Shuichi Mihara

Emphysema detected by lung cancer screening with low-dose spiral CT: Prevalence, and correlation with smoking habits and pulmonary function in Japanese male subjects

Objective:  Screening with low‐dose spiral CT is a promising new tool for early lung cancer detection. A study was undertaken to assess the prevalence of emphysema detected by CT screening, and to assess the correlation between the extent of emphysema and the severity defined according to the recently published Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

Early detection of renal cell carcinoma by ultrasonographic screening—based on the results of 13 years screening in Japan

Abdominal ultrasonographic (US) screening of 219,640 persons has been performed in the past 13 y, and 723 (0.33%) cases of malignant neoplasm were detected. Renal cell carcinoma (RCC) was detected in 192 cases (0.09% of the examinees). In almost all cases of RCC, no symptoms were evident and no abnormalities were detected in the blood chemistry tests or urinalyses. A total of 189 cases (98%) were resected curatively, and 38% of the tumors were less than 25 mm in size (T1). With respect to pTNM classification, 35% were pT1 and 52% were pT2. No metastasis to the lymph nodes or other organs was found in any case. The cumulative survival rate for cases resected was 97% at 5 y, and 95% at 10 y. Regarding US features of RCC, the internal echo pattern of half of T1 tumors showed homogeneous and hyperechoic, and became heterogeneous as they grew. Other notable US findings in cases of RCC were marginal hypoechoic zone (29%), anechoic component in the tumor (23%), and protrusion from the kidney (85%, 71% of the T1 tumors). US screening is useful for detection of RCC in the early stage. However, to detect small tumors, it is very important to know well the US features of RCC. For cost-effectiveness analysis, it is more effective to examine, not only the kidney, but other abdominal organs. It is expected that many other abdominal cancers, such as hepatocellular carcinoma, gallbladder cancer, pancreatic cancer, and so on, could be found in the early stage by broad implementation of US screening.

The combination of mitochondrial low enzyme-activity aldehyde dehydrogenase 2 allele and superoxide dismutase 2 genotypes increases the risk of hypertension in relation to alcohol consumption.

A cooperative role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and superoxide dismutase 2 (SOD2) to maintain the vascular function has recently been demonstrated in nitrate tolerance. The present study examined whether the combination of low enzyme-activity variants of ALDH2 and SOD2 increases the risk of hypertension in relation to alcohol consumption. A total of 444 Japanese participants in a health-screening program were evaluated. The risk of hypertension among the individuals harboring both the ALDH2*2 allele and the SOD2 Val/Val genotype was significantly higher in drinkers than in nondrinkers (adjusted odds ratio, 6.22; 95% confidence interval, 2.26–17.1; P<0.001). Among these individuals, the systolic/diastolic blood pressure also increased by 0.24/0.14 mmHg for each 1g/day increase in alcohol consumption (P<0.001/P=0.003). These associations were observed, but the degree was lower among those with the other genotype combinations (0.11/0.10 mmHg; P=0.012/P=0.001). Information about the genetic predisposition to alcohol-related diseases may thus be useful to promote lifestyle modifications for high-risk individuals.

Correlation of C-reactive protein with disease severity in CT diagnosed emphysema

Background and objective:  Recent studies suggest that CRP levels are related to airflow obstruction. However, limited data exist on the relevance of CRP levels in individuals with or without emphysema. The aim of this study was to assess the relationship between the extent of emphysema, COPD severity and serum CRP levels.

Interactive effects of smoking and glutathione S-transferase polymorphisms on the development of non-alcoholic fatty liver disease

Glutathione S-transferases (GSTs) protect cells against exogenous and endogenous oxidative stress. GST polymorphisms are associated with the development of cardiovascular disease (CVD) and diabetes mellitus (DM), especially in current-smokers. Non-alcoholic fatty liver disease (NAFLD) is a predictor of future CVD or DM, because oxidative stress contributes to their pathogenesis. This study investigated whether the combination of smoking status and GST genotypes could affect the risk for NAFLD. A cross-sectional analysis was conducted among 713 Japanese participants (458 males and 255 females) during a health screening program. The GSTM1 null, GSTT1 null, GSTP1 A/B or B/B and GSTA1 A/B or B/B genotypes were determined and deemed to be high-risk genotypes. The prevalence of NAFLD was 18.7%. Among never-smokers, carriers of one, and those of two or more high-risk GSTM1, GSTP1 or GSTA1 genotypes were at a higher risk for NAFLD than those who were not carriers [odds ratio (95% confidence interval): 2.6 (1.1-5.9) and 3.3 (1.3-8.1), respectively], and the risk was further increased among current-smokers [4.6 (1.6-13.0) and 5.4 (1.2-23.7), respectively]. This is the first report to show that the combination of current-smoking and harboring high-risk GSTM1, GSTP1 and/or GSTA1 genotypes is interactively associated with the risk of NAFLD.

Possible associations between antioxidant enzyme polymorphisms and metabolic abnormalities in patients with schizophrenia

Background This study investigated the possible association between common and potentially functional polymorphisms of antioxidant enzymes and metabolic abnormalities in patients with schizophrenia. Methods The possible associations of the glutathione S-transferase (GST) M1 null and GSTT1 null genotypes, and the superoxide dismutase 2 (SOD2) Val16Ala polymorphism with the risks of being overweight and having metabolic syndrome were examined using a logistic regression analysis in 154 schizophrenic Japanese patients and 203 controls. Results Among smokers with schizophrenia, the risks of being overweight and having decreased high-density lipoprotein cholesterol were significantly higher in those with the GSTM1 null genotype than in those with the present genotype (odds ratio 3.20 and 3.15, P=0.03 and P=0.04, respectively), while among nonsmokers with schizophrenia, the risk of an abnormal waist circumference was lower in those with the GSTM1 null genotype (odds ratio 0.34, P=0.04). The risk of a decreased high-density lipoprotein cholesterol level was significantly higher in patients with the combined GSTM1 null and GSTT1 present genotypes than in those with the present genotypes of both genes (odds ratio 3.60, P<0.01). The SOD2 Val16Ala polymorphism was not associated with risk of metabolic abnormalities in either group. Conclusion The present study suggests that the GSTM1 null genotype, in combination with smoking status or GSTT1 genotype, might be associated with the metabolic abnormalities in patients with schizophrenia.

Efficacy of Ultrasonic Mass Survey for Abdominal Cancer

From August 1983 through March 1995, 204,099 people received ultrasonic mass survey of the abdomen for the first time. Among these examinees, 631 (0.31%) malignant neoplasm cases, such as 201 hepatocellular carcinoma (HCC), 81 gallbladder (GB) cancer, 57 pancreatic cancer, and 169 renal cell carcinoma (RCC), were detected. Three hundred seventy six out of 590 cases (64%), excluding chronic leukemia cases and metastatic liver cancer cases, were surgically resected. The resection rate of HCC, GB cancer, pancreatic cancer, and RCC were 25%, 88%, 49%, and 99%, respectively. The cumulative survival rate of the 376 resected cases was 79.5% at 10 years. The cumulative survival rates of resected cases of HCC, GB cancer, pancreatic cancer and RCC were 34% at ten years, 83% at 10 years, 49% at 7 years, and 99% at 10 years, respectively. Ultrasonic mass survey is dramatically useful for early detection of various kinds of abdominal cancers, especially RCC and GB cancer. From now on, many earlier abdominal cancers will be found by establishing and promoting ultrasonic mass survey systems.

Glutathione S-transferase A1 polymorphism as a risk factor for smoking-related type 2 diabetes among Japanese

Glutathione S-transferases protect cells against exogenous and endogenous oxidative stress. Type 2 diabetes is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This study investigated whether GSTA1*A/*B and GSTP1Ile105Val polymorphisms could affect the risk for type 2 diabetes. A cross-sectional case-control analysis included 468 (326 men and 142 women) Japanese participants in a health screening program. The prevalence of type 2 diabetes was 11.3% (63 subjects: 52 male and 11 female). The frequency of GSTA1*B allele carriers was higher in diabetes than in non-diabetes, though the difference was not statistically significant (adjusted OR, 1.8; 95% CI, 0.9-3.4). The risk among the GSTA1*B allele carriers was significantly increased by current-smoking status (adjusted OR, 3.7; 95% CI, 1.1-12.7; vs. never-smoking non-carriers), whereas the smoking status was not an independent risk factor. The GSTP1 genotype alone or in combination with the smoking status did not affect the risk for diabetes. This is the first report to show that the GSTA1*B allele is a potential risk factor for smoking-related type 2 diabetes.

Present status and technique for early detection of renal cell carcinoma and urinary tract cancer in US screening

1983年度から2003年度までの腹部超音波検診受診者延べ1,375,565名から1,403例の悪性疾患が発見された．そのうち腎泌尿器の悪性疾患は，腎細胞癌337例，腎盂尿管癌18例，膀胱癌123例，前立腺癌62例など545例で，38.8％を占めた．腎細胞癌，腎盂尿管癌，膀胱癌，前立腺癌の切除例はそれぞれ332例（98.5％），16例（88.9％），121例（98.4％），10例（16.1％），切除例の10年生存率は腎細胞癌96.8％，腎盂尿管癌52.0％，前立腺癌100％，膀胱癌では7年生存率99.1％であった．腎細胞癌は病期 I が86％，膀胱癌は病期 I が98.3％を占めたのに対し，腎盂尿管癌では病期 I が33.3％，病期III・IVが60％であった．膀胱癌では98.3％がTUR-Btにて治療された．超音波検診は，腎細胞癌，膀胱癌の早期発見にきわめて有用である．小腎細胞癌は高エコー均一な腫瘍が多く，血管筋脂肪腫との鑑別が重要である．また，腫瘍径の増大とともに，不均一になる．嚢胞タイプの腎癌では，壁の肥厚や内部の充実エコーに注意することが発見のポイントになる．腎盂尿管癌では，CEC内の充実エコー像やCECの経時的変化，水腎・水尿管に注意する．膀胱癌は後壁（三角部）に多発し，隆起性病変の検出がポイントである．

Evaluation of the Results of Mass Colorectal Cancer Screening by Immunological Fecal Occult Blood Test.

1987年4月から行なってきた免疫便潜血検査 (OCヘモディア) による大腸癌検診の評価を行なうとともに, 今後の課題と対策について検討した。1993年3月までの6年間の延べ受診者数は172,474名, 要精検者数6,952例 (4.0%), 精検受診者数4,706例 (受診率67.7%) で, 大腸癌144例 (発見率0.08%, 153病変) が発見され, 93例 (64.6%) が早期癌であった。153病変のうち早期癌は101例 (66.0%) で, 71例 (70.3%) がポリペクトミーにて治癒していた。大腸癌発見率は女性より男性で高率であった。特に50歳以上の男性の発見率は極めて高く, この年齢層に対する検診受診勧奨が重要と思われた。さらに, 効果的な大腸癌検診を行なっていくためには, 精検未受診者に対する徹底した精検受診勧奨を行ない, 精検受診率を高めていく努力が必要である。精検方法および検診受診歴の分析からは, 必ずしも十分な精査が行なわれていないことが伺えた。便潜血検査のみで再検を行なう医療機関も存在し, 大腸癌検診に対する認識を高める必要がある。精検の精度を高めるためには, 十分な精査・治療が可能な医療機関との連携が不可欠と思われた。1992年度の成績をもとに, 免疫便潜血検査の診断精度を検討した。一日法の感度は70.8%, 特異度97.0%, 陽性反応適中度2.1であったのに対し, 二日法では感度86.7%, 特異度95.3%, 陽性反応適中度2.7と一日法より良好であった。便潜血陰性癌も高頻度に存在することから, 大腸癌検診の評価を高めていくためには, 二日法による徹底した逐年検診が必要と思われた。