Variability of serum CYFRA 21 - 1 and its susceptibility to clinical characteristics in individuals without cancer: a 4-year retrospective analysis.

BACKGROUND: CYFRA 21 - 1 is a useful marker for diagnosing and monitoring lung cancer. However, its stability remains unclear. Moreover, while its applicability to screening is now being investigated, CYFRA 21 - 1 levels in individuals without cancer, who are targets for cancer screening, have not yet been the focus of research. Therefore, the present study investigated variability in and the factors increasing serum CYFRA 21 - 1 levels. METHODS: This retrospective study recruited 951 individuals undergoing annual medical examinations for six years. We used data obtained in the first four years. Variability in serum CYFRA 21 - 1 levels over a period of four years were investigated. CYFRA 21 - 1 was categorized as normal (≤ 3.5 ng/ml) or elevated (> 3.5 ng/ml). The rate of an elevated level in one visit and the transition from an elevated to normal level between visits were visualized. A multiple logistic regression model was used to study the relationships between the frequency of elevated CYFRA 21 - 1 levels and clinical characteristics, such as age, sex, body mass index, weight changes, and the smoking status. RESULTS: Approximately 5% of subjects had elevated CYFRA 21 - 1 levels once in five tests over four years, while 15% had elevated CYFRA 21 - 1 levels once or more. Among subjects with elevated CYFRA 21 - 1 levels in one blood test, between 63 and 72% had normal levels in the next test. The median CYFRA 21 - 1 level in subjects with elevations in one blood test significantly decreased in the next test at all four time points. The frequency of elevated CYFRA 21 - 1 levels was associated with an older age [odds ratio (OR) = 6.99, 95% confidence interval (CI) = 3.01-16.2], current heavy smoking (OR = 3.46, 95% CI = 1.52-7.9), and weight loss (OR = 1.86, 95% CI = 1.07-3.24). CONCLUSIONS: Variability in and the factors increasing serum CYFRA 21 - 1 levels beyond the cut-off value need to be considered when interpretating CYFRA 21 - 1 test results. The future application of CYFRA 21 - 1 to lung cancer screening may require more than a single measurement.

Age and Smoking Status Affect Serum Cytokeratin 19 Fragment Levels in Individuals Without Cancer.

BACKGROUND/AIM: Lung cancer is a frequent and fatal cancer that is difficult to diagnose in the early stages. CYFRA 21-1 is a serological marker currently used to diagnose and monitor lung cancer; however, its clinical use for screening is controversial. Therefore, the present study investigated the relationship between serum CYFRA 21-1 levels and clinical confounders. PATIENTS AND METHODS: We recruited 3,674 individuals who had never been diagnosed with any cancer. The relationships between high serum CYFRA 21-1 levels (≥3.5 ng/ml) and age, sex, body mass index, and smoking status were investigated. RESULTS: High serum CYFRA 21-1 levels (≥3.5 ng/ml) were detected in 5.1% of all subjects. High serum CYFRA 21-1 levels were observed in 7.3% of current smokers and 4.3% of non-smokers. The proportion of subjects with high serum CYFRA 21-1 levels was markedly higher in the older group (65 years and older, 11%) than in the younger group (younger than 45 years, 2.0%). High serum CYFRA 21-1 levels (≥3.5 ng/ml) were associated with older age [odds ratio (OR)=3.39, 95% confidence interval (CI)=1.79-6.41 for 55-64 years vs. <45 years, and OR=7.34, 95% CI=3.86-13.9 for ≥65 years vs. <45 years, respectively] and current smoking (OR=2.09, 95% CI=1.38-3.15 for current smoker vs. non-smoker). CONCLUSION: High serum CYFRA 21-1 levels were associated with an older age and current smoking, which may be considered as factors influencing CYFRA 21-1 levels.

Hepatic angiomyolipoma associated with splenic hamartoma.

A 52-year-old woman was admitted to our hospital with thrombophlebitis of the internal jugular vein. Abdominal ultrasonography demonstrated a high echogenic mass measuring 4.5 cm in diameter in the liver, and abdominal CT revealed another liver tumor and an isodensity mass in the spleen. Abdominal MRI and angiography were performed and we presumed the tumors to be two hepatic angiomyolipoma and a splenic hamartoma. As an abdominal CT 21 months later revealed that all tumors were growing, these tomors were surgically resected. The histological diagnoses were hepatic angiomyolipoma and splenic hamartoma.

Bradykinin inhibits serum-depletion-induced apoptosis of human vascular endothelial cells by inducing nitric oxide via calcium ion kinetics.

Vascular endothelial cells play important roles in atherogenesis, and bradykinin is associated with atherosclerosis. The effect of bradykinin on apoptosis in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on Ca2+ kinetics and nitric oxide production. In serum-free conditions, the number of apoptotic cells increased in a time-dependent manner, but this increase was inhibited by bradykinin in a dose-dependent manner. The apoptosis inhibited by bradykinin was reduced by nitric oxide inhibitor N(G)-monomethyl-L-arginine (L-NMMA) and consequently restored by combined treatment with L-NMMA and L-arginine. Bradykinin increased influx of extracellular Ca2+, generation of inositol 1,4,5-trisphosphate, and release of Ca2+ from intracellular storage sites, thus increasing the total intracellular Ca2+ concentration ([Ca2+]i). Bradykinin increased nitric oxide production, which was inhibited by L-NMMA and restored by combined treatment with L-NMMA and L-arginine. Sodium nitroprusside (SNP) dose-dependently increased nitric oxide production and inhibited apoptosis; however, 10(-5) M SNP did not inhibit apoptosis. Caspase-3 inhibitor, acetyl-Asp-Met-Gln-Asp-aldehyde, enhanced bradykinin-induced inhibition of apoptosis but did not effect bradykinin-induced nitric oxide production. These findings suggest that bradykinin inhibits serum-depletion-induced apoptosis in HUVECs by enhancing nitric oxide production via an increase in [Ca2+]i.