Point-of-Care Tests for Bladder Cancer: The Influencing Role of Hematuria

Introduction. Several point-of-care tests (POCT) are available for the diagnosis of bladder cancer (BC). We evaluate the impact of HU (hematuria) on performance of POCTs. Materials and Methods. Urine from 10 donors was diluted with blood from 0.5 to 0.00625%. BladderCheckR, BTAstatR, BCMR, and BTAR tests were applied. Tests were additionally conducted in 54 patients with HU. HU was stratified according to the amount of erythrocytes (RBC)/μL using two systems: (1) no HU; mild microscopic HU; severe microscopic HU; gross HU; (2) I <25 RBCs; <250 II; ≥250 III. Results were compared to HU status and histopathology. Results. Gross HU became evident between 2090 RBCs/μL and 1065/μL. Addition of blood led to default tests in all 4: BladderCheckR 0.25%; BCM 0.025%, BioNexia 0.00625%, and BTAstat <0.00625%. Rates of false positives for BladderCheck, BTAstat, BCM, and BioNexia were 5.9, 11.8, 0, and 1.8% without HU and 0, 66.7, 44.4, and 66.7% with HU. BTAstat, BCM, and BioNexia were independently influenced by HU (P < 0.0002). Conclusions. NMP22-BladderCheck was most resistant to blood. The diagnostic yield of all others was significantly influenced by HU. A well-defined HU grading helps to define limits of HU for a reliable interpretation of BC-POCTs

Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.</p> <p>Case presentation</p> <p>A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.</p> <p>Conclusions</p> <p>Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.</p

RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of the RAS association domain family 1A (<it>RASSF1A</it>) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for <it>RASSF1A </it>methylation in normal kidney, thus it is not clear whether a significant difference between <it>RASSF1A </it>methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.</p> <p>Results</p> <p>Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; <it>P </it>< 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.</p> <p>Conclusion</p> <p>Our methylation and expression data support the hypothesis that <it>RASSF1A </it>is involved in early tumorigenesis of renal cell carcinoma.</p

Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer

<p>Abstract</p> <p>Background</p> <p>Fibronectin 1 (<it>FN1</it>) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of <it>FN1 </it>in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.</p> <p>Methods</p> <p>212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of <it>FN1 </it>mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.</p> <p>Results</p> <p>Mean tissue specific <it>FN1 </it>mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean <it>FN1 </it>expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10^-5; Wilcoxon rank sum test). Patients with advanced disease had higher <it>FN1 </it>expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher <it>FN1 </it>mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).</p> <p>Conclusions</p> <p>To our knowledge, this is the first study to show that <it>FN1 </it>mRNA expression is higher in RCC compared to normal renal tissue. <it>FN1 </it>mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.</p

Neural correlates of the processing of co-speech gestures

In communicative situations, speech is often accompanied by gestures. For example, speakers tend to illustrate certain contents of speech by means of iconic gestures which are hand movements that bear a formal relationship to the contents of speech. The meaning of an iconic gesture is determined both by its form as well as the speech context in which it is performed. Thus, gesture and speech interact in comprehension. Using fMRI, the present study investigated what brain areas are involved in this interaction process. Participants watched videos in which sentences containing an ambiguous word (e.g. She touched the mouse) were accompanied by either a meaningless grooming movement, a gesture supporting the more frequent dominant meaning (e.g. animal) or a gesture supporting the less frequent subordinate meaning (e.g. computer device). We hypothesized that brain areas involved in the interaction of gesture and speech would show greater activation to gesture-supported sentences as compared to sentences accompanied by a meaningless grooming movement. The main results are that when contrasted with grooming, both types of gestures (dominant and subordinate) activated an array of brain regions consisting of the left posterior superior temporal sulcus (STS), the inferior parietal lobule bilaterally and the ventral precentral sulcus bilaterally. Given the crucial role of the STS in audiovisual integration processes, this activation might reflect the interaction between the meaning of gesture and the ambiguous sentence. The activations in inferior frontal and inferior parietal regions may reflect a mechanism of determining the goal of co-speech hand movements through an observation-execution matching process

Embodiment and emotional memory in first vs. second language

Language and emotions are closely linked. However, previous research suggests that this link is stronger in a native language (L1) than in a second language (L2) that had been learned later in life. The present study investigates whether such reduced emotionality in L2 is reflected in changes in emotional memory and embodied responses to L2 in comparison to L1. Late Spanish/English bilinguals performed a memory task involving an encoding and a surprise retrieval phase. Facial motor resonance and skin conductance (SC) responses were recorded during encoding. The results give first indications that the enhanced memory for emotional vs. neutral content (EEM effect) is stronger in L1 and less present in L2. Furthermore, the results give partial support for decreased facial motor resonance and SC responses to emotional words in L2 as compared to L1. These findings suggest that embodied knowledge involved in emotional memory is associated to increased affective encoding and retrieval of L1 compared to L2

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58–0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70–0.76) for high-grade (HG) BC, respectively. Age, UBC Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC