Urinary tract cancers (UTCs), including bladder cancer, remain a significant public health challenge, particularly among individuals aged 75 and older. Despite declining bladder cancer-specific mortality rates between 2015 and 2020, the broader trends in UTC mortality and associated demographic disparities remain underexplored.

We analyzed mortality data from 1999 to 2022 using the CDC WONDER database. UTC deaths were identified using ICD- 10 codes C64 to C68. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, stratified by sex, race/ethnicity, and census regions. Joinpoint regression identified annual percent changes (APCs) to assess temporal trends.

From 1999 to 2022, 477,157 UTC deaths were recorded, 66% of which occurred among individuals aged 75 and older. The AAMR increased from 97.1 in 1999 to 103.5 in 2022, with a rise between 1999 and 2007 (APC: 0.63%), a decline from 2007 to 2019 (APC: - 0.33%), and a resurgence from 2019 to 2022 (APC: 2.42%). Older males exhibited higher AAMRs than females (178.7 vs. 53.6 in 2022), and Whites had the highest AAMR (108.5) among racial groups. The Western region recorded the highest AAMR (84.3) during the study period.

The resurgence in UTC mortality post- 2019 highlights emerging challenges, particularly among older males, Whites, and residents of the Western region. Targeted interventions, including improved screening and equitable healthcare access, are essential to mitigate these disparities and improve outcomes.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract, with urothelial bladder cancer accounting for approximately 90% of cases. Metastatic UC (mUC) is a particularly aggressive subset that presents significant treatment challenges, especially in patients who are often older than 70 years and have multiple comorbidities. For several decades, cisplatin-based chemotherapy has been the standard first-line treatment for locally advanced (LA) mUC. However, its utility has been limited as many patients are ineligible owing to their health status, and overall survival rates remain suboptimal. Recent advancements, including antibody-drug conjugates and immunotherapies, have begun to reshape the treatment landscape for LA/mUC. The combination of enfortumab vedotin and pembrolizumab has shown promising clinical outcomes. The approval of multiple novel drugs and combination therapies not only provides new opportunities for patient care but also creates the need for physicians to adapt to this evolving therapeutic paradigm. This review explores the latest clinical data on the management of LA/mUC and offers insights into sequencing therapies for patients with LA/mUC.

Gender differences in medicine are playing an increasingly important role in diagnostic testing as well as therapy choices. Risk factors and mortality vary depending on gender. Diseases often manifest differently depending on gender. In diagnostic testing, gender-specific aspects need to be taken into consideration. For instance, bladder cancer diagnosis is often delayed in women compared to men as haematuria is frequently attributed to benign conditions like urinary tract infections. In therapy, decisive gender disparities should also be considered. To state an example, immune-checkpoint inhibitors have shown better response in men than in women when treating renal cell carcinoma. Furthermore, outcomes after treatment for urological tumours differ depending on gender.

Bladder cancer (BCa) is among the most frequently diagnosed urinary tract cancers, characterized by a high recurrence rate and significant clinical heterogeneity. Effective diagnosis and treatment of BCa demand continuous advancements in medical technologies, particularly given the limitations of classical methods such as cystoscopy and urine cytology. A comprehensive search of PubMed and Web of Science was conducted using relevant keywords to structure this narrative review. Additionally, specialist journals were reviewed. Only articles in English were included, with selection based on titles, abstracts, and availability of full texts. In recent years, biomarkers have emerged as crucial tools complementing traditional techniques, providing more precise, sensitive, and non-invasive methods for early detection, prognosis, and monitoring treatment response in BCa. Molecular, genetic, and protein biomarkers enable a deeper understanding of BCa biology, creating opportunities for personalized therapy tailored to individual patient needs. However, despite their potential, certain challenges remain, including standardization, validation, and integration into routine clinical practice. This review highlights recent advancements in BCa biomarkers and their transformative potential in oncological care. It underscores the importance of incorporating these innovations to refine diagnostic and therapeutic approaches, ultimately improving patient outcomes. Modern diagnostic and prognostic tools for BCa can enhance treatment outcomes by enabling early disease detection and reducing recurrence risks. This progress promises to improve patients' quality of life by minimizing disease burden and fostering effective, tailored care strategies.

This publication represents a summary of the updated 2025 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). The aim is to provide practical recommendations on the clinical management of MMIBC with a focus on diagnosis, treatment, and follow-up.

For the 2025 guidelines, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences.

The key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with MMIBC. The guidelines stress the importance of a multidisciplinary approach to the treatment of MMIBC patients and the importance of shared decision-making with patients. The key changes in the 2025 muscle-invasive bladder cancer (MIBC) guidelines include the following: a new recommendation for the use of susceptible FGFR3 alterations to select patients with unresectable or metastatic urothelial carcinoma for treatment with erdafitinib; significant adaption and update of the recommendations for pre- and postoperative radiotherapy and sexual organ-preserving techniques in women; new recommendation related to radical cystectomy and extent of lymph node dissection based on the results of the SWOG trial; recommendation related to hospital volume; new recommendations for salvage cystectomy after trimodality therapy and for the management of all patients who are candidates for trimodality bladder-preserving treatment in a multidisciplinary team setting using a shared decision-making process; significant adaption and update to the recommendation for adjuvant nivolumab in selected patients with pT3/4 and/or pN+ disease not eligible for, or who declined, adjuvant cisplatin-based chemotherapy; and addition of a new recommendation for metastatic disease regarding the antibody-drug conjugate trastuzumab deruxtecan in case of HER2 overexpression; in addition, removal of the recommendations on sacituzumab govitecan as the manufacturer has withdrawn the US Food and Drug Administration approval for this product; update of the follow-up of MIBC; and full update of the management algorithms of MIBC.

This overview of the 2025 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up of MIBC patients and is designed for effective integration into clinical practice.

Opium is used recreationally and for pain relief in certain regions and has been classified as a human carcinogen by the IARC. While its use is rare in Europe and Oceania, it remains a major public health issue in other parts of the world. This study evaluates the risk of bladder cancer (BCa) among opium users compared to non-users.

A comprehensive search of MEDLINE, Scopus, and Web of Science was conducted up to July 2024 to identify studies examining the link between opium use and BCa. A meta-analysis was performed to calculate the pooled risk ratio (RR) with 95% confidence intervals (CIs) (PROSPERO: CRD42024562623).

A total of 15 studies (n=60,149) were included. The analysis showed that opium users had a significantly higher risk of developing BCa than non-users (RR: 2.36; 95% CI: 1.92-2.90; P<.001). The risk increased with the amount of opium consumed, regardless of type or method of use.

Opium consumption increase the risk of developing BCa by more than twofold among users. Awareness of its carcinogenic potential and public health implications is crucial. Our findings underscore the need for global prevention strategies and further research into opium-related BCa risks.

The tumor microenvironment is a dynamic and complex three-dimensional network comprising the extracellular matrix and diverse non-cancerous cells, including fibroblasts, adipocytes, endothelial cells and various immune cells (lymphocytes T and B, NK cells, dendritic cells, monocytes/macrophages, myeloid-derived suppressor cells, and innate lymphoid cells). A constantly and rapidly growing number of studies highlight the critical role of these cells in shaping cancer survival, metastatic potential and therapy resistance. This review provides a synthesis of current knowledge on the modulating role of the cellular microenvironment in cancer progression and response to treatment.

The nonmuscle invasive bladder cancer treated with BCG instillations in patients who smoke could potentially lead to poorer oncological results in the light of the new EAU risk groups classification for NMIBC that did not include BCG treated patients or smoking status.

Outcomes from 1313 patients with nonmuscle invasive bladder cancer treated with TURBT, re-TURBT and BCG instillations at 13 academic hospital centers, since 2002, has been included in this retrospective study. The study variables, including cumulative smoking exposure have been analyzed. A multivariable Cox proportional hazard model was used to assess associations between smoking variables and disease progression and repeated in the EAU high risk and very high-risk group. The statistical significance threshold was set at 0.05, and the statistical analysis was performed using Stata/SE version 17 (StataCorp, College Station, TX, USA).

Cox regression analysis revealed in 1313 patients diagnosed with T1G3 NMIBC that patients with a history of heavy and long-term smoking faced a more than twofold increased risk of disease progression compared to nonsmoker patients (HR 2.35; 95% CI: 1.7-3.2; P < 0.01) and a significantly poorer PFS for patients with a history of heavy long-term smoke exposure (P < 0.01). Patients with heavy long-term smoking exposure according to the EAU21 high-risk group had a PFS comparable to very high-risk patients and high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group (HR 1.4; 95% CI: 1.3-1.6; P < 0.01).

This study adds valuable information on the relationship between smoking and the progression of NMIBC and BCG therapy. The findings emphasize the need for healthcare providers to consider a patient's smoking history when managing NMIBC and express the need for individualized smoking cessation counseling and individualized treatment approach.

Bladder cancer (BCa) is a very common urological cancer. Literature showed smoking as a main risk factor for BCa however patients may not be well-informed about the relation between smoking and BCa. Urologists play a crucial role in educating patients about smoking risks and encouraging cessation. The objective is to discover sociodemographic factors that influence the success rate of smoking cessation and other behavioral changes in a sample of smoking Lebanese patients diagnosed with BCa.

A cross sectional study was conducted using a phone survey composed of 53 questions assessing the patients' knowledge that they had or received from their treating physician about smoking as risk factor for BCa. A sample of patients diagnosed with BCa between 2015 and 2020 were contacted and data was collected between the months of September 2022 and May 2023. Inclusion criteria consisted of adult patients with a diagnosis of BCa and a history of smoking while exclusion criteria consisted of unreachable patients. 260 patients were chosen, 182 patients responded making the response rate 70 % RESULTS: Our sample size consisted of 182 patients was composed of 143 males (78.6 %) and 39 females (21.4 %), 97 (53.3 %) are currently smokers of which 50 (51.5 %) tried but failed, 41 (42.3 %) found no benefit in stopping and 6 (6.2 %) were not counseled. 145 patients (79.7 %) knew about smoking as a risk factor for BCa, with only 6 (3.3 %) knowing before their diagnosis. The multivariate analysis has shown that women (p = 0.010), patients with higher educational level (p = 0.004) tend to stop smoking after diagnosis with BCa more than men and people with lower educational level. Also there was a positive correlation between urologist counseling and smoking cessation (p = 0.03).

These findings showed that people had little knowledge about smoking as risk factor for BCa. A need for nationwide awareness campaigns about smoking risks specially targeting lower educational level patients and men or implicating stricter laws for smoking. Also a need of improving in smoking cessation counseling of urologists.

Bladder cancer is a public health concern, with smoking and occupational exposure being major risk factors. However, specific risks in women, particularly hormonal, lifestyle, and environmental factors, are underexplored. This study aimed to assess these risk factors in women, focusing on smoking, occupational exposure, recurrent urinary tract infections (UTIs), body mass index (BMI), menopausal status, and family history of cancer.

This retrospective cohort study included 850 women diagnosed with bladder cancer (2018-2023) and age-matched controls. Data on smoking, occupational exposure, UTIs, BMI, menopausal status, and family history were collected from medical records: multivariate logistic regression and propensity score matching identified independent risk factors. Subgroup analysis explored interactions between menopausal status and other factors.

Smoking (OR = 2.15, p = 0.002), occupational exposure (OR = 1.89, p = 0.007), and recurrent UTIs (OR = 1.72, p = 0.013) were significant risk factors, particularly in post-menopausal women. Menopausal status amplified the effects of smoking and UTIs but was not an independent predictor. BMI and family history showed no significant associations.

Smoking, occupational exposure, and recurrent UTIs are key risk factors for bladder cancer in women, especially post-menopausal women, highlighting the need for targeted prevention strategies.

To assess the association of being overweight or obese with Nonmuscle invasive bladder cancer (NMIBC) recurrence, stage progression, and grade progression.

Patients with NMIBC were included and categorized into 3 groups based on their body mass index (BMI): normal weight, overweight, and obese. Recurrence was defined as any histologically proven bladder cancer on subsequent transurethral resection of bladder tumor (TURBT). Progression was defined as upgrading from low to high grade, upstaging to pT1 from pTa, or to muscle-invasion from pT1 disease.

A total of 457 patients were analyzed, 135 (29.5%) had normal weight, 192 (42.6%) were overweight, and 130 (28.4%) were obese, with a median BMI of 27.1 (24.4-30.7) Kg/m2. The study found no significant difference in the time to recurrence, stage progression, and grade progression within the BMI categories (P < .05). Additionally, no increased risk was observed in BMI categories (Obesity recurrence HR: 1.067, CI 95%: 0.783-1.453; Obesity stage progression HR: 1.315, 95% CI: 0.635-2.724; Obesity grade progression HR: 0.586, 95% CI: 0.195-1.760).

In our cohort, body weight category showed no association with NMIBC recurrence, stage progression, or grade progression. These findings highlight the need to identify other potential risk factors that could improve NMIBC risk stratification. Further studies are warranted to validate our results and explore additional predictors of NMIBC outcomes.

Background/Objectives: It is said that genes that escape from X chromosome inactivation (XCI) contribute to gender differences. We analyzed the prognostic role of these genes and identified a gender-biased difference in prognosis according to KDM6A mutation in the immune therapy cohort (IMvigor 210). We also investigate the gender-biased differential effect of KDM6A mutation in several public databases of urothelial carcinoma (UC). Methods: We used AACR GENIE, The Cancer Genome Atlas, International Cancer Genome Consortium, several public databases related to immune therapy, chemotherapy, and BCG treatment. We studied the gender-biased prognostic role of KDM6A mutation in several cohorts and the association between KDM6A mutation and immune-related fractions according to gender. Results: The expression of KDM6A was higher in females than in males in several cohorts. Mutation of KDM6A was observed in about 20-25% of the patients. The rate of KDM6A mutation was higher in females than in males in several cohorts. Kaplan-Meier analysis revealed a gender-biased difference in prognosis between patients with KDM6A mutations and those with the wild-type KDM6A in several cohorts, including the immune therapy cohort. The rate of immune-inflamed type was higher in males than in females in the patients with KDM6A mutation in the IMvigor 210 and UC-GENOME studies. Single-sample Gene Set Enrichment Analysis showed that CD8+ cells and type 1 IFN response fractions and APC co-inhibition fraction were higher in the male than female patients with KDM6A mutation. Similar findings were observed in other immune-related studies (UC-GENOME). Conclusions: The effect of KDM6A mutation on immune therapy varied according to gender, and the status of KDM6A mutation may be a promising biomarker in immune therapy in UC.

Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease is preoperative chemotherapy followed by radical cystectomy. Dose-dense MVAC (ddMVAC), a two-day chemotherapy regimen, is the reference treatment protocol in this setting. The presented study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy-a one-day regimen given before the resection of the bladder due to muscle-invasive disease. Methods: A retrospective analysis included 119 consecutive patients diagnosed with urothelial muscle-invasive bladder cancer (MIBC) who underwent preoperative chemotherapy with the aMVAC regimen. The planned treatment included 4-6 cycles of preoperative chemotherapy. The analysis of the degree of histopathological response to treatment was based on the three-grade TRG (tumor regression grade) classification. Results: A complete pathological response (TRG1) was observed in 44 patients (36.7%), and a major pathologic response ( Collapse

Urine is an attractive biospecimen for noninvasive tests to facilitate bladder tumor diagnostics. Three different point-of-care (POC) tests based on lateral flow immunoassays (LFAs) are currently commercially available: UBC® Rapid Test, BTA stat®, and NMP22TM BladderChek. The present review discusses these different tests based on their performance, clinical utility and the nature of the respective analytes. The level of sensitivities of UBC Rapid Test® and BTA stat® for detection of high-grade nonmuscle invasive bladder cancer using urine is in the order of 80%. Estimations of performance are highly dependent on patient selection criteria. UBC® Rapid Test shows a sensitivity of approximately 85% in patients presenting with macrohematuria which is the most common initial clinical symptom. Estimations of specificity are complicated by differences in how control groups are selected in different studies and are therefore more difficult to compare between published reports. Different POC tests differ with regard to the source of the analytes that are measured. The BTA Stat® test is based on detection of plasma proteins (Factor H/Factor H-related proteins), potentially leading to a lack of specificity during conditions of renal dysfunction. A large number of analytes to be used for urine-based bladder cancer tests have been described in the literature, including cytokines and proteases implicated in tumor invasion. These proteins, although biologically relevant, are often present at very low levels in urine that may be unsuitable for development of LFAs. Release of abundant intracellular structural proteins from cells such as cytokeratins (UBC® Rapid Test) and nuclear matrix proteins (NMP22TM) may therefore be advantageous. We conclude that available data support the use of urine-based POC tests as adjuncts during the clinical work up of suspected bladder cancer.

ObjectivesThis study aims to analyze urinary bladder cancer (UBC) incidence rates in Lebanon over a 12-year period (2005-2016) and compare them with rates in other countries. It also discusses UBC risk factors in Lebanon.IntroductionLebanon has one of the highest estimated age-standardized incidence rates (ASIRw) of UBC worldwide.MethodsData on UBC were obtained from the Lebanese national cancer registry for the years 2005-2016. The study calculated age-standardized incidence rates (ASIRw) and age-specific rates per 100 000 population. It also estimated the population attributable fractions of smoking, water pollution, and air pollution for UBC incidence in Lebanon in 2016. However, limited data precluded sensitivity analyses, potentially affecting the robustness of the estimates.ResultsDuring this period, UBC ranked as the third most common cancer in males (12.9% of all new cancer cases) and the eighth most common in females (2.8% of all new cancer cases), excluding non-melanoma skin cancer. The average ASIRw was 28.8 in men and 6.6 in women, placing Lebanon among the countries with the highest UBC incidence rates globally. UBC incidence rates increased with age. Estimates indicated that 46.4% of UBC cases in the Lebanese population were attributed to current smoking, 8.6% to water pollution with disinfection byproducts, and 6.0% to air pollution with PM2.5.ConclusionThis study underscores the urgent need to mitigate UBC risk in Lebanon through tobacco control and by reducing exposure to preventable environmental and occupational risk factors, including tobacco smoking, water pollution, and air pollution.

Although men have a higher risk of developing a bladder cancer, women appear to have a poorer prognosis and a more advanced stage at diagnosis. We performed a retrospective population-based study on muscle invasive bladder cancer (MIBC) using data from a cancer registry in a French department to compare overall and specific survival data according to sex.

We included all patients living in the department of Hérault and diagnosed with MIBC between January 1, 2017 and December 12, 2019. Univariable and multivariable analyses were performed on all variables of interest.

We included 124 women and 432 men. There was no significant difference in age or stage at diagnosis according to sex. Squamous cell carcinomas were more common in women (P<0.001). Cystectomy was more frequent in men than in women (50.7% vs 35.4%) (P=0.0039). By multivariable analysis, the independent factors for being treated by cystectomy were sex (P=0.004), age (P<0.001) and stage (P<0.001). Forty-seven percent of women received no treatment or palliative treatment. Overall mortality was 79% in women and 63.2% in men (P<0.001). The median specific survival was 10.8months in women and 32.7months in men (P<0.0001). By multivariable analysis, the independent risk factors for mortality were female sex (P=0.047), cT4 stage (P=0.005) and absence of cystectomy (P<0.001).

Our study shows that women are less often treated with cystectomy and have worse prognosis than men. The reasons for this gender difference are multifactorial.

C.

Urological cancers are one of the most prevalent malignancies around the globe. Specifically, bladder cancer severely threatens the health of humans because of its heterogeneous and aggressive nature. Extensive studies have been conducted for many years in order to address the limitations associated with the treatment of solid tumors with selective substances. This article aims to provide a summary of the therapeutic drugs that have received FDA approval or are presently in the testing phase for use in the prevention or treatment of bladder cancer. In this review, FDA-approved drugs for bladder cancer treatment have been listed along with their dose protocols, current status, pharmacokinetics, action mechanisms, and marketed products. The article also emphasizes the novel preparations of these drugs that are presently under clinical trials or are in the approval stage. Thus, this review will serve as a single point of reference for scientists involved in the formulation development of these drugs.

Biomarkers that identify tumors with better/worse prognosis can help reduce treatment costs and contribute to patient survival. In urothelial bladder cancer (UBC), accurate prediction of recurrence and progression is essential to inform therapeutic management. Herein, we explore the role of genetic variants of xenobiotic metabolic pathways in UBC susceptibility and prognosis. In total, 295 participants with UBC and 295 controls were genotyped using TaqMan® probes. CYP1A1 (rs1048943), CYP3A4 (rs4646437), CYP3A5 (rs4646450), UGT2B7 (rs7438135), and UGT2B15 (rs3100) allele frequencies were compared between UBC patients and controls and were analyzed concerning tumor grade, invasion, and recurrence. CYP3A4 (AA) increased susceptibility to UBC 3-fold when interacting with CYP3A5 (AA+AA). The susceptibility was higher in CYP3A4 (AA) males (OR=3.189) and individuals exposed to pesticides (OR=5.492). When interacting with hypertension, the allele C of CYP1A1 also increased UBC susceptibility by 2-fold. The UGT2B15 mutant allele was associated with high-grade tumors (OR=2.196) and recurrences (OR=2.561), as well as tumor grade when associated with mutated alleles of CYP3A4 (OR=6.171) and CYP3A5 (OR=3.492). Genes-encoding proteins were further analyzed using the STRING program, demonstrating that the proteins had known interactions in databases and were co-expressed. This study is a pioneer in evaluating these variants in a Latin American population from Brazil and confirms occupational pesticide exposure as a risk factor for UBC, mainly in genetically susceptible individuals. Furthermore, these variants may have additional clinical value for predicting susceptibility and prognostic stratification in patients with exposure-related cancers such as UBC.

Traditional methods of bladder cancer (BC) diagnosis include clinical examination, imaging, urine tests, cystoscopy, and biopsy. Due to the complexity of detection, diagnostic markers of bladder cancer measured in blood are still being sought. The pathogenesis of BC is complex and depends on many factors. However, the available literature data suggest that gasdermin D (GSDM D) has an influence in the pathogenesis of cancers. This study is the first that assesses the significance and diagnostic utility of serum GSDM D in bladder cancer.

A total of 80 serum samples were obtained and analysed from healthy volunteers (C) and bladder cancer patients. The cancer patients were further classified into two groups, low-grade (LG) and high-grade (HG) bladder cancer, according to the TNM classification. The serum levels of GSDM D, CEA, and CA19-9 were assessed following the manufacturer's instructions using immunoassay techniques.

The concentrations of GSDM D were nearly twice as high in the serum of BC patients compared to controls. Additionally, the median of GSDM D concentration was notably elevated in LG and HG bladder cancer than in C. In the total study group, the GSDM D concentration correlated with CRP and CEA levels. The diagnostic sensitivity of GSDM D was higher than that of CEA, but slightly lower in comparison to CA19-9. Moreover, the negative predictive value of GSDM D was the highest among all tested markers. The highest positive predictive value and diagnostic accuracy were observed for CEA, while the accuracy of GSDM D was comparable. GSDM D had an AUC value of 0.741, which was similar to the AUC value of CEA.

GSDM D in serum appears to be a valuable diagnostic biomarker, especially when its measurement is used in conjunction with other markers such as CEA. Its high sensitivity makes it effective for the early detection of bladder cancer.

Several studies indicate that smoking is one of the major risk factors for bladder cancer. Nicotine and its metabolites, the main components of tobacco, have been found to be strongly linked to the occurrence and progression of bladder cancer. However, the function of nicotine metabolism-related genes (NRGs) in bladder urothelial carcinoma (BLCA) are still unclear.

NRGs were collected from MSigDB to identify the clusters associated with nicotine metabolism. Prognostic differentially expressed genes (DEGs) were filtered via differentially expression analysis and univariate Cox regression analysis. Integrative machine learning combination based on 10 machine learning algorithms was used for the construction of robust signature. Subsequently, the clinical application of signature in terms of prognosis, tumor microenvironment (TME) as well as immunotherapy was comprehensively evaluated. Finally, the biology function of the signature gene was further verified via CCK-8, transwell migration and colony formation.

Three clusters associated with nicotine metabolism were discovered with distinct prognosis and immunological patterns. A four gene-signature was developed by random survival forest (RSF) method with highest average Harrell's concordance index (C-index) of 0.763. The signature exhibited a reliable and accurate performance in prognostic prediction across TCGA-train, TCGA-test and GSE32894 cohorts. Furthermore, the signature showed highly correlation with clinical characteristics, TME and immunotherapy responses. Suppression of MKRN1 was found to reduce the migration and proliferation of bladder cancer cell. In addition, enhanced migration and proliferation caused by nicotine was blocked down by loss of MKRN1.

The novel nicotine metabolism-related signature may provide valuable insights into clinical prognosis and potential benefits of immunotherapy in bladder cancer patients.

Urological tumors are an important disease affecting global human health, and their pathogenesis and treatment have been the focus of medical research. With the in - depth study of microbiomics, the role of the microbiome in urological tumors has gradually attracted attention. However, the current research on tumor - associated microorganisms mostly focuses on one type or one site, and currently, there is a lack of attention to the microbiome in the immunity and immunotherapy of urological tumors. Therefore, in this paper, we systematically review the distribution characteristics of the microbiome (including microorganisms in the gut, urine, and tumor tissues) in urologic tumors, the relationship with disease prognosis, and the potential mechanisms of microbial roles in immunotherapy. In particular, we focus on the molecular mechanisms by which the microbiome at different sites influences tumor immunity through multiple "messengers" and pathways. We aim to further deepen the understanding of microbiome mechanisms in urologic tumors, and also point out the direction for the future development of immunotherapy for urologic tumors.

Faced with the current global ageing situation, advanced age has become a risk factor for bladder carcinogenesis progression and immunotherapy. Exploring the common mechanisms of aging and immune in bladder cancer and finding new prognostic markers and immunotherapeutic targets has become an urgent issue.

Aging-immune related genes (AIGs) were collected from the public databases MSIGDB, HAGR and ImmPort, and hub AIGs were finally identified in the TCGA-BLCA disease cohort by expression, prognosis, and clinicopathological correlation analysis, and the correlation of hub AIGs with immune microenvironment, immunotherapeutic response, ferroptosis and m6A methylation was verified. Subsequently, prognostic clusters and risk-prognosis models for AIGs was constructed by cluster analysis and multifactorial Cox regression analysis, and the gene mutation and immune infiltration characteristics of the different clusters were explored. Finally, the expression level of related genes was verified by immunohistochemical experiments using patient samples from our medical center.

145 potential prognostic AIGs were collected in bladder cancer and finally clarified NFKB1 and IL7 with significant expression differences, prognostic value and age correlation. By single gene analysis, hub AIGs were explored to be significantly correlated with immunotherapeutic response, immune microenvironment, ferroptosis and m6A methylation. Subsequently, the risk-prognosis model was constructed with Riskscore = (0.0581)*NFKB1 + (- 0.2285)*IL7. And prognostic clusters based on hub AIGs was performed by cluster analysis, which clarified that the high-risk group was the pro-cancer group, which had a lower mutation rate of hub genes and higher of neutrophil infiltration. Finally, immunohistochemistry of patients confirmed that IL7 and NFKB1 were underexpressed in bladder cancer, and the proliferation and migration ability of tumor cells were significantly decreased after overexpression of these genes.

This study is the first to identify NFKB1 and IL7 as hub AIGs in bladder cancer, which provide new prognostic markers and immunotherapeutic targets.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Bladder cancer (BC) is known for its high recurrence rate and requires constant patient monitoring. To confirm the diagnosis, a tissue sample from a cystoscopy is required, which the patient often avoids. Urine has the potential to be utilized as a diagnostic fluid because of its non-invasive nature and various biomarker contents. The aim of this study was to determine the diagnostic value of cytokeratin fragment-19 (CYFRA21-1) levels in urine for diagnosing BC. This single-center cross-sectional study included adults aged ≥18 years who presented with hematuria and had suspected BC based on imaging findings. Patients with a history of intravesical chemotherapy, radiotherapy and immunotherapy were excluded. Urine samples were collected prior to the cystoscopy. Detection of urinary CYFRA21-1 was carried out using the enzyme-linked immunosorbent assay (ELISA) method. Of 154 patients included in the study, the diagnosis of BC was confirmed in 92 patients. Patients with BC had significantly higher urinary CYFRA21-1 levels compared to the non-bladder cancer group. The sensitivity, specificity, positive and negative predictive value, and positive likelihood ratio of the CYFRA21-1 were 80.4%, 43.5%, 67.9%, 60% and 1.425, respectively. The area under the curve (AUC) for CYFRA21-1 was 0.608, computed from a receiver operating curve (ROC) with a cut-off value of 13.3 ng/mL. In conclusion, urinary CYFRA21-1 levels have moderate diagnostic accuracy in determining BC among suspected individuals. Due to its high sensitivity, this biomarker could potentially be used alongside other screening tools for BC detection.

Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70-75% of all bladder cancer cases. The standard treatment for high-risk NMIBC involves transurethral tumour resection followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. While BCG immunotherapy is both safe and effective, it frequently leads to the development of lower urinary tract symptoms (LUTS) such as urinary urgency, frequency, dysuria, and pelvic discomfort. These symptoms can significantly diminish patients' quality of life and may result in the discontinuation of BCG treatment, adversely affecting oncological outcomes. Despite the considerable clinical impact of BCG-induced LUTS, the underlying mechanisms remain unclear, hindering the implementation or development of effective treatments. This review provides novel insights into the potential mechanisms underlying BCG-induced LUTS, focusing on the integrated roles of afferent and efferent nerves in both normal and pathological bladder sensation and function. Specifically, this review examines how the body's response to BCG-through the development of inflammation, increased urothelial permeability, and altered urothelial signalling-might contribute to LUTS development. Drawing from known mechanisms in other common urological disorders and data from successful clinical trials involving NMIBC patients, this review summarises evidence supporting the likely changes in both sensory nerve signalling and bladder muscle function in the development of BCG-induced LUTS. However, further research is required to understand the intricate mechanisms underlying the development of BCG-induced LUTS and identify why some patients are more likely to experience BCG intolerance. Addressing these knowledge gaps could have profound implications for patients' quality of life, treatment adherence, and overall outcomes in NMIBC care.

Bladder cancer (BC) currently ranks as the 9th most common cancer worldwide. It is characterised by very high rates of recurrence and metastasis. Most cases of BC are of urothelial origin, and due to its ability to penetrate muscle tissue, BC is divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The current diagnosis of BC is still based primarily on invasive cystoscopy, which is an expensive and invasive method that carries a risk of various complications. Urine sediment cytology is often used as a complementary test, the biggest drawback of which is its very low sensitivity concerning the detection of BC at early stages, which is crucial for prompt implementation of appropriate treatment. Therefore, there is a great need to develop innovative diagnostic techniques that would enable early detection and accurate prognosis of BC. Great potential in this regard is shown by epigenetic changes, which are often possible to observe long before the onset of clinical symptoms of the disease. In addition, these changes can be detected in readily available biological material, such as urine or blood, indicating the possibility of constructing non-invasive diagnostic tests. Over the past few years, many studies have emerged using epigenetic alterations as novel diagnostic and prognostic biomarkers of BC. This review provides an update on promising diagnostic biomarkers for the detection and prognosis of BC based on epigenetic changes such as DNA methylation and expression levels of selected non-coding RNAs (ncRNAs), taking into account the latest literature data.

Bladder cancer in patients under 45 is poorly characterized and rarely described, with variabilities in clinical outcomes and tumor properties. Our study aimed to elucidate the clinical and pathological features and outcomes of bladder cancer in this younger demographic to better inform management strategies.

We conducted a retrospective analysis at the Urology Department of "Pius Brînzeu" County Emergency Clinical Hospital in Timișoara, Romania, on 60 patients aged 18-45 who underwent transurethral resection of bladder tumor (TURBT) during a 9-year period.

The cohort had a mean age of 38.5 ± 5.6 years with a male predominance (70%). Most tumors were non-muscle-invasive (NMIBC; 80%), with 16.7% being papillary urothelial neoplasms of low malignant potential (PUNLMP), 50% stage pTa, and 30% stage pT1. High-grade tumors were present in 43.3% of the patients. Recurrence occurred in 40% of the patients, while progression was observed in 16.7%. The 3-year overall survival rate was 93.3%, and the progression-free survival rate was 83.3%. Patients with high-grade tumors had a significantly higher recurrence rate (61.5% vs. 23.5%, p = 0.003) and lower survival rates compared to those with low-grade tumors.

Young patients predominantly present with low-to-intermediate-stage tumors, yet a significant portion exhibit high-grade tumors associated with poorer outcomes. These findings suggest that while bladder cancer in younger patients tends to be less invasive, aggressive follow-up and treatment are crucial in those with high-grade tumors.

Bladder cancer is the ninth most common tumour entity worldwide. Aberrant expression of different keratins has been described in bladder cancer, which is used for diagnostic purposes, but it can also have prognostic value. However, not all keratins have been analysed in bladder cancer, and whether keratins are important for cell viability of bladder cancer tumour cells is not yet known.

We analyse the expression of CK10, CK13, and CK14 in 4 different urinary bladder transitional cell carcinoma cell lines via western blot. Furthermore, we downregulate the expression of CK13 and CK14 using siRNAs and evaluate the cell viability of the carcinoma cells.

In this study, we show that different urinary bladder transitional cell carcinoma cell lines have distinct expression pattern of the keratins CK10, CK13, and CK14. Using several siRNAs targeting either CK13 or CK14, we show that both keratins have long protein half-lives. Although we achieve a reduction in CK13 and CK14 protein levels, these reductions do not influence the cell viability of the cell lines.

In conclusion, we provide evidence that CK10, CK13, and CK14 are expressed on the protein level in different urinary bladder transitional cell carcinoma cell lines, but that their targeting does not affect the viability of the carcinoma cells.

Bladder cancer is among the most prevalent tumors in the urinary system and is known for its high malignancy. Although traditional diagnostic and treatment methods are established, recent research has focused on understanding the molecular mechanisms underlying bladder cancer. The primary objective of this study is to identify novel diagnostic markers and discover more effective targeted therapies for bladder cancer. This study identified differentially expressed genes (DEGs) between bladder cancer tissues and adjacent normal tissues using data from The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the functional roles of these genes. A protein-protein interaction (PPI) network was also constructed to identify and analyze hub genes within this network. Gene set variation analysis (GSVA) was conducted to investigate the involvement of these genes in various biological processes and pathways. Ten key genes were found to be significantly associated with bladder cancer: IL6, CCNA2, CCNB1, CDK1, PLK1, TOP2A, AURKA, AURKB, FOXM1, and CALML5. GSVA analyses revealed that these genes are involved in a variety of biological processes and signaling pathways, including coagulation, UV-response-down, apoptosis, Notch signaling, and Wnt/beta-catenin signaling. The diagnostic relevance of these genes was validated through ROC curve analysis. Additionally, potential therapeutic drug interactions with these key genes were identified. This study provides valuable insights into key genes and their roles in bladder cancer. The identified genes and their interactions with therapeutic drugs could serve as potential biomarkers, presenting new opportunities for enhancing the diagnosis and prognosis of bladder cancer.

Radical Cystectomy is indicated in muscle-invasive bladder cancer and select cases of nonmuscle invasive bladder cancer. Women often undergo additional reproductive organ removal, greatly impacting sexual function and quality of life. Pelvic organ-preserving radical cystectomy aims to mitigate these effects, but its oncologic outcomes are not well-defined. This presents a meta-analysis of available literature on oncological outcomes of pelvic organ-preserving radical cystectomy in women with muscle invasive disease.

A systematic search across PubMed, Web of Science, Scopus, and Google Scholar was performed to identify studies comparing oncological outcomes between pelvic organ-preserving radical cystectomy and standard radical cystectomy in women with muscle-invasive bladder cancer or high-risk or recurrent nonmuscle invasive cancer. The search included English or Spanish studies, statistically comparing overall survival, cancer-specific survival, and recurrence-free survival. Statistical analysis used Review Manager, employing fixed or random-effects models based on heterogeneity.

Six retrospective studies met inclusion criteria, totaling 597 patients of which 303 received pelvic organ-preserving radical cystectomy and 294 received standard radical cystectomy. Overall Survival was not different between the 2 groups (HR 1.05 [0.77, 1.43]; P = 0.77). Cancer-Specific Survival also was found to be not different between the 2 groups (HR 1.27 [0.86, 1.87]; P = 0.22). Additionally, recurrence-free survival was not different between the 2 groups (HR 0.85 [0.41, 1.75]; P = 0.65. Four of the included studies exhibited a moderate risk of bias, with 1 study demonstrating low risk and the remaining study manifesting a serious risk of bias.

The comparison showed no significant differences in overall survival, cancer-specific survival, or recurrence-free survival rates.

Previous meta-analysis has demonstrated that no association was validated between passive smoking and pancreatic cancer. However, there is growing evidence on this issue recently. This study aimed to confirm this association.

PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to April 2024 for retrieval of full articles. Studies with the exposure of passive smoking and outcome of pancreatic cancer were eligible for the analysis. We generated pooled relative risks (RRs) and 95% confidence intervals (CIs) using DerSimonian-Laird random-effects models. Quality of evidence was assessed using the GRADE system.

Fourteen studies were included, with 5,560 pancreatic cancer patients. Passive smoking was associated with a moderate increased risk of pancreatic cancer (RR = 1.20, 95% CI: 1.11-1.30, p < 0.001). The results were consistent in both case-control (p=0.013) and cohort studies (p < 0.001) and in studies with high (p = 0.007) and moderate quality (p < 0.001). In subgroup analysis, the risk was significant for both current (RR=1.91, 95% CI: 1.45-2.51, p < 0.001) and non-current smokers (RR = 1.17, 95% CI: 1.01-1.36, p = 0.037), for exposure both in adulthood (RR = 1.18, 95% CI: 1.06-1.31, p = 0.002) and childhood (RR = 1.20, 95% CI: 1.08-1.34, p = 0.001). However, only regular or daily exposure (RR=1.28, 95% CI: 1.08-1.50, p = 0.003), rather than exposing occasionally, seldom or few times per week (p = 0.421), to passive smoking could increase the risk of pancreatic cancer.

Passive smoking exposure confers a significant increased risk for pancreatic cancer. The risk was valid in both case-control and cohort, high and moderate quality studies, in current and non-current smokers, and for both childhood and adulthood exposure. Regular or daily exposure rather than exposing occasionally, seldom or few times per week could exert a detrimental effect on pancreatic cancer.

Bladder cancer is a heterogeneous disease with varying prognostic outcomes based on the primary tumor site within the bladder. This study aims to evaluate the impact of tumor location on overall survival and cancer-specific survival in bladder cancer patients.

The authors conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database. Patients with primary transitional cell carcinoma of the bladder were categorized based on their tumor locations. Survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazards regression models, adjusted for age, sex, race, cancer stage, and treatment modalities. Additionally, binary logistic regression models were employed to predict overall mortality (OM) and cancer-specific mortality (CSM) at 1, 5, and 10 years.

The study included 107 909 patients diagnosed with primary bladder cancer between 2000 and 2021. Significant differences in survival outcomes were observed across different tumor sites. Bladder cancer originating in the urachus had the worst OS before 100 months and the worst CSS overall. Tumors in the anterior wall showed the worst OS after 100 months. In the Cox multivariable analysis, anterior wall tumors were associated with a 1.513-fold increased risk of death compared to lateral wall tumors. The binary logistic regression models showed that anterior wall tumors predicted the highest OM and CSM at 1-year, while urachal tumors had the worst outcomes at 5 and 10 years.

The primary site of bladder cancer is a significant predictor of survival outcomes, with tumors in the urachus and anterior wall associated with a poorer prognosis. These findings underscore the importance of considering tumor location in the prognosis and management of bladder cancer. Future studies should aim to validate these findings in more diverse populations and explore the underlying biological mechanisms that drive these differences.

Non-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk.

The data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan-Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence.

Among patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m2) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90; 95% confidential interval [CI] 4.01-15.55; p<0.001), current or former smoking (HR 1.85; 95% CI 1.07-3.20; p=0.027), and a high-grade tumor (HR 4.03; 95% CI 1.59-10.25; p=0.003) were significant predictors of tumor recurrence. The Kaplan-Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence.

The study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter, Cutibacterium, Alloscardovia, Moryella, and Anaeroglobus, that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium, and Bifidobacterium, exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue.

To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients.

A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research.

A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients.

Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Background  Previous research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. Aim  To investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. Materials and Methods  In the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence-specific primers. We compared ABO phenotypes, genotypes, and alleles between patients and the healthy controls and investigated their distribution according to the clinical and histological stage and recurrence rate. Results  No statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 ( p  < 0.001), A1 ( p  < 0.001), and B ( p  = 0.013), and a lower proportion of metastatic disease in A2 (0%, p  = 0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, p  < 0.001), A1 (70.1%, p  = 0.019), of nonmuscle invasive tumors in patients with O1 (55.1%, p  < 0.001), O2 (100%, p  = 0.045), and recurrent tumors in patients with O1 (70.2%, p  < 0.001) and A1 (74.2%, p  = 0.007) alleles. Conclusion  We did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage, and recurrence rate, respectively.

The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran's Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000-1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000-1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer.

Urinary bladder neoplasms constitute a heterogeneous group of tumors with diverse clinical behaviors and outcomes. Understanding the correlation between clinicopathological characteristics and the prognostic significance of molecular biomarkers in bladder cancer is vital for personalized treatment strategies and improved patient outcomes.

This prospective observational study aimed to comprehensively investigate the clinicopathological correlations and prognostic significance of molecular biomarkers in urinary bladder neoplasms.

A cohort of 174 patients diagnosed with urinary bladder neoplasm participated in this study. Clinicopathological data, including demographic information, medical history, imaging findings, and histopathological reports, were collected from the patient records. Tissue samples obtained from transurethral resection or biopsy were subjected to molecular biomarker analysis using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular profiling techniques. Longitudinal follow-up assessments were conducted to monitor disease progression, recurrence, and overall survival.

Out of 174 patients diagnosed with bladder neoplasms, the mean age of the patients was 62.4 years (±8.7), indicating that the study cohort primarily comprised elderly individuals. The majority of patients were male (126, 72.4%), reflecting the higher prevalence of bladder cancer among men compared to women. Preliminary analysis revealed significant associations between clinicopathological parameters, molecular biomarker expression profiles, and clinical outcomes in patients with urinary bladder neoplasms. Elevated expression levels of specific biomarkers such as tumor protein p53 (p53), Ki-67, and estimated glomerular filtration rate (EGFR) were observed in advanced tumor stages (p < 0.001) and higher histological grades (p < 0.05), indicating their potential prognostic significance. Furthermore, genetic alterations detected using molecular profiling techniques, including chromosomal gains and losses, were significantly correlated with aggressive disease phenotypes and increased recurrence risk (p < 0.01). Longitudinal follow-up data demonstrated that patients with elevated biomarker expression levels or genetic alterations had poorer treatment responses and shorter overall survival durations than those with lower biomarker expression levels.

This study highlights the importance of integrating clinicopathological parameters and molecular biomarker data for the risk stratification, treatment selection, and prognostic assessment of urinary bladder neoplasms.

Smoke exposure is associated with bladder cancer (BC). However, little is known about whether the histologic changes of BC can predict the status of smoke exposure. Given this knowledge gap, the current study investigated the potential association between histology images and smoke exposure status. A total of 483 whole-slide histology images of 285 unique cases of BC were available from multiple centers for BC diagnosis. A deep learning model was developed to predict the smoke exposure status and externally validated on BC cases. The development set consisted of 66 cases from two centers. The external validation consisted of 94 cases from remaining centers for patients who either never smoked cigarettes or were active smokers at the time of diagnosis. The threshold for binary categorization was fixed to the median confidence score (65) of the development set. On external validation, AUC was used to assess the randomness of predicted smoke status; we utilized latent feature presentation to determine common histologic patterns for smoke exposure status and mixed effect logistic regression models determined the parameter independence from BC grade, gender, time to diagnosis, and age at diagnosis. We used 2,000-times bootstrap resampling to estimate the 95% Confidence Interval (CI) on the external validation set. The results showed an AUC of 0.67 (95% CI: 0.58-0.76), indicating non-randomness of model classification, with a specificity of 51.2% and sensitivity of 82.2%. Multivariate analyses revealed that our model provided an independent predictor for smoke exposure status derived from histology images, with an odds ratio of 1.710 (95% CI: 1.148-2.54). Common histologic patterns of BC were found in active or never smokers. In conclusion, deep learning reveals histopathologic features of BC that are predictive of smoke exposure and, therefore, may provide valuable information regarding smoke exposure status.

Mobility limitations (e.g., using wheelchair) have been closely linked to diminished functional independence and quality of life in older adults. The regulation of mobility is pertaining to multiple neurophysiologic and sociodemographic factors. We here aimed to characterize the relationships of these factors to the risk of restricted mobility in older adults.

In this longitudinal study, 668 older adults with intact mobility at baseline completed the baseline assessments of clinical characteristics, cognitive function, sleep quality, activities of daily living (ADL), walking performance, beat-to-beat blood pressure, and structural MRI of the brain. Then 506 of them (mean age = 70.7 ± 7.5 years) responded to the follow-up interview on the mobility limitation (as defined by if using wheelchair, cane, or walkers, or being disabled and lying on the bed) after 18 ± 3.5 months. Logistic regression analyses were performed to examine the relationships between the baseline characteristics and the follow-up mobility restriction.

At baseline, compared to intact-mobility group (n = 475), restricted-mobility group (n = 31) were older, with lower score of ADL and the Montreal Cognitive Assessment (MoCA), greater score of Pittsburgh Sleep Quality Index (PSQI), poorer cardio- and cerebral vascular function, and slower walking speeds (ps < 0.05). The logistic regression analysis demonstrated that participants who were with history of falls, uncontrolled-hypertension, and/or greater Fazekas scale (odds ratios (ORs):1.3 ~ 13.9, 95% confidence intervals (CIs) = 1.1 ~ 328.2), walked slower, and/or with lower ADL score (ORs: 0.0026 ~ 0.9; 95%CI: 0.0001 ~ 0.99) at baseline, would have significantly greater risk of restricted mobility (p < 0.05; VIFs = 1.2 ~ 1.9).

These findings provide novel profile of potential risk factors, including vascular characteristics, psycho-cognitive and motor performance, for the development of restricted mobility in near future in older adults, ultimately helping the design of appropriate clinical and rehabilitative programs for mobility in this population.