KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients.

Along with a recent remarkable decrease in Helicobacter pylori-infected individuals, reports of gastric neoplasms such as sporadic foveolar-type gastric adenoma (FGA) in H. pylori-naive patients have been increasing. This tumor, with its raspberry-like appearance, is common in H. pylori-naive gastric mucosa. The current study investigated the genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori-naive patients were subjected to whole genome analysis using a next-generation sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial cells, along with plasmid transfection of candidate variants, were examined. A mean of 6.65 × 108 total reads were obtained for each sample. Common genetic abnormalities in well-known proliferation driver genes of conventional gastric dysplasia/cancer were not found. However, a common single-nucleotide variation (SNV) was noted within the DNA-binding domain of the tumor suppressor gene KLF4. This novel SNV was located in the zinc finger 2 region. Additional experiments showed that it significantly suppressed proliferation of gastric epithelial cells compared with wild-type KLF4 plasmid-transfected cells, although suppression was reduced in early apoptotic phase-related genes. A novel SNV in the KLF4 zinc finger 2 region was commonly found in sporadic FGA tissue samples, which may explain the slow-growing properties of this neoplasm.

Endoscopic findings of cardiac lymphoid hyperplasia and Helicobacter pylori infection status.

Objective: Lymphoid hyperplasia is endoscopically observed as multiple small whitish round nodules or spots. This retrospective study was performed to examine the prevalence of that finding in patients with Barrett's epithelium and its relationship with the status of H. pylori infection. Methods: The study subjects were 3353 patients (males 2186, females 1167; mean age 55.2 ± 9.4 years) in whom the status of H. pylori infection had been determined. The presence of Barrett's epithelium ≥ 5 mm in length was endoscopically determined, and then endoscopic observations with blue laser imaging were used to investigate the presence of lymphoid hyperplasia in those areas. Results: Barrett's epithelium was diagnosed in 1884 (56.2%) of the subjects, and endoscopic findings of lymphoid hyperplasia were observed in 402 (21.3%) of those with Barrett's epithelium. Lymphoid hyperplasia in Barrett's epithelium was not present in any without a current or prior H. pylori infection, while the prevalence of lymphoid hyperplasia in H. pylori-positive and post-eradicated subjects was 48.4% and 30.4%, respectively (p < 0.001). Multiple logistic regression analysis revealed that female gender, younger age, and higher degree of gastric mucosal atrophy were significant factors related to lymphoid hyperplasia positivity. In addition, the duration after H. pylori eradication was negatively correlated with its prevalence. Conclusion: Endoscopic findings of cardiac lymphoid hyperplasia were well correlated with H. pylori infection, although prevalence decreased over time following bacterial eradication.

Prevalence of Angiodysplasia Detected in Upper Gastrointestinal Endoscopic Examinations.

Background This study was performed to examine the prevalence of asymptomatic angiodysplasia detected in upper gastrointestinal endoscopic examinations and of hereditary hemorrhagic telangiectasia (HHT) suspected cases. Methodology The study participants were 5,034 individuals (3,206 males, 1,828 females; mean age 53.5 ± 9.8 years) who underwent an upper gastrointestinal endoscopic examination as part of a medical check-up. The presence of angiodysplasia was examined endoscopically from the pharynx to duodenal second portion. HHT suspected cases were diagnosed based on the presence of both upper gastrointestinal angiodysplasia and recurrent nasal bleeding episodes occurring in the subject as well as a first-degree relative. Results Angiodysplasia was endoscopically detected in 494 (9.8%) of the 5,061 subjects. Those with angiodysplasia lesions in the pharynx, larynx, esophagus, stomach, and duodenum numbered 44, 4, 155, 322, and 12, respectively. None had symptoms of upper gastrointestinal bleeding or severe anemia. Subjects with angiodysplasia showed significant male predominance and were significantly older than those without. A total of 11 (0.2%) were diagnosed as HHT suspected cases by the presence of upper gastrointestinal angiodysplasia and recurrent epistaxis episodes from childhood in the subject as well as a first-degree relative. Conclusions Asymptomatic angiodysplasia was detected in 9.8% of the subjects who underwent screening upper gastrointestinal endoscopic examinations.

Prevalence of Barrett's Epithelium Shown by Endoscopic Observations with Linked Color Imaging in Subjects with Different H. pylori Infection Statuses.

Objective This study was conducted to clarify the prevalence of short segment Barrett's esophagus (SSBE) using endoscopic observations with linked color imaging (LCI). In addition, the relationship between the presence of Barrett's epithelium (BE) and the status of H. pylori infection was investigated. Methods The study subjects were 3,353 individuals (2,186 men, 1,167 women; mean age 55.2±9.4 years old) whose status of H. pylori infection had been determined. An endoscopic observation using LCI was performed to examine the distal margin of palisade vessels and confirm the area of BE. The prevalence of BE ≥5 mm in length was investigated. Results BE was diagnosed in 1,884 (56.2%) subjects, with lengths of <10, 10-19, 20-29, and ≥30 mm found in 1,005, 851, 27, and 1, respectively. Its prevalence in H. pylori-negative, H. pylori-positive, and post-eradicated subjects was 41.7%, 64.4%, and 69.9%, respectively (p<0.001). The duration since successful eradication of H. pylori did not affect the prevalence of BE. The degree of gastric mucosal atrophy was higher in cases with BE (p<0.001), although negativity for H. pylori infection and mild gastric mucosal atrophy were significant factors for the development of longer BE. Conclusion A high prevalence of SSBE was noted when LCI was used to determine the area of BE, as the distal end of the palisade vessels was easily visualized. Negativity for H. pylori infection and mild gastric mucosal atrophy were not correlated with SSBE prevalence.

Serum Anti-Helicobacter pylori IgG Antibody Titer in H. pylori-negative Cases with a Different Gastric Mucosal Atrophy Status.

Objective This retrospective study was performed to investigate the anti-Helicobacter pylori IgG antibody serum titers in H. pylori-negative subjects with different degrees of gastric mucosal atrophy including C0 grade atrophy. Methods The absence of H. pylori infection was determined based on both negative serum anti-H. pylori IgG antibody test findings and no endoscopic evidence of that infection. Cases negative for the antibody and with positive endoscopic findings of H. pylori infection were defined as H. pylori-positive. The serum anti-H. pylori IgG antibody titers were analyzed in H. pylori-negative (n=1,087), -positive (n=69), and post-eradicated (n=278) subjects. Results The serum antibody titer in subjects with H. pylori-positive endoscopy findings was significantly higher than that in H. pylori-negative subjects, even when the serum titer indicated a negative result. In addition, the anti-H. pylori IgG antibody serum titer was higher in H. pylori-negative subjects with a greater degree of gastric mucosal atrophy. In a comparison between H. pylori-negative C0 and C1 gastric mucosal atrophy cases, the antibody serum titer in those classified as C0 was significantly lower. An analysis of H. pylori post-eradicated cases showed that the serum antibody titer decreased over time after successful eradication. Conclusion The disappearance of H. pylori infection in H. pylori-negative individuals may occur later in those with a greater degree of gastric mucosal atrophy. The serum antibody titer difference between the H. pylori-negative C0 and C1 groups might have been caused by the differences in distribution between H. pylori-uninfected subjects and those in whom the infection had disappeared, thus additional investigation is needed to clarify the significance of gastric mucosal classification including the C0 grade.

Fundic gland polyp prevalence according to Helicobacter pylori infection status.

BACKGROUND AND AIM: The prevalence of fundic gland polyp (FGP) occurrence has not been clarified in individuals with Helicobacter pylori infection post-eradicated status. This study was performed to examine the relationship between FGP prevalence and H. pylori infection status. METHODS: We enrolled 3400 subjects (2185 male subjects and 1215 female subjects; mean age 54.7 ± 9.5 years) with known H. pylori infection status and who underwent an upper gastrointestinal endoscopy examination as part of an annual check-up. Subjects without and with H. pylori infection numbered 1617 and 239, respectively, while 1544 had a post-eradication status. The presence of FGP and degree of gastric mucosal atrophy were determined in each subject using an endoscopic method. RESULTS: Endoscopy findings showed FGPs in 1029 (30.3%) of all subjects. The prevalence ratio of FGP positivity in H. pylori-negative, H. pylori-positive, and post-eradicated subjects was 51.9%, 1.7%, and 12.0%, respectively. Multiple logistic regression analysis revealed that female gender, older age, milder gastric mucosal atrophy, and anti-secretory therapy were significant risk factors for FGP occurrence. As compared with H. pylori-positive subjects, the odds ratios for H. pylori-negative and post-eradication status were 48.3 and 6.6, respectively (P < 0.001). In the post-eradication status subjects, longer duration following bacterial eradication was a significant risk factor for occurrence of FGPs. CONCLUSION: The risk of FGP occurrence in individuals who have undergone H. pylori eradication treatment is lower as compared with those who have never been infected. However, that risk increases over time following eradication.

Long-term effect of Helicobacter pylori eradication on prevalence of reflux esophagitis.

BACKGROUND AND AIM: This study aimed to clarify the long-term effect of Helicobacter pylori eradication on the prevalence of reflux esophagitis (RE). METHODS: We enrolled 8123 individuals (male 5286, female 2837; mean age 54.2 ± 9.3 years) who visited our medical center for an annual checkup between April 2016 and December 2018 and in whom the status of H. pylori infection could be determined. The presence of endoscopically proven RE was determined and compared based on that infection status. RESULTS: Reflux esophagitis was observed in 898 subjects (11.1%). The rates of prevalence in subjects without and with H. pylori infection and with a post-eradication status were 14.0%, 3.7%, and 10.1%, respectively (P < 0.001). Multiple logistic regression analysis of those positive for RE showed male gender, elevated body mass index, habitual drinking, habitual smoking, larger diaphragmatic hiatus size, and milder gastric mucosal atrophy to be significant risk factors. As compared with H. pylori negative, the odds ratios for H. pylori-positive and post-eradication status were 0.225 and 0.703, respectively. When post-eradication subjects were divided according to duration following eradication, RE prevalence was increased in association with a longer duration. Multiple logistic regression analysis revealed longer duration after H. pylori eradication to be a significant risk factor for RE. CONCLUSIONS: The risk of RE developing in individuals following eradication of H. pylori is considered to be lower as compared with those never infected. However, the risk for RE increases as the period following H. pylori eradication is extended.

Prevalence of Autoimmune Gastritis in Individuals Undergoing Medical Checkups in Japan.

Objective Based on both endoscopic findings and serum auto-antibody levels, we determined the prevalence of autoimmune gastritis (AIG), which has not been previously reported, in individuals who underwent health checkup examinations in Japan. Methods At total of 6,739 subjects (4,288 males, 2,451 females; mean age 52.1 years) underwent an upper gastrointestinal endoscopic examination as part of an annual medical checkup. Those suspected to have AIG based on endoscopic evidence of proximal-predominant gastric mucosal atrophy were further examined for the presence of anti-parietal cells and anti-intrinsic factor antibodies, with a final diagnosis of AIG made in cases found to be positive for either or both of those factors. Results Of the 6,739 examined subjects, 46 were suspected to have AIG based on the endoscopic findings, of whom 33 were finally diagnosed with AIG, for an overall prevalence 0.49% (females 0.65%, males 0.40%). Seven with AIG also had thyroid disease, including Hashimoto's and Basedow disease, while none with AIG showed anemia in blood test findings. The prevalence of AIG was not different regardless of the H. pylori infection status (negative, positive, post-eradicated). Conclusion In individuals who underwent an upper gastrointestinal endoscopic examination as part of an annual checkup in Japan, the prevalence of AIG was 0.49%. We concluded that it is not uncommon for asymptomatic and healthy individuals to have AIG, and propose that additional studies are needed to clarify its prevalence as well as to establish the criteria used for diagnosis.

Vertical and Circumferential Localization of Esophageal Mucosal Breaks in Patients with Mild Reflux Esophagitis.

Objective Esophageal mucosal breaks are considered to occur circumferentially in locations with high exposure to acid. In the present study, we investigated the circumferential localization of esophageal mucosal breaks based on their distance from the esophagogastric junction. Methods The vertical and circumferential localization of 625 esophageal longitudinal mucosal breaks was examined in 398 patients with mild reflux esophagitis. Results The number of mucosal breaks in which the distal end was located 0-1 cm from the esophagogastric junction was 454, while those in which the distal end was located 1-2, 2-3, and >3 cm from the junction were 125, 28, and 18, respectively. There was a marked difference in the circumferential distribution among the groups defined by distance from that junction. Esophageal mucosal breaks whose distal end were located 0-1 cm from the esophagogastric junction were mainly found on the right anterior wall of the esophagus, while those located 1-2 cm from the junction were mainly found on the right wall, and those located 2-3 and >3 cm from the junction were mainly found on the posterior wall. Conclusion Esophageal mucosal breaks occurring relatively near the esophagogastric junction mainly exist on the right anterior wall, whereas those farther from that junction tend to exist on the posterior wall of the esophagus. The circumferential location of esophageal mucosa highly exposed to refluxed gastric contents changes based on the distance from the esophagogastric junction.

Influence of Helicobacter pylori infection on periodontitis.

AIM: The relationship of Helicobacter pylori infection with periodontitis was examined. METHODS: The study subjects were 686 individuals (males 504, females 182; mean age 53.8 years) who underwent a screening test for periodontitis between April 2015 and March 2018 and whose H. pylori infection status could be determined. The periodontitis test was performed by examining saliva concentrations of lactate dehydrogenase and hemoglobin (Hb), with a lactate dehydrogenase level ≥ 350 U/L and/or hemoglobin level ≥ 2 µg/mL defined as positive for periodontitis. RESULTS: Among subjects found positive in screening for periodontitis, those classified as negative and positive for H. pylori infection, as well as post-eradicated were 81 (39.7%), 30 (14.7%), and 93 (45.6%), respectively, while those among subjects shown negative for periodontitis numbered 241 (50.0%), 52 (10.8%), and 189 (39.2%), respectively. Subjects noted as negative, positive, and post-eradicated for H. pylori infection comprised 25.2%, 36.6%, and 32.9%, respectively, of all shown positive for periodontitis. Multiple logistic regression analysis indicated that the risk for positive in the periodontitis test was higher among subjects with H. pylori infection as compared with those without, while post-eradicated status tended to reduce that risk. Repeated examinations performed following H. pylori eradication showed that the number of subjects positive for periodontitis was decreased among those who underwent successful eradication. CONCLUSION: Helicobacter pylori infection increases the risk for occurrence of periodontitis, which can be reduced by successful eradication.

Relationship of Helicobacter pylori Infection with Gastric Black Spots Shown by Endoscopy.

Objective The recently reported endoscopic finding of black spots is defined as black pigmentation in gastric mucosa. We attempted to clarify the relationship between the Helicobacter pylori infection status and black spot occurrence. Methods The study subjects were 1,600 individuals who underwent an annual medical checkup and whose H. pylori status could be determined. Upper endoscopic examinations were performed in all, and the presence of black spots in the stomach as well as the degree of gastric mucosal atrophy were determined. Results Among the 1,600 enrolled subjects, 784 underwent eradication for H. pylori, of whom 144 were originally H. pylori-positive and 672 H. pylori-negative. Black spots in the stomach were observed in 156 (9.8%). The rate of prevalence of black spots in the H. pylori-positive and H. pylori-negative subjects was 2.1% and 1.5%, respectively, while that in subjects after undergoing eradication of H. pylori was 18.2%. A multiple logistic regression analysis demonstrated that an older age and post-eradication status were significant factors for black spot occurrence, while proton pump inhibitor treatment showed a tendency to be a risk factor. In subjects with post-eradication status, a higher grade of gastric mucosal atrophy was a significant risk factor for the occurrence of black spots. Conclusion H. pylori post-eradication status and an older age were significant factors related to the appearance of black spots, and a higher grade of gastric mucosal atrophy was also a significant risk factor in subjects who had undergone successful eradication.