National Cancer Institute®
Last Modified: March 1, 2002
UI - 11377304
AU - De Dominicis C; Liberti M; Perugia G; De Nunzio C; Sciobica F; Zuccala
TI - A; Sarkozy A; Iori F Role of 5-aminolevulinic acid in the diagnosis and treatment of superficial bladder cancer: improvement in diagnostic sensitivity.
SO - Urology 2001 Jun;57(6):1059-62
AD - Dipartimento di Urologia U. Bracci, Universita di Roma La Sapienza,, Rome, Italy.
OBJECTIVES: To use 5-aminolevulinic acid (5-ALA) in diagnostic cystoscopy and during transurethral resection of the bladder (TURB) to treat transitional cell carcinoma. The efficacy of this new technique was compared with standard cystoscopy. METHODS: The 5-ALA, instilled in the bladder 2 hours before cystoscopy, makes the pathologic tissue fluorescent when illuminated with blue light (375 to 400 nm). This allows a better recognition of the neoplastic forms for both diagnostic and therapeutic purposes during TURB. This method has been used since immediately or during postchemotherapy follow-up. RESULTS: One hundred seventy-nine biopsies were taken of fluorescent and nonfluorescent areas (3.5 per patient) to check the effectiveness of the new method compared with standard cystoscopy. A good correlation was found between 5-ALA cystoscopy and the histopathologic diagnosis, with a good sensitivity (87%). The 5-ALA cystoscopy allowed the diagnosis of a tumor in 24 patients with negative standard cystoscopic findings. Furthermore, 5-ALA cystoscopy detected 7 cases of carcinoma in situ. Neither local nor systemic (because of endovesical instillation) side effects were noted. CONCLUSIONS: We believe that 5-ALA could be routinely used in the diagnosis of superficial bladder tumors, as it was shown to improve the diagnostic sensitivity for carcinoma in situ and to reduce the risk of recurrence related to missed cancerous lesions or incomplete TURB.
UI - 11377305
AU - Chang BS; Kim HL; Yang XJ; Steinberg GD
TI - Correlation between biopsy and radical cystectomy in assessing grade and depth of invasion in bladder urothelial carcinoma.
SO - Urology 2001 Jun;57(6):1063-6; discussion 1066-7
AD - Pritzker School of Medicine, Chicago, Illinois, USA.
OBJECTIVES: To assess the degree of correlation between the pathologic characteristics of the specimens obtained from biopsy and radical cystoprostatectomy. The stage and grade of bladder urothelial (transitional cell) carcinoma are important predictors of prognosis. METHODS: We retrospectively identified 169 cases of urothelial carcinoma from 222 radical cystectomies performed at University of Chicago Hospitals from 1992 to 1999. RESULTS: For all the cases in this study, the histologic grade, using the 1998 World Health Organization and International Society of Urological Pathologists (WHO/ISUP) classification, was identical when the biopsy specimen and radical cystectomy specimen were compared. However, when the same cases were assessed using the traditional three-grade system, the histologic grade increased or decreased by one grade in 19 (11%) and 8 (5%) of 169 cases, respectively. Patients with invasion of the lamina propria on biopsy had tumor extending outside the bladder in 15 (27%) of 55 cases. Patients with invasion of the muscularis propria on biopsy had tumor extending outside the bladder in 47 (49%) of 96 cases, including nodal metastasis in 22 (23%) of 96 cases. Overall, bladder biopsy underestimated the true extent of the disease in 78 (46%) of 169 cases. CONCLUSIONS: Using either the WHO/ISUP (1998) classification or the traditional three-grade system, the histologic grade of the biopsy specimen is a fairly good predictor of the final histologic grade. The preoperative biopsy tends to understage bladder cancer. Patients with muscularis propria invasion demonstrated by biopsy have a significantly higher risk of non-organ-confined disease than those with lamina propria invasion.
UI - 11544830
AU - Zlatnik EIu; Kapkina NN; Zaderin VP; Zakora GI
TI - [Immunocorrective effect of alternating magnetic field in the postoperative period in malignant bladder cancer]
SO - Vopr Onkol 2001;47(3):312-4
AD - Research Institute of Oncology, Ministry of Health of the RF, Rostov-on-Don.
The study deals with immune status of patients operated for bladder cancer and exposed postoperatively to alternating magnetic field (MF) (hypothalamus and operative field). MF application was followed by higher T- and B-lymphocyte and CD4+, CD16+ cell levels as well as enhanced T-cell activity; no postoperative complications were registered and tumor relapse rates were relatively low. The effect was likely to be due to antistressor influence of MF. The procedure may substitute drug therapy for immunocorrection and to avoid recurrence of bladder cancer.
UI - 11797592
AU - Altwein JE
TI - [Dysuria. Typical symptoms for proper diagnosis]
SO - MMW Fortschr Med 2001 Nov 26;143 Suppl():121-30; quiz 131-2
AD - Urologische Abteilung, Krankenhaus der Barmherzigen Bruder, Munchen.
UI - 11830537
AU - Hartmann A; Schlake G; Zaak D; Hungerhuber E; Hofstetter A; Hofstaedter
TI - F; Knuechel R Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder.
SO - Cancer Res 2002 Feb 1;62(3):809-18
AD - Institute of Pathology, University of Regensburg, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany.
To define the genetic changes of flat urothelial lesions, carcinoma in situ (CIS) and moderate dysplasias (DII) were investigated for alterations in the two chromosomal regions most frequently involved in bladder cancer. Overall, 33 CIS and 16 DII from 21 patients were used to microdissect urothelium. Dual color fluorescence in situ hybridization (FISH) using gene locus probes of 9q22 (FACC), 9p21 (CDK), 17p13 (p53), and related centromeric probes was applied on interphase nuclei. In parallel, preamplified DNA of these samples was used for loss of heterozygosity (LOH) analyses with eight microsatellite markers on chromosomes 9p, 9q and 17p, and for sequencing of exons 5-9 of p53. Data indicated nearly identical deletion frequencies for chromosomes 9 and 17 for CIS (chromosome 9, 86%; p53, 84%). DII showed a lower deletion rate in comparison with CIS (chromosome 9, 75%; p53, 53%). A very high correlation between the results of FISH and LOH analyses was found. p53 mutations were detected in 12 of 15 patients (CIS, 72%; DII, 67%). In three of 16 patients with multifocal tumors, oligoclonal lesions were identified by LOH analyses, a finding further supported by sequencing of p53, by which two different p53 deletions were detected in two cases. In conclusion, data from microdissected flat urothelial lesions indicate that chromosome 9 deletions cannot be regarded as indicators of papillary growth, because they are found frequently in both types of flat lesions of the urothelium: those associated with papillary tumors and those that are not. The similar distribution and lower amount of genetic changes in DII render DII a possible precursor lesion of CIS.
UI - 11857385
AU - Dangles V; Validire P; Wertheimer M; Richon S; Bovin C; Zeliszewski D;
TI - Vallancien G; Bellet D Impact of human bladder cancer cell architecture on autologous T-lymphocyte activation.
SO - Int J Cancer 2002 Mar 1;98(1):51-6
AD - Laboratoire d'Immunologie des Tumeurs, ESA 8067 CNRS, Faculte des Sciences Pharmaceutiques et Biologiques de Paris, Universite Paris V-Rene Descartes, Paris, France.
To investigate the influence of tumor cell architecture on T-cell activation, we used an autologous human model based on 2 bladder tumor cell lines as targets for cytotoxic tumor-infiltrating lymphocytes (TILs). These tumor cell lines were grown in vitro as either standard 2-dimensional (2D) monolayers or 3-dimensional (3D) spheroids. T-cell activation was determined by measuring the production of three major cytokines (tumor necrosis factor, granulocyte/macrophage colony-stimulating factor and interferon-gamma), known to be secreted by most activated TILs. Changes in the architecture of target cells from 2D to 3D induced a dramatic decrease in their capacity for stimulating TILs. Interestingly, neither TIL infiltration nor MHC class I, B7.1 costimulatory or lymphocyte function-associated factor-3 adhesion molecule downregulation played a major role in this decrease. These findings demonstrate that tumor architecture has a major impact on T-cell activation and might be implicated in the escape of tumor cells from the immune system. Copyright 2001 Wiley-Liss, Inc.
UI - 11857299
AU - Numahata K; Satoh M; Handa K; Saito S; Ohyama C; Ito A; Takahashi T;
TI - Hoshi S; Orikasa S; Hakomori SI Sialosyl-Le(x) expression defines invasive and metastatic properties of bladder carcinoma.
SO - Cancer 2002 Feb 1;94(3):673-85
AD - Department of Urology, Tohoku University, School of Medicine, Sendai, Japan.
BACKGROUND: Two types of transitional bladder carcinoma have been distinguished based on macroscopic morphology: type A papillary carcinomas, with papillomatous surface outgrowth without infiltration into muscular layer, and type B nodular carcinomas, with a nonpapillomatous surface appearance, most of which display infiltrative growth through muscular layer, and some of which display lymphatic or blood-borne metastasis. However, there is no specific predictor at early stages for later invasive and metastatic clinical outcome of patients with type B tumors. METHODS: The study included 1) glycosphingolipid (GSL) composition of type A and B tumors; 2) histologic and immunohistologic patterns of nodular (type B) bladder carcinoma from 44 patients based on a special sampling procedure termed whole-layer core biopsy (WLCB) using the antisialosyl-Le(x) (anti-SLe(x); SLe(x): NeuAcalpha3Galbeta4[Fucalpha3]GlcNAcbeta3Galbeta4GlcCer) SNH3 antibody or other antibodies; 3) comparison of the incidence of metastasis in patients with SNH3 positive versus SNH3 negative primary tumors and of 5-year survival curves; 4) comparison of bladder carcinoma cell lines from tumors with high versus low malignancy in terms of expression patterns of SLe(x), SLe(a), and other carbohydrates, E-selectin dependent adhesion, and transcript levels of five fucosyltransferases. RESULTS: Anti-SLe(x) monoclonal antibody (mAb) SNH3 staining of WLCB samples from 44 type B tumors showed that the majority of tumors (n = 31 patients) were SNH3 positive and the minority (n = 13 patients) were SNH3 negative. SNH3 positive patients had more lymph node or blood-borne metastasis and lower 5-year and 7-year survival rates, as indicated by Kaplan-Meier curves (P = 0.001). Staining of samples with other antibodies, including FH6 and CA19-9, was not correlated with long-term survival. Determination of GSL composition in extracts showed that SLe(x) ganglioside was present in all three patients with nodular tumors but absent in all three patients with papillary tumors tested. Bladder carcinoma cell lines from invasive tumors that maintained their metastatic properties were SNH3 positive, showed high levels of alpha1,3-fucosyltransferase VI (FT-VI) and FT-VII, and displayed E-selectin dependent adhesion. Cell lines from noninvasive tumors or normal bladder epithelia were negative for SNH3 reactivity, FT-VI, and FT-VII, and E-selectin dependent adhesion. CONCLUSIONS: SLe(x) expression in primary bladder carcinoma, defined by the mAb SNH3, is a predictor of invasive and metastatic outcome. No other carbohydrate epitope examined to date has equal prognostic value. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10268
UI - 11850792
AU - Muller M
TI - Telomerase: its clinical relevance in the diagnosis of bladder cancer.
SO - Oncogene 2002 Jan 21;21(4):650-5
AD - Department of Urology, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. firstname.lastname@example.org
More than 50 years ago, Papanicolaou recognized the importance of a non-invasive technique for the diagnosis and follow-up of patients with carcinoma of the urinary bladder. Cystoscopy, however, has remained the 'gold standard' since no currently available non-invasive method can compete with cystoscopy's sensitivity and specificity. The detection of the ribonucleoprotein telomerase or the telomerase subunits human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in urine samples offer new diagnostic perspectives. The present article presents a review of publications in the literature and evaluates their clinical relevance. The experimental studies reported to date are very promising and show that telomerase exactly fulfils the requirements for a good diagnostic marker for carcinoma of the urinary bladder. The diagnostic application remains in an experimental stage and telomerase is still several steps away for routine use as a clinical parameter. The remaining steps leading to its routine clinical application will be discussed.
UI - 11776593
AU - Shou J; Wang M; Ma J
TI - [Molecular cytogenetic study of bladder transitional cell carcinoma by FISH]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jan;22(1):36-8
AD - Department of Urology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To study the molecular cytogenetic alterations of transitional cell carcinoma of the urinary bladder with exfoliated cells. METHODS: Fluorescence in situ hybridization (FISH) was performed using centromeric probes of chromosome 7, 9, 11 and 17 to examine chromosome aberration of exfoliated cells in 34 urine samples and 30 bladder washings from patients with transitional cell urinary bladder carcinoma. RESULTS: (1) The frequency of numerical aberration of chromosome 7, 9, 11, 17 was 23.5%, 38.2%, 14.7% and 11.8% in urine and 30.0%, 50.0%, 26.7% and 16.7% in bladder washing, respectively. Loss of chromosome 9 was the most common finding, but it was not correlated with pathological grade of cancer and stage of the disease. Abnormality of chromosome 7 was however associated with the clinical stage. (2) The positive rate of examination by cytology and FISH was 29.4% and 55.9% in urine, 27.6% and 73.7% in bladder washing, respectively. When the results of cytology and FISH were combined, the positive rate increased to 67.6% and 80.0% for urine and bladder washing, respectively. CONCLUSION: A number of chromosome aberrations is detected in transitional cell carcinoma of the urinary bladder by FISH technique which provides a basis for further understanding of its molecular pathogenesis and clinical applications.
UI - 11848469
AU - Mahdy E; Pan Y; Wang N; Malmstrom PU; Ekman P; Bergerheim U
TI - Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer are linked to stage and grade.
SO - Anticancer Res 2001 Sep-Oct;21(5):3167-73
AD - Department of Urology, Karolinska Hospital, Stockholm, Sweden. Ensaf.Mahdy@kirurgi.ki.se
Chromosome 8 aberration and c-myc amplification have been suggested as playing important roles in the development of different human cancers. Using fluorescence in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can be detected in cells from bladder cancer. We investigated the correlation of chromosome 8 polysomy, c-myc gene alteration and p53 deletion with histopathological parameters. Twenty-four tumors obtained from patients with bladder cancer were analyzed by interphase cytogenetics using FISH with chromosome 8 and 17 centromere probes together with an YAC clone covering the c-myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8 polysomy was found in 12 tumors. The average copy number of chromosome 8 centromere signals were significantly higher in high grade and stage, cancers. Also the c-myc copy gain and p53 deletion were significantly correlated with grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy (p<0.001). On the contrary there was no significant correlation between c-myc protein over-expression and c-myc gene amplification. These results may indicate that alteration of chromosomal regions on 8q and 17p, including c-myc and p53 genes, may be linked to progression of bladder cancer.
UI - 11859578
AU - Bellaoui H; Chefchaouni MC; Lazrak N; Khalfaoui LC; Yassine F; Elhamany
TI - Z [Flow cytometric DNA analysis and cytology in diagnosis and prognosis of bladder tumors: preliminary results of a comparative study of bladder lavage]
SO - Ann Urol (Paris) 2002 Jan;36(1):45-52
AD - Universite Cadi Ayyad, faculte des sciences et technique, BP 523, Beni Mellal, Maroc. email@example.com
OBJECTIVE: To compare flow cytometric data (ploidy and proliferative activity or percentage SG2M-phase cells) to cytologic and histologic data of the bladder carcinomas. MATERIALS AND METHODS: Cytologic and flow cytometric analysis of DNA content were performed on 48 bladder washings: 28 bladder washings from patients being followed for urothelial carcinomas and 20 control washings from individuals undergoing cytoscopy for other reasons. RESULTS: Cytological sensitivity and specificity of bladder washing were 75% and 91% respectively. Specificity was increased to 94% using flow cytometric DNA analysis whereas sensibility was moderately decreased to 68%. Combination of flow cytometry and cytology increased the diagnostic yield to 100%. The study of the patient group showed an increased abnormalities (aneuploidy and/or proliferate activity SG2M > 10%) according to the tumor grading and tumor staging. A cytometric test was positive in 80% for G3 tumours and in 68% for G2 tumours. The staging tumor was positive in 46%, 89% and 100% of the pTa-pT1, pT2 and pT4 tumours respectively. Otherwise the comparison of control group with patients showed a statistical correlation between cytometric test, staging tumour and tumoral grading as showed in the following groups: control/G1-G2 (p < 0.05), control/G3 (p < 0.001), control/pTa-pT (p < 0.05), control/pT2-pT4 (p < 0.001). CONCLUSION: We confirmed through this study the interest of the flow cytometric DNA analysis in the diagnosis and prognosis of bladder carcinomas, and we showed the importance of the histogram classification in order to facilitate their interpretation and to avoid the trap of false aneuploidy.
UI - 10792157
AU - Corrigan NT; Crooks J; Shand J
TI - Are dedicated bladder films necessary as part of intravenous urography for haematuria?
SO - BJU Int 2000 May;85(7):806-10
AD - Departments of Radiology and Urology, Stobhill General Hospital, Glasgow, UK.
OBJECTIVE: To determine the use and assess the value of full-bladder films during intravenous urography (IVU) which, despite the widespread availability of flexible cystoscopy, remain part of IVU in many radiology departments. Materials and methods A telephone survey of all Scottish radiology departments where IVU is regularly used showed that half routinely included a full-bladder film in the series. The reports of all IVU over 2 years in the authors' department were analysed retrospectively. The index urogram of all patients with bladder tumours confirmed during this period was reviewed independently by three observers, and together with the initial radiological reports was correlated with the cystoscopic and histological findings. RESULTS: From 2625 patients, 139 (5.2%) IVU reports commented on the bladder; 1423 patients presented with no haematuria. None of the patients without haematuria, where a comment was made about the bladder, had pathological evidence of a tumour. Overall 121 of 464 (26%) new bladder tumours were diagnosed on IVU before cystoscopy. Multiple tumours were always undetected and large tumours were often overlooked. CONCLUSIONS: Despite its continuing popularity, IVU is a poor means of identifying bladder tumours and routine views of the full bladder should be abandoned.
UI - 10848689
AU - Krupski T; Moskaluk C; Boyd JC; Theodorescu D
TI - A prospective pilot evaluation of urinary and immunohistochemical markers as predictors of clinical stage of urothelial carcinoma of the bladder.
SO - BJU Int 2000 Jun;85(9):1027-32
AD - Departments of Urology, Pathology and Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. firstname.lastname@example.org
OBJECTIVE: To determine, in patients newly diagnosed with bladder cancer, whether p53, epidermal growth factor receptor (EGFR), microvessel density (MVD), urinary bladder tumour antigen (BTA TRAKtrade mark, Bion Diagnostic Sciences, Redmond, WA) and cytology were predictive of clinical stage, evaluated as a function of the clinical stage obtained at transurethral resection of the bladder tumour with and without the addition of clinical grade, a known strong predictor of urothelial bladder carcinoma were prospectively enrolled in the study. Urine was collected for cytological and BTA TRAK evaluation before transurethral resection. Tumour grade and clinical stage were obtained from the transurethral resection specimen. MVD was evaluated by computerized calculations of 'optimal MVD' (OMVD) and 'area-weighted MVD' (AWMVD) while p53 and EGFR information was obtained by manual immunohistochemical techniques; 21 patients had sufficient tissue for all immunohistochemical assessments and comprised the study group. Univariate and multivariate comparisons were carried out to determine the contribution of each variable to the prediction of clinical stage. RESULTS: Although there was a trend, cytological analysis and p53 and MVD immunoreactivity did not significantly correlate with clinical stage, while tumour grade, BTA TRAK and EGFR immunoreactivity did. In a univariate analysis, tumour grade and BTA TRAK were related to clinical stage. In a multivariate analysis, grade was the single best predictor of clinical stage. This analysis also showed that the addition of BTA TRAK and MVD information to grade incrementally improved the predictive ability of grade. CONCLUSIONS: This pilot study suggests that BTA TRAK and MVD contribute incremental information to tumour grade in predicting the clinical stage of urothelial carcinomas of the bladder; grade remains the most important predictor. These results suggest that further work with BTA TRAK and MVD in more patients and on biopsy material obtained during clinic cystoscopy is warranted for the future development of less invasive methods of identifying patients with invasive bladder cancer.
UI - 11119116
AU - Keegan PE
TI - Re: A prospective pilot evaluation of urinary and immunohistochemical markers as predictors of clinical stage of urothelial carcinoma of the bladder.
SO - BJU Int 2000 Dec;86(9):1096
UI - 11692873
AU - Orlow I; Cordon-Cardo C
TI - Evaluation of alterations in the tumor suppressor genes INK4A and INK4B in human bladder tumors.
SO - Methods Mol Biol 2002;179():43-59
AD - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
UI - 11852762
AU - Rischmann P
TI - [Diagnosis of bladder tumors]
SO - Rev Prat 2002 Jan 1;52(1):32-5
AD - Service d'urologie Hopital Rangueil 31403 Toulouse. email@example.com
Prompt diagnosis of bladder cancer is essential to improve the management of this disease. Hematuria and lower urinary tract symptoms must draw attention to bladder difficulties. The diagnosis is based on cystoscopy and biopsy of any lesions. Once the diagnosis has been established, the tumour should be staged using the TNM system before treatment. Research efforts are continuing to identify biological markers sensitive and specific enough to predict the diagnosis and behavior of this disease accurately.
UI - 11706928
AU - Spyridonos P; Ravazoula P; Cavouras D; Berberidis K; Nikiforidis G
TI - Computer-based grading of haematoxylin-eosin stained tissue sections of urinary bladder carcinomas.
SO - Med Inform Internet Med 2001 Jul-Sep;26(3):179-90
AD - Computer Laboratory, School of Medicine, University of Patras, Rio, Greece.
PURPOSE: A computer-based image analysis system was developed for assessing the malignancy of urinary bladder carcinomas in a more objective manner. Tumours characterized in accordance with the WHO grading system were classified into low-risk (grades I and II) and high-risk (grades III and IV). MATERIALS AND METHODS: Images from 92 haematoxylin-eosin stained sections of urinary bladder carcinomas were digitized and analysed. An adequate number of nuclei were segmented from each image for morphologic and textural analysis. Image segmentation was performed by an efficient algorithm, which used pattern recognition methods to automatically characterize image pixels as nucleus or background. Image classification into low-risk or high-risk tumours was performed by means of the quadratic non-linear Bayesian classifier, which was designed employing 36 textural and morphological features of the nucleus. RESULTS: Automatic segmentation of nuclei on all images was about 90% on average. Overall system accuracy in correctly classifying tumours into low-risk or high-risk was 88%, employing the leave-one-out method and the best combination of three textural and one morphological feature. Classification accuracy for low-risk tumours was 88.8% and for high-risk tumours 86.2%. CONCLUSION: The proposed image analysis system may be of value to the objective assessment of the malignancy of urine bladder carcinomas, since it relies on nuclear parameters that are employed in visual grading and their prognostic value has been proved.
UI - 11830611
AU - Primdahl H; Wikman FP; von der Maase H; Zhou XG; Wolf H; Orntoft TF
TI - Allelic imbalances in human bladder cancer: genome-wide detection with high-density single-nucleotide polymorphism arrays.
SO - J Natl Cancer Inst 2002 Feb 6;94(3):216-23
AD - Molecular Diagnostic Laboratory and Department of Clinical Biochemistry, Aarhus University Hospital at Skejby, Denmark.
BACKGROUND: Bladder cancer is characterized by genomic instability. In this study, we investigated whether genome-wide screening using single-nucleotide polymorphism (SNP) arrays could detect allelic imbalance (loss or gain of at least one allele) in bladder cancers. METHODS: For microarray analysis, DNA was isolated from microdissected bladder tumors and leukocytes from 11 patients. The stage T1 tumor (connective tissue invasive) and the subsequent stage T2-4 tumor (muscle invasive) were available from eight of these patients, and only the first muscle-invasive stage T2-4 tumor was available from three of the 11 patients. The microarray contained 1494 biallelic polymorphic sequences. For microsatellite analyses, DNA was isolated from tumors and leukocytes of nine patients with primary T2-4 tumors and 13 patients with Ta (noninvasive) tumors. All statistical tests were two-sided. RESULTS: We assigned a genotype to 1204 loci, 343 of which were heterozygous. Allelic imbalance was detected in known areas of imbalance on chromosomes 6, 8, 9, 11, and 17, and a new area of imbalance was detected on the p arm of chromosome 6. Microsatellite analysis of nine other T2-4 tumors and 13 Ta tumors showed that allelic imbalance was more frequent in T2-4 tumors than in Ta tumors (P<.001). We detected 8.5 allelic imbalances (median) in 348 informative loci in T1 tumors and 28 allelic imbalances (median) in 329 informative loci in T2-4 tumors. When pairs of T1 and T2-4 tumors were analyzed from eight patients, 68% of imbalances detected in T1 tumors (146 imbalances) occurred in the subsequent T2-4 tumors (99 imbalances). Homozygous TP53 mutations were more often associated (P =.005) with high allelic imbalance than with low allelic imbalance. CONCLUSION: SNP arrays are feasible for high-throughput, genome-wide scanning for allelic imbalances in bladder cancer.
UI - 11857355
AU - Wang L; Habuchi T; Takahashi T; Kamoto T; Zuo T; Mitsumori K; Tsuchiya
TI - N; Sato K; Ogawa O; Kato T No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer.
SO - Int J Cancer 2002 Feb 20;97(6):787-90
AD - Department of Urology, Akita University School of Medicine, Akita, Japan.
The amplification and overexpression of the human epidermal growth factor receptor 2 gene HER-2 (also known as c-erb-B2 or neu) have been shown to be associated with bladder cancer and its progression. Recent studies indicated an association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer. To investigate the correlation between the Ile/Val polymorphism and the susceptibility and progression of bladder cancer, we analyzed the polymorphism in 232 patients with transitional cell carcinoma of the bladder and 408 normal controls. The frequencies of the Ile/Ile, Ile/Val and Val/Val genotype were 75.9%, 21.6% and 2.6%, respectively, in patients with bladder cancer and 75.7%, 23.0% and 1.2%, respectively, in controls. Statistical analyses of the genotype prevalence showed no significant difference between bladder cancer patients and normal controls (p = 0.419). Moreover, no significant differences in the genotype prevalence were observed when the patients were stratified according to the tumor grade, stage and smoking habits. When the Ile/Ile genotype was compared to the Ile/Val and Val/Val genotypes, a significant difference was found only between the patients with tumor stage Ta and those with T1-4 (age, gender and smoking habits-adjusted odds ratio = 2.13, 95% confidence interval = 1.09-4.15, p = 0.027). When the Ile/Ile + Ile/Val genotypes compared to the Val/Val genotype, no significant findings were observed. These results suggested that the HER-2 polymorphism at codon 655 is unlikely to be associated with the onset of bladder cancer. Furthermore, the findings suggest no association between this polymorphism and the disease progression in bladder cancer, although the possibility remains that the Ile/Ile genotype may be related to an increased risk of disease progression. Copyright 2001 Wiley-Liss, Inc.
UI - 11844817
AU - Kuball J; Wen SF; Leissner J; Atkins D; Meinhardt P; Quijano E; Engler
TI - H; Hutchins B; Maneval DC; Grace MJ; Fritz MA; Storkel S; Thuroff JW; Huber C; Schuler M Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation.
SO - J Clin Oncol 2002 Feb 15;20(4):957-65
AD - Department of Medicine III, Johannes Gutenberg University, Mainz, Germany.
PURPOSE: To study safety, feasibility, and biologic activity of adenovirus-mediated p53 gene transfer in patients with bladder cancer. PATIENTS AND METHODS: Twelve patients with histologically confirmed bladder cancer scheduled for cystectomy were treated on day 1 with a single intratumoral injection of SCH 58500 (rAd/p53) at cystoscopy at one dose level (7.5 x 10(11) particles) or a single intravesical instillation of SCH 58500 with a transduction-enhancing agent (Big CHAP) at three dose levels (7.5 x 10(11) to 7.5 x 10(13) particles). Cystectomies were performed in 11 patients on day 3, and transgene expression, vector distribution, and biologic markers of transgene activity were assessed by molecular and immunohistochemical methods in tumors and normal bladder samples. RESULTS: Specific transgene expression was detected in tissues from seven of eight assessable patients treated with intravesical instillation of SCH 58500 but in none of three assessable patients treated with intratumoral injection of SCH 58500. Induction of RNA and protein expression of the p53 target gene p21/WAF1 was demonstrated in samples from patients treated with SCH 58500 instillation at higher dose levels. Distribution studies after intravesical instillation of SCH 58500 revealed both high transduction efficacy and vector penetration throughout the whole urothelium and into submucosal tumor cells. No dose-limiting toxicity was observed, and side effects were local and of transient nature. CONCLUSION: Intravesical instillation of SCH 58500 combined with a transduction-enhancing agent is safe, feasible, and biologically active in patients with bladder cancer. Studies to evaluate the clinical efficacy of this treatment in patients with localized high-risk bladder cancer are warranted.
UI - 11693557
AU - Dulewicz A; Pietka BD; Jaszczak P; Nechay A; Sawicki W; Pykalo R;
TI - Kozminska E; Borkowski A Computer identification of neoplastic urothelial nuclei from the bladder.
SO - Anal Quant Cytol Histol 2001 Oct;23(5):321-9
AD - Department of Biomedical Information Processing Methods, Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw. firstname.lastname@example.org
OBJECTIVE: To introduce computer-based analysis of Feulgen-stained urinary bladder cell nuclei from voided urine to identify neoplastic urothelial nuclei. STUDY DESIGN: Nuclei from 23 healthy people and 33 patients with urinary bladder cancer were analyzed. The nuclei from 9 cancer patients with grade G1 (stage Ta), 17 with grade G2 (stages Ta, T1, T1a and T2) and 7 with grade G3 (stages Cis, Ta + Tis, T1 and T3b) were analyzed. Image analysis was carried out by means of a digital image processing system designed by the authors. Features describing nuclei were selected as the first step of the procedure. Then a multistage classifier was constructed to identify positive and negative cases. RESULTS: The results of this pilot study of a group of 56 patients yielded a 71% correct classification rate in the control group, while a 66% rate was obtained among the cancer patients. The sensitivity of the method was 100% and the specificity was 77%. CONCLUSION: This approach to the identification of neoplastic urothelial nuclei may be sufficiently well developed to be used successfully both in screening high-risk populations and in clinical practice.
UI - 11757669
AU - Toruner GA; Akyerli C; Ucar A; Aki T; Atsu N; Ozen H; Tez M; Cetinkaya
TI - M; Ozcelik T Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and bladder cancer susceptibility in the Turkish population.
SO - Arch Toxicol 2001 Oct;75(8):459-64
AD - Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Turkey.
We investigated the effect of the GSTM1 and GSTT1 null genotypes, and GSTP1 313 A/G polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients, and 121 age- and sex-matched controls of the Turkish population. The adjusted odds ratio for age, sex, and smoking status is 1.94 [95% confidence intervals (CI) 1.15-3.26] for the GSTM1 null genotype, and 1.75 (95% CT 1.03-2.99) for the GSTP1 313 A/G or G/G genotypes. GSTT1 was shown not to be associated with bladder cancer. Combination of the two high-risk genotypes. GSTM1 null and GSTP1 313 A/G or G/G, revealed that the risk increases to 3.91-fold (95% CI 1.88-8.13) compared with the combination of the low-risk genotypes of these loci. In individuals with the combined risk factors of cigarette smoking and the GSTM1 null genotype, the risk of bladder cancer is 2.81 times (95% CI 1.23-6.35) that of persons who both carry the GSTM1-present genotype and do not smoke. Similarly, the risk is 2.38-fold (95% CI 1.12-4.95) for the combined GSTP1 313 A/G and G/ G genotypes and smoking. These findings support the role for the GSTM1 null and the GSTP1 313 AG or GG genotypes in the development of bladder cancer. Furthermore, gene-gene (GSTM1-GSTP1) and gene-environment (GSTM1-smoking, GSTP1-smoking) interactions increase this risk substantially.
UI - 11880082
AU - Peyromaure M; Weibing S; Sebe P; Verpillat P; Toublanc M; Dauge MC;
TI - Boccon-Gibod L; Ravery V Prognostic value of p53 overexpression in T1G3 bladder tumors treated with bacillus Calmette-Guerin therapy.
SO - Urology 2002 Mar;59(3):409-13
AD - Department of Urology, Bichat-Claude Bernard Hospital, Paris, France.
OBJECTIVES: To evaluate the correlation between the overexpression of mutant protein p53 and disease recurrence and progression in patients treated with bacillus Calmette-Guerin (BCG) intravesical therapy for T1G3 bladder cancer. METHODS: We analyzed the outcome of 29 consecutive patients treated for T1G3 bladder tumor with transurethral resection. Patients previously treated for a bladder tumor, those who underwent incomplete resection, and those in whom no assessment of the muscle cell layer was possible were excluded from the study. p53 overexpression was determined using monoclonal p53-DO7 antibody, with a 20% cutoff for definition of positivity. After the initial transurethral resection, all patients were treated with Pasteur BCG (75 mg in 50 mL saline), weekly for 6 weeks. The correlation between p53 overexpression and disease recurrence and progression was assessed by the Fisher exact test. RESULTS: The median follow-up was 36.7 months (range 1 to 108). Of the 29 patients, 18 (62.1%) were p53 positive and 11 (37.9%) were p53 negative. Both groups were similar according to age, tumoral substage (T1a/T1b), association with carcinoma in situ, multifocality, and length of follow-up. The recurrence rate was 54.4% in the p53-negative group versus 38.9% in the p53-positive group (P = 0.47). The progression rate was 18.2% in the p53-negative group versus 33.3% in the p53-positive group (P = 0.67). CONCLUSIONS: These findings suggest that overexpression of p53, as determined immunohistochemically, has no predictive value for recurrence and progression in T1G3 bladder cancers treated with intravesical BCG.
UI - 11697410
AU - Jeon SS; Kang I; Hong JH; Choi HY; Chai SE
TI - Diagnostic efficacy of fluorescence cystoscopy for detection of urothelial neoplasms.
SO - J Endourol 2001 Sep;15(7):753-9
AD - Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
BACKGROUND AND PURPOSE: A major problem diagnosing bladder cancer using conventional white-light cystoscopy is that flat and tiny papillary neoplasms can be overlooked. Fluorescence cystoscopy is based on the detection of protoporphyrin IX (PpIX)-induced fluorescence in urothelial neoplasms through the topical administration of 5-aminolevulinic acid (ALA). The diagnostic efficacy of fluorescence cystoscopy in urothelial neoplasms was evaluated in this study. The focus of this investigation was to ascertain whether fluorescence cystoscopy could make a major contribution to staging and improving the choice of adjuvant therapy after transurethral resection. PATIENTS AND METHODS: A series of 62 patients with suspected bladder cancer were investigated by fluorescence cystoscopy. An intravesical instillation of ALA was conducted 2 hours prior to fluorescence. A total of 274 tissue samples were obtained from the fluorescing and nonfluorescing areas of the bladder. RESULTS: The sensitivity and negative predictive value of fluorescence cystoscopy were 98.0% and 94.7%, respectively, but the specificity was low (42.9%). Among a total of 148 lesions of urothelial neoplasm, 58 foci (dysplasia in 5, carcinoma in situ in 19, stage Ta in 15, T1 in 15, above T2 in 4) that were invisible under white-light cystoscopy were detected by fluorescence cystoscopy. The final histopathologic status was changed in 45% of patients (28/62) according to this technique. Among these patients, eight (13%) needed additional therapy, including a radical cystectomy in one patient and intravesical therapy in 10. CONCLUSIONS: The ALA-based fluorescence cystoscopy technique is a safe and simple procedure that enhances the detection of flat and papillary urothelial neoplasms. Moreover, it will be able to provide useful information that will enable proper staging and appropriate further treatment.
UI - 11851765
AU - Honda N; Yamada Y; Okada M; Aoki S; Kamijyo A; Taki T; Mitsui K; Hibi H;
TI - Fukatsu H Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma.
SO - Int J Urol 2001 Dec;8(12):662-8
AD - Department of Urology, Aichi Medical University School of Medicine, Nagakute, Japan. email@example.com
BACKGROUND: Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. RESULTS: Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. CONCLUSIONS: Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.
UI - 11861364
AU - Liang G; Gonzales FA; Jones PA; Orntoft TF; Thykjaer T
TI - Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2'-deoxycytidine.
SO - Cancer Res 2002 Feb 15;62(4):961-6
AD - USC/Norris Comprehensive Cancer Center, Department of Urology, Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9181, USA. firstname.lastname@example.org
Hypermethylation of the promoters of cancer-related genes is often associated with their inactivation during tumorigenesis. Several preclinical and clinical trials have been developed to use DNA methylation inhibitors, such as 5-aza-2'-deoxycytidine (5-Aza-CdR) in attempts to reactivate silenced genes in human cancers. We used high-density oligonucleotide gene expression microarrays to examine the effects of 5-Aza-CdR treatment on human fibroblast cells (LD419) and a human bladder tumor cell line (T24). Data obtained 8 days after recovery from 5-Aza-CdR treatment showed that more genes were induced in tumorigenic cells (61 genes induced; >or=4-fold) than nontumorigenic cells (34 genes induced; >or= 4-fold). Approximately 60% of induced genes did not have CpG islands within their 5' regions, suggesting that some genes activated by 5-Aza-CdR may not result from the direct inhibition of promoter methylation. Interestingly, a high percentage of genes activated in both cell types belonged to the IFN signaling pathway, confirming data from other tumor cell types.
UI - 11887115
AU - Groah SL; Weitzenkamp DA; Lammertse DP; Whiteneck GG; Lezotte DC; Hamman
TI - RF Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer.
SO - Arch Phys Med Rehabil 2002 Mar;83(3):346-51
AD - Department of Physical Medicine and Rehabilitation, Santa Clara Valley Medical Center, 751 S Bascom Avenue, San Jose, CA 95128, USA. SLGroah@hotmail.com
OBJECTIVES: To evaluate whether the risk of bladder cancer is greater in individuals with spinal cord injury (SCI) than in the general population and whether indwelling catheter (IDC) use is a significant independent risk factor for bladder cancer. DESIGN: Historical cohort study in which subjects with SCI were stratified according to bladder management method and followed for the development of bladder cancer. SETTING: A large rehabilitation hospital in the Spinal Cord Injury Model Systems. PARTICIPANTS: A total of 3670 patients with SCI who were evaluated for bladder cancer on at least 1 occasion by cystoscopy over a period of 1 to 47 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bladder cancer occurring after SCI determined by diagnosis at our facility, by subject report, or by report of next of kin. RESULTS: Twenty-one cases of bladder cancer were found in the 3670 study participants. The risk of bladder cancer for subjects with SCI using IDC is 77 per 100,000 person-years, corresponding to an age- and gender-adjusted standardized morbidity ratio (SMR) of 25.4 (95% confidence interval [CI], 14.0--41.9) when compared with the general population. After controlling for age at injury, gender, level and completeness of SCI, history of bladder calculi, and smoking, those using solely IDC had a significantly greater risk of bladder cancer (relative risk [RR] = 4.9; 95% CI, 1.3--13.8) than those using nonindwelling methods. Mortality caused by bladder cancer in individuals with SCI was significantly greater than that of the US population (SMR = 70.6; 95% CI, 36.9--123.3). CONCLUSIONS: Bladder cancer risk and mortality are heightened in SCI compared with the general population. IDC is a significant independent risk factor for the increased risk of and mortality caused by bladder cancer in the SCI population. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
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