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Functional dyspepsia (FD), one of the functional gastrointestinal disorders, is highly prevalent. Impaired gastric accommodation is proposed as a pathophysiology of FD. In order to assess gastric accommodation, a slow nutrient drinking test was developed. This study aims to evaluate the effectiveness of this slow nutrient drinking test among patients with FD in Japan.Asymptomatic/healthy participants (n = 26) and those with FD (n = 16), were enrolled. An infusion pump was used to deliver the liquid meal into cups. They were requested to score their meal-related and abdominal symptoms at 5-minute intervals, using a 100 mm visual analog scale. They were instructed to end the test when they felt unable to ingest more or until after 50 minutes.The test ending time was significantly shorter in patients with FD than in healthy participants (22.3 ± 10.6 vs 45.0 ± 7.5 minutes, P0.001). The receiver operating characteristic curve indicated that the optimal cutoff time for detecting patients with FD was 30 minutes. The severity of meal-related and abdominal symptoms between healthy participants and those with FD was continuously different. Univariate and multivariate analyses revealed that the presence of symptoms of postprandial distress syndrome contributed to the short test ending time.The 30-minute slow nutrient drinking test is a minimally invasive method of effectively evaluating symptoms of postprandial distress syndrome among patients with FD, in Japan.

Background Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan. Methods The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts. Results Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not. Conclusions HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired.

Background Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). Methods Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. Results HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0–4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5–19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09–0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16–0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P Conclusions A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.

Introduction: Diagnosing functional dyspepsia requires excluding organic disease and gastrointestinal function evaluation; however, there are no modalities to evaluate these simultaneously. This preclinical study examined the possibility of an endoscopic barostat. Methods: Ultrathin endoscopy and our newly developed pressure-regulated endoscopic insufflator, which insufflates the gastrointestinal tract until the preset pressure is achieved, were used. The actual intragastric pressure was measured using an optical fiber manometer placed in the stomach. Experiment-1: in an ex vivo experiment, we insufflated the isolated stomach and verified whether the intragastric pressure reached the preset pressure. Experiment-2: we inserted the endoscope orally in a porcine stomach, insufflated the stomach, and verified whether the intragastric pressure reached the preset pressure. Finally, we insufflated the stomach at a random pressure to verify the functional tests for proof-of-concept. Results: Experiment-1: the intragastric pressure reached the preset pressure. After reaching the plateau, the pressure remained stable at the preset pressure (Huber M value: 1.015, regression line: 0.988, 95% confidence interval [CI]: 0.994–0.994). Experiment-2: the intragastric pressure reached the preset pressure. After reaching the plateau, the pressure remained stable at the preset pressure (Huber M value: 1.018, regression line: 0.971, 95% CI: 0.985–0.986). At randomly preset pressures, the transendoscopic theoretical intragastric pressure detected by using the insufflator was correlated with the actual pressure measured by using the pressure manometer. Conclusions: This proof-of-concept study shows that a pressure-regulated endoscopic insufflator provides stable intragastric pressure at the preset level, with the potential of an endoscopic barostat to assess the visceral hypersensitivity related to functional dyspepsia.

Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection.Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using aIntention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%-99% and 92.7%, 95% CI: 86%-100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy.This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.

Background/Aims: 5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. Methods: We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. Results: Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P

Prokinetics is one of the therapeutic agents for functional and motility disorders of the stomach. However, its efficacy is limited. Kampo medicine is a unique medical system that was developed in Japan. In Kampo medicine, herbal medicine is prescribed based on the patient’s condition. Therefore, even for functional and motility disorders of the stomach, some herbal medicines are considered as a therapeutic option. Recently, there has been an increase in evidence for the efficacy or the mechanism of herbal medicine for functional and motility disorders of the stomach. Among these, rikkunshito is a well-studied herbal medicine that could be used as an alternative to prokinetics. In this review, we discuss the possibilities of rikkunshito for functional dyspepsia with its prokinetic and non-prokinetic effects and provide an overview of their current use with a focus on their therapeutic mechanism.

Background/Aims: Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day ­STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls. Methods: Patients in whom eradication treatment using both first- and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009–2011 and 2012–2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-analysis was attempted. Results: The overall eradication rates, the eradication rate for gyrA mutation negative- and positive- strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones. Conclusion: Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.

BACKGROUND: Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. OBJECTIVE: A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). METHODS: Patients with NADETs were chronologically divided into a discovery and a validation sets. Two age- and sex-matched control individuals for each case in the discovery set were randomly selected from individuals without NADET. A prediction model for the presence of NADET, constructed in the discovery set, was evaluated in the validation set. RESULTS: In total, 368 adenomas, 81 adenocarcinomas, and 314 controls were analysed. Current smoking, Barrett oesophagus, fundic gland polyps, history of malignant disease, and absence of dyslipidaemia were independently associated with the presence of NADET. The combination of these five factors enabled significant discrimination for NADET in the bulb with a sensitivity of 0.81 in the validation set. We also showed that duodenal adenocarcinomas in the bulb had greater invasive potential than adenocarcinomas in the second portion. CONCLUSION: The presence of a duodenal tumour in the bulb could be predicted by clinical and endoscopic findings, which helps improve the prognosis and quality of life of patients.

The number of patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) is increasing. We describe a case of MTX-LPD of the stomach. After treatment with methotrexate for rheumatoid arthritis, the patient developed left cervical lymphadenopathy and an ulcerative lesion in the stomach, which was presumed to be a mucosa-associated lymphoid tissue (MALT) lymphoma. However, we suspected MTX-LPD, based on the clinical course and the positivity of in situ hybridization for the detection of the Epstein-Barr encoding region. After the cessation of MTX, the left cervical lymphadenopathy and the gastric lesion disappeared. This is first report of gastric MTX-LPD that was presumed to be MALT lymphoma.

Background/Aims Potassium-competitive acid blockers are expected to be the next generation of drugs for the treatment of diseases caused by gastric acid. In 2015, vonoprazan fumarate, a novel potassium-competitive acid blocker, was approved by the Japanese health insurance system. Since its approval, patients refractory to vonoprazan can be encountered in clinical settings. We designed this study to clarify the pathophysiology of gastroesophageal reflux disease refractory to vonoprazan. Methods In this retrospective study, we involved patients who had refractory symptoms after administration of standard-dose proton pump inhibitors or vonoprazan and underwent diagnostic testing with esophageal high-resolution manometry and 24-hour multichannel intraluminal impedance and pH monitoring while using proton pump inhibitors or vonoprazan. Patients were diagnosed based on the Rome IV criteria for functional gastrointestinal disorders and diagnostic test results. Results Twenty-seven patients were analyzed during this study. Gastric pH ≥ 4 was sustained for a longer period of time, and the esophageal acid exposure time and number of acid reflux events were shorter in the vonoprazan group than in the proton pump inhibitor group. The percentage of patients diagnosed with acidic gastroesophageal reflux disease in the vonoprazan group was lower than that in the proton pump inhibitor group. Conclusions Intra-gastric pH and acid reflux were strongly suppressed by 20-mg vonoprazan. When patients with gastroesophageal reflux disease present symptoms after administration of 20-mg vonoprazan, the possibility of pathophysiologies other than acid reflux should be considered. (J Neurogastroenterol Motil 2018;24:577-583)

Background The need for a blood transfusion, defined as hemoglobin

Diabetes is the main cause of gastroparesis accompanying decreased neuronal nitric oxide synthase (nNOS) in myenteric ganglia of the stomach. Decreased nNOS expression in the stomach also results from defects in apolipoprotein E (ApoE), which is secreted by astrocytes and has neuroprotective effects on the central nervous system. However, the roles of ApoE and enteric glial cells on gastric motility are uncertain. In this study, ApoE and enteric glial cell alterations in gastroparesis were investigated. Type 2 diabetic (db/db) mice and ApoE-knockout mice were analyzed. Gastric emptying was measured using the 13C acetic acid breath test. Expression levels of the pan-neuronal marker, protein gene product 9.5 (PGP 9.5), and glial marker, glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. Neural stem cells (NSCs) were injected into the gastric antral wall of ApoE-knockout mice. Delayed gastric emptying was observed in 27% of db/db mice with significant decreases in serum ApoE levels and GFAP expression in the gastric antrum. Gastric emptying was also delayed in ApoE-knockout mice, with a significant decrease in GFAP expression, but no change in PGP 9.5 expression. Transplantation of NSCs improved gastric emptying in ApoE-knockout mice through supplementation of GFAP-positive cells. Our results suggest that decreased enteric glial cells in ApoE-knockout mice are crucial for development of delayed gastric emptying, and NSC transplantation is effective in restoring myenteric ganglia and gastric motility.

Background and aim Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated. Methods We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H. pylori before and after unsuccessful eradication with STFX-containing regimens at Keio University Hospital between December 2011 and March 2015. Results A total of 266 patients treated with STFX-containing regimens for third-line H. pylori eradication were evaluated. Double mutations in gyrA were acquired by 20.8% of strains that exhibited seven-fold increased STFX MICs, compared to pre-treatment MICs. The STFX MICs did not increase, however, when the location of the gyrA mutations did not change after treatment. Double mutations in gyrA developed in 60.0% of the strains in which eradication failed, which exhibited a baseline mutation at position D91, and in 11.1% of strains with baseline mutations at position N87. Conclusion Acquisition of double mutations in gyrA evoked high-level resistance to STFX in H. pylori after unsuccessful eradication with STFX-containing regimens.

Background and aimHelicobacter pylori (H. pylori) eradication regimen has not been standardized for patients with penicillin allergy. We investigated the association between the efficacy of a 10-day sitafloxacin, metronidazole, and esomeprazole triple regimen and antibiotic resistance, in patients with penicillin allergy.MethodsPenicillin-allergic patients infected with H. pylori were enrolled between March 2014 and November 2015. The minimum inhibitory concentrations (MICs) of sitafloxacin and metronidazole, and the gyrA mutation status of the H. pylori strains were determined before treatment. The cut-off points for antimicrobial resistance were defined as 8.0 µg/ml for metronidazole and 0.12 µg/ml for sitafloxacin. The patients received the triple therapy (20 mg esomeprazole, bid; 250 mg metronidazole, bid; and 100 mg sitafloxacin, bid) for 10 days. Successful eradication was evaluated using the [13C] urea breath test or the H. pylori stool antigen test.ResultsFifty-seven patients were analyzed, and th...

Background Impaired sleep quality is common, and can reduce work productivity in patients with functional dyspepsia (FD). Objective The objective of this article is to evaluate whether there is a direct association between the presence of FD and the severity of impaired sleep quality, and to calculate the economic loss due to the decreased work productivity associated with sleep quality. Methods In Study 1, using a web-based survey completed by workers with and without FD, we evaluated impaired sleep quality, work and daily productivity, and the severity of reflux and bowel symptoms. In Study 2, the association between the presence of FD and the severity of impaired sleep quality was validated in a hospital-based cohort. Results In both Study 1 and 2, although impaired sleep quality was more frequent in participants with FD than in those without FD, the independent association between the presence of FD and the severity of impaired sleep quality was not observed after adjustment for the severity of reflux and bowel symptoms. FD participants with impaired sleep quality reported additional economic loss of 53,500 Japanese yen/month. Conclusion Although the association between impaired sleep quality and FD was indirect, concomitant impaired sleep quality could worsen economic loss.

Background/Aims: Colonoscopy and computed tomography (CT) are used primarily to exclude organic diseases in patients with irritable bowel syndrome (IBS), rather than to assess the pathophysiology of IBS. We aimed to evaluate colonic dysmotility and morphology in Japanese patients with IBS.Methods: One hundred eighty-four patients with IBS and 49 asymptomatic controls who underwent colonoscopy in combination with CT colonography or barium enema were retrospectively reviewed between 2008 and 2012. Water-aided colonoscopy was performed without sedation by a single endoscopist. The duration and pattern of colonic movement and cecal intubation time were recorded. To assess colonic morphology, barium enema or CT colonography were performed immediately after colonoscopy.Results: Colonic dysmotility was more frequent in the IBS group (28.8% vs. 2.0% in controls, P

Aims/Introduction To evaluate the efficacy and safety of once‐weekly (q.w.) extended‐release exenatide after switching from twice‐daily (b.i.d.) exenatide in patients with type 2 diabetes. Materials and Methods This was an investigator‐initiated, prospective, single‐arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end‐point was change in HbA1c at week 24 to test the glucose‐lowering effect of exenatide q.w. versus exenatide b.i.d. Results A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval −0.4 to −0.03%, P, In the present study, we report the efficacy and safety of once‐weekly extended‐release exenatide after switching from twice‐daily exenatide in Japanese patients with type 2 diabetes.

Background and aimsThere is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO2 insufflation.MethodsNon-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO2 (EtCO2) was continuously monitored during the procedure under CO2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system.ResultsEleven patients were enrolled. Measurement of EtCO2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s).ConclusionThis study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO2 insufflation.

Background and aims There is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO2 insufflation. Methods Non-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO2 (EtCO2) was continuously monitored during the procedure under CO2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system. Results Eleven patients were enrolled. Measurement of EtCO2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s). Conclusion This study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO2 insufflation.

Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD), are common chronic disorders even in the younger population. Physical activity is advocated for patients with FGIDs, although the evidence is insufficient. We investigated the association between the intensity of regular exercise and gastric emptying to determine the effect of physical activity on dyspeptic symptoms. Thirty healthy individuals were selected and divided into three groups (low, moderate, and high) using the index of total exercise intensity in a week. Gastric emptying was evaluated by the 13C-acetate breath test. Gastroesophageal reflux symptoms, dyspeptic symptoms, stool forms, scores of anxiety and depression, and scores of sleep quality were also compared. Baseline scores of gastroesophageal reflux symptoms, anxiety, depression, and sleep quality were not different among the three groups. Gastric emptying was significantly faster in low-intensity exercise group than the moderate-intensity exercise group. Although the presence of loose stool and alcohol consumption were also associated with the intensity of regular exercise, these variables were not confounders. In conclusion, the intensity of regular exercise was independently associated with gastric emptying in healthy individuals. These baseline data would be useful for consideration of an optimal exercise intervention for the treatment of FD.

Although upper GI bleeding (UGIB) is a significant cause of inpatient admissions, no scoring method has proven to be accurate and simple as a standard for triage purposes. Therefore, we compared a previously described 3-variable score (1 point each for absence of daily proton pump inhibitor use in the week before the index presentation, shock index [heart rate/systolic blood pressure] ≥1, and blood urea nitrogen/creatinine ≥30 [urea/creatinine≥140]), the Horibe gAstRointestinal BleedING scoRe (HARBINGER), with the 8-variable Glasgow-Blatchford Score (GBS) and 5-variable AIMS65 to evaluate and validate the accuracy in predicting high-risk features that warrant admission and urgent endoscopy.Consecutive patients presenting with suspected UGIB between 2012 and 2015 were prospectively enrolled in 3 acute care Japanese hospitals. On presentation to the emergency setting, an endoscopy was performed in a timely fashion. The primary outcome was the prediction of high-risk endoscopic stigmata.Of 1486 enrolled patients, 637 (43%) harbored high-risk endoscopic stigmata according to international consensus statements. The area under the receiver operating characteristic curve (AUC) for the HARBINGER was .76 (95% confidence interval [CI], .72-.79), which was significantly superior to both the GBS (AUC, .68; 95% CI, .64-.71; P .001) and the AIMS65 (AUC, .54; 95% CI, .50-.58; P .001). When the HARBINGER cutoff value was set at 1 to rule out patients who needed admission and urgent endoscopy, its sensitivity and specificity was 98.8% (95% CI, 97.9-99.6) and 15.5% (95% CI, 13.1-18.0), respectively.The HARBINGER, a simple 3-variable score, provides a more accurate method for triage of patients with suspected UGIB than both the GBS and AIMS65.

The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms.We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured.At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT.The small sample size with no control group.Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.

This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy.Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy.Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively.Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy.

Background and Aim Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection. Methods Male H2R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H+/K+-ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H+/K+- ATPase, sonic hedgehog (Shh), and trefoil factor-2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Results In the H2R knockout mice, the distribution of AQP4-positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H+/K+ ATPase were elevated in H2R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H. pylori infection. In H2R knockout mice with H. pylori infection, the expression level of TFF2 mRNA was elevated while the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased compared with the H2R knockout mice without H. pylori infection. Conclusions In the H2R knockout mice, massive SPEM was induced by H. pylori colonization and the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased.

Background/Aims: Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT. Methods: This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale. Results: Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT. Conclusions: FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.

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.

Hypersensitivity to gastric distention, an important feature of functional dyspepsia, is assessed by stepwise balloon distention of the proximal stomach in fasting patients. However, symptoms of functional dyspepsia are often worse after a meal, so studies of postprandial balloon distentions might be more relevant. We compared the effects of fasting and postprandial stomach distention in patients with functional dyspepsia.Twenty healthy controls and 62 patients with functional dyspepsia participated in a gastric barostat study at Leuven University Hospital with graded isobaric distentions before and after a liquid meal. On a separate day, all patients underwent a gastric emptying breath test with assessment of postprandial severity of 6 different dyspeptic symptoms scored at 15-minute intervals for 4 hours. For each symptom, a meal-related severity score was obtained by adding all scores; the cumulative symptom score (CSS) was obtained by adding individual symptom severity scores.In patients, but not in controls, postprandial sensitivity to balloon distention was significantly greater than fasting sensitivity. The CSS and individual symptom scores did not differ between patients with normal or hypersensitivity to fasting distention, but patients who were hypersensitive to postprandial distention had a significantly higher CSS, along with scores for postprandial fullness, bloating, and nausea (all P.05). On multivariate analysis, hypersensitivity to postprandial distention was associated with hypersensitivity to fasting distention and with impaired accommodation to a meal.Postprandial, but not fasting, distention thresholds are related to the severity of meal-related symptoms in patients with functional dyspepsia.