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  • 1
    Language: English
    In: BJU International, Oct, 2015, Vol.116(4), p.556(12)
    Keywords: Prostate Cancer -- Development And Progression ; Cancer Genetics -- Development And Progression ; Ubiquitin ; Cellular Signal Transduction ; Genetic Research ; Gene Expression ; Proteolysis
    ISSN: 1464-4096
    Source: Cengage Learning, Inc.
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  • 2
    In: BJU International, March 2013, Vol.111(3), pp.419-426
    Description: Byline: , Keywords: bladder cancer; randomized controlled trial; radical cystectomy; transurethral resection; radiation; chemotherapy What's known on the subject? and What does the study add? Results from well designed randomized controlled trials usually provide the strongest evidence possible in favour of one medical intervention over another. For this reason, it is of paramount importance to conduct such trials in bladder cancer, where randomized trials are lacking, in particular to answer questions that have so far confounded us or to investigate the efficacy of new diagnostic tools or interventions. This study provides a demographic analysis of randomized controlled trials published in bladder cancer between the years of 1995 and 2010, with only 238 articles identified. Less than one-third of these reported a statistical power calculation, and only 8% were double-blinded. With many publications inaccurately labelled as randomized trials, we reveal the scarcity of trials performed over the given time period, even compared with other cancers with similar incidence, and highlight the need for more well designed trials to be conducted. Objective To demographically examine randomized controlled trials (RCTs) that have been conducted in bladder cancer over a predefined time period. Methods Various techniques have been described to detect RCTs using different databases. We searched the MEDLINE database by crossing the heading 'Urinary bladder neoplasms' with the MeSHs 'Clinical trial$.mp. OR clinical trial.pt. OR random:.mp. OR tu.xs.' between 1995 and 2010. For the RCTs identified, analysis was performed on each RCT, placing particular emphasis on modality of intervention, cohort size, principal author, region, journal type, disease status, histology, blinding, number of centres involved, performance of a statistical power calculation, accrual status and trial support. Results Of 5002 RCT bladder cancer papers retrieved over the given period, only 238 represented actual RCTs after manual appraisal. More than half of the RCTs investigated medical and surgical therapies (54.2%), and only half had a sample size of 〉100 patients. A small percentage of studies were double-blinded (8.0%), and there was an almost equal distribution of multicentre vs single centre trials (54.6% vs 45.4%). More studies were conducted in Europe (61.3%) than the rest of the world combined, with urologists principally the lead investigators in the majority (72.3%). Most studies were conducted on patients with urothelial carcinoma (97.1%), with less than one-third reporting a statistical power calculation (31.5%). Conclusions Only 238 RCTs were published for bladder cancer between 1995 and 2010. RCTs are under-utilized in bladder cancer. More trials need to be designed with larger sample sizes in order to optimize diagnostic and treatment strategies for patients with bladder cancer. Author Affiliation: Article Note:
    Keywords: Bladder Cancer ; Randomized Controlled Trial ; Radical Cystectomy ; Transurethral Resection ; Radiation ; Chemotherapy
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 3
    In: BJU International, May 2014, Vol.113(5b), pp.E28-E33
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.12344/abstract Byline: Anthony N. Hoang, Piyush K. Agarwal, Annerleim Walton-Diaz, Christopher G. Wood, Adam R. Metwalli, Wassim Kassouf, Gordon A. Brown, Peter C. Black, Diana L. Urbauer, H. Barton Grossman, Colin P.N. Dinney, Ashish M. Kamat Keywords: bladder cancer; ureteral urothelial carcinoma; cystectomy; ureteral margin; upper tract recurrence Objective To assess the incidence and clinical significance of 'skip lesions' that are present in proximal but not in distal ureteric sections, which are occasionally found during the pathological examination of ureteric margins during radical cystectomy (RC). Patients and Methods We identified 660 patients who underwent a RC and had at least two permanent margins for a given ureter. In all, 1173 ureters were analysed and classified as follows: 'normal' (no tumour, reactive atypia, mild or moderate dysplasia) or 'abnormal' (severe dysplasia, carcinoma in situ (CIS), or tumour). Transitions from 'normal' distal pathology to 'abnormal' on proximal section(s) determined frequency of skip lesions. Fisher's exact test and the log-rank test were used to study correlations. Results Ureteric skip lesions were found in 4.8% patients (2.9% ureters). Pathology of skip lesions was CIS in 55.9%, transitional cell carcinoma in 23.5% and severe dysplasia in 20.6%. Skip lesions were associated with lymphovascular invasion (34.4% vs 13.7%, P = 0.004) and advanced pT stage (P = 0.007). On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs 8.2 years, P = 0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 vs 8.8 years, P = 0.066) in pTis disease. Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions. Conclusions The presence of a ureteric skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. Thus, while uncommon, ureteric skip lesions should be reported in pathological findings. Article Note: This research was supported by the M. D. Anderson Cancer Center Bladder SPORE (5P50CA091846-03) and a Department of Urology T32 Training Grant
    Keywords: Bladder Cancer ; Ureteral Urothelial Carcinoma ; Cystectomy ; Ureteral Margin ; Upper Tract Recurrence
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 4
    In: BJU International, July 2015, Vol.116(1), pp.72-78
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.12801/abstract Byline: Ilaria Lucca, Wassim Kassouf, Anil Kapoor, Adrian Fairey, Ricardo A. Rendon, Jonathan I. Izawa, Peter C. Black, Harun Fajkovic, Christian Seitz, Mesut Remzi, Peter Nyirady, Morgan Roupret, Vitaly Margulis, Yair Lotan, Michela Martino, Sebastian L. Hofbauer, Pierre I. Karakiewicz, Alberto Briganti, Giacomo Novara, Shahrokh F. Shariat, Tobias Klatte Keywords: adjuvant chemotherapy; upper tract urothelial carcinoma; radical nephroureterectomy; survival; lymph node positive Objective To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. Patients and methods We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. Results In all patients (T.sub.all N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. Conclusions AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.
    Keywords: Adjuvant Chemotherapy ; Upper Tract Urothelial Carcinoma ; Radical Nephroureterectomy ; Survival ; Lymph Node Positive
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 5
    In: BJU International, December 2010, Vol.106(11), pp.1799-1804
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1464-410X.2010.09424.x Keywords: animal model; bioluminescence imaging; MRI; hypoxia; bladder cancer Abstract: OBJECTIVE To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy. MATERIALS AND METHODS Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified. RESULTS The correlation between MRI volume and BLI was weak in KU7 xenografts (R.sup.2 〈 0.1) but strong in 253J B-V (R.sup.2= 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R.sup.2= 0.42). CONCLUSION The correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method. Author Affiliation: Departments of(*)Urology, ([dagger])Imaging Physics, and ([double dagger])Cancer Biology, the University of Texas, M.D. Anderson Cancer Center, TX, USA Article History: Accepted for publication 22 December 2009 Article note: Peter C. Black, Department of Urologic Sciences, University of British Columbia, Level 6, 2775 Laurel St., Vancouver, B.C. V5Z 1M9, Canada., e-mail: peter.black@ubc.ca
    Keywords: Animal Model ; Bioluminescence Imaging ; Mri ; Hypoxia ; Bladder Cancer
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 6
    In: BJU International, October 2015, Vol.116(4), pp.556-567
    Description: OBJECTIVE: To better characterize the genomics of patients with biochemical recurrence (BCR) who have metastatic disease progression in order to improve treatment decisions for prostate cancer.METHODS: The expression profiles of three clinical outcome groups after radical prostatectomy (RP) were compared: those with no evidence of disease (NED; n = 108); those with BCR (rise in prostate-specific antigen [PSA] level without metastasis; n = 163); and those with metastasis (n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow-up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology.RESULTS: Minimal gene expression differences were observed between adjuvant treatment-naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin-mediated proteolysis, DNA repair, androgen, G-protein coupled and NOTCH signal transduction pathways.CONCLUSION: This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision-making.
    Keywords: Prostate Cancer ; Gene Expression ; Metastasis ; Biochemical Recurrence ; Gene Functional Analysis
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 7
    In: BJU International, November 2019, Vol.124(5), pp.719-721
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 8
    In: BJU International, December 2007, Vol.100(6), pp.1377-1384
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1464-410X.2007.07165.x Keywords: bladder cancer; bioluminescence imaging; intravesical therapy; MRI; orthotopic mouse model Abstract: OBJECTIVES To describe a technique for transurethral tumour inoculation, bioluminescence imaging (BLI) and validation of this approach using ex vivo magnetic resonance imaging (MRI), as a reproducible and quantifiable model of orthotopic bladder cancer is required to enable preclinical pharmacological studies of intravesically administered anticancer agents and the use of BLI provides a sensitive method to monitor tumour growth over time. MATERIALS AND METHODS Human KU-7 bladder tumour cells were transduced with a lentiviral construct to stably express the firefly luciferase gene. These cells were then inoculated in female nude mice by intravesical instillation. BLI was performed weekly and the mice were killed after 4 weeks. Ex vivo MRI and whole-mount step-sections were obtained to assess bladder tumour volume. RESULTS KU-7 tumour cells were highly tumorigenic and were successfully inoculated in 96% of mice. After 4 weeks, all tumours were confined to the mucosa and submucosa ([less than or equal to]pT1). There was an excellent correlation between tumour volume and BLI for both ex vivo bladder MRI (R.sup.2 = 0.929) and end-point histological measurements (R.sup.2 = 0.836). CONCLUSIONS We have established and validated a reliable model of orthotopic bladder cancer that can be used to evaluate various methods of intravesical therapy. BLI allows excellent longitudinal surveillance and quantification of tumour burden. Author Affiliation: (*)The Prostate Centre at Vancouver General Hospital and ([double dagger])Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada, and ([dagger])Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Article History: Accepted for publication 25 May 2007 Article note: Alan I. So, Department of Urologic Sciences, 2775 Laurel Street, Level 6, Vancouver, BC, V5Z 1M9, Canada., e-mail: dralanso@interchange.ubc.ca
    Keywords: Bladder Cancer ; Bioluminescence Imaging ; Intravesical Therapy ; Mri ; Orthotopic Mouse Model
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 9
    In: BJU International, July 2007, Vol.100(1), pp.63-69
    Description: OBJECTIVE: To assess testosterone and haemoglobin kinetics in the Postoperative Adjuvant Androgen Deprivation (PAAD) trial, and correlate these with quality of life (QoL) in this prospective randomized study.PATIENTS AND METHODS: Forty-three patients met the criteria for high-risk cancer after RRP (Gleason score 〉 or = 8, pT3c or Gleason score 7 concomitant with pT3a/b and positive surgical margins) and were prospectively randomized to either observation or AD for 12 months. Haemoglobin and testosterone levels were determined and QoL surveyed at regular intervals for 24 months.RESULTS: Serum testosterone levels were castrate in 19 of 21 treated patients at 3 months and all at 6 months after starting AD. Levels failed to return to normal at 6 months after stopping treatment in six of 16 (38%) patients, and at 12 months in three of 17 (18%). AD caused a delay in the recovery of haemoglobin levels to normal after RRP. There was no statistically significant decline in the Short Form-36 QoL score with AD. Scores on the University of California-Los Angeles Sexual Functioning Scale were decreased during AD, but returned to a level not statistically significantly different from controls after stopping treatment.CONCLUSION: A year of adjuvant AD after RRP affected serum haemoglobin, testosterone and sexual function reversibly, with return to control levels within the subsequent year in most patients. No significant effect on overall QoL with AD was detected in the study.
    Keywords: Prostate Cancer ; Androgen Deprivation ; Adjuvant Therapy ; Testosterone ; Quality Of Life ; Haemoglobin
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 10
    In: BJU International, December 2016, Vol.118(6), pp.855-863
    Description: The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells (), cell‐free (cf) and offer the potential for non‐invasive characterisation of disease and molecular stratification of patients. Furthermore, a ‘liquid biopsy’ approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In prostate cancer, enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor () variants in have shown that such molecular characterisation of provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling axis, such as abiraterone and enzalutamide. New developments in isolation, as well as and analysis of will further promote the use of as a tool for retrieving molecular information from advanced tumours in order to identify mechanisms of therapy resistance. In addition to , nucleic acids such as and cf released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the and other genes detected in or cf of patients with castration‐resistant prostate cancer correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high‐throughput analysis techniques, it is likely that , cf and will be an important component of personalised treatment strategies in the future.
    Keywords: Prostate Cancer ; Biomarker ; Liquid Biopsy ; Circulating Tumour Cell ; Cell‐Free Dna
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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