National Cancer Institute®
Last Modified: October 1, 2002
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. email@example.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.
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.
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.
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.
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.
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. firstname.lastname@example.org
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.
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. email@example.com
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
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.
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.
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.
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
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.
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.
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.
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.
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. firstname.lastname@example.org
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.
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.
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.
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.
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.
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.
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. email@example.com
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.
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.
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.
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. firstname.lastname@example.org
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
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.
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. email@example.com
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.
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