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Daisuke Asaoka,1 Akihito Nagahara,2 Mariko Hojo,1 Kenshi Matsumoto,1 Hiroya Ueyama,1 Kohei Matsumoto,1 Kentaro Izumi,1 Tsutomu Takeda,1 Hiroyuki Komori,1 Yoichi Akazawa,1 Yuji Shimada,2 Taro Osada,1 Sumio Watanabe1 1Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, 2Department of Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, Japan Background: Because of a change in lifestyle, especially adoption of westernized eating habits, lifestyle-related diseases have become increasingly prevalent. The aim of this study was to investigate the association of medications for lifestyle-related diseases with reflux esophagitis (RE).Methods: We conducted a hospital-based, cross-sectional retrospective study of consecutive outpatients who received an upper gastrointestinal endoscopy in our department from February 2008 to November 2014, which was performed by one specialist who was a member of the Japan Gastroenterological Endoscopy Society. We investigated the patient profile, Helicobacter pylori (H. pylori) infection status, medications for lifestyle-related diseases (including calcium channel blockers, statins, and bisphosphonates), and upper gastrointestinal endoscopic findings (RE, hiatal hernia, Barrett’s mucosa, and endoscopic gastric mucosal atrophy [EGA]). Patients with gastrectomy, peptic ulcer disease, gastric or esophageal malignant disease, and those who used proton pump inhibitors or histamine-2 receptor antagonists were excluded. We divided the subjects into a group without RE (RE(–)) and a RE (RE(+)) group as judged by endoscopy, and investigated the risk factors for RE.Results: Of 1,744 consecutive cases, 590 cases (300 males and 290 females; mean age 60.5±13.2 years) were eligible. RE(–) and RE(+) cases numbered 507 and 83, respectively. Bivariate analysis showed significant positive associations of RE with male sex, body mass index (BMI), calcium channel blockers, Barrett’s mucosa, hiatal hernia and negative associations of RE with H. pylori positivity, EGA. Multivariate analysis showed significant positive associations of RE with BMI (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.10–1.29), use of calcium channel blockers (OR: 2.12, 95% CI: 1.16–3.87), Barrett’s mucosa (OR: 2.97, 95% CI: 01.64–5.38), hiatal hernia (OR: 3.13, 95% CI: 1.79–5.47) and negative associations of RE with H. pylori positivity (OR: 0.20, 95% CI: 0.07–0.57), use of statins (OR: 0.42, 95% CI: 0.18–0.96), and EGA (OR: 0.83, 95% CI: 0.70–0.98).Conclusion: Calcium channel blockers were positively associated with RE and statins were negatively associated with RE, while bisphosphonates were not associated with RE. Keywords: reflux esophagitis, calcium channel blockers, statins, bisphosphonates, H. pylori, hiatal hernia, Barrett’s mucosa, endoscopic gastric mucosal atrophy

Daisuke Asaoka, Akihito Nagahara, Yuji Shimada, Kenshi Matsumoto, Hiroya Ueyama, Kohei Matsumoto, Yuta Nakagawa, Tsutomu Takeda, Ippei Tanaka, Hitoshi Sasaki, Taro Osada, Mariko Hojo, Sumio Watanabe Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, Japan Background: A number of diseases and drugs may influence bone mineral density; however, there are few reports concerning the relationship between lifestyle-related diseases and osteoporosis in Japan as determined by multivariate analysis. The aim of this study was to investigate the risk factors for osteoporosis and whether infection by or eradication of Helicobacter pylori is associated with osteoporosis.Methods: Between February 2008 and November 2014, using a cross-sectional study design, we investigated patient profile (age, sex, BMI, alcohol, smoking), H. pylori infection status, comorbidities, internal medicine therapeutic agents (calcium channel blocker, HMG-CoA reductase inhibitors, proton pump inhibitor), serum parameters (Hb, calcium, ΥGTP), bone turn over markers (bone-specific alkaline phosphatase (BAP) and collagen type I cross-linked N telopeptide (NTX), findings on dual-energy x-ray absorptiometry (DEXA) and upper gastrointestinal endoscopy, and Frequency Scale for the Symptoms of GERD score in consecutive outpatients aged ≥50 years at our hospital. We divided the subjects into an osteoporosis group and a non-osteoporosis group and investigated risk factors for osteoporosis between the two groups by bivariate and multivariate analyses.Results: Of the 255 eligible study subjects, 43 (16.9%) had osteoporosis. Bivariate analysis showed that advanced age, female sex, lower body mass index, lower cumulative alcohol intake, lower Brinkman index, H. pylori positivity, lower hemoglobin, bone-specific alkaline phosphatase, lower prevalence of hiatal hernia, and endoscopic gastric mucosal atrophy were related to osteoporosis. Multivariate analysis showed that advanced age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.07–1.19, P

The article discusses a study that investigated the use of white light imaging (WLI) endoscopy and autofluorescence imaging videoendoscopy to detect differences between normal controls and the white-colored esophageal mucosa of reflux esophagitis grade M.

Background: The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years., Methods: Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated., Results: The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment., Conclusion: After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

To the best of our knowledge, little is known about the association between dietary variety status and sarcopenia in university-affiliated geriatric hospital in elderly. The present study aimed to investigate, in a multidisciplinary setting, the prevalence of sarcopenia and association between dietary variety status and sarcopenia in older outpatients at Juntendo Tokyo Koto Geriatric Medical Center (Tokyo, Japan). Between October 2020 and December 2021, a cross-sectional study of outpatients aged ≥65 years [458 male (44%) and 584 female (56%); mean age, 78.2±6.1 years] was conducted to assess prevalence of sarcopenia, according to Asian Working Group for Sarcopenia 2019 criteria, and the relationship between dietary variety status and sarcopenia. Patient profile, comorbidities, drug use, neuropsychological data, abdominal symptoms, pulmonary function and dietary variety status were collected. Of 1,042 subjects, there were 223 (21.4%) with [142 male (63.7%) and 81 female (36.3%); mean age, 80.6±6.3 years] and 819 (78.6%) without sarcopenia [316 male (38.6%) and 503 female (61.4%); mean age, 77.6±5.8]. In multivariate analysis, older age, male sex, low body mass index, high Brinkman Index and phase angle, low quality of life, history of daycare use, diabetes mellitus, osteoporosis and low Mini-Mental State Examination and Dietary Variety Score were related to sarcopenia. The prevalence of sarcopenia was higher in than in community-dwelling individuals. Dietary variety status was associated with sarcopenia., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Asaoka et al.)

Background: Barrett's esophagus and esophageal adenocarcinoma cases are increasing as gastroesophageal reflux disease increases. Using artificial intelligence (AI) and linked color imaging (LCI), our aim was to establish a method of diagnosis for short-segment Barrett's esophagus (SSBE). Methods: We retrospectively selected 624 consecutive patients in total at our hospital, treated between May 2017 and March 2020, who experienced an esophagogastroduodenoscopy with white light imaging (WLI) and LCI. Images were randomly chosen as data for learning from WLI: 542 (SSBE+/- 348/194) of 696 (SSBE+/- 444/252); and LCI: 643 (SSBE+/- 446/197) of 805 (SSBE+/- 543/262). Using a Vision Transformer (Vit-B/16-384) to diagnose SSBE, we established two AI systems for WLI and LCI. Finally, 126 WLI (SSBE+/- 77/49) and 137 LCI (SSBE+/- 81/56) images were used for verification purposes. The accuracy of six endoscopists in making diagnoses was compared to that of AI. Results: Study participants were 68.2 ± 12.3 years, M/F 330/294, SSBE+/- 409/215. The accuracy/sensitivity/specificity (%) of AI were 84.1/89.6/75.5 for WLI and 90.5/90.1/91.1/for LCI, and those of experts and trainees were 88.6/88.7/88.4, 85.7/87.0/83.7 for WLI and 93.4/92.6/94.6, 84.7/88.1/79.8 for LCI, respectively. Conclusions: Using AI to diagnose SSBE was similar in accuracy to using a specialist. Our finding may aid the diagnosis of SSBE in the clinic.

Linked color imaging (LCI) for image-enhanced endoscopy (IEE) highlights mucosal color differences. We investigated risk factors associated with mucosal redness of the duodenal bulb using LCI. Consecutive patients were retrospectively selected after their duodenal bulbs were observed via LCI. A symptom questionnaire (Izumo scale) was completed. The LCI of the duodenal bulb was subjectively evaluated on whether redness was present and objectively evaluated based on L* a* b* color values. The clinical characteristics of the 302 study participants were: male/female, 120/182; mean age, 70.9 years. Twenty-one cases (7.0%) were in the redness (+) group. After multiple regression analysis, independent predictors for the red component ( a* ) of the duodenal bulb using LCI were: age (β = -0.154, p < 0.01), female (β = -0.129, p < 0.05), body mass index (BMI; β = -0.136, p < 0.05), Helicobacter pylori eradication (β = 0.137, p < 0.05), endoscopic gastric mucosal atrophy score (EGAS; β = -0.149, p < 0.05), and constipation-related quality of life (QOL) (β = -0.122, p < 0.05) scores. Lower age, lower BMI, lower EGAS, a constipation-related QOL score, post- H. pylori eradication, and being male were associated with mucosal redness in the duodenal bulb with IEE using LCI.

Aim: This study aimed to clarify the prevalence, predictors, and prognosis of frailty and sarcopenia in both cross-sectional and longitudinal study of the real world., Methods: The JUSTICE-TOKYO study is a single-center, prospective observational study of elderly patients. Patients aged ≥65 years who regularly visited our center were enrolled and followed up for 4 years (n = 1042). The diagnosis of sarcopenia and frailty in the enrolled patients was based on the criteria established by the Asian Working Group for Sarcopenia and Japanese version of the Cardiovascular Health Study criteria, respectively. The primary end point is the incidence of all-cause mortality and hospitalization for treatment. The secondary end points are clinically significant bleeding, cardiovascular events, strokes, malignancies, incidence of falling, fractures, pneumonia, and the onset of new dementia cases., Results: A total of 1042 patients were enrolled in this study. The mean age of the cohort at baseline was 78.2 years, with 56% being women. Among the enrolled patients, 223 (21.4%) diagnosed with sarcopenia, 172 (16.5%) exhibited frailty, and 541 (51.9%) fell into the prefrailty category., Conclusions: The JUSTICE-TOKYO study provides valuable insights into the prevalence of sarcopenia and frailty among older adult outpatients in a real-world context and contributes to measures aimed at extending healthy life expectancy. Geriatr Gerontol Int 2024; 24: 168-172., (© 2023 Japan Geriatrics Society.)

Sarcopenia is a poor prognostic factor in patients with chronic kidney disease (CKD). Adequate dietary patterns are important for preventing sarcopenia; however, evidence regarding the underlying association between sarcopenia and diet is insufficient. Therefore, in this study, we aimed to investigate the association between sarcopenia and dietary patterns in CKD patients receiving conservative treatment. In this cross-sectional study, 441 patients with conservative CKD were examined using the Asian Working Group for Sarcopenia diagnostic criteria. CKD was defined as an eGFR of <60 mL/min/1.73 m 2 present for >3 months. The participants were divided into sarcopenia and non-sarcopenia groups, and dietary patterns were compared between the two groups using the dietary variety score, a simple dietary survey method that investigates the weekly frequency of consumption of 10 food groups. Logistic regression analysis for CKD G3 showed that female sex (odds ratio (OR): 0.166, 95% confidence interval (CI): 0.086-0.320), increased body mass index (OR: 0.663, 95% CI: 0.590-0.745), and almost daily consumption of green/yellow vegetables (OR: 0.350, 95% CI: 0.176-0.695) were positively associated with non-sarcopenia. Although further prospective studies are required, the results suggest that low frequent consumption of vegetables is associated with sarcopenia in patients with CKD.

Background and Aims: The endoscopic findings of non- Helicobacter pylori Helicobacter (NHPH) are not widely known. Linked-color imaging (LCI) has emerged as a new system for image-enhanced endoscopy (IEE) that enhances color tone and improves visibility. The aim of this case study was to assess how endoscopic findings of NHPH are enhanced with LCI., Methods: We report the case of a 72-year-old woman in whom an NHPH species was found during EGD using LCI., Results: The EGD did not reveal any endoscopic findings of diffuse redness, patchy redness, or atrophy. However, erosions, nonuniform redness, and crack-like mucosa were seen in the antrum, as well as LCI-enhanced endoscopic findings. In addition, nodular gastritis and a white marbled appearance were also observed in the antrum. LCI and blue-laser imaging enhanced the endoscopic findings. Floating bacterial bodies with a fine coil-like shape and diameter longer than that of H pylori were pathologically observed in the mucus, suggesting NHPH. A polymerase chain reaction test led to a diagnosis of Helicobacter suis ., Conclusions: Our case demonstrates that IEE is useful in diagnosing NHPH. The detection of NHPH using IEE enabled us to contribute to an improved diagnosis of NHPH., Competing Interests: Drs Takeda, Asaoka, and Nagahara were supported by a joint clinical research grant from Fujifilm Co, Ltd (2018-028). All other authors disclosed no financial relationships relevant to this publication., (© 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

BACKGROUND Texture and color enhancement imaging (TXI), a new type of image-enhanced endoscopy, may improve the detection of gastrointestinal lesions. Barrett's esophagus (BE) requires an accurate diagnosis since it may undergo neoplastic transformation. We aimed to evaluate the usefulness of TXI compared with white light imaging (WLI) in BE. MATERIAL AND METHODS In this prospective study at a single hospital from February 2021 to February 2022, we enrolled 52 consecutive patients with BE. Endoscopic images of BE using WLI, TXI mode 1 (TXI-1), TXI mode 2 (TXI-2), and narrow-band imaging (NBI) were compared by 10 endoscopists (5 experts and 5 trainees). Endoscopists scored visibility for the images as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Total visibility scores for all 10 endoscopists, and subgroups composed of the 5 expert endoscopists and the 5 trainee endoscopists, were evaluated. Main-group (10 endoscopists) scores of ≥40, 21-39, and ≤20, and subgroup (5 endoscopists) scores of ≥20, 11-19, and ≤10, were considered "improved", "equivalent", and "decreased", respectively. Inter-rater reliability (intra-class correlation coefficient [ICC]) was calculated and images were objectively assessed based on L*a*b* color values and color differences (ΔE*). RESULTS All 52 cases were diagnosed as short-segment BE (SSBE). TXI-1/TXI-2 improved visibility compared with WLI was: 78.8%/32.7% for all endoscopists; 82.7%/40.4% for trainees; and 76.9%/34.6% for experts. NBI did not improve visibility. The ICC for TXI-1 and TXI-2 compared with WLI was "excellent" for all endoscopists. The ΔE* between esophageal and Barrett's mucosae, and between Barrett's and gastric mucosae, was higher for TXI-1 than for WLI (P<0.01, P<0.05, respectively). CONCLUSIONS TXI, especially TXI-1, improves the endoscopic diagnosis of SSBE compared with WLI, regardless of the endoscopist's skill.

We herein report a rare case of Yersinia enterocolitica enteritis with a fever and abdominal pain followed by erythema nodosum (EN) a few days later. The diagnosis was confirmed based on characteristic colonoscopy and computed tomography findings, pathology, and mucosal culture. Yersinia enteritis is a curable disease provided a proper diagnosis and treatment are performed. Although EN is a rare clinical course, it should still be considered as a differential diagnosis.

Introduction: Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation., Methods: This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics ( B. longum BB536, 5 × 10 10 colony-forming unit, n = 39) or placebo (n = 41) once daily for up to 4 weeks. The severity of constipation was evaluated using the Constipation Scoring System. The primary end point was the difference in the changes from baseline in the constipation scoring system total score between the 2 groups at week 4., Results: A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary end point was not significant ( P = 0.074), although there was significant improvement ( P < 0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the stool frequency ( P = 0.008) and failure of evacuation ( P = 0.051) subscales, respectively, at week 4 between the 2 groups. Few adverse events related to the probiotics were observed., Discussion: The primary end points were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Evaluation of chronic constipation is important, although it is often difficult to satisfactorily treat due to the complex interplay of factors. This study aimed to determine whether the volume of intraluminal contents and lateral diameter of the colon measured from computed tomography (CT) images were correlated with the symptoms of chronic constipation and stool consistency. Consecutive patients who underwent the Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) questionnaires and simple abdominal CT were selected retrospectively. The intestinal tract diameter at each site was measured, and the amounts of stool and gas in the intestinal tract were evaluated at five levels. Of the 149 study participants, 54 were males and 95 were females and their mean age was 72.1 years. In the right hemi-colon, CSS5 (Time) correlated significantly with gas volume (p < 0.01). In the left hemi-colon, stool volume correlated significantly with CSS2 (Difficulty), CSS3 (Completeness), CSS5 (Time) and CSS total (p < 0.05). The BSFS negatively correlated with gas volume and diameter in the right hemi-colon and with gas volume in the rectum (p < 0.05). CT findings including stool volume, gas volume and diameter correlated with some constipation symptoms and stool consistency. These findings may be useful in evaluating and treating constipation.

The endoscopic features of gastric epithelial neoplasms of fundic gland mucosa lineage (GEN-FGML) have not been well investigated. We aimed to clarify the endoscopic features of GEN-FGML and differences between gastric adenocarcinoma of the fundic gland type (GA-FG) and fundic gland mucosa type (GA-FGM). A total of 62 GEN-FGML lesions, including 52 GA-FG and 10 GA-FGM, were retrospectively analyzed using endoscopic and clinicopathological findings to provide information of diagnostic value using white light imaging (WLI) and magnifying endoscopy with narrow-band imaging (M-NBI). GA-FG frequently presented with a whitish, submucosal tumor (SMT) shape with dilated vessels with branching architecture and background mucosa without atrophic change in WLI, an indistinct demarcation line (DL), dilatation of the crypt opening and intervening part (IP), and microvessels without distinct irregularity in M-NBI. GA-FGM frequently presented as a reddish, elevated lesion in WLI, with a distinct DL, dilatation of the IP, and an irregular microvascular pattern in M-NBI. As for an M-NBI diagnosis, five GA-FGM lesions met the diagnostic criteria for cancer, whereas none of the GA-FG lesions met the same criteria. We highlight the endoscopic features of GEN-FGML, and the differentiation between GA-FG and GA-FGM might be possible by combination of lesion color and morphology in WLI and M-NBI diagnoses.

Vedolizumab (VDZ) is an α4β7 integrin-antibody used to manage refractory ulcerative colitis (UC). This retrospective multicenter study aimed to identify predictors of efficacy or the time points when evaluation of VDZ therapy for UC would be most useful. We compiled data on 87 patients with moderate to severe active UC that was treated with VDZ. Overall clinical remission (CR) rates at 6 weeks and 52 weeks after VDZ administration were 44.4% (bio-naïve 44.2%, bio-failure 44.8%) and 52.8% (bio-naïve 53.5%, bio-failure 51.7%) respectively. Also, 83.3% (bio-naïve 81.3%, bio-failure 85.7%) of patients achieved mucosal healing at week 52. Among patients with a CR at week 52, 73.3% had a CR at week 6. In contrast, of patients who discontinued VDZ, 82.4% had not reached a CR at week 6. Our study demonstrated that VDZ was effective in a large percentage of UC patients, with a high mucosal healing rate even after prior biological exposures. This suggests that VDZ can be a treatment option even in bio-failure cases. Additionally, it was considered that early CR can predict long-term remission and that week 6 can be a helpful evaluation point for treatment decisions when using VDZ for UC.

Background: Recently, 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., Methods: We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS)., Results: Among 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%)., Conclusions: Overall, 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., (© 2022. Japanese Society of Gastroenterology.)

Bile acids are strongly associated with the pathogenesis of functional gastrointestinal diseases. In recent years, blue laser imaging (BLI) endoscopy has emerged as a novel image-enhanced endoscopic method, which illustrates bile as a reddish hue. The present study investigated the factors that affect the area of bile in duodenal bulbs using BLI. For this purpose, patients (356 cases) who underwent upper endoscopy with BLI between April, 2017 and December, 2019, and completed patient background and symptom questionnaires [Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) and Frequency Scale for Symptoms of gastroesophageal reflux disease (FSSG)], were retrospectively investigated. Each BLI bile score was calculated as a percentage of bile area in a field of view in the duodenal bulb using a KS400 image analysis system, and the association with abdominal symptoms was examined using multiple regression analysis. The patient characteristics included the following: Age (in years), 69.9±11.3; male/female ratio, 146/210; body mass index, 23.0±3.8; reflux esophagitis (M/A/B/C), 143/19/3/3; atrophic gastritis (C-0/C1-3/O1-3), 132/100/124; proton pump inhibitor potassium competitive acid blocker/aspirin/ursodeoxycholic acid/gall bladder stones/cholecystectomy, 105/27/18/43/18; BLI bile score, 7.10 (±14.34); CSS score, 3.55 (±3.80); BSFS score, 3.91 (±1.02); and FSSG score, 4.80 (±5.76). Correlation coefficients (P<0.05) for the BLI bile score were found for cholecystectomy (Rho=0.137) and aspirin use (Rho=0.118). In multiple regression analysis, independent predictors of the BLI bile score were cholecystectomy [standardized partial regression coefficient (β)=0.169, P=0.001] and the BSFS score (β=0.107, P=0.042). On the whole, the present study demonstrates that the duodenal bile area in BLI upper endoscopy is associated with cholecystectomy and fecal characteristics., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Abe et al.)

Background: Proton pump inhibitors (PPIs), including potassium ion-competitive acid blocker, are widely used worldwide and are often used for long periods of time. However, in recent years, potential side effects associated with long-term PPI use have been reported. Many patients take PPI for a long period of time, even though it is unnecessary, and it is necessary to discontinue PPI administration in such patients. However, sudden discontinuation may cause symptoms to recur and discontinuation may be unsuccessful. A strategy for safe and secure PPI discontinuation has not yet been established. The purpose of this study is to determine whether PPI can be safely discontinued by tapering the PPI dose or by abrupt discontinuation of PPI, and to establish a strategy for safe and secure PPI discontinuation., Methods: The evaluation will be conducted as a multicenter, randomized, parallel-group clinical trial with five assessment points at the start of the study and 2 weeks, 4 weeks, 6 months, and 12 months after the start of the study. One intervention group is the group in which PPI administration is abruptly discontinued (Group A), and the second group is the group in which the PPI dose is gradually tapered and then PPI administration is discontinued (Group B). The primary outcome and secondary outcome are the proportion of patients who successfully discontinued the PPI at 6 months and at 12 months after the start of the study in groups A and B, respectively., Discussion: We predict that the proportion of patients who successfully discontinue PPI will be higher in the group in which PPI administration was gradually tapered than in the group in which PPI administration was abruptly discontinued. On the other hand, we expect that many participants will succeed in discontinuing PPI regardless of the discontinuation strategy due to the explanation that discontinuation is necessary., Trial Registration: Japan Registry of Clinical Trials, jRCT1031180383. Registered 20 March 2019, https://jrct.niph.go.jp/latest-detail/jRCT1031180383 ., (© 2022. The Author(s).)

A man in his 70s visited our hospital for abdominal pain. Upon admission, abdominal computed tomography findings suggested a duodenal diverticular perforation. Upper gastrointestinal endoscopy revealed an incarcerated enterolith in the periampullary diverticulum. We achieved conservative management by inserting an endoscopic nasobiliary drainage tube into the duodenal diverticulum to aid drainage. The patient was discharged without serious complications 35 days after admission. We report a case of duodenal diverticular perforation with an incarcerated enterolith managed conservatively using endoscopic therapy.

Background: Probiotics have been reported to ameliorate cognitive impairment., Objective: We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI)., Methods: In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer's disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition., Results: Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale "orientation" was significantly improved compared to placebo at 24 weeks. MMSE subscales "orientation in time" and "writing" were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation., Conclusion: Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.

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., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

Background and Aim: We aimed to evaluate endoscopic findings of Helicobacter pylori ( H. pylori )-positive children and young adults based on the Kyoto classification, and to examine if there are age-associated changes in H. pylori -positive gastritis., Methods: H. pylori -positive patients under 40 years old who underwent upper gastrointestinal endoscopy from 1 April 2009 to 15 February 2017 were included. Subjects were classified into the Pediatric (<20 years) and Young adult groups (20-39 years). The patients' endoscopic photographs were retrospectively re-evaluated based on the Kyoto classification. We compared endoscopic findings between the two groups and examined alterations in the findings of H. pylori -associated gastritis in 5-year age groups., Results: Forty-three and 163 subjects were classified into the Pediatric and Young adult groups, respectively. In the Pediatric group, nodularity was seen in the majority (93.0%); other endoscopic findings in order of decreasing frequency included mucosal swelling (32.6%), spotty redness (25.6%), diffuse redness (18.6%), and atrophy (9.3%). In the Young adult group, endoscopic findings included atrophy (66.9%), mucosal swelling (49.7%), spotty redness (39.3%), nodularity (31.9%), and diffuse redness (30.3%). The difference in prevalence of nodularity or atrophy between the two groups reached statistical significance ( P  < 0.0001 each). The rate of nodularity decreased with increasing age in the Young adult group. The rate of atrophy was 33% in young adult patients aged 20-24, and the rate increased to >65% in patients over age 25., Conclusion: H. pylori -positive children had endoscopic findings besides nodularity based on the Kyoto classification. The prevalence of atrophy increased in patients over age 20., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Magnifying endoscopy (ME) diagnostic algorithm for early gastric cancer (EGC) relies on qualitative features such as microvascular (MV) architecture and microsurface structure; however, it is a "static" diagnostic algorithm that uses still images. ME can visualize red blood cell flow within subepithelial microvessels in real time. Here, we evaluated the utility of using the MV blood flow rate in combination with ME for the diagnosis of EGC as a retrospective study., Methods: Patients with differentiated-type EGC (n = 10) or patchy redness (n = 10) underwent ME with blue laser imaging. The mean MV blood flow rates of EGC, patchy redness, and background mucosa were calculated by the mean movement distance of one tagging red blood cell using split images of ME with blue laser imaging videos. We compared the mean MV blood flow rate between EGC, patchy redness, and background mucosa and also calculated the MV blood flow imaging ratio (inside lesion/background mucosa) between EGC and patchy redness., Results: Mean MV blood flow rate was significantly lower in EGC (1481 μm/s; range 1057-1762) than in patchy redness (3859 μm/s; 2435-5899) or background mucosa (4140.6 μm/s; 2820-6247) (P < 0.01). The MV blood flow imaging ratio was significantly lower in EGC (0.39; 0.27-0.62) than in patchy redness (0.90; 0.78-1.1) (P < 0.01)., Conclusions: Dynamic diagnosis with MV blood flow rate using ME may be useful for the differential diagnosis of EGC and patchy redness. Endoscopic assessment of dynamic processes within the gastric mucosa may facilitate the diagnosis of EGC., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aims: To identify areas that are difficult to access by the single scope at the time of endoscopic submucosal dissection (ESD) and examine the effectiveness, en-bloc, R0 resection, and perforation rate after changing to multibending scope at the same site., Material and Methods: When the direct visualization of the submucosal layer became impossible with Q260J or in the position where the device became vertical and peeling became impossible in parallel, we decided to change to the multibending 2TQ260M scope to record the position where the change was effective and the perforation rate., Results: A total of 315 lesions were studied. Of the 12 sites, ESD was completed using the Q260J alone at four sites. The 2TQ260M scope was used with greater frequency at the fornix (88.9%) and on the line of the lesser curvature of the stomach (37.1%). In the cases with observed perforations (0.9%), the submucosal layer was not elevated due to the adhesion caused by strong fibrosis. None of the cases involving the change to 2TQ260M was ineffective, nor were perforations observed, and all resected specimens were en-bloc and R0 resections., Conclusions: The success rate of this scope may help clinicians perform ESD with greater understanding.

The aim of the present study was to investigate the association between the severity of constipation and sarcopenia in elderly adults. We conducted a single-center university hospital-based, retrospective cross-sectional study of consecutive outpatients aged ≥65 years from 2017 to 2020. Patients were included in the study if all of the following information were available from medical records: Patient's profile (age, sex, body mass index), laxative/prokinetics use, evaluation of sarcopenia, nutritional status, and questionnaires concerning the severity of constipation [Constipation Scoring System (CSS)], abdominal symptom-related quality of life (QOL) (Izumo scale) and stool shape [Bristol Stool Form Scale (BSFS)]. Multiple regression analysis of risk factors for high CSS score was performed. The results revealed that of the 310 eligible study subjects, [149 men (48.1%) and 161 women (51.9%); mean age, 75.7±6.1 years; mean body mass index, 23.0±3.6 kg/m 2 ], sarcopenia was noted in 83 cases (26.8%). The CSS score was significantly higher in the sarcopenia group than that noted in the non-sarcopenia group (4.9±4.9 vs. 3.6±3.6, P=0.009). The CSS score was significantly associated with the albumin level (r=-0.148), lymphocyte count (r=-0.118), CONUT score (r=0.130), reflux-related QOL score (r=0.155), upper abdominal pain-related QOL score (r=0.171), fullness-related QOL score (r=0.299), constipation-related QOL score (r=0.615), diarrhea-related QOL score (r=0.235) and BSFS score (r=-0.114). In multiple regression analysis, independent predictors for CSS score were sarcopenia [standardized partial regression coefficient (β)=0.107, P=0.032], constipation-related QOL score (β=0.537, P<0.001), laxative/prokinetics use (β=0.211, P<0.001) and BSFS score (β=-0.098, P=0.031) (R 2 =0.436). In conclusion, sarcopenia, constipation-related QOL score, laxative/prokinetics use and BSFS score are associated with the severity of constipation in elderly adults., (Copyright: © Asaoka et al.)

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., (© 2020 The Authos(s) Published by S. Karger AG, Basel.)

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 13 C-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., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

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 (ΔE*) 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/aims: To compare white light imaging (WLI) with linked color imaging (LCI) and blue LASER imaging (BLI) in endoscopic findings of Helicobacter pylori presently infected, previously infected, and uninfected gastric mucosae for visibility and inter-rater reliability., Methods: WLI, LCI and BLI bright mode (BLI-bright) were used to obtain 1,092 endoscopic images from 261 patients according to the Kyoto Classification of Gastritis. Images were evaluated retrospectively by 10 experts and 10 trainee endoscopists and included diffuse redness, spotty redness, map-like redness, patchy redness, red streaks, intestinal metaplasia, and an atrophic border (52 cases for each finding, respectively). Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Visibility was assessed from totaled scores. The inter-rater reliability (intraclass correlation coefficient) was also evaluated., Results: Compared with WLI, all endoscopists reported improved visibility with LCI: 55.8% for diffuse redness; LCI: 38.5% for spotty redness; LCI: 57.7% for map-like redness; LCI: 40.4% for patchy redness; LCI: 53.8% for red streaks; LCI: 42.3% and BLI-bright: 80.8% for intestinal metaplasia; LCI: 46.2% for an atrophic border. For all endoscopists, the inter-rater reliabilities of LCI compared to WLI were 0.73-0.87., Conclusion: The visibility of each endoscopic finding was improved by LCI while that of intestinal metaplasia was improved by BLI-bright., (© 2019 S. Karger AG, Basel.)

Objective The association between frailty and abdominal symptoms has not been evaluated. Methods We conducted a hospital-based, retrospective cross-sectional study of consecutive outpatients ≥65 years old at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center from 2017 to 2019. Patients were included in the study if all of the following information was available from their medical records: patient's profile, the evaluation of osteoporosis, sarcopenia, frailty, nutritional status, findings of upper gastrointestinal endoscopy, and questionnaire results for abdominal symptoms [Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Constipation Scoring System (CSS)]. We divided the subjects into frailty and non-frailty groups and investigated the risk factors for frailty. Results Of the 313 eligible study subjects [134 men (42.8%) and 179 women (57.2%); mean age, 75.7±6.0 years; mean body mass index, 22.8±3.6 kg/m 2 ], frailty was noted in 71 cases (22.7%). In a univariate analysis, an older age (p<0.001), female gender (p=0.010), successful eradication of Helicobacter pylori (p=0.049), proton pump inhibitor (PPI) use (p<0.001), laxative/prokinetics use (p=0.008), sarcopenia (p<0.001), osteoporosis (p<0.001), hypozincemia (p=0.002), hypoalbuminemia (p<0.001), low lymphocytes (p=0.004), a high CONUT score (p<0.001), a high FSSG score (p=0.001), and a high CSS score (p<0.001) were significantly associated with frailty. A multivariate logistic regression analysis showed that an older age [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.08-1.24, p<0.001], PPI use (OR 2.42; 95% CI 1.18-4.98, p=0.016), sarcopenia (OR 7.35; 95% CI 3.30-16.40, p<0.001), hypozincemia (OR 0.96; 95% CI 0.92-0.99, p=0.027), a high FSSG score (OR 1.08; 95% CI 1.01-1.16, p=0.021), and a high CSS score (OR 1.13; 95% CI 1.03-1.23, p=0.007) were significantly associated with frailty. Conclusion Advanced age, PPI user, sarcopenia, hypozincemia, a high FSSG score, and high CSS score are associated with frailty.

While hospitalized due to severe aortic stenosis, an 84-year-old woman developed repeated bleeding from angiodysplasia in the stomach leading to a diagnosis of Heyde syndrome. Following transcatheter aortic valve implantation (TAVI), there was no recurrence of bleeding from the angiodysplasia, and the decrease in von Willebrand factor levels that caused Heyde syndrome also improved. It was felt that the TAVI was able to prevent the recurrence of gastrointestinal bleeding due to angiodysplasia in Heyde syndrome.

Background: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication., Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed., Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies., Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients., Competing Interests: Conflict of interest statement: During the last 3 years, HS received scholarship funds for the research from Daiichi-Sankyo Co., EA Pharma Co., Otsuka Pharmaceutical Co. Ltd., and Tsumura Co., and received service honoraria from Astellas Pharma Inc, AstraZeneca KK, Daiichi-Sankyo Co., EA Pharma Co., Otsuka Pharmaceutical Co. Ltd., Mylan EPD Co., Takeda Pharmaceutical Co., Ltd., Tsumura, Co., and Zeria Pharmaceutical Co. Ltd. AN received scholarship funds for the research from AstraZeneca KK, Daiichi-Sankyo Co., Otsuka Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd., EA Pharma Co., and received service honoraria from AstraZeneca KK, Daiichi-Sankyo Co., Otsuka Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co., Ltd. TM received service honoraria from Takeda Pharmaceutical Co., Ltd.

The aim of the present study was to evaluate symptomatic reflux esophagitis (RE) in proton pump inhibitor (PPI) users. The present study conducted a hospital-based, retrospective cross-sectional study of consecutive RE cases in PPI users at Juntendo University Hospital recruited between 2008 and 2016. Eligible patients were PPI users with a complete patient profile, who completed the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) questionnaire, and who underwent upper gastrointestinal endoscopy for the examination of RE, hiatal hernia (HH) and endoscopic gastric mucosal atrophy (EGA). The patients with RE who were administered PPIs were divided into two groups: Those with symptomatic RE (FSSG≥8) and those with non-symptomatic RE (FSSG<8). The present study investigated the risk factors for symptomatic RE among the patients with RE patients who were administered PPIs. Of the 13,052 cases who underwent patient profiling, the FSSG questionnaire and upper gastrointestinal endoscopy, a total of 2,444 PPI users were eligible. Of the PPI users, 206 cases (8.4%) had RE. Among the 206 patients with RE, 115 (55.8%) had symptomatic RE. The profile of the symptomatic and non-symptomatic RE groups were as follows: A total of 45 females (39.1%) vs. 32 females (35.2%; non-significant); mean ± standard deviation age, 54.8±13.5 vs. 62.9±11.1 years (P<0.01); mean body mass index, 23.5±3.3 vs. 23.2±3.8 (non-significant); severe RE, 12 (10.4%) vs. 2 (2.2%; P<0.05); HH, 70 (60.9%) vs. 40 (44.0%; P<0.05); and mean score of EGA, 1.2±1.8 vs. 1.8±2.1 (P<0.05). Multivariate analysis revealed that a younger age [odds ratio (OR)=0.94; 95% confidence interval (CI): 0.92-0.97, P<0.01] and HH(+) (OR=2.37; 95% CI: 1.30-4.34, P<0.01) were associated with symptomatic RE among patients with RE who were administered PPIs. In conclusion, a younger age and HH were associated with symptomatic RE in patients with RE who were administered PPIs.

Background/aims: Vonoprazan is a new a potassium-competitive acid blocker (P-CAB) that was recently developed in Japan. However, vonoprazan's efficacy in healing gastric ulcers after endoscopic submucosal dissection (ESD) remains controversial. This study aimed to compare the efficacy of P-CABs and proton pump inhibitors (PPIs) in healing post-ESD ulcers., Materials and Methods: This prospective randomized controlled trial (UMIN000017386) enrolled 40 patients with gastric neoplasia, who underwent ESD at our hospital from April 2015 to January 2016. Before ESD, patients were randomly divided into the following two groups: group V, vonoprazan 20 mg/day; or group R, rabeprazole 10 mg/day. Medications were taken 1 day before to 4 weeks after ESD. The ESD-induced artificial ulcer size was measured just after ESD and 4 weeks after ESD to calculate the reduction rate as follows: (ulcer area 4 weeks after ESD)/(ulcer area just after ESD) × 100., Results: Eighteen patients in group V and 15 patients in group R were analyzed. The mean reduction rate was significantly different in groups V and R (93.3% vs 96.6%, respectively). Post-ESD bleeding was observed in two patients in group R and drug-induced hepatic injury in one patient in group R., Conclusion: Rabeprazole facilitated the healing process post-ESD.

Background: Recently, problems associated with proton pump inhibitor (PPI) use have begun to surface. PPIs influence the gut microbiota; therefore, PPI use may increase the risk of enteric infections and cause bacterial translocation. In this study, we investigated fecal microbiota composition, fecal organic acid concentrations and pH, and gut bacteria in the blood of the same patients before and after PPI use., Methods: Twenty patients with reflux esophagitis based on endoscopic examination received 8 weeks of treatment with PPIs. To analyze fecal microbiota composition and gut bacteria in blood and organic acid concentrations, 16S and 23S rRNA-targeted quantitative RT-PCR and high-performance liquid chromatography were conducted., Results: Lactobacillus species were significantly increased at both 4 and 8 weeks after PPI treatment compared with bacterial counts before treatment (P = 0.011 and P = 0.002, respectively). Among Lactobacillus spp., counts of the L. gasseri subgroup, L. fermentum, the L. reuteri subgroup, and the L. ruminis subgroup were significantly increased at 4 and 8 weeks after treatment compared with counts before treatment. Streptococcus species were also significantly increased at 4 and 8 weeks after PPI treatment compared with counts before treatment (P < 0.01 and P < 0.001, respectively). There was no significant difference in the total organic acid concentrations before and after PPI treatment. Detection rates of bacteria in blood before and after PPI treatment were 22 and 28%, respectively, with no significant differences., Conclusions: Our quantitative RT-PCR results showed that gut dysbiosis was caused by PPI use, corroborating previous results obtained by metagenomic analysis.

Background: Endoscopic submucosal dissection (ESD) of esophageal tumors can cause stenosis, yet the effect of esophageal ESD on motility remains unclarified. This study aimed to compare esophageal motility and symptoms, before and after ESD, using high-resolution manometry (HRM) and symptom scoring., Methods: Twenty-eight patients with 35 cT1a cancers were prospectively enrolled between December 2014 and February 2016. Pre- and post-ESD symptom score and HRM were recorded. Based on circumferential resection (CR), patients were divided into group A ( n = 17, <2/3 CR) or B ( n = 11, 2/3 CR or greater). HRM parameters evaluated were distal contractile integral (DCI), contractile front velocity (CFV), intrabolus pressure, integrated relaxation pressure, distal latency, and peristaltic breaks., Results: Symptom scores worsened after ESD in 8/11 patients in group B, and 0/17 patients in group A. There was no significant difference in any HRM parameter after ESD in the whole study group but mean DCI tended to increase ( p = 0.07). In group B, DCI increased significantly after ESD ( p = 0.04), and CFV tended to decrease after ESD ( p = 0.08)., Conclusions: DCI tended to increase after esophageal ESD. ESD affected the symptom score and esophageal motility in cases with 2/3 CR or greater. This trial is registered with UMIN000015829.

Background: Chronic Helicobacter pylori infection in children induces lymphoid hyperplasia called nodular gastritis (NG) at the antral gastric mucosa. The aim of this study was to evaluate genes in gastric biopsy on microarray analysis, to identify molecules associated with NG on comparison with NG-negative pediatric corpus tissue and with H. pylori-infected adult tissue with atrophic gastritis (AG)., Methods: Eight pediatric and six adult H. pylori-infected patients, as well as six pediatric and six adult uninfected patients were evaluated. All infected adults had AG. NG was observed in the antrum of all eight pediatric patients and in the corpus of three patients. Adult and uninfected patients were free of NG; that is, only pediatric H. pylori-infected patients had NG. Total RNA was purified from gastric biopsy, and microarray analysis was performed to compare gene expression between groups. The three infected children with NG in both the antrum and corpus were excluded from analysis of corpus samples., Results: The number of genes significantly up- or downregulated (fold change >3, P < 0.01) compared with uninfected controls varied widely: 72 in pediatric antrum, 45 in pediatric corpus, 103 in adult antrum and 71 in adult corpus. Nineteen genes had significantly altered expression in the antrum of NG tissue compared with NG-negative pediatric corpus tissue and adult AG tissue. The CD20 B-cell specific differentiation antigen had the most pronounced increase. Previously described regulators of NG development were not predominantly upregulated in the NG mucosa., Conclusions: CD20 overexpression may play an important role in lymphoid follicle enlargement and NG., (© 2018 Japan Pediatric Society.)

Background/aims: To evaluate the usefulness of linked color imaging (LCI) and blue LASER imaging (BLI) in Barrett's esophagus (BE) compared with white light imaging (WLI)., Methods: Five expert and trainee endoscopists compared WLI, LCI, and BLI images obtained from 63 patients with short-segment BE. Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and one (decreased). Scores were evaluated to assess visibility. The inter- and intra-rater reliability (intra-class correlation coefficient) of image assessments were also evaluated. Images were objectively evaluated based on L* a* b* color values and color differences (ΔE*) in a CIELAB color space system., Results: Improved visibility compared with WLI was achieved for LCI: 44.4%, BLI: 0% for all endoscopists; LCI: 55.6%, BLI: 1.6% for trainees; and LCI: 47.6%, BLI: 0% for experts. The visibility score of trainees compared with experts was significantly higher for LCI (p = 0.02). Intra- and inter-rater reliability ratings for LCI compared with WLI were "moderate" for trainees, and "moderate-substantial" for experts. The ΔE* revealed statistically significant differences between WLI and LCI., Conclusion: LCI improved the visibility of short-segment BE compared with WLI, especially for trainees, when evaluated both subjectively and objectively., (© 2018 S. Karger AG, Basel.)

Background/aims: Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL)., Methods: Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated., Results: DL (-) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (-) cases had tub1-low or NE at the tumor border., Conclusion: ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication., (© 2018 S. Karger AG, Basel.)

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.