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Background and objective: Lymphovascular invasion (LVI) is a significant histopathological feature in prostate cancer (PCa) associated with higher risk of biochemical recurrence (BCR) and other adverse outcomes. Our aim was to assess the association of LVI found in radical prostatectomy (RP) specimens with BCR and adverse clinicopathological findings. Methods: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases in July 2023, with an additional search in May 2024. We included 94 prospective and retrospective studies reporting on LVI in RP specimens and its association with the specified outcomes. Key findings and limitations: Meta-analyses revealed that LVI is significantly associated with higher BCR risk (hazard ratio 1.96, 95% confidence interval [CI] 1.73–2.21), higher pathological tumour stage (odds ratio [OR] 5.77; 95% CI 3.96–8.40), higher Gleason score (OR 5.19, 95% CI 4.12–6.54), lymph node metastasis (OR 11.52, 95% CI 7.65–17.34), distant metastasis (OR 9.10, 95% CI 5.46–15.17), positive surgical margins (OR 2.38, 95% CI 1.83–3.09), extraprostatic extension (OR 5.01, 95% CI 3.11–8.06), seminal vesicle invasion (OR 7.50, 95% CI 3.47–16.23), and perineural invasion (OR 133.71, 95% CI 65.93–271.15). Major limitations of this study include high heterogeneity of the data and the reliance on nonrandomised studies. Conclusions and clinical implications: Our findings reveal that LVI is associated with nearly twofold higher risk of BCR, highlighting its potential role as a critical prognostic marker. Patient summary: We analysed data from multiple studies to understand the impact of the spread of prostate cancer into the lymph or blood vessels, called lymphovascular invasion (LVI). We found that LVI is linked to a higher risk of cancer recurrence after surgery and other negative outcomes. Our findings highlight the importance of considering LVI in treatment decisions for better management of prostate cancer.

The persistence of high incidence and mortality rates associated with urologic cancers underscores the urgent need for effective and safe treatments. Conventional chemotherapy regimens are often limited by their high toxicity, the cancer’s drug resistance, and the challenge of managing independently evolving multifocal spread. In this context, a repurposing strategy is particularly enticing. It allows for the introduction of a drug with a known safety profile, thus significantly reducing the costs and time necessary to introduce a new treatment. Nitroxoline (NIT), a drug with a well-established pharmacokinetic profile known for over 50 years and utilised in treating uncomplicated urinary tract infections, has recently garnered attention for its potential oncologic applications. Given the pharmacokinetic properties of NIT, our focus was specifically on urologic cancers in which its excretion profile is most advantageous. We examined all available studies, demonstrating significant effectiveness of NIT in inhibiting angiogenesis, tissue invasion, metastasis formation, and counteracting multidrug resistance. The efficacy and mechanism of action of NIT were found to vary across different cell lines. The findings to date are promising, suggesting that NIT or its derivatives could play a role in oncology, although further research is necessary to fully understand its potential and applicability in cancer treatment.

Eosinophilic cystitis (EC) is a rare inflammatory disease of unclear etiopathology and various clinical presentations. We present a case of a 10-year old boy who was referred to our center because of acute kidney injury. The imaging diagnostic showed hydronephrosis, irregular thickening and infiltration of the posterior bladder wall. During cystoscopy, no ureter orifices were identified. Based on histopathological examination of bladder biopsy specimens, EC in an acute phase was diagnosed. To our knowledge the presented case is the first where EC led to post-renal acute kidney injury requiring hemodialysis. In the article we describe the diagnostic difficulties, therapy, clinical outcomes, and patient’s follow-up.

Abstract Defects in the glycosaminoglycan layer (GAG) of the bladder mucosa have been identified as a significant contributor to the pathogenesis and clinical progression of chronic inflammatory diseases of the bladder, such as post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections. This narrative review aims to explore the contemporary evidence on the role of GAG reconstitution with intravesical installations of hyaluronic acid and chondroitin sulfate in the management of those patients, with a goal to provide valuable insights for clinical practice. The reviewed studies consistently demonstrate that GAG reconstitution can result in varying degrees of clinical improvement in patients with post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections, and is associated with a very favorable safety profile. While the available evidence is growing, its level is still limited, mainly by relatively low number of randomized controlled trials, with small sample sizes. Further research with larger, well-designed trials is needed to solidify the findings and optimize the clinical application of GAG reconstitution.

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive neoplasm. Currently, there are few reliable and widely used prognostic biomarkers of this disease. The purpose of this study was to assess the prognostic value of blood-, tissue- and urine-based biomarkers in patients with UTUC. A comprehensive literature search was conducted using the PubMed, Cochrane and Embase databases. Case reports, editorials and non-peer-reviewed literature were excluded from the analysis. As a result, 94 articles were included in this review. We evaluated the impact of 22 blood-based, 13 tissue-based and 4 urine-based biomarkers and their influence on survival outcomes. The neutrophil–lymphocyte ratio, albumin, C-reactive protein, De Ritis ratio, renal function and fibrinogen, which are currently mentioned in the European Association of Urology (EAU) guidelines, are well researched and most probably allow for a reliable prognosis estimate. However, our review highlights a number of other promising biomarkers that could potentially predict oncological outcomes in patients with UTUC. Nonetheless, the clinical value of some prognostic factors remains uncertain due to the lack of comprehensive studies.

Introduction In the majority of Western European countries, the coronavirus disease (COVID-19) pandemic has led to a dramatic reduction in urooncological surgeries. Our objective was to evaluate the impact of the pandemic on volume and patterns of urooncological surgery in Poland. Material and methods This is a retrospective analysis of 10 urologic centres in Poland. Data regarding major oncological procedures performed after the COVID-19 pandemic outbreak (March 15, 2020 – May 31, 2020) were evaluated and compared with data from the respective period in 2019. Results Between March 15, 2020 and May 31, 2020, a total of 968 oncological procedures were performed in participating centres. When compared to the respective period in 2019 (1063 procedures) the overall number of surgeries declined by 8.9%. The reduction was observed for transurethral resection of bladder tumour (TURBT) (20.1%) and partial nephrectomies (PN) (16.5%). Surgical activity considering radical nephrectomy (RN), nephroureterectomy (NU), and radical prostatectomy (RP) remained relatively unchanged, whereas radical cystectomy (RC) burden showed a significant increase (90.9%). Characteristics of patients treated with TURBT, RC, NU, PN, and RN did not differ significantly between the compared periods, whereas RP in the COVID-19 period was performed more frequently in patients with a higher grade group (p = 0.028) and positive digital rectal examination (p = 0.007). Conclusions Surgical activity for urological cancers in Poland has been maintained during the first wave of the COVID-19 pandemic. The Polish strategy in the initial period of the COVID-19 crisis mirrors the scenario of hard initial lockdown followed by adaptive lockdown, during which oncological care remained undisrupted and did not require particular priority triage.

Background: Microbiome dysbiosis plays a role in the pathogenesis of many urological diseases, including bladder cancer (BC). The aim of the study was to compare the urinary and gut microbiota of patients with BC with a healthy control (HC) group. Methods: The study group included patients hospitalized in 2020 to 2021 with diagnosed BC and HC. Prior to the transurethral resection of bladder tumor, patients collected their urine and stool which was then subjected to 16S rRNA gene sequencing. Results: Overall, 25 patients were enrolled in the study: 18 in the BC group and 7 in the HC group. Analysis of the urine and stool microbiome showed no statistically significant differences between patients with BC and HC in alpha diversity, beta diversity, and difference in taxa relative abundance. Detailed analysis of urine and stool microbiome depending on patient- and tumor-related characteristics also showed no statistically significant differences in alpha diversity and beta diversity. Differences in abundance (ANCOM) were noted in both types of samples in patients with BC. In the urine test, genus Lactobacillus was more common in patients with a positive history of Bacillus Calmette–Guérin (BCG) therapy, while genus Howardella and the strain Streptococcus anginosus were more common in women. In stool samples, abundance of phylum Desulfobacterota was most abundant in Grade G1 and least in G2. Class Alphaproteobacteria , order Rhodospirillales , order Flavobacteriales , and family Flavobacteriaceae were more common in women. Conclusions: The microbiome of urine and stool of patients with BC does not differ significantly from that of HC; however, its composition in patients with BC varies according to the patient’s sex.

IntroductionProstate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression.MethodsThe study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed.ResultsA positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP – the higher the expression of GOLPH3, the lower the efficacy of RP was (p

(1) Background: Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total laparoscopic approach offers decreased postoperative pain, less incisional morbidity, and a shorter recovery time. (2) Methods: We present the results of a series of 43 laparoscopic donor nephrectomies performed in a single center. The procedures were performed in a systematic approach with transperitoneal access using four ports. The main renal artery and vein were ligated using a linear stapler fixed with an alternate triple row of titanium staples. The specimen was extracted in an endoscopic bag through an additional incision. (3) Results: All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.73 min. In all recipients, immediate kidney allograft function was observed. (4) Conclusions: Total laparoscopic living donor nephrectomy is a safe procedure. It was performed successfully in all cases with a short surgical time, low morbidity, and 0% mortality.

BCG is the most efficient adjuvant therapy for high-risk, non-muscle-invasive bladder cancer (NMIBC). Both innate and adaptive immune responses have been implicated in BCG-mediated effects. BCG vaccination can boost innate immune responses via trained immunity (TI), resulting in an increased resistance to respiratory viral infections. Here we evaluated for the first time whether intravesical application of BCG triggers increased immunity against SARS-CoV-2 in patients with high-risk NMIBC. Serum and peripheral blood mononuclear cells (PBMCs) from heparinized whole blood samples of 11 unvaccinated SARS-CoV-2-naïve high-risk NMIBC patients were collected at baseline and during BCG treatment in a pre-COVID-19 era. To examine B-cell or T cell-dependent adaptive immunity against SARS-CoV-2, sera were tested for the presence of SARS-CoV-2 neutralizing antibodies. Using a SARS-CoV-2 peptide pool, virus-specific T cells were quantified via IFNγ ELISpot assays. To analyze innate immune responses, mRNA and protein expression levels of pro- and anti-inflammatory cytokines were measured after a 24-hour stimulation of PBMCs with either BCG or SARS-CoV-2 wildtype. ATAC- sequencing was performed to identify a potential epigenetic reprogramming in immune cells. We neither identified SARS-CoV-2 neutralizing antibodies nor SARS-CoV-2- reactive T cells, indicating that intravesical BCG did not induce adaptive immunity against SARS-CoV-2. However, a significant increase in mRNA as well as protein expression of IL-1β, IL-6 and TNFα, which are key cytokines of trained immunity, could be observed after at least four intravesical BCG instillations. Genomic regions in the proximity of TI genes (TLR2, IGF1R, AKT1, MTOR, MAPK14, HSP90AA1) were more accessible during BCG compared to baseline. Although intravesical BCG did not induce adaptive immune responses, repetitive intravesical instillations of BCG induced circulating innate immune cells that produce TI cytokines also in response to SARS-CoV-2.

Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p

Abstract Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes.

We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/computed tomography (PET/CT) with choline followed by salvage lymph node dissection (SLND) in three academic centers between 2013 and 2020. A total of 27 men were included in the analyses. Sensitivity, specificity, positive and negative predictive values, and accuracy of choline-PET/CT in predicting pathology-proven lymph node involvement were 75%, 43%, 79%, 38% and 67% on per-patient and 70%, 86%, 80%, 78%, and 79% on per-site analyses, respectively, with the differences in specificity and NPV between per-patient and per-site analyses being statistically significant (p = 0.03 and 0.04, respectively). The study provides further insight into the role of preoperative choline-PET/CT in patients undergoing SLND for recurrent PC.

Background: Vasculitides are specific inflammations of the blood vessel wall that can take place in any organ system of the human body. They may occur as a primary process (primary systemic vasculitides, PSV) or may be secondary to another underlying disease. In general, in association with the specific type of vasculitis, affected vessels vary in size, type, and location. In the following scoping review, we present clinical characteristics and manifestations of PSV with reference to the genitourinary system. Materials and methods: A non-systematic search of the relevant literature was conducted using three electronic databases (PubMed, Embase, and Web of Science) up to 29 October 2021. Results: Urogenital manifestations of PSV are infrequent, with the most commonly reported findings as prostatic or testicular involvements. However, almost all other organs of the genitourinary system can be affected. Conclusions: Because of the clinical heterogeneity and non-specific symptoms, the proper diagnosis of PSV is often delayed and constricted. Fast identification of urological manifestations of vasculitides is essential in implementing appropriate therapy and avoiding unnecessary, harmful, and invasive surgery.

The microbiome is the totality of microorganisms found in a specific biological niche. It has been proven that in the human body, the microbiome is responsible for its proper functioning. Dysbiosis, i.e., a disturbance in the composition of the microbiome, may be associated with the pathogenesis of many human diseases. Until recently, studies did not focus on the microbiome of the urinary tract, because, since the 19th century, there had been a dogma that urine in healthy people is sterile. Yet, advances in molecular biology techniques have allowed this dogma to be overthrown. The use of DNA sequencing has shown that the urinary tract has its own endogenous microbiome. This discovery enabled further research on the characteristics of the urine microbiomes of healthy people, as well as on the role of the urine microbiome in the pathogenesis of many urological diseases, including bladder diseases. The aim of this review is to summarize the current knowledge on the urinary microbiome in bladder diseases and to identify potential directions for further research.

Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

Transurethral cystoscopy (CS) is a common urological procedure, performed mostly for diagnostic but also for therapeutic purposes. Although CS is generally well tolerated, some patients describe the pain related to the procedure as high or even “unbearable”. As a result, many patients fear and avoid both primary and/or follow-up cystoscopies. This may lead to uncontrolled progression of neoplastic disease. Therefore, it is crucial to maximally increase the comfort of the patient and to implement safe and effective analgesia before the procedure. Providing the patients with appropriate care during CS can encourage them to comply with diagnostic schedules and improve their prognosis. The aim of this review is to analyze the available literature on various methods of pain reduction during transurethral CS. The PubMed electronic database limited to English articles published until January 2021 was used in the process. Meta-analyses, systematic reviews, randomized controlled trials, clinical trials, prospective randomized studies, multicenter comparisons, reviews and retrospective comparisons were used. As a result, 65 articles were included in this review.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.

Abstract Background During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. Materials and methods The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. Results Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60–1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62–1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85–1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94–1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. Conclusions Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

Background: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. Objective: The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Design, setting, and participants: An online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU. Outcome measurements and statistical analysis: Survey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons’ experience and caseloads with pIVC utilization. Results and limitations: Overall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7–10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%). Conclusions: Our research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted. Patient summary: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

Abstract 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.

Introduction We aimed to examine the change in the number and severity of visits to the emergency departments (EDs) and subsequent admissions for urgent urologic conditions in the early stage of the coronavirus disease 2019 (COVID-19) pandemic in Poland. Material and methods We evaluated data from 13 urologic centers in Poland and compared the number of visits to the EDs and subsequent admissions before and after the advent of COVID-19 in 2020, and before and after the escalating national restrictions. Furthermore, data on types of urologic complaints, crucial laboratory parameters, and post-admission procedures were analyzed. Results In total 1,696 and 2,187 urologic visits (22.45% decrease) and 387 and 439 urologic urgent admissions (11.85% decrease) were reported in given periods in 2020 and 2019, respectively. The year-over-year difference in daily mean visits was clear (36.1 vs. 46.5; p < 0.001). Declines were seen in all complaints but device malfunction. In 2020 daily mean visits and admissions decreased from 40.9 and 9.6 before lockdowns to 30.9 (p < 0.001) and 6.9 (p = 0.001) after severe restrictions, respectively. There was a trend towards more negative laboratory parameter profiles in 2020, with patients who visited the EDs after severe restrictions having twice as high median levels of C-reactive protein (15.39 vs. 7.84, p = 0.03). Conclusions The observed declines in ED visits and admissions were apparent with the significant effect of national lockdowns. Our results indicate that some of the patients requiring urgent medical help did not appear at the ED or came later than they would have done before the pandemic, presenting with more severe complaints.

Background: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential therapeutic agent against bladder cancer (BC). Also, we aimed to determine whether Degrasyn is more effective in terms of anti-cancer activity compared to the non-selective DUB inhibitor PR-619. To facilitate the translational value of the obtained results, our experiments were performed using both human and canine in vitro models of BC. Methods: Human T24 (urothelial grade III BC) and SV-HUC-1 (non-tumorigenic urothelial cell line), as well as canine K9TCC-PU-NK and RDSVS-TCC1 (both derived from invasive grade III urothelial bladder tumors) cell lines, were used in the present study. Cell proliferation was determined using the MTT assay and Ki-67 proliferation assay, and the level of apoptosis induced by Degrasyn and PR-619 was evaluated by Annexin V-FITC staining and caspase 3/7 activation assay. Western blot was used to assess DNA damage and key proteins involved in apoptosis. Results: Degrasyn inhibited the proliferation of all BC cell lines in a concentration- and time-dependent manner. Lower concentrations of Degrasyn were more potent against human and canine BC cell lines compared to PR-619. Degrasyn induced caspase-dependent apoptosis and triggered DNA damage. PR-619 did not show a significant pro-apoptotic effect. Conclusions: Our results demonstrate that Degrasyn significantly impairs the growth of in vitro models of human and canine BC. Selective USP inhibition with Degrasyn seems to be more effective in reducing BC cell proliferation and inducing apoptosis and DNA damage than non-selective USP inhibition with PR-619.

Background: The efficacy of intravesical chemotherapy maintenance for patients with non-muscle invasive bladder cancer (NMIBC) is inferior compared to intravesical bacillus Calmette–Guerin (BCG). How intravesical chemohyperthermia (CHT) compares with BCG is under investigation.Objective: To compare the oncological outcomes and safety profile between intravesical CHT and BCG treatment for intermediate- and high-risk NMIBC.Methods: We performed a systematic review and meta-analysis of clinical studies comparing CHT with BCG for intermediate- and high-risk NMIBC patients. A comprehensive literature search on OVID MEDLINE, EMBASE, and Cochrane Library was conducted. Risk of bias was assessed by the Cochrane RoB tool and ROBINS-I. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Results: A total of 2,375 articles were identified and five studies were finally included. Among them, four randomised trials comprising 327 patients (CHT group: 156 patients; BCG group: 171 patients) were included in the meta-analysis. There were no significant differences in the 24–36 months recurrence rates (CHT: 29.5%, BCG: 37.4%; RR: 0.83, 95% CI 0.61–1.13; moderate certainty of evidence) and the 24–36 months progression rates (CHT: 4.4%, BCG: 7.6%, RR = 0.62, 95% CI 0.26–1.49; low certainty of evidence). There were also no significant differences in grade 1–2 adverse events (CHT group: 59.9%, BCG group 54.5%; RR = 1.10, 95% CI 0.93–1.30; moderate certainty of evidence) and grade 3 or above adverse events (CHT group: 23.2%, BCG group 22.5%; RR = 0.99, 95% CI 0.69–1.43; low certainty of evidence).Conclusions: Intravesical CHT had equivalent oncological outcomes and similar safety profile when compared to BCG maintenance therapy for patients with intermediate- and high-risk NMIBC. CHT is a possible alternative treatment in the times of BCG shortage.

Bladder cancer is one of the most common malignancies worldwide. The transurethral resection of bladder tumour (TURB) remains the gold standard in both diagnostics and treatment. Because of the importance of TURB in bladder cancer management and the fact that TURB is one of the most commonly performed urologic procedures, it is the subject of continuous technological development. The latest advances in the field of endourology are aimed at increasing surgical accuracy and thus reducing the risk of bladder tumour recurrence and progression. However, despite the constant progress in technology and technique, there are still a lack of good quality data showing the superiority of any of the methods. The aim of this paper is to present available data on new technological developments in surgical technique of TURB. Advantages and disadvantages of currently available methods are discussed, and literature showing their effectiveness and safety is shown.

Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME. In the settings of PC treatment, this can be commonly achieved with radiation therapy (RT). In addition, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), and irreversible electroporation (IRE) were shown to boost the anti-cancer response. Nevertheless, the present guidelines restrict their application to the context of a clinical trial or a prospective cohort study. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Nowadays, molecular research is essential for the better understanding of tumor cells’ pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’; therefore, it is possible to discover the complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs, which comprises seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration, and angiogenesis. Inhibition of this transcription factor inhibits the previously mentioned effects in cancer cells, whereas normal cells are not affected. Hence, STAT3 might be a viable target for cancer therapy.

Background: Transurethral resection of the prostate (TURP) is the gold-standard treatment for benign prostatic hyperplasia (BPH). However, laser surgery techniques (e.g., photoselective vaporization of the prostate (PVP), holmium laser, thulium laser enucleation of the prostate (HoLEP or ThuLEP)), and minimally invasive treatment options (e.g., UroLift) are increasingly replacing TURP. This study seeks to report the annual incidence, management trends, and costs of BPH procedures in the U.S. Methods: Data analyses of U.S. health insurance claims from 2004 to 2017, collected from the de-identified Optum Clinformatics Claims Database, were performed to determine the number of BPH patients and the treatment selected. Results: A total of 51,448 patients underwent BPH procedures from 2004 to 2017. There was a significant increase in the annual rate from 770 in 2004 to 6571 in 2017. The mean patient age (±SD) increased from 67.6 years old (±8.4) in 2004 to 73.4 years old (±8.4) in 2017. More than 60% of patients underwent cystourethroscopy and a post-void residual urine check for workup prior to surgical management. TURP was the most-common, and PVP was the second-most-common BPH procedure. Medical and total treatment costs increased, while the detection rate of prostate cancer after BPH surgery gradually decreased from 19.87% in 2004 to 5.78% in 2017. Conclusions: Our study demonstrates a recent trend in BPH management that replaces the traditional TURP technique with alternative methods. Due to rising costs, future studies should assess whether these newer methods are cost effective over the long term.

Background: Chronic itch is the most common symptom in dermatology. End-stage renal disease-associated chronic itch (ESRDCI) is a common burden affecting up to 35% of patients treated with hemodialysis. Kidney transplant (KTx) is believed to be the best renal replacement therapy leading to the elimination of ESRDCI. The study was undertaken to characterize and assess the prevalence of itch among patients after renal transplantation.Methods: Between October 2019 and January 2020, we analyzed the data of 197 patients comprising 121 males (61.4%) and 76 females (38.6%) and aged 54.5 ± 13.6 years. The data collection was performed with a specially designed questionnaire. Level of itch after renal transplantation was assessed with the use of a Numeral Rating Scale, a Visual Rating Scale, and 4-Item Itch Questionnaire. Moreover, the previous 3 days of itching were evaluated.Results: The patients suffered from chronic renal disease for 20.2 ± 12.3 years, with a mean time of pre-transplant dialysis of 2.6 ± 2.4 years and a mean time after the KTx of 8.0 ± 6.5 years. The itch was present in 38.6% of the patients during the hemodialysis, and in 73.7% of cases, the itch ceased completely after the successful transplantation. Moreover, only 2.63% of the cases had no improvement. Nevertheless, the itch was reported in 42 (21.3%) renal transplant recipients (RTR), and in 22 (52.4%) cases, the itch appeared after transplantation. The majority of patients suffering from itch were women (54.8%). Itch in the last 3 days was reported in 21 patients. The itch's severity was assessed with a numerical rating scale (NRS), with the worst severity measured at 6 ± 2.2 points indicating moderate itch. In most cases (57.1%), itch affected multiple body areas. Extremities (50%) and the back (50%) were among the most frequently affected areas. The sensation had a mostly short duration and was most frequently reported in the evening. Only eight patients suffered for the whole day. Hot water was the most frequently reported (16.7%) alleviating factor, whilst sweat was responsible for itch aggravation in 35.9% of cases.Conclusion: Our analysis on representative patients' population indicates that itch after KTx is an important problem. Moreover, it is worth noting that more than half of the RTR did not suffer from itch during dialysis.

Bladder cancer (BC) constitutes approximately 2% of all spontaneously occurring cancers in dogs. It is characterized by a devastating clinical course in most cases, which emphasizes a constant need for the development of novel methods of disease characterization and treatment. Over the past years, advances in cell engineering have resulted in the development of various canine in vitro models of BC, emerging as complements for in vivo research. In this article, we aimed to review the available data on existing in vitro models of canine BC, focusing primarily on their characteristics, applications in veterinary medicine, as well as advantages and disadvantages. The most commonly used in vitro models of canine BC comprise immortalized cell lines grown as adherent monolayers. They provide an unlimited supply of research material, however, they do not faithfully reflect the conditions prevailing in vivo, since the spatial cellular interactions are lost. The importance of the three-dimensional (3D) features of solid tumors in relation to carcinogenesis or drug response process has resulted in the development of the first canine 3D models of BC available for in vitro research. So far, results obtained with in vitro and in vivo research should be interpreted together. With the constantly growing complexity of in vitro models of BC cancer, animal-based research might be reduced in the future.

The aim of this study was to validate the value of E-cadherin and -catenin expression and to test an alternative prognostic marker, epithelial membrane antigen (EMA). Forty-nine consecutive patients with primary stage T1 non-muscle-invasive bladder cancer (NMIBC) were enrolled in this study. Tissue specimens were stained with the following mouse anti-human antibodies: anti-E-cadherin, anti--catenin, and anti-EMA. Reaction intensity within cancer cells was assessed according to the immunoreactive score (IRS). Finally, the association between the expression of selected proteins and patient survival was assessed. The mean follow-up was 34.8 months. Recurrence-free survival, progression-free survival, and overall survival (OS) were 47.5%, 72.5%, and 72.5%, respectively. Differences in the IRS for -catenin and EMA were found clinically, but were not statistically significant in prediction of the risk of disease progression (p > 0.05). No difference in protein expression was observed regarding the risk of recurrence, OS, or cancer-specific mortality (p > 0.05). Stratification of patients based on the IRS into three groups (poor, moderate, and intensive reaction) failed to identify a prognostic marker among the tested proteins (p > 0.05). Expression of E-cadherin, -catenin, and EMA cannot reliably predict survival in patients with high-risk NMIBC. Further searches are needed to identify tissue markers of progression and recurrence in NMIBC.