Investigation on tumor hypoxia in resectable primary prostate cancer as demonstrated by <Superscript>18</Superscript>F-FAZA PET/CT utilizing multimodality fusion techniques

Purpose  

As hypoxia is believed to play an important role in the development and progression of prostate cancer, we evaluated whether ¹⁸F-labeled fluoroazomycin arabinoside (¹⁸F-FAZA) would be useful to identify tumor hypoxia in resectable prostate cancer.     

Value of fluorodeoxyglucose positron emission tomography in characterizing clinically‐significant thyroid carcinomas

Background: Despite the rising incidence of thyroid incidentalomas, their clinical significance remains unclear. The present study aimed to determine whether fluorodeoxyglucose positron emission tomography (FDG‐PET) is associated with a significantly higher risk of clinically‐significant thyroid carcinoma (CSC) in incidentalomas than other non‐functional imaging modalities. Methods: Over a 2‐year period, 89 patients were identified as having a thyroid incidentaloma. All patients had either surgery or fine needle aspiration cytology (FNAC) with a 12‐month follow up to confirm the nature of the incidentaloma. Surgery was carried out for nodules with malignant or indeterminate FNAC result, or those with in a retrosternal location, with size > 4 cm or local symptoms. Results: A total of 21 (23.6%) patients had their incidentaloma detected by FDG‐PET (PET group) and 68 (76.4%) by non‐PET imaging modalities (non‐PET group). Differentiated thyroid carcinoma was confirmed in 18 (20.2%) patients. The rate of malignancy was 61.9% in the PET group and 7.4% in the non‐PET group (P = 0.001). After excluding the occult microcarcinomas, the risk of malignancy reduced to 14.6%, but the difference in malignancy rate became more marked between the PET and non‐PET group (42.9% vs 2.9%, P = 0.001). The maximum standardized uptake value on FDG‐PET was similar between benign and malignant lesions (P = 0.124). Conclusion: The overall risk of CSC in thyroid incidentalomas was 14.6%. Those detected by FDG‐PET were significantly more likely to harbour CSC than those by non‐functional modalities. Incidentalomas with focal FDG uptake should be thoroughly investigated with USG and FNAC.     

Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes

OBJECTIVE

Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D–binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.

RESEARCH DESIGN AND METHODS

A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.

RESULTS

Serum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5–4,345.0; interquartile range 354.1–]586), intermediate in first-degree relatives (402.9 µg/mL [204.7–4,850.0; 329.6–492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3–1,305.0; 328.3–473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9–1,602.0; 326.9–449.9]) than female subjects (433.4 µg/mL [99.3–4,850.0; 359.4–567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.

CONCLUSIONS

Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.Various pathways and characteristics of vitamin D metabolism, such as vitamin D analogs and polymorphisms in the vitamin D receptor, as well as genes encoding specific vitamin D enzymes, recently have been associated with type 1 diabetes (1). For example, reduced serum vitamin D concentrations have been noted for those with type 1 diabetes (2–4), but the disease specificity ascribed to these reductions recently has been questioned (5). Indeed, vitamin D deficiency does not seem to be an uncommon event (6). Vitamin D therapy (active form) can modulate the development of disease in the nonobese diabetic (NOD) mouse model of autoimmune diabetes (7,8), and a variety of trials have tested whether vitamin D supplementation has the capacity to modify the development of this disease (2). To that question, a meta-analysis of trials seeking such a therapeutic benefit suggests that vitamin D supplementation can reduce disease risk (9,10).This said, despite our current understanding of the vitamin D pathway, including its capacity to modulate the immune system (6), the causal relationship between impaired vitamin D constituents and the development of type 1 diabetes remains uncertain. This is largely attributed to the intricate nature of vitamin D metabolic processes, as well as the extensive biological effects exhibited by its components. Therefore, understanding the influence of the vitamin D pathway on the pathogenesis of type 1 diabetes requires a systematic examination into the distinct roles of its various components.One essential component of the vitamin D pathway is the polymorphic vitamin D–binding protein (VDBP), also known as group-specific component (G_c). Aside from its main function of vitamin D transport and preservation, VDBP has been shown to scavenge actin, bind fatty acids, activate macrophages, stimulate osteoclasts, enhance the chemotactic activity of C5-derived peptides, and associate with immune cell surfaces, such as T and B cells (11). Even after ligand binding, 98–99% VDBP binding sites remain unoccupied, which suggests a function beyond vitamin D transport (11). Although several studies have associated specific VDBP gene polymorphisms with the presence of diabetes (i.e., type 1 and type 2 diabetes) (12,13), we sought to confirm this association and identify differences in VDBP levels in patients with type 1 diabetes.     

Polypoid pseudomyxoma of ascending aorta after replacement with a Dacron graft

We report a 58-year-old man who had a multi-lobulated pseudomyxomatous lesion in his ascending aorta 6 months after his root and ascending aorta was replaced by a Dacron graft.