[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pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime.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.

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.

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.

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.