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Journal of Healthcare Engineering 2022The aim of this study is to examine the treatment pattern and predictors of long-term survival of patients with primary signet ring cell carcinoma (PSRCC) of the urinary...
INTRODUCTION
The aim of this study is to examine the treatment pattern and predictors of long-term survival of patients with primary signet ring cell carcinoma (PSRCC) of the urinary bladder based on the analysis of the SEER database.
METHODS
The 3-year and 5-year overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method. Then, we compared the CSS curves by the log-rank test. The independent risk factors were determined using univariate and multivariate Cox regression.
RESULTS
The 3-year OS and CSS rates for PSRCC of the bladder were 25.3% and 33.3%. The 5-year OS and CSS rates for the entire cohort were 16.4% and 25.2%. The CSS rates, respectively, were 0, 25.0, 66.7, 33.2, 42.4, and 31.7% at 3 years and 0, 25.0, 34.3, 24.1, 27.2, and 31.7% at 5 years for none, transurethral resection of the bladder (TURB), partial cystectomy, radical cystectomy with reconstruction, pelvic exenteration, and other surgeries ( = 0.001). Multivariate analyses showed independent risk factors only including T stage, M stage, lymph node removal, and surgical approach.
CONCLUSIONS
T stage, M stage, lymph node removal, and surgical approach are independent risk factors of PSRCC of the urinary bladder. TURB and radical cystectomy with reconstruction appear to provide a better outcome.
Topics: Carcinoma, Signet Ring Cell; Cystectomy; Humans; Prognosis; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 36105716
DOI: 10.1155/2022/3224616 -
JCO Precision Oncology Jun 2022To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular...
PURPOSE
To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular differentiation, and UC, not otherwise specified (NOS) undergoing surgical resection, with emphasis on response to systemic therapy.
METHODS
We identified patients with bladder cancer with glandular variants who underwent surgical resection at Memorial Sloan Kettering from 1995 to 2018 (surgical cohort) and/or patients who had tumor sequencing using a targeted next-generation sequencing platform (genomics cohort). Pathologic complete and partial response rates to neoadjuvant chemotherapy (NAC) and recurrence-free and cancer-specific survival were measured. Alteration frequencies between histologic subtypes were compared.
RESULTS
Thirty-seven patients with bladder adenocarcinoma, 46 with urachal adenocarcinoma, 84 with UC with glandular differentiation, and 1,049 with UC, NOS comprised the surgical cohort. Despite more advanced disease in patients with bladder and urachal adenocarcinoma, no significant differences in recurrence or cancer-specific survival by histology were observed after adjusting for stage. In patients with UC with glandular differentiation, NAC resulted in partial (≤ pT1N0) and complete (pT0N0) responses in 28% and 17%, respectively. Bladder and urachal adenocarcinoma genomic profiles resembled colorectal adenocarcinoma with frequent , , and alterations while the genomic profile of UC with glandular differentiation more closely resembled UC, NOS. Limitations include retrospective nature of analysis and small numbers of nonurothelial histology specimens.
CONCLUSION
The genomic profile of bladder adenocarcinomas resembled colorectal adenocarcinomas, whereas UC with glandular differentiation more closely resembled UC, NOS. Differences in outcomes among patients with glandular bladder cancer variants undergoing surgical resection were largely driven by differences in stage. Cisplatin-based NAC demonstrated activity in UC with glandular differentiation, suggesting NAC should be considered for this histologic variant.
Topics: Adenocarcinoma; Carcinoma, Transitional Cell; Colorectal Neoplasms; Genomics; Humans; Phenotype; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35731998
DOI: 10.1200/PO.21.00392 -
European Urology Oncology Aug 2023Bladder cancer (BLCA) is a highly prevalent tumour and a health problem worldwide, especially among men. Recent work has highlighted the relevance of the tumour... (Review)
Review
CONTEXT
Bladder cancer (BLCA) is a highly prevalent tumour and a health problem worldwide, especially among men. Recent work has highlighted the relevance of the tumour microenvironment (TME) in cancer biology with translational implications. Cancer-associated fibroblasts (CAFs) are a prominent, heterogeneous population of cells in the TME. CAFs have been associated with tumour development, progression, and poor prognosis in several neoplasms. However, their role in BLCA has not yet been exploited deeply.
OBJECTIVE
To review the role of CAFs in BLCA biology and provide an understanding of CAF origin, subtypes, markers, and phenotypic and functional characteristics to improve patient management.
EVIDENCE ACQUISITION
A PubMed search was performed to review manuscripts published using the terms "cancer associated fibroblast" and "bladder cancer" or "urothelial cancer". All abstracts were reviewed, and the full content of all relevant manuscripts was analysed. In addition, selected manuscripts on CAFs in other tumours were considered.
EVIDENCE SYNTHESIS
CAFs have been studied less extensively in BLCA than in other tumours. Thanks to new techniques, such as single-cell RNA-seq and spatial transcriptomics, it is now possible to accurately map and molecularly define the phenotype of fibroblasts in normal bladder and BLCA. Bulk transcriptomic analyses have revealed the existence of subtypes among both non-muscle-invasive and muscle-invasive BLCA; these subtypes display distinct features regarding their CAF content. We provide a higher-resolution map of the phenotypic diversity of CAFs in these tumour subtypes. Preclinical studies and recent promising clinical trials leverage on this knowledge through the combined targeting of CAFs or their effectors and the immune microenvironment.
CONCLUSIONS
Current knowledge of BLCA CAFs and the TME is being increasingly applied to improve BLCA therapy. There is a need to acquire a deeper understanding of CAF biology in BLCA.
PATIENT SUMMARY
Tumour cells are surrounded by nontumoural cells that contribute to the determination of the behaviour of cancers. Among them are cancer-associated fibroblasts. The "neighbourhoods" established through these cellular interactions can now be studied with much greater resolution. Understanding these features of tumours will contribute to the designing of more effective therapies, especially in relationship to bladder cancer immunotherapy.
Topics: Humans; Male; Urinary Bladder; Cancer-Associated Fibroblasts; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Biology; Tumor Microenvironment
PubMed: 36890105
DOI: 10.1016/j.euo.2023.02.011 -
International Journal of Molecular... Aug 2023Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The... (Review)
Review
Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Cystoscopy; Epithelial Cells; Urine
PubMed: 37569864
DOI: 10.3390/ijms241512489 -
Seminars in Diagnostic Pathology Jul 2018Intravesical immunotherapy, chemotherapy, and neoadjuvant systemic chemotherapy are among the most frequent therapeutic procedures to treat malignancies of the urinary... (Review)
Review
Intravesical immunotherapy, chemotherapy, and neoadjuvant systemic chemotherapy are among the most frequent therapeutic procedures to treat malignancies of the urinary bladder. These treatment modalities produce reactive morphologic changes in the urothelium that can mimic urothelial carcinoma in situ, urothelial dysplasia or true invasive urothelial neoplasia. Mitomycin C used after transurethral resection of bladder tumor to reduce recurrences, BCG intravesical immunotherapy to treat high risk non-muscle invasive bladder cancer and urothelial carcinoma in situ, and platinum-based systemic chemotherapy to improve post-cystectomy disease-specific survival some of the causes of therapy related atypia in urinary bladder. In addition, a number of systemic drugs in use to treat other systemic diseases, such as cyclophosphamide used to treat certain auto-immune disorders or hematologic malignancies, or the anesthetics ketamine increasingly used as illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore, need to be differentiated from intraepithelial neoplasia. Immunohistochemical approach to reactive urothelium from CIS using CK20, p53, and CD44 may also be of utility in the pos-therapy scenario.
Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Transitional Cell; Drug-Related Side Effects and Adverse Reactions; Humans; Iatrogenic Disease; Immunohistochemistry; Immunotherapy; Neoadjuvant Therapy; Radiotherapy; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 29576423
DOI: 10.1053/j.semdp.2018.03.001 -
Aging Apr 2023Urinary bladder urothelial carcinoma (UBUC) encompasses about 90% of all bladder cancer cases, and the mainstream treatment is the transurethral resection of the bladder...
Urinary bladder urothelial carcinoma (UBUC) encompasses about 90% of all bladder cancer cases, and the mainstream treatment is the transurethral resection of the bladder tumor followed by intravesical instillation. High rates of mortality, recurrence, and progression in bladder cancer have stimulated the search for alternative adjuvant therapies. The aim of this study was to investigate the potential of melatonin as adjuvant therapy in bladder cancer. Cell viability and clonogenic ability were assessed by an MTT assay and colony formation. Cell cycle and apoptosis analysis were performed by flow cytometry and Hoechst 33342 staining, while cell metastasis capacity was measured by wound healing and transwell assays. Potential mechanisms were investigated by an oncology array and verified via western blotting. The melatonin treatment significantly reduced T24 and UMUC3 bladder cancer cell proliferation and clonogenic ability. G1 arrest and sub-G1 accumulation in the T24 and UMUC3 cells led to cell proliferation suppression and cell death, and Hoechst 33342 staining further verified the apoptosis induction directly by melatonin. Moreover, melatonin weakened cell motility and invasiveness. Based on the oncology array results, we demonstrated that melatonin exerts its anti-cancer effect by down-regulating the HIF-1α and NF-κB pathways and downstream pathways, including Bcl-2, leading to cell cycle arrest and apoptosis induction in the UBUC cells. Overall, these findings support the potential of melatonin as adjuvant therapy in bladder cancer.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Melatonin; Urinary Bladder; Cell Line, Tumor; Cell Cycle Checkpoints; Cell Proliferation; Cell Cycle; Apoptosis; Cell Movement
PubMed: 37086261
DOI: 10.18632/aging.204673 -
BMC Urology Aug 2022To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral...
OBJECTIVE
To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral resection of bladder tumor.
METHODS
A retrospective analysis was made of 194 specimens who underwent transurethral resection of bladder tumors in our hospital from January 2014 to January 2016 and completed follow-up. The expression intensity of CA-IX and the clinical data of the patients were analyzed, and the subjects were divided into positive group and negative group according to the expression intensity of CA-IX. The age, gender, T stage, degree of differentiation, tumor number, tumor diameter, recurrence of each group was analyzed. Logistic univariate and multivariate analysis was used successively to find independent influencing factors for predicting the recurrence of bladder urothelial carcinoma after resection. The Kaplan-Meier survival curve was drawn according to the relationship between CA-IX expression intensity and postoperative recurrence.
RESULTS
The positive expression rates of CA-IX in bladder urothelial carcinomas were 68.1% (132/194). The positive expression of CA-IX had no statistical significance with age, gender and tumor diameter (P > 0.05), while the positive expression of CA-IX had statistical significance with tumor T stage, tumor differentiation, tumor number and recurrence (P < 0.05); Logistic regression analysis showed that clinical T stage, tumor differentiation, tumor number, and CA-IX expression intensities were independent risk factors for predicting recurrence of bladder urothelial carcinoma after resection (P < 0.05); There were 59 cases of recurrence in the positive expression of CA-IX group, with a recurrence rate of 44.69% (59/132), and 17 cases of recurrence in the negative expression group, with a recurrence rate of 27.41% (17/62). The mean recurrence time of CA-IX positive group was 29.93 ± 9.86 (months), and the mean recurrence time of CA-IX negative group was 34.02 ± 12.44 (months). The Kaplan-Meier survival curve showed that the recurrence rate and recurrence time of patients with positive expression of CA-IX in bladder urothelial carcinomas were significantly higher than those of patients with negative expression of CA-IX.
CONCLUSION
CA-IX is highly expressed in bladder urothelial carcinoma, is a good tumor marker, and can be used as a good indicator for predicting the recurrence of bladder urothelial carcinoma after transurethral resection of bladder tumor.
Topics: Carbonic Anhydrase IX; Carbonic Anhydrases; Carcinoma, Transitional Cell; Humans; Prognosis; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35922856
DOI: 10.1186/s12894-022-01074-9 -
Der Pathologe Dec 2021Bladder cancer ranks among the top ten most common tumor types worldwide and represents a growing healthcare problem, accounting for a large part of total healthcare... (Review)
Review
BACKGROUND
Bladder cancer ranks among the top ten most common tumor types worldwide and represents a growing healthcare problem, accounting for a large part of total healthcare costs. Chemotherapy is effective in a subset of patients, while causing severe side effects. Tumor pathogenesis and drug resistance mechanisms are largely unknown. Precision medicine is failing in bladder cancer, as bladder tumors are genetically and molecularly very heterogeneous. Currently, therapeutic decision-making depends on assessing a single fragment of surgically acquired tumor tissue.
OBJECTIVE
New preclinical model systems for bladder cancer are indispensable for developing therapeutic strategies tailored to individual patient and tumor characteristics. Organoids are small 3D tissue cultures that simulate small-size organs "in a dish" and tumoroids are a special type of cancer organoid (i.e., malignant tissue).
MATERIALS AND METHODS
Since 2016, we have collaborated with the renowned Hubrecht Institute to provide proof of concept of tissue-based bladder tumoroids mimicking parental tumors. We have developed a living biobank containing bladder organoids and tumoroids grown from over 50 patient samples, which reflect crucial aspects of bladder cancer pathogenesis.
RESULTS
Histological and immunofluorescence analysis indicated that the heterogeneity and subclassification of tumoroids mimicked those of corresponding parental tumor samples. Thus, urothelial tumoroids mimic crucial aspects of bladder cancer pathogenesis.
CONCLUSION
Research with urothelial tumoroids will open up new avenues for bladder cancer pathogenesis and drug-resistance research as well as for precision medicine approaches.
Topics: Carcinoma, Transitional Cell; Humans; Organoids; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium
PubMed: 34623463
DOI: 10.1007/s00292-021-00988-9 -
Annals of Agricultural and... Dec 2017Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in...
INTRODUCTION AND OBJECTIVES
Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer.
MATERIAL AND METHODS
Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage.
RESULTS
While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively).
CONCLUSIONS
This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Chromium; Female; Humans; Male; Middle Aged; Neoplasm Staging; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 29284232
DOI: 10.5604/12321966.1232760 -
Archivio Italiano Di Urologia,... Sep 2022The aim of this study is to report our experience in managing bladder cancer in patients with variant pathology.
PURPOSE
The aim of this study is to report our experience in managing bladder cancer in patients with variant pathology.
METHODS
Retrospective data collection for all patients managed by radical cystectomy over the last 3 years for a variant pathol-ogy was completed. We specifically included micropapillary and nested variants.
RESULTS
Ten patients were identified, with eight having micropapillary carcinoma (MPC) and two having nested vari-ants. Nine patients were male. The median age was 75. The two patients with nested variant were 56 and 62 years old, respec-tively, whereas all patients with MPC were over the age of 70. Upon cystectomy of all micropapillary cases, three patients (37.5%) had positive lymph node invasion and the final patholo-gy was T2 (two patients), T3 (two patients), and T4 (four patients). Barring a grade III complication Clavien-Dindo classi-fication due to wound dehiscence that necessitated secondary surgical closure, there were no specific perioperative complica-tions. Given the urethral invasion, cystourethrectomy was per-formed on the female patient. Within a median 13-month fol-low-up, three patients developed local recurrence, including two urethral and one new lateral pelvic mass.
CONCLUSIONS
Considering the muscle invasive nature of micropapillary and nested bladder cancer, aggressive surgical management should not be postponed. Moreover, due to notable prevalence of concurrent and/or recurrent urethral involvement, initial urethrectomy or early and frequent postoperative ure-throscopy should be provided. Patients with variant histology bladder cancer may benefit from early radical cystectomy when compared to bladder sparing protocols and prostate sparing cystectomy treatment options.
Topics: Aged; Carcinoma, Papillary; Carcinoma, Transitional Cell; Cystectomy; Female; Humans; Male; Middle Aged; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 36165473
DOI: 10.4081/aiua.2022.3.291