like to stress the importance of following clinical protocols when using medical devices in animals to prevent unnecessary suffering and to reduce the number of animals needed.

Kinderurologie en etiologie: Radboudumc AGORA data- en biobank

SamenvattingInleiding:Het onderzoek naar de vraag ‘Waarom heeft mijn kind deze aandoening?’, ofwel de etiologie van kinderurologische afwijkingen, is gestart in 2002. Hiervoor werd een projectaanvraag ingediend bij de medisch-ethische toetsingscommissie om de komende 25 jaar bloed en aanvullende gegevens te mogen verzamelen die nu opgeslagen zijn binnen de Radboudumc AGORA data- en biobank.Materiaal en methoden:De basis van de Radboudumc AGORA data- en biobank wordt gevormd door klinische diagnosegegevens, vragenlijsten en genetisch materiaal. Om verzameling, gebruik en distributie van verzamelde gegevens mogelijk te maken, zijn informatiefolders, informed-consentformulieren, een samenwerkingsreglement, een aanvraagformulier en een material transfer agreement (MTA) ontwikkeld. Het AGORA-onderzoek betreft een samenwerking tussen klinische afdelingen, epidemiologie en genetica.Resultaten:In 2014 werden biobankdata verzameld van 1836 urologische en 616 uronefrologische patiënten. Vooral naar de aandoening hypospadie is veel onderzoek verricht en recent is er een internationale samenwerking ontstaan. Verder werd onderzoek gedaan naar aspecten voor maldescensus testis, vesico-ureterale reflux en blaasextrofie. Een samenvatting van de verschillende publicaties wordt in het kort weergegeven.Conclusie:Er zijn meerdere studies met betrekking tot de etiologische aspecten van hypospadie verricht, waaruit bekende en nieuwe resultaten zijn verkregen. Op dit moment is het nog niet mogelijk om de gehele etiologie vanuit een genetische of omgevingsfactor te verklaren, maar stap voor stap worden nieuwe verbanden gelegd. In kleine studies en in (inter)nationale samenwerkingsverbanden zijn momenteel ook nieuwe resultaten gevonden voor maldescensus testis, vesico-ureterale reflux en blaasextrofie. Een goede samenwerking met alle betrokkenen, goede afspraken en een goede logistiek zijn hierbij van essentieel belang.SummaryThe aetiology of paediatric urology anomalies: Radboudumc AGORA data- en biobankIntroduction:The research into the question ‘why does my child have this anomaly?’, or the aetiology of paediatric urology anomalies, started in 2002. For this purpose a project plan was submitted to the Internal Review Board on Human Studies to collect blood and additional information with a time schedule of 25 years. These data are currently stored in the Radboudumc AGORA data- en biobank.Methods:The basic collection of the Radboudumc AGORA data- and biobank data consists of the clinical diagnostic information, questionnaires and genetic material. To collect, use and distribute these data and materials an information brochure, informed consent forms, a collaboration contract, a study request form and a material transfer agreement (MTA) are part of the project. The AGORA program is a collaboration between clinical departments, epidemiology and genetics.Results:In 2014 there is a collection of biobank data of 1,836 urological and 616 uro-nefrological patients. Most research has been performed into the anomaly hypospadias and recently an international collaboration concerning these patients was established. Furthermore studies were performed concerning undescended testis, vesico-ureteral reflux and bladder exstrophy. A summary of the different publications is hereby presented.Conclusion:Different studies have been performed concerning the etiological aspects of hypospadias from which known and new findings were discovered. Currently, the aetiology cannot be totally explained by the environmental and genetic factors found, but step by step new associations are being found. In small studies and within (inter)national collaborations new results were also found for undescended testis, vesico-ureteral reflux and bladder exstrophy. For this kind of studies a pleasant and productive collaboration with all people involved, clear appointments and contracts, and good logistic procedures play an essential role.