Digital chest radiography: an update on modern technology, dose containment and control of image quality

The introduction of digital radiography not only has revolutionized communication between radiologists and clinicians, but also has improved image quality and allowed for further reduction of patient exposure. However, digital radiography also poses risks, such as unnoticed increases in patient dose and suboptimum image processing that may lead to suppression of diagnostic information. Advanced processing techniques, such as temporal subtraction, dual-energy subtraction and computer-aided detection (CAD) will play an increasing role in the future and are all targeted to decrease the influence of distracting anatomic background structures and to ease the detection of focal and subtle lesions. This review summarizes the most recent technical developments with regard to new detector techniques, options for dose reduction and optimized image processing. It explains the meaning of the exposure indicator or the dose reference level as tools for the radiologist to control the dose. It also provides an overview over the multitude of studies conducted in recent years to evaluate the options of these new developments to realize the principle of ALARA. The focus of the review is hereby on adult applications, the relationship between dose and image quality and the differences between the various detector systems

The role of Cyclin D1 and Ki‐67 in the development and prognostication of thin melanoma

Background Despite their low individual metastatic potential, thin melanomas (≤ 1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by pre‐clinical results, we investigated cyclin D1 protein and Ki‐67 expression in in situ, metastatic and non‐metastatic thin melanomas. Material and Methods Immunohistochemistry was performed on 112 melanoma specimens, thereof 22 in situ, 48 non‐metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki‐67 expression were semi‐quantitatively evaluated by three independent investigators and compared between groups. Results Epidermal Ki‐67 expression did not differ statistically in in situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in situ melanoma (P = 0.003). No difference was found in cyclin D1 expression between metastatic and non‐metastatic invasive tumours. Metastatic and non‐metastatic thin melanomas did not show significant differences in epidermal expression of Ki‐67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki‐67 was more frequent in metastatic than non‐metastatic samples (28.6 vs. 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki‐67 expression was confirmed by multivariate analysis (P = 0.047). Conclusion We found an increased expression of cyclin D1 invasive thin melanomas compared to in situ melanomas which supports a potential role of this protein in early invasion in melanoma, as suggested by pre‐clinical findings. Moreover, our results confirm that high dermal Ki‐67 expression is associated with an increased risk of metastasis development in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods

Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity

Abstract Background Growing evidence supports the use of low-carbohydrate/high-fat ketogenic diets as an adjunctive cancer therapy. However, it is unclear which genetic, metabolic, or immunological factors contribute to the beneficial effect of ketogenic diets. Therefore, we investigated the effect of ketogenic diets on the progression and metabolism of genetically and metabolically heterogeneous melanoma xenografts, as well as on the development of melanoma metastases in mice with a functional immune system. Methods Mice bearing BRAF mutant, NRAS mutant, and wild-type melanoma xenografts as well as mice bearing highly metastatic melanoma allografts were fed with a control diet or ketogenic diets, differing in their triglyceride composition, to evaluate the effect of ketogenic diets on tumor growth and metastasis. We performed an in-depth targeted metabolomics analysis in plasma and xenografts to elucidate potential antitumor mechanisms in vivo. Results We show that ketogenic diets effectively reduced tumor growth in immunocompromised mice bearing genetically and metabolically heterogeneous human melanoma xenografts. Furthermore, the ketogenic diets exerted a metastasis-reducing effect in the immunocompetent syngeneic melanoma mouse model. Targeted analysis of plasma and tumor metabolomes revealed that ketogenic diets induced distinct changes in amino acid metabolism. Interestingly, ketogenic diets reduced the levels of alpha-amino adipic acid, a biomarker of cancer, in circulation to levels observed in tumor-free mice. Additionally, alpha-amino adipic acid was reduced in xenografts by ketogenic diets. Moreover, the ketogenic diets increased sphingomyelin levels in plasma and the hydroxylation of sphingomyelins and acylcarnitines in tumors. Conclusions Ketogenic diets induced antitumor effects toward melanoma regardless of the tumors´ genetic background, its metabolic signature, and the host immune status. Moreover, ketogenic diets simultaneously affected multiple metabolic pathways to create an unfavorable environment for melanoma cell proliferation, supporting their potential as a complementary nutritional approach to melanoma therapy