Dynamic Contrast-Enhanced Imaging as a Prognostic Tool in Early Diagnosis of Prostate Cancer: Correlation with PSA and Clinical Stage.

Background and Purpose: Although several methods have been developed to predict the outcome of patients with prostate cancer, early diagnosis of individual patient remains challenging. The aim of the present study was to correlate tumor perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical prognostic factors and further to explore the diagnostic value of DCE-MRI parameters in early stage prostate cancer. Patients and Methods: Sixty-two newly diagnosed patients with histologically proven prostate adenocarcinoma were enrolled in our prospective study. Transrectal ultrasound-guided biopsy (12 cores, 6 on each lobe) was performed in each patient. Pathology was reviewed and graded according to the Gleason system. DCE-MRI was performed and analyzed using a two-compartmental model; quantitative parameters including volume transfer constant (K trans), reflux constant (K ep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results: K trans (0.11 ± 0.02 min-1 versus 0.16 ± 0.06 min-1; p < 0.05), K ep (0.38 ± 0.08 min-1 versus 0.60 ± 0.23 min-1; p < 0.01), and iAUC (14.33 ± 2.66 mmoL/L/min versus 17.40 ± 5.97 mmoL/L/min; p < 0.05) were all lower in the clinical stage T1c tumors (tumor number, n=11) than that of tumors in clinical stage T2 (n=58). Serum PSA correlated with both tumor K trans (r=0.304, p < 0.05) and iAUC (r=0.258, p < 0.05). Conclusions: Our study has confirmed that DCE-MRI is a promising biomarker that reflects the microcirculation of prostate cancer. DCE-MRI in combination with clinical prognostic factors may provide an effective new tool for the basis of early diagnosis and treatment decisions.

Diffusion-weighted MRI Provides a Useful Biomarker for Evaluation of Radiotherapy Efficacy in Patients with Prostate Cancer.

BACKGROUND: Diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) allows for assessment of tumor aggressiveness. The objective of this study was to evaluate the changes of ADC value in prostate cancer after volumetric-modulated arc radiotherapy (VMAT) and to identify magnetic resonance imaging (MRI) biomarkers for monitoring tissue changes after radiotherapy. PATIENTS AND METHODS: Thirty-seven patients with biopsy-proven prostate cancer treated with VMAT underwent serial MRI examinations including DWI before radiotherapy, and at 3 and 12 months after radiotherapy. ADC values of the tumor and healthy prostate tissue were measured and compared at these three time points. RESULTS: The tumor ADC value increased significantly 3 months after radiotherapy (p<0.0001). There was a further increase of tumor ADC from 3 to 12 months after radiotherapy (p<0.01). The ADC of healthy prostate tissue did not show any significant changes. CONCLUSION: The ADC value is a useful biomarker for evaluating the efficacy of radiotherapy in prostate cancer.

Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects.

YKL-40 is a chitinase-like glycoprotein produced by alternatively activated macrophages that are associated with wound healing and fibrosis. Asbestosis is a chronic asbestos-induced lung disease, in which injury of epithelial cells and activation of alveolar macrophages lead to enhanced collagen production and fibrosis. We studied if YKL-40 is related to inflammation, fibrosis, and/or lung function in subjects exposed to asbestosis. Venous blood samples were collected from 85 men with moderate or heavy occupational asbestos exposure and from 28 healthy, age-matched controls. Levels of plasma YKL-40, CRP, IL-6, adipsin, and MMP-9 were measured with enzyme-linked immunosorbent assay (ELISA). Plasma YKL-40 levels were significantly higher in subjects with asbestosis (n = 19) than in those with no fibrotic findings in HRCT following asbestos exposure (n = 66) or in unexposed healthy controls. In asbestos-exposed subjects, plasma YKL-40 correlated negatively with lung function capacity parameters FVC (Pearson's r -0.259, p = 0.018) and FEV1 (Pearson's r -0.240, p = 0.028) and positively with CRP (Spearman's rho 0.371, p < 0.001), IL-6 (Spearman's rho 0.314, p = 0.003), adipsin (Spearman's rho 0.459, p < 0.001), and MMP-9 (Spearman's rho 0.243, p = 0.025). The present finding suggests YKL-40 as a biomarker associated with fibrosis and inflammation in asbestos-exposed subjects.

Adipokine adipsin is associated with the degree of lung fibrosis in asbestos-exposed workers.

OBJECTIVES: Asbestos-exposure causes an inflammatory response driven by alveolar macrophages that can lead to pulmonary fibrosis. In addition to classical inflammatory cytokines, macrophages produce adipokines which regulate the inflammatory response. We studied if adipokines are related to the degree of parenchymal fibrosis, impaired lung function and inflammation in asbestos-exposed subjects. METHODS: Eighty-five males with moderate to heavy occupational exposure to asbestos and unexposed controls were studied. We measured plasma levels of adipokines adiponectin, adipsin, leptin and resistin, IL-6, IL-8, erythrocyte sedimentation rate (ERS), spirometry and D(L,CO). Degree of interstitial lung fibrosis (septal thickening, subpleural lines, parenchymal bands or honeycombing) was scored in classes 0-5 according to a validated scoring system. The subjects were divided into three groups: normal parenchymal finding (fibrosis class 0), borderline changes (classes 0.5-1.5) and fibrosis (i.e. asbestosis; classes 2-5). RESULTS: Adipsin correlated positively with parenchymal fibrosis (rho=0.412, p<0.001) and there was a linear increasing trend of mean plasma adipsin levels among the three groups of asbestos-exposed subjects (from normal parenchymal finding to borderline changes and to fibrosis) (p<0.0001). Accordingly, plasma adipsin levels correlated positively with the extent of pleural plaques (r=0.245, p=0.043), and negatively with D(L,CO) (r=-0.246, p=0.023). Also, a positive correlation was found between adipsin and inflammatory markers ESR (r=0.315, p=0.008) and IL-6 (r=0.256, p=0.018). CONCLUSIONS: Adipsin was associated with the degree of parenchymal fibrosis, impairment of pulmonary diffusing capacity and with inflammatory activity in asbestos-exposed subjects suggesting that adipsin may have a role in the pathogenesis or as a biomarker in asbestos-induced lung disease.

Pulmonary inflammation in asbestos-exposed subjects with borderline parenchymal changes on HRCT.

Many asbestos-exposed subjects have minor parenchymal changes on high resolution computed tomography (HRCT) that do not fulfil the diagnostic criteria for pulmonary fibrosis and asbestosis. We investigated if these borderline parenchymal changes in asbestos-exposed subjects are related to pulmonary inflammatory activity. Exhaled nitric oxide was measured, exhaled breath condensate collected and HRCT scanned in 104 subjects with moderate to high occupational asbestos exposure. Forty-one healthy unexposed subjects served as a comparison group. After excluding other pulmonary diseases, 35 asbestos-exposed subjects had normal parenchymal findings and 31 subjects had borderline parenchymal changes on HRCT. Lung function was poorer in the latter group, but there was no difference in the degree of asbestos exposure between these groups. As compared with the unexposed comparison group, asbestos-exposed subjects with borderline parenchymal changes had increased alveolar NO concentration (3.0 + or - 0.2 vs. 2.3 + or - 0.1 ppb, p = 0.008) and increased levels of leukotriene B(4) (12.2 + or - 1.1 vs. 3.3 + or - 0.8 pg/ml, p < 0.001) and 8-isoprostane (9.4 + or - 0.7 vs. 7.3 + or - 0.6 pg/ml, p = 0.021) in breath condensate. Asbestos-exposed subjects with normal parenchymal findings had only increased breath condensate levels of leukotriene B(4) (11.4 + or - 0.9, p < 0.001). Borderline parenchymal changes on HRCT in asbestos-exposed subjects are associated with increased markers of pulmonary inflammation. Such borderline parenchymal changes are likely a mild or early form of the same pathological process that leads to asbestosis.

Clinical and HRCT screening of heavily asbestos-exposed workers.

PURPOSE: To characterize asbestosis today and to clarify the indications for high-resolution computed tomography (HRCT) in the surveillance of heavily exposed workers. METHODS: Six hundred and twenty-seven workers were screened and HRCT findings were classified and divided in two groups: pulmonary fibrosis (n = 86) and no fibrosis (n = 541). RESULTS: Most (65/86 = 76%) of the detected fibrosis cases were mild. The magnitude of asbestos exposure showed an unexpected inverse relation with fibrosis. In multivariate analyses, age, forced expiratory volume in 1 s/forced vital capacity ratio, and poor diffusing capacity were associated with HRCT fibrosis, but asbestos exposure was not. CONCLUSIONS: Asbestosis seems to be characterized by mild fibrosis today even in heavily exposed workers. To avoid radiation exposure in HRCT, age and lung function data may be used only to a limited extent to select imaging candidates. Selection and recollection biases may distort the relation between asbestos exposure and fibrosis.

Psychological impact of computed tomography screening for lung cancer and occupational pulmonary disease among asbestos-exposed workers.

The objective of this study was to investigate the psychological impact of screening for lung cancer and occupational pulmonary disease among asbestos-exposed workers. Altogether, 633 workers were screened with chest computed tomography (627 men, 6 women, mean age 64.5 years). Participants' views on the necessity of screening,awareness of asbestos-exposure risks, their perceived lung cancer risk, trial adherence intention, health anxiety,and worry about lung cancer were assessed. Health anxiety was reduced significantly after screening (P < 0.001). After 1 year, no significant long-term psychological differences were found between those who immediately received clear results and those who were submitted to additional examinations because of positive findings. In conclusion,computed tomography screening of pulmonary disease was well accepted and did not produce excessive long-term anxiety or other negative psychological effects,which could prevent the participation in the future screening programs.

The effects of secondhand smoke exposure on HRCT findings among asbestos-exposed workers.

OBJECTIVES: There is evidence suggesting that secondhand smoke (SHS) exposure is causally linked to adverse respiratory effects. We examined the relations between the exposure to SHS and radiological signs in chest high-resolution computed tomography (HRCT). METHODS: Asbestos-exposed workers (n=633) were imaged with HRCT, primarily to investigate potential occupational lung disease. After excluding current smokers, the study population included 361 ex- and 141 never-smokers. They answered a questionnaire on occupational exposures, smoking habits and SHS exposure. HRCT images were assessed for emphysema, ground-glass, irregular/linear and rounded opacities, honeycombing and several other signs. Regression analyses were adjusted for asbestos exposure, ex-smoking, age, body mass index and potential reader effect. RESULTS: Due to missing data the multivariate analyses were restricted to 310 participants aged 47.5-87.0 years. Their lifetime SHS exposure ranged between 0 and 193.5 pack-years (mean 23.5), and exposure in the past 12 months 0-30 packs (0.43). Total (B=0.005, 95% confidence intervals (95% CI) 0.002-0.008, p=0.000) and workplace (B=0.006, 95% CI 0.003-0.009, p=0.001) cumulative SHS exposures were significantly related to ground-glass opacities. Total SHS exposure in the last 12 months (B=0.027, 95% CI 0.000-0.054, p=0.048) and workplace exposure (B=0.027, 95% CI 0.000-0.054, p=0.048) were also significantly related to ground-glass opacities. Positive effects of SHS were also detected on irregular/linear opacities. CONCLUSIONS: SHS exposure in the last 12 months and over lifetime significantly increases ground-glass opacity in HRCT, suggesting an early or subclinical desquamative interstitial pneumonia/respiratory bronchiolitis. This study further supports that SHS has adverse effects on the lungs that can be detected by X-ray methods.