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BackgroundRecently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated.MethodsWe evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS).ResultsAmong 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%).ConclusionsOverall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Introduction: Whether the incidence of reflux esophagitis (RE) increases after the eradication of Helicobacter pylori (H. pylori) is controversial. Few reports have evaluated the presence or absence of RE after a long period of time, taking into account the degree of atrophy and/or administration of acid secretion inhibitors. We investigated the relationship between H. pylori and RE taking into account these factors. Methods: This was a retrospective cohort study with approval by the Ethics Committee. Patients who succeeded in H. pylori eradication treatment, and in whom there were images of the gastroesophageal junction on endoscopic examinations within 1 year before eradication treatment and more than 3 years after eradication were included. The degrees of RE and atrophy were retrospectively determined from the endoscopic images. The prevalence of RE before and after eradication and the incidence of newly developed RE after eradication between patients with or without atrophy improvement were compared using Fisher’s exact test. Results: A total of 185 cases (male:female = 104:81; mean age, 63.5 years; mean observation period, 6.4 years) were examined. The prevalence of RE before and after eradication was 1.6% (3/185) and 7.0% (13/185), respectively (P = 0.019). RE was present in 8 (7.5%) of 106 cases with closed-type atrophy and in 5 (6.3%) of 79 cases with open-type atrophy after eradication (P = 0.75). Atrophy improved after eradication in 56 cases, of whom 4 (7.1%) had new onset of RE; the degree of atrophy did not improve in 126 cases, of whom 7 (5.4%) had new onset of RE (P = 0.74). There was no difference between the percentage of cases who took acid secretion inhibitors before and after eradication (P = 0.14). Conclusion: The prevalence of RE increased a long time after eradication, even in patients who were taking an acid secretion inhibitor. The prevalence of RE was not related to the degree of atrophy or change in atrophy.

Background and Aim: Inhibition of gastric acid secretion is important for eradicating Helicobacter pylori. Vonoprazan (VPZ) is a strong, long-lasting inhibitor of gastric acid secretion. Studies that examined the effectiveness of VPZ-based triple therapy in second-line treatment have been performed. However, there have been no randomized controlled studies to compare the effect between VPZ-based triple therapy and proton pump inhibitor (PPI)-based triple therapy in second-line treatment, and it is not known which is more effective between VPZ-based and PPI-based therapies. This study aimed to compare the effectiveness of second-line triple therapies including VPZ or rabeprazole (RPZ) as the PPI. Methods: Eligible patients with H. pylori infection who failed first-line triple therapy were assigned randomly to the VPZ [VPZ40 mg/day, amoxicillin (AMPC) 1500 mg/day, metronidazole (MNZ) 500 mg/day] or RPZ (RPZ20 mg/day, AMPC1500 mg/day, MNZ500 mg/day) group. A 13C-urea breath test result of less than 2.5% was considered as successful eradication. Results: In total, 46 and 41 patients were analyzed as intention to treat (ITT) and per protocol (PP), respectively. Eradication rates in the VPZ and RPZ groups were 73.9% [95% confidence interval (CI) 51.6–89.8%] and 82.6% (95% CI 61.2–95.0%) based on ITT analysis, respectively (p = 0.72). Based on PP analysis, the eradication rates in the VPZ and RPZ groups were 89.5% (95% CI 66.9–98.7%) and 86.4% (95% CI 65.1–97.1%), respectively (p = 1.00). Two patients in the VPZ group and one in the RPZ group discontinued treatment due to side effects (p = 1.00). Conclusion: There were no significant differences in efficacy and safety between second-line therapies including VPZ or RPZ.

Objective: To clarify the relationship between constipation and depressive symptoms among the elderly. Methods: This single-center, cross-sectional study was performed using baseline data obtained at the time of enrollment in the prospective cohort of the JUSTICE-TOKYO study. Participants underwent assessments including patient profiling, drug use history, the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale 15 (GDS-15), gastrointestinal-related quality of life (QOL), and the constipation scoring system (CSS). Geriatric depressive symptoms were evaluated based on GDS-15. We investigated correlations between GDS-15 scores and various abdominal symptoms and assessed risk factors for geriatric depressive symptoms using multiple regression analysis. Results: A total of 984 elderly participants (57% female, mean age 78.1 ± 6.1 year) were included. The GDS-15 scores were significantly correlated with body mass index (BMI) (r = −0.056) and MMSE (r = −0.092), reflex-related QOL (r = 0.253), pain-related QOL (r = 0.229), fullness-related QOL (r = 0.269), constipation-related QOL (r = 0.329), diarrhea-related QOL (r = 0.264), and CSS (r = 0.285) scores. Multiple regression analysis indicated that BMI (β = −0.069, p = 0.020) and MMSE (β = −0.074, p = 0.013), constipation-related QOL (β = 0.136, p = 0.002), reflex-related QOL (β = 0.126, p < 0.001), diarrhea-related QOL (β = 0.095, p = 0.006), and CSS (β = 0.098, p = 0.016) scores were significantly correlated with GDS-15 scores. Conclusions: Depressive symptoms among older individuals are associated with various abdominal symptoms, particularly constipation. However, the causality between depressive symptoms and constipation cannot be inferred due to the study’s cross-sectional design.

INTRODUCTION:Functional dyspepsia (FD) is subdivided into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), each with a different pathophysiological mechanisms driving the symptoms of these syndromes. Cine MRI aids observation in any continuous cross-section and measures gastrointestinal peristalsis without radiation exposure. In this study, we aimed to evaluate gastric peristalsis in FD using cine MRI.METHODS:This study was a prospective interventional study. Patients diagnosed with FD according to ROME IV diagnostic criteria were included. Cine MRI was performed before and after the test meal. Gastric maximum short axis diameter, amplitude, contraction frequency, peristaltic wave height, peristaltic wave velocity, and gastric motility index were evaluated and compared between healthy control (HC) and patients with FD (PDS/EPS).RESULTS:This study consisted of 18 HC and 31 patients with FD (including 22 with PDS and 9 with EPS). Preprandial comparison of the HC, PDS, and EPS groups showed no significant difference. Postprandial comparison of the 3 groups showed significant differences in maximum short axis diameter of fornix (HC: 51.5 ± 9.1/PDS: 47.1 ± 10.3/EPS: 59.0 ± 13.6 mm, P = 0.045), amplitude of fornix (HC: 7.3 ± 5.1/PDS: 12.1 ± 4.3/EPS: 11.3 ± 8.7 mm, P = 0.009), contraction frequency (HC: 2.9 ± 0.3/PDS: 2.7 ± 0.5/EPS: 2.6 ± 0.2 times/min, P = 0.007), peristaltic wave height (HC: 14.9 ± 4.0/PDS: 9.2 ± 2.5/EPS: 9.5 ± 3.2 mm, P < 0.001), and gastric motility index (HC: 24.5 ± 7.1/PDS: 16.8 ± 6.1/EPS: 15.9 ± 6.3 mm2/s, P = 0.002).DISCUSSION:Cine MRI can be used to visually evaluate gastric peristalsis dysfunction and impaired gastric accommodation in FD.

Background With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE). Methods Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21–39 points was comparable to white light, and < 20 points equaled decreased visibility. Inter- and intra-rater reliabilities (Intra-class Correlation Coefficient [ICC]) were also evaluated. Images showing color differences (Δ E *) and L * a * b * color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system. Results The mean age of patients was 67.1 years (range: 27–89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was “moderate” for LA grade M and “substantial” for erosive RE. The LCI intra-rater reliability was “moderate–substantial” for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE ( P  < 0.001 for WLI vs. LCI). Conclusion LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Abstract Introduction: In recent years, the frequency of idiopathic peptic ulcers (IPUs) has increased. However, the clinicopathological characteristics of IPU have not been fully elucidated and treatment methods for recurrent and refractory cases have not yet been established. Case Presentation: A man in his forties complained of epigastric discomfort. Esophagogastroduodenoscopy revealed a gastric ulcer in the lesser curvature of the gastric angle. After Helicobacter pylori was eradicated, the gastric ulcer recurred despite the administration of a potassium competitive acid blocker (PCAB), and a diagnosis of IPU was made. Twenty-four-hour intragastric pH monitoring revealed insufficient gastric acid suppression. Misoprostol was added to the patient’s treatment. Subsequently, the ulcer healed and recurrence was not observed. Conclusion: For refractory IPU, the evaluation of pathophysiological function through 24-h gastric pH monitoring may lead to the selection of an appropriate treatment. If a proton pump inhibitor and PCAB do not improve the IPU, combination treatment with misoprostol may be considered as an option.

Objectives Recently, the incidence of Helicobacter pylori‐uninfected gastric cancers, such as gastric epithelial neoplasm of fundic‐gland mucosa lineage (GEN‐FGML), has increased with the widespread use of eradication therapy. Because the detection and endoscopic diagnosis of GEN‐FGML are difficult, an effective observation method in screening endoscopy is required. We investigated whether texture and color enhancement imaging (TXI) improved the visibility of GEN‐FGML compared with white light imaging (WLI). Methods In this single‐center prospective clinical study, 50 GEN‐FGML lesions (35 patients) treated at our hospital between October 2020 and June 2023 were analyzed. The endoscopic images of GEN‐FGML obtained using WLI, TXI mode 1 (TXI‐1), TXI mode 2 (TXI‐2), and narrow‐band imaging were compared by 10 endoscopists. We analyzed the visibility score and inter‐rater reliability (intraclass correlation coefficient and conducted an objective evaluation based on L* a* b* color values and the color difference (ΔE*) in the CIE LAB color space system. Results Histologically, GEN‐FGML was classified as gastric adenocarcinoma of fundic‐gland type (n = 45) and gastric adenocarcinoma of fundic‐gland mucosa type (n = 5). The total visibility score for all endoscopists was significantly higher for TXI than for WLI (p < 0.01); and for TXI‐1 than for TXI‐2 (p < 0.01). The intraclass correlation coefficients for TXI‐1 and TXI‐2 were “almost perfect” and “substantial,” respectively, for all endoscopists. ΔE* was significantly higher for TXI than for WLI (p < 0.01). Conclusions TXI improved the visibility of GEN‐FGML for all endoscopists compared with WLI when evaluated subjectively and objectively.