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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Bladder Cancer - October 2002
National Cancer Institute®
Last Modified: October 1, 2002
- A study comparing various noninvasive methods of detecting bladder cancer in urine.
- Immunohistochemical detection of the 150-kDa oxygen-regulated protein in bladder cancer.
- Patterns of chromosomal aberrations in urinary bladder tumours and adjacent urothelium.
- Allelic deletions of Rb and L-myc in urine sediments from patients with bladder tumors or carcinoma in situ.
- Suspicious urine cytology (class III) in patients with bladder cancer: should it be considered as negative or positive?
- The role of BTA stat in clinical practice.
- Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract.
- [Application of microsatellite alteration of urine sediment in the early diagnosis of bladder cancer]
- Long term follow-up of superficial invasive bladder carcinoma with or without concomitant epithelial atypia--recurrence and progression.
- [The value of measuring membrane potentials of urothelial cells using cytofluorometry in the study of tumors of the bladder. Preliminary
- The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer.
- Positron emission tomography in urologic oncology.
- Recurrent prostatic stromal proliferation of uncertain malignant potential: a therapeutic challenge.
- Electrical impedance spectroscopy and the diagnosis of bladder pathology: a pilot study.
- Detection of the presence of catalytic subunit mRNA associated with telomerase gene in exfoliated urothelial cells from patients with
- Advanced bladder cancer...where are we now and where are we going?
- The role of chemotherapy and radiation in organ-preservation strategies for muscle-invasive bladder cancer.
- Management of locally advanced bladder cancer: early vs deferred chemotherapy.
- Surgical bladder preserving strategies in the treatment of muscle-invasive bladder cancer.
- Prognostic markers in muscle invasive bladder cancer.
- [Imaging and pathology of bladder tumors]
- Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer.
- Chorionic gonadotropin beta-subunit and core fragment in bladder cancer: mRNA and protein expression in urine, serum and tissue.
- Pathologic evaluation of radical cystectomy specimens.
- The current diagnosis of superficial bladder cancer must be reconsidered.
- Chromosomal aberrations in transitional cell carcinoma: its correlation with tumor behavior.
- Bladder cancer in women.
- WAF1/p21 protein expression is an independent prognostic indicator in superficial and invasive bladder cancer.
- Bladder tumor markers: need, nature and application. 1. Nucleus-based markers.
- Bladder tumor markers: need, nature and application. 2. Tumor and tumor-associated antigens.
- Bladder cancer in women.
- Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients.
Table of Contents
1
UI - 11872026
AU - Saad A; Hanbury DC; McNicholas TA; Boustead GB; Morgan S; Woodman AC
TI -
A study comparing various noninvasive methods of detecting bladder
cancer in urine.
SO - BJU Int 2002 Mar;89(4):369-73
AD - Department of Urology, Lister Hospital, Stevenage, UK.
adnansaad99_@hotmail.com
OBJECTIVES: To compare the nuclear matrix protein (NMP)-22 assay,
bladder tumour specific antigen (BTAstat) test, telomerase activity
(using the telomeric repeat amplification protocol assay, TRAP) and a
haemoglobin dipstick test for their ability to replace voided urine
cytology (VUC) for detecting bladder cancer. PATIENTS AND METHODS: The
study included 120 urological patients prospectively recruited and
assessed before surgery. A single freshly voided urine sample
(approximate 100 mL) was collected from each patient and aliquoted for
each test. All assays were conducted according to the manufactures'
guidelines; 79 patients were tested for telomerase activity. The results
were then compared with VUC and the diagnosis confirmed by cystoscopy
and histology. RESULTS: Fifty-two patients had histologically confirmed
transitional cell carcinoma. The overall sensitivity for BTAstat, NMP22,
telomerase, VUC and dipstick testing was 63%, 81%, 84%, 48% and 50%,
respectively. Combining the results for telomerase and NMP22 gave a
sensitivity of 100%. For G1 tumours the respective sensitivities were
23%, 62%, 56%, 23% and 15%, for G2 tumours, 68%, 86%, 92%, 50% and 41%
and for G3 tumours 88%, 88%, 100%, 71% and 82%. For pTa tumours the
respective detection rates were 48%, 70%, 84%, 39% and 30%, for pT1
tumours 80%, 90%, 90%, 50% and 50%, for pT2/pTis tumours, 100/100%,
100/100%, 100/100%, 88/100% and 88/83%. The overall specificity for the
respective tests was 82%, 87%, 93%, 87% and 54%; combining the results
of NMP22 and telomerase activity increased the specificity to 96%.
CONCLUSIONS: There was significantly better detection than VUC when
using the NMP22 and TRAP assay, especially for well-differentiated (P <
0.001 and 0.0027, respectively) and superficial tumours (P < 0.001 and
0.034, respectively). Combining the results of NMP22 and telomerase
activity yielded values comparable with cystoscopy.
2
UI - 12175409
AU - Asahi H; Koshida K; Hori O; Ogawa S; Namiki M
TI -
Immunohistochemical detection of the 150-kDa oxygen-regulated protein in
bladder cancer.
SO - BJU Int 2002 Sep;90(4):462-6
AD - Department of Urology and Third Department of Anatomy, Kanazawa
University School of Medicine, Kanazawa, Japan.
OBJECTIVE: To investigate the relationship between the expression of the
150-kDa oxygen-regulated protein (ORP150, which functions as a molecular
chaperone in the endoplasmic reticulum for the folding and trafficking
of newly synthesized proteins) and the aggressiveness of bladder cancer,
and the expression of vascular endothelial growth factor (VEGF) and
matrix metalloproteinases (MMPs), as the former is a secreting protein
through the endoplasmic reticulum and the latter are closely involved in
tumour invasion. MATERIALS AND METHODS: Thirty-nine cystectomy
specimens, comprising 12 superficial (pT1) and 27 invasive (pT2-pT4)
tumours, were immunohistochemically analysed using antibodies against
ORP150, VEGF, MMP-1, MMP-2 and MMP-9. Staining was scored from 0 to 3,
according to the ratio of positively staining cells. RESULTS: Staining
was positive (score 1-3) for ORP150 in 10 of 12 superficial and 25 (93%)
of the invasive tumours, with a significantly higher staining score for
stage T4 than stage T1 tumours. The trend was the same for the staining
score of MMP-2, and there was a significant correlation between ORP150
and MMP-2 expression. CONCLUSIONS: The expression of ORP150 was common
in bladder cancer, with a tendency for greater expression in higher
stages. The significant correlation between ORP150 and MMP-2 expression
suggests that ORP150 acts as a molecular chaperone for MMP-2 secretion
and thus tumour invasion.
3
UI - 12210071
AU - Steidl C; Simon R; Burger H; Brinkschmidt C; Hertle L; Bocker W; Terpe
TI -
HJ
Patterns of chromosomal aberrations in urinary bladder tumours and
adjacent urothelium.
SO - J Pathol 2002 Sep;198(1):115-20
AD - Gerhard-Domagk-Institute of Pathology and Department of Urology,
University of Muenster, Muenster, Germany.
Bladder cancer is often characterized by recurrent and multifocal
growth, and tumours are frequently accompanied by precancerous
alterations of the surrounding urothelium. These findings have led to
the hypothesis that cells from areas of genetically aberrant but
morphologically non-cancerous or even unremarkable mucosa may be the
source of bladder carcinomas. Fluorescence in situ hybridization (FISH)
was performed using ten probes targeting five different chromosomes that
are known to be frequently altered in bladder cancer (centromere 1, 8,
9, 11, 17 and 1p36, 8p23, 9p21, 11q13, 17p13) on paraffin-embedded
tissue sections of 11 superficial bladder cancers. Copy number changes
of the tumours were compared to those in the urothelium adjacent to the
tumour. Eleven of 11 (100%) tumours and eight of 11 (73%) samples of
adjacent urothelium showed copy number changes of at least one
chromosome. The occurrence of similar patterns of chromosomal
aberrations in the tumours and their associated urothelium supports the
hypothesis of a clonal relationship. It is concluded that FISH analysis
targeting five different chromosomes is more sensitive than conventional
histology for distinguishing between neoplastic and normal cells of the
urothelium. Copyright 2002 John Wiley & Sons, Ltd.
4
UI - 11956626
AU - Primdahl H; von der Maase H; Christensen M; Wolf H; Orntoft TF
TI -
Allelic deletions of Rb and L-myc in urine sediments from patients with
bladder tumors or carcinoma in situ.
SO - Oncol Rep 2002 May-Jun;9(3):551-5
AD - Department of Clinical Biochemistry, Aarhus University Hospital at
Skejby, 8200 Aarhus N, Denmark.
In a previous study we found allelic imbalances of Rb and L-myc
associated with disease stage and disease course in bladder cancer. The
primary aim of the present study was to determine whether the changes
found in tumors were reflected in urine sediments. Secondly we wanted to
test if Rb and L-myc were frequently lost in urine sediments from
patients with carcinoma in situ and no bladder tumor at present. Based
on this we examined allelic deletions of the Rb and L-myc genes in tumor
and urine from 55 patients with bladder tumors or carcinoma in situ.
Deletions were examined on extracted DNA from tumors and urine sediments
by the use of microsatellite markers located as close to the genes as
possible. Fifty-five patients and 10 controls were included. We found no
strict correlation between allelic deletions in bladder tumors and urine
sediments from the same patient. Allelic deletions in urine sediments
were at least as common in patients with carcinoma in situ and no
bladder tumor (32%) as in patients with bladder tumors (20%). It was
possible to identify allelic deletions in urine sediment from 1 patient
with cystitis and no history of malignant bladder disease (6%). In
conclusion we found no strict correlation between allelic deletions in
bladder tumors and urine sediments. Allelic deletions in urine sediments
seem to be at least as common in patients with carcinoma in situ as in
patients with bladder tumors.
5
UI - 12201938
AU - Raitanen MP; Aine RA; Kaasinen ES; Liukkonen TJ; Kylmala TM; Huhtala H;
TI -
Tammela TL; Finnbladder Group
Suspicious urine cytology (class III) in patients with bladder cancer:
should it be considered as negative or positive?
SO - Scand J Urol Nephrol 2002;36(3):213-7
AD - Department of Urology, Tampere University Hospital, Finland.
OBJECTIVES: Urine cytology is the gold standard in the diagnosis and
follow-up of bladder cancer. Cytology, however, exhibits variable
sensitivity depending on tumour grade and interpretation of urine
specimens is highly dependent on the skill of the examiner. Positive
cytology, classes IV and V by Papanicolaou classification, is a strong
predictor for coexisting or subsequent malignancy, while the role of
suspicious cytology, class III, is controversial. The objective of the
study was to evaluate the role of the suspicious finding in cytological
analysis, and whether it should be considered as a negative or positive
sign for coexisting malignancy. MATERIAL AND METHODS: Six hundred and
fifty-two consecutive patients with bladder cancer were studied in a
prospective multicenter trial. One hundred and fifty-one of the patients
were newly diagnosed, and the remaining 501 patients were under
follow-up. A voided urine sample was obtained prior to TURB or prior to
routine follow-up cystoscopy in those under the surveillance and split
for culture and cytology. The cytopathological results were analyzed by
a central review and only patients with samples available for review
analysis were included. Sensitivity and specificity, as well as positive
(PPV) and negative (NPV) predictive values of urine cytology were
calculated by classifying the class III samples as negative or positive.
RESULTS: A total of 570 patients were evaluable. One hundred and twenty
nine (22.6%) were newly diagnosed and 441 were under follow-up, of whom
117 (26.5%) had recurrence. Cytology was classified as suspicious in
33/129 (25.6%) patients with primary tumour, and in 41/441 (9.3%) of
those under the follow-up, of whom 20 (48.8%) had recurrence.
Sensitivity increased from to 31.0% to 56.6% in primary tumours (p <
0.001) and from 17.8% to 34.7% in recurrent tumours (p < 0.001) if class
III was determined as positive, whereas the specificity decreased from
96.6% to 90.1% (p < 0.001). Accordingly, the NPV increased from 76.3% to
79.1% and the PPV decreased from 65.6% to 56.2%. CONCLUSIONS: The poor
sensitivity of voided urine cytology improved significantly when
suspicious samples were determined as positive while the specificity
remained high, a clear advantage compared with most of the new tumour
marker tests. In addition, nearly half of the follow-up patients with
suspicious class III cytology had recurrence implying that this patient
category is at substantial risk for co-existing malignancy. Therefore,
it is recommended that suspicious class III cytology together with class
IV and V specimens should be considered positive.
6
UI - 11957560
AU - Quek P; Chin CM; Lim PH
TI -
The role of BTA stat in clinical practice.
SO - Ann Acad Med Singapore 2002 Mar;31(2):212-6
AD - Department of Urology, Changi General Hospital, 2 Simei Street 3,
Singapore 529889. pharoahpug@yahoo.co.uk
OBJECTIVE: BTA stat is a rapid, urine-based test for bladder cancer that
detects human complement factor H related protein (HCFHrp) by monoclonal
assay. This aim of this study was to assess the efficacy of BTA stat as
a diagnostic tool for bladder cancer in symptomatic patients suspected
of bladder cancer and in the surveillance of patients with a history of
treated bladder cancer. PATIENTS AND METHODS: One hundred and six
patients presenting with haematuria (gross or microscopic) or irritative
bladder symptoms presenting to the urology outpatient clinic of Changi
General Hospital and 13 patients under bladder cancer surveillance were
recruited for this prospective study. All underwent voided urine
cytology (VUC), urine culture, urine BTA stat, intravenous urogram and
cystoscopy. Sensitivity, specificity, positive and negative predictive
values were calculated for both tests. The stage and grade of bladder
tumours detected were also correlated with both test results. Causes of
false positives and specificity in different patient groups were
analysed. RESULTS: BTA stat is more sensitive than VUC in detecting
primary and recurrent bladder tumours (85% versus 55%) but is less
specific (62.6% versus 100%). Urinary tract infections and urinary
calculi accounted for 62% of false positives with BTA stat. When
patients with positive urine cultures and benign IVU abnormalities were
excluded, specificity of BTA stat improved (93.9% cf. 62.6%). BTA stat
was highly specific (100%) and more sensitive than VUC (75% versus 25%)
in detecting recurrent tumours in asymptomatic patients on cancer
surveillance. CONCLUSION: A high false positive rate and low predictive
value limits the use BTA stat in screening symptomatic patients.
However, it has a role in cancer surveillance and in the screening of
high-risk asymptomatic individuals. Further prospective trials should be
performed to better assess its role in this respect.
7
UI - 12237909
AU - Helpap B
TI -
Morphology and therapeutic strategies for neuroendocrine tumors of the
genitourinary tract.
SO - Cancer 2002 Oct 1;95(7):1415-20
AD - Department of Pathology, Singen, Academic Teaching Hospital of the
University of Freiburg, Singen, Germany. pathologie@hegau-klinikum.de
BACKGROUND: Although many articles have been published regarding
neuroendocrine tumors (NET) and neuroendocrine carcinomas of both low-
and high-grade malignancy (NEC) of the genitourinary tract, the
histologic diagnosis and therapeutic strategies for treating these
entities remains difficult. In the current study the author discusses
the significant differences between NET and NEC of the urinary bladder
and the prostate, including therapeutic consequences. METHODS: Four
hundred eighty neoplasms of the urinary bladder and prostate with a
small cell pattern were analyzed not only on slides stained with
hematoxylin and eosin but also by means of immunohistochemical stains
demonstrating a neuroendocrine origin. The avidin-biotin complex method
was used with the following markers: MIB-1, chromogranin A (Chr A),
synaptophysin (SNP), cytokeratin (CK) 34betaE12, CK20, androgen receptor
(AR), and prostate specific antigen (PSA). RESULTS: Twenty tumors of the
urinary bladder and 26 of the prostate demonstrated a diffuse
neuroendocrine pattern. Only two patients were found to have a low-grade
NEC of the prostate with a low proliferative index but strong expression
of neuroendocrine markers. All other patients with small cell
neuroendocrine carcinomas of the bladder and prostate demonstrated
extremely high proliferation activity (>80%) and expressed Chr A and
SNP. CK34betaE12, 20, PSA, and AR were not found to be expressed. The
mean survival time was 6.9 months. Fourteen of 20 patients with NEC of
the urinary bladder died of the disease and 19 of 24 patients with
prostatic NEC died. The therapy for urinary bladder NEC was repeated
transurethral resection and antiandrogen therapy was given for NEC of
the prostate. Only one patient was treated with chemotherapy, which to
the author's knowledge currently is the only treatment for NECs of the
genitourinary tract. CONCLUSIONS: Undifferentiated carcinomas of the
urinary bladder and prostate should be analyzed not only by means of
hematoxylin and eosin but also by immunohistochemical staining for Chr A
and SNP to demonstrate a neuroendocrine origin. Because the prognosis of
small cell NECs is very poor, pathologists should indicate in their
final report the peculiarities of small cell NECs of the prostate and
the urinary bladder with special emphasis on different therapeutic
strategies. Copyright 2002 American Cancer Society.DOI
10.1002/cncr.10840
8
UI - 11235570
AU - Qiu L; Cong X; Tan Y
TI -
[Application of microsatellite alteration of urine sediment in the early
diagnosis of bladder cancer]
SO - Zhonghua Zhong Liu Za Zhi 2000 Nov;22(6):483-6
AD - Department of Immunology, Institute of Clinical Medical Sciences,
China-Japan Friendship Hospital, Beijing 100029, China.
OBJECTIVE: To assess the usefulness of microsatellite DNA sequence (MS)
alterations in urine sediment for early diagnosis of human bladder
cancer. METHODS: Loss of heterozygosity(LOH) and microsatellite
instability(MIN) in urine sediment from 28 cases of bladder cancer were
detected by polymerase chain reaction (PCR) with selected primers of 10
microsatellite loci. The peripheral blood mononuclear cells and bladder
carcinoma cells were used as controls. RESULTS: In 24 of 28 bladder
cancer patients (85.7%) LOH and MIN were found in urine sediment on at
least one MS locus. Only in 3 of 28 patients(10.7%) was the urine
cytology positive while MS and MIN were detected in these 3 patients.
The conformance of MS alterations between cancer cells and urine
sediment in the same patients was 94.1%. No MS alteration was found in
15 normal controls. CONCLUSION: Application of microsatellite sequence
of urine sediment can be considered as a new tool for screening and
early diagnoses of bladder cancer.
9
UI - 12002359
AU - Zieger K; Olsen PR; Wolf H; Hojgaard K
TI -
Long term follow-up of superficial invasive bladder carcinoma with or
without concomitant epithelial atypia--recurrence and progression.
SO - Scand J Urol Nephrol 2002 Feb;36(1):52-9
AD - Department of Urology, Aarhus University Hospital, Skejby, Denmark.
OBJECTIVE: To examine the significance of concomitant epithelial atypia
on late recurrence and progression by long-term follow-up of superficial
invasive bladder tumours (stage T1). MATERIAL AND METHODS: Seventy
consecutive, unselected patients with newly diagnosed transurethral
resection (TURB)-treated stage T1 bladder tumour, and at least 1 year
progression-free survival. Preselected site biopsies (PSB) were obtained
prospectively to evaluate the significance of concomitant urothelial
atypia. Followed for up to 17.6 years. RESULTS: The cumulative
probability of recurrence (overall) was 85%, and for new stage T1 tumour
70% after 10 years. Forty per cent of those who survived 5 years without
recurrence, were readmitted with often invasive recurrence later.
Positive PSB significantly (p < 0.0001) predicted new T1 tumour.
Progression (T2+ or metastases) occurred in 27 cases (39%) after the
first year. The cumulative probability was 60% (15 years), with a mean
progression-free interval of 64 months. Positive PSB, size >3 cm and
early recurrence were significant predictive factors in multivariate
analysis. CONCLUSION: T1-tumours are at high risk for late invasive
recurrence and progression, especially if associated with urothelial
atypia elsewhere in the bladder.
10
UI - 3190164
AU - Nicolas J; Vieillefond A; Benoit G; Jardin A; Neveux Y; Martin E
TI -
[The value of measuring membrane potentials of urothelial cells using
cytofluorometry in the study of tumors of the bladder. Preliminary
analysis]
SO - Ann Urol (Paris) 1988;22(4):246-8
AD - Centre de Recherches du Service de Sante des Armees, Clamart.
In the context of investigation of a prognostic marker applicable to
bladder tumours, the authors propose the cytofluorometric study of the
membrane potential of malignant urothelial cells using a molecular
probe, 3,3' dihexyloxacarbocyanine. This preliminary study demonstrated
a significant increase in the membrane potential of malignant urothelial
cells in comparison with normal cells, which leads the authors to
propose this cellular parameter as a new tool in the prognostic
evaluation of bladder tumours.
11
UI - 11953885
AU - Turner KJ; Crew JP; Wykoff CC; Watson PH; Poulsom R; Pastorek J;
TI -
Ratcliffe PJ; Cranston D; Harris AL
The hypoxia-inducible genes VEGF and CA9 are differentially regulated in
superficial vs invasive bladder cancer.
SO - Br J Cancer 2002 Apr 22;86(8):1276-82
AD - ICRF Molecular Oncology Laboratory and Angiogenesis Group, Institute of
Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Regulation by hypoxia may underlie the expression of vascular
endothelial growth factor in bladder cancer. We have compared the
distribution of vascular endothelial growth factor mRNA with a hypoxia
marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor
mRNA was analysed by in situ hybridisation and CA IX by immunochemistry
in 22 cases of bladder cancer. The relationship of microvessels to the
distribution of CA IX was determined. In a separate series of 49
superficial tumours, CA IX immunostaining was compared with
clinico-pathological outcome. In superficial and invasive disease there
was overlap in the expression of vascular endothelial growth factor and
CA IX, CA IX being more widespread. Both were expressed predominantly on
the luminal surface, and surrounding areas of necrosis (invasive
tumours). Expression of both factors was greater in superficial disease.
Expression was absent within approximately 80 microm of microvessels.
Unlike vascular endothelial growth factor, CA IX did not predict outcome
in superficial disease. Differential responses to reoxygenation provide
one explanation: vascular endothelial growth factor mRNA declined
rapidly, while CA IX expression was sustained for >72 h. Expression of
vascular endothelial growth factor mRNA in bladder tumours is consistent
with hypoxic regulation and suggests differential regulation in
superficial vs invasive disease. The expression of CA IX on the luminal
surface justifies investigation of its utility as a therapeutic
target/prognostic indicator. Copyright 2002 Cancer Research UK
12
UI - 12228759
AU - Shvarts O; Han KR; Seltzer M; Pantuck AJ; Belldegrun AS
TI -
Positron emission tomography in urologic oncology.
SO - Cancer Control 2002 Jul-Aug;9(4):335-42
AD - Department of Urology, University of California Los Angeles School of
Medicine, Los Angeles, Calif 90095, USA.
BACKGROUND: Positron emission tomography (PET) is an emerging imaging
modality that is being investigated for use in urologic oncology. PET
scanning using the radioactive glucose analog FDG has proven to be a
highly accurate imaging test for diagnosing and staging a variety of
non-urologic cancer types. This review was performed to determine the
role of PET imaging in genitourinary malignancies. METHODS: A review of
the literature focusing on PET and urologic oncology was performed. The
role of PET imaging was reviewed in prostate, bladder, renal, and
testicular cancer. RESULTS: In testicular cancer, PET has a higher
diagnostic accuracy than computed tomography (CT) for both staging and
re-staging and should be the test of choice for the assessment of a
CT-visualized residual mass following chemotherapy. In prostate, renal,
and bladder cancer, the current role of PET is still being defined, but
it has a high positive predictive value and can be used for problem
solving in patients with indeterminate findings on conventional imaging.
Its role in the diagnosis and staging of prostate cancer is hampered by
the generally low glycolytic rate of most prostate tumors and their
metastases. It has shown promise for staging and re-staging patients
with advanced-stage disease and aggressive tumors suspected by a high
tumor grade and high prostate-specific antigen velocity. PET has also
demonstrated success when applied to renal cell carcinoma in classifying
indeterminate renal masses as well as residual renal fossa masses
following nephrectomy, gauging response to therapy, and staging and
re-staging patients with a known diagnosis of renal cell carcinoma.
CONCLUSIONS: PET imaging has demonstrated great potential in certain
applications, but further investigations are necessary to determine its
eventual place as an imaging modality in genitourinary malignancies.
13
UI - 12352429
AU - Klausner AP; Unger P; Fine EM
TI -
Recurrent prostatic stromal proliferation of uncertain malignant
potential: a therapeutic challenge.
SO - J Urol 2002 Oct;168(4 Pt 1):1493-4
AD - Department of Urology, Mount Sinai School of Medicine, New York, New
York, USA.
14
UI - 12352458
AU - Wilkinson BA; Smallwood RH; Keshtar A; Lee JA; Hamdy FC
TI -
Electrical impedance spectroscopy and the diagnosis of bladder
pathology: a pilot study.
SO - J Urol 2002 Oct;168(4 Pt 1):1563-7
AD - Academic Urology Unit and Department of Medical Physics and Engineering,
University of Sheffield, Royal Hallamshire Hospital, United Kingdom.
PURPOSE: Carcinoma in situ is an aggressive form of bladder cancer with
a high propensity for invasion if left untreated. On cystoscopy these
flat lesions cannot be differentiated from other erythematous,
potentially benign areas and they require biopsy for definitive
diagnosis. Other methods of detecting carcinoma in situ remain
experimental. We assessed the effectiveness of electrical impedance
spectroscopy, a method that measures the variation of electrical current
flow with frequency through the mucosa, for differentiating various
pathological changes in the urothelium. MATERIALS AND METHODS: We
obtained 250 impedance measurements immediately after resection in 35
cystectomy specimens using a custom designed probe. Three consecutive
readings were recorded per point to assess reproducibility and punch
biopsy was done at the measurement site. RESULTS: Changes in the
urothelium were classified histologically into 7 subgroups according to
the degree of edema and inflammation. Electrical impedance spectroscopy
measurements were able to separate benign and malignant changes when
tested as a group (p <0.001), although some individual points
overlapped. Edema also had a significant effect on tissue impedance (p
<0.001). CONCLUSIONS: Using measurements we established patterns of
electrical impedance in the human bladder. Early results suggest that
this minimally invasive technique is able to differentiate benign and
malignant bladder pathologies. However, it requires further refinement
and evaluation at lower frequencies, where the greatest impedance
difference in benign and malignant tissues is expected.
15
UI - 12352460
AU - Isurugi K; Suzuki Y; Tanji S; Fujioka T
TI -
Detection of the presence of catalytic subunit mRNA associated with
telomerase gene in exfoliated urothelial cells from patients with
bladder cancer.
SO - J Urol 2002 Oct;168(4 Pt 1):1574-7
AD - Department of Urology, Iwate Medical University School of Medicine,
Morioka, Japan.
PURPOSE: Telomerase has an important role in the immortalization and
oncogenesis of human cancer cells, and it appears to be a promising new
marker for carcinogenesis. We investigated whether expression of the
catalytic subunit of telomerase using reverse transcriptase-polymerase
chain reaction (RT-PCR) can be detected in exfoliated cells in bladder
washing from patients with bladder cancer. MATERIALS AND METHODS:
Exfoliated cells in bladder washing and voided urine samples from
patients with and without bladder cancer were analyzed. To determine the
number of cells required for successful detection of the subunit using
RT-PCR bladder tumor cell lines were used. RESULTS: At least 1 x 10(4)
cells were needed in the cell line study for RT-PCR of the subunit. The
number of cells in bladder washing fluid and voided urine specimens was
more than 5 x 10(4). Human telomerase RT (hTERT) mRNA was expressed in
62 of the 82 bladder washing fluid specimens from patients with bladder
cancer but in only 2 of the 86 with benign urological disorders. Overall
sensitivity for hTERT was 75.6%, that is 52.4%, 80% and 93.8% for grades
1 to 3 tumors, respectively. In contrast, human telomerase associated
protein 1 mRNA was expressed in 17 of the 18 patients with and in 12 of
the 23 without cancer. Overall sensitivity for human telomerase
associated protein 1 was 94.4%. In 4 (57.1%) of 7 spontaneously voided
urine specimens from patients with bladder cancer hTERT mRNA expression
was detected. CONCLUSIONS: Detecting hTERT mRNA expression in exfoliated
cells in bladder washing samples is more useful for the diagnosis,
screening and followup of patients with bladder cancer.
16
UI - 12196896
AU - Sarosdy MF; Machtens S
TI -
Advanced bladder cancer...where are we now and where are we going?
SO - World J Urol 2002 Aug;20(3):143
17
UI - 12196900
AU - Bradley BA; Wajsman Z
TI -
The role of chemotherapy and radiation in organ-preservation strategies
for muscle-invasive bladder cancer.
SO - World J Urol 2002 Aug;20(3):167-74
AD - University of Florida College of Medicine, Division of Urology, P.O. Box
100247, Gainesville, FL 32610-0247, USA. bbradley@ufl.edu
Radical cystectomy with pelvic lymph node dissection has been accepted
as the standard treatment for muscle-invasive bladder cancer. Radiation
therapy and chemotherapy are increasingly being implemented in
bladder-preservation protocols to provide an alternative treatment to
cystectomy. We review experience with radiation and chemotherapy in
treating bladder cancer and their use in bladder-preservation protocols.
Multimodality organ-sparing treatment strategies offer overall survival
rates comparable to radical cystectomy and pelvic lymph node dissection
in selected cases. However, bladder-preservation techniques risk local
recurrence of potentially aggressive tumors whose long-term effect on
cancer-specific survival has not been fully characterized. No
improvement in quality of life has clearly been demonstrated with
bladder-preservation regimens. Bladder-preservation protocols are costly
and require precise coordination of multiple specialists as well as
strict, life-long patient compliance. Bladder-preservation protocols
should only be performed at tertiary care centers with experience in
their administration and be limited to patients desiring an alternative
cystectomy or who are not surgical candidates.
18
UI - 12196901
AU - Syed S; Weiss GR
TI -
Management of locally advanced bladder cancer: early vs deferred
chemotherapy.
SO - World J Urol 2002 Aug;20(3):175-82
AD - The University of Texas Health Science Center at San Antonio, South
Texas Veterans Health Care System, San Antonio, TX 78284-6200, USA.
Locally advanced bladder cancer is associated with a high risk of local
recurrence and distant metastases. Clinical and pathologic variables
have been useful in predicting outcome in patients with muscle-invasive
bladder cancer. Recently, a number of molecular prognostic markers have
been identified that help predict tumor aggressiveness, response to
chemotherapy, and survival. Transitional cell carcinoma is a
chemosensitive tumor. The early use of chemotherapy to reduce the risk
of recurrence and improve survival has been the focus of many randomized
clinical trials. Unfortunately, the majority of studies have failed to
show a survival advantage for chemotherapy-treated patients.
Well-designed prospective trials that target high-risk patients, defined
by clinical, pathological, and molecular features, and incorporate new
more tolerable chemotherapeutic agents are needed to clarify the benefit
of early chemotherapy.
19
UI - 12196902
AU - Kuczyk M; Machtens S; Bokemeyer C; Kollmannsberger C; Hartmann J; Kondoh
TI -
M; Merseburger A; Jonas U
Surgical bladder preserving strategies in the treatment of
muscle-invasive bladder cancer.
SO - World J Urol 2002 Aug;20(3):183-9
AD - Department of Urology, Hanover University Medical School,
Carl-Neuberg-Str. 1, 30625 Hanover, Germany.
Single modality bladder-sparing therapy for muscle-invasive bladder
cancer, including transurethral resection (TUR), partial cystectomy,
systemic chemotherapy or radiotherapy, have been demonstrated to result
in insufficient local control of the primary tumour, as well as
decreased long-term survival in the patients when compared to radical
cystectomy. Therefore, multimodality treatment protocols that aim at
bladder preservation and involve all of the aforementioned approaches
have been established. Arguments for combining systemic chemotherapy
with radiation are to sensitise tumour tissue to radiotherapy and to
eradicate occult metastases that have already developed in as many as
50% of patients at the time of first diagnosis. It has been shown that
the clinical outcome observed with this approach approximates that after
radical cystectomy. Additionally, a substantial number of patients
survive with an intact bladder. However, bladder-sparing approaches are
costly, and require close co-operation between different clinical
specialists as well as careful follow-up. The good long-term results
that are observed after cystectomy and the creation of an orthotopic
neobladder make the substantial advantage of a bladder preservation
strategy questionable when the patient's quality of life is addressed.
Additionally, bladder-sparing therapy-related side effects might result
in an increased morbidity and mortality in those patients who need to
undergo surgery due to recurrent or progressive disease. Multimodality
bladder-sparing treatment is a therapeutic option that can be offered to
the patient at centres that have a dedicated multidisciplinary team at
their disposal. However, radical cystectomy remains the standard of care
for muscle-invasive bladder cancer.
20
UI - 12196903
AU - Tiguert R; Lessard A; So A; Fradet Y
TI -
Prognostic markers in muscle invasive bladder cancer.
SO - World J Urol 2002 Aug;20(3):190-5
AD - Laval University Cancer Research Center, CHUQ-L'Hotel-Dieu de Quebec,
Quebec, G1R 2J6, Canada.
Current tumor, node, and metastasis (TNM) staging and grading systems
are insufficient to accurately predict the evolution of most invasive
bladder cancers irrespective of treatment. Predicting which invasive
tumors will or will not recur or metastasize early is crucial in order
to dictate initial therapy and to better counsel the patient. A need for
tumor markers that could be incorporated into clinical practice to add
prognostic information to the conventional TNM and grading systems in
terms of treatment response and prognosis is crucial. This review
provides an update on the most promising reported single markers and
pathways, including the cell cycle markers p53, p21 and p27, and
potential targets for novel therapies, such as cyclooxygenase 2 (COX 2)
and factors of angiogenesis. The critical steps remain the availability
of large and well-characterized data sets to validate the combination of
markers, as well as high throughput methods to study tumor molecular
fingerprints, such as DNA microarrays.
21
UI - 12218858
AU - Roy C; Merran S
TI -
[Imaging and pathology of bladder tumors]
SO - J Radiol 2002 Jun;83(6 Pt 2):843-59, discussion 861-2
AD - Service de Radiologie B - Chirurgie A, Hopitaux Universitaires de
Strasbourg - Hopital Civil, 1 place de l'Hopital BP 426, 67091
Strasbourg Cedex, France.
Epithelial bladder tumors are very common. Multiple lesions are possible
with variable degrees of malignant potential. Benign and mesenchymal
tumors are much less frequent. The role of imaging is to first raise the
possibility of such a tumor and then to provide pretreatment staging.
Cystoscopy with tumoral resection and histological diagnosis remains
essential for adequate treatment selection. Ultrafast MR imaging may be
very valuable for evaluation of these tumors. Posttreatment follow-up is
needed to detect recurrent tumors. Intravenous urography remains
valuable for evaluation of the upper tracts.
22
UI - 12237776
AU - Watters AD; Latif Z; Forsyth A; Dunn I; Underwood MA; Grigor KM;
TI -
Bartlett JM
Genetic aberrations of c-myc and CCND1 in the development of invasive
bladder cancer.
SO - Br J Cancer 2002 Sep 9;87(6):654-8
AD - University Department of Surgery, Level II, Queen Elizabeth Building,
Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
Detrusor muscle invasive transitional cell carcinoma is associated with
poor prognosis and is responsible for the majority of bladder cancer
related deaths. Amplifications of c-myc and CCND1 are associated with
detrusor-muscle-invasive transitional cell carcinoma, however, their
precise role in driving disease progression is unclear. Fluorescence in
situ hybridisation on archival tissue from 16 patients with primary
diagnosis of > or = pT2 transitional cell carcinoma and 15 cases with
primary pTa/pT1 disease subsequently progressing to
detrusor-muscle-invasion was performed, in the latter group both pre and
post muscle invasive events were studied. No patients presenting with
>/=pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1
amplification. Of patients who developed > or = pT2, two out of 15
(13.3%) had amplification of c-myc, both in > or = pT2, five out of 15
(33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in > or =
pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of
patients' > or = pT2 TCCs were amplified for c-myc and six out of 31
(19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of
tumours were polysomic for chromosome 8 and 80% (37 out of 46) were
polysomic for chromosome 11 and this reflected the high copy numbers of
c-myc and CCND1 observed. In almost all cases an increase in c-myc/CCND1
copy number occurred prior to invasion and persisted in advanced
disease. Amplification of CCND1 or alterations in c-myc/CCND1 early in
bladder cancer may have clinical relevance in promoting and predicting
progression to detrusor-muscle-invasive transitional cell carcinoma.
23
UI - 12074787
AU - Hotakainen K; Haglund C; Paju A; Nordling S; Alfthan H; Rintala E;
TI -
Stenman UH
Chorionic gonadotropin beta-subunit and core fragment in bladder cancer:
mRNA and protein expression in urine, serum and tissue.
SO - Eur Urol 2002 Jun;41(6):677-85
AD - Biomedicum Helsinki, Room A418a, Helsinki University Central Hospital
Research Laboratory, PB 700, 00029, HUCH, Finland.
kristina.hotakainen@hus.fi
OBJECTIVES: Many transitional cell carcinomas (TCC) of the bladder
express the beta-subunit (CGbeta) of chorionic gonadotropin (CG), and
elevated serum levels occur especially in advanced disease. We have
compared the diagnostic utility of various methods for detecting CG and
CGbeta expression at the protein and mRNA level. METHODS: We used RT-PCR
to detect CGbeta mRNA in urinary cells and highly sensitive immunoassays
to determine CG and CGbeta in serum and the core fragment of CGbeta
(CGbetacf) in urine from patients under follow-up for bladder cancer.
Tissue expression was studied by immunohistochemistry. RESULTS: CGbeta
mRNA was detected in urinary cells in 50% (n=84) of the cancer cases and
in none of the healthy controls (n=15). Positive staining for CGbeta in
tissue samples was observed not only in 30% (n=96) of the TCC cases, but
also in 5 of 20 histologically benign samples from TCC patients, and in
10 of 21 samples from benign bladder diseases. Serum and urinary
concentrations of CGbeta were elevated in 29% (n=66) and 8% (n=72),
respectively, while serum CG was elevated in 18% of the TCC patients.
Urinary CGbetacf concentrations were higher in invasive (T1-T4) than
superficial (T in situ and Ta) tumors (p=0.037), in cases positive for
CGbeta mRNA (p=0.03) and cases with suspicious or malignant urinary
cytology (p=0.002). The ratio of urinary to serum concentration of
CGbeta showed the strongest correlation with tumor stage (p<0.00001),
grade (p<0.00001), and staining for CGbeta (p=0.019). CONCLUSIONS:
Although CGbeta expression may occur in benign bladder epithelium,
CGbeta mRNA in urinary cells is a potential marker of bladder cancer.
Urinary and serum CGbeta have low sensitivity in early disease, but the
urine/serum ratio appears to indicate local release of CGbeta into
urine. Further studies are needed to evaluate the clinical usefulness of
different forms of CGbeta expression.
24
UI - 12209761
AU - Herr HW
TI -
Pathologic evaluation of radical cystectomy specimens.
SO - Cancer 2002 Aug 1;95(3):668-9
AD - Department of Urology, Memorial Sloan-Kettering Cancer Center, New York,
NY 10021, USA.
25
UI - 12187034
AU - Zaak D; Hofstetter A
TI -
The current diagnosis of superficial bladder cancer must be
reconsidered.
SO - Urol Int 2002;69(2):85-90
AD - Department of Urology, Klinikum Grosshadern, Ludwig Maximilians
University, Munich, Germany. Dirk.Zaak@uro.med.uni-muenchen.de
The high recurrence and progression rates in superficial bladder cancer
are partially related to the deficiencies of the standard conventional
diagnostic modalities. Therefore, innovative noninvasive and invasive
detection devices have been studied during the last decade. New
diagnostic urine markers are under intensive investigation in order to
exclude the presence of urothelial cancer, but the value of all these
tests is still insufficiently validated in diagnosis and follow-up. With
the introduction of 5-amino-levulinic acid fluorescence endoscopy, the
efficacy of the detection device has been significantly improved. Flat
lesions such as carcinoma in situ can be completely detected besides
exophytic tumors. This is of particular importance because the fate of
the patient depends to an important extent on these tumor entities.
Furthermore, first experimental results using imaging devices like
optical coherence tomography and confocal laser scanning microscopy
promise new powerful noninvasive tools for 'optical sectioning' of the
bladder.
26
UI - 12187044
AU - Yu DS; Chen HI; Chang SY
TI -
Chromosomal aberrations in transitional cell carcinoma: its correlation
with tumor behavior.
SO - Urol Int 2002;69(2):129-35
AD - Uro-Oncology Laboratory, Division of Urology, Department of Surgery,
Tri-Service General Hospital, National Defense Medical Center, National
Defense College, Taipei, Taiwan/ROC. yuds@ms21.hinet.net
OBJECTIVE: Fluorescence in situ hybridization (FISH) was used to study
numerical aberrations of chromosomes 1, 3, 7, 9, 11, 15, 17, X and Y in
interphase nuclei of 16 transitional cell carcinoma (TCC) cell lines of
the urinary tract. The number of chromosomal signal copies was compared
with the DNA ploidy and correlated with the cellular grading and
original tumor staging. METHODS: The single-target FISH with the
repetitive DNA probes for chromosomes 1, 3, 5, 7, 9, 11, 15, 17, X and Y
were performed in 16 human TCC cell lines. For each test specimen, a
minimum of 200 nuclei were analyzed. The number of fluorescent signals
per nucleus was recorded. Tumor ploidy was analyzed using the DNA
propidium iodide flow cytometric method. These results were correlated
with tumor grade and stage. RESULTS: In two diploid TCC cell lines, on
average 67% of detected chromosomes were di-(i)somic. In 14 aneuploid
TCC cell lines, on average only 10% (0-44%) of detected chromosomes were
di-(i)somic. Chromosome X was completely changed into polysomism in 16
TCC cell lines (native male:female ratio = 12:4) but was unrelated to
tumor grade or stage. Chromosome Y was lost in 10 out of 12 (83%) TCC
cell lines which originated from male patients but was unrelated to
tumor grade or stage too. 31% of chromosomes 11 and 15 were disomic in
16 TCC cell lines, 38% of chromosome 3 was monosomic, and 81-88% (83 in
average) of chromosomes 1, 7, 9, 17 were polysomic. Disomic chromosome
11 associated with lower grade TCC and disomic chromosome 15 associated
with higher grade TCC were noted (p < 0.01). Higher incidence of low
stage tumors was observed in TCC cell lines with disomic chromosome 11
or chromosome 15 (p < 0.01). There was no correlation in somatic status
of chromosomes 1, 7, 9, 17 with tumor grade and stage. CONCLUSIONS: The
results of the study demonstrate that polysomism of chromosomes 1, 7, 9,
17 and X occurs in most of the TCC cells with aneuploidy. The stability
of chromosomes 11 and 15 is closely related to tumor grade and stage.
The role of chromosome Y loss and monosomism of chromosome 3 in
oncogenic relevant of bladder cancer is still unclear. Copyright 2002 S.
Karger AG, Basel
27
UI - 10614978
AU - Baniel J
TI -
Bladder cancer in women.
SO - Int Urogynecol J Pelvic Floor Dysfunct 1999;10(6):399-404
AD - Head, Urology Section, Rabin Medical Center, Beilinson Campus, Petach
Tikva, Israel.
In women bladder cancer usually occurs above the age of 60 and comprises
3% of all female cancers. The hallmark of presentation is hematuria,
which must be investigated by radiological imaging and cystoscopy. The
best prognostic indicators are grade and stage. Stage divides the
disease into two separate entities, superficial and invasive disease.
Approximately 70%-80% of patients will present with superficial disease,
10% will fail treatment or progress to invasive disease, and 20% present
with invasive disease. Superficial disease is managed by transurethral
resection and additional intravesical therapy when high-risk parameters
for recurrence or progression exist. Overall survival is good and the
morbidity acceptable. Invasive bladder cancer carries a worse prognosis,
with an average of 50% 5-year survival. Management of invasive disease
warrants extensive surgery, which is the best single treatment modality.
Chemotherapy and radiotherapy are implemented in the management of
progression or metastasis.
28
UI - 11127920
AU - Korkolopoulou P; Konstantinidou AE; Thomas-Tsagli E; Christodoulou P;
TI -
Kapralos P; Davaris P
WAF1/p21 protein expression is an independent prognostic indicator in
superficial and invasive bladder cancer.
SO - Appl Immunohistochem Mol Morphol 2000 Dec;8(4):285-92
AD - Pathology Department, National University of Athens, Greece.
pkorkol@cc.uoa.gr
The inhibitor of cyclin-dependent kinases WAF1 gene product p21 is able
to arrest mammalian cell cycle by mediating p53 and other factors. The
prognostic value and interrelationships between p21 expression and
various parameters in bladder cancer have not been fully elucidated. We
retrospectively investigated the immunohistochemical expression of p21
protein in consecutive paraffin sections from 131 transitional cell
carcinomas (TCCs) and related it to p53 protein expression,
clinicopathologic parameters, proliferative fraction, and survival.
Positivity was displayed in 45% of cases, among which one fourth was
accompanied by p53 accumulation. p21 expression was statistically
related to advanced T category. No association was shown between p21 and
p53 or proliferation rate. Low grade invasive TCCs tended to be more
often p21 positive than high grade invasive TCCs. Most superficial
tumors displayed neither p21 nor p53 expression, whereas the combined
phenotypes p53/p21+ and p53+/p21- predominated among invasive tumors.
P21 labeling index emerged by multivariate analysis as the single
independent indicator of shortened overall (P = 0.0294) and disease-free
(P = 0.0414) survival in superficial TCCs. Conversely, in invasive
tumors, loss of p21 expression was a predictor of shortened disease-free
survival (P = 0.0234) and was associated with poor outcome when
accompanied by p53 accumulation (P = 0.0033). In conclusion, our results
indicate that p21 activation occurs early in tumorigenesis, appears
associated with invasiveness, and is capable of cell cycle control in
TCCs mostly through p53-dependent pathways. Finally, p21 expression,
alone or in combination with p53 and irrespective of other
clinicopathologic parameters, plays distinct roles in determining
clinical outcome in superficial and invasive tumors, suggesting that
urothelial bladder cancer represents two different diseases.
29
UI - 9795828
AU - Kirollos MM; McDermott S; Bradbrook RA
TI -
Bladder tumor markers: need, nature and application. 1. Nucleus-based
markers.
SO - Int Urogynecol J Pelvic Floor Dysfunct 1998;9(4):221-7
AD - Urology Department, Torbay Hospital, South Devon Health Care Trust, UK.
Urothelial tumors are common: their diagnosis and long-term management
represent a large part of most urologists' workload. The majority of
such tumors are 'superficial' and are mostly managed by repeated
cystoscopic surveillance and treatment. A smaller but significant group
of patients either start with, or subsequently progress to, more
invasive disease, thus requiring an alternative and more invasive
treatment. Maximizing the benefit/risk ratio of the diagnosis and the
various trea
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