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BACKGROUND: Mini Chromosome Maintenance 5 (MCM5) is considered as a urinary biomarker of bladder cancer. ADXBLADDER is a commercially available test to detect MCM5 antibodies. OBJECTIVE: External validation of ADXBLADDER test as a urinary biomarker of histopathologically confirmed non-muscle invasive bladder cancer (NMIBC) recurrence. METHODS: The study enrolled 119 consecutive patients with a history of NMIBC and 37 healthy volunteers matched as controls. Single, full-void urine samples were collected from patients before cystoscopy ± TUR. To measure MCM5 expression, Arquer Diagnostics ADXBLADDER test was used. The study protocol was registered within the clinical trials database (NCT03796299). RESULTS: Among patients with NMIBC history, recurrence was diagnosed in 83 patients (69.7%). ADXBLADDER demonstrated sensitivity of 73.5% (95% confidence interval (CI) 62.7%–82.6%), specificity of 33.3% (95% CI 18.6% to 51%), overall negative predictive value (NPV) of 35.3% (95% CI 23.3% to 49.5%) and overall positive predictive value of 71.8% (95% CI 66.1% to 76.8%) for detecting recurrence. In a control group, false positive ADXBLADDER results were noticed in 18 patients (48.6%). The sensitivity and NPV were the highest in invasive tumors (100% and 100%, respectively) and in high-grade recurrences (81.8% and 94.1%, respectively). CONCLUSIONS: ADXBLADDER has a moderate sensitivity and poor specificity in detecting NMIBC recurrence. However, it properly diagnoses patients with T1+ stage recurrence or high-grade tumors.

Introduction Transurethral resection of bladder tumour (TURBT) is one of the most commonly performed urologic procedures. Because of the shortcomings of conventional TURBT, the en-bloc resection concept was created. Aim To analyse the influence of en-bloc technique on surgical and oncological outcomes of TURBT performed with electric current. Material and methods This non-randomized, prospective controlled multicentre study enrolled 427 consecutive patients undergoing TURBT performed by five experienced endourologists in five academic institutions. Choice of procedure was at the discretion of the surgeon. The vast majority of patients underwent monopolar resection. The en-bloc procedure was performed with Collin’s knife or the classic resection loop. Study end-points were surgery, catheterization and hospitalization time, presence of muscularis propria (MP) in the specimen and 3-month recurrence-free survival (RFS). Results The study included 427 (274 conventional TURBT vs. 153 en-bloc) patients with mean age of 69 years (range: 18–99). There were more cases with MP present in the specimen in the en-bloc group (91.3% vs. 75.5%; p < 0.001). Surgery and hospitalization times were statistically shorter in the en-bloc group (both p < 0.05). A borderline significant difference was noted when the number of residual tumours in reTURBTs was analysed, with fewer cases of residual tumour in the en-bloc group (p = 0.051). RFS at 3 months was higher in the en-bloc group (88.4% vs. 80.1%; p = 0.027). After propensity score matching, differences in MP presence, hospitalization time and 3-month RFS status remained statistically significant. Conclusions When compared to conventional TURBT, en-bloc resection of bladder tumour is associated with higher percentage of MP presence in histopathological specimen, higher 3-month RFS and shorter hospitalization time.

To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103–0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE −0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.

piRNAs (PIWI-interacting RNAs) are small non-coding RNAs capable of regulation of transposon and gene expression. piRNAs utilise multiple mechanisms to affect gene expression, which makes them potentially more powerful regulators than microRNAs. The mechanisms by which piRNAs regulate transposon and gene expression include DNA methylation, histone modifications, and mRNA degradation. Genitourinary cancers (GC) are a large group of neoplasms that differ by their incidence, clinical course, biology, and prognosis for patients. Regardless of the GC type, metastatic disease remains a key therapeutic challenge, largely affecting patients’ survival rates. Recent studies indicate that piRNAs could serve as potentially useful biomarkers allowing for early cancer detection and therapeutic interventions at the stage of non-advanced tumour, improving patient’s outcomes. Furthermore, studies in prostate cancer show that piRNAs contribute to cancer progression by affecting key oncogenic pathways such as PI3K/AKT. Here, we discuss recent findings on biogenesis, mechanisms of action and the role of piRNAs and the associated PIWI proteins in GC. We also present tools that may be useful for studies on the functioning of piRNAs in cancers.

Global and local initiatives were recently undertaken to reduce the burden of antibiotic resistance. The aim of the study was to describe the incidence and the aetiology of bacterial infections among hospitalized patients with special attention paid to the multidrug resistant (MDR) bacteria. This retrospective study was based on prospectively collected data from 150,529 consecutive patients hospitalized in a tertiary multidisciplinary hospital in the years 2017–2019. All consecutive microbiological tests from any biological material performed in the analyzed period were included. Microbiological screening tests (n = 10,677) were excluded. The analysis was focused on aetiological factors of bacterial infections, especially the incidence of MDR bacteria and mechanisms of antibiotic resistance. There were 58,789 microbiological tests performed in the analyzed period. The highest testing rate was noticed for intensive care unit (mean of 3.1 tests per one patient), followed by neonatal intensive care unit (2.7), internal medicine (1.9), pediatrics (1.8), and urology (1.2). Among 58,789 tests, 7690 (13.1%) were positive. MDR bacteria were responsible for 1783 infections (23.2%). The most common antibiotic resistance mechanism reported was ESBL production by Klebsiella spp. or Escherichia coli or Enterobacter spp. isolates (47.3% of all MDR cases). ESBL cases were followed by MRSA (14.7%), VRE (14.2%) and MBL producing Klebsiella spp. (5.6%). Among all infections caused by MDR bacteria, 1175 (65.9%) were diagnosed after 72 h of hospitalization (hospital-acquired infections). Apart from AmpC and ESBL producing Escherichia coli, all MDR bacteria were significantly more common in hospital-acquired infection. MDR bacteria are aetiological factors of a significant portion of infections in hospitalized patients with no remarkable change in the incidence in recent years. Production of ESBL is the most common mechanism of antibiotic resistance and should be regarded as one of the most urgent problems in clinical microbiology.

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.

Introduction Urine concentration of human kidney injury molecule-1 (KIM-1) is suggested to be increased in patients with renal cell carcinoma (RCC). However, it has never been tested in patients with urothelial tumors, while preoperative differentiation between RCC and upper tract urothelial carcinoma (UTUC) plays an essential role in therapeutic decisions.The aim of the study was to evaluate the role of urinary KIM-1 expression in preoperative differentiation between RCC and urothelial carcinoma (UC). Material and methods Sixty-four participants were enrolled in the study, including 30 patients with RCC and 27 with UC (16 with UTUC and 11 with bladder tumor). Preoperative urinary KIM-1 levels were measured using a commercially available ELISA kit and normalized to urinary creatinine levels. Results The median concentration of urinary KIM-1 normalized to urinary creatinine was lower in patients with RCC compared to UC (1.35 vs 1.86 ng/mg creatinine, p = 0.04). The comparison between RCC and UTUC shows even more significant difference (1.33 vs 2.23 ng/mg creatinine, p = 0.02). Urinary KIM-1 concentration did not correlate with tumor stage nor grade in any of the groups. ROC analysis to identify UC revealed AUC of 0.657 with sensitivity 33.3% and specificity 96.7% at the cut-off value of 3.226 ng/mg creatinine. Among patients with eGFR ≥60 mL/min/1.73 m², ROC analysis to detect UC achieved AUC of 0.727 with sensitivity 69.5% and specificity 70.2%. Conclusions Urine KIM-1 can potentially differentiate UC from RCC. However, a wide range of observed results and limited sensitivity and specificity requires caution in making clinical decisions before confirmatory studies.

Introduction Preoperative identification of high-grade bladder cancer presence can optimize patient management. The aim of this study was to assess the association between preoperative pyuria and the pathological features of bladder cancer. Material and methods This retrospective analysis enrolled 943 patients undergoing transurethral resection of a bladder tumor. Patients were divided into two study groups based on the presence of pyuria in preoperative urine analysis, defined as the presence of >5 leukocytes in the high power field. Pyuria status as a potential predictive factor was then confronted with pathological features based on standard microscopic examination of the surgical specimen. Results Among 943 recruited patients, 294 (31.2%) presented with pyuria. Patients with pyuria were older (71 vs. 68 years, p

Human Kidney Injury Molecule-1 (hKIM-1) was proposed as urinary biomarker of renal cell carcinoma (RCC). The aim of the study was to validate urinary hKIM-1 as a biomarker of RCC.Forty-six participants were enrolled into the study, including 30 patients with clear-cell or papillary RCC and 16 matched patients in the comparison group. Preoperative urinary hKIM-1 levels were measured using commercially available ELISA kit and normalized to urinary creatinine levels.The concentrations of urinary hKIM-1 normalized to urinary creatinine in patients with RCC and comparison group did not differ significantly (1.35 vs. 1.32 ng/mg creatinine, p=.25). There was also no difference in urinary hKIM-1 concentration regarding stage or grade of renal cancer. Additional analysis of patients without chronic kidney disease (defined as eGFR ≥60mL/min/1.73m²) also did not reveal significant difference in urinary hKIM-1 concentrations between the groups (1.54 vs. 1.37; p=.47).Results of our study do not confirm recent suggestions that urinary hKIM-1 may be a biomarker of RCC.

The main goal of this study was to assess the histopathological efficacy of renal mass biopsy and to check the concordance between pathological results and biopsy of the final specimen, as well as interobserver variability in the assessment of biopsy cores.A hundred sets of core biopsies of postoperative specimens (renal masses) have been performed. Three core biopsies of the intact specimen had been performed once the kidney with the tumor, or the tumor alone were resected. The urologist aimed to obtain two cores from the peripheral sides of the tumor and one core from its center. The surgical specimen was evaluated by a single pathologist, whereas biopsy samples were referred to three independent pathologists who were blinded to the final results of the renal mass biopsy.Nondiagnostic biopsy rates ranged from 13% to 22%. Sensitivity and specificity ranged 83-97% and 97-99% by excluding nondiagnostic results. The concordance between assessment of surgical specimen and biopsy in the Fuhrman grading system ranged 36.5-77.0%, respectively. Interobserver agreement between the three pathologists was substantial or moderate, depending on the tumor subtype. The Krippendorff's alpha coefficient, calculated by excluding the nondiagnostic results, was 0.28 (moderate agreement) for the Fuhrman grading system.The agreement regarding grading of biopsies between three pathologists ranged from moderate to substantial. Therefore, a team of dedicated uropathologists should be engaged in final diagnosis of renal mass biopsy rather than single one before implementing the proper treatment.

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). Methods: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, D&uuml, ren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. Results: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p &lt, 0.05), more commonly presented with chronic renal disease (OR 2.4, p &lt, 0.05), diabetes (OR 4.2, p &lt, 0.05) and overweight (OR 2.0, p &lt, 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p &lt, 0.05) and a higher rate of papillary RCCs (OR 8.3, p &lt, 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. Conclusions: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.

Background Transurethral resection of the bladder tumour (TUR) is associated with a risk of bladder perforation. The underlying mechanisms and risk factors are not fully understood. The aim of this study was to determine if the bladder wall structure affects the risk of bladder perforation during TUR. Methods Fifteen patients who underwent TUR complicated by a bladder perforation (group 1) and fifteen matched controls who underwent uncomplicated TUR (group 2) were retrospectively enrolled in this morphological analysis. Surgical specimens were collected from all participating patients to describe the quality and architecture of urothelium and bladder submucosa. Immunohistochemical studies were performed with primary mouse anti-human E-cadherin, beta-catenin, type IV collagen, cytokeratin 20 and epithelial membrane antigen antibodies. The intensity of the immunohistochemical reaction was assessed using an immunoreactive score (IRS). Ultrastructural examinations were performed by transmission electron microscopy. The microscopic assessment was focused on the intensity of fibrosis in the bladder submucosa and the presence of degenerative changes in the urothelium. Results Patients’ age, sex distribution, tumour diameters, surgeon experience or cancer stage did not differ between study groups. The immunohistochemical analysis did not reveal statistically significant differences between group 1 and group 2. From a clinical point of view, ultrastructural analysis by electron microscopy showed a higher rate of severe fibrosis in group 1 (63.6% vs. 38.5%), with no differences in the rate and degree of urothelial changes. However, these differences were not statistically significant (p = 0.32). Conclusions Bladder perforation during TUR is not a result of a deficient structure of the bladder wall. Based on available evidence, the surgical technique seems to play the most important role in its prevention.

Background Transurethral resection of the bladder tumour (TUR) is associated with a risk of bladder perforation. The underlying mechanisms and risk factors are not fully understood. The aim of this study was to determine if bladder wall structure affects the risk of bladder perforation during TUR. Methods Fifteen patients who underwent TUR complicated by a bladder perforation (group 1) and fifteen matched controls who underwent uncomplicated TUR (group 2) were retrospectively enrolled into this morphological analysis. Surgical specimens were collected from all participating patients to describe the quality and architecture of urothelium and bladder submucosa. Immunohistochemical studies were performed with primary mouse anti-human E-cadherin, beta-catenin, type IV collagen, cytokeratin 20 and epithelial membrane antigen antibodies. The intensity of the immunohistochemical reaction was assessed using an immunoreactive score (IRS). Ultrastructural examinations were performed by transmission electron microscopy. The microscopic assessment was focused on the intensity of fibrosis in bladder submucosa and the presence of degenerative changes in the urothelium. Results Patients’ age, sex distribution, tumour diameters, surgeon experience or cancer stage did not differ between study groups. Immunohistochemical analysis did not reveal statistically significant differences between group 1 and group 2. From clinical point of view, ultrastructural analysis by electron microscopy showed higher rate of severe fibrosis in group 1 (63.6% vs. 38.5%), with no differences in the rate and degree of urothelial changes. However, these differences were not statistically significant (p=0.32). Conclusions Bladder perforation during TUR is not a result of deficient structure of the bladder wall. Based on available evidence, surgical technique seems to play the most important role in its prevention.

Background. There is a growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic / latent viral infections with the clinical course of renal cell carcinoma (RCC).Methods. In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) from tumor tissue was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) or EZ1 Virus Mini Kit (Qiagen, Hilden, Germany). The number of viral copies in the tissue was assessed with the real-time PCR.Results. Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p

Beyond laboratory, imaging and endoscopic procedures, new diagnostic tools are increasingly being sought for the diagnosis of upper urinary tract urothelial carcinoma (UTUC), especially those that are non-invasive. In this systematic review, we aimed to determine the effectiveness of non-invasive tests in the diagnosis of UTUC. PubMed and Embase electronic databases were searched to identify studies assessing effectiveness of non-invasive tests in the primary diagnosis of UTUC. The study protocol was registered with PROSPERO (CRD42020216480). Among 10,084 screened publications, 25 were eligible and included in the analysis. Most of them were conducted on small samples of patients and the control groups were heterogenous. The test used in the largest number of studies was voided urinary cytology, which has poor sensitivity (11–71.1%) with favorable specificity (54–100%). Fluorescence in situ hybridization in diagnostic cytology showed higher sensitivity (35–85.7%) with equally good specificity (80–100%). There were also studies on the use of tests known to diagnose bladder cancer such as NMP22, uCYT or BTA test. Other urine or blood tests have been the subject of only isolated studies, with varying results. To conclude, currently there is a lack of high-quality data that could confirm good effectiveness of non-invasive tests used in the diagnosis of UTUC.

Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

Congenital abnormalities of the urinary tract were diagnosed in 28 per cent of authors' own cases of Mayer-Rokitansky-Kuster-Hauser syndrome. Different kinds of abnormalities were discussed and accurate diagnosis of urinary tract abnormalities before planned operation in that group of patients was emphasized.