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In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4+/CD3+ lymphocyte subsets (43.8 ± 19.4% vs 31.7 ± 14.6%) were elevated in the lesser curvature of the body, whereas CD8+/CD3+ (67.1 ± 21.3% vs 80.4 ± 12.0%), CD7+/CD3+ (91.2 ± 4.6% vs 93.7 ± 3.8%), CCR4+/CD3+ (7.7 ± 8.1% vs 10.4 ± 7.0%), CD45RA+/CD3+CD4+ (27.2 ± 24.8% vs 39.5 ± 20.8%), and CD45RA+/CD3+CD4- (14.2 ± 11.1% vs 18.7 ± 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4+/CD3+ (P < .05, R2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection., Methods: We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group)., Results: The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%)., Conclusions: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection., (© 2022. The Author(s).)

Background: Diffuse redness is a characteristic endoscopic finding that indicates current infection of Helicobacter pylori, which is reduced after successful eradication. Linked color imaging (LCI) has been reported to improve the visibility of diffuse redness compared to white light imaging (WLI); however, quantitative evaluation has not been reported., Aims: This study aimed to objectively evaluate the color change of the gastric mucosa after H. pylori eradication., Methods: Images of the greater curvature of the antrum and corpus were captured, and the sites were biopsied during esophagogastroduodenoscopy (EGD) before and 1 year after eradication. The region of interest (ROI) was set around the biopsied area on the images. The color difference (ΔE) before and after eradication was calculated using the CIE L*a*b* color space. The association between the histological evaluation and the color value of the corresponding ROI was determined., Results: At the antrum, there was no significant color change with either mode. At the corpus, the a* value, which reflected redness, decreased significantly after eradication with both modes (WLI: 41.2 to 36.0, LCI: 37.5 to 25.5); the b* value, reflecting yellowish, decreased with WLI, but increased significantly with LCI (WLI: 44.6 to 41.6, LCI: 23.9 to 29.2). The ΔE was significantly larger with LCI than with WLI (16.5 vs. 8.6). The a* values at the corpus were generally associated with histological neutrophil infiltration., Conclusions: Quantitative evaluation revealed that LCI emphasizes the change in color of the gastric mucosa due to the reduction in diffuse redness., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective The eradication of Helicobacter pylori (H. pylori) reduces the risk for gastric cancer (GC) development, but it cannot prevent GC completely. We investigated the risk factors of early GC development after the eradication of H. pylori, based on the histological characteristics of gastric mucosa. Methods Sixty-one patients who underwent endoscopic submucosal dissection for early GC after successful H. pylori eradication (Group A) and 122 patients without developing a gastric neoplasm over 3 years after successful H. pylori eradication (Group B) were analyzed. We compared the histological findings of the patients enrolled in Group A and Group B before and after the propensity score-matching. Results Comparing the characteristics of two the groups, Group A consisted predominantly of males, had significantly more elderly patients, and the years after successful eradication tended to be longer. We performed score matching for these three factors to reduce the influence of any confounding factors. After matching, the scores of inflammation for Group A (n=54) was significantly higher than those of Group B (n=54) at the greater curvature of the antrum, the lesser curvature of the corpus, and the greater curvature of the corpus. According to a multivariate analysis, inflammation of the greater curvature of the antrum and lesser curvature of the corpus were found to be independent risk factors. The risk ratio and 95% CI were 5.92 (2.11-16.6) (p<0.01), and 3.56 (1.05-13.2) (p=0.04), respectively. Conclusion A continuous high level of inflammation of the background gastric mucosa may be a risk factor for gastric cancer onset after H. pylori eradication.

Background/aims: The Kyoto Classification of Gastritis was published in 2014. Although this classification is now widely used in Japan, its usefulness and convenience have not been sufficiently evaluated. This study aimed to evaluate the usefulness and convenience of this classification in the endoscopic diagnosis of Helicobacter pylori infection., Methods: We made a test for the endoscopic diagnosis of H. pylori infection comprising 30 cases who had representative endoscopic features of non-, active, or inactive gastritis. Thirty-eight participants took the test before and after a brief mini-lecture on the Kyoto Classification of Gastritis. Eighteen participants took the test again 3 months later. We investigated the accuracy before, just after, and 3 months after the mini-lecture., Results: The accuracy of endoscopists after the lecture was significantly improved in comparison to before the lecture (77.6 vs. 83.3%). Medical students also showed significantly improved accuracy after the lecture (56.7 vs. 71.7%). Among endoscopists, this improvement was maintained after 3 months. Before the lecture, the accuracy of diagnosing non-gastritis was 90.3%; it tended to be further improved 3 months later (96.5%). A >10% point increase was observed in diagnosing active (72.7-83.3%) and inactive gastritis (73.2-84.3%) at 3 months after the lecture in comparison to before the lecture., Conclusion: A brief mini-lecture on the Kyoto Classification of Gastritis improved the accuracy in the endoscopic diagnosis of gastritis, indicating that understanding this classification is useful for the prompt diagnosis of H. pylori infection during esophagogastroduodenoscopy., (© 2019 S. Karger AG, Basel.)

Background: The details of gastric cancer in young patients remain unclear because of the low prevalence of the disease. This study aimed to clarify the clinicopathological features and prognosis of gastric cancer in young patients., Methods: From January 2007 to January 2016, patients in their 20s and 30s who were diagnosed with primary gastric cancer at 4 hospitals were enrolled. Their clinical characteristics and prognosis were evaluated., Results: The total number of patients was 72. The median age was 36 years, and the ratio of males to females was 1:1. The dominant histological type was undifferentiated type (66/72, 92%). Helicobacter pylori (H. pylori) was positive in 81% (54/67). Although there were some asymptomatic patients in stages I-III, all stage IV patients had some clinical symptoms at the diagnosis. The percentage of stage IV was significantly higher in patients in their 20s than in those in their 30s (75% vs. 25%, P < 0.001). The Kaplan-Meier method showed that the overall survival of patients in their 20s was significantly lower than that of patients in their 30s (P = 0.037)., Conclusions: A high rate of H. pylori infection was revealed in young gastric cancer patients. The patients in their 20s had a worse prognosis than those in their 30s. We should consider examining the H. pylori infection status for young patients as well as older patients to identify high-risk populations.

Aim: To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1., Methods: This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated., Results: Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10)., Conclusion: Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1., Competing Interests: Conflict-of-interest statement: All of the authors declare that they have no conflicts of interest associated with this article.

Background/aims: Patients who are Helicobacter pylori antibody negative and have normal pepsinogen (PG) levels (group A of ABC (D) stratification) are considered unlikely to develop gastric cancer. This study aimed to clarify the involvement (uninfection, present infection or previous infection) of H. pylori in group A patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) by examining their background gastric mucosa endoscopically and histologically., Methods: This study included 166 patients with gastric cancer who were treated by ESD. Patients were classified according to PG levels and H. pylori antibody titers. Three biopsies (greater curvature of the antrum, lesser curvature of the middle corpus and greater curvature of the middle corpus) from group A were histologically analyzed and compared with those of groups B, C, D and after eradication)., Results: In group A (34 patients), 32 patients had endoscopic atrophy (group A'). Histological neutrophil activity, chronic inflammation and atrophy scores were lower in group A' than in other groups. Group A' scores were similar to those of the after eradication group., Conclusion: Most of the group A patients with early gastric cancer were not uninfected with H. pylori, but had previous infections, thus carrying carcinogenic risk., (© 2016 S. Karger AG, Basel.)

We investigated the relationship of gastric mucosa-associated lymphoid tissue (MALT) lymphoma tumorigenesis to Helicobacter pylori infection, the t (11;18) translocation, and alterations in cell cycle regulators. We sought to assess the implications of altered expression of p27(Kip1), a cyclin-dependent kinase inhibitor, on high-grade transformation and responsiveness to eradication therapy. We used immunohistochemistry to examine p27(Kip1), p53, and Ki-67 expression in 23 MALT lymphomas, five diffuse large B-cell lymphomas (DLBCLs), and four DLBCLs with associated MALT lymphoma. All of the MALT lymphomas were positive for p27(Kip1) expression and negative for p53 with a low Ki-67 index, regardless of the sensitivity of these cells to eradication. All DLBCLs were negative for p27(Kip1) and positive for p53, exhibiting a high Ki-67 index. In DLBCLs with MALT lymphoma, p27(Kip1) expression was absent from both the MALT and large cells components. In all of these lymphomas, the MALT components were negative for p53 and displayed a low Ki-67 index, while the large cell components were positive for p53 with a high Ki-67 index. The expression patterns of the DLBCLs differed significantly from those of the MALT lymphomas. p27(Kip1) was not detected in either component of DLBCL with MALT lymphoma, suggesting that decreased expression of p27(Kip1) in the MALT component may be related to high-grade transformation. Thus, p27(Kip1) expression in morphological MALT lymphomas could be useful tool to predict high-grade transformation to DLBCL.

Introduction: Gastric cancer is divided into four subtypes by their molecular features linked with genetic alterations, e.g., Epstein-Barr virus (EBV), microsatellite instability-high (MSI-high), chromosomal instability (CIN), and genomically stable (GS), called as TCGA classification. In this study, we tried to clarify the epigenetic features of the four GC subtypes according to aberrant methylation status in 23 loci. Methods: A total of 98 gastric cancers and their normal gastric mucosa samples were included in this study. We divided gastric cancers into TCGA subtypes which were determined in line with MSI-high, EBV, CIN, to GS by their molecular features. The 13 loci of polymorphic microsatellite sequences were used to determine loss of heterogeneity for the detection of CIN. The MSI status was determined by three mononucleotide repeat markers. Infection of EBV was determined by recovering EBV BNRF1 sequence from genomic DNA collected from gastric cancers. Methylation status of 23 loci was investigated by the combined bisulfite restriction analysis. Status of other findings, e.g., KRAS mutations, HER2 expression status, and infection of helicobacter pylori were confirmed. Results: Gastric cancers were divided into MSI (13%), EBV (7%), CIN (53%), and GS (27%). By histological classification, poorly differentiated adenocarcinoma was more in tumors categorized in MSI-high, and GS and signet-ring cell carcinoma (sig) were more in GS. Among the 23 loci investigated their methylation status, 18 loci were significantly hypermethylated in caner tissues. An unsupervised clustering divided gastric cancers into two clusters and revealed that most GS tumors clustered together in a cluster that exhibited lower methylation levels, distinct from the other subtypes. The inter-variable clustering revealed that a cluster contained the three loci (SFRP2-region 1/2 and APC) belonging to the Wnt signal cascade (Wnt-associated loci). The mean methylation score of Wnt-associated loci was the lowest in GS tumors (MSI-high: 2.7 [95% confidence interval, 2.3–2.9]; EBV: 2.1 [1.2–3.1]; CIN: 2.4 [2.2–2.7]; GS: 1.3 [0.8–0.7]). In contrast, the mean methylation score of the other 15 loci was significantly higher in MSI-high, while that in GS was as same as that in EBV or CIN (MSI-high: 10.4 [8.3–12.4]; EBV: 5.7 [1.7–9.7]; CIN: 4.4 [3.6–5.1]; GS: 3.4 [2.2–4.6]). Additionally, the lower methylation score of Wnt-associated loci was observed only in sig tumors. Conclusions: GS subtype tumors have the potential to possess distinct signatures in DNA hypomethylation profiles in Wnt signaling pathway, especially in sig. [ABSTRACT FROM AUTHOR]

A 45-year-old Japanese man underwent esophagogastroduodenoscopy, which revealed spotty redness at the gastric fornix, mucosal swelling, diffuse redness in the corpus, and mucosal atrophy in the gastric angle and antrum. Histological examination showed rod-shaped bacteria that appeared larger than Helicobacter pylori. The patient tested positive for rapid urease test, and serum anti-H. pylori IgG antibody test results were negative. Further examination of the bacteria revealed that H. suis antibody test was positive, and the presence of H. suis was confirmed using H. suis-specific real-time PCR. H. suis was successfully eradicated after triple therapy with vonoprazan, amoxicillin, and clarithromycin. This case reinforces the notion that non-H. pylori Helicobacter species such as H. suis and H. heilmannii may be involved in the pathogenesis of active gastritis in patients who test negative for H. pylori antibodies. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The safety of gastric endoscopic submucosal dissection (ESD) in the antithrombotic drug users remains controversial. Methods: Patients who underwent gastric ESD at Okayama University Hospital between March 2006 and February 2016 were enrolled. This study investigated the risk of post‐ESD bleeding according to the management of the antithrombotic drugs. Results: One thousand twenty lesions (872 patients) were enrolled. In a multivariate analysis, heparin replacement (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.8–14), multiple antithrombotic drug use (OR 2.9, 95% CI 1.1–6.9), a resected specimen of ≥ 33 mm in diameter (OR 2.7, 95% CI 1.5–5.4), Helicobacter pylori negativity (OR 2.2, 95% CI 1.3–3.7), and tumors located in the lower third of the stomach (OR 1.7, 95% CI 1.0–2.9) were significant risk factors for post‐ESD bleeding, while the continuation of aspirin or cilostazol was not (OR 2.6, 95% CI 0.72–7.8). The bleeding rate of the continuation group was comparable with that of the all cessation group among single antithrombotic drug users (4.5% vs 4.4%, P = 1.0); however, the rate of the continuation group was significantly higher than that of the all cessation group among multiple antithrombotic drug users (67% vs 15%, P = 0.020). Conclusions: The risk of post‐ESD bleeding differed according to the management of the antithrombotic drugs. The gastric ESD under the cessation or continuation of aspirin or cilostazol monotherapy was acceptable. However, multiple antithrombotic drug use or heparin replacement was associated with a higher risk of post‐ESD bleeding. [ABSTRACT FROM AUTHOR]

Background/Aims: Few studies exist on the efficacy and long-term outcome of radiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-two patients with stage I or stage II1 disease were prospectively evaluated, including 14 patients without Helicobacter pylori(H. pylori) infection and 8 patients with persistent lymphoma after H. pylori eradication. RT dose was 30 Gy in daily fractions of 1.5 Gy. All patients underwent endoscopic and histological follow-up regularly. Results: The study included 22 patients with a mean age of 63 years. The t(11;18)(q21;q21) translocation occurred in 8 of the 22 cases. All patients showed complete remission without any serious toxicity. At a median follow-up evaluation 74 months (range 27-159) after completion of RT, the overall and relapse-free survival rates after 5 years were 91 and 84%, respectively. Although no patient showed local recurrence of lymphoma, distant recurrence was detected in 3 patients, all of whom were H. pylori negative; MALT lymphoma relapsed in two patients with the t(11;18)(q21;q21) translocation, and diffuse large-cell lymphoma developed in one patient without the translocation. Conclusion: RT provides excellent local control of the gastric MALT lymphoma. However, continuous follow-up is mandatory as relapse may occur in other sites. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors such as ipilimumab, a cytotoxic T-lymphocyte-associated antigen-4 inhibitor, have been widely used for advanced malignancies. As these inhibitors improve antitumor immunity via T-cell modulation, immune-mediated adverse events associated with T-cell activation, such as colitis, might occur. Herein, we describe a 75-year-old Japanese woman with metastatic malignant melanoma who developed hemorrhagic gastritis after ipilimumab treatment. There was no macroscopic or clinical improvement of gastritis after proton pump inhibitor treatment. However, her condition improved after approximately 3 weeks of corticosteroid therapy and Helicobacter pylori eradication. This case suggests a potential association between severe gastritis and immune checkpoint inhibitor treatment. Although several reports have mentioned ipilimumab-associated colitis, gastritis is considered to be rare. In the present case, H. pylori-associated gastritis might have been exacerbated by the T-cell modulation effect of ipilimumab. To date, no report has clarified the mechanism by which ipilimumab modifies H. pylori infection. The present treatment course provides a helpful perspective for similar cases. [ABSTRACT FROM AUTHOR]