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Sample records for bladder cancer detection

  1. Bladder cancer

    MedlinePlus

    Transitional cell carcinoma of the bladder; Urothelial cancer ... In the United States, bladder cancer usually starts from the cells lining the bladder. These cells are called transitional cells. These tumors are classified by the way ...

  2. Rationale for an early detection program for bladder cancer

    PubMed Central

    Khochikar, Makarand V.

    2011-01-01

    Introduction: A total of 356,557 new cases were diagnosed annually worldwide in 2009, it was estimated that 52,810 new patients were to be diagnosed with bladder cancer and there were 10,180 projected deaths from the disease in the USA. Despite being the fourth commonest cancer in men, we do not have an early detection/screening program for bladder cancer. The review was aimed at looking at the evidence for the rationale for an early detection program for bladder cancer. Materials and Methods: A detailed search on bladder cancer epidemiology, diagnosis, pathology, tumor markers, treatment outcomes, screening, morbidity and mortality of bladder cancer was carried out on Pubmed central/Medline. Original articles, review articles, monograms, book chapters on bladder cancer, text books on urological oncology, oncology and urology were reviewed. The latest information for new articles before publication was last accessed in June 2010. Discussion and Conclusions: Bladder cancer is the fourth commonest cancer in men, the annual death rate from this disease is significant and every year there is an increase in its incidence globally. The prognosis of bladder cancer is stage and grade dependent; the lower the stage (T2 or less) the better is the survival. Delay in the diagnosis and treatment does alter the overall outcome. Therefore, there is a clear need for early detection of bladder cancer and screening program. Although we do not have an ideal marker for bladder cancer, it is time we maximize the potential of markers such as UroVysion, NMP22 along with cytology to start such a program. May be as a first step the early detection and screening program could be started in high-risk population. It is not worth waiting till we find the best marker as it would be unfair to our patients. The fear of unnecessary tests and treatment in bladder cancer after its detection in screening program is without any substance. The cost-effectiveness of such a program is certainly

  3. Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer

    PubMed Central

    Ward, Douglas G.; Baxter, Laura; Gordon, Naheema S.; Ott, Sascha; Savage, Richard S.; Beggs, Andrew D.; James, Jonathan D.; Lickiss, Jennifer; Green, Shaun; Wallis, Yvonne; Wei, Wenbin; James, Nicholas D.; Zeegers, Maurice P.; Cheng, KK; Mathews, Glenn M.; Patel, Prashant; Griffiths, Michael; Bryan, Richard T.

    2016-01-01

    Background Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA. Methods DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free). Results Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity). Conclusion This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer. PMID:26901314

  4. Bladder Cancer Detection Using Electrical Impedance Technique (Tabriz Mark 1)

    PubMed Central

    Keshtkar, Ahmad; Salehnia, Zeinab; Keshtkar, Asghar; Shokouhi, Behrooz

    2012-01-01

    Bladder cancer is the fourth most common malignant neoplasm in men and the eighth in women. Bladder pathology is usually investigated visually by cystoscopy. In this technique, biopsies are obtained from the suspected area and then, after needed procedure, the diagnostic information can be taken. This is a relatively difficult procedure and is associated with discomfort for the patient and morbidity. Therefore, the electrical impedance spectroscopy (EIS), a minimally invasive screening technique, can be used to separate malignant areas from nonmalignant areas in the urinary bladder. The feasibility of adapting this technique to screen for bladder cancer and abnormalities during cystoscopy has been explored and compared with histopathological evaluation of urinary bladder lesions. Ex vivo studies were carried out in this study by using a total of 30 measured points from malignant and 100 measured points from non-malignant areas of patients bladders in terms of their biopsy reports matching to the electrical impedance measurements. In all measurements, the impedivity of malignant area of bladder tissue was significantly higher than the impedivity of non-malignant area this tissue (P < 0.005). PMID:22567538

  5. Emerging Endoscopic Imaging Technologies for Bladder Cancer Detection

    PubMed Central

    Lopez, Aristeo; Liao, Joseph C.

    2014-01-01

    Modern urologic endoscopy is the result of continuous innovations since early 19th century. White light cystoscopy is the primary strategy for identification, resection, and local staging of bladder cancer. While highly effective, white light cystoscopy has several well-recognized shortcomings. Recent advances in optical imaging technologies and device miniaturization hold the potential to improve bladder cancer diagnosis and resection. Photodynamic diagnosis and narrow band imaging are the first to enter the clinical arena. Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy, UV autofluorescence, and others have shown promising clinical and pre-clinical feasibility. We review their mechanisms of action, highlight their respective advantages, and propose future directions. PMID:24658832

  6. Bladder Cancer Advocacy Network

    MedlinePlus

    ... future bladder cancer research through the Patient Survey Network. Read More... Don’t Miss the 2016 BCAN ... Click here for more details Bladder Cancer Advocacy Network 4915 St. Elmo Avenue, Suite 202 Bethesda, Maryland ...

  7. Can CT Virtual Cystoscopy Replace Conventional Cystoscopy in Early Detection of Bladder Cancer?

    PubMed Central

    Abrol, Sachin; Jairath, Ankush; Ganpule, Sanika; Ganpule, Arvind; Mishra, Shashikant; Sabnis, Ravindra; Desai, Mahesh

    2015-01-01

    Aim. To correlate findings of conventional cystoscopy with CT virtual cystoscopy (CTVC) in detecting bladder tumors and to evaluate accuracy of virtual cystoscopy in early detection of bladder cancer. Material and Method. From June 2013 to June 2014, 50 patients (46 males, four females) with history and investigations suggestive of urothelial cancer, with mean age 62.76 ± 10.45 years, underwent CTVC by a radiologist as per protocol and subsequently underwent conventional cystoscopy (CPE) the same day or the next day. One urologist and one radiologist, blinded to the findings of conventional cystoscopy, independently interpreted the images, and any discrepant readings were resolved with consensus. Result. CTVC detected 23 out of 25 patients with bladder tumor(s) correctly. Two patients were falsely detected as negative while two were falsely labeled as positive in CTVC. Virtual and conventional cystoscopy were comparable in detection of tumor growth in urinary bladder. The sensitivity, specificity, positive predictive value, and negative predictive value of virtual cystoscopy were 92% each. Conclusion. CTVC correlates closely with the findings of conventional cystoscopy. Bladder should be adequately distended and devoid of urine at the time of procedure. However, more studies are required to define the role of virtual cystoscopy in routine clinical practice. PMID:26600802

  8. Drugs Approved for Bladder Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Bladder Cancer This page lists cancer ... in bladder cancer that are not listed here. Drugs Approved for Bladder Cancer Atezolizumab Cisplatin Doxorubicin Hydrochloride ...

  9. Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report.

    PubMed

    Ring, K S; Karp, F; Benson, M C

    1990-09-01

    The flow cytometry (FCM) technique allows for the rapid quantitative analysis of the DNA content of individual cells. In a variety of genitourinary tumors, DNA ploidy has a significant impact upon prognosis and ultimate patient survival. In patients having transitional cell cancer (TCC) of the bladder, FCM of voided urine and bladder barbotage specimens is highly correlated with cytologic analysis in the detection of malignant cells. One problem with this technique has been decreased sensitivity in samples containing large numbers of inflammatory cells. To improve FCM detection of TCC in bladder wash specimens, we developed a technique using a monoclonal antibody (Mab) specific to human, epithelial membrane antigen (EMA). The EMA cell-surface marker enabled us to differentiate bladder epithelial cells from lymphocytes and cellular debris. In combination with DNA analysis using propidium iodide, the EMA Mab increased the sensitivity and specificity of FCM compared to conventional analysis using propidium iodide alone. We conclude that epithelial cell-surface antigen staining using both EMA Mab and DNA staining can increase the FCM detection of TCC in bladder wash specimens. PMID:2074517

  10. Incidental Bladder Cancer Detected on Multiparametric Magnetic Resonance Imaging of the Prostate Gland

    PubMed Central

    Sardari, Al; Thomas, John V.; Nix, Jeffrey W.; Pietryga, Jason A.; Sanyal, Rupan; Gordetsky, Jennifer B.; Rais-Bahrami, Soroush

    2015-01-01

    The increased use of axial imaging in various fields of medicine has led to an increased frequency of incidental findings, specifically incidental cancer lesions. Hence, as the use of multiparametric magnetic resonance imaging (MP-MRI) for prostate cancer detection, staging, and management becomes more widespread, the potential for additional incidental findings in the pelvis increases. Herein, we report the case of a man on active surveillance for low-grade, early-staged prostate cancer who underwent MP-MRI and was incidentally found to have a high-grade bladder cancer lesion. PMID:26783492

  11. Origins of Bladder Cancer.

    PubMed

    Czerniak, Bogdan; Dinney, Colin; McConkey, David

    2016-05-23

    Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy. PMID:26907529

  12. Detecting Metastatic Bladder Cancer Using 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography

    PubMed Central

    Öztürk, Hakan

    2015-01-01

    Purpose The purpose of this study was to retrospectively investigate the contribution of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to detection of metastatic bladder cancer. Materials and Methods The present study included 79 patients (69 men and 10 women) undergoing 18F-FDG-PET/CT upon suspicion of metastatic bladder cancer between July 2007 and April 2013. The mean age was 66.1 years with a standard deviation of 10.7 years (range, 21 to 85 years). Patients were required to fast for 6 hours prior to scanning, and whole-body PET scanning from the skull base to the upper thighs was performed approximately 1 hour after intravenous injection of 555 MBq of 18F-FDG. Whole body CT scanning was performed in the cranio-caudal direction. FDG-PET images were reconstructed using CT data for attenuation correction. Suspicious recurrent or metastatic lesions were confirmed by histopathology or clinical follow-up. Results The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG-PET/CT were 89%, 78%, 90%, 75%, and 86%, respectively. Conclusion 18F-FDG-PET/CT can detect metastases with high sensitivity and positive predictive values in patients with metastatic bladder carcinoma. PMID:25687863

  13. Urine cytology and adjunct markers for detection and surveillance of bladder cancer

    PubMed Central

    Sullivan, Peggy S; Chan, Jessica B; Levin, Mary R; Rao, Jianyu

    2010-01-01

    Urine cytology coupled with cystoscopic examination has been and remains the standard in the initial evaluation of lower urinary tract lesions to rule out bladder cancer. However, cystoscopy is invasive and may miss some flat lesions, whereas cytology has low sensitivity in low-grade papillary disease. Additional lab-based or office-based markers are needed to aid in the evaluation of these lesions. Recently, many such markers have been developed for the purpose of improving the cytologic diagnosis of bladder malignancies. In this review, we will first discuss conventional cytomorphologic analysis of urine cytology followed by a discussion of markers that have been developed in the past for detection and surveillance of urothelial carcinoma. We will focus on how these markers can be used in conjunction with urine cytology in daily practice. PMID:20733951

  14. Bladder Preservation for Muscle Invasive Bladder Cancer

    PubMed Central

    Mirza, Arafat; Choudhury, Ananya

    2016-01-01

    The standard treatment for muscle invasive bladder cancer (MIBC) has been considered to be radical cystectomy (RC) with pelvic lymphadenectomy. However morbidity and impact on quality of life is significant. Radiotherapy has been used in MIBC patients who choose bladder preservation or who are unfit for RC with comparable outcomes. Evidence from some prospective and large retrospective series supports the use of radiotherapy as an attractive alternative option. In this paper we review the evidence and practice of bladder preservation strategies with radiotherapy for muscle invasive bladder cancer. PMID:27376137

  15. Lab on a chip for multiplexed immunoassays to detect bladder cancer using multifunctional dielectrophoretic manipulations.

    PubMed

    Chuang, Cheng-Hsin; Wu, Ting-Feng; Chen, Cheng-Ho; Chang, Kai-Chieh; Ju, Jing-Wei; Huang, Yao-Wei; Van Nhan, Vo

    2015-07-21

    A multiplexed immunosensor has been developed for the detection of specific biomarkers Galectin-1 (Gal-1) and Lactate Dehydrogenase B (LDH-B) present in different grades of bladder cancer cell lysates. In order to immobilize nanoprobes with different antibodies on a single chip we employed three-step programmable dielectrophoretic manipulations for focusing, guiding and trapping to enhance the fluorescent response and reduce the interference between the two antibody arrays. The chip consisted of a patterned indium tin oxide (ITO) electrode for sensing and a middle fish bone shaped gold electrode for focusing and guiding. Using ITO electrodes for the sensing area can effectively eliminate the background noise of fluorescence response as compared to metal electrodes. It was also observed that the three step manipulation increased fluorescence response after immunosensing by about 4.6 times as compared to utilizing DEP for just trapping the nanoprobes. Two different-grade bladder cancer cell lysates (grade I: RT4 and grade III: T24) were individually analyzed for detecting the protein expression levels of Gal-1 and LDH-B. The fluorescence intensity observed for Gal-1 is higher than that of LDH-B in the T24 cell lysate; however the response observed in RT4 is higher for LDH-B as compared to Gal-1. Thus we can effectively identify the different grades of bladder cancer cells. In addition, the platform for DEP manipulation developed in this study can enable real time detection of multiple analytes on a single chip and provide more practical benefits for clinical diagnosis. PMID:26087450

  16. Bladder cancer detection using a peptide substrate of the 20S proteasome.

    PubMed

    Gruba, Natalia; Wysocka, Magdalena; Brzezińska, Magdalena; Dębowski, Dawid; Sieńczyk, Marcin; Gorodkiewicz, Ewa; Guszcz, Tomasz; Czaplewski, Cezary; Rolka, Krzysztof; Lesner, Adam

    2016-08-01

    The 20S catalytic core of the human 26S proteasome can be secreted from cells, and high levels of extracellular 20S proteasome have been linked to many types of cancers and autoimmune diseases. Several diagnostic approaches have been developed that detect 20S proteasome activity in plasma, but these suffer from problems with efficiency and sensitivity. In this report, we describe the optimization and synthesis of an internally quenched fluorescent substrate of the 20S proteasome, and investigate its use as a potential diagnostic test in bladder cancer. This peptide, 2-aminobenzoic acid (ABZ)-Val-Val-Ser-Tyr-Ala-Met-Gly-Tyr(3-NO2 )-NH2 , is cleaved by the chymotrypsin 20S proteasome subunit and displays an excellent specificity constant value (9.7 × 10(5)  m(-1) ·s(-1) ) and a high kcat (8 s(-1) ). Using this peptide, we identified chymotrypsin-like proteasome activity in the majority of urine samples obtained from patients with bladder cancer, whereas the proteasome activity in urine samples from healthy volunteers was below the detection limit (0.5 pm). These findings were confirmed by an inhibitory study and immunochemistry methods. PMID:27326540

  17. Immunosensor for the ultrasensitive and quantitative detection of bladder cancer in point of care testing.

    PubMed

    Chuang, Cheng-Hsin; Du, Yi-Chun; Wu, Ting-Feng; Chen, Cheng-Ho; Lee, Da-Huei; Chen, Shih-Min; Huang, Ting-Chi; Wu, Hsun-Pei; Shaikh, Muhammad Omar

    2016-10-15

    An ultrasensitive and real-time impedance based immunosensor has been fabricated for the quantitative detection of Galectin-1 (Gal-1) protein, a biomarker for the onset of multiple oncological conditions, especially bladder cancer. The chip consists of a gold annular interdigitated microelectrode array (3×3 format with a sensing area of 200µm) patterned using standard microfabrication processes, with the ability to electrically address each electrode individually. To improve sensitivity and immobilization efficiency, we have utilized nanoprobes (Gal-1 antibodies conjugated to alumina nanoparticles through silane modification) that are trapped on the microelectrode surface using programmable dielectrophoretic manipulations. The limit of detection of the immunosensor for Gal-1 protein is 0.0078mg/ml of T24 (Grade III) cell lysate in phosphate buffered saline, artificial urine and human urine samples. The normalized impedance variations show a linear dependence on the concentration of cell lysate present while specificity is demonstrated by comparing the immunosensor response for two different grades of bladder cancer cell lysates. We have also designed a portable impedance analyzing device to connect the immunosensor for regular checkup in point of care testing with the ability to transfer data over the internet using a personal computer. We believe that this diagnostic system would allow for improved public health monitoring and aid in early cancer diagnosis. PMID:26777732

  18. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    PubMed Central

    2011-01-01

    Background The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Methods Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Results Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26). Conclusions CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests. PMID:21816094

  19. c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization.

    PubMed Central

    Sauter, G.; Carroll, P.; Moch, H.; Kallioniemi, A.; Kerschmann, R.; Narayan, P.; Mihatsch, M. J.; Waldman, F. M.

    1995-01-01

    Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression. Images Figure 1 PMID:7747807

  20. Use of urine-based markers for detection and monitoring of bladder cancer.

    PubMed

    Pirtskalaishvili, G; Getzenberg, R H; Konety, B R

    1999-12-01

    Diagnosis and monitoring of bladder cancer present a difficult clinical problem. Urine cytology with confirmatory cystoscopy form the cornerstone of diagnosis at the present time. The subjectivity and low sensitivity of cytology led to the development of numerous tests as adjuncts to cystoscopy for the diagnosis and follow-up of bladder cancer patients. These tests usually are objective, quantitative (NMP-22, BTA TRAK, BLCA-4, telomerase activity, etc.), or qualitative (BTA Stat and FDP) and have higher sensitivity than cytology, but some have lower specificity. We review the different, new urine-based tests that were developed recently for the diagnosis and monitoring of patients with bladder cancer. The advantages and disadvantages of these tests are discussed, as well as their possible future role in the management of patients with bladder cancer. PMID:10591254

  1. General Information about Bladder Cancer

    MedlinePlus

    ... Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  2. On the influence of the instillation time on the results of HAL (Hexvix) fluorescence detection of superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Jichlinski, Patrice; Aymon, Daniela; Wagnieres, Georges A.; Marti, Alexandre; Lange, Norbert; Guillou, Louis; Leisinger, Hans-Juerg; van den Bergh, Hubert

    2003-10-01

    Hexyl aminolevulinate (HAL) fluorescence cystoscopy is being investigated as a new diagnostic tool for the detection of flat urothelial malignancies in bladder cancers. However, the influence of the bladder instillation time on the performance of this detection modality has not been addressed up to now. We report our initial experience comparing different instillation schedules of HAL cystoscopy in the diagnosis of superficial bladder cancer. A total of 718 fluorescent positive (433) and fluorescence negative (285) biopsies have been taken in the bladder of 143 patients using the Storz D-light fluorescence imaging system (Karl Storz, Tuttlingen, Germany) which allows both white and blue light (380-450 nm) bladder wall inspection. Following hospitalisation, 50 ml of HAL (8mM) phosphate buffer solution was instilled into the bladder of patients during one hour (1 hour protocol involving 57 patients), or during two hours followed by a two hours resting time after removal of the solution (2+2 hours protocol involving 86 patients). Both instillation subgroups were homogeneous in terms of proportion of high risk disease, previous BCG treatment and/or recurrent disease. This study indicates that the instillation duration does not influence the results of HAL (Hexvix) fluorescence cystoscopy in our conditions. Compared to the standard use of ALA, HAL (Hexvix) fluorescence cystoscopy allows a significant reduction of the instillation time (to less than one hour) without prejudicing the efficacy of the method, what represents a real advantage in daily clinical practice.

  3. Superficial bladder cancer.

    PubMed

    Hall, R R

    1994-04-01

    Bladder cancer is almost certainly a product of the industrial revolution and the cigarette smoking that has accompanied it. Exposure to a chemical bladder carcinogen such as beta naphthylamine, benzidine, or 4-diphenylaniline can be proved in only a small proportion of patients and only a handful obtain industrial diseases benefit after developing "Prescribed Industrial Disease C23." None the less, the continued use of known carcinogenic substances in British industry for many years after their identification, the wide range of industries with a known or suspected increased risk of bladder cancer, and our ignorance of the carcinogenic potential of many materials used in current manufacturing should be a cause for continuing concern. PMID:8173377

  4. Application of Multi-SNP Approaches Bayesian LASSO and AUC-RF to Detect Main Effects of Inflammatory-Gene Variants Associated with Bladder Cancer Risk

    PubMed Central

    Calle, M. Luz; Rothman, Nathaniel; Urrea, Víctor; Kogevinas, Manolis; Petrus, Sandra; Chanock, Stephen J.; Tardón, Adonina; García-Closas, Montserrat; González-Neira, Anna; Vellalta, Gemma; Carrato, Alfredo; Navarro, Arcadi; Lorente-Galdós, Belén; Silverman, Debra T.; Real, Francisco X.; Wu, Xifeng; Malats, Núria

    2013-01-01

    The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk. PMID:24391818

  5. AB048. A urinary-metabolomics-based panel for non-invasive detection of bladder cancer

    PubMed Central

    Ma, Zhong

    2016-01-01

    Objective Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence. Early detection is vital to improve the overall survival rate. The common diagnostic modalities, such as cystoscopy and urinary cytology, have their limitations. In this study, potential metabolic biomarkers have been discovered through gas chromatography-mass spectrometry. Based on distinct metabolomics of urine between BCa patients and healthy people, we forged a non-invasive BCa diagnostic model and investigated its performance. Methods This study includes Training Phase, Modeling Phase and Test Phase. During the Training Phase, urine samples were collected from 32 patients diagnosed of bladder cancer and 21 healthy controls. We applied unsupervised principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) model used as a diagnostic model to distinguish two groups. We further constructed logistic regression model using combinations of the metabolites to improve the sensitivity and specificity for early BCa determination. In addition, we screened metabolites which AUC was more than 0.75 for establishing the model of diagnostic panel using logistic regressive analysis. In Test Phase, urine samples from 79 BCa patients and 51 non-BCa controls were subjected to test the diagnostic model. Moreover, by subgroup analysis of BCa, some metabolites were indentified to associate with tumor grade and stage. Results In Training phase, a set of 22 candidate differential metabolites was based on statistical significance and fold difference. Logistic diagnostic model has been established as below: Y=1.3333-8.891X(Glycine)×10-8-4.811X(3-Phosphoglycericacid)×10-5-5.625X(Cytosine)×10-5, with Area Under ROC Curve (AUC) =0.88, sensitivity =78.1% and specificity =95.2%. In Test phase, the efficiency of our diagnostic model shown AUC =0.705, sensitivity =62.0% and specificity =72.5%, better than that of urinary cytology. Besides

  6. Urinary bladder cancer: role of MR imaging.

    PubMed

    Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. PMID:22411938

  7. Pharmacogenomics in bladder cancer

    PubMed Central

    Dancik, Garrett M.; Theodorescu, Dan

    2014-01-01

    Bladder cancer is a common cancer worldwide. For patients presenting with muscle-invasive disease, the five year survival rate is approximately 50%. Cisplatinum-based combination chemotherapy is recommended in the neoadjuvant setting prior to cystectomy and is also the first line in the metastatic setting. However, the survival benefit of such therapy is modest. The identification of pharmacogenomic biomarkers would enable the rational and personalized treatment of patients by selecting those patients that would benefit most from such therapies sparing others the unnecessary toxicity. Conventional therapies would be recommended for an expected responder while a non-responder would be considered for alternative therapies selected on the basis of the individual’s molecular profile. Although few effective bladder cancer therapies have been introduced in the past 30 years, several targeted therapies against the molecular drivers of bladder cancer appear promising. This review summarizes pharmacogenomic biomarkers that require further investigation and/or prospective evaluation, publicly available tools for drug discovery and biomarker identification from in vitro data, and targeted agents that have been evaluated in preclinical models. PMID:24360659

  8. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  9. Bladder cancer biomarker array to detect aberrant levels of proteins in urine.

    PubMed

    Gogalic, S; Sauer, U; Doppler, S; Preininger, C

    2015-02-01

    Bladder cancer (BCa) is a serious malignancy of the urinary tract worldwide and also prominent for its high rate of recurrence incorporating 50% of all treated patients. To reduce relapse of BCa, lifelong surveillance of patients is essential leading to high treatment costs. The gold standard for the diagnosis of bladder cancer is cystoscopy. It is very sensitive, but due to high costs and its invasive nature this method for routine diagnosis of bladder cancer remains questionable. Because of this and the required surveillance of patients suffering from bladder cancer, urine based markers represent a new potential field of investigation. Literature at the National Center of Biological Information (NCBI) was retrieved for a potential marker panel offering specific protein signatures and used to develop a sensitive and accurate chip assay to monitor BCa. Discovery of possible bladder cancer protein markers is compiled by extensive literature search including 1077 recently (15.01.2008-20.03.2014) published research articles. Validation of this literature is done by selection based on prior defined inclusion and exclusion criteria. A set of six putative biomarkers (VEGF, IL-8, MMP-9, MMP-7, survivin and Cyfra 21.1) was identified and a non-invasive microarray developed to be used for further clinical validation. Investigation regarding optimized urine preparation and assay development, to enhance assay sensitivity for the marker panel, was carried out. This protein based BCa chip enables the fast (within 5 h), simultaneous, easy to operate, cheap, early and non-invasive determination of BCa and is ready for clinical evaluation. PMID:25427191

  10. [Diet in bladder cancer ethiopathogenesis].

    PubMed

    Radosavljević, V; Ilić, M; Janković, S; Djokić, M

    2005-01-01

    The aim of this paper is to show influence of different foods on bladder cancer appearance, as well as possible consequent ways of prevention. Consuption of food rich in animal fat and cholesterol, fried foods, especially several times used cookin oil for frying, processed meat with additives (nitrates, nitrites, azo-colourrs) can influence bladder cancer occurrence. Regularly, continous consumption of fermented milk products, which contains come types of milky--acids bacterias, is considered as protective factor in developing bladder cancer. Reports that fruit and vegetable are protective food items are pretty consistent. Data about mineral intake and bladder cancer are obscure. PMID:16812999

  11. Bladder Cancer and Genetic Mutations.

    PubMed

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  12. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  13. Contemporary Management of Bladder Cancer

    PubMed Central

    Bell, David; Fradet, Yves

    1991-01-01

    Bladder cancer is currently the fifth most common cancer in Western society, and its incidence appears to be increasing. Important advances have recently occurred in both diagnostic and therapeutic approaches to bladder neoplasms. Presentation is not unique, and physician awareness is important to identify patients who are at risk for bladder neoplasia and consequently require further investigation. A diagnostic approach and contemporary management are discussed. ImagesFigure 1Figure 4 PMID:21229043

  14. Immunotherapy for bladder cancer

    PubMed Central

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

    2015-01-01

    It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  15. Immunotherapy for bladder cancer.

    PubMed

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James Sa

    2015-01-01

    It is nearly 40 years since Bacillus Calmette-Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  16. Drugs Approved for Bladder Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  17. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... chemicals. Studies suggest that chronic bladder inflammation, a parasitic infection called schistosomiasis, and some medications used to treat ... Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Patient Support and Advocacy Resources (2 links) American Cancer ...

  18. New genetic variants of LATS1 detected in urinary bladder and colon cancer

    PubMed Central

    Saadeldin, Mona K.; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M.; Amleh, Asma; Siam, Rania

    2015-01-01

    LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5′UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer. PMID:25628642

  19. A Methylation Panel for Bladder Cancer — EDRN Public Portal

    Cancer.gov

    Participate in a prevalidation study for methylation based detection of bladder cancer. In addition, a panel of three markers identified will be evaluated for their ability to a) identify bladder cancer patients from those with benign urologic disease; b) identify patients with superficial (papillary) cancers from those with high grade invasive cancers

  20. Targeting EGFR in bladder cancer.

    PubMed

    Villares, G J; Zigler, M; Blehm, K; Bogdan, C; McConkey, D; Colin, D; Bar-Eli, Menashe

    2007-12-01

    Expression and overexpression of the epidermal growth factor receptor (EGFR) have been described in several solid tumors including bladder, breast, colorectal, NSCLC, prostate, and ovarian cancers. In addition to gene amplification, point mutations within the kinase domain also occur. Previous reports indicate that the patient's response to gefitinib depends on either the presence of mutations within the kinase domain of EGFR or the expression of the most frequent alteration, the truncated EGFR variant III (EGFRvIII). Therefore, it is important to determine if these EGFR alterations are present in urothelial carcinoma. The kinase domain of EGFR (exons 18-21) from 11 bladder cancer cell lines as well as from 75 patient tumors was analyzed by automated sequencing. No mutations were detected in all samples tested. Furthermore, analysis of EGFRvIII by immunohistochemistry revealed that almost half of all the patient samples expressed this truncation in a urothelial carcinoma tissue microarray. However, there have been previous reports of inconsistencies in detecting EGFRvIII by immunohistochemistry owing to the specificity of the antibodies and the methodologies utilized. Therefore, these results were validated by reverse transcription PCR, real-time PCR and western blot analysis. In these assays, none of the samples tested positive for EGFRvIII. Taken together, these results indicate that mutations within the tyrosine kinase domain of EGFR and expression of EGFRvIII are rare events in bladder cancer and therefore do not contribute to the malignant phenotype of this tumor. These results have clinical implications in selecting tyrosine kinase inhibitors for the therapy of urothelial carcinoma. PMID:17690890

  1. Cancer of the Urinary Bladder

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 76,960 % of All New Cancer Cases 4.6% Estimated Deaths in 2016 16,390 % of All Cancer ... of This Cancer : In 2013, there were an estimated 587,426 people living with bladder cancer in ...

  2. Ct2 Bladder Cancer.

    PubMed

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach. PMID:27457483

  3. Bladder Cancer in the Elderly

    PubMed Central

    Shariat, Shahrokh F.; Milowsky, Matthew; Droller, Michael J.

    2014-01-01

    Introduction Age is now widely accepted as the greatest single risk factor for developing bladder cancer, and bladder cancer is considered as primarily a disease of the elderly. Because of the close link between age and incidence of bladder cancer, it can be expected that this disease will become an enormous challenge with the growth of an aging population in the years ahead. Methods Using MEDLINE, a search of the literature between January 1966 and July 2007 was performed to describe normative physiologic changes associated with aging, elucidate genetic and epigenetic alterations that associate aging with bladder cancer and its phenotypes; and to characterize how aging influences efficacies, risks, side effects and potential complications of the treatments needed for the various stages of bladder cancer.. Results We discuss influence of aging on host physiology, genetic and epigenetic changes, environmental influences, and host factors in the development and treatment of bladder cancer. Treatments with intravesical Bacille Calmette Guerin, radical cystectomy, and perioperative chemotherapy are less well tolerated and have poorer response in elderly patients compared to their younger counterparts. Elderly patients face both clinical and broader institutional barriers to appropriate treatment and may receive less aggressive treatment and sub-therapeutic dosing. However, when appropriately selected, elderly patients tolerate and respond well to cancer treatments. Conclusions The decision to undergo treatment for cancer is a tradeoff between loss of function and/or independence and extension of life which is complicated by a host of concomitant issues such as co-morbid medical conditions, functional declines and “frailty”, family dynamics, and social and psychological issues. Chronological age should not preclude definitive surgical therapy. It is imperative that healthcare practitioners and researchers from disparate disciplines collectively focus efforts towards

  4. Clinical experience with the use of 5-ALA for the detection of superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Knuechel, Ruth; Kriegmair, M.; Stepp, H. G.; Zaak, D.; Hofstetter, Alfons G.

    2000-06-01

    We report about the experience obtained in the fluorescence cystoscopic evaluation of 647 patients investigated since 1993. Of all histologically confirmed tumors, 32 percent would have been missed with conventional cystoscopy. Only 16 of 38 CIS were also detected under white light. In patients with entirely normal or unspecifically inflamed appearing mucosa, 44 otherwise invisible malignant lesions could be localized by fluorescence, 16 of them being present in patients with negative bladder washing cytology. The specificity of fluorescence cystoscopy is comparable to white light cystoscopy. A prospective multi-center study was conducted to show, whether a fluorescence controlled transurethral two weeks revealed residual tumor in 53 percent in the white light arm compared to 33 percent in the fluorescence arm. This difference was statistically significant. Of the 33 percent tumor in the fluorescence arm, most was gathered within the resection margins of the first resection, indicating an insufficiently deep resection rather than a failure in detecting the lesion.

  5. Photodynamic management of bladder cancer

    NASA Astrophysics Data System (ADS)

    Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

    2009-06-01

    Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

  6. Bladder Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Bladder cancer detection by fluorescence imaging with Hexvix: analysis and processing of images obtained during high magnification cystoscopy

    NASA Astrophysics Data System (ADS)

    Lovisa, Blaise; Jichlinski, Patrice; Aymon, Daniela; Weber, Bernd-Claus; van den Bergh, Hubert; Wagnières, Georges

    2009-06-01

    Fluorescence cystoscopy has been recently acknowledged as a useful method to detect early superficial bladder cancer, even flat lesions. After the instillation of hexaminolevulinic acid (Hexvix) in the bladder for about an hour, photoactivable porphyrins (PaP), mainly protoporphyrin IX (PpIX) accumulate in the cancerous cells. Although we observe a selective production of PpIX and an outstanding sensitivity of this method, false positive (FP) lesions negatively impact its specificity. Carcinogenesis often combines with angiogenesis, and thus changes in vascular architecture. Therefore, the visualization of the vascular modifications on the fluorescence positive sites is likely to differentiate false and true positive (TP). New methods including high magnification (HM) cystoscopy are being investigated by our group, and will yield a reduced number of biopsies and a better characterization of the fluorescence positive sites. In this study, we are using a dedicated rigid cystoscope, allowing conventional magnification during "macroscopic" observation, as well as image acquisition with HM when the endoscope is in contact with the tissue. Each observed site is biopsied and described by histopathological analysis. The vascular organization (tortuosity, vascular loops, vascular area and diameter) of the fluorescence positive sites was characterized in parallel with an in situ visual grading and a dedicated software procedure. We describe here a simple image processing prototype that classifies the HM images into two classes, according to their pixel distributions. For that purpose, we developed an algorithm in the image spatial and frequency domain, so that the vascular architecture could be described objectively and quantitatively.

  8. Bladder cancer detection by fluorescence imaging with Hexvix: optimization of the excitation light during high magnification cystoscopy

    NASA Astrophysics Data System (ADS)

    Lovisa, Blaise; Jichlinski, Patrice; Aymon, Daniela; Weber, Bernd-Claus; van den Bergh, Hubert; Wagnières, Georges

    2009-07-01

    Fluorescence cystoscopy has been recently acknowledged as a useful method to detect early superficial bladder cancer, even flat lesions. After the instillation of hexaminolevulinic acid (Hexvix®) in the bladder for about an hour, photoactivable porphyrins (PaP), mainly protoporphyrin IX (PpIX) accumulate in the cancerous cells. Although we observe a selective production of PpIX and an outstanding sensitivity of this method, false positive (FP) lesions negatively impact its specificity. Carcinogenesis often combines with angiogenesis, and thus changes in vascular architecture. Therefore, the visualization of the vascular modifications on the fluorescence positive sites is likely to differentiate false and true positive (TP). New methods including high magnification (HM) cystoscopy are being investigated by our group, and will yield a reduced number of biopsies and a better characterization of the fluorescence positive sites. In this study, we are using a dedicated rigid cystoscope, allowing conventional magnification during "macroscopic" observation, as well as image acquisition with HM when the endoscope is in contact with the tissue. Each observed site is biopsied and described by histopathological analysis. The vascular organization (tortuosity, vascular loops, vascular area and diameter) of the fluorescence positive sites was characterized in situ. Intrinsic contrast between the vessels and the tissue was enhanced with an optimization of the spectral design. Preliminary results are presented here.

  9. Fluorescence photodetection of urothelial neoplastic foci in superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Jichlinski, Patrice; Forrer, Martin; Mizeret, Jerome C.; Braichotte, Daniel; Wagnieres, Georges A.; Zimmer, Georges; Guillou, Louis; Schmidlin, Franz R.; Graber, Peter; van den Bergh, Hubert; Leisinger, Hans-Juerg

    1997-05-01

    The prognosis of superficial bladder cancer in terms of recurrence and disease progression is related to the bladder tumor multiplicity and the presence of concomitant 'plane' tumors such as high grade dysplasia and carcinoma in situ (CIS). This study on 33 patients tries to demonstrate the interest of fluorescence cystoscopy in transurethral resection of superficial bladder cancer The method is based on the detection of the protoporphyrin IX (PpIX) induced fluorescence in urothelial cancer cells by topical administration of 5- aminolevulinic acid (ALA). The sensitivity and the specificity of this procedure on apparently normal mucosa in superficial bladder cancer is respectively estimated at 82.9% and 81.3%. Thus, fluorescence cystoscopy is a simple and reliable method in mapping the bladder mucosa, especially in case of multifocal bladder disease and it facilitates the screening of occult dysplasia.

  10. Pathobiology and Chemoprevention of Bladder Cancer

    PubMed Central

    Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

    2011-01-01

    Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

  11. Immunotherapeutic strategies for bladder cancer

    PubMed Central

    Chevalier, Mathieu F; Nardelli-Haefliger, Denise; Domingos-Pereira, Sonia; Jichlinski, Patrice; Derré, Laurent

    2014-01-01

    Bladder cancer is a common urologic malignancy with rising incidence in the elderly population. In most cases, bladder cancer is non-muscle-invasive at diagnosis and shows dramatically high recurrence rates, although current treatments often reduce the risk of disease progression. Immunotherapy using intravesical instillation of Bacillus Calmette-Guérin (BCG) remains the most effective therapy for patients with high risk tumors. However, BCG-therapy has important limitations including substantial adverse events and frequent treatment failure. Thus, it appears crucial to either improve or replace current therapy using new immunotherapeutic strategies. Here, we discuss the clinical trials that assessed therapeutic vaccination of bladder cancer patients using tumor associated antigens and we also argue for novel approaches arising from murine models. Vaccination routes to induce appropriate T-cell homing in the tumor site as well as the use of local immunostimulation to enhance recruitment of vaccine-induced T cells are discussed to highlight what we believe is a promising therapeutic vaccination strategy for patients with non-muscle-invasive bladder cancer. PMID:24384699

  12. Immunotherapeutic strategies for bladder cancer.

    PubMed

    Chevalier, Mathieu F; Nardelli-Haefliger, Denise; Domingos-Pereira, Sonia; Jichlinski, Patrice; Derré, Laurent

    2014-01-01

    Bladder cancer is a common urologic malignancy with rising incidence in the elderly population. In most cases, bladder cancer is non-muscle-invasive at diagnosis and shows dramatically high recurrence rates, although current treatments often reduce the risk of disease progression. Immunotherapy using intravesical instillation of Bacillus Calmette-Guérin (BCG) remains the most effective therapy for patients with high risk tumors. However, BCG-therapy has important limitations including substantial adverse events and frequent treatment failure. Thus, it appears crucial to either improve or replace current therapy using new immunotherapeutic strategies. Here, we discuss the clinical trials that assessed therapeutic vaccination of bladder cancer patients using tumor associated antigens and we also argue for novel approaches arising from murine models. Vaccination routes to induce appropriate T-cell homing in the tumor site as well as the use of local immunostimulation to enhance recruitment of vaccine-induced T cells are discussed to highlight what we believe is a promising therapeutic vaccination strategy for patients with non-muscle-invasive bladder cancer. PMID:24384699

  13. Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder

    PubMed Central

    Di Stasi, Savino M.; De Carlo, Francesco; Pagliarulo, Vincenzo; Masedu, Francesco; Verri, Cristian; Celestino, Francesco; Riedl, Claus

    2015-01-01

    Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL–PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152–0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069–0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014–0.103 and T1 proportion difference 1.2%, 95% CI 0.033–0.057). Moreover, there were 15% of patients (95% CI 0.098–0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL–PDD. This meta-analysis confirms the increased tumor detection rate by HAL–PDD with a most pronounced benefit for CIS lesion. PMID:26622319

  14. Metabolic phenotype of bladder cancer.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  15. Circulating miR-205: a promising biomarker for the detection and prognosis evaluation of bladder cancer.

    PubMed

    Fang, Zhenqiang; Dai, Wei; Wang, Xiangwei; Chen, Wei; Shen, Chongxin; Ye, Gang; Li, Longkun

    2016-06-01

    MicroRNA (miRNA) expression profile analysis indicated that miR-205 was upregulated in bladder cancer tissue compared to healthy tissue. The aim of this study is to analyze value of circulating miR-205 for the detection and prognosis evaluation of bladder cancer (BC). Eighty-nine patients with BC and 56 healthy controls (HC) were enrolled in the study. miR-205 expression was determined using TaqMan quantitative real-time polymerase chain reaction assay and further correlated with patients' clinicopathological parameters and follow-up data. The results indicated that plasma miR-205 was upregulated in BC compared with HC (P < 0.001) and in muscle invasive BC (MIBC) compared to nonmuscle invasive BC (NMIBC) (P = 0.016). miR-205 yielded an area under the receiver-operating characteristic curve of 0.950 with 76.4 % sensitivity and 96.4 % specificity in discriminating BC from HC, and 0.668 with 57.1 % sensitivity and 77.0 % specificity in distinguishing MIBC from NMIBC. Plasma miR-205 expression was significantly associated with tumor stage (P < 0.001) and pathological grade (P = 0.048). The results indicated that BC patients with high miR-205 expression experienced shorter disease-free survival and disease-specific survival (P = 0.022 and P = 0.026; P = 0.027 and P = 0.034; respectively), which was not proven by multivariate Cox regression analysis (multi-Cox) (P = 0.0765 and P = 0.279, respectively). Log-rank test showed that NMIBC patients with high miR-205 expression experienced shorter cancer-free survival (P = 0.044). Log-rank test and univariate and multivariate Cox regression analyses did not indicate that high miR-205 expression in NMIBC patients was associated with cancer-specific survival (P = 0.079, P = 0.089, and P = 0.201, respectively). In conclusion, miR-205 may be a promising biomarker for the detection and prognosis evaluation of BC. PMID:26715266

  16. [Specific types of bladder cancer].

    PubMed

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

  17. Hair Dye Use and Risk of Bladder Cancer in the New England Bladder Cancer Study

    PubMed Central

    Koutros, Stella; Silverman, Debra T.; Baris, Dalsu; Zahm, Shelia Hoar; Morton, Lindsay M.; Colt, Joanne S.; Hein, David W.; Moore, Lee E.; Johnson, Alison; Schwenn, Molly; Cherala, Sai; Schned, Alan; Doll, Mark A.; Rothman, Nathaniel; Karagas, Margaret R.

    2011-01-01

    Aromatic amine components in hair dyes, and polymorphisms in genes that encode enzymes responsible for hair dye metabolism, may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by NAT1, NAT2, GSTM1, and GSTT1 genotypes in a population-based case-control study of 1,193 incident cases and 1,418 controls from Maine, Vermont, and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration, or number of applications of hair dyes and bladder cancer among women or men was apparent but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer (OR=3.3, 95% CI: 1.2, 8.9). Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR=7.3, 95% CI: 1.6, 32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. While we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies. PMID:21678399

  18. Hair dye use and risk of bladder cancer in the New England bladder cancer study.

    PubMed

    Koutros, Stella; Silverman, Debra T; Baris, Dalsu; Zahm, Shelia Hoar; Morton, Lindsay M; Colt, Joanne S; Hein, David W; Moore, Lee E; Johnson, Alison; Schwenn, Molly; Cherala, Sai; Schned, Alan; Doll, Mark A; Rothman, Nathaniel; Karagas, Margaret R

    2011-12-15

    Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies. PMID:21678399

  19. Microsatellite instability in bladder cancer.

    PubMed

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, K

    1993-12-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis. PMID:8242615

  20. What Is Bladder Cancer?

    MedlinePlus

    ... Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is by far the most common type of ... cancer (other than sarcoma) are treated similar to TCCs, especially for early stage tumors, but if chemotherapy ...

  1. Bladder Cancer Screening in Aluminum Smelter Workers

    PubMed Central

    Taiwo, Oyebode A.; Slade, Martin D.; Cantley, Linda F.; Tessier-Sherman, Baylah; Galusha, Deron; Kirsche, Sharon R.; Donoghue, A. Michael

    2015-01-01

    Objective: To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. Methods: Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. Results: ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. Conclusions: Evidence to support continued surveillance of this cohort has not been demonstrated. PMID:25525927

  2. Bladder cancer immunotherapy.

    PubMed

    Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M

    1982-11-01

    A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy. PMID:6757467

  3. Photodynamic diagnosis of bladder cancer in ex vivo urine cytology

    NASA Astrophysics Data System (ADS)

    Fu, C. Y.; Ng, B. K.; Razul, S. Gulam; Olivo, Malini C.; Lau, Weber K. O.; Tan, P. H.; Chin, William

    2006-02-01

    Bladder cancer is the fourth common malignant disease worldwide, accounting for 4% of all cancer cases. In Singapore, it is the ninth most common form of cancer. The high mortality rate can be reduced by early treatment following precancerous screening. Currently, the gold standard for screening bladder tumors is histological examination of biopsy specimen, which is both invasive and time-consuming. In this study ex vivo urine fluorescence cytology is investigated to offer a timely and biopsy-free means for detecting bladder cancers. Sediments in patients' urine samples were extracted and incubated with a novel photosensitizer, hypericin. Laser confocal microscopy was used to capture the fluorescence images at an excitation wavelength of 488 nm. Images were subsequently processed to single out the exfoliated bladder cells from the other cells based on the cellular size. Intensity histogram of each targeted cell was plotted and feature vectors, derived from the histogram moments, were used to represent each sample. A difference in the distribution of the feature vectors of normal and low-grade cancerous bladder cells was observed. Diagnostic algorithm for discriminating between normal and low-grade cancerous cells is elucidated in this paper. This study suggests that the fluorescence intensity profiles of hypericin in bladder cells can potentially provide an automated quantitative means of early bladder cancer diagnosis.

  4. Detecting primary bladder cancer using delayed 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography imaging after forced diuresis

    PubMed Central

    Mertens, Laura S; Fioole-Bruining, Annemarie; Vegt, Erik; Vogel, Wouter V; van Rhijn, Bas WG; Horenblas, Simon

    2012-01-01

    Objective: The aim of this study was to evaluate the use of delayed pelvic 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography combined with the computed tomography (FDG-PET/CT) imaging, according to a standardized protocol including, pre-hydration and forced diuresis, for the detection of primary bladder cancer. Materials and Methods: We evaluated 38 consecutive patients with primary cT1-4 bladder cancer. They underwent standard FDG-PET/CT followed by delayed pelvic imaging after administration of 20 mg furosemide intravenously and extra oral water intake of 0.5 L. Two observers, blinded for patient data, scored both image sets for tumor visibility using a 3-point ordinal scale: (1) negative; (2) indeterminate; (3) positive. FDG-PET/CT findings were compared with histopathology and/or follow-up imaging. Results: The procedure was completed successfully in 37/38 patients and the reference standard revealed a bladder tumor in 26/37 patients. Delayed PET/CT images showed reduction of urinary bladder activity to (near) background levels in 17 of 37 cases (45.9%). Standard PET/CT detected hyper-metabolic bladder lesions in 15/37 patients (40.5%) of which 8 were indeterminate. Delayed FDG-PET/CT showed hyper-metabolic bladder lesions in 30/37 (81.1%) patients, of which 5 were indeterminate. When indeterminate lesions were considered positive, the sensitivity of standard and delayed PET/CT was 46% versus 88%, respectively. The specificity was 72% versus 36%. When indeterminate lesions were considered negative, the sensitivity of standard and delayed PET/CT was 23% and 85%. The specificity was 93% versus 73%. Conclusions: Our data suggest that delayed pelvic FDG-PET/CT imaging after forced detects more primary bladder tumors than standard FDG-PET/CT protocols. However, indeterminate bladder lesions on delayed PET/CT remain a problem and should be interpreted cautiously in order to avoid false positive results. PMID:23919066

  5. [Fabrication of silver ordered nanoarrays SERS-active substrates and their applications in bladder cancer cells detection].

    PubMed

    Liu, You; Huang, Li-qing; Wang, Jun; Tong, Hui-min; Yuan, Lin; Zhao, Li-hua; Zhang, Wei-wei; Wang, Leiz; Zhu, Jian

    2012-02-01

    Highly ordered silver nanopore and nanocap arrays, which were used as surface-enhanced Raman scattering active (SERS-active) substrates, were fabricated by electron-beam evaporating silver on the surface of porous layer and barrier layer of porous anodic alumina (PAA) membranes, respectively. The SERS characteristics of the SERS-active substrates were tested with bladder cancer cells as molecular probe. The results indicated that both the SERS-active substrates displayed a strong SERS enhancement effect. The silver nanocap ordered arrays SERS-active substrate displayed not only higher SERS and fluorescence quenching effect, but also no interferential spectrum related with oxalate impurity remaining in PAA membranes, and therefore can result in the high quality Raman spectroscopy of bladder cancer cells. PMID:22512174

  6. Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine

    PubMed Central

    Saeb-Parsy, K; Wilson, A; Scarpini, C; Corcoran, M; Chilcott, S; McKean, M; Thottakam, B; Rai, B; Nabi, G; Rana, D; Perera, M; Stewart, K; Laskey, R A; Neal, D E; Coleman, N

    2012-01-01

    Background: We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine. Methods: Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy. Results: In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05). Conclusions: Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups. PMID:22968648

  7. Urine BLCA-4 exerts potential role in detecting patients with bladder cancers: a pooled analysis of individual studies.

    PubMed

    Cai, Qiliang; Wu, Yudong; Guo, Zhanjun; Gong, Rui; Tang, Yang; Yang, Kuo; Li, Xiaodong; Guo, Xuemei; Niu, Yuanjie; Zhao, Yan

    2015-11-10

    Epidemiological studies have explored the diagnostic effect of urine BLCA-4 in bladder cancer. However, the results remain controversial. Therefore, we conducted this pooled analyses to determine the overall accuracy of urine BLCA-4 in bladder cancer. A comprehensive electronic and hand search was conducted for related literatures though several databases. QUADAS-2 was used to assess the quality of each included studies. Diagnostic parameters were calculated using Meta-Disc (version 1.4) and Stata (version 12.0) software. Nine published articles with 1,119 subjects were included. The summary estimates were: sensitivity 0.93 (95 % confidence interval [CI] = 0.90-0.95), specificity 0.97 (95% CI, 0.95-0.98), positive likelihood ratio 48.16 (95% CI, 11.77-197.01), negative likelihood ratio 0.08 (95% CI, 0.06-0.11), diagnostic odds ratio 534.03 (95% CI, 150.15-1899.31), and the AUC was 0.9607. In conclusion, urine BLCA-4 is a promising marker in diagnosing bladder cancer. PMID:26462026

  8. Soft agar colony formation of bladder cells during carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine and application to detection of bladder cancer promoters.

    PubMed

    Hashimura, T; Kanamaru, H; Yoshida, O

    1987-05-01

    N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to male Fischer 344 rats at a dose of 0.05% in drinking water for 2, 4, 6 and 12 weeks, and double soft agar colony formation of the uroepithelial cells was determined periodically, during and after this administration. In the group administered BBN for 2 weeks, no significant colony growth was observed until week 8. In the group given BBN for 4 weeks, colony growth was observed at week 4 and the numbers of colonies remained constant until week 8. In the group given BBN for 6 weeks, significant colony growth was observed at weeks 6 and 8. In the group on BBN for 12 weeks, colonies grew from week 4 and significant numbers of colonies were observed from week 6, increasing up to week 10. Colony formation preceded papilloma development in the rat bladder, and was dependent on the duration of BBN administration. The effect of amino acids and sodium saccharin on colony formation was also evaluated. The rats were given 0.05% BBN for 3 weeks, followed immediately by the administration for 9 weeks of 2% L-tryptophan, 1% D-tryptophan, 2% L-leucine, 2% D-leucine, 2% DL-leucine, 2% L-isoleucine, 2% DL-isoleucine or 5% sodium saccharin in the diet. At week 12, the numbers of colonies were significantly higher in the groups given sodium saccharin, L-leucine, DL-leucine, L-isoleucine, DL-isoleucine and D-tryptophan. This method provides a potentially useful approach toward analyzing the early events in bladder carcinogenesis and may be applicable to detect new bladder carcinogens and promoters. PMID:3112059

  9. Diagnostics techniques in nonmuscle invasive bladder cancer

    PubMed Central

    Soubra, Ayman; Risk, Michael C.

    2015-01-01

    Introduction: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. Methods: Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer” and various diagnostic techniques described in the article. Results: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. Conclusions: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC. PMID:26604438

  10. Metabolomics in bladder cancer: a systematic review

    PubMed Central

    Cheng, Yidong; Yang, Xiao; Deng, Xiaheng; Zhang, Xiaolei; Li, Pengchao; Tao, Jun; Qin, Chao; Wei, Jifu; Lu, Qiang

    2015-01-01

    Bladder cancer (BC) is the most common urological malignancy. Early diagnosis of BC is crucial to improve patient outcomes. Currently, metabolomics is a potential technique that can be used to detect BC. We reviewed current publications and synthesised the findings on BC and metabolomics, i.e. metabolite upregulation and downregulation. Fourteen metabolites (lactic acid, leucine, valine, phenylalanine, glutamate, histidine, aspartic acid, tyrosine, serine, uracil, hypoxanthine, carnitine, pyruvic acid and citric acid) were identified as potential biomarkers for BC. In conclusion, this systematic review presents new opportunities for the diagnosis of BC. PMID:26379905

  11. Pathogenesis of human urinary bladder cancer

    PubMed Central

    Bryan, George T.

    1983-01-01

    The pathogenesis of bladder cancer is being analyzed at several levels of biological organization, i.e., population groups, individual whole animal, tissue, cell, molecule, etc. Each of these levels provides opportunities for mechanistic studies. Yet the integration of these several levels into a cohesive fabric is incomplete. From a clinical point of view, the following seem of importance to human bladder cancer pathogenesis. The initiation, promotion, and progression of bladder cancer involves several factors acting concurrently or sequentially. These factors appear to be naturally occurring or synthetically created chemicals present in the external environment. Human exposures to these agents may begin in utero, and varying, dynamic qualitative and quantitative exposure patterns continue through developmental and adult life. Apparent latent periods of development of clinical bladder cancer may be as short as one, or as long as 50 years or more. Individuals may exhibit differential susceptibility to vesical carcinogens, perhaps through phenotypic differences in quantitative biotransformation routes. Differences in bladder epithelial cell susceptibilities probably also occur, as well as varying local tissue and generalized resistance to neoplasia formation. Older individuals do not appear to be more resistant to bladder carcinogenesis. A number of animal model systems have been developed for the study of the in vivo, cellular, and molecular pathogenesis of bladder cancer. These models replicate many of the known salient features of human bladder cancer. Through use of appropriate whole animal models in conjunction with investigations of human and animal bladder cells and tissues in culture, controlled mechanistic and quantitative studies of bladder cancer pathogenesis should rapidly develop. PMID:6832092

  12. Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

    ClinicalTrials.gov

    2016-06-09

    Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

  13. VEGF, CA9 and Angiogenin as a Urinary Biomarker for Bladder Cancer Detection

    PubMed Central

    Urquidi, Virginia; Goodison, Steve; Kim, Jeongsoon; Chang, Myron; Dai, Yunfeng; Rosser, Charles J.

    2012-01-01

    Objective To investigate whether elevated urinary levels of vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9) and angiogenin are associated with BCa. Methods This is a case-control study in which voided urines from 127 patients: control subjects (n = 63) and tumor bearing subjects (n = 64) were analyzed. The urinary concentrations of VEGF, CA9, angiogenin and BTA were assessed by enzyme-linked immunosorbent assay (ELISA). We used the area under the curve (AUC) of receiver operating characteristic curves to determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine samples. Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak©). Sensitivity, specificity, positive and negative predictive values were calculated. Results Urinary concentrations of VEGF, CA9, angiogenin and BTA were significantly elevated in BCa. VEGF was the most accurate urinary biomarker (AUC: 0.886; 95% confidence interval [CI]: 0.8301–0.9418). Furthermore, multivariate regression analysis highlighted VEGF (OR: 5.90; 95% CI: 2.60–13.40, p < 0.0001) as an independent variable. The sensitivities and specificities for VEGF (sensitivity, 83% and specificity, 87%) outperformed BTA (sensitivity, 80% and specificity, 84%). Conclusions VEGF may be a valuable addition to voided urine sample analysis for the detection of BCa. Larger, prospective studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the non-invasive evaluation of BCa patients. PMID:22386755

  14. Bladder cancer in the aluminium industry.

    PubMed

    Thériault, G; Tremblay, C; Cordier, S; Gingras, S

    1984-04-28

    The incidence of bladder cancer is unusually high in aluminium smelter workers. An epidemiological study showed that workers in Soderberg potrooms are at highest risk for bladder cancer, the adjusted overall relative risk being 2.39 (1.34-4.28). Exposure to polycyclic aromatic hydrocarbons, of which benz(a)pyrene (BaP) served as an indicator, seems to be the causative factor. The relative risk was evaluated at 12.38 for workers with 20 or more equivalent years of BaP exposure. Cigarette smoking contributed significantly to the appearance of bladder cancer in the population studied. There is a synergistic effect when cigarette smoking and BaP exposure are combined; the numbers in our population are too small to determine whether this interaction effect is multiplicative or additive. It is concluded that bladder cancer is associated with aluminium smelting (primarily with the Soderberg process). PMID:6143877

  15. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  16. Computer-aided detection of bladder tumors based on the thickness mapping of bladder wall in MR images

    NASA Astrophysics Data System (ADS)

    Zhu, Hongbin; Duan, Chaijie; Jiang, Ruirui; Li, Lihong; Fan, Yi; Yu, Xiaokang; Zeng, Wei; Gu, Xianfeng; Liang, Zhengrong

    2010-03-01

    Bladder cancer is reported to be the fifth leading cause of cancer deaths in the United States. Recent advances in medical imaging technologies, such as magnetic resonance (MR) imaging, make virtual cystoscopy a potential alternative with advantages as being a safe and non-invasive method for evaluation of the entire bladder and detection of abnormalities. To help reducing the interpretation time and reading fatigue of the readers or radiologists, we introduce a computer-aided detection scheme based on the thickness mapping of the bladder wall since locally-thickened bladder wall often appears around tumors. In the thickness mapping method, the path used to measure the thickness can be determined without any ambiguity by tracing the gradient direction of the potential field between the inner and outer borders of the bladder wall. The thickness mapping of the three-dimensional inner border surface of the bladder is then flattened to a twodimensional (2D) gray image with conformal mapping method. In the 2D flattened image, a blob detector is applied to detect the abnormalities, which are actually the thickened bladder wall indicating bladder lesions. Such scheme was tested on two MR datasets, one from a healthy volunteer and the other from a patient with a tumor. The result is preliminary, but very promising with 100% detection sensitivity at 7 FPs per case.

  17. Chemoimmunotherapy of murine bladder cancer.

    PubMed

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  18. Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer

    PubMed Central

    Andersson, Elin; Dahmcke, Christina M.; Steven, Kenneth; Larsen, Louise K.; Guldberg, Per

    2015-01-01

    Molecular analysis of cells from urine provides a convenient approach to non-invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells. A special feature of this device is a removable cartridge housing a membrane filter, which after filtration of urine can be transferred to a storage unit containing an appropriate preserving solution. In spiking experiments, the use of this device provided efficient recovery of bladder cancer cells with elimination of >99% of excess smaller-sized cells. The performance of the device was further evaluated by DNA-based analysis of urinary cells collected from 57 patients subjected to transurethral resection following flexible cystoscopy indicating the presence of a tumor. All samples were tested for FGFR3 mutations and seven DNA methylation markers (BCL2, CCNA1, EOMES, HOXA9, POU4F2, SALL3 and VIM). In the group of patients where a transitional cell tumor was confirmed at histopathological evaluation, urine DNA was positive for one or more markers in 29 out of 31 cases (94%), including 19 with FGFR3 mutation (61%). In the group of patients with benign histopathology, urine DNA was positive for methylation markers in 13 out of 26 cases (50%). Only one patient in this group was positive for a FGFR3 mutation. This patient had a stage Ta tumor resected 6 months later. The ability to easily collect, store and ship diagnostic cells from urine using the presented device may facilitate non-invasive testing for bladder cancer. PMID:26151138

  19. Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says

    MedlinePlus

    ... 157716.html Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says Herbicide was used during Vietnam ... the herbicide Agent Orange and bladder cancer and thyroid problems among U.S. military personnel exposed to the ...

  20. FDA Approves New Drug to Treat Bladder Cancer

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158937.html FDA Approves New Drug to Treat Bladder Cancer Tecentriq boosted survival ... 2016 THURSDAY, May 19, 2016 (HealthDay News) -- A new drug to treat bladder cancer was approved by ...

  1. Modeling bladder cancer in mice: opportunities and challenges

    PubMed Central

    Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

    2015-01-01

    The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

  2. Bladder cancer: smoking, beverages and artificial sweeteners

    PubMed Central

    Morgan, Robert W.; Jain, Meera G.

    1974-01-01

    A matched patient-control study of bladder cancer examined the relationship of the disease to occupation, smoking and intake of tea, coffee, cola, alcohol and artificial sweeteners. There was no association of disease with occupation for these patients. Heavy smoking gave relative risks of 6.37 and 4.36 for men and women respectively; there was evidence of a dose-response relationship. Tea and coffee intake did not increase the risk of disease nor did prolonged use of artificial sweeteners. Alcohol and cola intake increased the relative risk of bladder cancer among male smokers. There is some suggestion that smoking interacts with both alcohol and cola intake in the production of bladder cancer. PMID:4429932

  3. Targeting glycogen metabolism in bladder cancer

    PubMed Central

    Lew, Carolyn Ritterson; Guin, Sunny; Theodorescu, Dan

    2015-01-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis—two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist. PMID:26032551

  4. Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

    ClinicalTrials.gov

    2016-07-22

    Recurrent Bladder Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma

  5. Can we use methylation markers as diagnostic and prognostic indicators for bladder cancer?

    PubMed Central

    Kim, Yong-June

    2016-01-01

    Urothelial carcinomas of the urinary bladder have diverse biological and functional characteristics, and numerous factors are likely to be involved in recurrence, progression, and patient survival. While several molecular markers used to evaluate the development and prognosis of bladder cancer have been studied, they are of limited value; therefore, new molecular parameters useful for predicting the prognosis of bladder cancer patients (particularly patients at high risk of progression and recurrence) are required. Recent progress in the understanding of epigenetic modification and gene silencing has provided new opportunities for the detection, treatment, and prevention of cancer. Methylation is an important molecular mechanism in bladder cancer and may have utility as a prognostic and/or diagnostic marker. This review discusses the epigenetic issues involved in the detection and prediction of bladder cancer. PMID:27326410

  6. Incidence of bladder cancer discovered by urethrocystoscopy at prostate biopsy: extraordinary high incidence of tiny bladder cancer in elderly males.

    PubMed

    Okazaki, Hiroshi; Suzuki, Koichi; Suzuki, Takanori; Kurokawa, Kohei; Ito, Kazuto; Suzuki, Kazuhiro; Yamanaka, Hidetoshi

    2004-05-01

    In order to clarify the incidence of bladder cancer with and without prostate cancer, we investigated bladder cancer discovered incidentally by urethrocystoscopy at prostate biopsy. Between April 1997 and December 2003, 498 patients who were suspected prostate cancer were performed prostate biopsy and urethrocystoscopy simultaneously. We investigate possible invasion of prostate cancer into the urethra or bladder mucosa as well as bladder cancer, including other benign lesions of the bladder by urethrocystoscopy. Prostate cancer was confirmed in 175 (35.1%) of the 498 patients histologically, and bladder cancer was discovered incidentally in 12 patients (2.4 %). The incidence of bladder cancer in patients with prostate cancer of 2.3% (4/175) was not significantly different from that in patients without prostate cancer, which was 2.5% (8/323). Superficial and those with a size less than 1 cm were noted in 11 patients (92%) and 10 patients (83%) respectively. High incidence rate of bladder cancer with prostate cancer was reported previously, however, there was no study to compare the incidence rate of bladder cancer between cases with and without prostate cancer. The present study suggests that asymptomatic tiny bladder cancer may be present at an unexpectedly high incidence rate in elderly males. PMID:15185969

  7. An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese

    PubMed Central

    Li, Qiaoling; An, Dan; Fang, Lu; Lin, Youcheng; Hou, Yong; Xu, Abai; Fu, Yu; Lu, Wei; Chen, Xin; Chen, Mingwei; Zhang, Meng; Jiang, Huiling; Zhang, Chuanxia; Dong, Pei; Li, Chong; Chen, Jun; Yang, Guosheng; Liu, Chunxiao; Cai, Zhiming; Zhou, Fangjian; Wu, Song

    2016-01-01

    To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 148 individuals—which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)—were quantified by qMSP using the urine sediment DNA. Receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of possible combinations were calculated through logistic regression model. Subsequently, ROC curves of the three best performing combinations were constructed. Then, we validated the three best performing combinations and POU4F2 in another 72 UCC, 21 IUC, 26 KC and 22 PC, and 23 HV urine samples. The combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting BlCa effectively among pathologically varied sample groups. PMID:26700620

  8. New Optical Imaging Technologies for Bladder Cancer: Considerations and Perspectives

    PubMed Central

    Liu, Jen-Jane; Droller, Michael J.; Liao, Joseph C.

    2014-01-01

    Purpose Bladder cancer presents as a spectrum of different diatheses. Accurate assessment for individualized treatment depends on initial diagnostic accuracy. Detection relies on white light cystoscopy accuracy and comprehensiveness. Aside from invasiveness and potential risks, white light cystoscopy shortcomings include difficult flat lesion detection, precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and grade and stage determination. Each shortcoming depends on surgeon ability and experience with the technology available for visualization and resection. Fluorescence cystoscopy/photodynamic diagnosis, narrow band imaging, confocal laser endomicroscopy and optical coherence tomography address the limitations and have in vivo feasibility. They detect suspicious lesions (photodynamic diagnosis and narrow band imaging) and further characterize lesions (optical coherence tomography and confocal laser endomicroscopy). We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course. Materials and Methods Detailed PubMed® searches were done using the terms “fluorescence cystoscopy,” “photodynamic diagnosis,” “narrow band imaging,” “optical coherence tomography” and “confocal laser endomicroscopy” with “optical imaging,” “bladder cancer” and “urothelial carcinoma.” Diagnostic accuracy reports and all prospective studies were selected for analysis. We explored technological principles, preclinical and clinical evidence supporting nonmuscle invasive bladder cancer detection and characterization, and whether improved sensitivity vs specificity translates into improved correlation of diagnostic accuracy with recurrence and progression. Emerging preclinical technologies with potential application were reviewed. Results Photodynamic diagnosis and narrow band imaging improve nonmuscle invasive bladder cancer detection, including

  9. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  10. Metabolic alterations in bladder cancer: applications for cancer imaging.

    PubMed

    Whyard, Terry; Waltzer, Wayne C; Waltzer, Douglas; Romanov, Victor

    2016-02-01

    Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging-based technique is crucial for adequate staging. Although Magnetic Resonance Imaging (MRI) is currently the best in vivo imaging technique for BC staging because of its excellent soft-tissue contrast and absence of ionizing radiation it lacks cancer-specificity. Tumor-specific positron emission tomography (PET), which is based on the Warburg effect (preferential uptake of glucose by cancer cells), exploits the radioactively-labeled glucose analogs, i.e., FDG. Although FDG-PET is highly cancer specific, it lacks resolution and contrast quality comparable with MRI. Chemical Exchange Saturation Transfer (CEST) MRI enables the detection of low concentrations of metabolites containing protons. BC is an attractive target for glucose CEST MRI because, in addition to the typical systemic administration, glucose might also be directly applied into the bladder to reduce toxicity-related complications. As a first stage of the development of a contrast-specific BC imaging technique we have studied glucose uptake by bladder epithelial cells and have observed that glucose is, indeed, consumed by BC cells with higher intensity than by non-transformed urothelial cells. This effect might be partly explained by increased expression of glucose transporters GLUT1 and GLUT3 in transformed cells as compared to normal urothelium. We also detected higher lactate production by BC cells which is another cancer-specific manifestation of the Warburg effect. In addition, we have observed other metabolic alterations in BC cells as compared to non-transformed cells: in particular, increased pyruvate synthesis. When glucose was substituted by glutamine in culture media, preferential uptake of glutamine by BC cells was observed. The preferential

  11. Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer

    PubMed Central

    Palmer, Scott; Litvinova, Karina; Dunaev, Andrey; Fleming, Stewart; McGloin, David; Nabi, Ghulam

    2016-01-01

    Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. PMID:27446646

  12. Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer.

    PubMed

    Palmer, Scott; Litvinova, Karina; Dunaev, Andrey; Fleming, Stewart; McGloin, David; Nabi, Ghulam

    2016-04-01

    Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. PMID:27446646

  13. HAL fluorescence cystoscopy: towards a new paradigm in bladder cancer management

    NASA Astrophysics Data System (ADS)

    Jichlinski, Patrice

    2009-06-01

    Hexaminolevulinate fluorescence cystoscopy by the addition of a specific tissue fluorophore enhances the contrast between benign and malignant epithelial (urothelial) cells in the bladder. Improved detection of flat and papillary tumors as confirmed in recent phase III clinical trials allows the urologist to obtain a precise information on the disease extent at the whole surface of the bladder wall. With gaining experience, management of non muscle invasive bladder cancer improves in readiness and accuracy.

  14. Protein interactome of muscle invasive bladder cancer.

    PubMed

    Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P; Mischak, Harald; Jankowski, Vera

    2015-01-01

    Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

  15. Intravesical Treatments of Bladder Cancer: Review

    PubMed Central

    Shen, Zancong; Shen, Tong; Wientjes, M. Guillaume; O’Donnell, Michael A.

    2008-01-01

    For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy. PMID:18369709

  16. Cytochrome P4501A2 phenotype and bladder cancer risk: The Shanghai bladder cancer study.

    PubMed

    Tao, Li; Xiang, Yong-Bing; Chan, Kenneth K; Wang, Renwei; Gao, Yu-Tang; Yu, Mimi C; Yuan, Jian-Min

    2012-03-01

    Cytochrome P450 1A2 (CYP1A2) is hypothesized to catalyze the activation of arylamines, known human bladder carcinogens present in cigarette smoke. The relationship between CYP1A2 phenotype and bladder cancer risk was examined in a case-control study involving 519 patients and 514 controls in Shanghai, China. Both CYP1A2 and N-acetyltransferase 2 (NAT2) phenotypic status were determined by a caffeine-based urinary assay. Our study showed that among smokers at urine collection, patients with bladder cancer had statistically significantly higher CYP1A2 phenotype scores compared to control subjects (p = 0.001). The odds ratios (95% confidence intervals) of bladder cancer for the second, third and fourth quartiles of the CYP1A2 score were 1.31 (0.53-3.28), 2.04 (0.90-4.60) and 2.82 (1.32-6.05), respectively, relative to the lowest quartile (p for trend = 0.003). NAT2 slow acetylation phenotype was associated with a statistically significant 40% increased risk of bladder cancer, and the relationship was independent of subjects' smoking status. Subjects possessing the NAT2 slow acetylation phenotype and the highest tertile of CYP1A2 scores showed the highest risk for bladder cancer. Their odds ratios (95% confidence intervals) was 2.13 (1.24-3.68) relative to their counterparts possessing the NAT2 rapid acetylation phenotype and the lowest tertile of CYP1A2 scores. The findings of our study demonstrate that CYP1A2 phenotype may be an important contributing factor in the development of smoking-related bladder cancer in humans. PMID:21480221

  17. [The biochemical carcinogenesis of selected heavy metals in bladder cancer].

    PubMed

    Rorbach-Dolata, Anna; Marchewka, Zofia; Piwowar, Agnieszka

    2015-01-01

    Bladder cancer takes the second place in the classification of morbidity of urinary system cancers. Many chemical factors take part in cancerogenesis. It is suggested that exposure to heavy metals such as arsenic, chromium, nickel and cadmium as well as its metabolites may trigger the bladder cancer through inducing excessive reactive oxygen species production and oxidative stress formation which are responsible for DNA damage. In patients with bladder cancer is observed the disorder of processes regulated by p-53, including apoptosis. There are many patients with bladder cancer with confirmed absence of retinoblastoma protein, which is responsible of holding on the process of coming up the cells with mutation into synthesis, where the replication process undergoes. It is mentioned that excessive expression of proto-oncogenes may also cause the bladder cancer. The article concerns biochemical effects of exposure to chosen heavy metals and their potential role in bladder cancer progression. PMID:26689010

  18. Epigenetic silencing of S100A2 in bladder and head and neck cancers

    PubMed Central

    Lee, Juna; Wysocki, Piotr T.; Topaloglu, Ozlem; Maldonado, Leonel; Brait, Mariana; Begum, Shahnaz; Moon, David; Kim, Myoung Sook; Califano, Joseph A.; Sidransky, David; Hoque, Mohammad O.; Moon, Chulso

    2015-01-01

    S100A2, a member of the S100 protein family, is known to be downregulated in a number of human cancers, leading to its designation as a potential tumor suppressor gene. Here, we investigated the expression and methylation status of S100A2 in head&neck and bladder cancer. Reduced mRNA and protein expression was observed in 8 head&neck and bladder cancer cell lines. To explore the mechanism responsible for the downregulation of S100A2, we treated six cell lines with 5-aza-2′-deoxycytidine. We found S100A2 is silenced in association with aberrant promoter-region methylation and its expression is restored with 5-aza-2′-deoxycytidine treatment. Of 31 primary head&neck cancer cases and 31 bladder cancer cases, promoter methylation was detected in 90% and 80% of cases, respectively. Interestingly, only 1/9 of normal head&neck tissues and 2/6 of normal bladder tissues showed promoter methylation. S100A2 promoter methylation can be detected in urine and is more frequent in bladder cancer patients than in healthy subjects (96% vs 48% respectively). Moreover, increased methylation of S100A2 is linked to the progression of the tumor in bladder cancer (p<0.01). Together, this data shows that methylation-associated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer. PMID:26097874

  19. Electrochemical immunosensor for detecting typical bladder cancer biomarker based on reduced graphene oxide-tetraethylene pentamine and trimetallic AuPdPt nanoparticles.

    PubMed

    Ma, Hongmin; Zhang, Xiaoyue; Li, Xiaojian; Li, Rongxia; Du, Bin; Wei, Qin

    2015-10-01

    A highly sensitive electrochemical immunosensor for detection of typical bladder cancer biomarker-nuclear matrix protein 22 (NMP22) was developed by using reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) and trimetallic AuPdPt nanoparticles (NPs). rGO-TEPA was used as the ideal material for signal amplification and AuPdPt NPs immobilization due to its excellent conductivity and large surface area. An effective platform was constructed for antibodies anchoring by using AuPdPt NPs, which kept the antibodies' high stability and bioactivity. Moreover, AuPdPt NPs could accelerate the electron transfer and enhance the signal response, which assisted by the synergistic effect of the three different metals (Au, Pd and Pt). The proposed immunosensor showed satisfied performance such as simple fabrication, low detection limits (0.01 U/mL), wide linear range (from 0.040 to 20 U/mL), short analysis time (2 min), high stability and selectivity in the detection of NMP22. Furthermore, the proposed immunosensor was employed to test real urine samples with satisfactory results. PMID:26078131

  20. Lymphadenectomy in Management of Invasive Bladder Cancer

    PubMed Central

    Youssef, Ramy F.; Raj, Ganesh V.

    2011-01-01

    Radical cystectomy with pelvic lymphadenectomy represents the gold standard for treatment of muscle-invasive bladder cancer. Extent of the lymph node dissection and lymph node involvement during radical cystectomy are the most powerful prognostic factors associated with poor oncological outcome. However, the optimal boundaries of the lymph node dissection during a radical cystectomy are controversial. The published literature based mostly on retrospective studies suggests that increasing the number of nodes excised may have therapeutic and diagnostic benefits without significantly increasing the surgical morbidity. These conclusions are, however, influenced by selection and surgeon biases, inconsistencies in the quality of the surgery, and node count variability. In this paper, we establish the current understanding about the utility of lymphadenectomy during a radical cystectomy for muscle-invasive bladder cancer. PMID:22312522

  1. Paraneoplastic retinopathy associated with occult bladder cancer.

    PubMed

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-03-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  2. Paraneoplastic retinopathy associated with occult bladder cancer

    PubMed Central

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-01-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  3. Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy

    ClinicalTrials.gov

    2014-12-22

    Bladder Adenocarcinoma; Bladder Squamous Cell Carcinoma; Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Bladder Cancer; Stage II Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer

  4. Dietary factors associated with bladder cancer.

    PubMed

    Piyathilake, Chandrika

    2016-06-01

    It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk. PMID:27326403

  5. Dietary factors associated with bladder cancer

    PubMed Central

    2016-01-01

    It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk. PMID:27326403

  6. p300 mediates cellular resistance to doxorubicin in bladder cancer.

    PubMed

    Takeuchi, Ario; Shiota, Masaki; Tatsugami, Katsunori; Yokomizo, Akira; Tanaka, Shingo; Kuroiwa, Kentaro; Eto, Masatoshi; Naito, Seiji

    2012-01-01

    Bladder cancer is one of the most common urogenital malignancies. At the non-invasive stage, bladder cancer can be completely resected transurethrally. However, 70% of patients experience intravesical tumor recurrence within 5 years. Patients with advanced bladder cancer frequently receive a chemotherapy regimen containing doxorubicin. However, doxorubicin resistance is a major obstacle to cancer chemotherapy. Previously, we reported that the histone acetyltransferase p300/CBP-associated factor is involved in doxorubicin resistance in bladder cancer. However, the role of another histone acetyltransferase, p300, in bladder cancer resistance to doxorubicin remains unclear. In this study, we investigated the molecular mechanism of doxorubicin resistance in bladder cancer with regard to p300. The result showed that p300 expression was reduced in doxorubicin-resistant bladder cancer cells and in response to doxorubicin exposure. Furthermore, p300 suppression rendered bladder cancer cells resistant to doxorubicin. Taken together, the results from this study indicate that p300 may be a promising molecular therapeutic target through the modulation of cellular sensitivity to doxorubicin in bladder cancer. PMID:21935574

  7. Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

    PubMed

    Zhong, Jianhua; Chen, Yan; Liao, Xinhui; Li, Jiaqiang; Wang, Han; Wu, Chenglong; Zou, Xiaowen; Yang, Gang; Shi, Jing; Luo, Liya; Liu, Litao; Deng, Jianping; Tang, Aifa

    2016-06-01

    Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer. PMID:26695143

  8. Well Water a Suspected Cause of Bladder Cancer in New England

    MedlinePlus

    ... Water a Suspected Cause of Bladder Cancer in New England Researchers believe arsenic exposure might contribute to ... elevated bladder cancer risk among people in three New England states, a new study suggests. Bladder cancer ...

  9. Discrimination of healthy and cancer cells of the bladder by metabolic state, based on autofluorescence

    NASA Astrophysics Data System (ADS)

    Palmer, S.; Litvinova, Karina; Rafailov, E. U.; Nabi, G.

    2015-02-01

    Bladder cancer is among the most common cancers worldwide (4th in men). It is responsible for high patient morbidity and displays rapid recurrence and progression. Lack of sensitivity of gold standard techniques (white light cystoscopy, voided urine cytology) means many early treatable cases are missed. The result is a large number of advanced cases of bladder cancer which require extensive treatment and monitoring. For this reason, bladder cancer is the single most expensive cancer to treat on a per patient basis. In recent years, autofluorescence spectroscopy has begun to shed light into disease research. Of particular interest in cancer research are the fluorescent metabolic cofactors NADH and FAD. Early in tumour development, cancer cells often undergo a metabolic shift (the Warburg effect) resulting in increased NADH. The ratio of NADH to FAD ("redox ratio") can therefore be used as an indicator of the metabolic status of cells. Redox ratio measurements have been used to differentiate between healthy and cancer breast cells and to monitor cellular responses to therapies. Here, we have demonstrated, using healthy and bladder cancer cell lines, a statistically significant difference in the redox ratio of bladder cancer cells, indicative of a metabolic shift. To do this we customised a standard flow cytometer to excite and record fluorescence specifically from NADH and FAD, along with a method for automatically calculating the redox ratio of individual cells within large populations. These results could inform the design of novel probes and screening systems for the early detection of bladder cancer.

  10. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2016-05-06

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

  11. Proteomics Analysis of Bladder Cancer Exosomes*

    PubMed Central

    Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

    2010-01-01

    Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the

  12. PET/CT and MRI in Bladder Cancer

    PubMed Central

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L

    2013-01-01

    Bladder Cancer (BCa) is the most common malignancy arising from the urinary tract. One of the mainstays of diagnosis, staging, and therapeutic decision-making for BCa is accurate and appropriate imaging. The ability to identify metastatic disease preoperatively is of utmost importance in determining treatment. Advances in standard cross sectional imaging techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have improved imaging of bladder cancer. Over the last decade, 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) in combination with CT (18F-FDG PET/CT) has become an important non-invasive imaging modality for the preoperative staging of various malignancies. 18F-FDG PET/CT is useful for detection of metastatic disease in BCa, but the ability to detect primary bladder wall lesions remains to be elucidated. To overcome the problem with urinary excretion of 18F-FDG, new PET tracers are being tested. MRI is an accurate technique for the local staging of BCa due to its superior spatial and contrast resolution. Anatomical MRI has a modest utility in NM-staging of BCa. However, incorporation of functional MR techniques, such as diffusion weighted MRI can improve the results for lesion detection and staging and multi-parametric MRI`s role is yet to be explored widely. The aim of this review is to present the recent advances in PET/CT and MRI in BCa, with particular focus on improvements in staging. PMID:23471167

  13. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  14. Bladder Cancer Patient Advocacy: A Global Perspective

    PubMed Central

    Quale, Diane Zipursky; Bangs, Rick; Smith, Monica; Guttman, David; Northam, Tammy; Winterbottom, Andrew; Necchi, Andrea; Fiorini, Edoardo; Demkiw, Stephanie

    2015-01-01

    Abstract Over the past 20 years, cancer patient advocacy groups have demonstrated that patient engagement in cancer care is essential to improving patient quality of life and outcomes. Bladder cancer patient advocacy only began 10 years ago in the United States, but is now expanding around the globe with non-profit organizations established in Canada, the United Kingdom and Italy, and efforts underway in Australia. These organizations, at different levels of maturity, are raising awareness of bladder cancer and providing essential information and resources to bladder cancer patients and their families. The patient advocacy organizations are also helping to advance research efforts by funding research proposals and facilitating research collaborations. Strong partnerships between these patient advocates and the bladder cancer medical community are essential to ensuringsustainability for these advocacy organizations, increasing funding to support advances in bladder cancer treatment, and improving patient outcomes. PMID:27398397

  15. Incidental Diagnosis of Bladder Cancer in a 17-year-old Patient.

    PubMed

    Facio, Fernando Nestor; Facio, Maria Fernanda W; Spessoto, Luis Cesar F; Gatti, Marcio; Ferraz Arruda, Pedro F; Ferraz Arruda, Jose G; Gabriotti, Luis Francisco B; Polotto, Pedro Paulo Silva L

    2015-07-01

    Bladder cancer is the fourth most common type of cancer among males and the ninth most common cause of cancer death. Bladder cancer can occur at any age. This paper reports the incidental diagnosis of bladder cancer in a 17-year-old female patient. Data on bladder cancer at this age are uncommon in the literature. PMID:26793515

  16. Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis

    PubMed Central

    Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

    2015-01-01

    Background It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. Methods The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. Results The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11–1.55). Conclusion The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer. PMID:26715854

  17. Biomarkers for non-muscle invasive bladder cancer: Current tests and future promise

    PubMed Central

    Darwiche, Fadi; Parekh, Dipen J.; Gonzalgo, Mark L.

    2015-01-01

    The search continues for optimal markers that can be utilized to improve bladder cancer detection and to predict disease recurrence. Although no single marker has yet replaced the need to perform cystoscopy and urine cytology, many tests have been evaluated and are being developed. In the future, these promising markers may be incorporated into standard practice to address the challenge of screening in addition to long-term surveillance of patients who have or are at risk for developing bladder cancer. PMID:26604437

  18. Pathological diagnosis of bladder cancer by image analysis of hypericin induced fluorescence cystoscopic images

    NASA Astrophysics Data System (ADS)

    Kah, James C. Y.; Olivo, Malini C.; Lau, Weber K. O.; Sheppard, Colin J. R.

    2005-08-01

    Photodynamic diagnosis of bladder carcinoma based on hypericin fluorescence cystoscopy has shown to have a higher degree of sensitivity for the detection of flat bladder carcinoma compared to white light cystoscopy. The potential of the photosensitizer hypericin-induced fluorescence in performing non-invasive optical biopsy to grade bladder cancer in vivo using fluorescence cystoscopic image analysis without surgical resection for tissue biopsy is investigated in this study. The correlation between tissue fluorescence and histopathology of diseased tissue was explored and a diagnostic algorithm based on fluorescence image analysis was developed to classify the bladder cancer without surgical resection for tissue biopsy. Preliminary results suggest a correlation between tissue fluorescence and bladder cancer grade. By combining both the red-to-blue and red-to-green intensity ratios into a 2D scatter plot yields an average sensitivity and specificity of around 70% and 85% respectively for pathological cancer grading of the three different grades of bladder cancer. Therefore, the diagnostic algorithm based on colorimetric intensity ratio analysis of hypericin fluorescence cystoscopic images developed in this preliminary study shows promising potential to optically diagnose and grade bladder cancer in vivo.

  19. Marker evaluation of human breast and bladder cancers

    SciTech Connect

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. )

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  20. A Case of Multiple Myeloma Following Bladder Cancer

    PubMed Central

    Shafi, Hamid; Vakili Sadeghi, Mohsen; Ghorbani, Hosein; Sharbatdaran, Majid

    2016-01-01

    Second primary malignancy following multiple myeloma (MM) was reported several years ago. There are also rare reports of cases with synchronous MM and other malignancies. To our knowledge, only one case of MM following bladder cancer has been reported in the literature. Here, we report the second case occurred three months after diagnosis of bladder cancer. PMID:27252812

  1. [Bladder cancer: interpretation of international recommendations].

    PubMed

    Rivière, Adrien; Ploussard, Guillaume; Desgrandchamps, François

    2014-12-01

    European and North-American onco-urology guidelines represent a thorough synthesis of published scientific data regarding the diagnosis and the therapeutic management of bladder cancer. Even though they have the same bases, their goal is very different. North American recommendations exhaustively present the whole set of available diagnostic and therapeutic options; they apparently aim at defining and legitimizing them all. European recommendations offer a precise stratification of patients according to their prognosis and therefore propose a specific and oriented management/care. They are more guiding and favor a homogenization of the various practices. PMID:25668833

  2. Bladder Cancer Immunotherapy: BCG and Beyond

    PubMed Central

    Askeland, Eric J.; Newton, Mark R.; O'Donnell, Michael A.; Luo, Yi

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10. PMID:22778725

  3. Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Al-Muslet, Nafie A.; Ali, Essam E.

    2012-03-01

    Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

  4. Nanotechnology in bladder cancer: current state of development and clinical practice

    PubMed Central

    Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

    2015-01-01

    Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

  5. Optimal management of asymptomatic workers at high risk of bladder cancer.

    PubMed

    Schulte, P A; Ringen, K; Hemstreet, G P

    1986-01-01

    Many cohorts of industrial workers at increased risk of occupationally induced bladder cancer are still in the preclinical disease stage. A large proportion of workers in these populations have been exposed to aromatic amines, but have not yet experienced the average latent period for bladder cancer. A need exists for definition of what constitutes optimal management for asymptomatic workers in these cohorts. Promising advances in the epidemiology, pathology, detection, and treatment of bladder cancer pressure for a reassessment of current practices and the application of the most current scientific knowledge. Some of these apparent advances, however, have not yet been rigorously evaluated. The time has come to evaluate these advances so that their application can occur while high risk cohorts are still amenable to and likely to benefit from intervention. This commentary calls for such an evaluation leading to a comprehensive approach to managing cohorts at high risk of bladder cancer. PMID:3950777

  6. Radical cystectomy for the treatment of T1 bladder cancer: the Canadian Bladder Cancer Network experience

    PubMed Central

    Chalasani, Venu; Kassouf, Wassim; Chin, Joseph L.; Fradet, Yves; Aprikian, Armen G.; Fairey, Adrian S.; Estey, Eric; Lacombe, Louis; Rendon, Ricardo; Bell, David; Cagiannos, Ilias; Drachenberg, Darrell; Lattouf, Jean-Baptiste; Izawa, Jonathan I.

    2011-01-01

    Background: Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system. Methods: We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis. Results: The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival. Interpretation: These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies. PMID:21470529

  7. The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer

    PubMed Central

    Li, Fei; Yu, Zhe; Chen, Pengliang; Lin, Guangzheng; Li, Tieqiu; Hou, Lina; Du, Yuejun; Tan, Wanlong

    2016-01-01

    Improving the early detection rate and prediction of bladder cancer remains a great challenge in management of this disease. To examine the value of urinary orosomucoid 1 (ORM1) for the early detection and surveillance of bladder cancer, two-dimensional differential gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOFMS) were applied to identify the differently expressed proteins in urine between bladder cancer and healthy controls. Thirteen different proteins including ORM1 were identified. After verification by western blotting, the ORM1 expressions were quantified in 186 urine samples by enzyme-linked immunosorbent assay (ELISA) correcting for creatinine expression. ELISA quantification showed the urinary ORM1-Cr was found to be higher in bladder cancer patients compared to controls and benign cases (7172.23±3049.67 versus 2243.16±969.01, 2493.48±830.37 ng/ml, respectively, P<0.0001). Furthermore, the pearson correlation analysis indicated that urinary ORM1 had high positive correlation with the pathology classification of bladder cancer. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off value for early diagnosis of bladder cancer, and rendered an optimum cut-off value of 3912.97 ng/mg corresponding to 91.96% sensitivity and 94.34% specificity. Moreover, a cut-off value with 7351.28 ng/mg was utilized to distinguish infiltrating urothelial carcinoma from bladder cancer patients corresponding to 91.89% sensitivity and 90.67% specificity. In conclusion, our findings suggested the elevated urinary ORM1 could be a useful biomarker for bladder cancer. Further research is warranted to elucidate the pathogenic mechanisms of elevated ORM1. PMID:27186407

  8. Bladder Cancer Associated Gene Expression Signatures Identified by Profiling of Exfoliated Urothelia

    PubMed Central

    Rosser, Charles J.; Liu, Li; Sun, Yijun; Villicana, Patrick; McCullers, Molly; Porvasnik, Stacy; Young, Paul R.; Parker, Alexander S.; Goodison, Steve

    2009-01-01

    Bladder cancer is the fifth most commonly diagnosed malignancy in the United States and one of the most prevalent worldwide. It harbors a probability of recurrence of >50%, thus rigorous, long-term surveillance of patients is advocated. Flexible cystoscopy coupled with voided urine cytology (VUC) is the primary diagnostic approach, but cystoscopy is an uncomfortable, invasive procedure and the sensitivity of VUC is poor in all but high-grade tumors. Thus, improvements in non-invasive urinalysis assessment strategies would benefit patients. We applied gene expression microarray analysis to exfoliated urothelia recovered from bladder washes obtained prospectively from 46 patients with subsequently confirmed presence or absence of bladder cancer. Data from microarrays containing 56,000 targets was subjected to a panel of statistical analyses to identify bladder cancer-associated gene signatures. Hierarchical clustering and supervised learning algorithms were used to classify samples on the basis of tumor burden. A differentially expressed geneset of 319 gene probes was associated with the presence of bladder cancer (P<0.01), and visualization of protein interaction networks revealed VEGF and AGT as pivotal factors in tumor cells. Supervised machine learning and a cross-validation approach were used to build a 14-gene molecular classifier that was able to classify patients with and without bladder cancer with an overall accuracy of 76%. Our results show that it is possible to achieve the detection of bladder cancer using molecular signatures present in exfoliated tumor urothelia. Further investigation and validation of the cancer-associated profiles may reveal important biomarkers for the non-invasive detection and surveillance of bladder cancer. PMID:19190164

  9. Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

    PubMed Central

    2011-01-01

    Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors. PMID:21507255

  10. Molecular substratification of bladder cancer: moving towards individualized patient management

    PubMed Central

    Mitra, Anirban P.

    2016-01-01

    Despite advances in surgical techniques, perioperative therapies and postoperative management, outcomes for patients with bladder cancer have largely remained unchanged. Current management of bladder cancer still relies on pathologic staging that does not always reflect the risk for an individual patient. Studies assessing molecular alterations in individual tumors are offering insights into the myriad of cellular pathways that are deregulated in bladder tumorigenesis and progression. Alterations in pathways involved in cell-cycle regulation, apoptosis, cell signaling, angiogenesis and tumor-cell invasion have been shown to influence disease behavior. High-throughput assays are now allowing multiplexed assessment of biomarker alterations, thereby enabling characterization of novel molecular subtypes of bladder cancer. Such approaches have also been used for discovery and validation of robust prognostic molecular signatures. The future of bladder cancer management will rely on the use of validated multimarker panels for risk stratification, optimal surgical management, and theranostic strategies to identify and target specific alterations in individual tumors. PMID:27247631

  11. Occupation, smoking, and alcohol in the epidemiology of bladder cancer

    SciTech Connect

    Brownson, R.C.; Chang, J.C.; Davis, J.R.

    1987-10-01

    We conducted a case-control study to evaluate the effects of occupation, smoking, and alcohol consumption on bladder cancer risk. A total of 823 male cases and 2,469 age-matched controls were identified through the Missouri Cancer Registry. Relative risk estimates of 2.0 or greater were observed for janitors and cleaners, mechanics, miners, and printers. Current cigarette smoking was associated with a two-fold excess risk of bladder cancer, whereas alcohol consumption showed no association with bladder cancer risk.

  12. Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

    PubMed

    Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

    2016-08-01

    The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. PMID:27196763

  13. Clinical pitfalls in diagnosis of nonmuscle-invasive bladder cancer.

    PubMed

    Serretta, Vincenzo; Scalici Gesolfo, Cristina

    2015-10-01

    Current global economic crisis imposes healthcare system to reduce unnecessary investigations and increase early detection of tumors, to decrease the costs of an advanced disease. Several diagnostic pitfalls may occur dealing with bladder cancer (BC), particularly in nonmuscle-invasive (NMIBC) one. Hematuria, the commonest sign in NMIBC, is often underestimated. Urinary cytology is highly specific for high-grade tumors, but has a low sensitivity for low-grade BC, is operator dependent, and not always obtainable in clinical practice. Numerous urinary tests are available to ameliorate the accuracy of cytology, but none of them is routinly used in urological practice. Ultrasound could hardly detect a small bladder tumor, especially if located in the bladder neck or in the anterior wall. Computed tomography (CT) is widely adopted as an alternative to conventional urography, but its usefulness in patients with hematuria is still debated. MRI has a higher accuracy than CT for staging BC and evaluate the bladder-wall invasion. A negative cystoscopy cannot exclude Tis and should be accompanied by urinary cytology in patients with suspected Tis or high-risk NMIBC; however, new techniques such as narrow band imaging (NBI) and photodynamic (PDD) increase the detection rate of BC and flat lesions. Nearly half of all diagnostic resections present omission of muscle in the specimen or its mention in the pathology report, which is associated with an increased mortality. An adequate muscle sampling during endoscopic resection is mandatory, particularly in patients with high-grade disease. Recognition of pitfalls in diagnosis and management of BC represents the first step for a correct approach. PMID:26481718

  14. Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor Growth in Mouse Bladders.

    PubMed

    Lin, Mei-Yi; Lee, Ying-Ray; Chiang, Su-Yin; Li, Yi-Zhen; Chen, Yueh-Sheng; Hsu, Cheng-Da; Liu, Yi-Wen

    2013-01-01

    Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2 mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer. PMID:24282433

  15. Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.

    PubMed

    Pan, Ying; Volkmer, Jens-Peter; Mach, Kathleen E; Rouse, Robert V; Liu, Jen-Jane; Sahoo, Debashis; Chang, Timothy C; Metzner, Thomas J; Kang, Lei; van de Rijn, Matt; Skinner, Eila C; Gambhir, Sanjiv S; Weissman, Irving L; Liao, Joseph C

    2014-10-29

    A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer. PMID:25355698

  16. A case–control study on the association between bladder cancer and prior bladder calculus

    PubMed Central

    2013-01-01

    Background Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. Methods This case–control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Results Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. Conclusions These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening. PMID:23497224

  17. Metallothionein isoform 3 as a potential biomarker for human bladder cancer.

    PubMed Central

    Sens, M A; Somji, S; Lamm, D L; Garrett, S H; Slovinsky, F; Todd, J H; Sens, D A

    2000-01-01

    The goal of the present study was to determine if the expression of metallothionein isoform 3 (MT-3) might serve as a biomarker for human bladder cancer. To accomplish this goal, we defined the localization and expression of MT-3 protein and mRNA using fresh and archival biopsy specimens obtained from patients undergoing differential diagnosis for a variety of bladder disorders. We used immunohistochemistry, immunoblot, and RT-PCR analysis to define the localization and expression of MT-3 protein and mRNA. Immunohistochemical analysis disclosed no immunoreactivity for MT-3 in normal bladder cells. The absence of MT-3 expression in the normal bladder was further confirmed by demonstrating that MT-3 mRNA could not be detected using reverse transcriptase-polymerase chain reaction (RT-PCR) or MT-3 protein using immunoblot. Immunohistochemistry also disclosed no immunoreactivity for MT-3 in archival biopsy specimens from patients with interstitial cystitis and related disorders. Immunohistochemical analysis demonstrated that MT-3 was expressed in carcinoma in situ (CIS), high-grade bladder cancer, low-grade bladder cancer, and dysplastic lesions. MT-3 immunostaining was intense in both CIS and high-grade bladder cancer, and low to moderate in low-grade bladder cancer and dysplastic lesions. We determined MT-3 mRNA expression in a subset of these bladder cancer specimens; expression was elevated as compared to that of the housekeeping gene, ss-actin. The cDNA from the RT-PCR reaction primed for MT-3 contained a FokI restriction site, a site unique for MT-3 as compared to other MT family members. In conclusion, this study demonstrates that MT-3 is up-regulated in human bladder cancer and that this up-regulation increases with increasing tumor grade. The finding that MT-3 expression is minimal in normal bladder suggests that MT-3 might be developed into an effective biomarker for bladder cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10811567

  18. Bladder cancer arising in a spina bifida patient.

    PubMed

    Game, X; Villers, A; Malavaud, B; Sarramon, J

    1999-11-01

    We report the case of a 52-year-old patient with spina bifida, neurologic bladder, and a history of recurrent urinary tract infections (UTIs) in whom a bladder cancer was incidentally discovered. Cytology, cystoscopy, and cystography showed nonspecific, extensive inflammatory lesions. Cystography demonstrated a complex of diverticulae and cellules. Pathologic examination of a diverticulectomy specimen revealed a grade III pT3b transitional and squamous cell carcinoma. Because of the similar disease causation (recurrent UTIs, stones, and indwelling catheterization), we suggest extension of the guidelines proposed for patients with spinal cord injuries (ie, annual serial bladder biopsies) to patients with nontraumatic neurogenic bladder. PMID:10754152

  19. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    PubMed Central

    Ho, Melissa E.; Quek, Sue-Ing; True, Lawrence D.; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R.; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J.; Gao, Yuqian; Liu, Alvin Y.

    2016-01-01

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

  20. Magnetic Fluid Hyperthermia for Bladder Cancer: A Preclinical Dosimetry Study

    PubMed Central

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea D.; Etienne, Wiguins; Ashcraft, Kathleen A.; McNerny, Katie L.; Mashal, Alireza; Nouls, John; Maccarini, Paolo F.; Beyer, Wayne F.; Inman, Brant; Dewhirst, Mark W.

    2014-01-01

    Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:24050253

  1. Immune checkpoint blockade therapy for bladder cancer treatment.

    PubMed

    Kim, Jayoung

    2016-06-01

    Bladder cancer remains the most immunogenic and expensive malignant tumor in the United States today. As the 4th leading cause of death from cancer in United States, Immunotherapy blocking immune checkpoints have been recently been applied to many aggressive cancers and changed interventions of urological cancers including advanced bladder cancer. The applied inhibition of PD-1-PD-L1 interactions can restore antitumor T-cell activity and enhance the cellular immune attack on antigens. The overall goals of this short review article are to introduce current cancer immunotherapy and immune checkpoint inhibitors, and to provide new insight into the underlying mechanisms that block immune checkpoints in tumor microenvironment. Furthermore, this review will address the preclinical and clinical trials to determine whether bladder cancer patients could benefit from this new cancer therapy in near future. PMID:27326412

  2. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  3. Current animal models of bladder cancer: Awareness of translatability (Review)

    PubMed Central

    DING, JIE; XU, DING; PAN, CHUNWU; YE, MIN; KANG, JIAN; BAI, QIANG; QI, JUN

    2014-01-01

    Experimental animal models are crucial in the study of biological behavior and pathological development of cancer, and evaluation of the efficacy of novel therapeutic or preventive agents. A variety of animal models that recapitulate human urothelial cell carcinoma have thus far been established and described, while models generated by novel techniques are emerging. At present a number of reviews on animal models of bladder cancer comprise the introduction of one type of method, as opposed to commenting on and comparing all classifications, with the merits of a certain method being explicit but the shortcomings not fully clarified. Thus the aim of the present study was to provide a summary of the currently available animal models of bladder cancer including transplantable (which could be divided into xenogeneic or syngeneic, heterotopic or orthotopic), carcinogen-induced and genetically engineered models in order to introduce their materials and methods and compare their merits as well as focus on the weaknesses, difficulties in operation, associated problems and translational potential of the respective models. Findings of these models would provide information for authors and clinicians to select an appropriate model or to judge relevant preclinical study findings. Pertinent detection methods are therefore briefly introduced and compared. PMID:25120584

  4. TCGA bladder cancer study reveals potential drug targets

    Cancer.gov

    Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

  5. Genetic variant as a marker for bladder cancer therapy

    Cancer.gov

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  6. The Value of Extended Nursing Services on Patients with Bladder Cancer after Endoscopic Bladder Resection

    PubMed Central

    LI, Xueqin; ZHANG, Yan; GAO, Hang; SUN, Xiujuan; LV, Weifeng; XU, Guangyu

    2016-01-01

    Background: In this study, specific measures of extended nursing services and its values on patients with bladder cancer after endoscopic bladder electrosection were examined. Methods: Sixty-six patients diagnosed with bladder cancer in Laiwu People’s Hospital(NO. 001, Xueyehu Street, Changshao Road, Laiwu, Shandong, China) between February 2012 and February 2014, and underwent endoscopic bladder electrosection were enrolled in the study. Patients were randomly allocated into the control group (n=30 cases) or the observation group (n=36 cases) according to the order of hospitalization. Conventional nursing measures were given to the control group while extended nursing service measures were given to the observation group, and the differences of nursing effect were compared. Results: The occurrence rate of postoperative complications within the hospital for the observation group was significantly lower than that of the control group, as was the length of hospital stay. The nursing service satisfaction was also significantly improved within the observation group. These differences were statistically significance (P<0.05). The anxiety and depression scores for the observation group were significantly lower than that of control group and these differences were also of statistical significance (P<0.05). The follow-up compliance after hospitalization for the observation group was significantly enhanced, quality of life scores were significantly improved, and both differences were of statistical significance (P<0.05). Conclusion: Extended nursing service improves the effect and long-term prognosis of patients with bladder cancer after undergoing endoscopic bladder electrosection. PMID:27057521

  7. Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

    PubMed Central

    Lin, Wei-Ching; Chen, Jeon-Hor

    2015-01-01

    Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

  8. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer

    PubMed Central

    McBeth, Lucien; Grabnar, Maria; Selman, Steven; Hinds, Terry D.

    2015-01-01

    Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. PMID:26347776

  9. Tumor markers of bladder cancer: the schistosomal bladder tumors versus non-schistosomal bladder tumors

    PubMed Central

    Abdulamir, Ahmed S; Hafidh, Rand R; Kadhim, Haider S; Abubakar, Fatimah

    2009-01-01

    Background The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT). Methods This study explored the role of p53, p16, bcl-2, ki-67, c-myc, Rb and EGFR, by using Immunohistochemistry assay, in 45 SBT and 39 NSBT patients in comparison with 16 schistosomal chronic cystitis (SC), 28 non-schistosomal chronic cystitis (NSC), and 20 normal control (CTL) subjects. The studied markers in SBT and NSBT were correlated with different clinicopathological criteria namely, tumor histopathology, grading, invasiveness, stage, and presentation of the disease. Results SBT was associated with high grade invasive squamous cell carcinoma (SCC) while NSBT was associated with lower grade less invasive transitional cell carcinoma (TCC). The expression of p53, bcl-2, c-myc, and EGFR was higher in SBT than in NSBT while Rb was higher in NSBT than in SBT. However, p16 and ki-67 were not different between SBT and NSBT. The profile of molecular markers in SC was similar to NSC except for EGFR which was higher in SC than in NSC. Both SC and NSC showed higher level of p53, bcl-2, ki-67, and EGFR than in CTL group while p16, Rb, and c-myc were not different. p53 was associated with high grade SCC in both SBT and NSBT. Bcl-2 was associated with high grade invasive tumors in SBT and NSBT. P16 was associated with low grade, late stage, and recurrent SBT and high grade, invasive, late stage, and recurrent NSBT. Rb was associated with SCC in SBT, invasive tumors in NSBT, and late stage and recurrent presentation in both SBT and NSBT. C-myc was associated with high grade, invasive, and late stage SBT and SCC, high grade, invasive, and late stage NSBT. EGFR was associated with invasive SCC in SBT and invasive, high grade, and late stage TCC in NSBT. ki-67 was associated with invasive SBT and high grade late stage NSBT. Conclusion SBT and NSBT showed distinct

  10. Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer.

    PubMed

    Yang, D L; Xin, M M; Wang, J S; Xu, H Y; Huo, Q; Tang, Z R; Wang, H F

    2015-01-01

    It is well known that chemokine receptors and their ligands play important roles in mediating the invasion and metastasis of malignant tumors. This aim of this study was to investigate the expression and clinical significance of chemokine receptor CXCR4 and its ligand CXCL12 in bladder tumor tissues. Cancerous and adjacent normal bladder tissues were collected from 42 patients. The expressions of CXCR4 and CXCL12 proteins were then detected by immunohistochemistry, and the expressions of CXCR4 and CXCL12 mRNAs were detected by RT-PCR. Bladder cancer tissues showed higher positive expressions of CXCR4 and CXCL12 than those in normal bladder mucosal tissues (z = 7.332, 6.758, P < 0.001). Positive expressions of CXCR4 and CXCL12 were related to the differentiation degree and invasive depth of cancer tissues (z = 2.598-4.594, P < 0.05), but not to patient gender or age (z = 0.273-0.554, P > 0.05). The expression of CXCR4 was positively correlated to CXCL12 expression in bladder cancer tissues (r = 0.661, P < 0.05). RT-PCR revealed that CXCR4 and CXCL12 mRNAs were not expressed in normal tissues. Moreover, with increased depth of invasion, CXCR4 and CXCL12 mRNA expressions gradually increased in bladder cancer tissues and showed significant intergroup differences (F = 56.642, 67.928, P < 0.01). Taken together, these results indicate that the chemokine receptor CXCR4 and its ligand CXCL12 play important roles in the occurrence and development of bladder cancer. PMID:26782415

  11. Novel non invasive diagnostic strategies in bladder cancer

    PubMed Central

    TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066

  12. Lung metastasis of ta bladder cancer: a case report and literature review.

    PubMed

    Sano, Takeshi; Hamada, Shinshichi; Haitani, Takao; Nakashima, Masakazu; Kajita, Yoichiro; Shichiri, Yasumasa

    2013-04-01

    A 66-year-old man with a history of multiple transurethral resections for recurrent bladder tumors, staged as Ta according to the International Union Against Cancer staging guidelines, presented with a complaint of dry cough. A round nodule with a diameter of 7.5 cm was detected in the lung by chest computed tomography, and a video-assisted thoracoscopic lobectomy was performed. Pulmonary metastasis of recurrent bladder cancer was diagnosed by immunohistochemistry staining for the urothelium-specific protein uroplakin Ia. Subsequently, 2 cycles of systemic chemotherapy were administered. Two and a half years after treatment, no recurrence of pulmonary lesions has been detected. A combination of complete resection of pulmonary lesions and systemic chemotherapy may result in a good prognosis for patients with non-muscle-invasive bladder cancer. PMID:23614067

  13. Molecular Subtypes of Non-muscle Invasive Bladder Cancer.

    PubMed

    Lerner, Seth P; Robertson, A Gordon

    2016-07-11

    In this issue of Cancer Cell, Hedegaard et al. report a comprehensive multi-center transcriptional analysis of non-muscle invasive urothelial bladder cancer. They describe three molecular subtypes similar to those seen in other cohorts, as well as a unique CIS signature associated with risk of progression to muscle invasive cancer. PMID:27411578

  14. Immune Response Following Photodynamic Therapy For Bladder Cancer

    NASA Astrophysics Data System (ADS)

    Raymond K.

    1989-06-01

    This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

  15. The role of microRNAs in bladder cancer.

    PubMed

    Enokida, Hideki; Yoshino, Hirofumi; Matsushita, Ryosuke; Nakagawa, Masayuki

    2016-06-01

    Bladder cancer (BC) is the fifth most common cancer worldwide and is associated with significant morbidity and mortality. The prognosis of muscle invasive BC is poor, and recurrence is common after radical surgery or chemotherapy. Therefore, new diagnostic methods and treatment modalities are critical. MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs have important roles in the regulation of genes involved in cancer development, progression, and metastasis. The availability of genomewide miRNA expression profiles by deep sequencing technology has facilitated rapid and precise identification of aberrant miRNA expression in BC. Indeed, several miRNAs that are either upregulated or downregulated have been shown to have associations with significant cancer pathways. Furthermore, many miRNAs, including those that can be detected in urine and blood, have been studied as potential noninvasive tumor markers for diagnostic and prognostic purposes. Here, we searched PubMed for publications describing the role of miRNAs in BC by using the keywords "bladder cancer" and "microRNA" on March 1, 2016. We found 374 papers and selected articles written in English in which the level of scientific detail and reporting were sufficient and in which novel findings were demonstrated. In this review, we summarize these studies from the point of view of miRNA-related molecular networks (specific miRNAs and their targets) and miRNAs as tumor markers in BC. We also discuss future directions of miRNA studies in the context of therapeutic modalities. PMID:27326409

  16. CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration

    PubMed Central

    Gong, Yanqing; Qiu, Wei; Ning, Xianghui; Yang, Xinyu; Liu, Libo; Wang, Zicheng; Lin, Jian; Li, Xuesong; Guo, Yinglu

    2015-01-01

    The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer. PMID:26312564

  17. The Promise of Novel Molecular Markers in Bladder Cancer

    PubMed Central

    Miremami, Jahan; Kyprianou, Natasha

    2014-01-01

    Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

  18. Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

    PubMed

    Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

    2016-04-01

    Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. PMID:26897070

  19. Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

    SciTech Connect

    Ma, Ning; Thanan, Raynoo; Kobayashi, Hatasu; Hammam, Olfat; Wishahi, Mohamed; Leithy, Tarek El; Hiraku, Yusuke; Amro, EL-Karef; Oikawa, Shinji; Ohnishi, Shiho; Murata, Mariko; Kawanishi, Shosuke

    2011-10-22

    Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.

  20. Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer.

    PubMed

    Yuan, Jian-Min; Chan, Kenneth K; Coetzee, Gerhard A; Castelao, J Esteban; Watson, Mary A; Bell, Douglas A; Wang, Renwei; Yu, Mimi C

    2008-07-01

    Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual's susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case-control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19-48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19-1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12-1.81) and 1.71 (1.25-2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12-3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

  1. An Orthotopic Bladder Cancer Model for Gene Delivery Studies

    PubMed Central

    Kasman, Laura; Voelkel-Johnson, Christina

    2013-01-01

    Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are needed. The tumor microenvironment can significantly influence tumor development and therapy response. It is therefore often desirable to grow tumor cells in the organ from which they originated. This protocol describes an orthotopic model of bladder cancer, in which MB49 murine bladder carcinoma cells are instilled into the bladder via catheterization. Successful tumor cell implantation in this model requires disruption of the protective glycosaminoglycan layer, which can be accomplished by physical or chemical means. In our protocol the bladder is treated with trypsin prior to cell instillation. Catheterization of the bladder can also be used to deliver therapeutics once the tumors are established. This protocol describes the delivery of an adenoviral construct that expresses a luciferase reporter gene. While our protocol has been optimized for short-term studies and focuses on gene delivery, the methodology of mouse bladder catheterization has broad applications. PMID:24326612

  2. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    PubMed

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. PMID:27080594

  3. Androgen activates β-catenin signaling in bladder cancer cells.

    PubMed

    Li, Yi; Zheng, Yichun; Izumi, Koji; Ishiguro, Hitoshi; Ye, Bo; Li, Faqian; Miyamoto, Hiroshi

    2013-06-01

    Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also been reported to correlate with bladder cancer progression and poor patients' outcomes. However, cross talk between AR and β-catenin pathways in bladder cancer remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression of β-catenin especially in aggressive tumors. There was a strong association between nuclear expressions of AR and β-catenin in bladder tumors (P=0.0215). Kaplan-Meier and log-rank tests further revealed that reduced membranous β-catenin expression (P=0.0276), nuclear β-catenin expression (P=0.0802), and co-expression of nuclear AR and β-catenin (P=0.0043) correlated with tumor progression after cystectomy. We then assessed the effects of androgen on β-catenin in AR-positive and AR-negative bladder cancer cell lines. A synthetic androgen R1881 increased the expression of an active form of β-catenin and its downstream target c-myc only in AR-positive lines. R1881 also enhanced the activity of β-catenin-mediated transcription, which was abolished by an AR antagonist hydroxyflutamide. Using western blotting and immunofluorescence, R1881 was found to induce nuclear translocation of β-catenin when co-localized with AR. Finally, co-immunoprecipitation revealed androgen-induced associations of AR with β-catenin or T-cell factor (TCF) in bladder cancer cells. Thus, it was likely that androgen was able to activate β-catenin signaling through the AR pathway in bladder cancer cells. Our results also suggest that activation of β-catenin signaling possibly via formation of AR/β-catenin/TCF complex contributes to the progression of bladder cancer, which may enhance the feasibility of androgen deprivation as a potential therapeutic approach. PMID:23447569

  4. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report

    PubMed Central

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    Patient: Male, 71 Final Diagnosis: Neuroendocrine cancer bladder Symptoms: Dysuria • haematuria Medication: — Clinical Procedure: Transurethral resection of the bladder tumor Specialty: Oncology Objective: Rare disease Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. Case Report: A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. Conclusions: A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder. PMID:27072610

  5. Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.

    PubMed

    Gupta, Sounak; Hau, Andrew M; Al-Ahmadie, Hikmat A; Harwalkar, Jyoti; Shoskes, Aaron C; Elson, Paul; Beach, Jordan R; Hussey, George S; Schiemann, William P; Egelhoff, Thomas T; Howe, Philip H; Hansel, Donna E

    2016-05-01

    Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β-induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. PMID:26988652

  6. Detection of Bladder CA by Microsatellite Analysis (MSA) — EDRN Public Portal

    Cancer.gov

    Goal 1: To determine sensitivity and specificity of microsatellite analysis (MSA) of urine sediment, using a panel of 15 microsatellite markers, in detecting bladder cancer in participants requiring cystoscopy. This technique will be compared to the diagnostic standard of cystoscopy, as well as to urine cytology. Goal 2: To determine the temporal performance characteristics of microsatellite analysis of urine sediment. Goal 3: To determine which of the 15 individual markers or combination of markers that make up the MSA test are most predictive of the presence of bladder cancer.

  7. Occupational risk of bladder cancer among Iranian male workers

    PubMed Central

    Aminian, Omid; Saburi, Amin; Mohseni, Hossein; Akbari, Hamed; Chavoshi, Farzaneh; Akbari, Hesam

    2014-01-01

    Background: Approximately 5-10% of human cancers are thought to be caused by occupational exposure to carcinogens. Compare to other cancers, bladder cancer is most strongly linked to occupational exposure to chemical toxins. This study has been performed to understand which occupations and exposures are related to bladder cancer in Iran. Materials and Methods: This study is a case-control study which is conducted on cases with bladder cancer (160 cases) diagnosed in Baharlou hospital in 2007-2009. One hundred sixty cases without any occupational exposure were considered as controls matched for demographic characteristics. Demographic data and characteristics of occupation were compared. Results: Mean age of cases and controls were 63.7 and 64 years, respectively (P = 0.841). History of urinary tract stone had significantly difference in two groups (P = 0.039). Occupations such as bus and truck driving, road and asphalt making, mechanics, working in refinery and Petrochemical, plastic, metal manufactory, welding, and pipeline founded a higher risk for bladder cancer rather than controls. Conclusion: Our findings on Iranian workers are concurrent and compatible with findings of previous reports about occupational and environmental risk factors of bladder cancer. Although our study population was PMID:24833825

  8. Optical coherence tomography in diagnostics of precancer and cancer of human bladder

    NASA Astrophysics Data System (ADS)

    Zagaynova, Elena V.; Streltsova, Olga S.; Gladkova, Natalia D.; Shakhova, Natalia M.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Snopova, Ludmila B.; Donchenko, Ekaterina V.

    2004-07-01

    Our goal was statistical assessment of the in vivo cystoscopic optical coherence tomography (OCT) ability to detect neoplasia in human urinary bladder. We analyzed major reasons of false positive and false negative image recognition results. Optical coherence tomography was performed to image the bladder during cystoscopy. The study enrolled 63 patients with suspicion for bladder cancer and scheduled for cystoscopy. The diagnosis was established by histopathology examination of a biopsy. Each biopsy site was examined by OCT. Benign conditions were diagnosed for 31 patients, and dysplasia or carcinoma were diagnosed for 32 patients. Six physicians blinded to all clinical data participated in the dichotomy recognition (malignant or benign) of the OCT images. 98% sensitivity and 72% specificity for the OCT recognition of dysplastic/malignant versus benign/reactive conditions of the bladder are demonstrated. Total error rate was 14.8%. The interobserver agreement multi-rater kappa coefficient is 0.80. The superficial and invasive bladder cancer and high-grade dysplasia were recognized with minimum error rate ranging from 0 to 3.3%. High sensitivity and good specificity of the OCT method in the diagnostics of bladder neoplasia makes OCT a promising complementary cystoscopic technique for non-invasive evaluation of zones suspicious for high-grade dysplasia and cancer.

  9. Key concerns about the current state of bladder cancer: a position paper from the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology.

    PubMed

    Lotan, Yair; Kamat, Ashish M; Porter, Michael P; Robinson, Victoria L; Shore, Neal; Jewett, Michael; Schelhammer, Paul F; deVere White, Ralph; Quale, Diane; Lee, Cheryl T

    2009-09-15

    Bladder cancer is the fifth most common cancer in the United States and, on a per capita basis, is the most expensive cancer from diagnosis to death. Unfortunately, National Cancer Institute funding for bladder cancer is quite low when compared with other common malignancies. Limited funding has stifled research opportunities for new and established investigators, ultimately encouraging them to redirect research efforts to other organ sites. Waning interest of scientists has further fueled the cycle of modest funding for bladder cancer. One important consequence of this has been a lack of scientific advancement in the field. Patient advocates have decidedly advanced research efforts in many cancer sites. Breast, prostate, pancreatic, and ovarian cancer advocates have organized highly successful campaigns to lobby the federal government and the medical community to devote increased attention and funding to understudied malignancies and to conduct relevant studies to better understand the therapy, diagnosis, and prevention of these diseases. Bladder cancer survivors have lacked a coordinated advocacy voice until recently. A concerted effort to align bladder cancer advocates, clinicians, and urologic organizations is essential to define the greatest needs in bladder cancer and to develop related solutions. This position paper represents a collaborative discussion to define the most concerning trends and greatest needs in the field of bladder cancer as outlined by the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology. PMID:19536899

  10. Treatment of bladder cancer in the elderly.

    PubMed

    Erlich, Annette; Zlotta, Alexandre R

    2016-06-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  11. Treatment of bladder cancer in the elderly

    PubMed Central

    Erlich, Annette

    2016-01-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  12. Bladder filling variation during radiation treatment of prostate cancer: Can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

    SciTech Connect

    Stam, Marcel R. . E-mail: m.stam@rther.umcn.nl; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

    2006-06-01

    Purpose: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. Methods and Materials: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. Results: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 Sd = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. Conclusions: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations.

  13. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    PubMed

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers. PMID:27455559

  14. HPLC assisted Raman spectroscopic studies on bladder cancer

    NASA Astrophysics Data System (ADS)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  15. Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.

    PubMed

    Daugherty, Sarah E; Pfeiffer, Ruth M; Sigurdson, Alice J; Hayes, Richard B; Leitzmann, Michael; Schatzkin, Arthur; Hollenbeck, Albert R; Silverman, Debra T

    2011-04-01

    Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers. PMID:21367875

  16. Bladder cancer, a review of the environmental risk factors

    PubMed Central

    2012-01-01

    Background Many epidemiological studies and reviews have been performed to identify the causes of bladder cancer. The aim of this review is to investigate the links between various environmental risk factors and cancer of the bladder. Methods A systematic literature search was performed using PubMed, Science Direct, Scopus, Scholar Google and Russian Google databases to identify reviews and epidemiological studies on bladder cancer risk factors associated with the environment published between 1998 and 2010. Only literature discussing human studies was considered. Results Smoking, mainly cigarette smoking, is a well known risk factor for various diseases, including bladder cancer. Another factor strongly associated with bladder cancer is exposure to arsenic in drinking water at concentrations higher than 300 µg/l. The most notable risk factor for development of bladder cancer is occupational exposure to aromatic amines (2-naphthylamine, 4-aminobiphenyl and benzidine) and 4,4'-methylenebis(2-chloroaniline), which can be found in the products of the chemical, dye and rubber industries as well as in hair dyes, paints, fungicides, cigarette smoke, plastics, metals and motor vehicle exhaust. There are also data suggesting an effect from of other types of smoking besides cigarettes (cigar, pipe, Egyptian waterpipe, smokeless tobacco and environmental tobacco smoking), and other sources of arsenic exposure such as air, food, occupational hazards, and tobacco. Other studies show that hairdressers and barbers with occupational exposure to hair dyes experience enhanced risk of bladder cancer. For example, a study related to personal use of hair dyes demonstrates an elevated bladder cancer risk for people who used permanent hair dyes at least once a month, for one year or longer. Conclusion Smoking, in particular from cigarettes, exposure to arsenic in drinking water, and occupational exposure to aromatic amines and 4,4'-methylenebis(2-chloroaniline) are well known risk

  17. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice

    PubMed Central

    Luong, Richard; Yu, Eun-Jeong; He, Yongfeng; Gonzalgo, Mark L.; Sun, Zijie

    2016-01-01

    Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC) than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development. PMID:26862755

  18. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice.

    PubMed

    Johnson, Daniel T; Hooker, Erika; Luong, Richard; Yu, Eun-Jeong; He, Yongfeng; Gonzalgo, Mark L; Sun, Zijie

    2016-01-01

    Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC) than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development. PMID:26862755

  19. PET/CT in renal, bladder and testicular cancer

    PubMed Central

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

  20. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method

    PubMed Central

    Yang, Ganglong; Xu, Zhipeng; Lu, Wei; Li, Xiang; Sun, Chengwen; Guo, Jia; Xue, Peng; Guan, Feng

    2015-01-01

    The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer. PMID:26230496

  1. Nur77 inhibits androgen-induced bladder cancer growth.

    PubMed

    Wu, Jianping; Liu, Jun; Jia, Ruipeng; Song, Hongbin

    2013-12-01

    Currently, bladder cancer ranks as the second most common genitourinary malignancy which is exacting significant morbidity and mortality worldwide. Although there are abundant epidemiological and basic studies which strongly suggest the role of androgen hormone in bladder cancer, the underlying mechanism is not fully understood. In the current study, we sought to identify a new competitive inhibitor for androgen receptor in bladder cancer cells. Our results showed that Nur77 hyperexpression inhibits UM-UC-3 cell growth and cell cycle progression while Nur77 knockdown exerts the opposite effect. In our cell culture model, we also demonstrated that Nur77 competitively inhibits androgen-dependent transcription activity and more specifically, Nur77 competes with androgen receptor for binding to src-1, a well-known coactivator for steroids. More importantly, we also showed that a small molecule agonist for Nur77, Cytosporone B, significantly inhibits androgen-dependent bladder cancer cell growth in two different cell lines. These data provide a good proof-of-principle that Nur77 signaling machinery could be a new target for growth control of androgen-dependent bladder cancer cells. PMID:24299210

  2. Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer

    PubMed Central

    Owusu, Richmond A.; Abern, Michael R.; Inman, Brant A.

    2013-01-01

    Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer. PMID:24073396

  3. Cigarette smoking implicated in half of bladder cancers in women

    Cancer.gov

    Current cigarette smokers have a higher risk of bladder cancer than previously reported, and the risk in women is now comparable to that in men, according to a study by scientists from the National Cancer Institute (NCI), part of the National Institutes o

  4. [Benzidine dyes and risk of bladder cancer].

    PubMed

    Miyakawa, M; Yoshida, O

    1989-12-01

    Until the early 1970's there was little concern about dyes which contain benzidine as an integral part of their chemical structure. Furthermore, use of the finished dyes was not considered dangerous. To ascertain whether azo dyes are associated with risk of development of bladder tumors in workers who handpaint Yuzen-type silk kimonos in Kyoto, we investigated the disintegration of dyes to benzidine. In these studies, we found that in rats and mice benzidine-based dyes are metabolized to benzidine and that the azo linkage of benzidine dyes is reduced by Escherichia coli and soil bacteria. These experimental findings were reported previously. In this report, we outline an approach to these studies. Many of the dyes used to color paper, textiles, lipstick, bait used by fishermen, as well as hair dyes, and dyes used in research, for pharmaceutical products, and by defence personnel for the detection of liquid chemical warfare agents, have been shown to be potentially mutagenic or carcinogenic. We review the literature on these dyes. PMID:2618904

  5. Novel fusion transcripts in bladder cancer identified by RNA-seq.

    PubMed

    Kekeeva, T; Tanas, A; Kanygina, A; Alexeev, D; Shikeeva, A; Zavalishina, L; Andreeva, Y; Frank, G A; Zaletaev, D

    2016-05-01

    Urothelial carcinoma (UC) is the most common type of bladder cancer and is the second most frequently diagnosed genitourinary tumor. The identification of fusion genes in bladder cancer might provide new perspectives for its classification and significance. In this study, we present a thorough search on three UC samples for novel fusion transcripts in bladder cancer using high-throughput RNA sequencing. We used stringent requirements for 819 fusion candidates and nominated 10 candidate fusion transcripts. Among them four novel fusion genes SEPT9/CYHR, IGF1R/TTC23, SYT8/TNNI2 and CASZ1/DFFA were validated and characterized in 48 formalin-fixed paraffin-embedded (FFPE) specimens of bladder cancer. Chromosomal rearrangements of regions 17q25, 15q26.3 and 1p36.22 resulting in the fusion transcripts SEPT9/CYHR, IGF1R/TTC23 and CASZ1/DFFA, appeared to be rare or unique events because they were not detected in the 48 UC samples. In contrast, the SYT8/TNNI2 fusion transcript resulting from transcription-induced chimerism by read-through mechanisms was a rather common and tumor-specific event occurring in 37.5% (18/48) of the UC specimens. Further investigation of functional and clinical relevance of novel fusion genes remains to be elucidated to reveal their role in bladder carcinogenesis. PMID:26898937

  6. Review of current optical diagnostic techniques for non-muscle-invasive bladder cancer

    PubMed Central

    Kołodziej, Anna; Matuszewski, Michał; Tupikowski, Krzysztof

    2016-01-01

    Introduction Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination – cystoscopy. Material and methods A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms ‘bladder cancer’ in conjunction with ‘cystoscopy’, ‘diagnosis’, ‘detection’, ‘fluorescence’, ‘blue-light’, ‘PDD’, ‘narrow band imaging’, ‘molecular imaging’, ‘optical coherence tomography’ or ‘confocal laser endomicroscopy’. Results The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high-resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as ‘optical biopsy’. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies. Conclusions In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle-invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness. PMID:27551551

  7. Meta-analysis of the relationship between slow acetylation of N-acetyl transferase 2 and the risk of bladder cancer.

    PubMed

    An, Y; Li, H; Wang, K J; Liu, X H; Qiu, M X; Liao, Y; Huang, J L; Wang, X S

    2015-01-01

    The incidence of bladder cancer is closely associated with exposure to aromatic amines, that can cause cancer only after metabolic activation regulated by N-acetyl transferase 1 and 2 (NAT1 and NAT2). Many studies have indicated that slow acetylation of NAT2 increases the risk of bladder cancer. The major risk factor is tobacco smoke; however, some studies have failed to prove this. This study attempted to explore the correlation between NAT2 slow acetylation and bladder cancer risk through a meta-analysis of published case-control studies. Studies detecting NAT2 gene status in bladder cancer patients and healthy controls were retrieved from PubMed, Cochrane, EMchrane, CBM, and CNKI. We retrieved the data of cited articles and publications to identify and compare NAT2 gene in bladder cancer patients and healthy controls. The variables within and between the studies were also considered. The META module in the Stata v.6.0 software was used for data analysis. Twenty independent studies were enrolled in our meta-analysis according to the inclusion and exclusion criteria. Individual differences in the bladder cancer susceptibility were, in part, attributed to the effect of carcinogens. The merged odds ratio of the effect of slow acetylation on bladder cancer was 1.31 (95% confidence interval = 1.11-1.55). In conclusion, NAT2 slow acetylation state was associated with bladder cancer risk, and was shown to modestly increase the risk of bladder cancer. PMID:26681036

  8. Reexamination of Total Fluid Intake and Bladder Cancer in the Health Professionals Follow-Up Study Cohort

    PubMed Central

    Zhou, Jiachen; Smith, Scott; Giovannucci, Edward; Michaud, Dominique S.

    2012-01-01

    It has been hypothesized that high fluid intake may reduce contact time between carcinogens and bladder epithelium and consequently reduce carcinogenesis. Epidemiologic studies examining fluid intake and bladder cancer have been extremely inconsistent, ranging from strong inverse to strong positive associations. The authors reevaluated the association between fluid intake and bladder cancer among 47,909 participants in the prospective Health Professionals Follow-up Study over a period of 22 years. During follow-up (1986–2008), 823 incident bladder cancer cases were diagnosed. Information on fluid intake was collected by using the food frequency questionnaire at baseline and every 4 years thereafter. Cox proportional hazard regression analysis was used to adjust for risk factors for bladder cancer. Total fluid intake was inversely associated with bladder cancer when the analysis was based on the baseline diet (relative risk = 0.76, 95% confidence interval: 0.60, 0.97), comparing the highest total daily fluid intake quintile (>2,531 mL/day) with the lowest quintile (<1,290 mL/day) (Ptrend = 0.01). However, no association was detected when the analysis was based on recent diet or cumulative updated diet. The updated analysis for total fluid intake and bladder cancer was attenuated compared with the original findings from the first 10-year follow-up period. PMID:22355034

  9. Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

    SciTech Connect

    Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei; Guzzo, Thomas; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; Malkowicz, S. Bruce; Christodouleas, John

    2013-03-01

    Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

  10. Immunological Basis in the Pathogenesis and Treatment of Bladder Cancer

    PubMed Central

    Thompson, David B.; Siref, Larry E.; Feloney, Michael P.; Hauke, Ralph J.; Agrawal, Devendra K.

    2015-01-01

    The pathogenesis and transition of normal urothelium into bladder carcinoma are multifactorial processes. Chronic inflammation causes initiation and progression of the underlying pathophysiology of invasive and metastatic cancer. A dichotomy is observed in the role of immune cells in bladder cancer. While the immune response defends the host by suppressing neoplastic growth, several immune cells, including neutrophils, macrophages, and T-lymphocytes, promote tumor development and progression. The levels of human neutrophil peptide-1, -2, and -3, produced by neutrophils, increase in bladder cancer and might promote tumor angiogenesis and growth. The effect of macrophages is primarily mediated by pro-inflammatory cytokines, IL-6 and TNF-α. Additionally, the underlying immunological mechanisms of two treatments, BCG and cytokine gene-modified tumor vaccines, and future directions are critically discussed. PMID:25391391

  11. High resolution photoacoustic imaging of microvasculature in normal and cancerous bladders

    NASA Astrophysics Data System (ADS)

    Xie, Zhixing; Roberts, William; Carson, Paul L.; Liu, Xiaojun; Tao, Chao; Wang, Xueding

    2013-03-01

    We explored the potential of an emerging laser-based technology, photoacoustic imaging (PAI), for bladder cancer diagnosis through high resolution imaging of microvasculature in the interior bladder tissues. Images of ex vivo canine bladders demonstrated the excellent ability of PAI to map three-dimensional microvasculature in optically scattering bladder tissues. By comparing the results from human bladder specimens affected by cancer to those from the normal control, the feasibility of PAI in differentiating malignant from benign bladder tissues was explored. The reported distinctive morphometric characteristics of tumor microvasculature can be seen in the images from cancer samples, suggesting that PAI may allow in vivo assessment of neoangiogenesis that is closely associated with bladder cancer generation and progression. By presenting subsurface morphological and physiological information in bladder tissues, PAI, when performed in a similar way to that in conventional endoscopy, provides an opportunity for improved diagnosis, staging and treatment guidance of bladder cancer.

  12. Contemporary management of muscle-invasive bladder cancer

    PubMed Central

    Dall’Era, Marc A; Cheng, Liang; Pan, Chong-Xian

    2012-01-01

    The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected patients and for those medically unfit for surgery. Even though there are no level 1 data, the treatment outcomes for highly select patients given bladder-sparing therapy appear promising, with many patients retaining a functional bladder. Personalized chemotherapy is currently being actively pursued to target the underlying molecular changes and tailor to individual needs. PMID:22845409

  13. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    PubMed

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine. PMID:27133452

  14. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    NASA Astrophysics Data System (ADS)

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-02-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder >1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  15. Preclinical Dosimetry of Magnetic Fluid Hyperthermia for Bladder Cancer

    PubMed Central

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-01-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder ≥1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:23837123

  16. Nonmuscle invasive bladder cancer: a primer on immunotherapy

    PubMed Central

    Maruf, Mahir; Brancato, Sam J.; Agarwal, Piyush K.

    2016-01-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer. PMID:27458527

  17. Nonmuscle invasive bladder cancer: a primer on immunotherapy.

    PubMed

    Maruf, Mahir; Brancato, Sam J; Agarwal, Piyush K

    2016-06-01

    Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer. PMID:27458527

  18. Individualized management of advanced bladder cancer: Where do we stand?

    PubMed

    Burgess, Earle F

    2015-04-01

    Despite recent progress in the development of novel targeted therapies in various malignancies, the management of advanced urothelial cancer has changed little over the past 2 decades. Comorbidities inherent to patients with bladder cancer often preclude the use of standard cisplatin-based chemotherapy and underscore the need for individualized treatment recommendations and the development of more effective therapies. This review discusses current issues relevant to the management of patients with locally advanced and metastatic urothelial carcinoma of the bladder and highlights recent advances in defining molecular aberrations that may ultimately lead to personalized therapeutic decision making. PMID:24332641

  19. [Epidemiological study of risk factors for bladder cancer].

    PubMed

    Nakata, S; Sato, J; Ohtake, N; Imai, K; Yamanaka, H

    1995-12-01

    A case-control study was conducted on 303 male bladder cancer patients and controls. General population controls were chosen from 15 areas in Gunma Prefecture and were matched by age (+/- l y.o.) to the subjects. Age-adjusted and smoking-adjusted odds ratio (O.R.) and a 95% confidence interval (C.I.) were calculated for each item. Risk factors for bladder cancer in men were investigated. The O.R. tended to be significantly higher for those who had history of smoking, who smoked more per day, who had smoked longer, whose Brinkman index was higher, who began smoking younger and who inhaled deeper than it was for non-smokers. O.R.s of having a past history or complication of cystitis (age-adjusted) and benign prostatic hypertrophy (age- and smoking-adjusted) were significantly higher, but the difference was supposed to be caused by bias. There was a significantly lower age- and smoking-adjusted O.R. for bladder cancer in men who engaged in sales, whose blood type was O, who drank milk frequently, who ate grains frequently, who age vegetables frequently and who had a past history or complication of hypertension. The number of cases and controls with first degree family members who developed cancer respectively supposed to be highly related to smoking, were as follows; 16 and 8 for lung cancer, 3 and 0 for larynx cancer and 6 and 3 for bladder cancer. The following characteristics failed to show any significant difference between subjects with bladder cancer and the control group; height and weight now and 20 years ago, jobs which deal with dye, academic career, marriage, number of children, alcohol drinking and the use of hair dye or analgesics. PMID:8578986

  20. The underactive bladder: detection and diagnosis

    PubMed Central

    Osman, Nadir; Mangera, Altaf; Hillary, Christopher; Inman, Richard; Chapple, Christopher

    2016-01-01

    The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the “underactive bladder” (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration. PMID:27081483

  1. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report.

    PubMed

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    BACKGROUND Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. CASE REPORT A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. CONCLUSIONS A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder. PMID:27072610

  2. Genotyping of the polymorphic N-acetyltransferase (NAT2) and loss of heterozygosity in bladder cancer patients.

    PubMed

    Schnakenberg, E; Ehlers, C; Feyerabend, W; Werdin, R; Hübotter, R; Dreikorn, K; Schloot, W

    1998-05-01

    Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distribution of allelic constellations of the N-acetyltransferase (NAT2) by genotyping patients with bladder cancer. We analysed NAT2 gene of blood and tumor DNA from 60 patients with primary bladder cancer and DNA of blood samples from 154 healthy individuals. Using ASO-PCR/RFLP techniques we identified 70% of patients with bladder cancer (n = 42) to be slow acetylators while genotyping of controls resulted in 61% with slow acetylators (n = 94). In addition, dividing bladder cancer patients in males and females the genotype NAT2*5B/NAT2*6A occured with much higher frequencies in males (OR = 4, 95%); CI = 1.8-8.9). Furthermore, investigating bladder cancer tissues we could detect loss of heterozygosity (LOH) in slow and rapid acetylator genotypes. In eleven out of 60 tumor samples (18.3%) we observed allelic loss at the NAT2 locus while in control DNA of blood from the same patients both alleles were still detectable. PMID:9660060

  3. Bladder cancer incidence and exposure to polycyclic aromatic hydrocarbons among asphalt pavers

    PubMed Central

    Burstyn, Igor; Kromhout, Hans; Johansen, Christoffer; Langard, Sverre; Kauppinen, Timo; Shaham, Judith; Ferro, Gilles; Boffetta, Paolo

    2007-01-01

    Objectives To investigate the association between exposures to polycyclic aromatic hydrocarbons (PAH) that arises during asphalt paving, and risk of bladder cancer. Methods 7298 men included in the historical cohort were first employed between 1913 and 1999 in companies applying asphalt in Denmark, Norway, Finland and Israel. The minimal duration of employment for inclusion in the cohort was two seasons of work. Occupational histories were extracted from personnel files. A follow‐up for cancer incidence was conducted through national cancer registries. The authors estimated exposures to benzo(a)pyrene as a marker for 4–6 ring PAH. Exposures were reconstructed by using information about changes in asphalt paving technology in each company over time, the modelled relation between production characteristics and exposure levels, and job histories. Relative risks and associated 95% confidence intervals were estimated using Poisson regression. Results 48 bladder cancers among asphalt paving workers were detected; of these, 39 cases were exposed at least 15 years before the diagnosis. Cumulative exposure to PAH was not associated with the incidence of bladder cancer. The association with average exposure became stronger when 15‐year lag was considered, revealing a twofold increase in relative bladder cancer risk in the two higher exposure categories. There was an indication of exposure‐response association with lagged averaged exposure. Risk estimates were adjusted for age, country, duration of employment and calendar period, did not show heterogeneity among countries and did not materially change when re‐estimated after excluding non‐primary cancers from follow‐up. Previously conducted sensitivity analysis indicates that confounding by cigarette smoking is an unlikely explanation for the observed exposure‐response trends. Conclusions The authors were unable to control for all possible sources of confounding and bias. The results do not allow conclusion on

  4. Cruciferous vegetables, isothiocyanates, and prevention of bladder cancer

    PubMed Central

    Veeranki, Omkara L.; Bhattacharya, Arup; Tang, Li; Marshall, James R.; Zhang, Yuesheng

    2015-01-01

    Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50–80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues. PMID:26273545

  5. Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer.

    PubMed

    Wang, Yu; Chen, Wei; Yang, Chen; Wu, Wenjing; Wu, Shouzhen; Qin, Xuebin; Li, Xu

    2012-07-01

    Our previous studies identified UCA1 as a novel biomarker for bladder cancer and detected three variant transcripts of UCA1 in the human bladder TCC cell line BLZ-211 using northern blot analysis. One (1.4 kb) of the three transcripts has been shown to play a pivotal role in bladder cancer progression and embryonic development. In this study, we cloned a second transcript (2.2 kb), designated UCA1a, which was identical to previously reported cancer upregulated drug resistant gene (CUDR). Sequence comparison of UCA1 (1.4 kb transcript) and UCA1a(CUDR) cDNA revealed a 1,265 bp common region. Previous studies have demonstrated that CUDR is upregulated in various human tumors, including colon, cervical and lung cancer. However, the exact role of UCA1a(CUDR) in bladder cancer has not yet been reported. In this study, RT-PCR analysis indicated that UCA1a(CUDR) was also an embryonic development and bladder cancer-associated RNA. Overexpression of UCA1a(CUDR) significantly enhanced proliferation, migration and invasion of the bladder cancer cell line UM-UC-2. Moreover, microarray analysis demonstrated that overexpression of UCA1a(CUDR) was associated with signaling pathways regulating cell apoptosis and tumorigenesis. Furthermore, overexpression of UCA1a(CUDR) could antagonize cell apoptosis induced by cisplatin and promote the tumorigenicity of UM-UC-2 cells in vivo. Taken together, our data strongly suggest that similar to the 1.4 kb transcript of UCA1, UCA1a(CUDR) may also play an important role in the growth and tumorigenesis of human bladder cancer, and their common region may be critical for biological activity, thereby indicating that their common region may serve as a new therapeutic target for bladder cancer. PMID:22576688

  6. Simultaneous radical cystectomy and colorectal cancer resection for synchronous muscle invasive bladder cancer and cT3 colorectal cancer: Our initial experience in five patients

    PubMed Central

    Liu, Zhuo; Chen, Guiping; Zhu, Yuping; Li, Dechuan

    2014-01-01

    To review cases of simultaneous radical cystectomy and colorectal cancer (CRC) resection for synchronous carcinoma of bladder and colorectum. Between May 1997 and September 2010, five patients were diagnosed with synchronous bladder cancer and CRCs. The primary colorectal tumors included three sigmoid cancers, one ascending colon cancer and one rectal cancer. All patients underwent simultaneous radical cystectomy and CRC resection. Pathologic types were confirmed by the biopsies of cystoscopy and colonoscopy. All patients were performed synchronous radical cystectomy and CRC resection. Four of them received adjuvant chemotherapies for CRC. Two of them died of liver metastasis 32.8 months and 13 months after surgery. Although patients with synchronous carcinoma of bladder and colorectum are rare, the Urologist should be alerted to this possibility when evaluating patients for the initially presenting symptoms and/or detected tumors. The simultaneous surgery is technically feasible for the selected patients. PMID:25538788

  7. Bladder Diseases

    MedlinePlus

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  8. Bladder cancer and occupation in Shanghai, 1980-1984.

    PubMed

    Zheng, W; McLaughlin, J K; Gao, Y T; Silverman, D T; Gao, R N; Blot, W J

    1992-01-01

    To investigate occupational determinants of bladder cancer in the urban area of Shanghai, occupation and industry information for 1,219 incident bladder cancer cases diagnosed during the period 1980 to 1984 were compared with 1982 census data on employment. Standardized incidence ratios (SIR) for bladder cancer were estimated for occupation and industry classifications. Significant excess risks were observed for plastic products workers (male: SIR = 432; female: SIR = 368); textile bleachers, dyers, and finishers (male: SIR = 169); metal refining and processing workers (male: SIR = 139; female: SIR = 197); petroleum refining workers (male: SIR = 2152); railway engine drivers and firemen (male: SIR = 683); and workers employed in industries of apparel and other textile products manufacturing (female: SIR = 204); paper processing (male: SIR = 146; female: SIR = 226); organic chemical manufacturing (male: SIR = 186); plastic product manufacturing (male: SIR = 218; female: SIR = 272); and metallurgy (male: SIR = 107; female: SIR = 561). This study indicates that many of the industries and occupations that are responsible for increased risk throughout the world are also associated with occupational bladder cancer in Shanghai. PMID:1621696

  9. Chemotherapeutic potential of quercetin on human bladder cancer cells.

    PubMed

    Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

    2016-07-28

    In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection. PMID:27149655

  10. What Are the Risk Factors for Bladder Cancer?

    MedlinePlus

    ... of all bladder cancers in both men and women. If you or someone you know smokes and would like help quitting, see Guide to Quitting Smoking , or call us at 1-800-227-2345 for more information. Workplace exposures Certain industrial chemicals have been linked with ...

  11. Computer-aided detection of bladder mass within contrast-enhanced region of CTU

    NASA Astrophysics Data System (ADS)

    Cha, Kenny; Hadjiiski, Lubomir; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Zhou, Chuan

    2015-03-01

    We are developing a computer-aided detection system for bladder cancer on CTU. The bladder was automatically segmented with our Conjoint Level set Analysis and Segmentation System (CLASS). In this preliminary study, we developed a system for detecting mass within the contrast-enhanced (C) region of the bladder. The C region was delineated from the segmented bladders using a method based on maximum intensity projection. The bladder wall of the C region was extracted using thresholding to remove the contrast material. The wall on each slice was transformed into a wall profile. Morphology and voxel intensity along the profile were analyzed and suspicious locations were labeled as lesion candidates. The candidates were segmented and 20 morphological features were extracted from each candidate. A data set of 35 patients with 45 biopsy-proven bladder lesions within the C region was used for system evaluation. Stepwise feature selection with simplex optimization and leave-one-case-out method was used for training and validation. For each partition in the leave-one-case-out method, features were selected from the training cases and a linear discriminant (LDA) classifier was designed to merge the selected features into a single score for classification of the lesion candidates into bladder lesions and normal findings in the left-out case. A single score was generated for each lesion candidate. The performance of the CAD system was evaluated by FROC analysis. At an FP rate of 2.5 FPs/case, the system achieved a sensitivity of 82%, while at 1.7 FPs/case, a sensitivity of 71%.

  12. A review on thiazolidinediones and bladder cancer in human studies.

    PubMed

    Tseng, Chin-Hsiao

    2014-01-01

    There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison

  13. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    SciTech Connect

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo; Guoyong Wu; Hongqin Yang; Shusen Xie; Yonghong He

    2014-12-31

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

  14. Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-03-14

    Metastatic Ureteral Neoplasm; Metastatic Urethral Neoplasm; Stage III Bladder Urothelial Carcinoma; Stage III Ureter Cancer; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Ureter Cancer; Stage IV Urethral Cancer; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

  15. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    NASA Astrophysics Data System (ADS)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  16. Targeted therapy in Advanced Bladder cancer- what have we learned?

    PubMed Central

    Jordan, Emmet; Iyer, Gopa

    2016-01-01

    Synopsis Urothelial carcinoma (UC) is the second most common genitourinary malignancy in the United States. In the metastatic setting, cisplatin-based chemotherapy results in a median overall survival (OS) of 12–15 months and remains the only standard of care for this disease. Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been FDA-approved for UC in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared to cytotoxic therapy. The Cancer Genome Atlas (TCGA) has detected numerous potentially actionable genetic alterations in bladder cancer, providing a roadmap for the use of small molecule inhibitors in this disease. Additionally, the advancement of Next Generation sequencing technologies within the past five years has allowed for rapid, deep sequencing to define the molecular profile of tumors in real time. In this chapter, we outline representative trials of targeted therapies in UC and discuss the significance of genetic pre-selection in trial design as a method to optimize responses to these agents, thus hopefully expanding the armamentarium of treatment options against this lethal disease. PMID:25882566

  17. Role of Sonic Hedgehog (Shh) Signaling in Bladder Cancer Stemness and Tumorigenesis.

    PubMed

    Syed, Islam S; Pedram, Akbari; Farhat, Walid A

    2016-02-01

    Sonic hedgehog (Shh) signaling pathway has emerged as a critical component of bladder development, cancer initiation, and progression. While the role of Shh signaling in bladder development is well documented, its role in bladder cancer progression is uncertain. Additionally, epithelial-to-mesenchymal transition (EMT) has been identified to promote bladder cancer progression in the initial stages and also contribute to drug resistance in the later stage and ultimately metastasis. We speculate that epithelial-to-mesenchymal transitions (EMT) and Shh fuel the carcinogenesis process. This review presents the most recent studies focusing on the role of Shh signaling in bladder cancer progression. PMID:26757905

  18. Well Water a Suspected Cause of Bladder Cancer in New England

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_158607.html Well Water a Suspected Cause of Bladder Cancer in New ... May 2, 2016 (HealthDay News) -- Arsenic in drinking water from private wells may explain the elevated bladder ...

  19. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  20. Deregulation of Rab and Rab Effector Genes in Bladder Cancer

    PubMed Central

    Ho, Joel R.; Chapeaublanc, Elodie; Kirkwood, Lisa; Nicolle, Remy; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Southgate, Jennifer; Radvanyi, François; Goud, Bruno

    2012-01-01

    Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis

  1. Assessing Symptom Burden in Bladder Cancer: An Overview of Bladder Cancer Specific Health-Related Quality of Life Instruments

    PubMed Central

    Danna, Bernard J.; Metcalfe, Michael J.; Wood, Erika L.; Shah, Jay B.

    2016-01-01

    Background: A key component to monitoring and investigating patient QOL is through patient reported health related quality of life (HRQOL) outcome measures. Many instruments have been used to assess HRQOL in bladder cancer and each instrument varies in its development, validation, the context of its usage in the literature and its applicability to certain disease states. Objective: In this review, we sought to summarize how clinicians and researchers should most appropriately utilize the available HRQOL instruments for bladder cancer. Methods: We performed a comprehensive literature search of each instrument used in bladder cancer, paying particular attention to the outcomes assessed. We used these outcomes to group the available instruments into categories best reflecting their optimal usage by stage of disease. Results: We found 5 instruments specific to bladder cancer, of which 3 are validated. Only one of the instruments (the EORTC-QLQ-NMIBC24) was involved in a randomized, prospective validation study. The most heavily used instruments are the EORTC-QLQ-BLM30 for muscle-invasive disease and the FACT-Bl which is used across all disease states. Of the 5 available instruments, 4 are automatically administered with general instruments, while the BCI lacks modularity, and requires co-administration with a generalized instrument. Conclusion: There are multiple strong instruments for use in gauging HRQOL in bladder cancer patients. We have divided these instruments into three categories which optimize their usage: instruments for use following NMIBC treatments (EORTC-QLQ-NMIBC24), instruments for use following radical cystectomy (FACT-Bl-Cys and EORTC-QLQ-BLM30) and more inclusive instruments not limited by treatment modality (BCI and FACT-Bl). PMID:27500200

  2. Compensating bladder cancer victims employed in aluminum reduction plants.

    PubMed

    Armstrong, B; Tremblay, C; Theriault, G

    1988-10-01

    A criterion for eligibility to compensation is sought for bladder cancer cases among workers in the aluminum smelting industry. Probability that a case of bladder cancer was caused by occupational exposure can be estimated from a relationship derived from results of epidemiologic studies. Because the effects of occupational exposure and smoking apparently combine multiplicatively, this probability is independent of whether a case patient smoked. Estimated probabilities of causation have been used in a criterion for eligibility to compensation by the Quebec workers' compensation board. Workers with cancer for whom the upper 95% confidence limit of the probability of causation is at least 50% are compensated. This implies a minimum cumulative exposure to benzo[a]pyrene (concentration in micrograms per cubic meter times duration in years) of 19 micrograms/m3 years. Possible alternative approaches to compensation are discussed. PMID:2976422

  3. Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

    PubMed Central

    Cimino, George D; Pan, Chong-xian; Henderson, Paul T

    2013-01-01

    The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

  4. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

    PubMed Central

    Ohishi, Tomokazu; Koga, Fumitaka; Migita, Toshiro

    2015-01-01

    Bladder cancer (BC), the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs), which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory. PMID:26729098

  5. Alternating chemo-radiotherapy in bladder cancer: A conservative approach

    SciTech Connect

    Orsatti, M.; Franzone, P.; Giudici, S.

    1995-08-30

    The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy. 34 refs., 4 figs., 5 tabs.

  6. Organic cation secretion by Cancer borealis urinary bladder

    SciTech Connect

    Miller, D.S.; Holliday, C.W.

    1987-01-01

    In the crab, Cancer borealis, initial clearance studies showed a potent renal excretory system for the model organic cation, tetraethylammonium (TEA). (/sup 14/C)-TEA clearance averaged 145 +/- 32 ml/day, which was 18 times the paired polyethylene glycol clearance. TEA uptake by slices of urinary bladder was concentrative, saturable, inhibitable by N/sup 1/-methylnicotinamide chloride, and dependent on glycolytic, but not oxidative, metabolism. When mounted in flux chambers, bladders exhibited a large net secretory flux. For 0.1 mM TEA, the ratio of secretory to reabsorptive fluxes was 65. Urinary bladders from another crab, Cancer irroratus, and a lobster, Homarus americanus, also exhibited net TEA secretion. In C. borealis bladder, secretory transport was concentrative, saturable, and nearly abolished by addition of 1 mM quinine to the serosol bath. Reabsorptive transport was not concentrative and was not reduced by luminal quinine. The data are consistent with a secretory pathway that is transcellular and mediated by carriers at both the serosal and luminal membranes.

  7. Bladder cancer diagnosis during cystoscopy using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Grimbergen, M. C. M.; van Swol, C. F. P.; Draga, R. O. P.; van Diest, P.; Verdaasdonk, R. M.; Stone, N.; Bosch, J. H. L. R.

    2009-02-01

    Raman spectroscopy is an optical technique that can be used to obtain specific molecular information of biological tissues. It has been used successfully to differentiate normal and pre-malignant tissue in many organs. The goal of this study is to determine the possibility to distinguish normal tissue from bladder cancer using this system. The endoscopic Raman system consists of a 6 Fr endoscopic probe connected to a 785nm diode laser and a spectral recording system. A total of 107 tissue samples were obtained from 54 patients with known bladder cancer during transurethral tumor resection. Immediately after surgical removal the samples were placed under the Raman probe and spectra were collected and stored for further analysis. The collected spectra were analyzed using multivariate statistical methods. In total 2949 Raman spectra were recorded ex vivo from cold cup biopsy samples with 2 seconds integration time. A multivariate algorithm allowed differentiation of normal and malignant tissue with a sensitivity and specificity of 78,5% and 78,9% respectively. The results show the possibility of discerning normal from malignant bladder tissue by means of Raman spectroscopy using a small fiber based system. Despite the low number of samples the results indicate that it might be possible to use this technique to grade identified bladder wall lesions during endoscopy.

  8. Loss of SPARC in bladder cancer enhances carcinogenesis and progression

    PubMed Central

    Said, Neveen; Frierson, Henry F.; Sanchez-Carbayo, Marta; Brekken, Rolf A.; Theodorescu, Dan

    2013-01-01

    Secreted protein acidic and rich in cysteine (SPARC) has been implicated in multiple aspects of human cancer. However, its role in bladder carcinogenesis and metastasis are unclear,with some studies suggesting it may be a promoter and others arguing the opposite. Using a chemical carcinogenesis model in Sparc-deficient mice and their wild-type littermates, we found that loss of SPARC accelerated the development of urothelial preneoplasia (atypia and dysplasia), neoplasia, and metastasis and was associated with decreased survival. SPARC reduced carcinogen-induced inflammation and accumulation of reactive oxygen species as well as urothelial cell proliferation. Loss of SPARC was associated with an inflammatory phenotype of tumor-associated macrophages and fibroblasts, with concomitant increased activation of urothelial and stromal NF-κB and AP1 in vivo and in vitro. Syngeneic spontaneous and experimental metastasis models revealed that tumor- and stroma-derived SPARC reduced tumor growth and metastasis through inhibition of cancer-associated inflammation and lung colonization. In human bladder tumor tissues, the frequency and intensity of SPARC expression were inversely correlated with disease-specific survival. These results indicate that SPARC is produced by benign and malignant compartments of bladder carcinomas where it functions to suppress bladder carcinogenesis, progression, and metastasis. PMID:23321672

  9. Screening for Bladder and Other Urothelial Cancers

    MedlinePlus

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... symptoms appear, cancer may have begun to spread. Scientists are trying to better understand which people are ...

  10. Randomized-Control Screening Trials to Lower Gall Bladder Cancer Mortality in High Risk Populations.

    PubMed

    Krishnatreya, Manigreeva; Kataki, Amal Chandra

    2016-01-01

    Gall bladder cancer is generally fatal. The high morbidity and mortality due to gall bladder cancer exerts a significant impact on efforts towards cancer control in high risk populations of the World and a rationale program for control of gall bladder cancer mortality has remained as an unmet need in these populations. Currently there are no effective strategies for controlling gall bladder cancer mortality. This mini review is to highlight the need and feasibility for secondary prevention of gall bladder cancer by screening in high risk populations. A way forward is to assess the role of secondary prevention of gall bladder cancers by conducting randomized- controlled screening trials in high risk populations. PMID:27221939

  11. Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node-Negative Invasive Bladder Cancer: Single-Institution Experience

    SciTech Connect

    Tunio, Mutahir A.; Hashmi, Altaf; Qayyum, Abdul; Mohsin, Rehan; Zaeem, Ahmed

    2012-03-01

    Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRT (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT.

  12. Human Insulin Does Not Increase Bladder Cancer Risk

    PubMed Central

    Tseng, Chin-Hsiao

    2014-01-01

    Background Whether human insulin can induce bladder cancer is rarely studied. Methods The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression. Results There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. Conclusions This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication. PMID:24466131

  13. Investigation of a bladder cancer cluster in northwestern Illinois

    SciTech Connect

    Mallin, K. )

    1990-07-01

    Cancer maps from 1950 through 1979 revealed areas of high mortality from bladder cancer for both males and females in several northwestern Illinois counties. In order to further explore this excess, a bladder cancer incidence study was conducted in the eight counties comprising this region. Eligible cases were those first diagnosed with bladder cancer between 1978 and 1985. Age adjusted standardized incidence ratios were calculated for each county and for 97 zip codes within these counties. County results revealed no excesses. Zip code results indicated elevated risks in a few areas, but only two zip codes had significantly elevated results. One of these zip codes had a significant excess in males (standardized incidence ratio = 1.5) and females (standardized incidence ratio = 1.9). This excess was primarily confined to one town in this zip code, in which standardized incidence ratios were significantly elevated in males (1.7) and females (2.6). Further investigation revealed that one of four public drinking water wells in this town had been closed due to contamination; two wells were within a half mile (0.8 km) of a landfill site that had ceased operating in 1972. Tests of these two wells revealed traces of trichloroethylene, tetrachloroethylene, and other solvents. Further investigation of this cluster is discussed.

  14. Point-of-care clinical documentation: assessment of a bladder cancer informatics tool (eCancerCareBladder): a randomized controlled study of efficacy, efficiency and user friendliness compared with standard electronic medical records

    PubMed Central

    Bostrom, Peter J; Toren, Paul J; Xi, Hao; Chow, Raymond; Truong, Tran; Liu, Justin; Lane, Kelly; Legere, Laura; Chagpar, Anjum; Zlotta, Alexandre R; Finelli, Antonio; Fleshner, Neil E; Grober, Ethan D

    2011-01-01

    Objective To compare the use of structured reporting software and the standard electronic medical records (EMR) in the management of patients with bladder cancer. The use of a human factors laboratory to study management of disease using simulated clinical scenarios was also assessed. Design eCancerCareBladder and the EMR were used to retrieve data and produce clinical reports. Twelve participants (four attending staff, four fellows, and four residents) used either eCancerCareBladder or the EMR in two clinical scenarios simulating cystoscopy surveillance visits for bladder cancer follow-up. Measurements Time to retrieve and quality of review of the patient history; time to produce and completeness of a cystoscopy report. Finally, participants provided a global assessment of their computer literacy, familiarity with the two systems, and system preference. Results eCancerCareBladder was faster for data retrieval (scenario 1: 146 s vs 245 s, p=0.019; scenario 2: 306 vs 415 s, NS), but non-significantly slower to generate a clinical report. The quality of the report was better in the eCancerCareBladder system (scenario 1: p<0.001; scenario 2: p=0.11). User satisfaction was higher with the eCancerCareBladder system, and 11/12 participants preferred to use this system. Limitations The small sample size affected the power of our study to detect differences. Conclusions Use of a specific data management tool does not appear to significantly reduce user time, but the results suggest improvement in the level of care and documentation and preference by users. Also, the use of simulated scenarios in a laboratory setting appears to be a valid method for comparing the usability of clinical software. PMID:21816957

  15. Targeting Signaling Transduction Pathways in Bladder Cancer.

    PubMed

    Abbosh, Phillip H; McConkey, David J; Plimack, Elizabeth R

    2015-12-01

    Systemic therapy for urothelial carcinoma (UC) of the bladder has largely revolved around cytotoxic chemotherapy regimens. However, several recent clinical trials have explored the roles of targeted therapies which specifically inhibit signal transduction pathways. Simultaneously, a rationale for such therapies has come to the forefront of management of this disease because an overabundance of signaling pathways are genetically deranged as a result of point mutation or copy number alteration (CNA) as identified by several recent next generation sequencing (NGS) studies. Importantly, these derangements are found in all stages of disease, and therefore targeted therapies hold promise as a next step in the evolution of the medical management of both localized and metastatic UCC. We review the rationale for and progress in studying inhibition of signal transduction as a means of treatment of UCC. PMID:26472299

  16. Reducing aluminum: an occupation possibly associated with bladder cancer.

    PubMed Central

    Thériault, G; De Guire, L; Cordier, S

    1981-01-01

    A case-control study, undertaken to identify reasons for the exceptionally high incidence of bladder cancer among men in the Chicoutimi census division of the province of Quebec, revealed an increased risk associated with employment in the electrolysis department of an aluminum reduction plant. The estimated relative risk was 2.83 (95% confidence interval; 1.06 to 7.54). An interaction was found between such employment and cigarette smoking, resulting in a combined relative risk of 5.70 (95% confidence interval: 2.00 to 12.30). These findings suggest that employment in an aluminum reduction plant accounts for part of the excess of bladder cancer in the region studied. PMID:7214271

  17. Cross-species comparison of orthologous gene expression in human bladder cancer and carcinogen-induced rodent models

    PubMed Central

    Lu, Yan; Liu, Pengyuan; Wen, Weidong; Grubbs, Clinton J; Townsend, Reid R; Malone, James P; Lubet, Ronald A; You, Ming

    2011-01-01

    Genes differentially expressed by tumor cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. This study examined the suitability of rodent models of bladder cancer in B6D2F1 mice and Fischer-344 rats to model clinical bladder cancer specimens in humans. Using a global gene expression approach cross-species analysis showed that 13-34% of total genes in the genome were differentially expressed between tumor and normal tissues in each of five datasets from humans, rats, and mice. About 20% of these differentially expressed genes overlapped among species, corresponding to 2.6 to 4.8% of total genes in the genome. Several genes were consistently dysregulated in bladder tumors in both humans and rodents. Notably, CNN1, MYL9, PDLIM3, ITIH5, MYH11, PCP4 and FM05 were found to commonly down-regulated; while T0P2A, CCNB2, KIF20A and RRM2 were up-regulated. These genes are likely to have conserved functions contributing to bladder carcinogenesis. Gene set enrichment analysis detected a number of molecular pathways commonly activated in both humans and rodent bladder cancer. These pathways affect the cell cycle, HIF-1 and MYC expression, and regulation of apoptosis. We also compared expression changes at mRNA and protein levels in the rat model and identified several genes/proteins exhibiting concordant changes in bladder tumors, including ANXA1, ANXA2, CA2, KRT14, LDHA, LGALS4, SERPINA1, KRT18 and LDHB. In general, rodent models of bladder cancer represent the clinical disease to an extent that will allow successful mining of target genes and permit studies on the molecular mechanisms of bladder carcinogenesis. PMID:21139803

  18. Radiochemotherapy With Cisplatin and 5-Fluorouracil After Transurethral Surgery in Patients With Bladder Cancer

    SciTech Connect

    Weiss, Christian . E-mail: Christian.Weiss@strahlen.med.uni-erlangen.de; Engehausen, Dirk G.; Krause, Frens S.; Papadopoulos, Thomas; Dunst, Juergen; Sauer, Rolf; Roedel, Claus

    2007-07-15

    Purpose: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. Methods and Materials: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m{sup 2}/day as 30-min infusion) and 5-FU (600 mg/m{sup 2}/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Results: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. Conclusion: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.

  19. The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

    SciTech Connect

    Conde, Vanessa R.; Oliveira, Pedro F.; Ramalhosa, Elsa; Pereira, José A.; Alves, Marco G.; Silva, Branca M.

    2015-07-01

    Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

  20. Diagnostic accuracy of cytokeratin-19 fragment (CYFRA 21-1) for bladder cancer: a systematic review and meta-analysis.

    PubMed

    Huang, Yuan-Lan; Chen, Jie; Yan, Wei; Zang, Ding; Qin, Qin; Deng, An-Mei

    2015-05-01

    Previous studies have evaluated the accuracy of serum and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer; however, the results have been inconsistent. The aim of this study was to evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer. We performed a search for English-language publications reporting on the detection of CYFRA21-1 levels for the diagnosis of bladder cancer through November 2, 2014, using public medical databases, including EMBASE, Web of Science, and Medline. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and analyzed using a bivariate model. Publication bias was explored with the Deek's test. Sixteen studies, with a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were included in the study. The pooled sensitivities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70-0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90-0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major design deficiencies of the included studies were participant-selection bias, potential review, and verification bias. Therefore, we concluded that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. Additional, well-designed studies should be performed to rigorously evaluate the diagnostic value of CYFRA 21-1 for bladder cancer. PMID:25854170

  1. Pesticide, Gene Polymorphisms and Bladder Cancer among Egyptian Agricultural Workers

    PubMed Central

    Amr, Sania; Dawson, Rebecca; Saleh, Doa’a A.; Magder, Laurence S.; St. George, Diane Marie; El-Daly, Mai; Squibb, Katherine; Mikhail, Nabiel N.; Abdel-Hamid, Mohamed; Khaled, Hussein; Loffredo, Christopher A.

    2013-01-01

    We examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H:quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. We used logistic regression to analyze data from a multi-center case-control study and estimate adjusted odds ratio (OR) and 95% CI (confidence interval) Exposure to pesticides was associated with increased bladder cancer risk (1.68 (1.23–2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25–2.56) than for squamous cell carcinoma (1.55 (1.03–2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19–3.85) activities as compared to those with high NQO1 and low SOD2 genotypes (1.53 (0.73–3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism. PMID:24219772

  2. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    SciTech Connect

    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. )

    1991-01-01

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

  3. Treatment of muscle-invasive bladder cancer: A systematic review.

    PubMed

    Chou, Roger; Selph, Shelley S; Buckley, David I; Gustafson, Katie S; Griffin, Jessica C; Grusing, Sara E; Gore, John L

    2016-03-15

    There is uncertainty regarding the use of bladder-sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal chemotherapeutic regimens. This study was conducted to systematically review the benefits and harms of bladder-sparing therapies, lymph node dissection, and systemic chemotherapy for patients with clinically localized muscle-invasive bladder cancer. Systematic literature searches of MEDLINE (from 1990 through October 2014), the Cochrane databases, reference lists, and the ClinicalTrials.gov Web site were performed. A total of 41 articles were selected for review. Bladder-sparing therapies were found to be associated with worse survival compared with radical cystectomy, although the studies had serious methodological shortcomings, findings were inconsistent, and only a few studies evaluated currently recommended techniques. More extensive lymph node dissection might be more effective than less extensive dissection at improving survival and decreasing local disease recurrence, but there were methodological shortcomings and some inconsistency. Six randomized trials found cisplatin-based combination neoadjuvant chemotherapy to be associated with a decreased mortality risk versus cystectomy alone. Four randomized trials found adjuvant chemotherapy to be associated with decreased mortality versus cystectomy alone, but none of these trials reported a statistically significant effect. There was insufficient evidence to determine optimal chemotherapeutic regimens. PMID:26773572

  4. Bladder cancer in a young patient: Undiscovered risk factors

    PubMed Central

    KHAN, RAFAY; IBRAHIM, HIYAM; TULPULE, SUNIL; IROKA, NNEKA

    2016-01-01

    Bladder cancer is one of the most common forms of malignancies involving the urinary system and multiple risk factors have been associated with its etiology. The most common of which include cigarette smoking and various occupational or chemical exposures. It is usually diagnosed in older individuals with an average age of 70. In rare cases it is observed in children as well as young adults where it usually presents as a low-grade, non-invasive disease. In the present case report a 27-year-old male patient is discussed: The patient presented with no significant risk factors and was treated for mucinous adenocarcinoma of the bladder while further investigations were performed to identify other associated factors related to this form of malignancy. Debate in the literature exists in regards to the characteristics of bladder neoplasms in younger patients compared with older patients, however there is a lack of research into the etiology or prognosis in young patients. The present case study illustrates the case of a young adult with no clear risk factors who was diagnosed with a rare case of mucinous adenocarcinoma of the bladder. PMID:27123090

  5. Interobserver Agreement of Confocal Laser Endomicroscopy for Bladder Cancer

    PubMed Central

    Chang, Timothy C.; Liu, Jen-Jane; Hsiao, Shelly T.; Pan, Ying; Mach, Kathleen E.; Leppert, John T.; McKenney, Jesse K.; Rouse, Robert V.

    2013-01-01

    Abstract Background and Purpose Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. Methods Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. Results Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. Conclusions CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone. PMID:23072435

  6. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

    SciTech Connect

    Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Kaufman, Donald S.; Heney, Niall M.; Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U.

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  7. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    SciTech Connect

    Shipley, W.U.; Kaufman, S.D.; Prout, G.R. Jr.

    1987-10-01

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references.

  8. TERT Core Promotor Mutations in Early-Onset Bladder Cancer.

    PubMed

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  9. TERT Core Promotor Mutations in Early-Onset Bladder Cancer

    PubMed Central

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  10. Screening for Bladder Cancer: Recommendations from the U.S.Preventive Services Task Force

    MedlinePlus

    ... known about it so far? In the United States, bladder cancer is the fourth and ninth most commonly diagnosed cancer in men and women, respectively. In 2009, about 70,000 new cases of bladder cancer were diagnosed in the United States and about 14,000 persons died of the ...