Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis.

AIMS: Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. METHODS: High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. RESULTS: We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. CONCLUSION: Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.

Novel biochemical markers for non-invasive detection of pancreatic cancer.

To identify non-invasive biomarkers of non-metastatic pancreatic cancer (PC), the blood from 186 patients (PC n=28; DM-diabetes mellitus n=60; ChP-chronic pancreatitis n=47; healthy controls n=51) was analyzed for 58 candidate biomarkers. Their effectiveness to identify PC was compared with CA19-9. Panel defined by Random-forest (RF) analysis (CA19-9, AAT, IGFBP2, albumin, ALP, Reg3A, HSP27) outperforms CA19-9 in discrimination of PC from DM (AUC 0.92 vs. 0.82). Panel (S100A11, CA72-4, AAT, CA19-9, CB, MMP-7, S100P-s, Reg3A) is better in discrimination PC from ChP than CA19-9 (AUC 0.90 vs. 0.75). Panel (MMP-7, Reg3A, sICAM1, OPG, CB, ferritin) is better in discrimination PC from healthy controls than CA19-9 (AUC 0.89 vs. 0.78). Panel (CA19-9, S100P-pl, AAT, albumin, adiponectin, IGF-1, MMP7, S100A11) identifies PC among other groups better than CA19-9 (AUC 0.91 vs. 0.80). Panel defined by logistic regression analysis (prealbumin, IGFBP-2, DJ-1, MIC-1, CA72-4) discriminates PC from DM worse than CA19-9 (AUC 0.80 vs. 0.82). Panel (IGF-1, S100A11, Reg1alfa) outperforms CA19-9 in discrimination PC from ChP (AUC 0.76 vs. 0.75). Panel (IGF-2, S100A11, Reg3A) outperforms CA19-9 in discrimination PC from healthy controls (AUC 0.95 vs. 0.78). Panel (albumin, AAT, S100P-serum, CRP, CA19-9, TFF1, MMP-7) outperforms CA19-9 in identification PC among other groups (AUC 0.89 vs. 0.8). The combination of biomarkers identifies PC better than CA19-9 in most cases. S100A11, Reg3A, DJ-1 were to our knowledge identified for the first time as possible serum biomarkers of PC.

Optimal Surgical Outcome of Minimally Invasive Partial Nephrectomy (MIPN) Based on an Early Postoperative Estimated Glomerular Filtration Rate (eGFR).

PURPOSE OF REVIEW: To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition - "MIC" - and a new optimal surgical definition: the "Novel TRIFECTA" (NT) concept. We sought to strengthen the PN evidence and to test the NT's performance. RECENT FINDINGS: The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

Novel serum markers HSP60, CHI3L1, and IGFBP-2 in metastatic colorectal cancer.

Colorectal cancer (CRC) is the second leading tumor diagnosis in women and men in the Czech Republic. Patient outcome depends on tumor stage at the time of diagnosis and, in metastatic disease, on the localization and extent of distant metastases. The early detection of metastatic liver disease is an important indication for liver surgery. Therefore, novel biomarkers are urgently required. Serum samples were collected from 97 patients with histologically confirmed metastatic CRC at the time of diagnosis or at the time of progression during palliative treatment, and 79 samples from healthy controls. All patients exhibited adequate liver and renal function and signed informed consent was obtained from all patients included in the current study. The serum levels of Heat shock protein 60 (HSP60), Chitinase-3-like protein 1 (CHI3L1) and Insulin-like growth factor binding protein 2 (IGFBP-2) were measured using immunochemistry. The serum levels of HSP60, CHI3L1 and IGFBP-2 were significantly higher in patients with CRC compared with healthy controls. When compared with carcinoembryonic antigen (CEA), HSP60 exhibited the same sensitivity and specificity, while CHI3L1 and IGFBP-2 exhibited decreased sensitivity. Additionally, the serum levels of HSP60 and IGFBP-2 were indicated to be correlated with the presence of liver metastases, which is in contrast to CEA and Cancer antigen 19-9 (CA19-9). Patients with higher HSP60 and IGFBP-2 levels exhibited a significantly worse survival (P<0.001 and 0.007, respectively). The results of the current study indicate HSP60 to be an effective biomarker in patients with metastatic CRC, with it exhibiting an equal sensitivity to CEA. Additionally, HSP60 and IGFBP-2 levels also strongly correlated with extension of liver metastases and exhibited a prognostic value that contrasted that of CEA.

Serum levels of TIMP-1 and MMP-7 as potential biomarkers in patients with metastatic colorectal cancer.

OBJECTIVE: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. RESULTS: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). CONCLUSION: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.

Gene Expression Analysis of Immunomagnetically Enriched Circulating Tumor Cell Fraction in Castration-Resistant Prostate Cancer.

BACKGROUND: Molecular characterization of tumors could be a key to therapeutic decision-making with regards to targeted therapies in castration-resistant prostate cancer (CRPC). A convenient solution may be non-invasive liquid biopsy testing of circulating tumor cells (CTCs). For this reason, CTC-enriched samples obtained by immunomagnetic separation (AdnaTest®) were studied as a source material for high-throughput gene expression analysis using BioMark™. PATIENTS AND METHODS: CTC-enriched samples from 41 CRPC patients previously determined to be CTC positive using the AdnaTest® were retrospectively re-analysed for androgen receptor (AR) messenger RNA (mRNA), using the updated AdnaTest®. Blood samples were drawn two times from each patient: at the time of CRPC diagnosis and after the third docetaxel cycle. A gene expression panel of 27 genes related to CRPC therapeutic decision-making, including AR full length (ARFL) and splice variant 7 (ARV7), was retrospectively analyzed on a BioMark™ platform in 29 of 41 patients. RESULTS: The AdnaTest® detected AR mRNA in three-quarters of CTC-positive samples taken at the time of CRPC diagnosis and after the third docetaxel cycle. AR detection was associated with a shorter disease-specific survival (45.0 vs. 20.4 months) at the time of CRPC diagnosis. ARFL expression at the time of CRPC diagnosis, measured on the BioMark™ platform, was associated with a lower decrease of serum level of prostate-specific antigen (sPSA) (p = 0.029), i.e., worse therapy response. ARV7 was found in 38% of the ARFL--positive samples at both analyzed timepoints. CONCLUSION: Detection of AR expression by AdnaTest® in CTC-enriched samples may help predict patients' survival. These AdnaTest® CTC-enriched samples can be used in a high-throughput quantitative polymerase chain reaction (qPCR) analysis of gene expression, provided that the specificity of the assay for each individual gene is properly validated. The BioMark™ platform can be used for the simultaneous detection of ARFL and ARV7 and other genes in CTC-enriched samples from CRPC patients.

Growth/differentiation factor 15 (GDF-15) as new potential serum marker in patients with metastatic colorectal cancer.

BACKGROUND: GDF-15 is a protein belonging to the transforming growth factor beta superfamily that has a role in regulating inflammatory and apoptotic pathways. High level GDF-15 in tumor tissues and plasma correlate with an increased risk of recurrence and reduced overall survival. OBJECTIVE: The aim of this study was to screen GDF-15 capacity to detecting metastatic CRC and compare it with standard tumor markers CEA and CA19-9. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of GDF-15, CEA and CA19-9 were measured by immunochemically. A Kaplan-Meier curve was applied for analysis of survival rates, and a log-rank was used for univariate analysis. RESULTS: Serum levels of GDF-15 were significantly higher in patients with colorectal cancer compared to healthy controls (p< 0.001). In addition, serum levels of GDF-15 correlated with extent of liver involvement and patients with higher GDF-15 levels had significantly worse outcome (p< 0.0001). CONCLUSIONS: Our results show GDF-15 as an effective biomarker in patients with metastatic colorectal cancer with the same sensitivity as CEA. In addition, GDF-15 levels strongly correlate with extension of liver involvement in contrast with CEA.

Is it possible to cure the symptoms of the overactive bladder in women?

PURPOSE: To evaluate the feasibility of discontinuing treatment with mirabegron once symptoms have subsided in patients with overactive bladder (OAB). METHODS: The present study evaluated a total of 159 female OAB patients (age 62.9 ± 12.36), each of which were prescribed 50 mg/day mirabegron (Time point 1-T1). Data obtained from voiding diaries and patient-reported outcome variables were assessed during follow-up visits at months 1, 3, 6, 12, 18 (T2), and 21 (T4). At the 18-month visit, patients with an Urgency Bother-Visual Analog Scale score of ≤ 50% were advised to stop treatment with mirabegron. Upon re-emergence or worsening of OAB symptoms, patients were allowed to start taking medication again at their discretion (T3). Statistical analysis was performed using a Chi-square test. An ANOVA analysis and a two-sample t test were used to evaluate differences between groups. RESULTS: A total of 56 out of 159 (35.3%) patients took 50 mg of mirabegron daily between T1 and T2. A total of 17 out of 56 patients (30.4%) did not meet the criteria for mirabegron discontinuation (Group A). A total of 24 out of 56 patients (42.9%) stopped taking the medication temporarily, but later returned to treatment (Group B). The average time span between T2 and T3 was 53.9 days. Fifteen of 56 patients (26.8%) ceased treatment with mirabegron without starting it again before T4 (Group C). The average time span between T2 and T4, in Group C, was 124.7 days. CONCLUSION: A small percentage of OAB patients were able to discontinue mirabegron due to symptom cessation.

Placental Growth Factor in Bladder Cancer Compared to the Diagnostic Accuracy and Prognostic Performance of Vascular Endothelial Growth Factor A.

BACKGROUND/AIM: To evaluate the diagnostic accuracy and prognostic performance of urinary and plasma levels of placental growth factor (PLGF) and provide their comparison with the results of vascular endothelial growth factor A (VEGF-A) in patients with primary and recurrent urinary bladder cancer. MATERIALS AND METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to assess urinary and plasma concentrations of PLGF and VEGF-A in 240 individuals. RESULTS: PLGF levels in urine and plasma were significantly higher in patients with primary bladder cancer than in healthy individuals (p=0.003, p=0.005, respectively). Area under the curve (AUC) of urinary PLGF was 0.68; AUC of plasma PLGF levels was 0.65. Patients with the urine levels of PLGF higher than 82.33 pg/ml had three times higher risk of recurrence. In patients with recurrent bladder cancer, the urinary concentrations of PLGF did not significantly differ from the concentrations in patients without current disease (p=0.61). However, plasma PLGF levels were significantly higher in patients diagnosed with tumor recurrence (p=0.001); AUC of plasma PLGF levels was 0.69. Moreover, patients with plasma levels higher than 10.09 pg/ml had a five-times higher risk of future tumor recurrence. The diagnostic accuracy of PLGF was comparable with VEGF-A. CONCLUSION: From a clinical point of view, PLGF could be considered a valid diagnostic test for the detection of primary and recurrent bladder cancer. In patients with recurrent bladder cancer, plasma PLGF levels can differentiate individuals at risk of tumor recurrence.

Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients.

AIM: To assess the prognostic importance of serum levels of retinol, retinol-binding protein 4 (RBP4) and vitamin E at the time of diagnosis in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In this prospective study, in a cohort of 102 renal cell carcinoma patients, relationships between serum levels of the aforementioned markers and recurrence-free survival (RFS), overall survival (OS), as well as cancer-specific survival (CSS), were evaluated. The vitamin A and vitamin E levels were determined by high-performance liquid chromatography (HPLC), while the RBP4 level by enzyme-linked immunosorbent assay (ELISA). RESULTS: The median follow-up period was 39 months. Renal cell carcinoma recurred in 9 patients; 23 patients died with 12 of them from RCC. The preoperative vitamin E level was associated to RFS (p=0.02). We found a significant relationship between OS and the level of RBP4 (p=0.002), retinol (p=0.037) and vitamin E (p=0.007). The CSS period was significantly associated with the level of RBP4 (p=0.0001) and retinol (p=0.0003). Patients with an RBP4 level less than 21.0 mg/l at the time of diagnosis had a 13.5-times higher risk of death due to RCC progression; this risk was up to 7.7-times higher with vitamin A levels under 0.52 mg/l. CONCLUSION: Low levels of vitamin A, E and RBP4 at the time of RCC diagnosis are associated with a poorer prognosis after surgery.

Persistence in the treatment of overactive bladder syndrome (OAB) with mirabegron in a multicenter clinical study.

OBJECTIVE: The objective of this project was to evaluate treatment persistence in patients being treated for overactive bladder syndrome (OAB) with mirabegron, employing clinical follow-up in a prospective, multicenter study. STUDY DESIGN: This is an analysis of patients who started treatment with mirabegron between May and September 2014 and were evaluated 1year after treatment commenced. During this evaluation we determined how many patients stopped treatment and established their reasons for discontinuation. RESULTS: 206 patients being treated for OAB with mirabegron were evaluated a year after starting treatment. It emerged that 60 patients (29.1%) had discontinued the treatment, citing the following reasons: 24/60 insufficient treatment efficacy, 26/60 other reasons, while 10 members of the group discontinued treatment because of side effects. 75 out of 206 patients were ≤60 years old and 28% terminated the study prematurely: 131 out of 206 were >60years old and 29.2% terminated the study prematurely. In the group of patients without previous OAB treatment 35.7% discontinued treatment with mirabegron, while 28.1% of patients with previous anticholinergic treatment discontinued treatment. CONCLUSION: In our clinical prospective multicenter study, persistence in treatment with mirabegron reached a figure of 71%.

Comparison of MicroRNA Content in Plasma and Urine Indicates the Existence of a Transrenal Passage of Selected MicroRNAs.

MicroRNAs (miRNAs) in urine are examined as potential biomarkers. We examined the urine samples from 70 individuals (45 males, 25 females, mean age 65 years, range 20-84 years). Of the urine donors, 15 were healthy volunteers, 5 were patients with non-cancer diseases, 50 were patients with different stages of bladder cancer. To examine the spectrum of miRNAs in the cell-free fraction of urine, TaqMan Human miRNA Array Card A v.2.1 was used. A set of 30 miRNAs were found that are constantly present in urine supernatants independently of sex, age and health status of the subjects. We compared this set with miRNAs found in plasma, expressed in kidney and genito-urinary tract. Our results indicate that some miRNA could be transferred from the circulation into urine.

Prognosis of Castration-resistant Prostate Cancer Patients - Use of the AdnaTest® System for Detection of Circulating Tumor Cells.

BACKGROUND: Detection of circulating tumor cells (CTC) in patients with castration-resistant prostate cancer (CRPC) may improve the estimate of chemotherapy response. We evaluated the AdnaTest® system in patients receiving docetaxel. PATIENTS AND METHODS: CTC analysis was carried out in 37 patients by immunomagnetic separation. Correlation between serum prostate-specific antigen (sPSA) change and CTC presence and the influence of each parameter on the overall survival (OS) were evaluated. RESULTS: We detected CTCs in 32 and 16 patients before and after three docetaxel cycles, respectively. The sPSA level correlated with CTC positivity during docetaxel therapy (p=0.0031). The longest OS was in patients negative for CTCs in both samples (p=0.0228). Change in sPSA levels was associated with treatment response (p=0.033). CONCLUSION: We detected CTCs in a considerable number of patients with CRPC. The absolute change of sPSA level correlated with OS. CTC presence during docetaxel therapy was associated with shorter OS.

The meaning of sampling density in multiple repeat prostate biopsies.

INTRODUCTION: Extended transrectal ultrasound-guided prostate biopsy is a state-of-the-art tool for prostate cancer detection. Nevertheless, approximately 1/3 of cancers are missed when using this method and repeat biopsy sessions are often required. The aim of this study was to investigate how sampling density (a compound variable reflecting the number of biopsy cores and prostate volume) impacts on detection rate in multiple repeat TRUS-biopsies. MATERIAL AND METHODS: A total of 1007 consecutive patients undergoing their 1st, 2nd, 3rd and any further repeat prostate biopsies were included. The relationship between sampling density and other clinical variables (age, prostate-specific antigen level, free/total PSA ratio, digital rectal examination, number of previous biopsies) and cancer detection rate were assessed by interaction analysis. RESULTS: There were 562 primary re-biopsies, 267 second re-biopsies and 178 third and further re-biopsies included in the study. Detection rate was 25.4%, 25.8% and 25.3%, respectively. Interaction of sampling density with age was demonstrated in patients undergoing their first repeat biopsy (but not further re-biopsies). No interaction was observed with other variables investigated. CONCLUSIONS: A more extensive prostate sampling leads to a higher cancer detection rate on repeat prostate biopsies, as shown previously. However, this effect seems to be particularly pronounced in men younger than 65 years undergoing their first repeat prostate biopsy.

Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.

INTRODUCTION: Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker. MATERIAL AND METHODS: In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined. RESULTS: The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively. CONCLUSION: Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer.

Impact of body mass index on treatment efficacy of mirabegron for overactive bladder in females.

OBJECTIVE: Conclusive data comparing treatment efficacy of OAB pharmacotherapy in normal weight versus obese patients are not available. Obesity represents a risk factor for OAB/LUTS. We hypothesized that the effect of treatment with mirabegron might be diminished in obese patients. STUDY DESIGN: One hundred sixty nine women were prescribed mirabegron, 50mg/day. Subjective and objective parameters were compared prior to and following three months of treatment. The study population was stratified into three groups according to a patients' BMI (A-normal weight, B-overweight, C-obese). We compared the change in parameters before and after treatment within each group. Subsequently the differences between groups were correlated. The same analysis was performed separately in patients who failed anticholinergic therapy (n=85). A paired t-test was used to compare the parameters before and after the procedure within groups, and a two-sample t-test was applied to conduct a comparison between groups. A p value of <0.05 was considered statistically significant. RESULTS: Significant improvement (p<0.001) within all groups was observed in all parameters, with an exception in the number of severe urgency episodes per 24h (p=0.291) in Group B. We did not observe any statistically significant difference between groups A, B and C. The same trend has been observed in subgroup of patients, who did not respond previous antimuscarinic treatment. CONCLUSIONS: This study provides evidence in support of previously documented data indicating good efficacy of mirabegron in the treatment of OAB. The data obtained do not confirm our hypothesis that the body weight influences the treatment outcome of mirabegron.

Diagnostic Importance of Selected Protein Serum Markers in the Primary Diagnostics of Prostate Cancer.

OBJECTIVE: To determine a predictive model for the primary diagnosis of prostate cancer (PC) based on a multiple serum biomarker assay. MATERIAL AND METHODS: Between August 2011 and February 2013, a total of 387 prostate biopsies were performed. Serum or plasma concentrations of 22 biomarkers (neopterin, IGF-1, IGFBP-2, IGFBP-3, sarcosine, endoglin, TGF-ß1, periostin, sPLA2-IIa, chromogranin A, ZAG2, clusterin, PSP94, PSP94bp, leptin, cathepsin D, hepsin, KLK11, PSMA, AMACR, CRISP3 and A1AT) were determined. Biomarker levels were correlated with the prostate biopsy results. Several statistical models for PC detection were created. RESULTS: A total of 167 of the 373 evaluated patients (44.8%) were diagnosed with PC. None of the tested biomarkers reached statistical significance using the univariate analysis. However, the level of serum clusterin was not associated with any other tested parameter. Several basic models showed a higher positive predictive value than individual parameters. Addition of serum clusterin to the base model with prostate-specific antigen, digital rectal exam and prostate size significantly improved the area under curve value (0.723 vs. 0.716). CONCLUSION: Our findings suggested that multiple serum assays based on some promising markers may only have a limited practical benefit for the prediction of PC in the prostate biopsy.

Panel of Urinary Diagnostic Markers for Non-Invasive Detection of Primary and Recurrent Urothelial Urinary Bladder Carcinoma.

OBJECTIVES: To determine the combination of urinary protein markers for noninvasive detection of primary and recurrent urothelial bladder carcinomas. METHODS: Urinary concentrations of 27 biomarkers (NSE, ATT, AFABP, Resistin, Midkine, Clusterin, Uromodulin, ZAG2, HSP27, HSP 60, NCAM1/CD56, Angiogenin, Calreticulin, Chromogranin A, CEACAM1, CXCL1, IL13Ra2, Progranulin, VEGFA, CarbAnhydIX, Annexin-V, TIM4, Galectin1, Cystatin B, Synuclein G, ApoA1 and ApoA2) were assessed by enzyme-linked immunosorbent assay or by electrochemiluminiscence immunoassay. RESULTS: During the primary diagnostics, a group of 70 patients with primary occurrence of bladder cancer and 49 healthy control subjects were compared. For this clinical situation, the most accurate combination proved to be the combination of cytology with markers Midkine and Synuclein G (sensitivity 91.8%, specificity 97.5%). During the monitoring of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared with the group of 61 patients with a history of NMIBC without current disease. For this clinical situation, the most accurate combination proved to be the combination of cytology and erythrocytes count in urine sediment with markers Midkine, ZAG2, CEACAM1, and Synuclein G (sensitivity 92.68%, specificity 90.16%). A lower accuracy of the diagnostic panel and the necessity to use more markers in the case of recurrence was connected with a different structure of patients. CONCLUSIONS: Multi-marker test can significantly improve the bladder cancer detection both during the primary diagnostics and monitoring of patients with NMIBC. This outcome should result in other, larger studies.

[Circulating tumor cells and prostate cancer prognosis]. / Cirkulující nádorové bunky a prognóza karcinomu prostaty.

Prostate cancer (PC) is the most common malignant disease in men. Prognosis of patients with metastatic PC is generally unfavourable; however there are significant differences in survival at this stage of the disease. The definition of prognosis is essential for the selection of therapy, respecting an individual risk. In recent years, the association between circulating tumor cells (CTC) detection and response to PC treatment has been widely investigated. Detection of CTC is based on a metastatic process theory and uses well-known tumor-specific antigens on the cell surface. Individual methods assess CTC with different sensitivity and are not yet efficient at the localised PC stage. Only the method of immunomagnetic separation and semi-automatic visualisation (CellSearchTM) has been validated and approved for the use in the PC management. Assessment of the CTC count directly correlates with the prognosis of patients with castration-resistant PC. Change in the CTC count during the therapy also considerably improves risk estimation and represents a marker of overall survival. New methods of CTC cultivation and gene profiling may contribute to individualisation of the treatment similarly to breast cancer. The authors present a review article about theory, methods of detection and clinical use of CTC in castration-resistant PC.

[Principal value of surgical therapy in the renal cell cancer, chances of the biological treatment]. / Zásadní význam chirurgické lécby u karcinomu ledvin, moznosti biologické lécby.

Renal cell cancer belongs to the most malignant tumours in urology; the incidence in the Czech Republic is highest world. Surgical treatment is the first method of choice both in localized and metastatic renal cell cancer due to its chemo and radioresistance. Cytoreductive nephrectomy in case of metastatic renal cell cancer can prolong the overall survival. Lymfogenic propagation is rare, but involvement of lymphatic retroperitoneal nodes is the most unfavourable risk factor. Patients with vein tumour thrombus profit from the radical surgical treatment; the most important thing is the removal of whole tumour thrombus. Miniinvasive methods in treatment of renal cell cancer are getting more and more popular nowadays. Partial nephrectomy is a method of choice in the treatment of small suitable localised renal cell cancers. Adjuvant therapy is not indicated in localised renal cell cancer. Immunotherapy was the most convenient method of treatment generalised renal cell cancer in the last decade of 20th century. Understanding of signalling pathways for growth factors in angiogenesis was the cue for targeted therapy. This method pushes back immunotherapy. Unfortunately targeted therapy fails to cure patients with generalized renal cell cancer; it can only stabilize disease and prolong the overall survival.