Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients' quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC.

Does Vitamin Supplementation Play a Role in Chronic Kidney Disease?

Although the role of vitamins in the human body is proven, guidelines for patients with chronic kidney disease (CKD) remain unclear. This narrative review summarizes the findings of 98 studies of CKD and the effects of vitamin D, B, C, A, E, and K supplementation on patients on dialysis for CKD, with the aim of summarizing the existing guidelines. The findings are promising, showing the potential effectiveness of vitamin supplementation with, for example, vitamins B, D, or C. However, recommendations are still ambiguous, especially in the case of vitamins A and K, due to the potential toxicity associated with higher doses for patients. Continued research is needed to rigorously evaluate the effectiveness and carefully consider the potential risks of some vitamin supplementation for patients with CKD.

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.

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

The COVID-19 pandemic is associated with a global health crisis and the greatest challenge for scientists and doctors. The virus causes severe acute respiratory syndrome with an outcome that is fatal in more vulnerable populations. Due to the need to find an efficient treatment in a short time, there were several drugs that were repurposed or repositioned for COVID-19. There are many types of available COVID-19 therapies, including antiviral agents (remdesivir, lopinavir/ritonavir, oseltamivir), antibiotics (azithromycin), antiparasitics (chloroquine, hydroxychloroquine, ivermectin), and corticosteroids (dexamethasone). A combination of antivirals with various mechanisms of action may be more efficient. However, the use of some of these medicines can be related to the occurrence of adverse effects. Some promising drug candidates have been found to be ineffective in clinical trials. The knowledge of pharmacogenetic issues, which translate into variability in drug conversion from prodrug into drug, metabolism as well as transport, could help to predict treatment efficiency and the occurrence of adverse effects in patients. However, many drugs used for the treatment of COVID-19 have not undergone pharmacogenetic studies, perhaps as a result of the lack of time.

Can Diet Prevent Urological Cancers? An Update on Carotenoids as Chemopreventive Agents.

Urological cancers, namely prostate, bladder, kidney, testicular, and penile cancers, are common conditions that constitute almost one-quarter of all malignant diseases in men. Urological cancers tend to affect older individuals, and their development is influenced by modifiable metabolic, behavioral, and environmental risk factors. Phytochemicals may have cancer-fighting properties and protect against cancer development, slow its spread, and reduce the risk of cancer deaths in humans. This paper aims to review the current literature in regard to the effects of carotenoids in reducing urological cancer risk.

Are We Sentenced to Pharmacotherapy? Promising Role of Lycopene and Vitamin A in Benign Urologic Conditions.

Benign prostatic hyperplasia, urolithiasis, recurrent urinary tract infections, and chronic prostatitis are diseases that are commonly diagnosed worldwide. Carotenoids, including lycopene, are widely available in fruits and vegetables, and it is postulated that they can be used in the prevention and treatment of benign urological conditions. The aim of this review is to familiarize doctors and their patients with the current knowledge on carotenoids and their conversion products in selected urological diseases. Most of the experimental and clinical trials show a moderate effect of lycopene and vitamin A on studied parameters. Lycopene was shown to improve the IPSS score in BPH patients, and alleviate symptoms in those with chronic prostatitis. Intake of Vitamin A was associated with decrease of urinary tract reinfection rates. In studied rat models retinol also decreased urolithiasis formation. Although the results of the cited studies are generally promising, it is evident that more detailed and extensive research must be done in this field of medicine.

The Role of Long Noncoding RNA (lncRNAs) Biomarkers in Renal Cell Carcinoma.

Renal cell carcinoma is one of the common cancers whose incidence and mortality are continuously growing worldwide. Initially, this type of tumour is usually asymptomatic. Due to the lack of reliable diagnostic markers, one-third of ccRCC patients already have distant metastases at the time of diagnosis. This underlines the importance of establishing biomarkers that would enable the prediction of the disease's course and the risk of metastasis. LncRNA, which modulates genes at the epigenetic, transcriptional, and post-transcriptional levels, appears promising. The actions of lncRNA involve sponging and sequestering target miRNAs, thus affecting numerous biological processes. Studies have confirmed the involvement of RNAs in various diseases, including RCC. In this review, we focused on MALAT1 (a marker of serious pathological changes and a factor in the promotion of tumorigenesis), RCAT1 (tumour promoter in RCC), DUXAP9 (a plausible marker of localized ccRCC), TCL6 (exerting tumour-suppressive effects in renal cancer), LINC00342 (acting as an oncogene), AGAP2 Antisense1 (plausible predictor of RCC progression), DLEU2 (factor promoting tumours growth via the regulation of epithelial-mesenchymal transition), NNT-AS1 (sponge of miR-22 contributing to tumour progression), LINC00460 (favouring ccRCC development and progression) and Lnc-LSG1 (a factor that may stimulate ccRCC metastasis).

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.

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.

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.

[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.

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.

Usefulness of clearance parametric images in detection of regional renal parenchyma dysfunction.

BACKGROUND: The aim of the study was to examine whether parametric clearance images (PAR) enhance diagnostic potential of a dynamic renal scintigraphy with detection of local dysfunction of kidneys, on a model of kidneys after treatment with extracorporeal shock wave lithotripsy (ESWL), MATERIAL AND METHODS: Kidneys after ESWL were accepted as a proper model for the implementation of this objective because of the previously proven damaging effect of a shock wave on renal parenchyma and known region of ESWL application. Forty patients (23 males and 17 females) at the age of 37 to 70 years (mean value 54) with untreated earlier single, one-sided nephrolithiasis, currently treated with ESWL, underwent a study. A dynamic renal 99mTc-EC scintigraphy was performed three times: before ESWL, a week and a month after this therapeutic intervention. PAR images generated with use of an in-house developed software were compared with summation (SUM) of images obtained from radiopharmaceutical uptake phase and quantitative global function parameters (GFP) of each kidney, like split function, MTT - mean transit time and PTT - parenchymal transit time. RESULTS: PAR and SUM images of all 40 kidneys before ESWL were normal. PAR images revealed local or diffused defects a week and a month after therapeutic intervention in statistically significantly larger numbers of kidneys than SUM images (19 vs. 6, p = 0.002 and 16 vs. 5, p = 0.003, respectively). A week after ESWL, when defects in PAR images were observed in about a half of all renal segments (29/57 - 51%) all GFP values were significantly worse than in kidneys without defects. A month after ESWL defects in PAR images could be observed in ab. 1/3 (17/48 - 35%) of segments and were less extensive, whereas GFP values did not differ significantly from values in kidneys without clearance function impairment in the PAR images. CONCLUSIONS: PAR images enhance diagnostic potential of a dynamic renal scintigraphy with detection of local function defects. These images allow to detect more local renal function defects than SUM images.

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.

Emphysematous pyelonephritis in a diabetic patient with obstructed kidney.

Emphysematous pyelonephritis (EPN) is an acute, rare, inflammatory disease, which typically occurs in patients who suffer from diabetes mellitus. We report the case of a patient who was admitted to the Department of Urology with septic signs, in whom, after performing computed tomography, the diagnosis of EPN was established. The patient underwent organ-preserving treatment, which consisted of pyelolithotomy with nephrostomy, and the insertion of a double J catheter into the left ureter. The importance of the classification of EPN is also discussed. The need for individualized procedures is highlighted.

MMP7 and MMP8 genetic polymorphisms in bladder cancer patients.

INTRODUCTION: Breakdown of the extracellular matrix by matrix metalloproteinases (MMPs), as we know, is one of mechanisms involved and required in tumor invasion. MMP7 is a negative prognostic factor of various malignances, while MMP8 exhibits an inhibitory effect on tumorigenesis and metastasis. We evaluated the potential association of functional polymorphisms in the promoter of the MMP7 (rs11568818) and MMP8 (rs11225395) genes and bladder cancer (BCa) risk. MATERIALS AND METHODS: The study included 241 BCa cases and 199 healthy population controls that were collected at the First Department of Urology, Medical University (Lódz, Poland) and at the Nofer Institute of Occupational Medicine (Lódz, Poland). Genomic DNA samples were isolated from venous blood and genetic polymorphisms were analyzed by real-time polymerase chain reaction using TaqMan fluorescent probes. Associations between genotype and allele status were estimated by logistic regression models adjusted for classic risk factors (e.g. age, gender and cigarette smoking). RESULTS: MMP7 and MMP8 genotypes were distributed similarly in BCa patients and in controls and at least one variant allele was not associated with BCa cancer risk (OR, 0.91; 95% CI, 0.60-1.39; p = 0.662 for MMP7 and OR, 0.96; 95% CI, 0.63-1.46; p = 0.836 for MMP8). We observed higher prevalence of MMP7 GG genotypes among BCa patients than in controls (OR, 1.54; 95% CI, 0.93-2.55; p = 0.093). Additionally, genetic polymorphisms in the MMP7 and MMP8 were not associated with the tumor grade or stage. CONCLUSIONS: Our results suggest that genetic variations in two genes encoding members of the MMP7 and MMP8 are not associated with a risk of BCa in the Caucasian population.