Histone H3 posttranslational modified enzymes defined neutrophil plasticity and their vulnerability to IL-10 in the course of the inflammation.

BACKGROUND: Neutrophils are a heterogeneous population capable of antimicrobial functions associated with pre-activation/activation and tissue regeneration. The specific polarisation of immune cells is mediated by the modification of 'chromatin landscapes', which enables differentiated access and activity of regulatory elements that guarantee their plasticity during inflammation No specific pattern within histone posttranslational modifications (PTMs) controlling this plasticity has been identified. METHODS: Using the in vitro model of inflammation, reflecting different states of neutrophils from resting, pre-activated cells to activated and reducing tissue regeneration, we have analysed 11 different histone posttranslational modifications (PTMs), PTM enzymes associated with remodelling neutrophil chromatin, and H3K4me3 ChIP-Seq Gene Ontology analysis focusing on the processes related to histone PTMs. These findings were verified by extrapolation to adequate clinical status, using neutrophils derived from the patients with sepsis (systemic septic inflammation with LPS-stimulated neutrophils), neuromyelitis optical spectrum disorders (aseptic inflammation with pre-activated neutrophils) and periodontitis (local self-limiting septic inflammation with IL-10-positive neutrophils). RESULTS: Physiological activation of neutrophils comprises a pre-activation characterised by histone H3K27ac and H3K4me1, which position enhancers; direct LPS exposure is induced explicitly by H3K4me3 which marked Transcription Start Site (TSS) regions and low-level of H3K9me3, H3K79me2 and H3K27me3 which, in turn, marked repressed genes. Contrary to antimicrobial action, IL-10 positively induced levels of H3S10p and negatively H3K9me3, which characterised processes related to the activation of genes within heterochromatin mediated by CHD1 and H3K9me3 specific demethylase JMJD2A. IL-10 protects changes within histone PTMs induced by TNF or LPS that affected H3K4me3-specific methyltransferase SETD1A and MLL1. Neutrophils previously exposed to inflammatory factors become unvulnerable to IL-10 because previous LPS stimulation interrupts TSS regions marked by H3K4me3 of CHD1 and JMJD2A genes. Therefore, LPS-activated neutrophils are disabled to induce CHD1/JMJD2A enzymes by IL-10, making this process irreversible. Because transcription of JMJD2A and CHD1 also depends on TSS positioning by H3K4me3, neutrophils before LPS stimulation become insensitive to IL-10. CONCLUSION: Neutrophils, once pre-activated by TNF or directly stimulated by LPS, become insensitive to the anti-inflammatory effects of IL-10, and vice versa; IL-10 protects neutrophils against these proinflammatory stimuli. This phenomenon is responsible for disturbing the natural process of resolving inflammation and tissue regeneration.

Clinical value of microRNA-19a-3p and microRNA-99a-5p in bladder cancer.

Introduction: MicroRNAs (miRNA) are small (approximately 17 to 25 nucleotides in length), single stranded, non-coding RNAs that play an important role in the control of gene expression at the post-transcriptional stage, by inhibiting protein translation or promoting mRNA degradation. The main aim of the study was to evaluate the clinical utility of the tested markers (miRNAs 19a-3p and 99a-5p), which might be important in the diagnostics of non-invasive bladder cancer (BC). Material and methods: The study involved a group of 60 patients suffering from BC (histopathologically confirmed), in which 20 patients were diagnosed with muscle invasive BC (INBC) and 40 patients with non-muscle invasive BC (NINBC). The control group consisted of 20 samples of normal urothelium, which did not show any cancerous changes during histopathological examination. We assessed the expression of microRNA, using real-time PCR and the miRCURY LNA Universal RT microRNA PCR Kit by Exiqon, Denmark. Results: Reduced expression of both analyzed markers was observed in most cases: miR-19a-3p in 51.8% and miR-99a-5p in 65.5% (as follows Mann-Whitney U test p < 0.000001 and Student's t test p = 0.034262). Moreover, miR-19a-3p in our tested group was useful to differentiate between low and high grade disease in non-invasive stages (t test p = 0.0315435). Furthermore, miR-19a-3p and miR-99a-5p were able to discriminate patients in low grade for groups with or without recurrence. Conclusions: Our data indicated that miR-19a-3p and miR-99a-5p were significantly altered in bladder cancer samples and useful as diagnostic markers.

Changes Within H3K4me3-Marked Histone Reveal Molecular Background of Neutrophil Functional Plasticity.

Neutrophils are a heterogenous population capable of both antimicrobial functions and suppressor ones, however, no specific pattern of transcription factors controlling this plasticity has been identified. We observed rapid changes in the neutrophil status after stimulation with LPS, pre-activating concentration of TNF-α, or IL-10. Chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3 allowed us to identify various transcriptional start sites (TSSs) associated with plasticity and heterogeneity of human neutrophils. Gene Ontology analysis demonstrated great variation within target genes responsible for neutrophil activation, cytokine production, apoptosis, histone remodelling as well as NF-κB transcription factor pathways. These data allowed us to assign specific target genes positioned by H3K4me3-marked histone with a different pattern of gene expression related to NF-κB pathways, apoptosis, and a specific profile of cytokines/chemokines/growth factors realised by neutrophils stimulated by LPS, IL-10, or TNF-α. We discovered IL-10-induced apoptotic neutrophils being transcriptionally active cells capable of switching the profile of cytokines/chemokines/growth factors desired in resolving inflammation via non-canonical NF-κB pathway with simultaneous inhibition of canonical NF-κB pathway. As apoptotic/suppressive neutrophils induced by IL-10 via positioning genes within H3K4me3-marked histone were transcriptionally active, newly described DNA binding sites can be considered as potential targets for immunotherapy.H3K4me3 histone ChIP-Seq analysis reveals molecular drivers critical for switching neutrophils from their pro- to anti-inflammatory properties.

Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence.

Human leukocyte antigen class I (HLA class I) antigen processing and presentation pathway (APP) defines anti-tumor immune response. ERAP, TAP, tapasin (TAPBP), and IFNγ modulate APP: control HLA class I expression in the tumor and the repertoire of presented tumor antigens. At the same time, vascular endothelial growth factor (VEGF) acts as an immunomodulator in the tumor microenvironment. The objective of the current study was to examine the association of single nucleotide polymorphisms (SNPs) in the ERAP1, ERAP2, TAP1, TAP2, TAPBP, IFNG genes with the corresponding mRNA expression in bladder cancer (BC) risk and recurrence after transurethral resection of BC. Moreover, we assessed the relationship between HLA class I and VEGF plasma levels and BC recurrence. We analyzed 9 SNPs in 124 BC patients using TaqMan genotyping and compared them with the data from 503 healthy individuals from the 1000 Genomes Project. In addition, we quantified the effects of SNPs on the corresponding mRNA expression in tumor and non-tumor adjacent tissue in 60 BC patients with primary and 30 with recurrent tumor by quantitative real-time PCR. Furthermore, the plasma HLA class I and VEGF levels were analyzed in BC patients and healthy controls by ELISA. IFNG (rs1861493) was associated with BC risk, TAPBP (rs3106189, rs2071888) with recurrence-free survival (RFS). Moreover, TAPBP mRNA expression was lower in tumors than in the adjacent tissue. The SNPs ERAP2 (rs251339) and TAP2 (rs241447, rs241448) variants affected mRNA expression in BC tissue. In tumor tissue, the high mRNA expression of ERAP1 was more common in BC patients with single tumors, ERAP2 in non-smokers, and TAP2 mRNA in recurrence. The lower HLA and higher VEGF plasma levels were observed in BC patients compared with healthy controls. We conclude that the genetic elements responsible for MHC class I APP may influence the BC risk, risk of recurrence, and RFS.

Expression profile of microRNAs (106b-3p, 130b-3, 145-3p, 199a-5p) in urine and serum samples from patients with the diagnosis of bladder cancer.

MicroRNAs (miRNA) are short, single stranded, non-coding RNAs that play an important role in controlling gene expression at the posttranscriptional stage. There is no bladder cancer marker that has been approved as an alternative for diagnostic cystoscopy and urine cytology so far, thus research for alternative, more sensitive, and less invasive methods of bladder cancer detection are being made. AIM: The aim of the study was to compare the relative expression levels of miRNAs in patients with bladder cancer. MATERIALS AND METHODS: Urine and serum samples were collected from patients with the diagnosis of bladder cancer (NMIBC 71%, MIBC 29%). We assessed expression of 4 miRNAs (106b-3p, 130b-3, 145- 3p and 199a-5p) using real-time PCR and double delta (ΔΔCt) method. The analysis was performed with the Mann-Whitney U test. RESULTS: miRNA 145-3p was significantly underexpressed in urine (p=0,0111) compared with control group, whereas in serum we did not find relevant differences between groups (p=0,0903). Overexpression was observed for miRNA 199a-5p tested in urine (p=0,0262) and for miRNA 106b-3p for both urine and serum (p=0,0262 and p=0,0149 respectively). For miR-130b-3 we did not find statistically significant differences neither for urine (p=0,6335) nor serum (p=0,2443). CONCLUSIONS: A correlation between the relative levels of expression for miRNA 106b-3p, 199a-5p and miRNA 145-3p was detected. We also observed differences between the results obtained for urine and serum. In the context of urinary cancers diagnosis urine seems to be more useful material than serum. We plan to continue our studies assessing expression levels of miRNA 106b-3 and miRNA 145-3p.

The Correlation between Lipid Metabolism Disorders and Prostate Cancer.

Prostate cancer is the second most common cancer affecting the male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signaling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signaling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with a higher risk of a more aggressive course of the disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, constitute an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aims to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (Stearoyl-CoA Desaturase) in particular, that may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions or even sub-fractions of e.g. HDL cholesterol.

Assessment of complications after laparoscopic surgery of kidney tumors using Clavien-Dindo classification.

<b>Introduction:</b> Surgical procedures are accepted, basic method of treating kidney cancer. <br><b>Aim:</b> The aim of the study was to assess postoperative complications according to the Clavien-Dindo classification after laparoscopic procedures in the treatment of kidney cancer. <br><b>Material and methods: </b>A retrospective study involved 112 patients. The research was based on the analysis of data from the medical records of the clinic and the documentation of the urological polyclinic. Classification of postoperative complications according to Clavien and Dindo in the operated patients was assessed on a 7-point scale. <br><b>Results:</b> Less severe complications occurred in 24 patients (21.4%). All the above-mentioned TNMtransfusions. Grade IIIb complication occurred in one patient (0.9%) and required kidney removal. <br><b>Conclusions: </b>The use of the Clavien-Dindo classification in the assessment of postoperative complications of laparoscopic renal procedures is a simple and objective diagnostic tool for establishing the postoperative condition of patients. The results of our examination of complications after laparoscopic renal surgery according to the Clavien-Dindo classifications are similar to those obtained in renowned urological centers.

Prediction of the risk of surgical complications in patients undergoing monopolar transurethral resection of bladder tumour - a prospective multicentre observational study.

INTRODUCTION: The aim of the study was to identify predictors of surgical complications of transurethral resection of bladder tumour (TURBT). MATERIAL AND METHODS: We prospectively recruited 983 consecutive patients undergoing TURBT within 7 months in six academic institutions. All patients were followed up from the surgery up to 30 days postoperatively with at least one telephone contact at the end of the observation. The primary study endpoint was any intra- or postoperative surgical complication. For the identification of predictors of complications, univariate and multivariate logistic regression models were used. Trial registration: ClinicalTrials.gov (NCT03029663). Registered 24 January 2017. RESULTS: Surgical complications were noticed in 228 (23.2%) patients, including 83 (8.4%) patients with more than one complication and 33 cases of Clavien-Dindo grade 3 complications (3.3%). The most common in-hospital complications were bleeding (n = 139, 14.1%) and bladder perforation (n = 46, 4.7%). In a multivariate analysis, nicotine use, high ASA score, and the presence of high-grade tumour were the most significant predictors of high-grade complications. The stage of the disease was the strongest predictor of bleeding, while the presence of muscle in the specimen and resident surgeon were the strongest predictors for bladder perforation. CONCLUSIONS: TURBT poses a significant risk of surgical complications, the majority of which are of low grade.

Dysregulation of Redox Status in Urinary Bladder Cancer Patients.

The alteration of redox homeostasis constitutes an important etiological feature of common human malignancies. We investigated DNA damage, selenium (Se) levels and the expression of cytoprotective genes involved in (1) the KEAP1/NRF2/ARE pathway, (2) selenoprotein synthesis, and (3) DNA methylation and histone deacetylation as putative key players in redox status dysregulation in the blood of urinary bladder cancer (UBC) patients. The study involved 122 patients and 115 control individuals. The majority of patients presented Ta and T1 stages. UBC recurrence occurred within 0.13 to 29.02 months. DNA damage and oxidative DNA damage were significantly higher in the patients compared to the controls, while plasma Se levels were significantly reduced in the cases compared to the controls. Of the 25 investigated genes, elevated expression in the peripheral blood leukocytes in patients was observed for NRF2, GCLC, MMP9 and SEP15, while down-regulation was found for KEAP1, GSR, HMOX1, NQO1, OGG1, SEPW1, DNMT1, DNMT3A and SIRT1. After Bonferroni correction, an association was found with KEAP1, OGG1, SEPW1 and DNMT1. Early recurrence was associated with the down-regulation of PRDX1 and SRXN1 at the time of diagnosis. Peripheral redox status is significantly dysregulated in the blood of UBC patients. DNA strand breaks and PRDX1 and SRXN1 expression may provide significant predictors of UBC recurrence.

MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer.

Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors.

Usefulness of droplet digital PCR and Sanger sequencing for detection of FGFR3 mutation in bladder cancer.

OBJECTIVE: The purpose of our research was to determine the usefulness of different methods for detecting Y373C mutation of gene FGFR3. PATIENTS AND METHODS TOTAL: 138 primary bladder cancer patients (71cases G1 and 67 cases G2-G3) were included in the study. Tumor tissue and urine samples were collected and kept frozen until the isolation of DNA. Sanger sequencing was applied for detecting mutation in cancer and ddPCR was utilized for urine assessment. RESULTS: ddPCR appears to be more effective and it identified FGFR3 mutation (Y373C) in urinary sediment in 20.3% of cases whereas Sanger sequencing did in 15.5%. Only in 8/39 (20.5%) cases the mutation was observed both in urine and tissue. In 12/39 (30.8%) cases (5G1 and 7 G2-G3) we did not detect any FGFR3 mutation in urine although it was confirmed by sequencing. We only found mutation in urine in 20/39 cases (15 G1, 5 G2-G3) (51.3%). The correlation between the presence of FGFR3 mutations and better survival was confirmed. The Log-Rank test indicates a significant difference in the likelihood of survival for patients with the FGFR3 mutation but without recurrence (Cox's F-test P = 0.17006; Log-Rank Test P = 0.00059). CONCLUSION: ddPCR appeared to be more sensitive method for detection FGFR3 gene mutation particularly for detecting low levels of tumor DNA amongst a large excess of nontumor DNA. It is significant as the implementation of such markers into routine practice could be beneficial. The prospective study in larger cohort is needed.

Hexaminolevulinate in the Management of Nonmuscle Invasive Bladder Cancer: A Meta-Analysis.

Objective: The objective of this study was to assess the effect of photodynamic diagnosis (PDD) using hexaminolevulinate on the diagnostic and therapeutic outcomes in nonmuscle invasive bladder cancer (NMIBC) patients. Methods: PubMed, Embase, and the Cochrane Library databases together with conference proceedings were searched. Results: Recurrence-free survival was significantly higher at 3, 6, 9, and 12 months in the PDD groups than in the white light cystoscopy (WLC) groups with the cumulative values of differences in recurrence rates at different follow-up intervals ranging from 8% to 11%. PDD identified additional tumors in 25% of all NMIBC patients and in 35% of carcinoma in situ (CIS) patients. In a patient-based analysis mean sensitivity of PDD versus WLC for all tumor detection was 94% and 84%, respectively. The assessed patient-based specificity was comparable for PDD and WLC in all types of tumors (55-56%); however, in CIS it was higher for PDD (82% vs. 72%). Conclusions: The meta-analysis confirms that PDD in conjunction with WLC detects significantly more tumors than WLC alone. Better diagnostic abilities of PDD transpose to significantly lower short-term recurrence rates after transurethral resection procedure and may improve treatment of NMIBC patients.

Necrosis of the duodenal wall with retroperitoneal perforation as a complication of perirenal abcess. Case report and management.

Duodenal perforation is a rare and severe acute surgical condition which commonly follows the complications of endoscopic and laparoscopic procedures. Small degree of damage in this mechanism and an early diagnosis allow for an effective primary management. The most difficult surgical challenge is an effective management of retroperitoneal duodenal perforation together with coexisting pathological changes of its wall. In this work we present a case of duodenal necrosis with excessive necrosis of a fragment of its wall due to perinephric abscess, with an effective method of management of a defect in an isolated free small intestinal loop in association with gastroduodenal passage exclusion.

[Concordance evaluation of gleason score between laparoscopic prostatectomy and needle biopsy specimens].

OBJECTIVE: Introduction: Prostate cancer is currently one of the most important health issues especially for developed countries. It is the most common solid organ malignancy amongst men in Europe with 214 new cases per 100.000 men per year and the second most common cause of cancer death. The choice of therapy depends upon the clinical stage (cTNM), PSA level and Gleason histological score. Gleason score of radical prostatectomy specimens is the strongest predictor of disease progression. PATIENTS AND METHODS: Material and methods: Prospective analysis of the pathology reports in 54 patients who underwent TRUS-guided prostate biopsies and subsequent radical prostatectomy in the first department of urology Medical Univeristy in Lodz between 2015-2016. Gleason-score differences were examined for possible correlation with the following factors: age, prostate volume measured by TRUS, preoperative serum PSA level, abnormal digital rectal examination (DRE), pathologic stage (TNM system), positive surgical margins and the presence of metastasis in regional lymph nodes at prostatectomy. RESULTS: Results: The prostate biopsy and prostatectomy Gleason scores did not differ significantly (>0.05) when compared as a combined score and within the groups of primary and secondary grades. There were no differences in Gleason scores in 66 % of patients. Gleason scores differed by one unit in 13 patients (24%) and by 2 units in 5 patients (9%). There was a correlation between Gleason-score difference (prostatectomy minus biopsy) and positive surgical margin at radical prostatectomy with significantly higher Gleason score difference was higher in patients with positive surgical margin. CONCLUSION: Conclusion: There were no significant differences between Gleason score on needle-biopsy and in prostatectomy specimens in the evaluated group of patients.

Urine miRNA as a potential biomarker for bladder cancer detection - a meta-analysis.

INTRODUCTION: White light cystoscopy (WLC), often supported by urine cytology, is considered the 'goldstandard' in the diagnosis and follow-up of bladder cancer (BCa). In recent years, urine microRNA (miRNA) tests have been performed for the detection of bladder cancer. MATERIAL AND METHODS: A systematic review of the PubMed platform was performed by searching for articles in which miRNA in the urine was used for the detection of BCa. RESULTS: The greatest sensitivity (86.6%) in BCa detection was achieved for multi-miRNA in urine sediment. The greatest specificity (85.3%) was achieved for multi-miRNA from voided urine. There were significant differences (p <0.01) between single-miRNA (OR 8.96; CI 6.37-12.59) and the multi-miRNA group (OR 19.95; CI 13.35-29.81). There were no differences among the specimens (voided urine, supernatant, sediment) used for the test. CONCLUSIONS: Urine miRNAs have the potential to be a valid marker for bladder cancer detection. They can successfully compete with other non-invasive diagnostic tests.

[The analysis of perioperative complications of percutaneous nephrolithotomy in the treatment of nephrolithiasis with the use of modified Clavien-Dindo classification]. / The analysis of perioperative complications of percutaneous nephrolithotomy in the treatment of nephrolithiasis with the use of modified Clavien-Dindo classification.

The improvement of surgical care requires transparent, consistent and accurate reports concerning surgical outcomes which are assessed and documented in a standardized manner. No consensus has yet been reached as to how to define and assess postoperative complications with regard to the specificity of urological procedures. Therefore, the comparison of data from different centres is difficult. The modified Clavien-Dindo classification allows for a more uniform analysis of surgical complications. This study analyses the occurrence of perioperative complications after percutaneous nephrolithotomy assessed on the basis of the aforementioned classification. AIM: The aim of this study was to analyse perioperative complications with the use of modified Clavien-Dindo classification. Obtained results were compared with those from the multicentre Endourological Society Percutaneous Nephrolithotomy Global Study. MATERIALS AND METHODS: This retrospective analysis involved 201 patients who underwent percutaneous nephrolithotomy during the period from 01.01.2013 to 31.12.2016. We assessed the frequency of complication and the characteristics of deposits. The modified Clavien- Dindo classification was used here. The surgery was performed by one operator in one centre. RESULTS: In 83.08% of patients normal postoperative course was reported. In case of 12.44%, there were minor deviations from the standard intraoperative and postoperative course. 2,49% of patients required transfusions of red blood cell (Clavien II) after the procedure. Less than 1.5% of patients required surgical, endoscopic or radiological intervention under local anaesthesia (Clavien IIa) and one patient required such intervention under general anaesthesia (Clavien IIb). Serious complications were not reported. The most common complications were as follows: low-grade fever (15.42%), fever (5.97%) and bleeding (3.48%). Among the least frequent complications there were: injuries of renal pelvis or ureter 2.99%, residual stones (1.99%), urinary leakage (1.49%), urinary retention (0.995%), arteriovenous fistula (0.497%). CONCLUSIONS: Percutaneous nephrolithotomy is a highly effective treatment of stones removal from the kidney. It is characterized by a small percentage of serious complications, especially when it is performed by an experienced operator. The modified Clavien-Dindo classification of complications is useful in monitoring and comparing the results obtained for this procedure.

Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome.

In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value. Due to the development of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, the introduction of novel techniques will allow for the identification of novel biomarkers in renal diseases. This review presents some new possible biomarkers in the diagnosis of CKD and in the prediction of outcome, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), uromodulin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic biomarkers. Complicated pathomechanisms of CKD development and progression require not a single marker but their combination in order to mirror all types of alterations occurring in the course of this disease. It seems that in the not so distant future, conventional markers may be exchanged for new ones, however, confirmation of their efficacy, sensitivity and specificity as well as the reduction of analysis costs are required.

Photodynamic Diagnosis and Narrow-Band Imaging in the Management of Bladder Cancer: A Review.

BACKGROUND: Bladder cancer is the most common malignancy of the urinary tract. Its proper diagnosis and efficient treatment is still considered a challenge in urology today. White light cystoscopy is a gold standard for the diagnosis, follow-up, and endoscopic treatment of bladder cancer. To improve the efficacy of bladder cancer management, photodynamic diagnosis and narrow-band imaging have been introduced to the urological armamentarium. OBJECTIVE AND METHODS: The article presents the current state of knowledge of technical solutions that are intended to improve the diagnosis and management of bladder cancer. A nonsystemic review of relevant PubMed literature was performed. RESULTS: Photodynamic diagnosis and narrow-band imaging improve the detection of bladder cancer and decrease recurrence rates of bladder tumors. CONCLUSIONS: Although the high cost of the equipment may limit its introduction to everyday use, it is a cost-effective method of bladder cancer management for long-term follow-up.

Different Gene Expression and Activity Pattern of Antioxidant Enzymes in Bladder Cancer.

The aim of this study was to evaluate the possible role in and contribution of antioxidant enzymes to bladder cancer (BC) etiology and recurrence after transurethral resection (TUR). We enrolled 40 patients with BC who underwent TUR and 100 sex- and age-matched healthy controls. The analysis was performed at diagnosis and recurrence, taking into account the time of recurrence. Gene expression of catalase (CAT), glutathione peroxidase 1 (GPX1) and manganese superoxide dismutase (SOD2) was determined in peripheral blood leukocytes. The activity of glutathione peroxidase 3 (GPX3) was examined in plasma, and GPX1 and copper-zinc containing superoxide dismutase 1 (SOD1) in erythrocytes. SOD2 and GPX1 expression and GPX1 and SOD1 activity were significantly higher in patients at diagnosis of BC in comparison to controls. In patients who had recurrence earlier than 1 year from TUR, CAT and SOD2 expression was lower (at diagnosis p=0.024 and p=0.434, at recurrence p=0.022 and p=0.010), while the GPX1 and GPX3 activity was higher (at diagnosis p=0.242 and p=0.394, at recurrence p=0.019 and p=0.025) compared to patients with recurrence after 1 year from TUR. This study revealed that the gene expression and activity of the antioxidant enzymes are elevated in blood of patients with BC, although a low expression of CAT might contribute to the recurrence of BC, in early prognosis.

Quality of life in a population of Polish patients with prostate cancer.

INTRODUCTION: Recent advances in treatment have led to the prolongation of life among patients with prostate cancer (PCa), which implies greater interest in the issue of the quality of life (QoL) in patients who undergo treatment. The quality of life of patients with cancer questionnaire (QLQ-C30) and the quality of life questionnaire specific to PCa (QLQ-PR25) are tools used worldwide to conduct research on this subject. In our study we assessed the quality of life in a population of Polish patients suffering from prostate cancer. Differences in the quality of life depending on the stage of the disease were highlighted. MATERIAL AND METHODS: We conducted a prospective, multicenter, observational study using the QLQ-C30 and QLQ-PR25 questionnaires in a group of 1047 patients. RESULTS: The highest QoL scores (according to the QLQ-C30 questionnaire) were observed in patients with localized prostate cancer, while the lowest were recorded in the metastatic group. Sexual activity and sexual functioning assessed on the basis of QLQ-PR25 was best in the group of patients suffering from localized prostate cancer, and the worst in patients with locally advanced PCa. CONCLUSIONS: The assessment of QoL showed a significant correlation with the stage of the disease. Sexual activity and sexual functioning were the best in patients with localized cancer; worst among patients with locally advanced tumor.