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Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes and the prognostic factors of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).This retrospective study involved patients aged ≥ 65 years who had undergone gastric ESD for EGC at our institution between January 2009 and December 2019. Patients were divided into two groups, namely, a sarcopenia group (109 patients) and a non-sarcopenia group (658 patients), based on the skeletal muscle index and intramuscular adipose tissue content (IMAC). Clinicopathological features, ESD-related adverse events, and outcomes were then compared.In the sarcopenia group, the mean age was higher, whereas performance and nutritional statuses were lower. There were no between-group differences in terms of treatment outcomes. Multivariate analyses (odds ratio [95% confidence interval (CI)]) indicated that a geriatric nutritional risk index score (GNRI) 92 (2.12 [1.09-4.11], p = 0.03), anticoagulant therapy (1.76 [1.13-2.76], p = 0.01), tumor size ≥ 30 mm (2.09 [1.23-3.55], p = 0.01), and sarcopenia (1.90 [1.05-3.45], p = 0.03) were significantly associated with ESD-related adverse events. High Charlson comorbidity index, low prognostic nutritional index, low GNRI, and high IMAC were significantly associated with poor overall survival (OS). OS was significantly shorter in the sarcopenia group even after matching.Patients with sarcopenia had significantly more adverse events and shorter OS; therefore, evaluation of a patient's general condition, including sarcopenia, before ESD is important.

Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes.Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells.Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

Endoscopic submucosal dissection (ESD) is one of the main methods of treatments for early gastric cancer. Sarcopenia is a known risk factor for postoperative adverse events; however, the effect of sarcopenia on gastric ESD is unclear. We investigated the impact of sarcopenia on short-term prognosis after gastric ESD.This was a retrospective cohort study. We reviewed 832 patients who underwent gastric ESD between January 2015 and December 2019 and classified them into two groups: sarcopenia and non-sarcopenia groups. The curative resection rate, adverse events, and lengths of hospital stay were evaluated. We also evaluated risk factors associated with adverse events.700 patients were analyzed (239 in the sarcopenia group and 461 in the non-sarcopenia group). The curative resection rates were similar in both groups. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 (17% vs. 10%) were significantly more common, and the length of hospital stay was longer (8 vs. 7 days) in the sarcopenia group. Univariate analysis identified age ≥ 75 years, antithrombotic medication, history of gastric surgery, submucosal (SM) invasion, and sarcopenia as risk factors for CTCAE grade ≥ 2. Multivariate analysis showed that sarcopenia [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-2.89, p = 0.016], history of gastric surgery (OR 9.32, 95% CI 1.97-44.05, p = 0.005), and SM invasion (OR 2.14, 95% CI 1.24-3.70, p = 0.006) were significant independent risk factors.Sarcopenia significantly affected short-term prognosis and is a novel risk factor for gastric ESD.

Supplementary Data from Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development

Supplementary Tables S1-S2, Figures 1-7 from Frequent Loss of Brm Expression in Gastric Cancer Correlates with Histologic Features and Differentiation State

The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference–based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major gastric cancer types (well- or moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy. [Cancer Res 2007;67(22):10727–35]

Our study aimed to evaluate the relationship between visceral obesity and its associated factors, especially sleep duration in East Asia. We conducted univariate and multivariate analyses using the data of 2538 participants (mean age 56.4 ± 10.8 years) who underwent medical checkups and computed tomography of the abdomen to calculate the visceral fat area from 2008 to 2020. We additionally performed logistic regression analyses using each sleep-duration group (2), 1147 of 1918 men (59.8%) and 131 of 620 women (21.1%) had visceral obesity. In multivariate analyses, visceral obesity was significantly associated with age, body mass index and triglyceride in both genders, high-density lipoproteins, uric acid levels, and daily alcohol consumption in men; and glycated hemoglobin (HbA1c) in women. In both multivariate and propensity score matching analyses, sleep duration of > 8 h and visceral obestiy showed a positive association in men but a negative association in women with statistical significance. In conclusion, our large-scale cross-sectional study in East Asia identified various gender-specific factors associated with visceral obesity including the long sleep duration.

Mucosal atrophy and enlarged folds of stomach by double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) are two major features of Helicobacter pylori-induced chronic gastritis. These were previously shown to be risk indicators of gastric cancer, but their predictability for clinicopathological characters of developed gastric cancer is unelucidated. In addition, evidence for decreasing the mortality of gastric cancer by appropriate follow-up of UGI screening is needed. The 5134 generally healthy UGI-XR examinees, who underwent follow-up UGI-XR or upper gastrointestinal endoscopy (UGI-ES) more than once, were prospectively observed for 10 years. At the beginning of follow-up, 1515 (29.5%) had mucosal atrophy and 990 (19.5%) had enlarged folds. For the serum anti-H. pylori IgG, 1301 (25.3%) were positive, 177 (3.4%) were possibly positive, and 3656 (71.2%) were negative. During the 10-year observation period, gastric cancer developed in 15 subjects, among which 13 had mucosal atrophy and 10 had enlarged folds. These two features were expectedly useful indicators for gastric cancer incidence, but they showed no significant association with tumor stage or histological type of developed cancer. Only one of the 5134 subjects died of gastric cancer during 10 years, which was significantly lower than the predicted number of gastric cancer death (6.78 for 10 years) according to the mortality rate in Japan. Neither mucosal atrophy nor enlarged folds of stomach showed a significant association with clinicopathological features of developed gastric tumors. Appropriate follow-up of cancer screening by UGI-XR or UGI-ES can reduce the risk of gastric cancer-related death.

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.

A non-invasive method to evaluate the fibrosis stage and the risk stratification of non-alcoholic fatty liver disease (NAFLD) is required. A total of 416,066 generally healthy subjects who underwent health check-ups between 1990 and 2019 were investigated. Fatty liver prevalence greatly increased from the 1990s (21.9%) to the 2000s (37.1%) but showed no considerable change between 2001–2010 (39.2%) and 2011–2019 (35.5%). During the 30 years, the rate of high FIB-4 index (≥2.67) and mean body mass index (BMI) did not markedly change. Fatty liver was significantly associated with BMI, but not with alcohol intake or FIB-4 index. Cox regression analyses for development of chronic hepatitis or liver cirrhosis identified that the risk of developing chronic hepatitis and liver cirrhosis was higher in subjects without fatty liver than in those with it (hazard ratio [HR]=0.09; 95% confidence interval [CI], 0.03–0.22, p p =0.001, respectively), and much larger in subjects with a high FIB-4 index (≥ 2.67) than in those without it (HR=78.6; 95% CI, 29.0–213.1, p p

This study assessed the effect of magnifying endoscopy with narrow-band imaging (M-NBI) on the endoscopic differential diagnosis between intramucosal gastric carcinomas and adenomas with matched characteristics. Associations between magnified endoscopic findings and pathological high-grade cellular and architectural atypia were also investigated. In total, the records of 50 adenomas and 50 intramucosal well-differentiated adenocarcinomas matched by tumor size (≥ 20 mm or

The objective of this study was to elucidate the molecular background of sessile serrated adenoma/polyp (SSA/P) endoscopically resected with comprehensive gene expression analysis. Gene expression profiling was performed for 10 tumor-normal pairs of SSA/P. Cluster analysis, gene set enrichment analysis (GSEA), and consensus molecular subtype (CMS) classification of colorectal cancer (CRC) were applied to our transcriptome analysis. Unsupervised cluster analysis showed that the gene expression profile of SSA/Ps is different from that of adjacent normal epithelial cells, even in the very early stage of tumorigenesis. According to the CMS classification, our microarray data indicated that SSA/Ps were classified as CMS1. GSEA demonstrated a strong association between SSA/P and microsatellite instability-high (MSI-H) CRC (p 10

Introduction: Helicobacter pylori eradication is expected to significantly change the prevalence of Barrett’s esophagus (BE). However, few reports on this relationship exist. We analyzed the risk factors of BE using the current consensus on length of BE considering H. pylori infection status. Methods: We analyzed 10,122 individuals (5,962 men; mean age = 52.9 ± 9.9 years) who had undergone esophagogastroduodenoscopy as part of a medical checkup. Correlations among factors including H. pylori infectious status, endoscopic findings, and BE ≥1 cm were analyzed. Results: Prevalence of BE, long-segment BE, and esophageal adenocarcinoma was 22.5%, 0.014%, and 0%, respectively. Logistic regression analysis showed that the risk factors for BE were hiatal hernia (odds ratio [OR]: 2.89 [2.59–3.24]), female sex (OR: 0.52 [0.46–0.59]), social drinking (OR:0.77 [0.68–0.87]), H. pylori eradication therapy (OR: 1.34 [1.19–1.51]), proton pump inhibitor (PPI) use (OR: 1.52 [1.18–1.96]), bile reflux (OR: 1.18 [1.04–1.33]), age ≥50 years (OR: 1.13 [1.02–1.26]), and nonsteroidal anti-inflammatory drug (NSAID) use (OR: 1.29 [1.02–1.62]). Although reflux esophagitis (RE) was more common in H. pylori-negative patients (17.2%) than in those after H. pylori eradication therapy (11.8%, p < 0.00001), the latter was correlated with BE, disputing RE as a strong risk factor for BE. Therefore, we conducted a subgroup analysis; most of the risk factors except for PPI use (p = 0.75), H2-receptor antagonist use (p = 0.078), and atrophic gastritis absence (p = 0.72) were positively correlated with BE after H. pylori eradication therapy compared with H. pylori-negative status. Conclusions: H. pylori eradication, bile reflux, PPI use, and NSAID use were risk factors for BE along with hiatal hernia, male sex, and older age.

Aberrant DNA methylation, induced by aging and accelerated by chronic inflammation, accumulates in normal tissue. Accumulation of DNA methylation in multiple genes, namely epimutation burden, is closely associated with cancer risk. Indeed, we demonstrated that the measurement of the methylation level of a marker gene in normal tissue is useful for cancer risk prediction of metachronous cancers, by a multicenter prospective study with gastric cancer patients (Asada, Gut, 64:388, 2015: Maeda, Gut, 66:1721, 2017). In this study, we attempted to predict the risk of primary gastric cancer by performing a new multicenter prospective study. We recruited 1,880 healthy people, after Helicobacter pylori eradication, with a clinically high risk of gastric cancer. Biopsy specimens were obtained from the antrum and body, and the methylation level of RIMS1, which is a preselected epigenomic risk marker for this study, was measured in 1,757 participants. The participants are annually being followed-up to detect primary gastric cancer, for 5-8 years. Currently, the median follow-up is 4.05 years, and 27 people have developed primary gastric cancers (as of September 2022). The results of statistical analysis are being determined. This study will establish the clinical utility of a cancer risk diagnosis by epimutation burden in normal tissue, and is promising for application in various inflammation-associated cancers. Citation Format: Harumi Yamada, Masahiro Maeda, Seiichiro Abe, Taichi Shimazu, Takayuki Ando, Kazunari Murakami, Shinji Tanaka, Takao Maekita, Osamu Inatomi, Ken Sugimoto, Tetsuro Kawagoe, Nobutake Yamamichi, Toshikazu Ushijima. Cancer risk diagnosis by epimutation burden: a multicenter prospective study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6014.

The increasing usage of proton pump inhibitors (PPIs) has been reported worldwide, but information on PPI use in East Asia is inadequate. This study aimed to examine the trends in PPI use in Japan, along with the changes in histamine H2 receptor antagonist (H2RA) use, disease rate of reflux esophagitis, and the prevalence of upper gastrointestinal symptoms. We analyzed 217,712 healthy subjects (127,607 men and 90,105 women; 51.4 ± 9.7 years old) participating in the health check program from 2010 to 2019. Various upper gastrointestinal symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire. Reflux esophagitis was diagnosed by esophageal erosion using the Los Angeles classification grades A, B, C, and D. From 2010 to 2019, the percentage of PPI users increased markedly from approximately 1.8% to 5.3%, whereas that of H2RA users decreased gradually from approximately 2.5% to 1.9%. The use of all classical types of PPIs (omeprazole, lansoprazole, rabeprazole, and esomerazole) and a new type of PPI, a potassium-competitive acid blocker (vonoprazan), greatly increased during the 10 years. An upward trend in the prevalence of reflux esophagitis was observed from 2010 to 2015, but not from 2016 to 2019, indicating that the monotonic rising prevalence of reflux disease stopped in the middle of the 2010s in Japan. In contrast, various upper gastrointestinal symptoms significantly improved between 2010 and 2019. All 12 FSSG symptoms of PPI users were significantly worse than those of non-PPI users, suggesting that PPIs still cannot completely control upper gastrointestinal symptoms. In conclusion, this study revealed a significant increase in PPI use and a slight decrease in H2RA use from 2010 to 2019. Despite a plateau in the prevalence of reflux esophagitis and considerable improvement in various upper gastrointestinal symptoms, PPI use has continued to increase in Japan.

Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes.Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Aim: Obesity and metabolic syndrome (MetS) frequently coexist and are both important risk factors for cardiovascular disease. However, the pathophysiological role of obesity without MetS, also referred to as metabolically healthy obesity (MHO), remains unclear. In this study, we aim to clarify the effect of MHO on the development of carotid plaque using a community-based cohort. Methods: We examined 1,241 subjects who underwent health checkups at our institute. Obesity was defined as body mass index of ≥ 25.0 kg/m2. Subjects were divided into three groups: non-obese, MHO, and metabolically unhealthy obesity (MUO). Results: The prevalence of carotid plaque, defined as intima-media thickness (IMT) ≥ 1.1 mm, was higher in subjects with MUO and MHO than in non-obese subjects. Multivariable analysis demonstrated that MHO (odds ratio 1.6, p = 0.012) and MUO (odds ratio 1.9, p = 0.003) as well as age of ≥ 65 years, male sex, hypertension, and diabetes mellitus were independently associated with carotid plaque formation. A similar trend was observed in each subgroup according to age and sex. Conclusions: MHO increased the prevalence of carotid plaque when compared with non-obese subjects, suggesting the potential significance of MHO in the development of subsequent cardiovascular diseases.

Body weight gain in middle age is thought to be mainly attributable to body fat gain. However, the association between the change in body weight and change in fat weight is not fully understood. In this study, we aimed to clarify the association between the changes in body weight and fat weight in a middle-aged general population using a community-based cohort. We studied 3,193 subjects who underwent health check-ups. Fat weight was measured using a TANITA DC-270A body composition analyzer (Tanita Corporation, Tokyo). Good correlation was observed between the changes in body weight and fat weight (Pearson r = 0.88, P < 0.001). Among the study subjects, 408 (13%) were categorized in the weight loss group (weight loss ≥ 5%), 2,442 (76%) in the weight stable group, and 343 (11%) in the weight gain group (weight gain ≥ 5%). The percentage of change in fat weight in relation to the change in body weight was 65% on average in subjects with body weight loss, and 70% on average in those with body weight gain. Good correlation between changes in body weight and fat weight was observed regardless of age, gender, and baseline body mass index. A change in body weight was closely correlated with a change in fat weight among the middle-aged general population. Body weight change in the middle-age population appears to be mainly attributable to the change in fat weight.

The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m2 who underwent health check-ups. Among the study subjects, 175 (15%) were categorized in the weight loss group (weight loss ≥ 5%), 869 (74%) in the weight stable group, and 126 (11%) in the weight gain group (weight gain ≥ 5%). There were no significant differences in baseline BP between the 3 groups. In the weight loss group, systolic and diastolic BP, and the rates of stage 2 (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) and stage 1 hypertension (130 mmHg≤ systolic BP < 140 mmHg or 80 mmHg≤ diastolic BP < 90 mmHg) decreased. In contrast, in the weight gain group, systolic and diastolic BP and the rate of stage 2 hypertension increased. Subgroup analysis showed that the correlation between change in body weight and BP was seen in each subgroup according to age, sex, and BMI. The results of the present study suggest the significance of body weight control for BP control in subjects with BMI ≥ 22 kg/m2.

Cigarette smoking is closely associated with the development of cardiovascular diseases. However, the relationship between cigarette smoking and subclinical atherosclerosis has not been fully studied. We sought to clarify the association between cigarette smoking and carotid intima-media thickness (cIMT) in a general Japanese population. Among 1,209 participants who received a medical check-up with cardiovascular examination at our institution, 450 participants (37.2%) were smokers (including both past and current smokers). We evaluated cIMT as a marker of subclinical atherosclerosis. The value of cIMT and rate of carotid plaque defined as IMT ≥ 1.1 mm did not differ between smokers and never smokers. However, the rate of carotid high-risk atheroma, defined as carotid artery atheroma including hypoechoic dominant and ulceration, was significantly higher among smokers than never smokers (30.4%, vs 23.6%, p = 0.009). Even after adjustment for covariates, cigarette smoking was independently associated with high-risk atheroma formation (odds ratio 1.384, 95% CI 1.019–1.880; p = 0.038). The value of cIMT and the rate of high-risk atheroma were significantly higher in smokers than never smokers in the subgroup of participants aged ≥ 60 years, whereas the rate of high-risk atheroma only was higher in smokers than never smokers in the subgroup of participants aged

BackgroundWe previously showed that the endoscopic Kyoto classification for gastritis could predict Helicobacter pylori infection in individuals with a high negative titer of serum anti-H pylori an...

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.

The numbers of Helicobacter pylori (HP)-infected individuals and deaths due to gastric cancer are decreasing in Japan. We aimed to determine whether the serological test for chronic gastritis (the ABC method) is still useful for gastric cancer risk stratification in the 2010s and to analyze risk factors for developing gastric cancer in Japan.In this prospective study, we monitored 20773 individuals for the incidence of gastric cancer from 2010 to 2019. The relationships between blood sampling results, physical examination, and lifestyle in 2010 and the cumulative incidence of gastric cancer were analyzed.A total of 19343 participants who met the study criteria were analyzed. Overall, 0.08% of participants in group A (9/11717), 0.63% in group B (28/4452), 2.05% in group C (43/2098), 1.52% in group D (1/66), and 0.30% in group E (3/1010) developed gastric cancer. Cox hazard analysis showed that age ≥ 50 years; groups B, C, and D according to the ABC method; and current smoking habits were independent risk factors for gastric cancer. The hazard ratios (HRs) of the incidence of gastric cancer were 6.7 in group B and 21.7 in groups C and D, while the HRs of group E was 2.8, which was not significantly different from that of group A. The incidence of gastric cancer was not statistically significantly different between those with and without successful HP eradication in groups B, C, and D during follow-up.The ABC method was still useful for gastric cancer risk stratification in the 2010s.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.

Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown.Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR.The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation.AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Diagnosis of gastric adenocarcinoma using small biopsy samples is occasionally difficult. Various markers have been employed for improving the diagnostic accuracy, but there remains room for improvement. A total of 129 endoscopically biopsied samples were studied, consisting of 104 intramucosal tubular adenocarcinomas, 24 non-cancerous lesions and one cancer sample originally suspected of non-cancer but revised as cancer after immunostaining. We evaluated the association between histopathology and immunohistochemical expression of MUC1, HER2, p53, CEA, E-cadherin, β-catenin and claudin-18. Regarding β-catenin and claudin-18, not only membranous expression (β-catenin(M) and claudin-18(M)) but also nuclear expression (β-catenin(N) and claudin-18(N)) were analyzed. When subtyped with mucin core protein expression, the gastric-type cancers dominantly expressed claudin-18(M), while claudin-18(N) was significantly encountered in intestinal- and mixed-types. Expression of MUC1 (P = 0.0010), HER2 (P = 0.0173), p53 (P = 0.0002), CEA (P = 0.0019) and claudin-18(N) (P < 0.0001) revealed significant correlation with gastric cancers. Negative correlation of claudin-18(M) (P = 0.0125) was also noted. MUC1 and p53 were negative in non-cancer lesions. The non-cancer group exceptionally expressed HER2 and β-catenin(N). Membranous expression of E-cadherin was consistent in both groups. Logistic regression analysis showed that MUC1 (P = 0.0086), p53 (P = 0.0031), claudin-18(M) (P = 0.0158) and claudin-18(N) (P = 0.0190) were independently associated with gastric cancers. Nuclear expression of claudin-18 should be the novel diagnostic marker for gastric cancer.

Background Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Recent reports have described the efficacy of the endoscopic shielding method with polyglycolic acid (PGA) sheets and fibrin glue for the prevention of adverse events after ESD. The aim of the present study was to investigate whether the PGA shielding method provides additional benefit in preventing post-ESD bleeding compared with standard care. Methods This was a prospective, multicenter, randomized controlled trial. Patients at high risk of post-ESD bleeding were enrolled in the study. Before ESD, patients were randomized to either the PGA group or the control group. After completing ESD in the PGA group, PGA sheets were placed onto the ulcer floor and adhered with fibrin glue. The primary end point was the post-ESD bleeding rate. Results 140 eligible patients were enrolled from September 2014 to September 2016, and 137 were included in the intention-to-treat analysis (67 in the PGA group and 70 in the control group). Post-ESD bleeding occurred in three patients (4.5 %) in the PGA group and in four patients (5.7 %) in the control group; there was no significant difference between the two groups (P > 0.99). Post-ESD bleeding tended to occur later in the control group than in the PGA group (median 12.5 days [range 8 – 14] vs. 2 days [range 0 – 7], respectively). Conclusion The PGA shielding method did not demonstrate a significant effect on the prevention of post-ESD bleeding.

Recent studies have highlighted the role of gut microbiota in the pathogenesis of cardiometabolic diseases. In particular, microbially produced metabolites have been shown to affect the host metabolism, however, their impacts on metabolic diseases have not been fully elucidated. For instance, the findings from an obese mouse model have suggested that polysaccharide fermentation could serve as the additional energy sources, yet the effects on human pathology has not been reported. To address this question, we applied a multi-omics strategy, which integrated gut microbiome analyses with multi-platform metabolomic techniques. We sampled from 306 Japanese males and females with obesity (49.7%) and prediabetes (32.7%). Fecal microbiome was analyzed by 16S rRNA amplicon and metagenomic shot-gun sequencings, while fecal hydrophilic and lipid metabolites were measured using GC-MS and LC-MS-based platforms respectively, and were clustered by their co-expression profiles. We found that three out of 19 fecal hydrophilic clusters and three out of 86 lipid clusters were significantly associated with insulin resistance (IR) defined by HOMA-IR. Notably, the identified fecal hydrophilic clusters were classified as sugar derivatives such as monosaccharides and disaccharides. These metabolites were indeed increased in not only the fecal contents but also the plasma samples of IR group. In addition, microbes belonging to genera Dorea and Coprococcus, which are known to degrade polysaccharides, were abundant in the IR group, and were highly correlated with fecal sugar derivatives, while other microbes such as Alistipes showed negative correlation. Finally, we confirmed that the oral administration of a Dorea strain to HFD-fed mice exacerbated obesity and IR compared with Alistipes administration. Collectively, we report a novel mechanistic insight into the effects of gut microbes on metabolic diseases, where microbial fermentation of polysaccharides and its derivatives impact the host metabolism. Disclosure T. Takeuchi: None. Y. Nakanishi: None. K. Ikeda: None. H. Tsugawa: None. W. Suda: None. Y. Mizuno: None. N. Yamamichi: None. M. Arita: None. M. Hattori: None. N. Kubota: None. T. Kubota: None. T. Kadowaki: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Cosmic Corporation, Daiichi Sankyo, Eli Lilly Japan K.K., FUJIFILM, Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Medscape Education, Medtronic, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, NIPRO Medical Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Asahi Mutual Life Insurance. S. Koyasu: None. H. Ohno: None.

Deep learning has become a new trend of image recognition tasks in the field of medicine. We developed an automated gastritis detection system using double-contrast upper gastrointestinal barium X-ray radiography. A total of 6520 gastric X-ray images obtained from 815 subjects were analyzed. We designed a deep convolutional neural network (DCNN)-based gastritis detection scheme and evaluated the effectiveness of our method. The detection performance of our method was compared with that of ABC (D) stratification. Sensitivity, specificity, and harmonic mean of sensitivity and specificity of our method were 0.962, 0.983, and 0.972, respectively, and those of ABC (D) stratification were 0.925, 0.998, and 0.960, respectively. Although there were 18 false negative cases in ABC (D) stratification, 14 of those 18 cases were correctly classified into the positive group by our method. Deep learning techniques may be effective for evaluation of gastritis/non-gastritis. Collaborative use of DCNN-based gastritis detection systems and ABC (D) stratification will provide more reliable gastric cancer risk information.

Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity, atrophy, and age: A cross-sectional study

Gastric cancer (GC) is rich in many different histological types, but how the histological pattern is defined remains to be proved. The relation between GC histological types and the expression of nectin1, which is one of the cell adhesion molecules that composes adherens junction, has not been reported. According to a publicly available database of 406 GC patients, the median overall survival of Nectin1 high expression patients was 55.4 months and that of low expression patients was 25.6 months (P = 0.0246). Using surgically or endoscopically resected GC samples, nectin1 expression was analyzed by immunohistochemistry. Nectin1 expressed at adherens junction in all the normal epithelial cells. However, nectin1 expressed not at adherens junction but at apical membrane in epithelial cells in intestinal metaplasia. The expression pattern of nectin1 in intestinal type GC resembled to intestinal metaplasia. In order to analyze the difference in nectin1 expression between GC histological types, a total of 116 intestinal type GC and 33 diffuse type GC. The expression of necitin1 in diffuse type GC (3.0%) was remarkably decreased compared to that in intestinal type GC (65.5%) (P < 0.0001). In conclusion, this is the first report showing an association between nectin1 expression and histological subtypes of GC.

The mechanism behind the pathogenesis and carcinogenesis of these neoplasms is not fully understood. The objective of this study was to identify genetic markers and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas through gene expression analysis. Gene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. Genes with consistent expression differences were identified and confirmed in 7 independent pairs. Gene set enrichment analysis (GSEA) was performed to characterize gene expression profiles of duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of candidate oncogenic genes. 626 probes consistently demonstrated over a twofold expression difference between tumor–normal pairs. Reverse transcriptase polymerase chain reaction of genes with the most prominent difference in expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17, LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p

Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed. In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features. We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed. The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37–85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6. Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers.

Although high-resolution three-dimensional imaging of endoscopically resected gastrointestinal specimens can help elucidating morphological features of gastrointestinal mucosa or tumor, there are no established methods to achieve this without breaking specimens apart. We evaluated the utility of transparency-enhancing technology for three-dimensional assessment of gastrointestinal mucosa in porcine models. Esophagus, stomach, and colon mucosa samples obtained from a sacrificed swine were formalin-fixed and paraffin-embedded, and subsequently deparaffinized for analysis. The samples were fluorescently stained, optically cleared using transparency-enhancing technology: ilLUmination of Cleared organs to IDentify target molecules method (LUCID), and visualized using laser scanning microscopy. After observation, all specimens were paraffin-embedded again and evaluated by conventional histopathological assessment to measure the impact of transparency-enhancing procedures. As a result, microscopic observation revealed horizontal section views of mucosa at deeper levels and enabled the three-dimensional image reconstruction of glandular and vascular structures. Besides, paraffin-embedded specimens after transparency-enhancing procedures were all assessed appropriately by conventional histopathological staining. These results suggest that transparency-enhancing technology may be feasible for clinical application and enable the three-dimensional structural analysis of endoscopic resected specimen non-destructively. Although there remain many limitations or problems to be solved, this promising technology might represent a novel histopathological method for evaluating gastrointestinal cancers.

Background and study aims Endosurgical devices with injection function have been reported to decrease endoscopic submucosal dissection (ESD) operation times for experts, but the efficacy of these devices for inexperienced endoscopists is unclear. The aim of this study was to evaluate the feasibility of ESD using a novel ESD knife (DN-D2718B). Patients and methods This is a single-center prospective pilot clinical feasibility study. Patients diagnosed with superficial gastrointestinal neoplasms were enrolled. A pre-specified group of ESD trainees with ESD experience on a porcine gastric model and fewer than 30 cases of ESD in their selected fields performed ESD under expert supervision, using the DN-D2718B. En bloc resection rates, R0 resection rates, procedure times, and incidence of intra-operational/post-operational adverse events were assessed. Results Between June 2015 and January 2016, 13 esophageal, 27 gastric, and 14 colorectal ESD cases were performed per-protocol with mean resection speeds of 10.2, 12.0, and 15.5 mm2/min, respectively. There were no intra-operational complications. Conclusion ESD with this novel knife is feasible even when performed by non-experts.

Background and Aims: Esophageal adenocarcinoma develops in the setting of gastroesophageal reflux and columnar metaplasia in distal esophagus. Columnar metaplasia arising in gastroesophageal reflux models has developed in rat; however, gastroesophageal reflux models in mice have not been well-characterized. Methods: One hundred thirty-five C57Bl/6J mice aged 8 weeks old were divided into the following operations: esophagogastrojejunostomy (side-to-side) (EGJ), esophageal separation and esophagojejunostomy (end-to-side) (EJ), and EJ and gastrectomy (end-to-side) (EJ/TG). The animals were euthanized after 40 weeks and the histology of the junction was examined. Immunohistochemistry for p53, PDX-1, and CDX-2 was performed. Results: Metaplasia developed in 15/33 (45.5%) of EGJ, 0/38 (0%) of EJ, and 6/39 (15.4%) of EJ/TG (P < .05) and dysplasia developed 7/33 (21.2%) of EGJ, 0% of EJ, and 1/39 (2.6%) of EJ/TG. p53 was positive in all of the dysplastic regions, 12/15 (80%) metaplasias in the EGJ model, and 1/6 (16.7%) metaplasia in the EJ/TG model. CDX-2 was positive in all cases of metaplasias, but decreased in some cases of dysplasia. PDX-1 was positive in 7/8 (88%) cases of dysplasia and in 15/21 (71%) cases of metaplasia (P < .05). Conclusions: The EGJ model, which causes reflux of gastric acid and duodenal content, developed metaplasia and dysplasia most frequently. No metaplasia developed in the EJ model in which gastric juice and duodenal content mixed before reflux. Thus, duodenal contents alone can induce columnar metaplasia and dysplasia; however, the combination of gastric acid with duodenal content reflux can cause metaplasia and dysplasia more efficiently. Keywords: GERD, Esophageal Reflux, Barrettâs Esophagus, Esophageal Adenocarcinoma

Body weight gain in middle age is thought to be mainly attributable to body fat gain. However, the association between the change in body weight and change in fat weight is not fully understood. In this study, we aimed to clarify the association between the changes in body weight and fat weight in a middle-aged general population using a community-based cohort. We studied 3,193 subjects who underwent health check-ups. Fat weight was measured using a TANITA DC-270A body composition analyzer (Tanita Corporation, Tokyo). Good correlation was observed between the changes in body weight and fat weight (Pearson r = 0.88, P0.001). Among the study subjects, 408 (13%) were categorized in the weight loss group (weight loss ≥ 5%), 2,442 (76%) in the weight stable group, and 343 (11%) in the weight gain group (weight gain ≥ 5%). The percentage of change in fat weight in relation to the change in body weight was 65% on average in subjects with body weight loss, and 70% on average in those with body weight gain. Good correlation between changes in body weight and fat weight was observed regardless of age, gender, and baseline body mass index. A change in body weight was closely correlated with a change in fat weight among the middle-aged general population. Body weight change in the middle-age population appears to be mainly attributable to the change in fat weight.

Waist circumference (WC) is measured for the assessment of abdominal obesity, whereas carotid intima-media thickness (IMT) is a marker of preclinical atherosclerosis. The relationship between WC and carotid IMT in the general population is not fully understood. In this study, we examined 1,182 subjects (658 men and 524 women, 62.3 ± 11.7 years on average) who underwent voluntary health check-ups and sought to determine the optimal cut-off value of WC for predicting carotid IMT thickness. Receiver operating characteristic curve analysis of WC was utilized to predict high carotid IMT (defined as carotid IMT ≥ 1.1 mm). We determined that the appropriate WC cut-off value was a WC ≥ 79 cm for men and women. There was a statistically significant difference in the prevalence of high carotid IMT between WC ≥ 79 cm and WC < 79 cm in both men and women. However, multivariable logistic regression analysis demonstrated that the WC category was independently associated with high carotid IMT in men, but not in women. Our study indicates that the optimal cut-off value of WC to identify preclinical atherosclerosis may be lower than the current Japanese diagnostic criteria for metabolic syndrome (MetS) in both men and women. Compared to women, the association between WC and preclinical atherosclerosis may be more pronounced in men.

Background and Aims Postoperative stricture after expansive esophageal endoscopic submucosal dissection (ESD) is a severe adverse event. Previous single-arm reports have suggested that polyglycolic acid (PGA) shielding may prevent stricture. This study was performed to assess the efficacy of this method through a comparative analysis. Methods This is a retrospective analysis of 500 consecutive cases of esophageal ESD performed between 2002 and 2018 at the University of Tokyo Hospital. After 2013, patients with a diagnosis of superficial esophageal carcinoma covering more than half of the esophageal circumference underwent preventive treatment with either PGA shielding or steroid injection + PGA shielding after ESD. The efficacy of these methods for preventing post-ESD stricture was assessed through multivariable logistic regression analysis. Results The risk of postoperative stricture was especially high in the cervical esophagus (odds ratio [OR], 4.60; 95% confidence interval [CI], 0.65-61.09) and after total circumferential resection (OR, 3.58×103; lower bound of 95% CI, >185). Steroid injection + PGA shielding was the only method significantly effective in preventing stricture (OR, 0.30; 95% CI, 0.10-0.78; P = .009). In the relatively low-risk subgroup (excluding cervical esophageal cancer and complete circumferential resection), the postoperative stricture rates for steroid injection + PGA shielding versus PGA shielding versus control were 18.9% versus 41.4% versus 51.7%, respectively (P = .015). However, the efficacy of this was limited in extremely high-risk cases. Conclusion The combination of steroid injection and PGA shielding is effective for preventing post-ESD stricture. There is a need for even more effective methods for cervical esophageal cancer and complete circumferential resection.

BackgroundSeveral previous studies have suggested that Helicobacter pylori (H. pylori) infection affects the serum lipid profile. However, it remains controversial and the mechanism has not been elucidated. The purpose of this study is to use an epidemiological perspective to evaluate the association between H. pylori infection and the serum lipid profile.MethodsMultivariate analysis was performed using the data of serum lipid profile, infection status of H. pylori, fitness/lifestyle habits, and various subjects' characteristics which were derived from the 15,679 generally healthy individuals in Japan. The average treatment effects (ATEs) of H. pylori infection on the serum lipid profile were estimated using augmented inverse probability weighting (AIPW). A meta-analysis was also performed using the 27 studies worldwide in which the status of H. pylori infection and at least one serum examination value (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), or triglyceride (TG)) were described.ResultsThe ATEs determined with AIPW showed that H. pylori infection has significant positive effects on LDL-C and TC (ATE (95% confidence interval [95%CI]) = 3.4 (2.36-4.49) and 1.7 (0.58-2.88), respectively) but has significant negative effects on HDL-C and TG (ATE (95%CI) = -1.2 (-1.74 to -0.72) and -3.5 (-5.92 to -1.06), respectively). The meta-analysis to estimate the association between H. pylori infection and the serum lipid profile revealed that H. pylori infection is positively associated with LDL-C, TC, and TG (standardized mean difference [SMD] (95%CI) = 0.11 (0.09-0.12), 0.09 (0.07-0.10) and 0.06 (0.05-0.08), respectively) and negatively associated with HDL-C (SMD = -0.13 (-0.14 to -0.12)).ConclusionBoth our multivariate analyses and meta-analysis showed that H. pylori infection significantly affects the serum lipid profile, which might lead to various dyslipidemia-induced severe diseases like coronary thrombosis or cerebral infarction.

The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m

Introduction Obesity is a common and independent risk factor for all-cause mortality. More specifically, obesity is a major component of atherosclerosis in association with metabolic disorders including metabolic syndrome (MetS), resulting in various cardiovascular diseases (CVD). Alternatively, obese subjects without MetS are prevalent, also referred to as metabolically healthy obesity (MHO). However, most preceding studies regarding MHO have been limited by small cohorts. Therefore, the effect of MHO on atherosclerosis in the general population remains unclear. Purpose In this study, we sought to clarify the effect of MHO on carotid intima-media thickness (IMT) as a marker of early stage atherosclerosis using a community-based cohort in general population. Methods We examined subjects who underwent medical check-up at our University Hospital. We defined obesity as body mass index ≥25.0 kg/m2. Abdominal obesity, defined as waist circumstance at umbilical level ≥85 cm in men and ≥90 cm in women, was obligatory for the diagnosis of MetS. In addition to abdominal obesity, any two of the following three abnormalities should be observed for the diagnosis of MetS, [1] Dyslipidemia: triglyceride ≥150 mg/dL, HDL-C Results Among 1,241 subjects, 857 subjects (69%) were categorized in the normal body weight group, whereas 275 subjects (22%) were categorized as MHO, and 109 subjects (9%) were categorized as MUO. Compared to non-obese subjects, prevalence of classical cardiovascular risk factors including hypertension, diabetes mellitus, and dyslipidemia increased in subjects with MHO, and further increased in those with MUO. IMT was higher in obese subjects compared to those without obesity. Similarly, the prevalence of carotid plaque formation was also higher in obese subjects. Multivariable logistic regression analysis demonstrated that age ≥60 years, male sex, hypertension, diabetes mellitus, MHO subjects (Odds ratio [OR]; 1.6, p=0.005), and MUO subjects (OR 1.7, p=0.04) were independently associated with carotid plaque formation. There was no statistical difference in the risk of carotid plaque formation between subjects with MHO and MUO. IMT and Carotid Plaque Conclusions IMT and the prevalence of carotid plaque are higher in both subjects with MHO and MUO compared to non-obese subjects in the general population. We need to take obesity regardless of the presence of MetS into consideration as high-risk subjects for subsequent CVD.

Background Cigarette smoking is closely associated with the development of cardiovascular diseases (CVD), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines recommend smoking bans.On the other hand, the relationship between cigarette smoking and subclinical atherosclerosis has not been fully studied. Carotid intima-media thickness (cIMT) is commonly used as a subclinical atherosclerosis marker, and a carotid plaque feature is also known to be an important predictor of cardiovascular diseases. Purpose We sought to clarify the association between cigarette smoking and subclinical atherosclerosis by evaluating carotid plaque including cIMT and carotid plaque features in general population. Methods and results Among 1,209 participants with no prior coronary artery disease who received a medical check-up with cardiovascular examination at our institution, 450 participants (37.2%) were smokers (including both past and current smokers). We defined carotid plaque as cIMT ≥1.1 mm and high-risk plaque as carotid plaque with hypoechoic dominant and/or plaque ulceration. The value of cIMT and the rate of carotid plaque were not different between smokers and never smokers (Figure A & B). However, the rate of carotid high-risk plaque was significantly higher in participants with smokers than those with never smokers (29.7%, vs 23.5%, p=0.011) (Figure C). Even after adjustment with covariates including age, gender and traditional cardiovascular risk factors, cigarette smoking was independently associated with high-risk plaque formation (odds ratio 1.384, 95% CI 1.020–1.877; p=0.037). According to the subgroup analysis classified by age, cigarette smoking was associated with not only the development of high-risk plaque but also the increased value of cIMT in the subgroup over 60 years old, whereas only the rate of high-risk plaque was higher in smokers than never smokers in the subgroup under 60 years old. Carotid plaque and smoking Conclusion The development of high-risk carotid artery plaque may precede thickening of cIMT in cigarette smokers, suggesting that the novel insight for the pathological mechanism underlying cardiovascular events and cigarette smoking.

The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for hypertension have lowered the threshold of normal blood pressure (BP). However, how this updated guideline should be applied to the general population is still under debate, and may depend on gender because of a substantial gender difference in the risk of cardiovascular disease. We aimed to clarify the gender difference in the association between BP category and cardio-ankle vascular index (CAVI), as a marker of subclinical atherosclerosis, using a community-based cohort.We examined 1,241 subjects (699 males and 542 females) who underwent health check-ups at our institute. We defined normal pressure as systolic (s)BP130 mmHg and diastolic (d)BP80 mmHg, stage 1 hypertension as 130 mmHg ≤ sBP 140 mmHg or 80 mmHg ≤ dBP 90 mmHg and stage 2 hypertension as sBP ≥140 mmHg or dBP ≥90 mmHg, including subjects on antihypertensive medications. High CAVI was defined as CAVI ≥9.0.Age and the prevalence of most of atherosclerotic risk factors increased with increasing BP category in both male and female subjects. A linear relationship between the prevalence of high CAVI and high BP category was observed in males, but not in females. Multivariable logistic regression analysis revealed that BP category was independently associated with high CAVI in males but not in females.There was a difference seen between males and females in the association between BP category, according to the updated ACC/AHA guideline, and CAVI, suggesting that the optimal management strategy for hypertension may depend on not only age, obesity, and diabetes mellitus, but also gender.

Background and Aims Diagnosing the invasion depth of gastric cancer (GC) is necessary to determine the optimal method of treatment. Although the efficacy of evaluating macroscopic features and EUS has been reported, there is a need for more accurate and objective methods. The primary aim of this study was to test the efficacy of novel artificial intelligence (AI) systems in predicting the invasion depth of GC. Methods A total of 16,557 images from 1084 cases of GC for which endoscopic resection or surgery was performed between January 2013 and June 2019 were extracted. Cases were randomly assigned to training and test datasets at a ratio of 4:1. Through transfer learning leveraging a convolutional neural network architecture, ResNet50, 3 independent AI systems were developed. Each system was trained to predict the invasion depth of GC using conventional white-light imaging (WLI), nonmagnifying narrow-band imaging (NBI), and indigo-carmine dye contrast imaging (Indigo). Results The area under the curve of the WLI AI system was .9590. The lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the WLI AI system were 84.4%, 99.4%, 94.5%, 98.5%, and 92.9%, respectively. The lesion-based accuracies of the WLI, NBI, and Indigo AI systems were 94.5%, 94.3%, and 95.5%, respectively, with no significant difference. Conclusions These new AI systems trained with multiple images from different angles and distances could predict the invasion depth of GC with high accuracy. The lesion-based accuracy of the WLI, NBI, and Indigo AI systems was not significantly different.