Search

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.

Fabry disease (FD), which is a lysosomal storage disease resulting from a deficiency of α-galactosidase A, leads to the accumulation of globotriaosylceramide in various tissues and multiorgan impairment. Early diagnosis is important to improve long-term prognosis. Early clinical manifestations of FD include neuropathic pain, vascular skin lesions, and sweating abnormalities. Hypohidorosis is one of the clinical findings in the early stage of FD. However, there have been no studies on prospective screening of FD in patients with definitive diagnosis of hypohidrosis. We examined α-galactosidase A activity in white blood cells in 17 (one female and 16 male) patients with generalized hypohidorosis. Among 17 patients, one male patient (approximately 5.8%) had significantly reduced α-galactosidase A activity. He presented with a history of hypohidrosis with heat intolerance and neuropathic tingling pain in a warm environment from 6 years ago. He had a few angiokeratoma on the trunk and extremities. Ultrastructural examination of skin biopsy from the angiokeratoma revealed lamellar inclusions in endothelial cells. Kidney biopsy revealed swollen podocytes and Gb3 deposition in the glomerulus, and urinalysis revealed mulberry bodies. He was finally diagnosed with FD and started on enzyme replacement therapy with agalsidase alpha in the early stage. In addition, his family screening led to find the patients of four additional FD. Screening for FD in patients with hypohidrosis may lead to efficient early detection of FD.

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.

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.

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

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.

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is the standard gastric cancer screening method in Japan. Atrophic gastritis and enlarged gastric folds are considered the two major features of Helicobacter pylori-induced chronic gastritis, but the clinical meaning of evaluating them by UGI-XR has not been elucidated. We analyzed healthy UGI-XR examinees without a history of gastrectomy, previous Helicobacter pylori eradication and usage of gastric acid suppressants. Of the 6433 subjects, 1936 (30.1 %) had atrophic gastritis and 1253 (19.5 %) had enlarged gastric folds. During the 3-year prospective observational follow-up, gastric cancer developed in seven subjects, six of whom (85.7 %) had atrophic gastritis with H. pylori infection and five of whom (71.4 %) had enlarged gastric folds with H. pylori infection. The Kaplan-Meier method with log-rank testing revealed that both UGI-XR-based atrophic gastritis (p = 0.0011) and enlarged gastric folds (p = 0.0003) are significant predictors for future gastric cancer incidence.

Background and Aims The aim of this study was to clarify whether dental floss clip (DFC) traction improves the technical outcomes of endoscopic submucosal dissection (ESD). Methods A superiority, randomized control trial was conducted at 14 institutions across Japan. Patients with single gastric neoplasm meeting the indications of the Japanese guidelines for gastric treatment were enrolled and assigned to receive conventional ESD or DFC traction-assisted ESD (DFC-ESD). Randomization was performed according to a computer-generated random sequence with stratification by institution, tumor location, tumor size, and operator experience. The primary endpoint was ESD procedure time, defined as the time from the start of the submucosal injection to the end of the tumor removal procedure. Results Between July 2015 and September 2016, 640 patients underwent randomization. Of these, 316 patients who underwent conventional ESD and 319 patients who underwent DFC-ESD were included in our analysis. The mean ESD procedure time was 60.7 and 58.1 minutes for conventional ESD and DFC-ESD, respectively ( P = .45). Perforation was less frequent in the DFC-ESD group (2.2% vs .3%, P = .04). For lesions located in the greater curvature of the upper or middle stomach, the mean procedure time was significantly shorter in the DFC-ESD group (104.1 vs 57.2 minutes, P = .01). Conclusions Our findings suggest that DFC-ESD does not result in shorter procedure time in the overall patient population, but it can reduce the risk of perforation. When selectively applied to lesions located in the greater curvature of the upper or middle stomach, DFC-ESD provides a remarkable reduction in procedure time.

Triamcinolone Injection and Shielding with Polyglycolic Acid Sheets and Fibrin Glue for Postoperative Stricture Prevention after Esophageal Endoscopic Resection: A Pilot Study

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is a method broadly used for gastric cancer screening in Japan. Gastric polyp is one of the most frequent findings detected by UGI-XR, but how to handle it remains controversial. Gastric polyps of the 17,264 generally healthy subjects in Japan who underwent UGI-XR or upper gastrointestinal endoscopy (UGI-ES) in 2010 were analyzed. Of the 6,433 UGI-XR examinees (3,405 men and 3,028 women, 47.4 ± 9.0 years old), gastric polyps were detected in 464 men (13.6 %) and 733 women (24.2 %) and were predominantly developed on the non-atrophic gastric mucosa (p

Upper gastrointestinal endoscopy (UGI-ES) and double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) are two major image-based methods to diagnose atrophic gastritis, which is mostly induced by Helicobacter pylori infection. However, there have been few studies directly comparing them.Atrophic gastritis was evaluated using the data of 962 healthy subjects who underwent UGI-ES and UGI-XR within 1 year.Based on UGI-ES and UGI-XR, 602 subjects did not have atrophic gastritis and 254 subjects did have it. Considering UGI-ES-based atrophic gastritis as the standard, sensitivity and specificity of UGI-XR-based atrophic gastritis were 92.0 % (254/276) and 92.8 % (602/649), respectively. The seven-grade Kimura-Takemoto classification of UGI-ES-based atrophic gastritis showed a strong and significant association with the four-grade UGI-XR-based atrophic gastritis. Sensitivity and specificity of serum anti-Helicobacter pylori IgG to detect UGI-ES/UGI-XR-based atrophic gastritis were 89.4 % (227/254) and 99.8 % (601/602), indicating that atrophic gastritis can be overlooked according to serum anti-Helicobacter pylori IgG alone.

Background Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan. Methods We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors. Results Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that age (β = 0.217-0.674, OR = 1.24-1.96), male gender (β = 0.185, OR = 1.20), smoking (β = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (β = 0.153, OR = 1.17), HbA1c (β = 0.136, OR = 1.15), drinking (β = 0.109, OR = 1.11), and serum triglyceride (β = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not. Conclusions The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.

Background There have been very few reports assessing the relationship between various upper gastrointestinal (GI) symptoms or evaluating each individual upper GI symptom separately. Methods Based on the answers to Frequency Scale for the Symptoms of GERD from a large-scale population of healthy adults in Japan, a hierarchical cluster analysis was performed to categorize the typical 12 upper GI symptoms. The associations between the 12 symptoms and 13 background factors were systematically analyzed among the 18,097 digestive drug-free subjects, 364 proton-pump inhibitor (PPI) users, and 528 histamine H2-receptor antagonist (H2RA) users. Results The derived relationship between the 12 upper GI symptoms suggests the five symptom categories: heartburn (2), dyspepsia (4), acid regurgitation (3), pharyngo-upper esophageal discomfort (2), and fullness while eating (1). Among the digestive drug-free subjects, inadequate sleep, weight gain in adulthood, NSAID use, meals immediately prior to sleep, and frequent skipping of breakfast showed significant positive association with most upper GI symptoms. Compared to the digestive drug-free subjects, significantly associated factors for PPI and H2RA users are respectively different in “4 of 5” and “5 of 5” symptoms in heartburn and acid regurgitation categories, “1 of 2” and “1 of 2” symptoms in pharyngo-upper esophageal discomfort category, and “0 of 5” and “3 of 5” symptoms in dyspepsia and fullness while eating categories. These differences between digestive drug-free subjects and gastric acid suppressant users seem to correlate with our experiences in clinical situations: heartburn and acid regurgitation category symptoms are effectively controlled with PPI and H2RA whereas other category symptoms are not. Conclusions The 12 upper GI symptoms can be classified into five categories, which are statistically associated with various background factors. The differences of associated factors between digestive drug-free subjects and digestive drug users may be useful in studying the drug effects upon diverse upper GI symptoms.

Our aim is to elucidate causative factors for gallstones, especially focusing on Helicobacter pylori (HP) infection.We analyzed 15,551 Japanese adults who had no history of gastrectomy, cholecystectomy, HP eradication, and didn't use proton pump inhibitors, anti-diabetic drugs, or anti-cholesterol drugs. 1,057 subjects who previously had HP eradication were analyzed separately.Gallstones were detected in 409 of 8,625 men (4.74%) and 285 of 6,926 women (4.11%) by ultrasonography. Among the 25 factors univariately analyzed, age, HP infection, alcohol intake, weight, body mass index (BMI), and 14 blood test values (AST, ALT, ALP, γ-GTP, T-Chol, HDL-Chol, LDL-Chol, TG, TP, Hb, HbA1c, pepsinogen I, pepsinogen II, and pepsinogen I/II ratio) displayed significant association with gallstones (p0.05), whereas gender, smoking, height, and three blood test values (Alb, T-Bil, MCV) did not. Multivariate analysis showed that age, gender, alcohol intake, BMI, γ-GTP, LDL-Chol, TP, and HP infection had significant association (p0.05). Successive multiple logistic regression analysis calculating odds ratio (OR) and standardized coefficients (β) showed that age (OR/β = 1.57/0.450), BMI (OR/β = 1.30/0.264), HP infection (OR/β = 1.51/0.206), lower alcohol intake (OR/β = 1.33/0.144), γ-GTP (OR/β = 1.15/0.139), and pepsinogen I/II ratio (OR/β = 1.08/0.038) have significant positive association with gallstones, whereas gender does not. The gallstone prevalence among HP-negative, HP-eradicated, and HP-positive subjects was 3.81, 4.73 and 6.08%, respectively. The matched analysis controlling age, BMI, γ-GTP, alcohol intake, pepsinogen I/II ratio and gender also demonstrated that gallstone prevalence among HP-eradicated subjects was significantly lower compared with HP-positive subjects (p0.05).HP infection is positively associated with gallstones. HP eradication may lead to prevention of gallstones.

Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. Methods We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Results Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p