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Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Background: Superoxide dismutase (SOD) is an antioxidant enzyme that degrades superoxide, a major causative factor in carcinogenesis. We assessed associations between serum SOD activities and incidence of colorectal carcinoma (CRC) in a case-control study nested in the Japan Collaborative Cohort (JACC) study., Methods: At baseline, 39,242 subjects donated serum samples. Participants diagnosed with CRC during follow-up were regarded as cases. Odds ratios (ORs) for CRC incidence associated with SOD were evaluated with conditional logistic regression models. In the current study, 176 cases and 524 controls were analyzed., Results: For the overall cohort, a decreasing trend in risk of CRC with increasing SOD was observed (P for trend=0.054) and the fourth quartile of SOD level showed the lowest risk compared to the first (OR=0.52, 95% confidence interval [CI]=0.29-0.93). This was significant in men (P for trend=0.001), with the fourth quartile of SOD level showing the lowest risk compared to the first (OR, 0.23; 95%CI, 0.09-0.60). It was also exclusively observed for rectal cancer and left-sided CRC (P for trend, 0.037 and 0.020, respectively), with the fourth quartile again showing the lowest risk compared to the first (OR, 0.28 and 0.38; 95%CI, 0.09-0.84 and 0.16-0.91, respectively). Limiting subjects to those followed-up over 2 years, all trends remained unchanged., Conclusions: Our findings suggest that serum SOD activity correlates inversely with risk of CRC, particularly in men and individuals with rectal cancer/left-sided CRC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasushi Adachi reports financial support was provided by JSPS KAKENHI. Yasushi Sasaki reports financial support was provided by JSPS KAKENHI. Mitsuru Mori reports financial support was provided by JSPS KAKENHI. Kenji Wakai reports financial support was provided by MEXT and JSPS KAKENHI. Akiko Tamakoshi reports financial support was provided by MEXT and JSPS KAKENHI., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults., Design: A 2-year follow-up cohort., Setting and Participants: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019., Methods: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated., Results: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline., Conclusions and Implications: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort Study., Methods: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects. Patients diagnosed with liver cancer were regarded as cases. Two or three controls were selected and matched for sex, age, and geographic area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with sFas., Results: This study contained 86 cases and 249 controls. After controlling for alcohol intake, body mass index, smoking, and hepatitis viral infection, participants with high sFas showed elevated risk of cancer (Ptrend = 0.003) and the third tertile of sFas showed a higher risk compared with the first tertile [OR, 3.53; 95% confidence interval (CI), 1.28-9.69]. In hepatocellular carcinoma, high sFas was associated with elevated risk (Ptrend < 0.001). In men and the elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for 3 years, high sFas was related to liver cancer risk (Ptrend = 0.033) and the third tertile showed a higher risk compared with the first (OR, 2.94; 95% CI, 0.94-9.14)., Conclusions: High serum sFas may be related to future risk of liver cancer., Impact: Our findings highlight this biomarker for further analysis in pooled investigations with different/larger prospective cohorts., (©2022 American Association for Cancer Research.)

The decline in physical function with age is a major contributor to the need for long-term care. Age-related changes in hand grip strength, knee extension, and walking speed have been reported in cross-sectional studies, but longitudinal data are needed. This longitudinal study measured changes in these three measures among community-dwelling adults aged 65-89 years who participated in general health examinations between 2017 and 2019. Analyses were stratified by sex. Linear mixed-effects models adjusted for confounding factors were used to examine the interaction of different patterns of change with age of the three measures. A total of 284 participants were included in the analysis. The interaction term of age × walking speed, with age × handgrip strength as the reference, was statistically significant in women and showed different patterns in walking speed and hand grip strength. In men, none of the age × physical function interaction terms were significant in any model. For early recognition of the onset of physical function decline in older adults, any of the three measures may be used in men, but walking speed may be more suitable than hand grip strength in women. These findings may be useful in devising sex-specific screening strategies.

Previous studies have indicated that social capital and locus of control influence mental health. Accordingly, we investigated the effect of social capital and locus of control on perceived physical and mental health in the general Japanese population during the COVID-19 pandemic. In order to conduct a cross-sectional study, in 2021, three thousand citizens were randomly selected from the Chitose City Resident Register according to ten strata of sex and age classes between 30 years and 79 years. Because thirteen persons moved away from the city, the survey was conducted for the remaining 2987 citizens. A total of 1430 citizens (712 males, 718 females) responded to the survey with their written informed consent (response rate, 47.9%). As a result, social capital measured three dimensions, namely social support, social participation, and trust and reciprocity, and internal locus of control was significantly inversely associated with it, but external locus of control was significantly positively associated with impaired physical and mental health in male and female subjects after adjustment of lifestyle habits and lifestyle change affected by the pandemic. Strengthening social capital and internal locus of control, and weakening external locus of control, may improve physical and mental health, even if the pandemic would bring about distress. Further longitudinal study is needed to examine the causal relationship among them.

Background: Insulin-like growth factor (IGF)2 is a potent mitogen. To elucidate the relationship between IGF2 and risk of tumorigenesis, we analyzed associations between serum levels of IGF2 and incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort study., Methods: A baseline survey was conducted from 1988 using blood samples from 39,242 subjects. Those who had been diagnosed with liver cancer by 1997 were regarded as cases. For each case, we randomly selected two or three controls matched for sex, age, and residential area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF2., Results: This analysis included 86 cases and 294 controls. Low IGF2 was associated with risk of future liver cancer ( P trend <0.001). After controlling for alcohol intake, body mass index, smoking, hepatitis viral infection, IGF1, and IGF-binding protein-3, participants with low IGF2 displayed a higher risk of liver cancer ( P trend < 0.001). Individuals in quintiles 2 to 5 showed lower risk compared with quintile 1 (OR range, 0.05-0.16). In both sexes and in both nonelderly and elderly groups, subjects in the lowest quintiles showed higher risks of liver cancer. Limiting subjects to those followed for 3 years, low IGF2 was associated with cancer risk ( P trend < 0.001)., Conclusions: Our findings suggest that low serum IGF2 level, especially below 460 ng/mL, is related to future risk of liver cancer., Impact: Our findings highlight this important biomarker for further analysis in large prospective cohorts and pooled investigation with other cohorts., (©2021 American Association for Cancer Research.)

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large-scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988-1990. The subjects of the present study were 26,464 men (age range: 40-79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose-dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose-response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To prove the efficacy of contrast-enhanced ultrasound (CEUS) in determining the extent of resection, more evidence about B-mode and CEUS as opposed to pathology is required. We compared maximum tumor width measured on B-mode/CEUS images with that determined pathologically., Methods: In this retrospective multicenter study, 152 operable breast cancer patients who had undergone both B-mode and CEUS were analyzed. Maximum tumor width on B-mode and CEUS, and on the postoperative pathological examination (P), was measured by the participating investigators. In addition, maximum width was assessed in B-mode and CEUS image sets by independent reviewers blinded to all patient information. We analyzed differences in maximum width between CEUS, B-mode and P., Results: The mean widths as measured by the participating investigators were 15 ± 7 mm (B-mode), 19 ± 8 mm (CEUS), and 17 ± 9 mm (P). The difference subtracted P from B-mode was - 3 ± 7 mm (p < 0.0001), and that from CEUS was 1 ± 6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 ± 7 mm (B-mode) and 18 ± 7 mm (CEUS). The difference subtracted P from B-mode was - 2 ± 8 mm (p = 0.0114), while that from CEUS was 1 ± 7 mm (p = 0.1921)., Conclusions: Maximum lesion width measurement showed a tendency to increase in the order of B-mode, to P and CEUS. The difference in measurement between P and B-mode was significant, but there was no significant between CEUS and P. These results provide additional information of tendency patterns in measuring the maximum lesion width through enhancement on CEUS.

Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Background/purpose: Epidemiological data on immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are scarce., Method: We randomly selected healthcare facilities from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with IgG4-SC in 2018. Among responding facilities, we further inquired about the clinical characteristics of the patients with IgG4-SC., Results: We selected 1180 departments from health centers across Japan. Of them, 532 (45.1%) responded to the questionnaires. The number of reported patients with IgG4-SC was 1045, and the estimated point prevalence was 2.18 (95% confidence interval, 2.13-2.23) per 100 000 population. In addition, we enrolled 1096 patients with IgG4-SC, combining data from previously and newly registered patients. Male patients comprised 79.5% of the population and patients aged 60-80 years had the highest risk for developing the disease. The follow-up period was 5.1 ± 4.0 years and the 5- and 10-year overall survival rates were 95.3% and 89.0%, respectively., Conclusions: The point prevalence of IgG4-SC was 2.18 per 100 000 population. The epidemiological features were similar to those observed in previous studies., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10 -8 ), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10 -9 ), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

This study investigated the association between intake of common alcoholic and non-alcoholic beverages and breast cancer risk among Japanese women. This study included 33,396 Japanese women aged 40-79 years from 24 areas in Japan from the Collaborative Cohort study. During the follow-up period (≥20 years), 245 incidents or mortal breast cancers were documented. Multivariable logistic regression analysis was performed to assess the independent association between breast cancer risk and the intake of Japanese green tea, coffee, and alcohol. Japanese green tea was the most commonly consumed non-alcoholic beverage (81.6% of participants), followed by coffee (34.7%) and alcohol (23.6%). No significant associations were identified between the intake of green tea and coffee with breast cancer risk (odds ratio OR 1.15, 95% confidence interval [CI] 0.82-1.60, and OR 0.84, 95% CI 0.64-1.10, respectively). Alcohol intake was associated with significant breast cancer risk (OR 1.46, 95% CI 1.11-1.92), and even infrequent alcohol consumption (.

Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both IGF1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case-control study nested in the Japan Collaborative Cohort Study. A baseline survey was started in 1988-1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples. Those who had been diagnosed with malignant tumors by 1997 were considered cases. The analysis involved 1,349 cases and 4,012 controls. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF-related molecules. After controlling for alcohol intake, body mass index (BMI), and smoking, participants with high total-IGFBP3 and free-IGFBP3, which is estimated by the molar difference of (IGFBP3 - IGF1), had a risk of future neoplasms ( P trend = 0.014 and 0.009, respectively), but those with IGF1 did not. People in the second to fifth quintiles had a lower risk than those in the first quintile (ORs 0.676-0.736 and 0.657-0.870, respectively). Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-IGFBP3, whereas a positive relationship of free-IGF1, which was estimated by the molar ratio of IGF1/IGFBP3, was seen ( P trend = 0.004, 0.002, and 0.013, respectively). After controlling for alcohol intake, smoking, BMI, and diabetes mellitus, the results were confirmed. These findings suggest that serum IGF1 and IGFBP3 are related to future risk of malignant neoplasms., (©2020 American Association for Cancer Research.)

Aim: The aim of the present study was to investigate the effects of individualized nutritional treatment on the activities of daily living of acute stroke patients., Methods: This was a randomized controlled study. The eligibility criteria were acute stroke, age >65 years and the presence of malnutrition risk. Between September 2016 and December 2017, 128 patients were assigned to either the standard or intensive group (individualized nutritional treatment). The intensive group received energy that was calculated using the Harris-Benedict equation. The main outcome measures were the total functional independence measurement gain from the time of assignment to the time of discharge from the recovery hospital or at 3 months after the stroke onset, and motor and cognitive functional independence measurement gains., Results: Compared with the standard group, the intensive group had significantly higher median energy intake (P < 0.001); significantly greater functional independence measurement gains in the total score (42 vs. 22; P = 0.02) and motor subscore (P = 0.01), but similar cognitive subscore., Conclusion: Individualized nutritional treatment improved the activities of daily living of older acute stroke patients with malnutrition risk. Geriatr Gerontol Int 2019; ••: ••-••., (© 2019 Japan Geriatrics Society.)

Background and Aim: Insulin-like growth factor-1 (IGF1) is a potent mitogen and is inhibited by IGF-binding protein-3 (IGFBP3). High serum IGF1 and low IGFBP3 are associated with increased risk of several carcinomas. Here, we assessed the relationship of these peptides with the risk of gastrointestinal malignancies, in a prospective case-control study nested in the Japan Collaborative Cohort Study., Methods: The analysis involved 916 cases who had been diagnosed as gastrointestinal malignancies (C15-25) and 2306 controls. To estimate odds ratios for incidence of malignancies associated with these levels, a conditional logistic model was used., Results: Both higher total and free IGFBP3 were associated with a decreased risk of tumor (P for trend < 0.001 and = 0.003, respectively). People in the second to fifth quintiles had lower risk compared to the first quintile (odds ratios ranged 0.532-0.650 and 0.582-0.725, respectively). After adjustment for IGF1, body mass index, drinking, and smoking, total IGFBP3 was inversely correlated with cancer risk (P for trend = 0.031). After adjustment, free IGFBP3 was inversely associated with the risk (P for trend = 0.007). Although total IGF1 was inversely correlated with tumor risk, it was not after controlling for IGFBP3 (P for trend = 0.007 and 0.589, respectively). Free IGF1 was not associated with the risk (P for trend = 0.361). Limiting subjects to those followed for over 3 years reinforced the inverted relationships of total and free IGFBP3 with risk for tumors (P for trend = 0.005 and 0.008, respectively)., Conclusion: Both total and free IGFBP3 may be inversely associated with the incidence of gastrointestinal malignancies., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: We examined the association of muscle mass and muscle strength with insulin resistance, focusing on lower limb muscles., Methods: This was a cross-sectional study, and participants were registered in 2017 from the Tanno-Sobetsu Study, a population-based cohort study. After excluding individuals aged <64 years or with a history of diabetes mellitus, 272 non-diabetic older adults (116 men, 156 women) met the inclusion criteria. According to the homeostasis model assessment of insulin resistance, the participants were divided into two groups; that is, the insulin resistance group (homeostasis model assessment of insulin resistance ≥1.73) and non-insulin resistance group (homeostasis model assessment of insulin resistance <1.73). Muscle mass (lower limb, upper limb, appendicular and trunk) and muscle strength (grip strength and knee extension torque) were measured and divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). The adjusted odds ratio (OR) of each muscle index for risk of insulin resistance was calculated separately for both men and women., Results: Lower limb muscle mass (OR 0.72, 95% CI 0.55-0.92 in men; OR 0.69, 95% CI 0.51-0.96 in women, respectively) and appendicular muscle mass (OR 0.75, 95% CI 0.61-0.94 in men; OR 0.72, 95% CI 0.54-0.95 in women, respectively), but not other muscle indexes, were associated with risk of insulin resistance, after adjusting for age, body mass index, highly sensitive C-reacting protein and smoking habits., Conclusions: Lower limb muscle mass of non-diabetic older adults is independently related to insulin resistance. Geriatr Gerontol Int 2019; 19: 1254-1259., (© 2019 Japan Geriatrics Society.)

Background and Purpose: Muscle strength measurements with the handheld dynamometer are sometimes performed according to manual muscle testing. However, measuring hip extensor muscle strength in the prone position is difficult, since the some older adults have kyphosis or flexion contracture of the lower limbs. Alternatively, there is the standing position method of manual muscle testing, which accomodates those malalignments; however, it is known that the muscle strength of the lower limb that is not measured affects the measurement result. Hence, we devised the hip extensor strength measurement in a sitting position for healthy males in previous studies. This study examined the reliability and validity of the sitting measurement by a handheld dynamometer in older adults., Methods: Participants were 40 older adults (age [SD] = 82.4 [4.3] years). Measurements of isometric hip extensor muscle strength using a handheld dynamometer in 3 positions (sitting, standing, and prone) were conducted twice. A surface electromyogram was used to measure the activity of the gluteus maximus and the semitendinosus muscles. The reliability of muscle strength in each posture was examined with Cronbach α coefficient, intraclass correlation coefficients (ICCs1,1), and Bland-Altman analysis. The concurrent validity of muscle strength for the sitting and standing positions with reference to the prone position was examined with Spearman rank correlation and Bland-Altman analysis. Furthermore, muscle strength and muscle activity were compared between each posture., Results: The Cronbach α coefficient was 0.75. For each posture, the ICC1,1 was 0.86 to 0.87, with no systematic error in the sitting and prone positions. The sitting and standing positions were significantly associated with the prone position (rs = 0.72 and 0.42), with no systematic error between the sitting and prone positions. Proportional error was demonstrated between the standing and prone positions (P < .01). There was no significant difference in muscle strength between any posture. Gluteus maximus muscle activity was significantly higher in the sitting versus standing position (P < .05)., Conclusion: The measurement of hip extensor muscle strength in the sitting position is a reliable and valid method in older adults, which can be effective even when the prone position is not possible.

Aim: Autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) impose a significant burden on public health, and it is important to estimate their prevalence. We carried out a nationwide, hospital-based, epidemiological survey of AIH, PBC, and PSC, and compared the results with those from previous surveys., Method: We randomly selected health-care facilities used in the survey from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with AILD who visited the facility in 2016. An identical survey was undertaken for AIH/PBC in 2004 and for PSC in 2007; we carried out a comparative analysis of these data., Results: We selected 1793 departments from health centers all over Japan. Of them, 1078 (60.1%) responded to the questionnaires. The number of reported patients with AIH, PBC, and PSC was 8505, 10 847, and 906, respectively, and point prevalence was 23.9 (95% confidence interval, 23.3-24.5) for AIH (8.7 in 2004), 33.8 (33.0-34.6) for PBC (11.6 in 2004), and 1.80 (1.75-1.85) for PSC (0.95 in 2007) per 100 000 population. Male-to-female patient ratio of AILD was 1:4.3 for AIH (1:6.9 in 2004), 1:3.9 for PBC (1:7.1 in 2004), and 1:0.88 for PSC (1:1.4 in 2007)., Conclusion: The current study indicates an increasing trend of prevalence as well as male-to-female patient ratio of AILD in Japan., (© 2019 The Japan Society of Hepatology.)

Severe early childhood caries (S-ECC) has serious consequences for primary dentition, affecting the overall health, well-being, and quality of life of the child. The aim of this study was to investigate the association of risk factors, including environmental tobacco smoke (ETS), with S-ECC in 3-year-old Japanese children by a cross-sectional study. Study subjects were 2,825 children aged 3 years old. Of these individuals, after excluding the study subjects with missing values, a total of 2,277 children were included in the present analysis. The self-administered questionnaire included such items as sex, whether a smoker resides in the home, the number of smokers in the home, snack time, drinking or eating sweets after dinner, frequency of parents brushing their child's teeth, the use of fluoride toothpaste, and socioeconomic status. We obtained the number of decayed, missing, or filled teeth per person (dmft) from dental examinations. Logistic regression analysis was performed to estimate the odds ratio for S-ECC. The average number of decayed, missing, and filled teeth (dmft index) was 0.77. The prevalence of dental caries was 20.6%. There was at least 1 smoker in the homes of 1,370 subjects (60.2%). After excluding items of multicollinearity, the results of multivariate analysis were as follows: drinking or eating sweets after dinner, irregular snack times, parents brushing their child's teeth less frequently, existence of smokers in the home, and no residence tax were significantly associated with S-ECC. This study suggests that there is a significant association between ETS from family members and S-ECC., (© 2018 S. Karger AG, Basel.)

Aims : To determine the structural validity, construct validity, cross-cultural validity, internal consistency and test-retest reliability of the Japanese version of the ABILOCO-Kids in children with cerebral palsy. Methods : One-hundred sixteen parents of children with cerebral palsy (Gross Motor Function Classification System level I [ n  = 66], II [ n  = 32], and III [ n  = 18]) reported on walking ability using the Japanese version of the ABILOCO-Kids. For test-retest reliability, 23 participants were evaluated. Results : The mean ABILOCO-Kids logit score was 2.48 (range -7.44 to 5.83). Rasch analysis and principal component analysis were used to determine the structural validity. The construct validity was confirmed on the basis of differences in the ABILOCO-Kids scores among the Gross Motor Function Classification System levels. Cronbach's α and the item-to-total correlation coefficient supported the internal consistency. The intra-class correlation coefficient was 0.96, standard error of measurement 0.56 and minimal detectable change 1.55. The cross-cultural validity analyses showed differential item functioning according to the analyses of the invariance of item difficulty and person's ability estimates. Conclusions : The ABILOCO-Kids is a reliable and valid measure of walking ability in children with cerebral palsy in Japan. The lack of evidence on cross-cultural validity indicates we should interpret results cautiously in cases of international comparison.

[Purpose] This study aimed to examine the influence of climatic conditions on the daily physical activities of elderly individuals by comparing the physical activity during seasons with and without snowfall. [Participants and Methods] In total, 35 participants attending the Health Promotion Program conducted by Chitose City Office participated in this study. The survey for the seasons with snowfall was conducted in February 2016, while the survey for the seasons without snowfall was conducted in September 2015. The physical activity of the participants was measured using a Kenz Lifecorder GS accelerometer. [Results] Physical activity was found to be significantly lower during seasons with snowfall than in seasons without snowfall. Multivariate analysis revealed that physical activity significantly increased with lower temperature during the seasons with snowfall, and it significantly increased with higher temperature and decreased with larger amounts of precipitation during the seasons without snowfall. [Conclusion] It was found that the climatic conditions affect the level of physical activity during seasons with and without snowfall. A lower level of physical activity was observed in areas that received snowfall than in areas that did not receive snowfall.

Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and 1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development., Competing Interests: The authors have declared that no competing interests exist.

Aim: In order to clarify the risks of institutionalization or mortality among older adults living alone compared with those not living alone, we carried out a prospective study on older adults in Hamanaka Town in the far eastern part of Hokkaido, Japan., Methods: All 978 community-dwelling residents aged 70-85 years in the town were chosen as study candidates between February and May of 2014. Written informed consent was obtained from 562 residents (57.5%), and a self-administered questionnaire, including a question about living arrangements, was mailed to them. They returned the completed questionnaire to us in 2014. A follow-up survey was carried out with a questionnaire mailed to each participant about institutionalization and mortality, three times, in February of 2015 and 2016, and in April of 2017. Hazard ratios and 95% confidence intervals were calculated with the Cox proportional hazards model., Results: Living alone was significantly associated with an increased risk of institutionalization in the male participants, after adjusting for age, sex and having daily support from family around a participant (hazard ratio 5.71, 95% confidence interval 1.17-27.83), although it was not significant in the total participants or the female participants. Additional adjustments for a history of having common diseases did not change the results meaningfully. Living alone was not associated with the risk of mortality in the total participants, the male participants or the female participants., Conclusions: Poor social support in social networks for older men living alone may be etiologically associated with increased risk of institutionalization in rural area. Further study with a larger sample size is necessary to confirm this finding. Geriatr Gerontol Int 2018; 18: 867-872., (© 2018 Japan Geriatrics Society.)

The aim of the present study was to evaluate the potential advantages of the ultrasonic scalpel compared with the conventional technique in thyroid surgery. Patients with resectable thyroid cancer and Basedow's disease were assigned to ultrasonic scalpel or conventional technique (knot-tying and electrocoagulation). The present study used the Harmonic FOCUS ® (HF) as an ultrasonic scalpel. Between February 2013 and May 2016, 45 patients were enrolled into the study. Duration of the surgery was significantly decreased in the HF group compared with the conventional surgery (CS) group (median 142 vs. 151 min; P=0.0406). Intraoperative blood loss and total volume of drainage fluid were significantly decreased in the HF group compared with the CS group (median 40 vs. 125 ml; P=0.0054, and median 120 vs. 175.5 ml; P=0.0490). Duration of drain placement and length of hospitalization stay were similar in the two groups. Furthermore, the overall incidence of postoperative complications did not differ between the two groups. Overall, the present study suggests that open thyroidectomy using the HF is safe and effective and not associated with any increase in complications.

Purpose: Seventy-five percent of epidemiological studies have reported that sedentary behavior is associated with ovarian cancer incidence. Although Japan has one of the most sedentary populations, with median sitting times of 7 h/day, this association has not been investigated. This study aimed to elucidate the association between average daily television (TV) viewing time, which is a major sedentary behavior, and the incidence of ovarian cancer in a large-scale nationwide cohort study in Japan., Methods: A total of 34,758 female participants aged 40-79 years without a history of cancer at baseline were included in the study. The inverse probability weighted competing risk model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the incidence of ovarian cancer., Results: During a median follow-up of 19.4 years, 59 participants developed ovarian cancer (ICD-10: C56), 2,706 participants developed other types of cancer, and 4,318 participants died. Participants who watched TV for ≥ 5 h/day were more likely to develop ovarian cancer than those who watched TV for < 2 h/day (HR 2.15; 95% CI 1.54-2.99)., Conclusion: Our findings suggest that reducing the amount of time spent sedentarily may be beneficial for preventing ovarian cancer.

Objective: The purpose of this study was to develop a Japanese version of the Functional Mobility Scale (FMS), and examine the criterion validity and intra-rater reliability of the FMS in Japan., Methods: The translation of the FMS was performed according to international standards for the translation of measurements. For criterion validity, 111 children with cerebral palsy (mean age; 12year 1mo±3year 7mo; range 5-18) were rated the Japanese version of the FMS and Gross Motor Function Classification System (GMFCS). For intra-rater reliability, the Japanese version of the FMS was rated twice by 24 parents of children with cerebral palsy by interview and/or telephone with a one- to two-week interval between assessments., Results: The criterion validity was confirmed with a strong correlation between GMFCS level and FMS scores (r 2 =-0.71 to -0.75). For intra-rater reliability, there was a substantial to excellent level of agreement (kappa=0.72-0.87)., Conclusion: The study provides evidence of the criterion validity and intra-rater reliability of the Japanese version of the FMS as a measurement of mobility in children with cerebral palsy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: We assessed the association of personal factors with Family APGAR not only among the subjects in nonsingle households, but also in single households., Methods: We randomly chose 1 000 persons aged from 50 to 89 years in Rumoi City of the west area of Hokkaido as study candidates, and 493 subjects responded to the survey. We compared the group of high Family APGAR (FA) score of more than or equal to seven with the group of low FA score of less than or equal to 6 with regard to health-related QOL (HRQOL), measured with SF-8, Index of Social interaction (ISI), and other personal characteristics. Being in the low FA group indicates living with a status of poor family function., Results: As a result of the multivariate logistic regression model, living in single households, currently smoking, a low score of mental component summary (MCS) in HRQOL, and a low score of lSI were all significantly associated with being in the low FA group. A low score of MCS was significantly associated with being in the low FA group both in the stratum of nonsingle households, and in the stratum of single households., Conclusions: There were three risk factors of low FA. The first is a single household, second is currently smoking in a nonsingle household, and the third is low ISI. Worse mental status is found to be associated with low FA among the subjects not only in nonsingle households, but also in single households.

Objective: Since the 1990s, self-controlled designs including self-controlled case series (SCCS) studies have been occasionally used in post-marketing evaluation of drug or vaccine safety. An SCCS study was tentatively applied to evaluate the relationship between oseltamivir use and abnormal behavior Type A (serious abnormal behavior potentially leading to an accident or harm to another person) in influenza patients., Methods: From the original prospective cohort study with approximately 10,000 Japanese children and adolescents with influenza (aged <18years), 28 subjects (mean age: 7.3years) who developed abnormal behavior Type A after the first visit to the collaborating hospitals/clinics were analyzed. We hypothesized four combination patterns of the effect period (i.e., the period that effect of oseltamivir on occurrence of abnormal behavior Type A is likely) and the control period. Mantel-Haenszel rate ratio (M-H RR) and its 95% confidence interval (CI) were calculated as the relative risk estimate., Results: Among 28 subjects in the SCCS study, 24 subjects (86%) were administered oseltamivir and 4 subjects (14%) were not. Abnormal behavior Type A was more likely to occur in the effect period than the control period in every pattern (M-H RR: 1.90-29.1). We observed the highest estimate when the effect period was set between the initial intake of oseltamivir and T max (M-H RR: 29.1, 95% CI: 4.21-201)., Conclusion: Abnormal behavior Type A was more likely to develop up to approximately 30 times during the period between the initial intake of oseltamivir and T max . However, this period overlapped with the early period of influenza where high fever was observed. Since useful approaches to control the influence of the natural disease course of influenza were not available in this study, we could not deny the possibility that abnormal behavior was induced by influenza itself. The SCCS study was not an optimal method to evaluate the relationship between oseltamivir use and abnormal behavior., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: It has widely been proven that metabolic syndrome (MetS) increases the risk of ischemic heart disease (IHD). MetS is confirmed based upon insulin resistance (IR). Our aim of this study is to evaluate the role of MetS and IR in the prediction of IHD incidence., Methods: A total of 404 non-diabetic participants who underwent 75 g oral glucose tolerance test (75 g OGTT) were enrolled from 2001 to 2009. Risk factors for IHD were measured as well. The homeostatic index of IR (HOMA-IR) and the homeostatic model assessment beta cell function (HOMA-β) were calculated according to the homeostasis model assessment. Cox proportional-hazard regression model was used to estimate hazard ratio (HR). All data were analyzed using SPSS 21 software (IBM, Armonk, NY, USA)., Results: In our study, the average follow-up period was 6.7 years. Eighteen subjects of IHD incidence were recorded. After adjusting for age and sex, subjects with IR or hyperinsulinemia had a high risk of IHD, the hazard ratio (95% confidence intervals) for IHD were 4.58 (1.59-13.15), 4.25 (1.64-11.91), respectively. The highest hazard ratio was 7.56 (2.27-25.18) which was found among the subjects with both IR and hyperinsulinemia. In addition, the hazard ratio (95% confidence intervals) of subjects with MetS was 2.80(1.10-7.09)., Conclusions: IR and hyperinsulinemia are related to the risk of IHD. IR combined with hyperinsulinemia may be superior to MetS for predicting the IHD incidence.

Background: The aim of this study was to compare perceptions between physical therapists and parents about family-centered care for preterm infants., Methods: Translated versions of the Measure of Processes of Care-20 and Measures of Processes of Care for Service Providers were used to evaluate the family-centered care for preterm infants., Results: A total of 42 parents of 44 preterm infants and nine physical therapists completed questionnaires. Parent perceptions of the family-centered care were generally positive. The highest rating was in the domain Enable and Partnership. Physical therapists gave lower scores in all information domains. There were some gaps between parent and physical therapist perceptions of information domains., Conclusions: Strengths and weaknesses in family-centered care for preterm infants have been identified. Parents viewed the role of physical therapists in family-centered care for preterm infants as positive., (© 2017 Japan Pediatric Society.)

Aim: To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma., Methods: We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples. Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels., Results: Thirty-one cases and 86 controls were eligible for the present assessment. The molar ratio of IGF1/IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and IGF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma ( P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95%CI: 0.017-0.669). After adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma ( P = 0.0150)., Conclusion: The free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence., Competing Interests: Conflict-of-interest statement: The authors have declared no conflicts of interest.

Objective: The aims of this systematic review were to identify quick, simple and easy-to-use measures of walking ability currently used to assess children and adolescents with cerebral palsy (CP), and to evaluate the clinical utility and psychometric properties of these measures., Data Sources: The PubMed, CINAHL, SPORTDiscus and MEDLINE databases were searched up to March 2015., Review Methods: Two independent reviewers rated the methodological quality of the identified measures using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist., Results: The 1-Minute Walk Test, Timed Up and Go Test, ABILOCO-Kids, Gillette Functional Assessment Questionnaire and Functional Mobility Scale were identified. Each measure can be carried out within 5 min with limited equipment, and does not require examiner training. There was "limited" to "strong" evidence on the reliability and validity of these measurements, whereas evidence on measurement error and responsiveness was limited., Conclusion: The identified measures in this systematic review may be considered for the clinical measurement of walking ability in children and adolescents with CP in a quick, simple and easy-to-use manner. However, there is overall a lack of evidence on the psychometric properties of these tools. The lack of evidence regarding measurement error and responsiveness might limit their value in measuring change over time. Implications for Rehabilitation The ABILOCO-Kids, 1-Minute Walk Test, Timed Up and Go Test, Gillette Functional Assessment Questionnaire, Functional Mobility Scale can be performed within 5 min with limited equipment, and do not require examiner training for measuring of walking ability in children and adolescents with cerebral palsy. The clinicians should use these measurement tools carefully when assessing change over time as the available evidence on measurement error and responsiveness is limited. When clinicians use these measurement tools, the psychometric properties reported in this systematic review should be considered in the selection of tools and subsequent interpretation of results.

Aim: Endocervical curettage (ECC) at the time of conization has been reported to be effective for diagnosing cervical intraepithelial neoplasia and/or early stage cervical cancer. We aimed to verify the accuracy of ECC with conization., Methods: We retrospectively analyzed the records of 540 patients with suspected neoplastic cervical lesions who underwent conization at the Yokohama City University Hospital from January 2008 to December 2015. To validate the effectiveness of ECC for evaluating endocervical lesions, histopathologic findings from ECC samples were compared with those from endocervical specimens obtained by conization. In patients who subsequently underwent hysterectomy, specimens of residual endocervical stump lesions were compared with the specimens obtained by ECC., Results: ECC was performed in 58.9% of patients who underwent conization. Positive findings were only observed in 7.9%, while negative findings were found in 67.3% of ECC samples; however, 24.8% of the samples were inadequate for diagnosis. None of the patients had an upgraded diagnosis according to ECC results. The sensitivity of ECC in predicting endocervical stump lesions that were identified by conization specimens was 25.0%, the specificity was 94.2% and the positive predictive value was 55.0% (κ = 0.238; P < 0.001). ECC samples yielded a sensitivity of 42.9%, a specificity of 83.9%, and positive predictive value of 54.5% (κ = 0.284; P = 0.053) in predicting residual endocervical lesions in the uterus., Conclusions: As it offers low sensitivity and positive predictive value, ECC at the time of conization is of limited benefit for evaluating endocervical lesions., (© 2017 Japan Society of Obstetrics and Gynecology.)

Background: The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2009, after which there was a rapid decline in invasive pneumococcal disease. There are few data, however, on the effectiveness of PCV7 against community-acquired pneumonia (CAP). We conducted an ambispective cohort study among children aged 0-6 years old who attended day-care centers., Methods: A total of 624 children at 10 day-care centers in Sapporo, Japan participated in the study. The parents reported whether their child had received PCV7 one or more times, as well as the exact dates of vaccination from records in maternal and child health handbooks marked by pediatricians. Each CAP event was reported by parents according to doctor diagnosis. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) and 95%CI of CAP incidence reduced by PCV7 inoculation., Results: During the observational period, 94 subjects contracted CAP. After adjusting for potentially confounding variables, inoculation with PCV7 was significantly associated with a reduced risk of CAP (HR, 0.22; 95%CI: 0.13-0.34). On stratified analysis by age, PCV7 was significantly associated with a reduced risk of CAP in both children aged <3 years (HR, 0.31; 95%CI: 0.14-0.71), and those ≥3 years (HR, 0.20; 95%CI: 0.09-0.43)., Conclusion: PCV7 is highly effective in reducing the risk of CAP in children attending day-care centers., (© 2016 Japan Pediatric Society.)

Background: The association between dietary patterns and breast cancer has been inconsistent., Methods: This study examined associations between dietary patterns and risk of developing breast cancer among 23,172 women from the Japan Collaborative Cohort Study, including 119 incidences of breast cancer diagnosed during a median 16.9-year follow-up period. Factor analysis was conducted to obtain dietary patterns, and Cox proportional models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for breast cancer morbidity., Results: Three dietary patterns were identified: ''vegetable pattern'' (vegetables, potatoes, seaweed, tofu, fruits, fresh fish, eggs, and miso soup); ''animal food pattern'' (meat, deep-fried foods, fried vegetables, fish paste and salt-preserved fish); and "dairy product pattern'' (milk, dairy products, fruits, coffee and tea). After adjusting for potential confounders, the vegetable and dairy product patterns were not significantly associated with risk of breast cancer. However, the animal food pattern was significantly associated with a decreased risk of breast cancer morbidity among premenopausal women by HR 0.47 for the 2nd tertile (95 % CI 0.22-1.00) and HR 0.42 for the 3rd tertile (95 % CI 0.18-0.93), compared with the bottom tertile (p for trend 0.04)., Conclusion: We found no significant association between the vegetable and dairy product dietary patterns and breast cancer risk; however, an animal product diet may reduce risk of breast cancer among premenopausal Japanese women.

Objectives: To investigate the longitudinal changes of sexual function of Japanese men., Methods: From 1992 to 1993, we carried out a cross-sectional community-based study on sexual function in Japanese men aged 40-79 years. After 15 years, a follow-up study was carried out to determine longitudinal changes of their sexual function. Of the 319 participants in the initial study, 135 participated again in the follow-up study. Sexual function was assessed using the same validated questionnaire in the two studies., Results: Erectile rigidity declined in men of each age decade at baseline (40s, 50s, 60s and 70s) of the initial study (P < 0.01, <0.01, <0.01 and <0.05). The frequency of sexual drive was significantly decreased in men aged in their 40s, 50s and 60s (P < 0.05, <0.01 and <0.01). Men aged in their 40s were dissatisfied with their decreased sexual function (P < 0.05). In contrast, men aged in their 70s were satisfied with their sexual life (P < 0.01)., Conclusions: Over a 15-year period, the sexual function of Japanese men declined in each age decade. However, the perception of this decline differed among different age group. Most elderly Japanese men did not worry about their impaired sexual function., (© 2016 The Japanese Urological Association.)

Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026-0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma.

Fine-needle aspiration (FNA) is commonly used as a preoperative assessment to diagnose thyroid cancer. However, misdiagnosis of malignancy by FNA is not rare, even if image examination suggests the possibility of thyroid cancer. In the present study, the clinicopathological factors of patients whose preoperative FNA examination had not led to a diagnosis of thyroid cancer were examined. In total, 125 patients with thyroid cancer who underwent FNA and surgery (total thyroidectomy, subtotal thyroidectomy or hemithyroidectomy) at the Department of Surgery, Surgical Oncology and Science of the Sapporo Medical University Hospital between 2006 and 2013 were retrospectively analyzed. The patients were divided into two groups: Group A, malignancy determined by FNA, and group B, no malignancy. The groups were then compared by gender, age, tumor size, stage, tumor stage, lymph node metastasis, histology, surgical procedure methods, presence or absence of calcification and thyroglobulin levels. The mean age of the patients in group A (5 males and 59 females) was 53.0 years. The mean age in group B (11 males and 49 females) was 54.2 years. The mean tumor size in both groups was 1.6 cm. The mean thyroglobulin levels were 82.7 ng/ml in Group A and 525.5 ng/ml in group B. There were also significant differences between the groups for tumor stage (P=0.046), histological type (P=0.024) and thyroglobulin levels (P=0.035). The results of the present study suggested that it may be difficult to diagnose thyroid cancer by FNA in cases with non-papillary carcinoma and higher thyroglobulin levels.

Objective: Our aim was to estimate whether diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC) mortality in Japan. Methods: The Japan Collaborative Cohort (JACC) Study is a nationwide prospective study, initiated in 1988, which involves 110,585 subjects (age range: from 40 to 79 years; 46,395 males and 64,190 females). Our present analysis population comprised 96,081 (40,510 men and 55,571 women) who provided details on DM history. The questionnaire also included age, sex, weight, height, family history of CRC, smoking, drinking and exercise habits, and education. Cox proportional-hazard regression was used to estimate the hazard ratio (HR). We used SPSS 21 software to analyze all data. Results: Among the participants with DM, we followed up for 71,174 person-years and 640. deaths from CRC were confirmed; and, among the non-diabetic participants, 785 CRC deaths were identified during 1,499,324 person-years. After adjusting for multivariate confounding factors, such as age, sex, body mass index (BMI), family history of colorectal cancer, smoking habit, drinking habit, physical activity (sports and walking) and education, DM was associated with an increased risk of CRC death (HR 1.4, 95% confidence interval [CI] 1.0-2.0). Diabetic women, but not diabetic men, experienced increased mortality from CRC (HR 1.7, 95% CI 1.0-3.0). Conclusion: The risk of CRC mortality is significantly increased in both sexes and women with diabetes, but no significant increase was seen for diabetic men among Japanese., (Creative Commons Attribution License)

Background: We investigated the effect of longitudinal status change in metabolic syndrome (MetS) assessed by two different criteria on new onset of type 2 diabetes (NODM) in a Japanese population., Methods: The participants were 827 non-diabetic citizens who had undergone medical examinations in 1994 and 2003 or 2004. We used two different criteria of MetS: the interim criteria by 6 institutions (MetS-INT) and Japanese criteria (MetS-JP). According to the interim criteria, individuals defined as having MetS have any three of the following five components of MetS: obesity, hyperglycemia, high blood pressure, hypertriglyceridemia and low HDL cholesterolemia. According to the Japanese criteria, individuals defined as having MetS must have abdominal obesity plus any two of the following three factors; hyperglycemia, high blood pressure and dyslipidemia (hypertriglyceridemia and/or low HDL-cholesterolemia). According to the status change in MetS, participants were divided into four groups: a non-MetS to non-MetS group, a non-MetS to MetS group, a MetS to non-MetS group and a MetS to MetS group. We calculated odds ratios of these four groups for NODM., Results: NODM occurred in 65 participants. The odds ratios for NODM were 4.86, 4.97 and 7.50 in the non-MetS-INT to MetS-INT group, MetS-INT to non-MetS-INT group and MetS-INT to MetS-INT group, respectively. On the other hand, the odds ratios were 4.28 and 15.55 in the non-MetS-JP to MetS-JP group and MetS-JP to MetS-JP group, respectively. After adjustment for high fasting plasma glucose at baseline, magnitude of the odds ratio of MetS to MetS group was larger in the Japanese criteria group than in the interim criteria group., Conclusions: Determining the status of MetS routinely and paying attention to status change in MetS may be important for prevention of type 2 diabetes. MetS defined by the criteria which includes obesity as a prerequisite component may be a stronger risk for type 2 diabetes than MetS defined by the criteria which includes obesity as one of components.

Breast cancer is the most common cancer in women. However, it remains unproven whether psychological factors have an influence on breast cancer incidence. In our earlier study, subjects possessing two personality traits, decisiveness and "ikigai" (a Japanese word meaning something that makes one's life worth living), showed a significantly lower risk of developing breast cancer, although no psychological factors have been convincingly demonstrated to have an influence on breast cancer development in other studies. Therefore, we conducted this follow-up analysis to confirm the association between breast cancer incidence and psychological traits, using the final dataset of a large-scale prospective cohort study in Japan. We identified 209 cases of incident breast cancer out of a maximum 21-year follow-up of 29,098 Japanese women. Cox proportional hazard regression analysis, adjusted for the same potential confounders used in our previous study, did not reveal any significant relationships between breast cancer incidence and four psychological traits: having "ikigai", decisiveness, ease of anger arousal, and perceived stress. Our finding is consistent with previous studies, and suggests that the psychological traits are unlikely to be an important risk factor for breast cancer.

Background: The clinical course of idiopathic pulmonary fibrosis (IPF) shows great inter-individual differences. It is important to standardize the severity classification to accurately evaluate each patient׳s prognosis. In Japan, an original severity classification (the Japanese disease severity classification, JSC) is used. In the United States, the new multidimensional index and staging system (the GAP model) has been proposed. The objective of this study was to evaluate the model performance for the prediction of mortality risk of the JSC and GAP models using a large cohort of Japanese patients with IPF., Methods: This is a retrospective cohort study including 326 patients with IPF in the Hokkaido prefecture from 2003 to 2007. We obtained the survival curves of each stage of the GAP and JSC models to perform a comparison. In the GAP model, the prognostic value for mortality risk of Japanese patients was also evaluated., Results: In the JSC, patient prognoses were roughly divided into two groups, mild cases (Stages I and II) and severe cases (Stages III and IV). In the GAP model, there was no significant difference in survival between Stages II and III, and the mortality rates in the patients classified into the GAP Stages I and II were underestimated., Conclusions: It is difficult to predict accurate prognosis of IPF using the JSC and the GAP models. A re-examination of the variables from the two models is required, as well as an evaluation of the prognostic value to revise the severity classification for Japanese patients with IPF., (Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: Isoflavones may play a role in the prevention of hormone-related cancers. Equol is an isoflavone metabolized from daidzein in the presence of certain intestinal bacteria. Slackia sp. strain NATTS, a newly identified equol-producing bacterium, was recently isolated from human feces in Japan. We investigated the association of serum levels and dietary intake of isoflavones and Slackia sp. strain NATTS with the risk of prostate cancer in a case-control study among Japanese men., Methods: Fifty-six patients with newly diagnosed prostate cancer and 56 hospital controls were enrolled in this study. Isoflavones were assessed by measurement of serum levels and administration of a food frequency questionnaire. Slackia sp. strain NATTS in feces was also measured. The odds ratios (ORs) and 95 % confidence intervals (CIs) for prostate cancer were then determined using a logistic regression model., Results: The adjusted ORs for prostate cancer in comparison with the highest to lowest categories were 0.06 (95 % CI 0.02-0.24) for serum genistein, 0.18 (95 % CI 0.06-0.52) for daidzein, 0.16 (95 % CI 0.06-0.46) for glycitein, 0.52 (95 % CI 0.22-1.22) for equol, 0.86 (95 % CI 0.30-2.48) for dietary genistein, and 0.80 (95 % CI 0.28-2.28) for dietary daidzein. The adjusted OR for prostate cancer in comparison with values above versus below the median was 0.95 (95 % CI 0.42-2.16) for Slackia sp. strain NATTS., Conclusion: Our study findings suggest that high serum levels of genistein, daidzein, and glycitein are significantly associated with a decreased risk of prostate cancer among Japanese men.

Objectives: The first aim of this study was to evaluate the association between time spent living near a contaminated area and concentration of arsenic (As) compounds in the urine among study subjects. The second aim is to assess the association between consumption of various foods or beverages and As concentration in urine among them., Methods: Urine sampling was performed on 177 persons who voluntarily participated in the survey in May 2014. The median value of the sum of inorganic As (iAs) and total As (tAs) compounds was used for us to divide into two groups, such as the high and low iAs and high and low tAs groups. We analyzed data separately in two-age strata of age group A (the subjects <18 years old), and age group B (the subjects ≥18 years old). A multivariate analysis was performed with the logistic regression model to adjust for potential confounding variables., Results: No link between time spent living near a contaminated area and urinary As concentration was observed in our study. For age group B, frequently drinking beer was significantly associated with risk of being in the high tAs group (p = 0.008). Compared to not drinking beer, odds ratios (95 % confidence intervals) of drinking beer <1 or 2 times per week, and drinking beer ≥3 or 4 times per week were 3.09 (1.32-7.24) and 3.00 (1.02-8.80), respectively, after adjusting for age, sex, and smoking index., Conclusion: Frequent consumption of beer may be associated with high tAs in age group B., Competing Interests: No conflict of interest was declared by any author.

Background: Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects., Methods: Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk., Results: Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk., Conclusions: Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.

Background: Malnutrition induced by swallowing difficulties (SD) impairs the quality of life and gives rise to SD-related costs in Parkinson's disease (PD) patients. With results of a swallowing difficulty questionnaire and data of resources specifically obtained such as SD-related costs, caregivers, and dietary therapies, this study is to suggest statistically supported ideas for improvements in arrangements for how participants cope with SD and maintain general well-being., Methods: We interviewed 237 PD patients. The SD-related costs involved those incurred by the provision of dietary modifications, care oriented foods, alternatives, and supplements. Dietary therapies included rice porridge and commercially available care foods. The relationships between BMI (body mass index) and the severity of SD assumed in this paper as indicators for general well-being and as resources for coping with SD for PD patients were statistically analyzed., Results: A lower BMI was found in participants eating porridge consistency rice (p = 0.003) and eating porridge rice is significantly related to the severity of SD (p < 0.0001) and PD (p = 0.002). The severity of SD increased with age and PD duration (p = 0.035, p = 0.0005). Outlays for dietary modifications are the lowest reported here (p < 0.004) but the number of participants using dietary modifications is the largest among the SD-related items (n = 58). Eating care foods were reported for 11 older participants (p < 0.0001), most female (10/11). No lower BMI was found in participants eating care foods when compared with participants eating ordinary foods. Dietary modifications were performed by caregivers (OR: 6.8, CI: 3.1-15.2, p < 0.0001) and were related to the presence of children (OR: 3.4, CI: 1.2-11.4. p = 0.024). Older participants commonly live with spouses and children., Conclusions: Severe SD is associated with higher costs of coping with SD. A lower BMI is associated with modified foods, mostly eaten to cope with SD. Presence of caregivers and other persons residing with the participants here are related to dietary modifications but not to care food-related costs. Care foods may be effective in preventing malnutrition although the number who are able to cover the added expenses is limited because of the higher prices and shortage of information on the usefulness of care foods.

Aim: We conducted a cross-sectional study to investigate risk factors for births of light-for-gestational-age (LGA) infants., Methods: A survey was conducted at the Department of Obstetrics and Gynecology at Sapporo Medical University Hospital in Sapporo, Japan from 2013 to 2014. LGA and appropriate for gestational age (AGA) are defined as having a birthweight below the 10th percentile and between the 10th percentile and 90th percentile for gestational age at birth in the population standard of gestational age, sex, and parity, respectively. An odds ratio (OR) and its 95% confidence interval (95%CI) for LGA were calculated by analysis using the logistic regression model., Results: In total, 307 inpatients (94.2%) participated in the study out of 326 consecutive post-partum inpatients. Among them, 37 infants and 237 infants were classified into the LGA and AGA groups, respectively. As a result of multivariable analysis, prevalence of gestational hypertension (OR = 8.96, 95%CI 1.81-44.35) and the presence of placental infarction (OR = 9.65, 95%CI 1.76-53.01) were significantly associated with an increased risk of LGA. Placentas weighing 510-603 g and ≥604 g were significantly associated with reduced risk of LGA (OR = 0.04, 95%CI 0.01-0.29 and OR = 0.03, 95%CI 0.01-0.32, respectively), and higher placental weights were significantly observed in the trend for reduced LGA risk (P for trend < 0.001)., Conclusion: We found that the prevalence of gestational hypertension, lower placental weight, and the presence of placental infarctions were all independently associated with the risk of LGA. Placental abnormalities may be etiologically important for LGA risk, though further research is necessary., (© 2016 Japan Society of Obstetrics and Gynecology.)

Background: Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes., Methods: Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed., Results: BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002)., Conclusions: BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.

YTH domain containing 2 (YTHDC2) is a member of the DExD/H-box family of ATP-dependent RNA helicases. We previously found that YTHDC2 expression is up-regulated in several human cancer cells. In this study, we demonstrate novel roles for YTHDC2 in metastasis of colon tumor cells via translation-dependent pathway. Knockdown of YTHDC2 attenuated protein expression of metastasis-related genes, such as hypoxia-inducible factor-1alpha (HIF-1α), and inhibited metastasis of colon tumor cells in vitro and in vivo. To confirm that YTHDC2 promotes translation initiation by unwinding the 5'-untranslated region (5'UTR) of mRNA, we constructed a firefly luciferase reporter containing the 5'UTR of the HIF-1α mRNA and showed reduction in luciferase activity in YTHDC2-silenced cells. Furthermore, we examined expression levels of YTHDC2 by immunohistochemical staining in human colon cancer tissues from 72 patients and found a significantly positive correlation between YTHDC2 expression and the tumor stage, including metastasis. In conclusion, these results suggest that the RNA helicase YTHDC2 contributes to colon tumor metastasis by promoting translation of HIF-1α and that YTHDC2 is potentially a diagnostic marker and target gene for treating colon cancer patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)