[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology]. / Einsatz von synthetischen Band- und Netzimplantaten bei der Behandlung von Belastungsinkontinenz und Descensus genitalis der Frau : Stellungnahme des Arbeitskreises Urologische Funktionsdiagnostik und Urologie der Frau der Akademie der Deutschen Gesellschaft für Urologie.

Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

Influence of body mass index, surgical approach and lymphadenectomy on the development of symptomatic lymphoceles after radical prostatectomy.

PURPOSE: Identification of factors influencing lymphocele formation requiring intervention after radical prostatectomy. METHODS: 302 patients undergoing radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal-Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p = 0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008). Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on SLC. In a multivariate analysis surgical method, the number of resected LN and the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower incidence of SLC after RALP compared to RRP probably results from peritoneal drainage of lymphatic fluid. The correlation of removed LN and SLC might be explained by increased injury of lymphatic vessels during more extended LN dissection. Why patients with lower BMI are more prone to develop SLC still remains unclear. However, early postoperative mobilization in nonobese patients might be a contributing factor.

[Primary monosymptomatic enuresis: diagnostics and therapy]. / Primäre Monosymptomatische Enuresis: Diagnostik und Therapie.

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.

[Laparoendoscopic single-site surgery in urology using reusable systems]. / Laparoendoskopische Single-site-Chirurgie in der Urologie durch Einsatz eines wieder verwendbaren Systems.

PURPOSE: Many disposable platforms have been available for laparoendoscopic single-site surgery (LESS) for a long time. Besides technical challenges cost remains the limiting factor for the widespread use of LESS. We present our experiences with the first completely reusable LESS platform. METHODS: We performed LESS procedures in 52 patients, including nephrectomy (n=18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with a simplified combination of standard and preformed instruments. Perioperative and demographic data including a visual analogue pain scale (VAS) were obtained. Complications were recorded using the Clavien classification. RESULTS: The mean age of the patients was 50.04 years. Conversion to standard laparoscopy was necessary in 3 cases and the additional use of a 3 mm needle instrument in 6 cases. There were no open conversions. Intraoperative and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml, respectively. CONCLUSIONS: The LESS technique with a completely reusable platform is applicable to various indications in urology yielding favorable functional and cosmetic results. This novel simplified combination of instruments facilitates handling and shortens the learning curve. Reusable materials may help to reduce cost leading to a wider acceptance of LESS.

Videourodynamic changes of botulinum toxin A in patients with neurogenic bladder dysfunction (NBD) and idiopathic detrusor overactivity (IDO) refractory to drug treatment.

PURPOSE: To document the videourodynamic changes and the efficacy and safety profile of botulinum toxin A (BoNT-A, Dysport(®)) in neurogenic bladder dysfunction (NBD) including neurogenic detrusor overactivity, low-compliance and break-low-compliance and idiopathic detrusor overactivity (IDO), in patients refractory to drug treatment. METHODS: Sixty-four patients with NBD and 170 patients with IDO were treated between 2002 and 2007. Diagnostic approach included medical history, bladder diary, standardised questionnaire rating quality of life, sonography, videourodynamic and temporary sacral nerve block. All patients received BoNT-A-injection under local anaesthesia. Patients with NBD received 500 mouse units (MU) and patients with IDO received 250 MU BoNT-A, injected into ten sites including the trigonum. Patients were followed up 6 weeks after injection. RESULTS: For NBD, 58/64 (91%) patients achieved satisfactory continence during the day as well as significant reduction in incontinence episodes and improvement in quality of life. For IDO, 158/170 (93%) were responders with regard to urgency and urge incontinence. Urodynamical changes included significant improvement in the following parameters in both groups: increase in maximum cystometric capacity and decrease in detrusor pressure. BoNT-A was well tolerated; no drug-related side effects were documented. No de novo vesicoureteral reflux was induced. Long-term follow-up revealed a mean duration effect of BoNT-A of 5.7 months in NBD and 4.9 months in IDO. CONCLUSIONS: BoNT-A is highly effective in NBD as well as in IDO suggesting that this is a good treatment option for patients with detrusor overactivity. Furthermore, intratrigonal injection is safe and not associated with vesicoureteral reflux.

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma.

Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

[The importance of lymphadenectomy for muscle invasive transitional cell carcinoma of the human bladder - a review of the literature]. / Die Wertigkeit der Lymphadenektomie beim muskelinvasiven Urothelkarzinom der Harnblase - Ein Überblick über die aktuelle Datenlage.

INTRODUCTION: The extent of the lymphadenectomy (LAE) as well as the appearance of lymph node metastasis are important prognostic factors in the treatment of the muscle invasive transitional cell carcinoma of the bladder (TCC). However there is still the need to discuss the dimension of the LAE. MATERIAL AND METHODS: Pubmed was searched with regard to guidelines for the treatment of muscle invasive TCC. In particular, operation techniques, the appearance of lymph node metastasis, lymph node mapping, histopathological and radiological detection methods, as well as the risk of positive lymph nodes were analysed. RESULTS: The confirmation of lymph node metastasis is associated with a poorer outcome. Besides knowledge of metastasis pathways, an extensive and careful pathological reprocessing is one cornerstone of the procedure. Molecular markers seem to support the detection of micrometastasis. The extended LAE is associated with a better long-term survival rate compared to the limited LAE. New operation techniques such as laparoscopic or robot-assisted cystectomy are associated with lower peri- and postoperative morbidity, but the extended LAE is more challenging using these techniques. There are no long-term results available yet for these methods. Most data regarding lymphadenectomy and survival rate are based on retrospective studies thus decreasing the level of evidence. CONCLUSION: An extended LAE shows retrospectively a better outcome in patients with lymph node metastasis in TCC. Therefore an extended LAE should be performed in patients with muscle invasive TCC. New methods for detecting lymph node metastasis are elevating the confirmation rate.

Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development.

PURPOSE: Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients. METHODS: Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations. RESULTS: AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient. CONCLUSIONS: Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.

Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective.

OBJECTIVE: To evaluate outcomes of desmopressin treatment in monosymptomatic enuresis (ME) and nonmonosymptomatic enuresis (NME). MATERIALS AND METHODS: PubMed was searched for all studies investigating enuresis, up to July 2009, in which desmopressin was administered alone or combined with other treatments. Each study was graded according to its respective level of evidence. RESULTS: Altogether, 99 studies enrolling 7422 patients were identified as fulfilling the inclusion criteria. In 76 studies, desmopressin was administered as monotherapy; in 29 it was combined with other treatments such as antimuscarinics and enuresis alarm. CONCLUSION: Studies incorporating a minor invasive versus a non-invasive diagnostic approach seem to achieve superior long-term success rates. Primary efficacy outcomes following desmopressin treatment are more favourable in ME than NME. Desmopressin administered with adjunct measures achieves superior outcomes compared to monotherapy, especially in NME. Compared to sudden withdrawal, the structured withdrawal programs show better long-term success and lower relapse rates. So far, no superiority has been shown for either time- or dose-dependent structured withdrawal programs. Most studies incorporated only small case series; only 25 studies with level of evidence 1 or 2 have been conducted. The broad range of mono- and adjunct treatments were evaluated according to the evidence based criteria recommended by the European Association of Urology.

Evidence for PTEN-independent Akt activation and Akt-independent p27(Kip1) expression in advanced bladder cancer.

In the treatment of advanced bladder cancer (BC), attention has recently focused on small molecule therapy concerning EGFR and the downstream Akt signalling pathway. Cellular deregulation processes are poorly understood, and biological determinants for the selection of therapy and monitoring are currently not available. The proteins PTEN, p-Akt and p27(Kip1) are suggested to be potentially significant biomarkers of Akt signalling. In this study, we investigated the expression of these proteins in advanced BC. PTEN, p-Akt and p27(Kip1) expression was determined immunohistochemically in 86 T2-4 BC specimens using a tissue microarray technique. Staining was documented with regard to intensity, cellular frequency and a multiplied staining score. Staining characteristics of the three proteins were correlated by regression analysis with the parameters of tumour stage and grade. A positive correlation was observed in the expression scores of PTEN and p-Akt, p-Akt and p27(Kip1) as well as PTEN and p27(Kip1) (p<0.02 for all combinations). The positive correlation between PTEN and p-Akt resulted mainly due to the strong correlation of PTEN intensity with p-Akt (p=0.0003 and p=0.0006 to p-Akt frequency and intensity, respectively). A positive correlation between p-Akt and p27(Kip1) was noted for p-Akt frequency as well as intensity (p<0.05 for all combinations). The positive correlation between PTEN and p27(Kip1) resulted due to the correlation of PTEN intensity alone with p27(Kip1) (p<0.03 for p27(Kip1) frequency and intensity), whereas no significance was noted for PTEN frequency. No correlation was found between T or G and expression of the proteins. However, activation of Akt in BC is known to occur independently of PTEN protein loss and appears not to cause a decrease of p27(Kip1). However, a direct regulatory impact of PTEN on p27(Kip1) was found. PTEN intensity, rather than frequency, appears to be a superior biomarker. These results may provide information to support research into protein profiling-predicted targeted therapy for BC. Correlations to benign urothelium, superficial BC specimens and follow-up data remain to be investigated.

A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis.

AIMS: Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5-15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet/MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets identical with 120/240 microg MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded. RESULTS: Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged < 12 years had a statistically significant preference for desmopressin MELT (p = 0.0089). Efficacy was similar for both formulations (MELT: 1.88 +/- 1.94 bedwetting episodes/week; tablet: 1.90 +/- 1.85 episodes/week). Ease of use of both formulations was high. Compliance (> or = 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. CONCLUSIONS: There was an overall preference for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5-11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5-6 years.

[Therapy for overactive detrusor using propiverine]. / Therapie der Detrusorhyperaktivität mit Propiverin.

BACKGROUND: Our aim was to evaluate the efficacy and tolerability of propiverine hydrochloride (propiverine) in daily practice and to check the risk-benefit relation using previously collected data on 4,390 patients. PATIENTS AND METHODS: A total of 2,932 patients with symptoms of overactive bladder were treated with propiverine over a period of 12 weeks using a multicentre post marketing surveillance. At three visits (inclusion, after 4 weeks, after 12 weeks), parameters from the micturition diary (incontinence episodes, frequency of micturition, micturition volume) were recorded. RESULTS: The number of incontinence episodes during daytime decreased during therapy from 3.6+/-3.8 to 1.2+/-2.3. The number of episodes at night decreased from 1.5+/-2.1 to 0.4+/-0.8 (both P<0.001). The mean volume per micturition improved during therapy (from 142.7 ml to 213.3 ml; +49.5%; P<0.0001). Some 85% of the investigators judged the efficacy of propiverine to be good or very good, 2.1% as not sufficient. The most frequent adverse event was dry mouth (17.3% of the patients after 12 weeks) mostly with low severity. More than 70% of the patients reported good or very good tolerability. Only 0.6% of the patients reported insufficient tolerability.

A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence.

OBJECTIVE: To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial. PATIENTS AND METHODS: In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented. RESULTS: A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo. CONCLUSION: Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence.

[Orthotopic urinary bladder replacement in the woman. Initial clinical experiences]. / Der orthotope Harnblasenersatz bei der Frau. Erste klinische Erfahrungen.

Ileum neobladder after cystectomy is mainly reserved for male patients. Female patients are normally excluded from this kind of urinary diversion for fear of incontinence following orthotopic bladder substitution. In addition as in the male, the question of urethral recurrence of urothelial carcinoma is still not settled. We report on seven cases of successful orthotopic bladder reconstruction in females by means of an ileum neobladder according to Hautmann with follow up of up to 4.5 years. One of these patients had a complicated bladder-vaginal fistula and almost complete loss of bladder function because of a shrunken bladder after radiation therapy for a cervical carcinoma and the other six had undergone radical cystectomy because of bladder carcinoma. The ileum neobladder is anastomosed with the preserved urethral stump. The original method of ileum neobladder is extended by a colposuspension plasty according to Marshall-Marchetti, which is the means of achieving continence. The first results are encouraging and open further possibilities for bladder reconstruction in the female.

[Radiotelemetric manometry of the urinary bladder]. / Radiotelemetrische Manometrie der Harnblase.

The standard procedure for manometric investigation of bladder function involves the use of a urethral catheter. The presence of this foreign body causes irritations, however, with a resultant increase in urethral resistance. This perturbs the micturition process, but it can be avoided by a new telemetric method of intravesical pressure measurements. A very small pressure gauge and radio emitter are introduced into the bladder, and the values measured are transmitted to an external receiver. Thus, for the first time, is possible to perform physiological studies of bladder function that do not require catheterization or special positioning of the patient and are well tolerated. Some examples are described, which show that this method allows repeated catheter-free investigations over longer periods of time and accurate evaluation of the effects of pharmacological products on bladder function.