Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy. Materials and Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series. Multivariable Cox regression models including substaged pT3 established clinicopathological features, and the expression of the predictive immunohistochemical feature E-cad was used to identify independent predictors on progression-free (PFS), cancer-specific (CSS) and overall survival (OS), respectively. Results: No significant differences were found addressing clinicopathological data and substaged pT3. In multivariable Cox regression models, lymph node involvement was an independent predictor for PFS (p < 0.001), CSS (p < 0.001) and OS (p = 0.002), respectively. Lymphovascular invasion (LVI) significantly influenced PFS (p = 0.016). ASA score 3/4 independently predicted CSS (p = 0.049) and OS (p = 0.032). Neither pT3 substages nor E-cad expression were significant prognosticators for survival. Conclusions: In pT3 UCB patients with ASA 3/4, positive lymph node status and/or presence of LVI, administration of chemotherapy should be considered due to the high risk of poor oncological outcome. The immunohistochemical marker E-cad was not an independent predictor

Immunohistochemical and molecular characterizations in urothelial carcinoma of bladder in patients less than 45 years

Bladder tumours in early-onset patients are rare and seem to exhibit unique clinicopathological features. Only few studies have investigated somatic alterations in this specific age of onset group and evidence is accumulating of a distinct molecular behaviour of early-onset bladder tumours. We collected the largest cohort of early-onset tumours of patients 45 years old or younger and aimed to test genomic alterations typically found in bladder cancer. Tumours of 118 early-onset patients were compared with a consecutive group of 113 cases. Immunohistochemistry of TP53, CK20 and Ki-67 was carried out. Molecular analysis was conducted to test for loss of heterozygosity of chromosome 9 and 17, as well as TP53 and FGFR3 mutations. Fisheŕs exact and chi-squared test were appropriately used. No differences in grade/stage characteristics were observed. Overexpressed TP53 was differentially distributed between the two groups. TP53 nuclear accumulation was significantly more frequent in early-onset papillomas, PUNLMPs and pTa low-grade tumours compared to the consecutive cohort (p=0.005). Moreover, chromosome 9 deletions (29.5% vs. 44.6%) and FGFR3 mutations (34.5% vs. 63.7%) were less often detected in early-onset patients (p=0.05 and p<0.0001). By comparing the largest cohort of early-onset bladder cancer patients with an unselected group, we demonstrated that the typical molecular features are not independent of age at diagnosis. Our study supports the hypothesis of a distinct biological behaviour in early-onset tumours

Mask collimation meets high-efficient data acquisition: A novel design of a low-dose-CT-scanner for breast-imaging.

A novel designed x-ray CT scanning geometry is proposed. Composed of a specially designed tungsten collimation mask and a flat panel detector, which is placed inside the mask, this scanning geometry provides high efficient data acquisition allowing dose reduction potential by a factor of two. In recent years a first prototype of the CTDOR geometry (CT with Dual Optimal Reading) has been evaluated. It consisted of a discontinuous ring of detectors fixated on X-Ray absorbing material. The source and an outer detector were mounted on a gantry rotating around the inner static detector and the patient. Despite many drawbacks, resulting images have shown promising potential of dual reading. Based on those results, the present work presents further development and improvement of the recommended scanner geometry. The main idea consists of collimating the X-ray beam through a specially designed shielding mask thereby reducing radiation dose and structuring data without compromising image quality. An especially developed high precision laser-beam cutting process assures an accurate mask crafting with tungsten shielding and window sizes of 300&mu;m. Additionally, simulation data were obtained with Monte Carlo calculations to test the dose reduction potential of the scanning device. Retaining advantages of the CTDOR geometry such as 3D-capability, built-in capacity of scatter correction and radiation structuring, a high-precision manufactured collimation mask of novel designed CT-scanner enables high resolution images for breast-imaging in low energy ranges

Sequential laser and EDM micro-drilling for next generation fuel injection nozzle manufacture

In this paper we present a novel Radio Frequency Identification (RFID) system for accurate indoor localization. The system is composed of a standard Ultra High Frequency (UHF), ISO-18006C compliant RFID reader, a large set of standard passive RFID tags whose locations are known, and a newly developed tag-like RFID component that is attached to the items that need to be localized. The new semi-passive component, referred to as sensatag (sense-a-tag), has a dual functionality wherein it can sense the communication between the reader and standard tags which are in its proximity, and also communicate with the reader like standard tags using backscatter modulation. Based on the information conveyed by the sensatags to the reader, localization algorithms based on binary sensor principles can be developed. We present results from real measurements that show the accuracy of the proposed system

TERT Core Promotor Mutations In Early-Onset Bladder Cancer

Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55,6% and 82,8% described so far, and are independent of stage and grade. Since only few data on molecular alterations of early-onset bladder tumors exist, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hot-spot-regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57,6% vs. 84,8%, p<0,001). Among the early-onset cohort cases younger than the cohort’s median age of 39 years at disease onset showed a significant reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67,5%; p=0,012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients