The gene for the tissue inhibitor of metalloproteinase 3 (TIMP3) on 22q12.3 had been reported to be inactivated by promoter methylation in various types of cancers, with controversial findings in meningiomas. We performed direct sodium bisulfite sequencing in a series of 50 meningiomas, including 27 benign meningiomas [World Health Organization (WHO) grade I], 11 atypical meningiomas (WHO grade II) and 12 anaplastic meningiomas (WHO grade III), and found hypermethylation of TIMP3 in 67% of anaplastic meningiomas, but only 22% of atypical and 17% of benign meningiomas. Moreover, TIMP3 methylation scores were significantly inversely correlated with TIMP3 mRNA expression levels (P = 0.0123), and treatment of the meningioma cell line Ben-Men-1 with demethylating agents induced an increased TIMP3 mRNA expression. TIMP3 is located in the chromosomal band 22q12, the allelic loss of which occurs early in meningioma tumorigenesis and preferentially targets the NF2 tumor suppressor gene. In our tumor panel, all meningiomas with TIMP3 hypermethylation--except for a single case--exhibited allelic losses on 22q12.3. Thus, TIMP3 inactivation by methylation seems fairly exclusive to meningiomas with allelic losses on 22q12 but--in contrast to NF2 mutation--appears to be involved in meningioma progression as it is associated with a more aggressive, high-grade meningioma phenotype.

IntroductionPenile carcinoma has an incidence of 4,000 cases in Europe. The therapy and prognosis depend decisively on the lymph node status. Lymph node metastases are detected in 23–65% cases depending on the histopathological pattern. Due to improved diagnostic methods an early detection of tumor stage is possible. Multimodal therapeutic concepts can offer curability for a subset of patients, even those suffering from advanced disease.Material and methodsCurrent data on penile cancer based on a selective review of the literature by PubMed and the EAU guidelines 2009.ResultsInvasive diagnostic tools, such as fine–needle biopsy (FNB) and dynamic sentinel node biopsy (DSNB), improved the diagnosis of lymph node status considerably and reduced the morbidity in specialized centers. The application of 18F–FDG–PET/CT for metastases detection needs further evaluation due to inconsistent results. Inguinal lymphadenectomy is the therapeutic standard in case of metastases proof. It was possible to reduce the complications due to the new modified operation techniques. Patients with extended lymph node and distant metastases have a poor prognosis. Different systemic polychemotherapy regimes are applied currently and are associated with poor outcome (response rates <50%) and high morbidity. Neoadjuvant chemotherapy is recommended in patients with unresectable and relapsing lymph node metastases.ConclusionsCurrently, inconsistent therapy regimens are applied for metastatic penile cancer. Standardization is urgently needed through the development of high–quality studies and long–term registers in order to lower the morbidity and increase the efficiency of diagnosis and therapy.

UBC Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

Background: Human amniotic membranes (HAMs) are assumed to have a number of unique characteristics including durability, hypoallergenic and anti-inflammatory properties.Materials and Methods: Multilayer HAMs from caesarian sections were applied to repair defined bladder defects in male Sprague-Dawley rats. The animals were sacrificed at 7, 21 and 42 days after implantation. Bladder volume capacity after grafting was measured. Histological analyses were performed to asses a number of parameters including HAM degradation, inflammatory reaction, graft rejection and smooth muscle ingrowth.Results: One rat died from sepsis in the treated group. No severe complications or signs of leakage were observed. Bladder capacity did not change over time. The initially increased inflammation in the HAM group diminished significantly over time (p<0.05). No signs of HAM degradation were observed and smooth muscle staining increased over time.Conclusions: HAMs appear to be durable and hypoallergenic grafts. The assumed suitability for the reconstruction of urinary tract justifies further research on detailed immunological process in larger grafts.

Purpose. To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. Materials and Methods. Three different meshes (TVT, UltraPro, and PVDF) were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a) interaperitoneally, (b) as fascia onlay, and (c) as muscle onlay (fascia sublay). At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. Results. Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. Conclusion. The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

Objectives: UBC® Rapid Test measures soluble fragments of cytokeratins 8 and 18 in urine. We present results of a multicenter study using an updated version of UBC® Rapid Test in bladder cancer patients, patients with urinary bladder cancer positive history, and healthy controls. Material and Methods: In total 530 urine samples have been included in this study. Clinical urine samples were used from 242 patients with tumors of the urinary bladder (134 non-muscle-invasive low-grade tumors (NMI-LG), 48 non-muscle-invasive high-grade tumors (NMI-HG), and 60 muscle-invasive high-grade tumors (MI-HG)), 62 patients with non-evidence of disease (NED), and 226 healthy controls. Urine samples were analyzed by the UBC® Rapid point-of-care (POC) assay and evaluated by Concile Omega 100 POC Reader. All statistical analyses have been performed using R version 3.2.3. Results: Elevated levels of UBC® Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). The sensitivity for the whole bladder cancer cohort was 53.3% (positive predictive value (PPV) 90.2%, negative predictive value (NPV) 65.2%) and was 38.8% (PPV 78.8%, NPV 72.1%) for non-muscle-invasive low-grade bladder cancer; 75.0% (PPV 72.0%, NPV 94.7%) for non-muscle-invasive high-grade bladder cancer and 68.3% (PPV 74.6%, NPV 91.8%) for muscle-invasive high-grade bladder cancer. The specificity for the statistical calculations was 93.8%. The cut-off value (10 µg/L) was evaluated for the whole patient cohort. The area under the curve of the quantitative UBC® Rapid Test using the optimal threshold obtained by receiver operating characteristics (ROC) analysis was 0.774. Elevated values of UBC® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumors and the healthy control group. Conclusions: UBC® Rapid Test has potential to be a clinically valuable urinary protein biomarker for detection of high-grade bladder cancer patients and could be added in the management of NMI-HG tumors. UBC® Rapid results generated in both study centers in the present multicenter study are very similar and reproducible. Furthermore UBC® Rapid Test is standardized and calibrated and thus independent of used batch of test as well as study site.

The sling procedures are the gold standard for SUI treatment. They are highly effective but not free from complications. The most common adverse effect for the surgery with the implant insertion is: overactive bladder occurring de novo after the surgery, voiding dysfunctions, urine retention, and unsatisfactory treatment outcome. The most important question that arises after 20 years of sling procedures is how to manage the complications and what can be offered to complicated patients. The above review summarises the ultrasound findings in complicated cases and shows the scheme of management of the clinical problems concerning the tape location in suburethral region.