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Cancer Medicine Nov 2022Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population-based cohorts. This study aimed to...
BACKGROUND
Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population-based cohorts. This study aimed to describe demographic, clinicopathological features, and survival outcomes of patients diagnosed with UCB.
METHODS
The National Cancer Database (2004-2016) was queried for UCB patients. Descriptive analyses characterized demographics and clinicopathologic features. We assessed 5-year overall survival (OS) rates of the entire cohort and subgroups of localized/locally advanced and metastatic disease. We utilized Cox proportional hazards models to assess the association between covariates of interest and all-cause mortality and to examine the impact of surgical technique and chemotherapy.
RESULTS
We identified 841 patients with UCB. The most common histologic subtype was non-mucinous adenocarcinoma (39.6%). Approximately 50% had ≥cT2 disease, and 14.3% were metastatic at diagnosis. Altogether, partial cystectomy (60%) was most performed, and lymph node dissection was performed in 377 patients (44.8%), with specific temporal increase in utilization over the study period (p < 0.001). Overall, median OS was 59 months, and 5-year OS was 49%. In patients with localized/locally advanced disease, we found no association between partial and radical cystectomy (Hazards ratio [HR] 1.75; 95% CI 0.72-4.3) as well as receipt of perioperative chemotherapy (HR 1.97, 95% CI 0.79-4.90) and outcomes. Lastly, receipt of systemic therapy was not associated with survival benefit (HR 0.785, 95% CI 0.37-1.65) in metastatic disease cohort.
CONCLUSION
This large population-based cohort provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the perioperative and metastatic setting.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder; Neoplasm Staging; Urinary Bladder Neoplasms; Cystectomy; Retrospective Studies
PubMed: 35509235
DOI: 10.1002/cam4.4786 -
Urologia Internationalis 2024Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for... (Review)
Review
BACKGROUND
Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for non-metastatic SCC of the bladder. However, several studies have shown that SCC of the bladder is associated with higher aggressiveness and worse survival outcomes, such as progression-free and cancer-specific survival, relative to the urothelial histological subtype. Moreover, metastatic SCC seems to poorly respond to systemic treatments and/or radiotherapy.
SUMMARY
This review summarizes the current knowledge and medical evidence regarding local and systematic treatment of mSCC of the bladder, including a case series of four initially locally advanced and later metastatic SCC patients of our tertiary care hospital.
KEY MESSAGES
Despite being the second most common variant histology of bladder cancer, current therapies for SCC do not provide satisfactory therapeutic responses.
Topics: Humans; Urinary Bladder; Retrospective Studies; Urinary Bladder Neoplasms; Cystectomy; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell
PubMed: 38128507
DOI: 10.1159/000534858 -
BMC Urology Mar 2024To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the...
PURPOSE
To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB).
MATERIAL AND METHODS
The clinical and preoperative CTU imaging data of continuous 103 patients with histologically confirmed BUC or IPB were retrospectively analyzed. The imaging data included 6 qualitative indicators and 7 quantitative measures. The recorded clinical information and imaging features were subjected to univariate and multivariate logistic regression analysis to find independent risk factors for BUC, and a combined multi-indicator prediction model was constructed, and the prediction model was visualized using nomogram. ROC curve analysis was used to calculate and compare the predictive efficacy of independent risk factors and nomogram.
RESULTS
Junction smoothness, maximum longitudinal diameter, tumor-wall interface and arterial reinforcement rate were independent risk factors for distinguishing BUC from IPB. The AUC of the combined model was 0.934 (sensitivity = 0.808, specificity = 0.920, accuracy = 0.835), and its diagnostic efficiency was higher than that of junction smoothness (AUC=0.667, sensitivity = 0.654, specificity = 0.680, accuracy = 0.660), maximum longitudinal diameter (AUC=0.757, sensitivity = 0.833, specificity = 0.604, accuracy = 0.786), tumor-wall interface (AUC=0.888, sensitivity = 0.755, specificity = 0.808, accuracy = 0.816) and Arterial reinforcement rate (AUC=0.786, sensitivity = 0.936, specificity = 0.640, accuracy = 0.864).
CONCLUSION
Above qualitative and quantitative indicators based on CTU and the combination of them may be helpful to the differential diagnosis of BUC and IPB, thus better assisting in clinical decision-making.
KEY POINTS
1. Bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB) exhibit similar clinical symptoms and imaging presentations. 2. The diagnostic value of CT urography (CTU) in distinguishing between BUC and IPB has not been documented. 3. BUC and IPB differ in lesion size, growth pattern and blood supply. 4. The diagnostic efficiency is optimized by integrating multiple independent risk factors into the prediction model.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Papilloma, Inverted; Retrospective Studies; Urography; Tomography, X-Ray Computed
PubMed: 38532363
DOI: 10.1186/s12894-024-01459-y -
Cancer Cytopathology Jul 2021Urine cytology can reliably diagnose high-grade urothelial carcinoma (HGUC) but not low-grade urothelial carcinoma (LGUC), and a more sensitive test is needed....
BACKGROUND
Urine cytology can reliably diagnose high-grade urothelial carcinoma (HGUC) but not low-grade urothelial carcinoma (LGUC), and a more sensitive test is needed. Previously, a pilot study highlighted the possible diagnostic utility of next-generation sequencing (NGS) in identifying both LGUC and HGUC in urine cytology specimens.
METHODS
Twenty-eight urine ThinPrep cytology specimens and preceding or subsequent bladder tumor biopsy/resection specimens obtained within 3 months were included in the study (LGUC, n = 15; HGUC, n = 13). A customized, bladder-specific NGS panel was performed; it covered 69 frequently mutated or altered genes in urothelial carcinoma (UC) that were reported by The Cancer Genome Atlas and the Catalogue of Somatic Mutations in Cancer.
RESULTS
The sequencing results were compared between the urine cytology specimens and the corresponding bladder tumor biopsies/resections. TP53 was the most frequently identified mutation in HGUC cases (11 of 13 [85%]). PIK3CA and KDM6A were the most frequently identified mutations in LGUC: they occurred in 7 of 15 cases (47%) and in 6 of 15 cases (40%), respectively. Additional frequent mutations identified in the panel included ARID1A (n = 5), EP300 (n = 4), LRP1B (n = 3), ERBB2 (n = 2), STAG2 (n = 2), FGFR3 (n = 3), MLL (n = 2), MLL3 (n = 2), CREBBP1 (n = 1), RB1 (n = 1), and FAT4 (n = 1). Overall, the concordance between the cytology and surgical specimens was 75%. The sensitivity and specificity for identifying mutations in urine cytology specimens were 84% and 100%, respectively.
CONCLUSIONS
A bladder-specific NGS panel increases the sensitivity and specificity of urine cytology's diagnostic utility in both low- and high-grade tumors and may serve as a noninvasive surveillance method in the follow-up of patients with UC harboring known mutations.
Topics: Aged; Carcinoma, Transitional Cell; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Urinary Bladder; Urinary Bladder Neoplasms; Urine
PubMed: 33539671
DOI: 10.1002/cncy.22410 -
Oncotarget Jan 2017Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive... (Review)
Review
Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive carcinogenic load to the bladder urothelium may result in the development of cancer. However, enzymes within the bladder can metabolize carcinogens into substrates that are safer. Importantly, these proteins, namely the UGT's (uridine 5'-diphospho-glucuronosyltransferases), have been shown to possibly prevent bladder cancer. Also, studies have shown that the UGT1 expression is decreased in uroepithelial carcinomas, which may allow for the accumulation of carcinogens in the bladder. In this review, we discuss the UGT system and its' protective role against bladder cancer, UGT genetic mutations that modulate risk from chemicals and environmental toxins, as well as targeting of the UGT enzymes by nuclear receptors.
Topics: Animals; Carcinoma, Transitional Cell; Gene Expression Regulation; Genetic Predisposition to Disease; Glucuronosyltransferase; Humans; Isoenzymes; Metabolic Detoxication, Phase II; Multigene Family; Mutation; Polymorphism, Single Nucleotide; Protein Binding; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Smoking; Substrate Specificity; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 27690298
DOI: 10.18632/oncotarget.12277 -
The Journal of Pathology. Clinical... May 2022Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2-5% of cases. It often presents late and is unresponsive to...
Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2-5% of cases. It often presents late and is unresponsive to cisplatin-based chemotherapy. The molecular features of these tumours have not been elucidated in detail. We carried out whole-exome sequencing (WES), copy number, and transcriptome analysis of bladder SCC. Muscle-invasive bladder cancer (MIBC) samples with no evidence of squamous differentiation (non-SD) were used for comparison. To assess commonality of features with urothelial carcinoma with SD, we examined data from SD samples in The Cancer Genome Atlas (TCGA) study of MIBC. TP53 was the most commonly mutated gene in SCC (64%) followed by FAT1 (45%). Copy number analysis revealed complex changes in SCC, many differing from those in samples with SD. Gain of 5p and 7p was the most common feature, and focal regions on 5p included OSMR and RICTOR. In addition to 9p deletions, we found some samples with focal gain of 9p24 containing CD274 (PD-L1). Loss of 4q35 containing FAT1 was found in many samples such that all but one sample analysed by WES had FAT1 mutation or deletion. Expression features included upregulation of oncostatin M receptor (OSMR), metalloproteinases, metallothioneins, keratinisation genes, extracellular matrix components, inflammatory response genes, stem cell markers, and immune response modulators. Exploration of differentially expressed transcription factors identified BNC1 and TFAP2A, a gene repressed by PPARG, as the most upregulated factors. Known urothelial differentiation factors were downregulated along with 72 Kruppel-associated (KRAB) domain-containing zinc finger family protein (KZFP) genes. Novel therapies are urgently needed for these tumours. In addition to upregulated expression of EGFR, which has been suggested as a therapeutic target in basal/squamous bladder cancer, we identified expression signatures that indicate upregulated OSMR and YAP/TAZ signalling. Preclinical evaluation of the effects of inhibition of these pathways alone or in combination is merited.
Topics: Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Oncostatin M Receptor beta Subunit; Receptors, Oncostatin M; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35289095
DOI: 10.1002/cjp2.261 -
World Journal of Urology Apr 2023To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery. (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery.
METHODS
The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed.
RESULTS
Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11-1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00-1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70-1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88-1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98-1.16) in patients with NMIBC.
CONCLUSIONS
Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.
Topics: Humans; Female; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Prognosis; Proportional Hazards Models
PubMed: 35963957
DOI: 10.1007/s00345-022-04116-x -
Biology of Sex Differences May 2022Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging...
Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.
Topics: Aging; Animals; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma, Transitional Cell; Female; Humans; Male; Mice; Sex Characteristics; Tumor Microenvironment; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35505436
DOI: 10.1186/s13293-022-00428-0 -
Biomedicine & Pharmacotherapy =... Jul 2022The role of HS in urothelial carcinoma (UC) is still unclear. Here we have evaluated the expression of HS producing enzymes as well as the effect of endogenous and...
The role of HS in urothelial carcinoma (UC) is still unclear. Here we have evaluated the expression of HS producing enzymes as well as the effect of endogenous and exogenous HS on human bladder UC cells. In human UC cells the expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST); is significantly lower as compared to healthy cells. A modulatory role for the HS pathway is supported by the finding that, the overexpression of CSE or CBS, but not 3-MST, inhibits cell proliferation and promotes apoptosis. A similar effect is obtained by using exogenous HS. Diallyl trisulfide (DATS), which is a fully characterized HS donor, inhibits the proliferation of UC cells in a time and concentration-dependent manner as well as promotes apoptosis. Moreover, DATS also induces autophagy, as determined by transcriptomic and western blot analysis. Finally, DATS inhibits mRNA expression levels of canonical markers of epithelial-mesenchymal transition by limiting migration and clonogenic ability of human UC cells in vitro. In conclusion, in urothelial carcinoma, there is an impairment of HS pathway that involves CSE and CBS- derived hydrogen sulfide. Thus, targeting HS signaling pathway in urothelial carcinoma could represent a novel therapeutic strategy.
Topics: Carcinoma, Transitional Cell; Cell Line; Cystathionine beta-Synthase; Humans; Hydrogen Sulfide; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35605291
DOI: 10.1016/j.biopha.2022.113137 -
BMC Medical Imaging Jan 2024To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC).
PURPOSE
To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC).
METHODS
The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed.
RESULTS
There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%.
CONCLUSION
The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Contrast Media; Diagnosis, Differential; Ultrasonography
PubMed: 38273224
DOI: 10.1186/s12880-024-01199-3