Objective: Bilirubin has strong antioxidative activity and thus may have a protective effect against the progression of atherosclerosis. We recently reported a significant correlation between serum levels of total bilirubin and smoking or obesity, As few studies have separately examined such correlations with direct or indirect bilirubin, in the present study we evaluated correlations between them and smoking.
Methods: Our subjects were 8,955 men (average age 48.1±10.1 years old) who underwent an annual heath check-up at our clinic in 2010 and had serum total bilirubin levels under 2.3mg/dl. A self-administered health questionnaire about smoking was used. Correlations among blood pressure, liver function, blood sugar, serum lipid levels and smoking were analyzed as dependent variables in logistic regression models.
Results: The questionnaire revealed that there were 2,570 smokers (28.7%). Both serum levels of direct and indirect bilirubin in non-smokers were significantly higher than those in smokers. Significantly positive correlations between direct bilirubin and AST, ALT or γ-GTP were observed, although correlation coefficients were not high. On the other hand, there were negative correlations between indirect bilirubin and ALT or γ-GTP. Logistic regression analyses showed that there was a significant correlation between smoking and indirect bilirubin (odds ratio; 0.243), but not between smoking and direct bilirubin.
Conclusions: The present study revealed a significant correlation between smoking and indirect bilirubin. This finding suggests that serum levels of indirect bilirubin may be a smoking indicator.

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Objective: Hepatic hemangiomas are often detected by abdominal ultrasonography. Many researchers have reported that most hepatic hemangiomas do not change in size over short-term observation but few have studied changes in size over long-term observation periods. We therefore examined changes in hepatic hemangioma size over a prolonged observation period of ≥20 years.
Methods: Out of examinees diagnosed with hepatic hemangioma by abdominal ultrasonography in our health management center, 16 who underwent prolonged observation of ≥20 years were enrolled in this retrospective cohort study. The rate of change in tumor size was evaluated from the difference between the initial size and the latest measured size.
Results: The rate of change in the size of tumors was -45.5 to +225.0% (mean: +47.4%, 95% confidence interval: -0.8 - +95.6%) for a prolonged observation period of 240 to 303 months (mean ± standard deviation : 263.4 ± 22.4 months). There was a decrease in size in 6 patients (37.5%) and an increase in size in 10 patients (62.5%). The size increased by 3-fold or more in 3 patients (18.8%).
Conclusion: Our results suggest that there is no change in hepatic hemangioma size over short-term observation, but sometimes the size increases over prolonged observation. Therefore, hepatic hemangiomas should be examined periodically.

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Objective: Because carbon dioxide (CO₂) is well absorbed by body tissue it should be useful for relieving distress after endoscopy by decreasing the insufflated gas volume, and have no effect on the results of subsequent examinations. In recent years, CO₂ has been used to reduce distress after colonoscopy. In the present study, we investigated whether the use of carbon dioxide alleviated distress in patients who underwent esophagogastroduodenoscopy (EGDS) and whether it affected the results of abdominal ultrasonography performed immediately after endoscopy.
Methods: Our subjects were those who underwent an annual health check-up that included EGDS and abdominal ultrasonography in our hospital. The relief of distress was compared with that in the previous year by means of a questionnaire. The effect of CO₂ on the results of ultrasonography were assessed using abdominal ultrasonographic images obtained after EGDS. Medical technology specialists compared the ultrasonographic images with those obtained in the previous year.
Results: Distress after EGDS was less or unchanged as compared with that in the previous year. The quality of the ultrasonographic images was considered to be poorer in about 27% of patients, but images were assessable in all patients.
Conclusions: Our findings suggested that the use of CO₂ in EGDS alleviated discomfort after examination, as compared with conventional methods. Abdominal ultrasonographic images obtained after EGDS using CO₂ use were slightly affected, but there was no apparent effect on image evaluation. These results suggested that abdominal ultrasonography can be performed after EGDS.

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Objective: Five years have passed since the Specific Health Examination and Specific Health Guidance were introduced with the aim of reducing metabolic syndrome. In their 6th year, these programs have entered a second phase, with some revisions. However, while hyperuricemia is recognized to be a lifestyle-related disease that is closely associated with obesity and metabolic syndrome, uric acid levels are not included in the basic tests. In the present study, we therefore examined a relationship between obesity-associated factors and uric acid levels.
Methods: The subjects were 909 persons (708 males and 201 females, average age 48.7 years, 45.3 years, respectively) who received a health check-up at our facility, in which visceral fat area was measured by CT scan. We examined a relationship between uric acid levels and the obesity-related factors, which are BMI, waist circumference, visceral fat area, subcutaneous fat area, and visceral fat/subcutaneous fat area ratio. We also examined a relationship between levels of uric acid and serum creatinine, an indicator of kidney function.
Results: The mean uric acid level was 6.1 ± 0.1 mg/dL in males and 4.3 ± 0.1 mg/dL in females. There was a significant positive correlation between all obesity-related factors showed and uric acid, with visceral fat area having the highest correlation coefficient (r=0.322, p<0.0001). The correlation coefficient between the uric acid level and all obesity-related factors was greater in females. The significant positive correlation between uric acid and serum creatinine showed that serum uric acid and renal function were closely related.
Conclusions: The findings of our study revealed that, among obesity-related factors, visceral fat was the most closely associated with serum uric acid levels and suggest that it should be included in the Specific Health Examination, aiming at further reducing metabolic syndrome. The closer relationship in females between uric acid levels and obesity-related factors including visceral fat is of interest and should be the subject of further studies.

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Objective: To examine the effectiveness of the FIB4 index as an indicator of fibrosis in fatty liver.
Methods: In fatty liver patients examined several times, we calculated the FIB4 index for the initial and final examinations. Taking the cutoff point for fibrosis as 2.67, 12,059 individuals in whom the index was less than 2.67 were enrolled as the subjects of this study. The change in the FIB4 index during the period from the initial to the final examination was determined. For subjects in whom the FIB4 index had risen to 2.67 or over at the final examination, we made comparisons by gender as well as by whether the fatty liver was alcoholic or non-alcoholic. We analyzed changes in the factors of the FIB4 calculation formula (age, AST, ALT, platelet counts) as well as those in ultrasonography images.
Results: The FIB4 index had risen to 2.67 or above in 161 subjects (1.3%) at the final examination and in these subjects it was significantly higher than at the initial examination. There had been an increase in FIB4 index in 1.1% of subjects followed up for less than 5 years, whereas FIB4 index had increased in 1.6% of those followed up for 5 years or more and the difference between these groups was significant. There were no differences in frequencies of rises in FIB4 index between males and females or between alcoholic and non-alcoholic fatty livers. Regarding the 4 factors of the FIB4 index calculation formula, the biggest change was in AST, with the AST/ALT ratio increasing from 0.86 at the initial examination to 1.18 at the final examination. The only change in ultrasonography images observed was dullness of the hepatic margin in 3 of the 161 subjects.
Conclusion: The length of time required for changes in the FIB4 index and the greater change in AST suggest that it could be used as a predictive index of fibrosis.

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Objective: Examination for early detection of glaucoma is now being reevaluated, since an epidemiological study by the Japan Glaucoma Society demonstrated the importance of normal tension glaucoma (NTG). Funduscope and intraocular pressure exam results were analyzed to investigate the current status of patients with glaucoma in our hospital.
Methods: A database of 76,245 subjects who underwent funduscope and intraocular pressure exams in health check-ups from January 2010 through December 2012 was used for our investigation. Among examinees considered to have NTG in health check-up exams, the proportion in whom a final diagnosis of glaucoma was made by an ophthalmologist was investigated. Also, prevalence of glaucoma by age was investigated in those being treated for glaucoma as outpatients and with a previous history of glaucoma in addition to patients with glaucoma diagnosed in health check-ups.
Results: Out of the 76,245 subjects, 272 were diagnosed with glaucoma (0.4%). Among them, 234 (86.0%) had NTG, which had been assumed to account for about 70% of glaucoma. Its prevalence in patients aged 40 and over was 3.3%, which was lower than that in a previous study (5%). We consider our prevalence was lower because there were not many subjects older than 70 in our sample.
Conclusion: Therefore, we believe that glaucoma is not satisfactorily identified in current examinations. It is difficult to detect glaucoma using the current basic exams in health check-ups so there is a need to consider introducing a visual field test.

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Esophagogastroduodenoscopy on a man in his 30s during a health check-up revealed multiple polypoid lesions in the esophagus, stomach and duodenum. In addition, colonoscopy showed that there were a few small polyps in the terminal ileum and colon, and multiple small polypoid lesions in the colon. As physical findings, there were small papules on his face and extremities, and papillomatous lesions in the oral cavity. Cowden disease (CD) was suspected from his family history. Based on this as well as the typical endoscopic findings and characteristic mucocutaneous lesions, we made the diagnosis of CD.

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We evaluated the socioeconomic significance regarding the standard testing items in the multiphasic health check-ups (Ningen Dock) by the Delphi survey among the Ningen Dock specialists. We surveyed by reference to the methods of the U.S. Preventive Services Task Force, which tackled with the issue of “insufficient evidence”. The 4 evaluation domains were “potential preventable burden”, “potential harm of the intervention”, “costs (both monetary and opportunity)”, and “current practice”. This study will contribute to the appropriate testing in Ningen Dock.

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