The potential use of ultra-low radiation dose images in digital mammography--a clinical proof-of-concept study in craniocaudal views.

OBJECTIVE: To estimate the potential of low-dose images in digital mammography by analysing the effect of substantial dose reduction in craniocaudal (CC) views on clinical performance. METHODS: At routine mammography, additional CC views were obtained with about 10% of the standard dose. Five radiologists retrospectively read the standard [mediolateral oblique (MLO) + CC] and combination low-dose mammograms (standard MLO + low-dose CC). If present, lesion type, conspicuity and suggested work-up were recorded. Final diagnoses were made by histology or follow up. A t-test or χ(2) test was used to compare results. RESULTS: 421 cases were included, presenting 5 malignancies, 66 benign lesions and multiple non-specific radiologic features. Using MLO with low-dose CC, all lesions were detected by at least one reader, but altogether less often than with standard mammography (sensitivity, 73.9% vs 81.5%). Missed lesions concerned all types. Lesions detected with both protocols were described similarly (p = 0.084) with comparable work-up recommendations (p = 0.658). CONCLUSION: Mammography with ultra-low-dose CC images particularly influences detection. While sensitivity decreased, specificity was unaffected. In this proof-of-concept study a lower limit was to be determined that is not intended nor applicable for clinical practice. This should facilitate further research in optimization of a low-dose approach, which has potential in a relatively young and largely asymptomatic population. ADVANCES IN KNOWLEDGE: Tungsten/silver-acquired mammography images might facilitate substantial dose reduction. Ultra-low-dose CC images reduce sensitivity, but not specificity. Low-dose images have potential in a largely young and asymptomatic population; a baseline is set for further research in optimization of a low-dose approach.

High-grade clear cell renal cell carcinoma has a higher angiogenic activity than low-grade renal cell carcinoma based on histomorphological quantification and qRT-PCR mRNA expression profile.

Clear cell renal cell carcinoma (CC-RCC) is a highly vascularised tumour and is therefore an attractive disease to study angiogenesis and to test novel angiogenesis inhibitors in early clinical development. Endothelial cell proliferation plays a pivotal role in the process of angiogenesis. The aim of this study was to compare angiogenesis parameters in low nuclear grade (n=87) vs high nuclear grade CC-RCC (n=63). A panel of antibodies was used for immunohistochemistry: CD34/Ki-67, carbonic anhydrase IX, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). Vessel density (MVD - microvessel density), endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. mRNA expression levels of angiogenesis stimulators and inhibitors were determined by quantitative RT-PCR. High-grade CC-RCC showed a higher ECP% (P=0.049), a higher TCP% (P=0.009), a higher VEGF protein expression (P<0.001), a lower MVD (P< 0.001) and a lower HIF-1alpha protein expression (P=0.002) than low-grade CC-RCC. Growth factor mRNA expression analyses revealed a higher expression of angiopoietin 2 in low-grade CC-RCC. Microvessel density and ECP% were inversely correlated (Rho=-0.26, P=0.001). Because of the imperfect association of nuclear grade and ECP% or MVD, CC-RCC was also grouped based on low/high MVD and ECP%. This analysis revealed a higher expression of vessel maturation and stabilisation factors (placental growth factor, PDGFB1, angiopoietin 1) in CC-RCC with high MVD, a group of CC-RCC highly enriched in low nuclear grade CC-RCC, with low ECP%. Our results suggest heterogeneity in angiogenic activity and vessel maturation of CC-RCC, to a large extent linked to nuclear grade, and, with probable therapeutic implications.