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.

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.

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.

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.

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.

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.

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.