Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study.

BACKGROUND & AIMS: Acid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking. METHODS: In this phase IV, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia. RESULTS: Overall, 202/208 patients (vonoprazan, n = 139; lansoprazole, n = 69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group. At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments. CONCLUSIONS: The exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. Although gastrin concentration, parietal cell hyperplasia, and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508).

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

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

Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report.

BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). The drug has been shown to act as a potent multikinase inhibitor by blocking not only the BCR-ABL1 gene sequence but also the SRC kinase family, though unexpected adverse events such as pleural effusion have recently been reported in patients undergoing treatment with dasatinib. Hemorrhagic colitis is a unique gastrointestinal adverse events associated with dasatinib and its pathogenesis remains poorly understood. CASE PRESENTATION: We report here a case of dasatinib-induced asymptomatic colitis in a patient with CML, who showed no exacerbation in careful observations and maintained deep molecular response (DMR) during a 3-year period. In addition, we performed transcriptome analysis of inflamed colonic mucosa specimens to clarify the possible mechanism of colitis that develops in association with dasatinib administration. Our results demonstrated that differential gene expression, especially lymphocyte-associated genes and chemokines, is substantially involved in inflammation of colonic mucosa in affected patients. CONCLUSION: Dasatinib induces immune-mediated colitis following lymphocyte infiltration.

Initial Computed Tomography Findings of Long and Distended Colon Are Risk Factors for the Recurrence of Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is a common condition in elderly patients with elongated colons. Although endoscopic de-torsion is effective as the primary treatment of sigmoid volvulus, elective surgery is recommended because of the high risk of recurrence and high mortality rate. AIM: The aim of this study was to determine the risk factors for the recurrence of sigmoid volvulus. METHODS: Clinical records of patients treated at Shimane Prefectural Central Hospital were reviewed retrospectively. Among 41 sigmoid volvulus patients who were successfully treated by endoscopic de-torsion and followed up, 30 were observed over 1 year. Among the 30 patients, eight (26.7%) did not experience recurrence, while 22 (73.3%) did. Initial computed tomography (CT) findings indicating the sigmoid colon extending to the diaphragm or ventral to the liver were defined as "extension findings." Extension findings and sigmoid diameter were evaluated in relation to sigmoid volvulus recurrence. RESULTS: Extension findings were significantly more frequent in the recurrent group (77.3%) than in the nonrecurrent group (25.0%) (P = 0.009). Distended sigmoid colon diameter was significantly larger in the recurrent group (11.7 ± 3.8 cm) than in the nonrecurrent group (7.1 ± 1.1 cm) (P = 0.044). Receiver operating characteristic curve analysis demonstrated that the performance threshold was greater than 8.9 cm. Kaplan-Meier analysis showed the significantly high sigmoid volvulus recurrence rate in the patients with extension findings and a distended sigmoid colon greater than 8.9 cm. CONCLUSIONS: CT findings of a long and distended sigmoid colon in initial sigmoid volvulus are risk factors for the recurrence of sigmoid volvulus.

Immunohistochemical expression of filaggrin is decreased in proton pump inhibitor non-responders compared with proton pump inhibitor responders of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, but the role of barrier dysfunction of the epithelium in its pathogenesis remains to be elucidated. Clinically, EoE is divided into proton pump inhibitor-non-responders (PPI-NR) and PPI-responders (PPI-R). Our main aims were to investigate the differences of expression of epidermal differential complex (EDC) proteins and desmoglein that are considered to play important roles in formation of the epidermal skin barrier between these two conditions and to seek the usefulness of the differences in pathological diagnosis. Conventional histopathological findings and allergic background were also compared. METHODS: Twenty-nine PPI-NR and 44 PPI-R were recruited, and 35 reflux esophagitis patients were also enrolled. After clinical information and histopathological findings were reviewed, immunohistochemical expression of EDC proteins (filaggrin, loricrin, and involucrin) and desmoglein in all three groups were examined and semi-quantitatively scored. RESULTS: Regarding allergic conditions, the prevalence of asthma was significantly higher in PPI-NR than in PPI-R. Other allergic conditions showed no differences. Histopathological findings did not exhibit the statistical difference between PPI-NR and PPI-R. However, immunostaining score of filaggrin in PPI-NR was significantly lower than in PPI-R, although the expressions of involucrin, loricrin and desmoglein demonstrated no differences. CONCLUSIONS: The results suggest a role of reduced filaggrin expression in the difference of effectiveness of PPI treatment between PPI-NR and PPI-R. Moreover, immunohistochemical determination of filaggrin expression in EoE patients could be informative in the clinical decision of how to treat the patients.

Interleukin-33 delays recovery of mucosal inflammation via downregulation of homeostatic ABCG5/8 in the colon.

Previous studies have suggested that interleukin-33 (IL-33) is involved in the pathogenesis of ulcerative colitis (UC), though the detailed mechanisms are not fully known. We investigated IL-33-mediated colonic homeostasis using a mechanistic method. Il33-/- mice were more tolerant to dextran sulfate sodium-induced acute colitis than the wild type and also showed delayed recovery from colitis with recombinant IL-33 (rIL-33) administration. Unexpectedly, microarray analysis identified significant downregulation of the Abcg5/8 genes in mouse colons following rIL-33 treatment. ABCG5/8 are known cholesterol transporters in the small intestine and liver, though their colon activities have not been elucidated, thus their role in IL-33-mediated inflammation was investigated. In vitro, toll-like receptor (TLR) stimulation upregulated ABCG5/8 mRNA expression in Caco2 and HCT-15 cells, with subsequent downregulation by rIL-33, while inhibition of ABCG5/8 along with their siRNA increased TLR-stimulated IL-8 production. Together, these results indicated that colonic ABCG5/8 play a regulatory role in TLR-induced inflammation, while histological inflammation in human UC was correlated positively with the level of mucosal IL-33 and inversely with that of colonic ABCG5/8. This is the first report of IL-33-mediated downregulation of colonic ABCG5/8 in a colitis recovery phase, indicating their involvement in UC pathogenesis and potential as a therapeutic target.

Low-dose rectal diclofenac does not prevent post-ERCP pancreatitis in low- or high-risk patients.

BACKGROUND AND AIM: The most common adverse event following an endoscopic retrograde cholangiopancreatography (ERCP) procedure is post-ERCP pancreatitis (PEP). Rectal nonsteroidal anti-inflammatory drug (NSAID) administration has shown promise to reduce the risk of PEP in high-risk patients. However, in contrast to high-risk patients, the role of NSAID administration in patients with low risk remains controversial. METHODS: We performed a prospective, single-center, single-blinded, two-arm parallel group, randomized controlled trial to clarify the efficacy of low dose (50 mg) rectal NSAID administration for preventing PEP in at-risk patients. Patients scheduled to undergo ERCP were randomized into two groups, those with and without rectal administration of diclofenac. Patients in the diclofenac group received 50 mg of rectal diclofenac 30 min before undergoing ERCP. The primary endpoint was rate of PEP. RESULTS: A total of 303 were randomized into the study groups. Four patients declined participation following randomization, and another two were withdrawn. As a result, a total of 147 patients were assigned to the diclofenac group and 150 to the control group. The baseline and procedural characteristics were similar in both groups. The primary endpoint of PEP occurrence was seen in 13 of 297 patients (4.4%), including eight (5.4%) in the diclofenac group and five (3.3%) in the control group (P = 0.286). Additionally, those results were not significantly different when patients were classified as low or high risk. CONCLUSIONS: Prophylactic low-dose rectal diclofenac did not reduce the incidence of PEP following ERCP in patients classified as low or high risk.

Prospective multicenter study of the esophageal triamcinolone acetonide-filling method in patients with subcircumferential esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: The esophageal triamcinolone acetonide (TA)-filling method is a novel local approach for stenosis prevention after extensive esophageal endoscopic submucosal dissection (ESD). We evaluated this method after subcircumferential ESD. METHODS: We enrolled 20 patients with esophageal cancer requiring subcircumferential ESD in a prospective multicenter study. Esophageal TA filling was carried out 1 day and 1 week after ESD, with follow-up endoscopy every 2 weeks. We treated severe stenosis preventing endoscope passage with endoscopic balloon dilatation (EBD) and additional TA filling, and mild stenosis allowing endoscope passage with additional TA filling only. Primary endpoint was incidence of severe stenosis; secondary endpoints were total number of EBD, rate of additional TA filling, time to stenosis and complete re-epithelialization, dysphagia score, and adverse events. Horizontal resection grade was divided into grades 1 (≥ 9/12 and <10/12 of the circumference), 2 (≥ 10/12 and <11/12), and 3 (≥ 11/12 but not circumferential) and analyzed statistically for correlation with endpoints. RESULTS: Incidence of severe stenosis was 5.0% (1/20; 0.1-24.8%) and was treated with three EBD. Six patients showed mild stenosis. Additional TA filling was carried out in these seven patients: 0% (0/9) for grade 1 resection, 40% (2/5) for grade 2, and 83% (5/6) for grade 3 (P < 0.05). Median time to stenosis and re-epithelialization was 3 and 7 weeks, respectively. Dysphagia score deteriorated in one patient. No adverse events occurred. CONCLUSIONS: The esophageal TA-filling method prevented stenosis after subcircumferential ESD. Grade ≥2 resection showed a high risk for stenosis, but additional TA filling for mild stenosis inhibited stenosis progression (UMIN000024384).

[A cross-sectional analysis of the health-related quality of life and work productivity in Japanese subjects with self-reported chronic constipation using the National Health and Wellness Survey 2017].

BACKGROUND: Chronic constipation (CC) is associated with lower health-related quality of life (HR-QoL) and work productivity in Western countries;however, limited data in Japanese subjects are available. METHODS: This retrospective, cross-sectional analysis used the data from the National Health and Wellness Survey (NHWS), a web-based questionnaire survey conducted in 2017 for the Japanese general population. Subjects were allocated to the self-reported CC group when they answered "yes" to the question "Did you have chronic constipation in the past 12 months?". Other subjects were allocated to the non-CC group. Self-reported CC population was sub-categorized as per the abdominal symptoms. The HR-QoL was assessed using the Medical Outcomes Study 12-Item Short-Form Health Survey version 2 using the Mental Component Summary (MCS), Physical Component Summary (PCS), and Role/Social Component Summary (RCS) scores (3-component method). Work productivity was assessed using the Work Productivity and Activity Impairment:General Health version 2.0 for absenteeism, presenteeism, work productivity loss, and activity impairment. RESULTS: Of the 30001 respondents, 3373 had self-reported CC (895 with abdominal symptoms, 2478 without abdominal symptoms) and 26628 did not report CC. The differences in the summary scores [95% confidence interval (CI) ] adjusted for potential confounders between self-reported CC and non-CC (self-reported CC - non-CC) were -1.60 (-1.98, -1.22) in MCS, -0.78 (-1.19, -0.37) in PCS, and -2.09 (-2.57, -1.61) in RCS;the differences in the adjusted summary scores (95% CI) between self-reported CC with and without abdominal symptoms (self-reported CC with abdominal symptoms - without abdominal symptoms) were -0.95 (-1.77, -0.14) in MCS, -1.67 (-2.66, -0.68) in PCS, and -2.05 (-3.55, -0.55) in RCS. All the summary scores were lower in those with self-reported CC and abdominal symptoms than in those with self-reported CC without abdominal symptoms;all the adjusted differences between the summary scores were statistically significant. The adjusted risk ratio (95% CI) of each outcome of self-reported CC relative to non-CC was 1.34 (1.04, 1.73) in absenteeism, 1.21 (1.12, 1.31) in presenteeism, 1.20 (1.11, 1.29) in work productivity loss, and 1.21 (1.15, 1.27) in activity impairment. In terms of statistics, the risk of decreased work productivity for all the outcomes was significantly higher in those with than in those without self-reported CC, indicating decreased work productivity in those with self-reported CC. CONCLUSION: HR-QoL and work productivity were lower in those with self-reported CC than in those who did not report CC, suggesting that CC negatively affects the HR-QoL and work productivity.

Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1,2 Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up.3,4 Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria.1,2 The clinical characteristics remain to be fully elucidated,5 thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference.

BACKGROUND & AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences. RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement. CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

Influence of Helicobacter pylori infection on periodontitis.

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

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

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

Irritable Bowel Syndrome-Like Symptoms in Ulcerative Colitis Patients in Clinical Remission: Association with Residual Colonic Inflammation.

Ulcerative colitis (UC) patients in clinical remission often experience irritable bowel syndrome (IBS)-like symptoms. The prevalence rate of UC patients meeting the definition of IBS, such as shown by the Rome criteria, is significantly higher in those without ongoing clinical activity as compared to healthy controls. Several studies have investigated residual low-grade inflammation found in colonic mucosa of quiescent UC patients and its association with development of IBS-like symptoms. In these patients, residual colonic inflammation was evaluated using endoscopy and histology findings, as well as fecal calprotectin level and shown to not be simply associated with the presence of IBS-like symptoms in UC patients in clinical remission. However, these results are limited by the low number of related investigations conducted. Additional appropriately designed studies are necessary to confirm the relationship of low-grade colonic inflammation with IBS-like symptoms associated with UC.

Adding Acotiamide to Gastric Acid Inhibitors Is Effective for Treating Refractory Symptoms in Patients with Non-erosive Reflux Disease.

BACKGROUND: Approximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief. AIMS: This study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD. METHODS: This was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible. RESULTS: Seventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes. CONCLUSION: Adding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.

Eosinophilic gastrointestinal diseases - Pathogenesis, diagnosis, and treatment.

Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved gastrointestinal tract, though both are considered to be chronic Th2-type allergic diseases caused by food or environmental allergens. In development of EoE, refluxed gastric acid may also have an important role. For diagnosis of EGIDs, the presence of symptoms possibly originating from the involved gastrointestinal tract and dense eosinophil infiltration are important factors. Imaging studies, including endoscopy and computed tomography, along with histopathological examinations of biopsy specimens are useful for diagnosis, whereas laboratory testing of blood, urine, and stool samples has limited value. Three useful options for treating EoE patients are acid inhibitors, swallowed topical corticosteroids, and an elimination diet, while systemic administration of glucocorticoids is the standard treatment of EGE, though information is limited. Since the prevalence of EGIDs is increasing in Western countries as well as Japan, development of effective treatments based on sufficient evidence is becoming an urgent need.

Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type.

Fecal calprotectin level in ulcerative colitis patients is correlated with endoscopic findings. However, its association with various ulcerative colitis disease types has not been elucidated. In the present study, we investigated the correlation of fecal calprotectin level with endoscopic findings as compared to blood biomarkers according to ulcerative colitis disease type. Fecal calprotectin as well as the blood biomarkers: C-reactive protein (CRP), white blood count (WBC), erythrocyte sedimentation rate (ESR), hemoglobin, platelet count (PLT), and serum albumin (Alb) were measured in patients who underwent a complete colonoscopy. Disease type was divided into proctitis, left-sided colitis, and extensive colitis. Correlations of fecal calprotectin and blood biomarker levels with Mayo endoscopic subscore were analyzed. A total of 186 colonoscopy examinations were performed in 124 patients with ulcerative colitis. Fecal calprotectin level showed a significant correlation with Mayo endoscopic subscore regardless of disease type (proctitis, r = 0.54, p<0.01; left-sided colitis, r = 0.75, p<0.01; extensive colitis, r = 0.78, p<0.01), and clearly discriminated inactive (Mayo endoscopic subscore 0) from active stages (Mayo endoscopic subscore 1-3). On the other hand, none of the examined blood biomarkers showed a correlation with Mayo endoscopic subscore in the proctitis group, while weak correlations of several biomarkers (CRP, WBC, ESR, PLT and Alb) with Mayo endoscopic subscore were found in left-sided colitis and extensive colitis cases. This is the first report to elucidate the capabilities of fecal calprotectin and blood biomarkers as endoscopic surrogate markers according to ulcerative colitis disease type.