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

Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential

Background: Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification. Methods: Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry. Results: Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM. Conclusion: The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets

The Prostate Cancer gene 3 assay: indications for use in clinical practice

The Prostate CAncer gene 3 (PCA3) assay is a novel tool that might aid in the diagnosis of prostate cancer and that might indicate the significance of the disease. In this review we discuss five clinical cases in which the PCA3 assay can be considered, based on scientific evidence and key patient cases from real-life clinical practice. The PCA3 assay might be used to guide biopsy decisions in: (i) Men with an elevated serum total prostate specific antigen (tPSA) level and one or more previous negative biopsies; (ii) men with a normal tPSA level and a family history of prostate cancer; (iii) men with an elevated tPSA level (2.5-10 ng/mL) and no previous biopsy; (iv) men with an elevated tPSA level and a concomitant urinary condition. In addition, in men diagnosed with prostate cancer, the PCA3 assay could aid in the decision of whether active therapy is needed or active surveillance is appropriate

Assessment of a new point-of-care system for detection of prostate specific antigen

Background: Measurement of the prostate specific antigen (PSA) remains an important tool in prostate cancer (PC) diagnosis. Due to limited availability of laboratory devices in an outpatient setting, compact and easy-to-handle point-of-care (POC) systems are desirable. Recently, a chip for PSA measurement on the concile® Ω100 POC reader platform was introduced. To investigate the clinical applicability, we evaluated the system in a consecutive cohort of patients undergoing PSA measurement in our outpatient clinic. Methods: Between 07/2014 and 01/2015, PSA was analyzed in a total of 198 patients by the POC reader system and in parallel by an Immulite 2000® and Centaur® standard laboratory system, respectively. By standard (Immulite®) measurement, 67 (34,2 %) had PSA > 4 ng/ml and 131 (65,8 %) had PSA ≤ 4 ng/ml. Results were correlated by linear regression analyses for all patients and within PSA subgroups. For patients with available prostate histology after PSA measurement (n = 68), receiver-operating characteristic curves were created and area under the curve (AUC), sensitivity and specificity for the prediction of PC at best cut-off value were calculated. Results: The coefficients of determination (r2) for the POC device compared to laboratory testing were 0.72 (Immulite®) and 0.63 (Centaur®), respectively (both p < 0.0001). In the PSA range of ≤4 ng/ml, the observed correlations were 0.75 and 0.70, respectively. For the POC test system, AUC for detection of PC was calculated with 0.745 while the standard laboratory tests showed 0.778 (Immulite®) and 0.771 (Centaur®). At best cut-off of 3.64 ng/ml, PSA analysis by the POC system showed a sensitivity of 85.7 % and a specificity of 66.7 %. Conclusions: The POC system obtained good concordance to elaborate laboratory measurement. In a screening scenario, the system provides quick and reliable PSA measurement, especially in the PSA range up to 4 ng/ml.Other UBCNon UBCReviewedFacult

Activation of PI3K is associated with reduced survival in renal cell carcinoma

OBJECTIVES: The epidermal growth factor receptor phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is associated with tumorigenesis and progression. The aims of the present study were to determine the expression patterns of Akt pathway parameters PI3K, phosphatase and tensin homolog (PTEN), phosphor-Akt (p-Akt) and their combination, for their possible prognostic value in renal cell carcinoma (RCC). PTEN dephosphorylates the liquid product of PI3K. METHODS: Tumor samples from 176 RCC patients were investigated for PTEN, p-Akt and PI3K expression by immunohistochemistry. Expression levels were correlated to clinical variables and postoperative outcom