Urinary Bladder Cancer Research Articles

TC-Sniffer: A Transformer-CNN Bibranch Framework Leveraging Auxiliary VOCs for Few-Shot UBC Diagnosis via Electronic Noses.

Utilizing electronic noses (e-noses) with pattern recognition algorithms offers a promising noninvasive method for the early detection of urinary bladder cancer (UBC). However, limited clinical samples often hinder existing artificial intelligence (AI)-assisted diagnosis. This paper proposes TC-Sniffer, a novel bibranch framework for few-shot UBC diagnosis, leveraging easily obtainable UBC-related volatile organic components (VOCs) as auxiliary classification categories. These VOCs are biomarkers of UBC, helping the model learn more UBC-specific features, reducing overfitting in small sample scenarios, and reflecting the imbalanced distribution of clinical samples. TC-Sniffer employs intensity-based augmentation to address small sample size issues and focal loss to alleviate model bias due to the class imbalance caused by auxiliary VOCs. The architecture combines transformers and temporal convolutional neural networks to capture long- and short-range dependencies, achieving comprehensive representation learning. Additionally, feature-level constraints further enhance the learning of distinctive features for each class. Experimental results using e-nose data collected from a custom-designed sensor array show that TC-Sniffer significantly surpasses existing approaches, achieving a mean accuracy of 92.95% with only five UBC training samples. Moreover, the fine-grained classification results show that the model can distinguish between nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), both of which are subtypes of UBC. The superior performance of TC-Sniffer highlights its potential for timely and accurate cancer diagnosis in challenging clinical settings.

Outcomes of nephrostomy and double J stent in malignant ureteral obstruction in the Palestinian practice

BackgroundMalignant ureteral obstruction (MUO) is a serious health condition in which a malignant tumor compresses the ureter. The optimal decompressive intervention in MUO remains unclear. This study was conducted to assess and compare renal function, the occurrence of ureterohydronephrosis (UHN), intraoperative, and postoperative complications among patients with MUO who underwent double J stenting (DJS) and percutaneous nephrostomy (PCN) in the Palestinian practice.MethodsThis study was conducted in retrospective design in one of the main tertiary care hospitals in the West Bank of Palestine. The data were collected from the electronic health information system of the hospital for the patients with MUO who received either DJS or PCN as a decompressive intervention from January 2018 to January 2024.ResultsIn this retrospective analysis, 62 patients who had stage 2 to stage 4 cancer and suffered MUO were included. The mean age of the patients was 60.8 ± 13.6 years. Of the patients, 40 (64.5%) were male and 22 (35.5%) were female. Of the patients, 26 (41.9%) had urinary bladder cancer. Of the patients, 23 (37.1%) had flank pain and 16 (25.8%) had lower urinary tract symptoms. Of the patients, 34 (54.8%) experienced bilateral UHN and 28 (45.2%) experienced unilateral UHN. In this study, 43 patients (69.4%) received PCN, and 19 (30.6%) received DJS as a decompressive intervention. Of the patients, 36 (58.1%) suffered postoperative complications. Stent migration/slip, UTIs, and urosepsis were the most commonly reported postoperative complications. There were no statistically significant differences in the occurrence of intraoperative complications, postoperative complications, time elapsed from receiving the decompression intervention to the diagnosis of complications, ICU admission, prognosis of UHN, serum creatinine, and serum BUN between both decompressive interventions.ConclusionDespite improvements in renal functions, creatinine and BUN levels remained abnormal even after receiving a decompressive intervention. Postoperative complications were frequently reported among patients who received DJS or PCN as decompressive interventions. Larger prospective studies are still needed to determine the optimal interventions to improve outcomes, quality of life, and survival rates of patients with DJS or PCN.

Urothelial Urinary Bladder Cancer Is Characterized by Stage-Dependent Aberrations in Metabolism of Bioactive Sphingolipids

Although dysregulated sphingolipid metabolism was observed in many malignant tumors, bladder cancer has not yet been examined in this regard. This study aims to investigate the metabolism of bioactive sphingolipids across different stages of urothelial urinary bladder cancer (UBC). Forty-eight patients with UBC were included in this study. The neoplasms were classified as either non-muscle-invasive (NMIBC, n = 24) or muscle-invasive (MIBC, n = 24). Samples of the healthy bladder tissue were taken from the patients who underwent radical cystectomy. The content of sphingolipids was measured using an HPLC method, and the mRNA expression of sphingolipid transporters and metabolizing enzymes was evaluated using RT-PCR. Compared to the healthy bladder tissue, the UBC, regardless of the stage, showed an elevated expression of SphK1, Spns2, and ABCC1. The changes in the level of bioactive sphingolipids were strongly stage-dependent. MIBC showed accumulation of sphingosine-1-phosphate (S1P) and ceramide, whereas the content of these sphingolipids in the NMIBC tumor was not different from that of healthy tissue. Moreover, MIBC, compared to NMIBC, was characterized by higher levels of sphingosine and dihydroceramide. We conclude that profound alterations in sphingolipid metabolism develop upon UBC transition from non-muscle-invasive to muscle-invasive. They include the accumulation of S1P, resulting from the increased availability of sphingosine generated from ceramide, which also builds up due to a further activation of its de novo synthesis. We hypothesize that the dysregulation of S1P metabolism leading to the accumulation of this tumor-promoting sphingolipid contributes to the progression of UBC.

Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.

Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. In this prospective study, we included 62 patients over the age of 18years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.

Prognostic value of isolated tumor cells and micrometastasis of lymph nodes in invasive urinary bladder cancer.

The prognostic significance of nodal micrometastasis and isolated tumor cells (ITC) in urinary bladder cancer (UBC) is unknown. We aimed to evaluate the prevalence, clinical impact, and clinicopathological characteristics of nodal micrometastasis and ITC in UBC. A total of 124 patients with UBC undergoing surgery were investigated. Detection of micrometastasis and ITC was performed using pancytokeratin immunohistochemistry (IHC). Histopathologic and clinical findings were correlated with patients' outcome. IHC detected nodal micrometastasis and ITC (pNmi group) in 12.9% (13/101) of originally node-negative patients and in 26.1% (6/23) of originally node-positive patients (pN+ group). The remaining 88 were truly node-negative patients (pN0 group). After IHC, all 13 patients in the pNmi group were upstaged from pN0 to pN1-2 and one patient in the pN+ group was changed from pN1 to pN2. Nodal micrometastasis and ITC were significantly associated with mixed urothelial carcinoma (UC) (p = 0.002), UC with discohesive pattern (p = 0.006), glandular differentiation (p = 0.043), lymphovascular invasion (p = 0.009), and budding-like tumor cell clusters (p = 0.002). The pNmi group had significantly worse cancer-specific survival than the pN0 group in univariate (p = 0.004) and multivariate (p = 0.040) analysis. IHC frequently identified nodal micrometastasis and ITC in originally node-negative UBC patients on routine pathological examination. Nodal micrometastasis and ITC were independently associated with cancer-related mortality in UBC. IHC might be selectively used to detect micrometastasis and ITC in UBC having specific pathological features.

Association between radiation therapy for primary endometrial cancer and risk of second primary malignancies: a retrospective cohort study

Our objective was to evaluate the association of adjuvant radiation therapy (RT) to subsequent second primary malignancies (SPMs) in endometrial cancer survivors. Patients with endometrial cancer as their first malignancy were identified from 8 registries of the Surveillance, Epidemiology, and End Results (SEER) database. SPMs were defined as any type of primary malignancy that occurred more than 12 months after the diagnosis of endometrial cancer. Fine-Gray competing risk regression and Poisson regression were used to evaluate the radiotherapy-associated risk (RR) for SPMs. The Kaplan-Meier method was applied to assess the survival outcomes of endometrial cancer patients. Of 62,108 endometrial cancer patients,16,846 patients (27.12%) were in the RT group, and 45,262 patients (72.88%) were in the no-RT group. During the 30-year follow-up period, the cumulative incidence of SPMs was 20.9% and 19.7% in each group, respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, adjuvant RT was found to be associated with a higher risk of developing colon and rectum cancer (adjusted hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.12–1.50; P < 0.001; adjusted RR, 1.29; 95% CI, 1.11–1.49; P < 0.001), lung and bronchus cancer (adjusted HR, 1.27; 95% CI, 1.08–1.50; P = 0.004; adjusted RR, 1.26; 95% CI, 1.07–1.49; P = 0.005), vulva cancer (adjusted HR, 1.72; 95% CI, 1.04–2.85; P = 0.036; adjusted RR, 1.74; 95% CI, 1.03–2.88; P = 0.035), urinary bladder cancer (adjusted HR, 1.86; 95% CI, 1.41–2.46; P < 0.001; adjusted RR, 1.85; 95% CI, 1.40–2.44; P < 0.001), and non-Hodgkin lymphoma (adjusted HR, 1.37; 95% CI, 1.06–1.77; P = 0.016; adjusted RR, 1.37; 95% CI, 1.05–1.76; P = 0.017). However, a slightly decreased risk of breast cancer was observed in patients who underwent adjuvant RT (adjusted HR, 0.89; 95% CI, 0.80–0.98; P = 0.021; adjusted RR, 0.88; 95% CI, 0.80–0.98; P = 0.020). The RR for colon and rectum cancer decreased with age and elevated with increasing latency since endometrial cancer diagnosis, and the RR for urinary bladder cancer showed a similar tendency with latency. SPMs can significantly impair the survival outcomes of primary endometrial cancer survivors. Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer. Long-term surveillance of these patients should be recommended for detecting SPMs.

Are TP53 Arg72Pro and MDM2 T309G polymorphisms associated with bladder cancer risk? A meta-analysis

Background: We still do not know the exact cause of bladder cancer (BC). Objectives: Evaluation of the effect of TP53 Arg72Pro and MDM2 T309G polymorphisms with the risk of Bladder cancer. Methods: A literature search was conducted followed by a meta-analysis. Then, sensitivity and subgroup analyses were performed. 14 relevant studies were included in the quantitative analysis. Results: No statistically significant associations were found. The results of the subgroup analysis revealed a significant association in the Turkish population for T309G: G vs. T (P-value= 0.015; OR 95%CI= 1.51 [1.084; 2.125]), GG vs.TT (P-value= 0.009; OR 95% CI= 2.60 [1.262; 5.370]). Sensitivity analysis revealed a significant association between the Arg72Pro: C vs G (OR= 1.22, 95% CI [1.05; 1.40]), CC vs. GG (OR= 1.54; 95% CI [1.13; 2.09]), CC+CG vs. GG (OR= 1.24; 95% CI [1.01; 1.53]), CC vs. CG+GG (OR= 1.33; 95% CI [1.01; 1.74]), and T309G: G vs. T (OR= 1.30; 95% CI [1.07; 1.57]), GG vs. GT+TT (OR= 1.53; 95% CI [1. 10; 2.11]), GG vs. GT (OR=1.44; 95% CI [1.02; 2.02]), GG vs. TT (OR= 1.88; 95% CI [1.25; 2.82]) with BC occurrence. Conclusion: The T309G polymorphism was found to be a predisposing allele for BC in Turkish population. Keywords: Bladder cancer (BC), polymorphism, Meta-analysis, T309G, Arg72Pro, TP53, MDM2.

Disulfiram-Copper Potentiates Anticancer Efficacy of Standard Chemo-therapy Drugs in Bladder Cancer Animal Model through ROS-Autophagy-Ferroptosis Signalling Cascade.

Cost-effective management of Urinary Bladder Cancer (UBC) is an unmet need. Our study aims to demonstrate the efficacy of a drug repurposing strategy by using disulfiram (DSF) and copper gluconate (Cu) as an add-on treatment combination to traditional GC-based chemother-apy against N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced UBC mice (C57J) model. Male C57BL/6J mice were given 0.05% BBN in drinking water ad libitum, and tumour for-mation was verified by histological and physical evaluation. Animals were subsequently divided into eight groups and received treatment with different drug combinations. Control animals received only ve-hicle (DMSO). At the end of the treatment schedule, the bladder tumour was excised and further used to check the expression (mRNA and protein) of ALDH1 isoenzymes using qRT-PCR, western blot, and IHC methods. Autophagy induction was assessed by quantifying the expression of LC3B and SQSTM1/p62 proteins through IHC. Biochemical analysis of superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation levels in the freshly isolated tumours was performed to check the alterations in the antioxidant system caused by combination treatment. We observed significant induction of an invasive form of bladder cancer in the mice after nine-teen weeks of BBN exposure. The animals began exhibiting early indications of inflammatory alterations as early as the sixth week following BBN treatment. Furthermore, the wet bladder weight and overall tu-mour burden were significantly decreased (p&#60; 0.0001) by DSF-Cu co-treatment in addition to the GC-based chemotherapy. Real-time PCR analysis revealed that treatment with disulfiram and copper glu-conate significantly decreased (p&#60;0.0001) the mRNA expression of ALDH1 isoenzymes. Comparing the triple drug combination group (GC+DSF-Cu) to the untreated mice, a significant rise in LC3B puncta (p&#60;0.0001) and a decrease in P62/SQSTM1 (p=0.0002) were noted, indicating the induction of autophagy flux in the add-on group. When GC+DSF-Cu treated mice were compared to the untreated tumour group, a substantial decrease in ALDH1/2 protein expression was observed (p= 0.0029 in IHC and p&#60;0.0001 in western blot). Lipid peroxidation was significantly higher (p&#60;0.0001) in the triple drug combination group than in untreated mice. There was a simultaneous decrease in reduced glutathione (GSH) and en-zyme superoxide dismutase (SOD) levels (p&#60;0.0001), which strongly suggests the generation of reactive oxygen species and induction of ferroptotic cell death in the add-on therapy group. Additionally, in both IHC and western blot assays, ALDH1A3 expression was found to be significantly increased (p=0.0033, &#60;0.0001 respectively) in GC+DSF-Cu treated mice relative to the untreated group, suggesting a potential connection between the ferroptosis pathway and ALDH1A3 overexpression. It was found that disulfiram with copper treatment inhibits bladder tumour growth through ferroptosis-mediated ROS induction, which further activates the process of autophagy. Our results prove that DSF-Cu can be an effective add-on therapy along with the standard chemotherapy drugs for the treatment of UBC.

Comparison of Tissue and Urine Microbiota in Male, Intervention Naive Patients with and without Non-Invasive Bladder Cancer

<bold></bold> Introduction: To investigate the presence of dysbiosis in patients with naive bladder cancer. Methods: Twelve male patients with non-invasive bladder cancer and twelve age-matched healthy males had midstream urine and tissue samples taken. A history of endourological interventions was determined as an exclusion criterion, ensuring that the study was designed solely with naïve participants. The bacterial 16s ribosomal RNA V3-V4 regions were used to examine urine and tissue samples. We compared the microbiota composition of the bladder cancer and control groups. Results: Escherichia Shigella (p < 0.001), Staphylococcus (p < 0.001), Delftia (p < 0.001), Acinetobacter (p < 0.001), Corynebacterium (p < 0.001), and Enhydrobacter (p < 0.001) were abundant in bladder cancer tissue samples. Escherichia Shigella (p < 0.001), Ureaplasma (p < 0.001), Lactobacillus (p = 0.005), Stenotrophomonas (p < 0.001), Streptococcus (p < 0.001), Corynebacterium (p < 0.001), and Prevotella (p = 0.039) were abundant in bladder cancer urine samples. Midstream urine has a sensitivity of 83% for detecting dysbiotic bacteria in cancer tissue. Conclusions: Our research is the first microbiota study of bladder cancer done with naive patients who have never had an endourological intervention. Escherichia Shigella, Staphylococcus, Acinetobacter, Enhydrobacter, Delftia, Corynebacterium, and Pseudomonas were detected as dysbiotic bacteria in bladder cancer. The sensitivity of the midstream urine sample in detecting dysbiosis in tissue is 83%.

Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021

BackgroundThe burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases.MethodsWe obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI).ResultsIn 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths.ConclusionsThe global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.

Genitourinary tumors and liver transplantation: A comprehensive review.

Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease, but the persistent organ shortage emphasizes a need to explore unconventional donor sources, including individuals with a history of malignancies. This review investigates the viability of liver donation from individuals with current or past genitourinary malignancies, focusing on renal, prostate and urinary bladder cancers. The rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor age. Analysis of transmission risks reveals low rates of donor-derived cancer transmission, particularly for early-stage renal and prostate cancers. Recipients with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer recurrence. Nonetheless, the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management strategies. Recommendations for pre-transplant evaluation and post-transplant surveillance are discussed, highlighting the need for individualized approaches in this patient population. Further prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.

Urinary bladder carcinogenic potential of 4,4'-methylenebis(2-chloroaniline) in humanized-liver mice.

Occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28 weeks. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the two models. At week 4, MOCA exposure induced simple hyperplasia, cell proliferation, and DNA damage in the urothelium of the humanized-liver mice, while in the non-humanized mice these effects were not observed. Notably, the concentration of 4-amino-4'-hydroxylamino-3,3'-dichlorodiphenylmethane (N-OH-MOCA) in the urine of humanized-liver mice was more than 10 times higher than that in non-humanized mice at the 4-week mark. Additionally, we observed distinct differences in the expression of cytochrome P450 isoforms between the two models. Although no bladder tumors were detected after 28 weeks of treatment in either group, these findings suggest that N-OH-MOCA significantly contributes to the carcinogenic potential of MOCA in humans.

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.

To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.

Cancer incidence in a cohort of Danish firefighters: An extended long-term follow-up 1968-2021.

To update and extend the examination of cancer incidence in a cohort of Danish firefighters, now adding 7 years of follow-up and 2766 additional firefighters. The primary focus was directed toward cancer sites that recently contributed to the hazard evaluation conducted by the International Agency for Research on Cancer (IARC). The updated cohort consisted of 11,827 male Danish firefighters who were followed up for cancer from 1968 to 2021. Cohort cancer morbidity was compared with a working population reference group, and standardized incidence ratios (SIR) were used for estimation of relative risks, along with 95% confidence intervals (95% CI). Among full-time firefighters, SIR of skin melanoma was 1.30 (95% CI: 1.02-1.66), and SIR = 1.37 (95% CI: 1.02-1.85) for over 5 years of employment. Slightly positive associations were also observed for cancer of the urinary bladder (SIR = 1.16; 95% CI: 0.93-1.45), prostate (SIR = 1.11; 95% CI: 0.97-1.28), and testis (SIR = 1.11; 95% CI: 0.75-1.63). This updated study provides evidence indicating an elevated risk of skin melanoma in firefighters. Consistent with IARC's evaluation, we also identified positive associations for urinary bladder, prostate, and testis cancer. In contrast, our findings did not suggest an increased risk of colon cancer, non-Hodgkin lymphoma, and mesothelioma. The latter may be due to small numbers in our still relatively young cohort. Continuous follow-up for cancer in firefighters is warranted, including assessment of influence from surveillance bias.

Insights into the Interplay between the Urinary Microbiome and Bladder Cancer: A Comprehensive Review.

New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis and therapeutic responses. Although several efforts have been made to identify a "core urinary microbiome", different fingerprints have been identified in men and women that shift with age. The main bacterial groups overall include Firmicutes, Actinobacteria, Fusobacteria, and Bacteroidetes. Although patients with bladder cancer have a microbiome that is similar to that of healthy individuals, differences have been observed at the species level with Fusobacterium nucleatum and Ralstonia, and at the genus level with Cutibacterium. Different bacterial representations may influence extracellular matrix composition, affecting tumor metastatic spreading and tumorigenic metalloproteinase expression. Furthermore, gene expression affecting targets of immune therapy, such as PD-L1, has been associated with changes in bacterial representations and therapeutic response to BCG. This comprehensive review aims to examine the influence of the urinary microbiome in bladder cancer.

Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer.

DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cut-off value of 6,5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising non-invasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.

Artemisinin pre-treatment fore cisplatin dosage enhances high grade urothelial carcinoma treatment in male albino mice via reverse gene expression modulation of FGFR3, HRAS, P53 and KDM6A

BackgroundUrinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma.MethodsSixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR.ResultsCompared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia.ConclusionsThis study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment.

Urothelial cancer: state of art in Ukraine and improvement pathways.

This study aims to assess the effectiveness of urothelial cancer treatment in Ukraine, utilizing population-based data from the National Cancer Registry. The primary goal is to evaluate trends and approaches to therapy, with a focus on overall survival rates in patients with urothelial tumors. A retrospective cross-sectional analysis was conducted based on the National Cancer Registry, involving 12698 patients (2008-2020) with urothelial tumors of the upper urinary tract (UTUC) and bladder cancer (BC) who underwent surgical treatment. Demographic indicators, surgical interventions, complications, and survival rates were analyzed. The average age for all patients was 70 years. The number of patients undergoing radical treatment was 1820 (15%) among BC and 573 (59%) among UTUC. The 30-day readmission rate was low for both, with a slightly higher preference for UTUC (2.3 vs. 4.6%). Whereas grade III or higher Cl-Dindo complications were seen in only 0.2% of cases. Notable findings include low frequency of neoadjuvant (7%) and adjuvant chemotherapy (28%) among patients with invasive urothelial carcinomas. Median eGFR for invasive UTUC before and after surgery was 63.2 and 51.4ml/min, respectively (P=0.00054). The directly opposite trend was seen in BC-61.2 and 68.7ml/min, respectively (P=0.0026).For BC, the overall survival rates by stages were: I-73%, II-49%, III-18%, and IV-11% (χ2=1807.207; P=0.000001). As for UTUC, the 5-year overall survival rates corresponded to the literature data, but there was a pronounced negative trend towards a decrease in this indicator after a 10-year period for all stages (χ2=146.298; P=0.000003). The study emphasizes the importance of effective systemic treatments, adherence to treatment guidelines, and the need for multidisciplinary consultations among Ukrainian patients with urothelial cancer.

Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment.

Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.

ROLE OF HAEMATOLOGY BIOMARKERS IN URINARY BLADDER AND RENAL CELL CANCER PATIENTS TREATED WITH IMMUNE-ONCOLOGICAL DRUGS

Background: Urinary bladder (UB) and Renal Cell Cancer (RCC) are common in men than women with poor outcome. The novel immunotherapy drugs like Immune Check Point Inhibitors (ICIs) are effective but expensive. However, a cost-effective and reliable biomarker to predict response and clinical outcomes is lacking. Objective: To study the association of pre-treatment haematological parameters with clinical outcome in urinary bladder and renal cell cancer patients treated with ICIs. Method: In a retrospective study, we included 52 patients with urinary bladder and RCC treated with ICIs from Jan 2008 to Dec 2019. Clinical evaluation and laboratory investigations were performed as a part of standard protocol. CBC parameters such as WBC, TLC, DLC, Hb, Platelet, Neutrophil:Lymplocyte Ratio(NLR), Platelet:Lymphocyte Ratio (PLR), Lymphocyte:Monocyte Ratio(LMR) were studied at the time of TMC enrolment(first) and before the start (pre-treatment) of the ICIs therapy(io). Results: Amongst the CBC parameters, WBC count, when categorized based on cut off from ROC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be significantly associated with progression of disease with p- value 0.012 with Hazard Ratio (HR) - 2.52 (95% C.I. - 1.2-5.31) &amp; p- value 0.060 with Hazard Ratio (HR) – 1.99 (95% C.I. – 0.96-4.12) respectively. The ROC - based cut off for WBC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be 7.16 X10e3/µL (AUC of 72%) with 71% sensitivity and 72% specificity and 6.48 X10e3/µL (AUC of 74%) with 67% sensitivity and 72% specificity respectively to predict progressed cases with respect to non-progressed cases. Along with WBC, the pre-treatment Absolute Neutrophil Count (ANC) (&gt;3.67)&amp; Absolute Monocyte count (AMC)(&gt;0.42) pre-treatment of the ICIs therapy(io)) showed a significance with Hazard Ratio (HR) – 3.09(95% C.I.– 1.26-7.6) with p-value 0.010, Hazard Ratio (HR) – 3.48(95% C.I. - 1.6-7.57)and p-value &lt;0.001 respectively. The ROC- based cut off for ANC at the pre-treatment of the ICIs therapy(io) were found to be 3.67 X10e3/µL (AUC of 68.4%) with 82.4% sensitivity and 50% specificity. Similarly The ROC- based cut off for AEC at the time of TMC enrolment(first) and AMC at the pre- treatment of the ICIs therapy(io) were found to be 0.22 X10e3/µL (AUC of 69.6%) with 55.9% sensitivity and 82.3% specificity and 0.42 X10e3/µL (AUC of 74.7%) with 72.7% sensitivity and 72.2% specificity respectively to predict progressed cases compared to non-progressed cases. Of 52 patients, 34 (65.4%) had progression. The median (m) PFS was 8.67 months (95% CI 2.26 - 15.09).The one year PFS rate was 46.5 (95% CI 31.2 -60.5). The mPFS in WBC &lt;=7.16 was 26.48 months (95% CI 0 - 53.08) higher than the mPFS of 5.75 (95% CI 0.21 - 11.29) in WBC &gt;7.16 with P value 0.012 at the time of TMC enrolment. Similarly, the mPFS in WBC pre- treatment of the ICIs therapy(io))&lt;=6.48 was13.11 months (95% CI 0 – 28.95) higher than the mPFS of 6.18 (95% CI 2.67-9.68) in WBC &gt;6.48 with P value 0.060.Along with WBC, the mPFS in ANC at the pre- treatment of the ICIs therapy(io)&lt;=3.67 was 27.4(95% CI 0-55.21) higher than the mPFS of 6.18(95% CI 1.47-10.88)in ANC &gt;3.67 with p value 0.010. The mPFS in AMC at the pre-treatment of the ICIs therapy(io)&lt; =0.415 was 27.4 (95% CI 9.41-45.39) higher than the mPFS of 3.91 (95% CI 0.06-7.76) in AMC &gt;0.415with p- value &lt;0.001.We observed mPFS in immunotherapy cycles &gt;=6 to be 15.9 (95% CI 6.98-24.82) was higher than the mPFS of 2.23 (95% CI 0.99-3.481) in immunotherapy cycles&lt;6 with p value 0.025. The patients were followed for a period of 40.35 months (95% CI 26.98 - 53.71). Of 52 patients, 32(61.5%) patients deceased with median OS of 18.46 months (95% CI 10.12 - 26.80) and the one year OS rate was 57.6 (95% CI 41.6 - 70.6). Conclusion: Simple, routinely available and cost effective WBC (TLC), Absolute Neutrophil Count (ANC) ,Absolute Monocyte Count (AMC) and Absolute Eosinophil Count (AEC) from CBC test has a great potential to be used as a biomarker to predict response and clinical outcomes in patients with urinary bladder cancer and RCC patients treated with ICIs.