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Biomedical subjects

James E Montie

Publications and source records attributed to James E Montie.

At least 19 recordsLinked to original sources

Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival.

PURPOSE: Some groups hypothesize that a delay in cystectomy may result in higher pathological stage and possibly alter survival in patients with bladder cancer. The timing of this delay has been somewhat arbitrary. We evaluated the timing from T2 bladder cancer diagnosis to cystectomy, its impact on survival and potential causes of delay. MATERIALS AND METHODS: A contemporary cohort of 214 consecutive patients presented with clinical T2 bladder cancer and underwent radical cystectomy as primary therapy. Clinicopathological parameters were maintained in an institutional database. A review of time to cystectomy, pathological stage, disease specific survival and OS was performed. Variables were tested in univariate and multivariate analyses. The log rank test was used for exploratory analyses to determine meaningful delay cutoff points. RESULTS: Mean followup and time to cystectomy in the entire cohort was 40 months and 60 days, respectively. A significant disease specific survival and OS advantage was observed in patients undergoing cystectomy by 93 days or less (3.1 months) compared to greater than 93 days (p = 0.05 and 0.02, respectively). Pathological staging was similar between the groups (p = 0.15). A multivariate benefit in OS was observed in patients treated with timely cystectomy. The most common factor contributing to cystectomy delay was scheduling delay, as seen in 46% of cases. CONCLUSIONS: A cystectomy delay of 3.1 months undermines patient survival, likely through the development of micrometastases, since local stage progression is not apparent at this point. Most delays are avoidable and should be minimized. Despite the need for second opinions and the impact of busy surgical schedules clinicians must strive to schedule patients efficiently and complete surgical treatment within this time frame.

Aged↗

Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.

Androgens↗

Autoantibody signatures in prostate cancer.

BACKGROUND: New biomarkers, such as autoantibody signatures, may improve the early detection of prostate cancer. METHODS: With a phage-display library derived from prostate-cancer tissue, we developed and used phage protein microarrays to analyze serum samples from 119 patients with prostate cancer and 138 controls, with the samples equally divided into training and validation sets. A phage-peptide detector that was constructed from the training set was evaluated on an independent validation set of 128 serum samples (60 from patients with prostate cancer and 68 from controls). RESULTS: A 22-phage-peptide detector had 88.2 percent specificity (95 percent confidence interval, 0.78 to 0.95) and 81.6 percent sensitivity (95 percent confidence interval, 0.70 to 0.90) in discriminating between the group with prostate cancer and the control group. This panel of peptides performed better than did prostate-specific antigen (PSA) in distinguishing between the group with prostate cancer and the control group (area under the curve for the autoantibody signature, 0.93; 95 percent confidence interval, 0.88 to 0.97; area under the curve for PSA, 0.80; 95 percent confidence interval, 0.71 to 0.88). Logistic-regression analysis revealed that the phage-peptide panel provided additional discriminative power over PSA (P<0.001). Among the 22 phage peptides used as a detector, 4 were derived from in-frame, named coding sequences. The remaining phage peptides were generated from untranslated sequences. CONCLUSIONS: Autoantibodies against peptides derived from prostate-cancer tissue could be used as the basis for a screening test for prostate cancer.

Aged↗

INSPstI polymorphism and prostate cancer in African-American men.

BACKGROUND: Both prostate cancer and diabetes mellitus are common diseases in African-American men. High insulin levels and insulin resistance have been implicated in prostate cancer development, which has prompted a recent investigation of a possible role for germline variation in the insulin gene (INS) and prostate cancer risk. METHODS: Four hundred sixty-six African-American men with and without prostate cancer from the Flint Men's Health Study were typed for the INS Pst1 genotype using restriction digest and direct sequencing. An association between the Pst1 genotype and prostate cancer was examined using crude and age-adjusted logistic regression models. RESULTS: African-American men who were homozygous for the INS PstI CC genotype were 1.59 times more likely to be diagnosed with prostate cancer compared to men with the TT or TC genotypes (95% CI = 0.93-2.72). The association appeared stronger among diabetics compared to non-diabetics; however this observation was not statistically significant. CONCLUSIONS: Our study, taken together with the report of Ho et al., suggests that the INS Pst1 CC genotype is associated with prostate cancer risk in African-American men. Germline variation in the INS gene should be more fully explored in multiethnic studies to elucidate the molecular variant(s) associated with prostate carcinogenesis.

Adult↗

Decreasing age at prostate cancer diagnosis over successive generations in prostate cancer families.

BACKGROUND: The decline in age at prostate cancer diagnosis over the past decade is partially attributable to prostate specific antigen (PSA) screening. We examined age at diagnosis over successive generations within prostate cancer families. METHODS: Families with at least two affected men were selected from the University of Michigan Prostate Cancer Genetics Project. The 1,345 individuals from 489 families were grouped into three generations. RESULTS: Risk of prostate cancer diagnosis at a given age was estimated to increase 1.31 (95% CI: 1.13-1.51) times from one generation to the next. Among men diagnosed prior to the PSA era, inferences were similar (hazard ratio = 1.28, 95% CI: 0.97-1.68). No maternal versus paternal disease transmission effect was observed. CONCLUSIONS: Age at prostate cancer diagnosis was observed to decrease over successive generations in families from an ongoing familial prostate cancer study. This finding, if confirmed, may have important implications for familial prostate cancer risk assessment.

Age Distribution↗

Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.

PURPOSE: We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. PATIENTS AND METHODS: Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. RESULTS: Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P < .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P < .0001) and bowel (P < .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. CONCLUSION: During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.

Aged↗