Dataset Information

Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers.

ABSTRACT: We aimed to identify interesting deleted chromosomal regions for bladder cancer diagnosis and carcinogenesis, and to evaluate the association between loss of heterozygosity (LOH) and clinico-pathological parameters. Microsatellite analysis was performed on urine sediment and tumor tissue from 43 consecutive patients with superficial transitional cell carcinoma (TCC) and from 42 consecutive controls. Informative cases were scored as LOH or allelic loss (AL) according to the decrease of the allelic-imbalance ratio. The prevalence of LOH and AL was 39.5% and 86%, respectively. Chromosome 9 was the most frequently altered, especially at 9p (35%). The total number of microsatellite alterations per analysis was correlated with age, grade, stade and EAU classification. The locus 17p13.1 was strongly associated with high-stage (p=0.01) and high-grade tumors (p=0.02). Specificity and sensitivity of LOH was 100% and 39.3% for diagnosis of malignant urinary disease. Specificity and sensitivity of AL was 73.8% and 88%, respectively. Allelic losses are a frequent and early event in bladder cancer, especially at 9p. Thanks to its high specificity, LOH may serve as a complementary tool for non invasive diagnosis of bladder cancer. Further study is warranted to evaluate the prognostic value of LOH on recurrence, progression and muscle invasion.

SUBMITTER: Legrand G

PROVIDER: S-EPMC3189821 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers.

Legrand Guillaume G Soliman Hany H Dubosq Francis F Vérine Jérôme J Desgrandchamps François F de Thé Hugues H Mongiat-Artus Pierre P Ploussard Guillaume G

American journal of cancer research 20110405 5

We aimed to identify interesting deleted chromosomal regions for bladder cancer diagnosis and carcinogenesis, and to evaluate the association between loss of heterozygosity (LOH) and clinico-pathological parameters. Microsatellite analysis was performed on urine sediment and tumor tissue from 43 consecutive patients with superficial transitional cell carcinoma (TCC) and from 42 consecutive controls. Informative cases were scored as LOH or allelic loss (AL) according to the decrease of the alleli ...[more]

PMID: 21994900

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Project description:A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality.This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected "clinical-optimal" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using "computed-optimal" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume.For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes.Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue.

Project description:PurposePrior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer.Materials and methodsUsing an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival.ResultsMedian patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04).ConclusionsPharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial.

Project description:BackgroundNonmuscle-invasive bladder cancer (NMIBC) disproportionately affects older adults who often have coexisting chronic conditions such as metabolic syndrome (MetS). Although prior research suggests that MetS is a risk factor for NMIBC, limited data exists on whether MetS is associated with NMIBC recurrence. Our objective was to evaluate the association between MetS and recurrence in older adults treated for NMIBC.MethodsWe identified 1,485 older (age ≥60 years) NMIBC patients (American Joint Committee on Cancer Stage ≤1) from 2community-based health systems. Using data from the health systems' electronic medical record, MetS was defined as the presence of three of the following: diagnosis codes indicating hypertension, hyperlipidemia, diabetes, or body mass index >30. Follow up time was determined by date of the last follow up in the tumor registry and censored at 10 years. Cox proportional hazards regression of time to recurrence that accounts for the competing risk of death included adjustment for age, sex, smoking status, health system, NMIBC stage/grade, tumor size, and number of specimens with cancer.ResultsOverall, 341 patients (23%) met MetS criteria. Median follow up was 5.9 years and 582 patients (39.2%) died. Patients with MetS were more frequently male (84.2%), and mostly current/former smokers (82.6%). By 10 years, 34.1% of the cohort had experienced a recurrence. After accounting for the competing risk of death, there was no association between MetS and time to recurrence (adjusted hazard ratio, 0.88, 95% confidence interval 0.70-1.11, P = 0.28). Patients without MetS had more 0a/low grade recurrences (49.1% vs. 41.4%), though differences were not significant.ConclusionWe found no association between MetS and risk of NMIBC recurrence in this large, multisite cohort of older adults with NMIBC. In order to design personalized care for older NMIBC patients, future research is needed to evaluate associations between common chronic conditions and a variety of oncologic outcomes.

Dataset Information

Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers.

Publications

Prevalence and spectrum of microsatellite alterations in nonmuscle invasive bladder cancers.

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