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Medicine May 2024The causal role of body mass index (BMI) in bladder cancer (BC) by Mendelian randomization (MR) has not yet been reported. We evaluated the causal associations between...
The causal role of body mass index (BMI) in bladder cancer (BC) by Mendelian randomization (MR) has not yet been reported. We evaluated the causal associations between the measures of obesity (BMI, waist circumference, and body fat percentage) and BC. We conducted a 2-sample MR analysis to assess the genetic effect of measures of obesity on BC. The BMI dataset (GWAS ID: ukb-b-2303) comprised 454,884 Europeans, and we identified 9,851,867 single nucleotide polymorphisms (SNPs). The waist circumference data (GWAS ID: ukb-b-9405) included 462,166 Europeans and 9,851,867 SNPs. The body fat percentage dataset (GWAS ID: ukb-a-264) contained data from 331,117 Europeans and 10,894,596 SNPs. For the outcome data, the GWAS ID was finn-b-C3_BLADDER, consisting of 1115 cases and 217,677 controls, with 16,380,466 SNPs. The inverse-variance weighted (IVW) model was used as the primary MR analysis. Cochran Q-statistic was used to identify heterogeneity between the SNPs. The MR-Egger and MR-PRESSO methods were employed to assess directional pleiotropy and outlier SNPs. We detected a decisive causal link between BMI and BC by the IVW analysis (odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.08-1.85, P = .011). The IVW analyses revealed a significant correlation between BC and waist circumference (OR = 1.55, 95% CI: 1.08-2.12, P = .016). However, the IVW method (OR = 1.49, 95% CI: 0.99-2.00, P = .05) did not report any statistical significance between body fat percentage and BC. We did not observe heterogeneity and directional pleiotropy in the 3 pairs of MR studies. The 2-sample MR analysis revealed a conceivable causal association between obesity (BMI, waist circumference) and BC.
Topics: Humans; Urinary Bladder Neoplasms; Mendelian Randomization Analysis; Body Mass Index; Waist Circumference; Polymorphism, Single Nucleotide; Obesity; Genome-Wide Association Study; Risk Factors; Adipose Tissue; Male; Female
PubMed: 38758881
DOI: 10.1097/MD.0000000000038231 -
Medicine May 2024Hematuria is the most common symptom of bladder cancer (BCa). It is well-known that the frequency of hematuria increases with the use of antithrombotic drugs (ATDs). We... (Observational Study)
Observational Study
Hematuria is the most common symptom of bladder cancer (BCa). It is well-known that the frequency of hematuria increases with the use of antithrombotic drugs (ATDs). We designed our study with the hypothesis that patients using antithrombotic drugs who present with the complaint of hematuria and are subsequently diagnosed with BCa may receive an earlier diagnosis, leading to lower tumor grades and stages. Data of 441 consecutive patients who presented to our urology outpatient clinic with macroscopic hematuria between 2020 and 2023 were retrospectively evaluated. A total of 88 patients (21.4%) with a primary diagnosis of BCa were included in our study. Patients were divided into 2 groups: those using ATDs during the episode of macroscopic hematuria (group 1) and those not using ATDs (group 2). Univariate and multivariate binary logistic regression analysis was performed to identify risk factors that could predict tumor grade. The incidence of multiple tumors (>1) was significantly lower in patients using ATDs (P = .033). The number of patients with tumor size larger than 3 cm was significantly higher in the group not using ATDs (P = .005). The rates of pathological T1 stage in the group using ATDs were significantly lower than those in the nonuser group (P = .038). According to the results of the multivariate model, the effect of pathology stage and ATD use on predicting tumor grade was significant (P = .002 and P < .001, respectively). The probability of having a high-grade tumor in patients with pathology stage T1 was 5.32 times higher than in patients with pathology stage TA. The probability of having a high-grade tumor in patients not using ATDs was 7.73 times higher than in those using ATDs. The effect of pathology stage and ATD use on predicting tumor grade was found to be significant. The probability of having a high-grade tumor was higher in patients not using ATDs compared to those using ATDs. In light of these results, we can state that the use of ATDs is a positive predictive factor in the early diagnosis of BCa, bringing along the chance of early diagnosis and treatment.
Topics: Humans; Urinary Bladder Neoplasms; Male; Female; Retrospective Studies; Aged; Middle Aged; Early Detection of Cancer; Hematuria; Fibrinolytic Agents; Risk Factors; Neoplasm Staging; Neoplasm Grading
PubMed: 38758868
DOI: 10.1097/MD.0000000000038228 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024Bladder cancer (BC) is one of the 3 common malignant tumors in the urinary system, with high incidence, easy metastasis, poor therapeutic efficacy, and poor prognosis,... (Review)
Review
Bladder cancer (BC) is one of the 3 common malignant tumors in the urinary system, with high incidence, easy metastasis, poor therapeutic efficacy, and poor prognosis, which seriously threatens the health of human. Tumor cells exhibit a strong demand for iron, and iron overload can induce ferroptosis, which is an iron dependent cell death caused by lipid peroxidation and cell membrane damage. Therefore, ferroptosis has strong anti-tumor potential. The molecular mechanisms of ferroptosis is associated with abnormalities in cellular phospholipid metabolism and iron metabolism, and dysregulation of antioxidant and non-antioxidant systems Xc/glutathione (GSH)/glutathione peroxidase 4 (GPX4). Ferroptosis relevant molecules play important roles in the occurrence and development, metastasis, drug resistance, and immune response of BC, and are expected to become targets for the treatment of BC.
Topics: Ferroptosis; Humans; Urinary Bladder Neoplasms; Iron; Phospholipid Hydroperoxide Glutathione Peroxidase; Lipid Peroxidation; Glutathione; Antioxidants; Phospholipids; Amino Acid Transport System y+
PubMed: 38755725
DOI: 10.11817/j.issn.1672-7347.2024.230352 -
Microbiome May 2024Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets...
BACKGROUND
Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.
RESULT
Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8 cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles.
CONCLUSION
These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.
Topics: Animals; Dietary Fiber; Mice; Gastrointestinal Microbiome; Psyllium; Inulin; Urinary Bladder Neoplasms; Mice, Inbred C57BL; Dietary Supplements; Humans; Female; Radiation Injuries; Intestines; CD8-Positive T-Lymphocytes
PubMed: 38745230
DOI: 10.1186/s40168-024-01804-1 -
Scandinavian Journal of Urology May 2024One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these...
BACKGROUND AND AIMS
One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up.
METHODS
Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register.
RESULTS
Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death.
CONCLUSIONS
For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.
Topics: Humans; Male; Prostatic Neoplasms; Urinary Bladder Neoplasms; Prostatectomy; Aged; Sweden; Cystectomy; Middle Aged; Prostate-Specific Antigen; Risk Assessment; Aged, 80 and over; Incidental Findings
PubMed: 38738332
DOI: 10.2340/sju.v59.40001 -
The Journal of Medical Investigation :... 2024The prevalence of bladder cancer increases rapidly among individuals. The knowledge, attitude, and healthy lifestyle behaviors of individuals in Turkey regarding bladder...
The prevalence of bladder cancer increases rapidly among individuals. The knowledge, attitude, and healthy lifestyle behaviors of individuals in Turkey regarding bladder cancer are unknown. The present study aim was to examine the knowledge and attitudes of the participants about bladder cancer and healthy lifestyle behaviors. Methods?:?This cross-sectional study was conducted with 400 participants from outpatient clinic at Erciyes University. Data were collected by using a socio-demographic form and Healthy Lifestyle Behaviors Scale. Results?:?Findings revealed that 55% of the participants were aware of bladder cancer risks?;?smoking 55.5%, older ages 67%, synthetic dyes and some chemicals 43.7%, and overweight 34.5% increases the risk of bladder cancer. The findings showed that economic status and education effect on the Healthy Lifestyle Behaviors Scale scores. The positive relationship was found between self-realization, exercise, and interpersonal subscale in those with high-income participants. It is found that exercise, nutrition, and stress management that have a positive attitude among non-smokers toward the risk factors of bladder cancer. Conclusion?:?The information obtained from the study can be used to inform patients about bladder cancer, risk factors, and cancer prevention. In this regard, healthcare professionals can increase patients f knowledge and create awareness by preparing informative brochures, giving information during the examination, or making presentations. J. Med. Invest. 71 : 40-46, February, 2024.
Topics: Humans; Urinary Bladder Neoplasms; Health Knowledge, Attitudes, Practice; Male; Female; Middle Aged; Cross-Sectional Studies; Turkey; Adult; Healthy Lifestyle; Aged; Health Behavior; Risk Factors
PubMed: 38735723
DOI: 10.2152/jmi.71.40 -
International Journal of Molecular... May 2024Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and... (Review)
Review Comparative Study
Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette-Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy's role in BC management, ultimately improving patient outcomes.
Topics: Humans; Urinary Bladder Neoplasms; Immune Checkpoint Inhibitors; Administration, Intravesical; Immunotherapy; Treatment Outcome
PubMed: 38732167
DOI: 10.3390/ijms25094945 -
International Journal of Molecular... Apr 2024Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label...
Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.
Topics: Humans; Riboflavin; Urinary Bladder Neoplasms; Gemcitabine; Deoxycytidine; Cell Line, Tumor; Light; Photosensitizing Agents; Oxidative Stress; Cell Survival; Lipid Peroxidation; Adenosine Triphosphate; Mitochondria; Blue Light
PubMed: 38732087
DOI: 10.3390/ijms25094868 -
International Journal of Molecular... Apr 2024Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG)...
Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.
Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, -value = 0.0002), CD8 (HR: 0.0379, -value = 0.005), and ICOS (HR: 0.0768, -value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, -value = 0.0001) and T1 tumor stage (HR: 2.04, -value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, -value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.
Topics: Humans; Tumor Microenvironment; Urinary Bladder Neoplasms; Male; BCG Vaccine; Neoplasm Recurrence, Local; Female; Immunotherapy; Aged; Middle Aged; Macrophages; Carcinoma, Papillary; Lymphocyte Subsets; Prognosis; Aged, 80 and over
PubMed: 38731992
DOI: 10.3390/ijms25094776 -
PloS One 2024This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally...
BACKGROUND
This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France.
METHODS
A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses.
RESULTS
Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER.
CONCLUSIONS
This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.
Topics: Humans; Antibodies, Monoclonal, Humanized; France; Cost-Benefit Analysis; Male; Female; Urinary Bladder Neoplasms; Quality-Adjusted Life Years; Aged; Middle Aged; Adult; Carcinoma, Transitional Cell; Neoplasm Metastasis; Urologic Neoplasms; Maintenance Chemotherapy
PubMed: 38728337
DOI: 10.1371/journal.pone.0302548