Health‐related quality of life after salvage high‐intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer

Objective: To evaluate health‐related quality of life (HRQOL) after salvage high‐intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Methods: Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA‐PCI) questionnaire at baseline and at follow‐up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow‐up. Results: Fifty‐seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6–29 months). The mean score for urinary function decreased from 79.7 ± 12.1 prior to HIFU to 67.4 ± 17.8 after HIFU (P < 0.001). The mean score for sexual function decreased from 32.1 ± 24.1 prior to HIFU to 17.2 ± 17.0 after HIFU (P < 0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Conclusion: Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow‐up of 17.5 months.     

A gene signature of primary tumor identifies metastasized seminoma

Background

The aim of this study was the prediction of metastatic status in seminoma based on examination of the primary tumor.

Methods

Total RNA was isolated from metastasized seminoma (n = 10, T1N1-2M0), non-metastasized seminoma (n = 21, T1-3N0M0), and corresponding normal tissues. Pooled RNA from 10 biopsies of each tissue type was hybridized on whole genome microarrays for screening purposes. Ninety-two selected gene candidates were quantitatively examined using real-time quantitative polymerase chain reaction (RTQ-PCR).

Results

Agreement in gene expression was 88% between the whole genome microarrays and RTQ-PCR. Metastasized seminoma showed 1,912 up-regulated and 2,179 down-regulated genes with ≥2-fold differences in gene expression compared non-metastasized seminoma. RTQ-PCR of selected genes showed that mean gene expression values were significantly reduced in metastasized compared with non-metastasized seminoma. The presence of metastases could be predicted based on an 85-gene expression signature by using logistic regression. Sensitivity and accuracy of the 10-fold cross-validation model were 77.8% and 84.2%, respectively.

Conclusion

A logistic regression model using an 85 gene expression signature allowed identification of metastasized seminoma from the primary tumor with a sensitivity of 77.8%.     

Second-order spatial analysis of epidermal nerve fibers

Breakthroughs in imaging of skin tissue reveal new details on the distribution of nerve fibers in the epidermis. Preliminary neurologic studies indicate qualitative differences in the spatial patterns of nerve fibers based on pathophysiologic conditions in the subjects. Of particular interest is the evolution of spatial patterns observed in the progression of diabetic neuropathy. It appears that the spatial distribution of nerve fibers becomes more 'clustered' as neuropathy advances, suggesting the possibility of diagnostic prediction based on patterns observed in skin biopsies. We consider two approaches to establish statistical inference relating to this observation. First, we view the set of locations where the nerves enter the epidermis from the dermis as a realization of a spatial point process. Secondly, we treat the set of fibers as a realization of a planar fiber process. In both cases, we use estimated second-order properties of the observed data patterns to describe the degree and scale of clustering observed in the microscope images of blister biopsies. We illustrate the methods using confocal microscopy blister images taken from the thigh of one normal (disease-free) individual and two images each taken from the thighs of subjects with mild, moderate, and severe diabetes and report measurable differences in the spatial patterns of nerve entry points/fibers associated with disease status.     

Analyzing direct and indirect effects of treatment using dynamic path analysis applied to data from the Swiss HIV Cohort Study

When applying survival analysis, such as Cox regression, to data from major clinical trials or other studies, often only baseline covariates are used. This is typically the case even if updated covariates are available throughout the observation period, which leaves large amounts of information unused. The main reason for this is that such time‐dependent covariates often are internal to the disease process, as they are influenced by treatment, and therefore lead to confounded estimates of the treatment effect. There are, however, methods to exploit such covariate information in a useful way. We study the method of dynamic path analysis applied to data from the Swiss HIV Cohort Study. To adjust for time‐dependent confounding between treatment and the outcome ‘AIDS or death’, we carried out the analysis on a sequence of mimicked randomized trials constructed from the original cohort data. To analyze these trials together, regular dynamic path analysis is extended to a composite analysis of weighted dynamic path models. Results using a simple path model, with one indirect effect mediated through current HIV‐1 RNA level, show that most or all of the total effect go through HIV‐1 RNA for the first 4 years. A similar model, but with CD4 level as mediating variable, shows a weaker indirect effect, but the results are in the same direction. There are many reasons to be cautious when drawing conclusions from estimates of direct and indirect effects. Dynamic path analysis is however a useful tool to explore underlying processes, which are ignored in regular analyses. Copyright © 2011 John Wiley & Sons, Ltd.