Pavel Dusek

Influence of tumour-associated symptoms on the prognosis of patients with renal cell carcinoma

Objective. To evaluate the prognostic significance of symptoms related to renal cell carcinoma (RCC) in comparison with incidentally detected tumours in a group of long-term observed patients. Material and methods. The study included 396 patients operated for RCC between 1982 and 2001. The patients were classified according to age, gender, detection mode, pathological stage and grade, tumour size, nodal involvement and Eastern Cooperative Oncology Group (ECOG) performance status. Special attention was given to the analysis of duration and quality of symptoms. The endpoint of the study was overall survival, which was assessed with univariate and multivariate analyses using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results. Of the 396 patients, 135 (34%) and 261 (66%) presented with incidental and symptomatic RCC, respectively. Compared with incidental cases, symptomatic tumours had significantly larger size (p<0.0001), and higher pathological stage (p<0.0001) and grade (p<0.02). Five-year survival in patients with incidental and symptomatic tumours was 88.1% and 59.4% (p<0.0001), respectively. In relation to the quality of symptoms, the 5-year survival in patients with local and systemic symptoms was 75.4% and 44.4% (p<0.0001), respectively. In the group of patients with a history of tumour-related symptoms shorter and longer than 3 months, the 5-year survival was 62.2% and 55.6% (p<0.0001), respectively. Multivariate analysis found tumour size [hazard ratio (HR) 1.22, p=0.05] tumour grade (HR 1.44, p=0.002), tumour stage (HR 1.35, p=0.001), presence of symptoms (HR 1.36, p=0.004) and ECOG (HR 1.25, p=0.005) to be independent prognostic variables. Conclusion: Preoperative somatic symptoms and performance status in patients with RCC provide readily available prognostic information in addition to tumour size, stage and grade.

Urine and Serum Cathepsin B Concentrations in the Transitional Cell Carcinoma of the Bladder

It has been shown that expression and activity of lysosomal proteolytic enzymes (i.e., cathepsin B) correlate with tumor progression in various neoplasms. We investigate possible correlation of cathepsin B concentrations with grading and invasivity of tumorous bladder tissue.

Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors

PURPOSE Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

Mitochondrial membrane protein-associated neurodegeneration: a case report and literature review

ABSTRACT Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an autosomal recessive disorder caused by mutation in the C19orf12 gene. We report a compound heterozygous c.[32C>T];[205G>A;424A>G] (p.[Thr11Met];[Gly69Arg;Lys142Glu]) Czech patient who manifested with right foot dystonia, impaired handwriting, attention deficit, and signs of iron accumulation on brain MRI. Gradually, he developed dysarthria, spastic-dystonic gait, pedes cavi, and atrophy of leg muscles. Additionally, we report demographic parameters, clinical signs, and allelic frequencies of C19orf12 mutations of all published MPAN cases. We compared the most frequent mutations, p.Thr11Met and p.Gly69ArgfsX10; the latter was associated with younger age at onset and more frequent optic atrophy in homozygotes.

Diagnostic Efficiency of Serum and Urine Procathepsin B and Cathepsin B in Patients with Carcinoma of the Urinary Bladder

BACKGROUND The aim of the study was to evaluate the diagnostic efficiency of cathepsins B (cathepsin B and procathepsin B) in patients with transient cell carcinoma of the urinary bladder. METHODS Serum and urine concentrations of cathepsin B and procathepsin B were measured by two commercially available enzymatic immunoassays in a group of 125 patients with bladder cell carcinoma without metastases and in a group of 72 healthy individuals. Concentrations in urine were adjusted to creatinine. RESULTS Concentrations of both cathepsin B and procathepsin B in serum and urine were significantly elevated in patients with bladder cell carcinoma (p < 0.0001 for U-procathepsin B, U-procathepsin B/creatinine, and U-cathepsin B/creatinine, p = 0.0001 for U-cathepsin B, p = 0.0002 for S-procathepsin B and p = 0.02 for S-cathepsin B). Comparison of all diagnostic efficiencies of cathepsin B and procathepsin B in serum and in urine showed the best diagnostic accuracy for procathepsin B in urine (AUC = 0.81 vs. 0.50). The ratio of U-procathepsin B/creatinine was also more efficient than the ratio of U-cathepsin B/creatinine (AUC = 0.81 vs. AUC = 0.70). The diagnostic efficiencies of both parameters in serum were low (S-procathepsin B: AUC = 0.50, S-cathepsin B: AUC = 0.60). U-procathepsin B and U-procathepsin B/creatinine ratio show significantly better diagnostic efficiency in patients with invasive bladder tumors than other parameters (S-procathepsin B, S-cathepsin B, U-cathepsin B and U-Cathepsin B/creatinine; U-procathepsin B: AUC = 0.82, U-procathepsin B/creatinine: AUC = 0.86, S-procathepsin B and cathepsin B: AUC = 0.51 - 0.68). CONCLUSIONS Procathepsin B concentration in urine is a valuable diagnostic marker in patients with bladder cell carcinoma.