Bladder Cancer
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2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yadong Xu ◽  
Cheng Luo ◽  
Jieqiong Wang ◽  
Lingwu Chen ◽  
Junxing Chen ◽  
...  

AbstractBladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management. Graphical Abstract


2021 ◽  
Vol 19 (4) ◽  
pp. 223-231
Author(s):  
Da Eun Han ◽  
Sun Tae Ahn ◽  
Jong Wook Kim ◽  
Mi Mi Oh ◽  
Du Geon Moon ◽  
...  

Purpose: This study investigated metabolic health status as a risk factor for female bladder cancer using the National Health Checkups databases of Korea.Materials and Methods: We defined obesity if body mass index was ≥25 kg/m2 and normal weight as <25 kg/m2. Metabolic unhealthiness was defined when 3 or more criteria of metabolic syndrome were met. A total of 11,461,618 women who took National health Checkups between 2009 and 2012 were categorized as metabolic healthy normal weight (MHNW), metabolic unhealthy normal weight (MuHNW), metabolic health obese (MHO), and metabolic unhealthy obese (MuHO). Multivariable-adjusted Cox regression was done to analyze the hazard ratio of bladder cancer.Results: The mean age was 48±11.55 years and body mass index was 23.19±2.13 kg/m2. During 5.4±1.1 years of follow-up, 3,893 patients were newly diagnosed with bladder cancer. Compared to MHNW group, the hazard ratio of MuHNW group and MuHO group were 1.237 and 1.288, respectively, while 0.997 in the MHO group. As the number of metabolic unhealthy criteria increased, the cumulative incidence of bladder cancer increased.Conclusions: As a result of a large-scale study conducted on the female population in Korea, the risk of bladder cancer increased with metabolic unhealthiness. Even with normal weight, if metabolically unhealthy, the risk of bladder cancer increased. The greater the degree of metabolic unhealthiness, the higher the risk of bladder cancer. Education on metabolic healthiness concerning female bladder cancer is necessary.


2021 ◽  
Vol 19 (4) ◽  
pp. 261-270
Author(s):  
Hak Ju Kim ◽  
Changhee Ye ◽  
Jin Hyuck Kim ◽  
Hwanik Kim ◽  
Sangchul Lee ◽  
...  

Purpose: To compare perioperative outcomes according to surgical methods among bladder cancer patients who underwent radical cystectomy (RC) with neobladder urinary diversion.Materials and Methods: Between June 2007 and January 2020, 89 bladder cancer patients who received RC with neobladder urinary diversion were enrolled in this study. Patients were stratified into surgical methods – (1) open RC with neobladder (ONB) reconstruction, (2) robotassisted RC (RARC) with extracorporeal neobladder (ECNB) reconstruction, and (3) RARC with intracorporeal neobladder (ICNB) reconstruction. Perioperative outcomes were compared among the 3 groups, with major complications defined according to Clavien-Dindo grades III–V within 90 days. Logistic regression analysis was performed to identify significant factors for postoperative complications.Results: Of 89 patients, 28 (31%) had ONB, 31 (35%) had ECNB, and 30 (34%) had ICNB. The median operative time was 471 minutes, and the ICNB group (424.5 minutes) was significantly less than ONB (444.5 minutes) and ECNB groups (542.9 minutes) (p=0.001). Transfusion rate was also significantly less in the ICNB group (13%) (p=0.001). Complications were recorded in 67 patients (75%) and major complications in 22 of all patients (25%). The major complication rate was significantly less in ICNB (13.4%) than in ONB (25%) and ECNB (35%) (p=0.003). Multivariate analysis showed surgical methods (ICNB) (odds ratio [OR], 0.709; p=0.003) and age (OR, 1.150; p=0.001) were significant factors related to occurrence of major postoperative complications.Conclusions: RARC with ICNB reduces postoperative complications compared to ONB and ECNB.


2021 ◽  
Vol 19 (4) ◽  
pp. 244-251
Author(s):  
Minuk Park ◽  
Bumjin Lim ◽  
Dalsan You ◽  
In Gab Jeong ◽  
Cheryn Song ◽  
...  

Purpose: To evaluate the association between microscopic hematuria (MH) detected by surveillance urinalysis and cancer recurrence in nonmuscle invasive bladder cancer (NMIBC) patients.Materials and Methods: A total of 1,082 NMIBC patients who underwent transurethral resection of bladder tumor (TURB) procedures at Asan Medical Center between January 2017 and December 2019 were included. We retrospectively reviewed the follow-up data for these cases including cystoscopy, urinalysis, and urine cytology. The association between urine testing and cancer recurrence was assessed by both univariable and multivariable logistic regression analysis.Results: The study patients had a median age of 68 years (interquartile range, 60–75 years) and comprised 898 men and 184 women. Among the 1,428 TURB procedures conducted in this series, 548 of the lesions (38.4%) were diagnosed as low-grade and 880 (61.6%) as highgrade cancers. A total of 3,309 follow-up cystoscopies were conducted during the study period and were divided into high-grade (HG) (2,011 cases) and low-grade (LG) (1,298 cases) groups according to the latest TURB pathology. MH was found to have a statistically significant association with NMIBC recurrence in both the LG (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.107–2.223; p=0.011) and HG (OR, 1.90; 95% CI, 1.434–2.517; p<0.001) groups.Conclusions: Urinalysis during follow-up may provide important information on cancer recurrence in NMIBC patients.


2021 ◽  
Vol 19 (4) ◽  
pp. 271-280
Author(s):  
Janghui Lee ◽  
Bumjin Lim ◽  
Dalsan You ◽  
In Gab Jeong ◽  
Cheryn Song ◽  
...  

Purpose: To identify the risk factors leading to radical cystectomy in patients who had undergone nephroureterectomy (NUx).Materials and Methods: We retrospectively reviewed the medical records of patients with upper tract urothelial carcinoma who underwent NUx during 2011–2019 and excluded patients with metastatic cancer. In total 646 patients were included in this study; of these, 532 had no previous bladder cancer history. Follow-up was performed every 3 months for 2 years after NUx was administered, and recurrence was confirmed using cystoscopy, urine cytology, computed tomography, and chest radiography. Bladder recurrence was confirmed through biopsy, urine cytology, or radiologic examination. Univariate and multivariate Cox regression analyzes were performed for statistical analysis of risk factors leading to radical cystectomy in patients undergoing NUx.Results: Lymphovascular invasion (LVI) (hazard ratio [HR], 4.728; 95% confidence interval [CI], 1.463–15.570; p=0.011), previous transurethral resection of bladder tumor history (HR, 3.825; 95% CI, 1.164–12.571; p=0.027), and intravesical recurrence (IVR) within 6 months (HR, 3.733; 95% CI, 1.091–12.778; p=0.036) in patients undergoing NUx are predictors of radical cystectomy implementation. In a multivariate analysis of patients without bladder cancer history, bladder recurrence was identified as a predictor of radical cystectomy implementation, if it occurred within 6 months of NUx (HR, 8.608; 95% CI, 1.545–47.976; p=0.014).Conclusions: LVI and IVR within 6 months and previous bladder cancer history are factors that can predict the need for radical cystectomy after NUx. Even in patients without bladder cancer history, early bladder recurrence within 6 months is a major predictor of radical cystectomy.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiao Hu ◽  
Belaydi Othmane ◽  
Anze Yu ◽  
Huihuang Li ◽  
Zhiyong Cai ◽  
...  

Abstract Background Depicting the heterogeneity and functional characteristics of the tumor microenvironment (TME) is necessary to achieve precision medicine for bladder cancer (BLCA). Although classical molecular subtypes effectively reflect TME heterogeneity and characteristics, their clinical application is limited by several issues. Methods In this study, we integrated the Xiangya cohort and multiple external BLCA cohorts to develop a novel 5-methylcytosine (5mC) regulator-mediated molecular subtype system and a corresponding quantitative indicator, the 5mC score. Unsupervised clustering was performed to identify novel 5mC regulator-mediated molecular subtypes. The principal component analysis was applied to calculate the 5mC score. Then, we correlated the 5mC clusters (5mC score) with classical molecular subtypes, immunophenotypes, clinical outcomes, and therapeutic opportunities in BLCA. Finally, we performed pancancer analyses on the 5mC score. Results Two 5mC clusters, including 5mC cluster 1 and cluster 2, were identified. These novel 5mC clusters (5mC score) could accurately predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities of BLCA. 5mC cluster 1 (high 5mC score) indicated a luminal subtype and noninflamed phenotype, characterized by lower anticancer immunity but better prognosis. Moreover, 5mC cluster 1 (high 5mC score) predicted low sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy, but high sensitivity to antiangiogenic therapy and targeted therapies, such as blocking the β-catenin, FGFR3, and PPAR-γ pathways. Conclusions The novel 5mC regulator-based subtype system reflects many aspects of BLCA biology and provides new insights into precision medicine in BLCA. Furthermore, the 5mC score may be a generalizable predictor of immunotherapy response and prognosis in pancancers.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vicky Smith ◽  
Debayan Mukherjee ◽  
Sapna Lunj ◽  
Ananya Choudhury ◽  
Peter Hoskin ◽  
...  

Abstract Introduction Recent data has demonstrated that hypoxia drives an immunosuppressive tumour microenvironment (TME) via various mechanisms including hypoxia inducible factor (HIF)-dependent upregulation of programmed death ligand 1 (PD-L1). Both hypoxia and an immunosuppressive TME are targetable independent negative prognostic factors for bladder cancer. Therefore we sought to investigate whether hypoxia is associated with upregulation of PD-L1 in the disease. Materials and methods Three human muscle-invasive bladder cancer cell lines (T24, J82, UMUC3) were cultured in normoxia (20% oxygen) or hypoxia (1 and 0.1% oxygen) for 24 h. Differences in PD-L1 expression were measured using Western blotting, quantitative polymerase chain reaction (qPCR) and flow cytometry (≥3 independent experiments). Statistical tests performed were unpaired t tests and ANOVA. For in silico work an hypoxia signature was used to apply hypoxia scores to muscle-invasive bladder cancers from a clinical trial (BCON; n = 142) and TCGA (n = 404). Analyses were carried out using R and RStudio and statistical tests performed were linear models and one-way ANOVA. Results When T24 cells were seeded at < 70% confluence, there was decreased PD-L1 protein (p = 0.009) and mRNA (p < 0.001) expression after culture in 0.1% oxygen. PD-L1 protein expression decreased in both 0.1% oxygen and 1% oxygen in a panel of muscle-invasive bladder cancer cells: T24 (p = 0.009 and 0.001), J82 (p = 0.008 and 0.013) and UMUC3 (p = 0.003 and 0.289). Increasing seeding density decreased PD-L1 protein (p < 0.001) and mRNA (p = 0.001) expression in T24 cells grown in both 20 and 1% oxygen. Only when cells were 100% confluent, were PD-L1 protein and mRNA levels higher in 1% versus 20% oxygen (p = 0.056 and p = 0.037). In silico analyses showed a positive correlation between hypoxia signature scores and PD-L1 expression in both BCON (p = 0.003) and TCGA (p < 0.001) cohorts, and between hypoxia and IFNγ signature scores (p < 0.001 for both). Conclusion Tumour hypoxia correlates with increased PD-L1 expression in patient derived bladder cancer tumours. In vitro PD-L1 expression was affected by cell density and decreased PD-L1 expression was observed after culture in hypoxia in muscle-invasive bladder cancer cell lines. As cell density has such an important effect on PD-L1 expression, it should be considered when investigating PD-L1 expression in vitro.


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