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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Bladder Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
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.
2
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.
3
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.
4
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.
5
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.
6
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.
7
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
8
UI - 11808144
AU - Miyanaga N; Akaza H
TI -
[Bladder cancer]
SO - Nippon Rinsho 2001 Nov;59 Suppl 7():379-85
AD - Department of Urology, Institute of Clinical Medicine, University of
Tsukuba.
9
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.
m.mueller@medizin.fu-berlin.de
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.
10
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.
11
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.
12
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. bellaouifst@yahoo.fr
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.
13
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.
14
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. theodorescu@virginia.edu
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.
15
UI - 11119112
AU - Nabi G
TI -
Re: Extravesical transitional cell carcinoma as a result of implantation
after perforation of the bladder.
SO - BJU Int 2000 Dec;86(9):1094-5
16
UI - 11119115
AU - Yip SK; Peh WC
TI -
Re: Are dedicated bladder films necessary as part of intravenous
urography for haematuria.
SO - BJU Int 2000 Dec;86(9):1095
17
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
18
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.
19
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.
rischmann.p@chu-toulouse.fr
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.
20
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.
21
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.
22
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.
23
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.
24
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. monika@ibib.waw.pl
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.
25
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.
26
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.
27
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.
28
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. 103492@gk.amu.aichi-med-u.ac.jp
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.
29
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.
gliang@hsc.usc.edu
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.
30
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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