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BACKGROUND In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PVO2) after ECR of 7% as either good (n=32; mean percentage change in PVO2[%∆PVO2]=23.2%) or poor (n=32; mean %∆PVO2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PVO2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PVO2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P

BACKGROUND Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as

Background and Aim Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with ADA. We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. Methods Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (

Gastric metastasis from ovarian cancer has rarely been reported. We herein report the case of a 64-year-old woman with gastric metastasis from ovarian cancer that was diagnosed as surgical stage IA. Diagnostic and staging laparotomy showed mucinous carcinoma of the right ovary. At one month after surgery, bone metastasis was detected via scintigraphy. On esophagogastroduodenoscopy, a 10-mm elevated lesion with ulceration on the top was seen in the stomach. The immunohistochemical analysis of biopsy specimens showed that these metastases arose from ovarian cancer. We recommend that physicians remain aware of the possibility of gastric metastasis in patients with ovarian cancer.

This study aimed to elucidate the predictors of improvements in exercise capacity during cardiac rehabilitation (CR) in the recovery phase after coronary artery bypass graft surgery (CABG) versus acute myocardial infarction (AMI). We studied 152 patients (91 after AMI and 61 after CABG) who participated in a 3-month CR program. All patients underwent a cardiopulmonary exercise test, blood tests, maximal quadriceps isometric strength (QIS) measurement, and bioelectrical impedance body composition measurement at the beginning and end of the 3-month CR program. At baseline, the percentage of predicted peak oxygen uptake (%pred-PVO2), maximal QIS, and hemoglobin (Hb) were significantly lower, while C-reactive protein (CRP) was significantly higher, in the CABG than the AMI group. After the 3-month CR, %change in PVO2 (%ΔPVO2) was significantly greater in the CABG than the AMI group (18 ± 15% vs 11 ± 12%, P

Objective Balloon-assisted endoscopy enables access to and treatment of strictures in the small intestine using endoscopic balloon dilation (EBD); however, the long-term outcomes of EBD have not been sufficiently evaluated. This study evaluated the long-term outcomes of EBD in Crohn's disease to identify the risk factors associated with the need for subsequent surgical intervention. Methods We retrospectively analyzed patients with Crohn's disease who had undergone EBD with double-balloon endoscopy (DBE) for small intestinal strictures at a single center between 2006 and 2015. The long-term outcomes were assessed based on the cumulative surgery-free rate following initial EBD. Results Seventy-two EBD with DBE sessions and 112 procedures were performed for 37 patients during this period. Eighteen patients (48.6%) required surgery during follow-up. Significant factors associated with the need for surgery in a multivariate analysis were multiple strictures (adjusted hazard ratio, 14.94; 95% confidence interval, 1.91-117.12; p=0.010). One patient (6.7%) required surgery among 15 who had single strictures compared to 17 (77.3%) among 22 patients with multiple strictures. Conclusion In a multivariate analysis, the presence of multiple strictures was a significant risk factor associated with the need for surgery; therefore, a single stricture might be a good indication for EBD using DBE for small intestinal strictures in Crohn's disease patients.

Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI.This study consisted of 760 patients with AMI who were admitted within 48h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3mg/dl or ≥50% within any 48h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48h after admission) and late-AKI (48h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI.Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p0.001) and no-AKI (3%, p0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p=0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p0.001). Patients with persistent early-AKI had the highest mortality (66%, p0.001).Early-AKI was associated with worse outcome. Even if renal function once returned to baseline level, patients with early-AKI tended to be at high risk of mortality.

BACKGROUND The efficacy of exercise training (ET) programs and its relationship with long-term clinical outcomes in advanced heart failure (HF) patients with high levels of B-type natriuretic peptide (BNP) remain uncertain.Methods and Results:We studied 340 consecutive HF patients with ejection fraction (EF)

BACKGROUND Although peak oxygen uptake (pVO2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pVO2.Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF)

In patients with functional dyspepsia (FD), mild duodenal inflammation correlates with increased mucosal permeability. Enteric glial cells can produce glial cell line-derived neurotrophic factor (GDNF) to repair disrupted epithelial barrier function. We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms. Duodenal biopsies taken from FD patients and control subjects were used for analysis. GDNF protein expression and localization were examined. Cellular infiltration of eosinophils and mast cells was measured. We also examined the intercellular space between the adjacent epithelial cells at the apical junction complex using transmission electron microscopy. In FD patients, expression of GDNF protein was significantly increased compared with controls, 107.3 (95.3–136.7) versus 49.3 (38.0–72.6) pg/mg protein (median (interquartile range), p = 0.006), respectively. GDNF was localized in enteric glial cells, eosinophils, and epithelial cells. The number of eosinophils was significantly greater in FD patients than in controls, 1039 (923–1181) versus 553 (479–598) cells/mm2 (p = 0.021), respectively. The intercellular space was dilated at the adherent junction in FD patients compared to control patients, 32.4 (29.8–34.8) versus 22.0 (19.9–26.1) nm (p = 0.002), respectively. Intercellular distance positively correlated with the frequency of postprandial fullness and early satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively). Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552). Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.

Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett’s esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma. We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model. Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett’s esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis. All rats in both groups developed Barrett’s esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group. Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.

Objective To determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2–8 sessions/patient. Methods Forty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR. Results No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p

Enteric glial cells (EGCs) modulate colonic motility in a maternal separation model. We aimed to investigate structural changes in gastric EGC and gastric emptying as responses to maternal separation and acute adulthood stress in rats to elucidate the pathophysiological roles of gastric EGC.As a chronic stress, we subjected male Wistar rats to 3h of maternal separation during postnatal days 2-14. As an acute adulthood stress (7weeks of age), we used the 8-h water-immersion method. We morphologically evaluated gastric EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. We analyzed gastric emptying by the phenol red method.The area of EGC processes that apparently overlapped with neurons increased according to stress intensity (acute stress, 10.4%; maternal separation, 10.2%; maternal separation plus acute stress, 26.6%; control, 5.0%). Ratios of morphologically changed leaf-like processes to the total processes were 8.1%, acute stress; 10.3%, maternal separation; 4.0%, control. Ratio dramatically increased in the combined stress group (20.5%, p=0.026 vs. control). The mean bulging head area of leaf-like processes in the combined stress group was greater by 6.4μm(2) (control, 2.4μm(2); p=0.042). Gastric emptying in the maternal separation group was gradually delayed (104.1% at 7weeks, 66.7% at 17weeks, and 48.5% at 48weeks; p0.05, respectively). Gastric emptying in the combined stress group tended to be delayed at 17weeks (45.7% vs. 81% in controls, p=0.066).Gastric EGCs exhibited structural changes according to stress intensity, which may be associated with stress-induced dysfunction of the stomach.

BACKGROUND AND AIM Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE2 in tissues is determined by a balance of PG biosynthesis and degradation pathways, which involve the PG transporter (PGT). We investigated PGT in gastric adenocarcinoma by determining its expression pattern and examining associations of PGT with prognosis and tumor angiogenesis. METHODS PGT expression was determined by immunohistochemistry in advanced gastric adenocarcinoma specimens obtained from 96 patients who underwent surgical resection. Correlations between PGT expression level and clinicopathological factors were statistically analyzed. Angiogenesis in the tumor tissue was evaluated by counting the number of microvessels. The role of PGT in mRNA and protein expression of vascular endothelial growth factor (VEGF) was examined in gastric cancer cells stimulated by PGE2 . RESULTS Based on multivariate and Kaplan-Meier analyses, negativity for PGT expression was an independent poor prognostic factor. There were more microvessels in PGT-negative tumors than in PGT-positive tumors. Transfection of AGS and MKN7 gastric cancer cells with PGT-specific siRNA led to increased VEGF mRNA and protein expression accompanied by increased PGE2 in the culture media. CONCLUSIONS PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.

Objective Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances; however, the detailed differences in the characteristics of sleep disturbances between GERD and non-GERD patients are unknown. The aim of the present study was to analyze the clinical characteristics as well as health-related quality of life in GERD and non-GERD patients with sleep disturbances. Methods Three hundred and fifty patients, including 124 patients with GERD and 226 patients without GERD, completed a self-administered questionnaire that evaluated clinical information. The Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and 8-item Short-Form Health Survey (SF-8) were also used. Sleep disturbance was considered to be present if the PSQI was >5.5. Results The prevalence of sleep disturbances was significantly higher in the GERD patients (66/124, 53.9%) than in the non-GERD patients (89/226, 39.3%). Depression and anxiety were significantly more common in the subjects with sleep disturbances than in those without sleep disturbances, although there were no differences between the GERD and non-GERD patients. Among the subjects with sleep disturbances, daytime sleepiness was more common in the GERD patients than in the non-GERD patients. The subjects with sleep disturbances had a poorer health-related quality of life. The physical components of quality of life were impaired, particularly in the GERD patients with sleep disturbances. Conclusion GERD patients with sleep disturbances commonly experience daytime sleepiness and an impaired health-related quality of life, especially in terms of physical components.

Background Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. Methods/design This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. Discussion This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. Trial registration The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316. Registered on 2 October 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2353-1) contains supplementary material, which is available to authorized users.

The necessity of additional gastrectomy for patients not meeting the inclusion criteria after endoscopic submu cosal dissection (ESD) is controversial. The aim of this study was to elucidate the risk factors for lymph node metastasis (LNM) and residual cancer (RC) in patients not meeting the inclusion criteria after ESD and to determine additional treatment strategies.Of 1443 gastric cancer patients who underwent ESD between 2004 and 2013, 167 patients diagnosed as having a lesion not meeting the inclusion criteria after ESD were retrospectively analyzed. Of the 167 cases, 100 cases underwent additional gastrectomy, and 67 cases were observed without surgery.Overall, 9.0 % (9/100) and 9.0 % (9/100) of patients not meeting the inclusion criteria after ESD presented with LNM and RC, respectively, but neither was observed in 83 patients (83.0 %). Multivariate analysis revealed that lymphovascular involvement (LVI) (OR 38.38; 95 % CI 1.94-761.43, p = 0.017) and undifferentiated type (OR 45.58; 95 % CI 2.88-720.94, p = 0.007) were independent risk factors for LNM, and positive horizontal margin was an independent risk factor for RC (OR 9.48; 95 % CI 1.72-52.13, p = 0.010). In differentiated types without LVI, no cases had LNM (0/38) in the additional gastrectomy group, and there was no lymph node or distant recurrence (0/39) in the observation group.Additional treatment is necessary for patients with LVI, undifferentiated type, and positive horizontal margin. Careful follow-up may be acceptable for patients with the differentiated type without LVI, especially for the elderly or patients with severe comorbidities.

The detailed risk factors such as bleeding pattern, comorbidities, and medication usage of patients with obscure gastrointestinal bleeding (OGIB) are largely unknown. We evaluated the risk factors related to ulcerative and vascular lesions of the small intestine diagnosed by capsule endoscopy or balloon-assisted endoscopy in OGIB cases. We retrospectively evaluated 390 OGIB cases (occult, n = 101; overt, n = 289) in our hospital between January 2005 and March 2011 using univariate and multivariate logistic regression analyses to determine the related risk factors. In occult (n = 36) and overt (n = 120) OGIB cases, some lesions were detected in the small intestine. Ulcerative and vascular lesions were detected in both occult (n = 25, 69.4 %; n = 8, 22.2 %, respectively) and overt (n = 57, 47.5 %; n = 39, 32.5 %, respectively) cases. For ulcerative lesions, non-steroidal anti-inflammatory drugs were identified as a risk factor in overt cases [odds ratio (OR) 2.974, 95 % confidence interval (CI) 1.522–5.809, P = 0.001]. For vascular lesions, lowest hemoglobin level (OR 0.634, 95 % CI 0.422–0.953, P = 0.028) and hematologic disease (OR 8.575, 95 % CI 1.076–68.309, P = 0.042) were identified as risk factors in occult cases, whereas hemodialysis (OR 3.71, 95 % CI 1.315–10.467, P = 0.013) was identified in overt cases. Additionally, liver cirrhosis was noted as a risk factor in both occult (OR 7.453, 95 % CI 1.213–45.773, P = 0.013) and overt (OR 4.900, 95 % CI 2.099–11.443, P

Once gastrointestinal (GI) graft-versus-host disease (GVHD) occurs after hematopoietic stem cell transplantation, it may be life-threatening. Therefore, an earlier accurate diagnosis of macroscopic and microscopic features using an appropriate modality improves the prognosis of patients with suspected GI-GVHD.In patients experiencing watery diarrhea within 100 days after hematopoietic stem cell transplantation, we evaluated the severity of mucosal injury at the proximal ileum, terminal ileum, and rectum according to previously reported criteria using transanal single balloon endoscopy. GI-GVHD was diagnosed by the presence of gland apoptosis without inflammatory or infectious factors in the biopsied specimens obtained from their respective site regardless of the mucosal lesion.Consecutive suspected GI-GVHD patients with watery diarrhea (11 men and 5 women, mean age: 45.6 years, coexistent symptoms: nausea [38%] and exanthema [69%]) were enrolled. GI-GVHD was identified pathologically in 11 patients (69%), all of whom had pathological findings of GI-GVHD at the rectum. However, eight patients (73%) had pathological findings of GI-GVHD at both the ileum and the rectum and none had pathological findings of GI-GVHD at the ileum alone. The accuracies for a pathological diagnosis of GI-GVHD based on endoscopic features were 44%, 44%, and 38% at the proximal ileum, terminal ileum, and rectum, respectively. The severity of mucosal injury had no association with the diagnostic rate of pathological GI-GVHD at any site.A pathological evaluation of the rectum but not the ileum may be important and useful for the accurate diagnosis of early GI-GVHD.

Background Enteric glial cells (EGCs) play important roles in enteric integrity and regulation of gastrointestinal function. However, whether EGCs undergo pathophysiological changes in stress-associated gastrointestinal disorders is unknown. We investigated structural and functional alterations in colonic EGCs and their roles in colonic contraction in an irritable bowel syndrome (IBS) model. Methods As a chronic stress, male Wistar rats underwent 3-h maternal separation during postnatal days 2–14. As an acute stress, we used water-immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. Colonic contraction was analyzed with electrical field stimulation (EFS). Key Results Glial fibrillary acidic protein (GFAP) expression and the number of total, cholinergic, and nitrergic neurons were unchanged in maternally separated rats with acute stress (combined stress: an IBS model) compared with controls. However, the density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity: control, acute stress, maternal separation, and combined stress. EFS-induced colonic contractions were significantly greater in the combined stress rats than in controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism, was required to inhibit both EFS-induced contraction and EGCs activation in the combined stress rats than in controls. Conclusions & Inferences Colonic EGCs exhibited structural alterations according to the stress intensity. EGCs were associated with stress-induced colonic hyper-contraction in the combined stress rats, which may underlie the pathogenesis of IBS.

A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.

Barrett’s esophagus (BE) is characterized by a distinct Th2-predominant cytokine profile. However, antigens that shift the immune response toward the Th2 profile are unknown. We examined the effects of rebamipide on the esophageal microbiome and BE development in a rat model. BE was induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided into control and rebamipide-treated group receiving either a normal or a 0.225 % rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples were examined by terminal-restriction fragment length polymorphism (T-RFLP) analysis to assess microbiome composition. The dynamics of four bacterial genera (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by real-time PCR. The incidences of BE in the control and rebamipide group at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP analysis of normal esophagus revealed that the proportion of Clostridium was 8.3 %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium increased and that of Lactobacillales decreased at 8 weeks in both groups. Such changes were consistently observed in the control but not in the rebamipide group. Clostridium and Lactobacillus expression was lower and higher, respectively, in the rebamipide group than in the control group. Rebamipide reduced BE development and altered the esophageal microbiome composition, which might play a role in BE development.

Background and Aim Mucosal healing is now the ideal treatment goal for patients with Crohn's disease (CD) and endoscopy is suitable for both visualizing the intestinal mucosa and optimizing treatment according to the objective endoscopic findings; however, passing through strictures with a conventional colonoscope is sometimes difficult. An ultrathin colonoscope (outer diameter 9.2 mm) has been developed for superior insertion performance. Methods CD patients with strictures that could not be passed with a conventional colonoscope were eligible for entry into the study. We investigated the rate of passage of the ultrathin colonoscope beyond strictures. We also investigated the clinical impact of optimizing the treatment strategy according to the endoscopic findings beyond the stricture. Results Of 49 patients, the ultrathin colonoscope could pass the stricture in 59.2% (29/49). The main reason for failure compared with the “pass” group was anal stricture (P = 0.005). When including finger bougie for severe anal stricture, passage of the stricture was achieved in 83.7% (41/49) of cases and the oral mucosa beyond the stricture was visualized. In these cases, 56.1% (23/41) had treatment efficacy confirmed and 43.9% (18/41) required a change of treatment. Importantly, half (9/18) of them were in clinical remission. There were no complications of the study. Conclusion The ultrathin colonoscope could provide optimized treatment based on objective findings of the activity of the oral-side mucosa in CD patients complicated with stricture. Selection of the appropriate endoscope to visualize the responsible lesion is essential to optimize the treatment strategy in each case of CD.

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate-to-severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent-awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances.

A 64-year-old man presented with epigastralgia and nausea after an acute exacerbation of chronic pancreatitis. Abdominal computed tomography revealed remarkable thickening of the gastric wall and intramural hypodense areas. Esophagogastroduodenoscopy showed a large gastric ulcer surrounded by an edematous mucosa and mucopus. The results of a culture from a biopsy of the lesion indicated phlegmonous gastritis. The patient was successfully treated with an antibiotic without gastrectomy.

Mucosal healing has been a focus of attention as an emerging ideal treatment goal of Crohn’s disease. Endoscopy is the gold standard for evaluating mucosal lesion. Objective precise monitoring, especially for the small bowel, is important for stratifying the treatment strategy. Some limitations and issues for definition of mucosal healing, accessibility of stricture or adhesion, feasible endoscopic score still remain. It is important in clinical practice to identify the appropriate time for intensifying the CD treatment for small ulcerative lesion endoscopically. There are characters for each imaging modality, for instance assessment of intestinal tract wall and extrawall information. The combination with other complementary imaging modalities or biomarkers is useful in optimizing the CD treatment strategy. An appropriate accelerated step-up treatment strategy combined with stratified precise monitoring of the SB should provide optimal prognosis in patients with CD. Endoscopic prediction of long-term prognosis or efficacy of treatment is an important subject for investigation.

Interruption of sedation due to a poor response to modified neuroleptanalgesia (m-NLA) with midazolam often occurs during endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) because most patients have a history of heavy alcohol intake. Recently, propofol has been used feasibly and safely during endoscopic procedures. The aim of this study was to clarify the efficacy and safety of propofol compared with that of midazolam during ESD for ESCC. This was a single-blind, randomized controlled trial in a single center. Patients with ESCC scheduled for ESD were included in the study. Patients were randomly assigned to one of two groups: the propofol group and the midazolam group. The main outcome was the incidence of discontinuation of the procedure due to a poor response to sedation. Secondary outcomes included risk factors for a poor response to sedation. Between April 2014 and October 2015, 132 patients (n = 66 per group) who underwent ESD for ESCC were enrolled in this study. The incidence of discontinuation due to a poor response to sedation in the propofol and midazolam groups was 0% (0/66) and 37.9% (25/66), respectively (p

The clinical significance of minimal changes in non-erosive reflux disease (NERD) is controversial. Multichannel intraluminal impedance–pH (MII-pH) monitoring enables classification of NERD. The aim of this study was to evaluate associations between endoscopic findings and functional assessment via MII-pH monitoring in patients with proton-pump inhibitor (PPI)-refractory NERD. Thirty-four PPI-refractory NERD patients were retrospectively analyzed. On the basis of the MII-pH monitoring results, cases were classified as acid reflux, non-acid reflux, and functional heartburn. Minimal changes such as white turbidity, erythema, loss of fine vascular network pattern at the esophagogastric junction, hyperplasia of vascular network at the middle esophagus, hernia, flap valve grade, and atrophic gastritis were evaluated endoscopically. Among 34 patients, 8 were categorized with acid reflux, 17 with non-acid reflux, and 9 with functional heartburn. There were no differences in the prevalence of minimal changes among the groups, but all cases showing white turbidity of the entire esophageal circumference involved non-acid reflux. The prevalence of hiatal hernia and abnormal flap valve did not differ among the three groups, but the presence of atrophic gastritis was significantly more common in patients with functional heartburn than in those with acid and non-acid reflux. The prevalence of hyperplasia of the vascular network at the middle esophagus was significantly higher in patients with proximal migration than in those without. There are associations between endoscopic findings and functional assessment via MII-pH monitoring. Future studies should pay more attention to the endoscopic findings at the middle esophagus.

New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.

This study was undertaken to assess the impact of acute hyperglycemia (acute-HG) and chronic hyperglycemia (chronic-HG) on short-term outcomes in patients with acute myocardial infarction (AMI). This study consisted of 696 patients with AMI. Acute-HG was defined as admission plasma glucose ≥200 mg/dl and chronic-HG as hemoglobin A1c ≥6.5%. Acute-HG was associated with higher peak serum creatine kinase (4,094 ± 4,594 vs 2,526 ± 2,227 IU/L, p0.001) and in-hospital mortality (9.8% vs 1.6%, p0.001). On the contrary, there was no significant difference in peak creatine kinase (2,803 ± 2,661 vs 2,940 ± 3,181 IU/L, p = 0.59) and mortality (3.3 vs 3.7%, p = 0.79) between patients with chronic-HG and those without. Multivariate analysis showed that admission plasma glucose was an independent predictor of in-hospital mortality (odds ratio 1.15, 95% confidence interval 1.05 to 1.27, p0.001), but hemoglobin A1c was not. When only patients with acute-HG were analyzed, chronic-HG was associated with a significantly smaller infarct size (3,221 ± 3,001 vs 5,904 ± 6,473 IU/L, p0.001) and lower in-hospital mortality (5.5 vs 18.9%, p = 0.01). In conclusion, these results suggested that acute-HG, but not chronic-HG, was associated with adverse short-term outcomes after AMI. Paradoxically, in patients with acute-HG, chronic-HG might abate the adverse effects of acute-HG.

Patients with dyspepsia/functional dyspepsia (FD) show frequent overlapping of other gastrointestinal (GI) diseases, such as irri-table bowel syndrome, and non-GI diseases, in addition to internal subgroup overlapping. These overlap patients have more frequent or more severe symptoms, poorer health-related quality of life and higher somatization scores, and they are more like-ly to experience anxiety, depression or insomnia compared to non-overlap patients. The higher prevalence of overlap in patients with dyspepsia/FD is not by chance, indicating common pathogeneses, including visceral hypersensitivity, altered GI motility, in-fection, and stressful early life events. There are few clinical trials targeting overlap in patients with dyspepsia/FD, and no ther-apeutic strategy has been established. Further studies in this research area are needed. In this review, we describe the epidemi-ology, pathogenesis and treatment of overlap in patients with dyspepsia/FD.(J Neurogastroenterol Motil 2014;20:447-457).

OBJECTIVES: The usefulness of non-magnifying endoscopy with narrow-band imaging (NBI; NM-NBI) in the screening of early esophageal squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN) remains unclear. Here, we aimed to compare NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms of the diagnostic performance, and to evaluate the usefulness of NM-NBI in detecting early esophageal SCC. METHODS: We prospectively enrolled 202 consecutive patients (male/female=180/22; median age, 67 years) with high-risk factors for esophageal SCC. All patients received endoscopic examination with NM-NBI and CE-Iodine to screen for early esophageal SCC or HGIN. We conducted the examinations sequentially, and calculated the accuracy, sensitivity, and specificity through a per-lesion-based analysis. A propensity score matching analysis was performed to reduce the effects of selection bias, and we compared the respective outcomes according to NM-NBI and CE-Iodine after matching. RESULTS: The accuracy, sensitivity, and specificity of NM-NBI were 77.0, 88.3, and 75.2%, respectively, and those for unstained areas by CE-Iodine were 68.0, 94.2, and 64.0, respectively. The accuracy and specificity of NM-NBI were superior to those of CE-Iodine (P=0.03 and P=0.01, respectively). However, the sensitivity did not significantly differ between NM-NBI and CE-Iodine (P=0.67). The accuracy and specificity of NM-NBI before matching were superior to those of CE-Iodine after matching (P=0.04 and P=0.03). CONCLUSIONS: NM-NBI was useful and reliable for the diagnosis of esophageal SCC and can be a promising screening strategy for early esophageal SCC.

Background and Study Aims There are a few reports about the efficacy of endoscopic submucosal dissection (ESD) for adenocarcinomas of the esophagogastric junction (EGJ). However, there is no detailed analysis that divides EGJ cancers into Barrett’s adenocarcinoma and gastric cardia adenocarcinoma. The aim of this study was to analyze the efficacy of ESD for EGJ cancers, comparing these two adenocarcinomas. Patients and Methods This study included 43 patients who underwent ESD for type II EGJ cancers between 2004 and 2011. Pathological examination of resected specimens confirmed 14 cases of Barrett’s adenocarcinoma and 29 cases of gastric cardia adenocarcinoma. Cutting margins on the oral side were placed 1 cm from the squamocolumnar junction, or 1 cm away from the slight elevation that is an endoscopic sign of subsquamous carcinoma extension. Clinical outcomes, prevalence and length of subsquamous carcinoma extension, and long-term outcomes were compared between these two types of adenocarcinoma. Results No significant differences in clinical outcomes were found between these two types of adenocarcinoma (en bloc, 100 % versus 100 %; complete, 100 % versus 89.7 %; curative, 85.7 % versus 75.9 %). No serious adverse events were encountered. The prevalence of subsquamous carcinoma extension was significantly higher in Barrett’s adenocarcinoma compared with gastric cardia adenocarcinoma. Local and distant recurrence were not observed in any cases with curative resection during the follow-up period (1.6 – 87.6 months). Conclusion ESD for EGJ cancers, including both Barrett’s adenocarcinoma and gastric cardia adenocarcinoma, was efficient and useful. ESD with a 1 cm safety margin may be acceptable for EGJ cancers.

Background and aims Appropriate influenza vaccination is important for patients with inflammatory bowel disease under immunosuppressive therapy. The purpose of this study was to evaluate the influence of immunosuppressive therapy on the immune response to the trivalent influenza vaccine in adult patients with inflammatory bowel disease. Methods In this cohort study, 91 participants received a single dose of influenza vaccine for the 2010/2011 season. Serum samples were collected at 3 different times (pre-vaccination, 3 weeks post-vaccination, and after flu season) to measure hemagglutination inhibition antibody titers. Immune responses were compared based on immunosuppressive therapy. Results Among the 88 subjects who completed the study, the influenza vaccine induced a more than 4-fold increase in the mean antibody level for all flu strains. The overall seroprotection proportion (post-vaccination titer ≥ 1:40) was 81% for H1N1, 61% for H3N2, and 86% for B. Treatment with an immunomodulator reduced the immune response to the H1N1 strain (OR = 0.20, p = 0.01), and treatment with infliximab reduced the immune response to the other strains (H3N2 strain: OR = 0.37, p = 0.02; B strain: OR = 0.18, p = 0.03). Combination therapy with azathioprine/6-mercaptopurine and infliximab significantly inhibited the immune response to H1N1 (OR = 0.056, p = 0.02). Conclusions Infliximab and/or immunomodulators inhibit immune responses to some strains of trivalent influenza vaccination in adults with inflammatory bowel disease. For optimization of the trivalent influenza vaccination for patients with adult inflammatory bowel disease treated with immunosuppressive agents, establishing an effective vaccination method is crucial. * Abbreviations : AZA : azathioprine CAI : clinical activity index CD : Crohn's disease CDAI : Crohn's disease activity index CI : confidence interval GMT : geometric mean titer HAI : hemagglutination inhibition IFX : infliximab IS : group immunosuppressive group 6MP : 6-mercaptopurine NIS : group non-immunosuppressive group OR : odds ratio SD : standard deviation UC : ulcerative colitis WHO : World Health Organization

The aim of this study was to investigate the efficacy of rikkunshito (RKT), a traditional Japanese medicine, combined with proton pump inhibitor (PPI) in patients with PPI-refractory non-erosive reflux disease (NERD). Patients with PPI-refractory NERD (n = 242) were randomly assigned to the RKT group [rabeprazole (10 mg/day) + RKT (7.5 g/t.i.d.) for 8 weeks] or the placebo group (rabeprazole + placebo). After the 4- and 8-week treatments, we assessed symptoms and quality of life (QOL) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG), Gastrointestinal Symptom Rating Scale (GSRS), and Short-Form Health Survey-8 (SF-8). There were no significant differences in FSSG and GSRS score improvement between these groups after the 4- and 8-week treatments. The mental component summary (MCS) scores of the SF-8 improved more in the RKT group (from 45.8 ± 8.1 to 48.5 ± 7.4) than in the placebo group (from 47.7 ± 7.1 to 48.4 ± 7.5) after the 4-week treatment (P

OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users.

Acute kidney injury (AKI) and acute hyperglycemia are associated with unfavorable outcomes. The impact of acute hyperglycemia on the development of AKI after acute myocardial infarction (AMI), however, remains unclear. This study was undertaken to assess the relationship between admission glucose and incidence of AKI after AMI.This study consisted of 760 patients with AMI admitted to the National Cerebral and Cardiovascular Center within 48h after symptom onset. Blood sample was obtained on admission and repeated sampling was done at least every 1 or 2 days during the first week. AKI was diagnosed as increase in serum creatinine ≥0.3mg/dl or ≥50% within any 48h. Ninety-six patients (13%) had AKI during hospitalization for AMI, and these patients had higher in-hospital mortality than those without AKI (25% vs. 3%, P0.001). Patients with AKI had higher plasma glucose (PG) on admission than those without (222±105mg/dl vs. 166±69mg/dl, P0.001). The incidence of AKI increased as admission PG rose: 7% with PG120mg/dl; 9% with PG 120-160mg/dl; 11% with PG 160-200mg/dl; and 28% with PG200mg/dl (P0.01). On multivariate analysis admission PG was an independent predictor of AKI (odds ratio, 1.10; 95% confidence interval: 1.03-1.18, P=0.02).Admission hyperglycemia might have contributed to the development of AKI in patients with AMI.

A 78-year-old Japanese woman presented with anemia. Oral double-balloon endoscopy (DBE) detected multiple ulcerative lesions covered with coagula extending up to approximately 20 cm from the mid-jejunum. Based on the histopathological findings, the patient's condition was diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma of the small intestine. During the second DBE examination, a small intestinal perforation occurred in one of the ulcerative lesions, and an emergency segmental small intestinal resection was performed. The present case suggests that in MALT lymphoma, intestinal wall fragility may lead to perforation even though the lesion may appear to be a superficial ulcer on endoscopy.

Background and Aim Until the approval of patency capsule, capsule endoscopy (CE) has not been routinely applied for the diagnosis of Crohn's disease (CD) in Japan. We aimed to survey current situation of CE use for patients with CD in Japan. Methods The nationwide survey of 40 Japanese institutions identified 94 patients with established CD (eCD) and 80 patients with suspected CD (sCD), who were examined by CE. Types and positive rates of mucosal injury under CE and capsule retention rate were investigated. In sCD, final diagnosis after CE was also analyzed. Results Patients with eCD comprised 82 patients of ileitis or ileocolitis type, while 12 patients had CD of colitis type. CE identified mucosal injuries in 83 of 94 patients. Eight of 12 patients with eCD of colitis type had ileal lesions under CE, thereby being reclassified as ileocolitis type. In patients with sCD, CE detected mucosal injuries in 58 patients. Linear ulceration and cobblestone appearance were depicted in 22 and 3 patients, respectively, thereby resulting in established diagnosis of CD in 23 patients. Mucosal lesion was not found in 22 patients with sCD, who were diagnosed as not having CD. Capsule retention rate was not statistically different between patients with eCD and those with sCD (7.4% vs 6.3%, P = 1.0). Conclusions CE is useful for the evaluation of small bowel mucosal injuries in Japanese patients with sCD and eCD. Possible intestinal stricture needs to be carefully evaluated before CE even in patients with sCD.

Eosinophilic esophagitis (EoE) is diagnosed on the basis of the presence of dysphagia and intraepithelial eosinophilic infiltration of ≥15 cells per high-power field; nevertheless, it is important to identify the endoscopic findings of EoE in general practice. EoE should be distinguished from gastroesophageal reflux disease (GERD); however, the associations between EoE and GERD are controversial. Herein, we aimed to determine the prevalence of EoE-like endoscopic findings and associations between an EoE-like endoscopic appearance and erosive esophagitis. Prospective endoscopic examination was performed in 804 consecutive cases. Cases with EoE-like endoscopic findings such as furrows, rings, white exudate, stricture, and mucosal tearing were examined by esophageal biopsy. Erosive esophagitis, hiatal hernia, atrophic gastritis, and gastroesophageal flap valve were assessed endoscopically, and clinical data, including age, gender, smoking and drinking habits, and presence of allergic diseases and symptoms such as dysphagia and heartburn, were analyzed. Of the 804 cases, 36 (4.5 %) showed an EoE-like endoscopic appearance, and 80 (10 %) had erosive esophagitis. Among the 36 cases with an EoE-like appearance, only 4 (0.5 %) showed significant esophageal eosinophilic infiltration with erosive esophagitis in 3 cases. Further, 28 % of the patients with erosive esophagitis had an EoE-like endoscopic appearance, while 61 % of those with an EoE-like endoscopic appearance had erosive esophagitis. There were no significant differences between the clinical characteristics and other endoscopic findings in cases of an EoE-like endoscopic appearance and erosive esophagitis. Erosive esophagitis and an EoE-like endoscopic appearance frequently showed overlapping features; thus, we believe they might have common pathogenic factors.

Treatment with kampo, the Japanese traditional medicine, is a form of pharmacological therapy that combines modern Western and traditional Asian medical practices. In Japan, various traditional medicines are often combined with Western medicines and prescribed for patients with diseases such as gastroesophageal reflux disease, functional dyspepsia, chronic gastritis, irritable bowel syndrome, and post-operative ileus. Based on numerous past observations, Japanese traditional medicines are thought to be particularly useful in the treatment of medically unexplained physical symptoms such as nausea, abdominal discomfort, and anorexia. However, the detailed mechanism by which they mediate their pharmacological action is yet unknown. In addition, the clinical evidence to support their use is insufficient. This review focuses on the basic evidence of the pharmacological action and the clinical efficacies of kampo medicines accumulated over several past decades. In addition, we introduce both the current novel insights into kampo medicines and the therapeutic approach employed when they are used to treat various disorders of the gastrointestinal tract.

There is strong evidence of a bidirectional relationship between gastroesophageal reflux disease and sleep disturbances. Gastroesophageal reflux (GER) events during the night result in sleep disturbances that include difficulty in falling asleep, sleep fragmentation, and early morning awakenings. In addition, sleep deprivation per se induces hyperalgesia of the esophageal mucosa in response to acid. Treatment includes lifestyle modifications, proton-pump inhibitors (PPIs), γ-aminobutyric acidB agonists, hypnotics, and antireflux surgery. Among these, PPIs are considered first-line treatment for the control of nighttime gastric acid secretion; however, the timing and dosing of PPI administration should be individualized for each patient.

Background The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. Patients and Methods This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0–25%, group B: 26–50%, group C: 51–75%, and group D: 76–100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group. Results Regarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H. pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H. pylori infection, in group D. Conclusion High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia.

The patient was a 40-year-old man who had suffered from Crohn's disease (CD) for 19 years and developed an intractable perianal fistula and two strictures in the small bowel. Dilatation of the two strictures using double-balloon endoscopy did not improve the subileus symptoms. An anal canal adenocarcinoma was also detected using double-balloon endoscopy. The ileum and rectoperianal area were partially resected, and a precise immunohistochemical pathologic assessment revealed that all three lesions were fistula-associated adenocarcinomas. Accumulating endoscopic findings of CD-associated cancer and precise pathologic diagnostic findings will help to establish a suitable surveillance method.

Background: Nighttime acid reflux that influences refractory symptoms is strongly associated with sleep disturbances. The aim of this study was to examine the associations between sleep disturbances and refractory gastroesophageal reflux disease (GERD) symptoms in patients receiving once daily proton pump inhibitors (PPI) and the efficacy of twice-daily rabeprazole treatment. Method: In a multicenter survey, 433 GERD patients receiving once-daily PPI treatment completed a self-report questionnaire that included the Frequency Scale for the Symptoms of GERD (FSSG) and questions about sleep disturbances. Study cases were defined as patients with an FSSG score ≥8. Of the 222 study cases, 106 individuals received rabeprazole 10 mg twice daily for 4-8 weeks. Results: Of the 433 subjects, 222 patients revealed FSSG scores of ≥8. Use of a half dose of PPI was associated with such cases. PPI-refractory symptoms were found in 46% of patients with standard-dose PPI treatment. Nighttime symptoms (OR = 2.56), daytime sleepiness (OR = 1.64), and poorer sleep quality (OR = 1.67) were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment significantly improved FSSG scores and sleep disturbances. Conclusion: About half of the GERD patients receiving once-daily standard-dose PPI treatment had refractory GERD symptoms. Sleep disturbances were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment was effective in such cases.

Background Several studies have reported a significant association between sleep disturbance and inflammatory bowel disease (IBD). The aim of the present study is to compare the clinical characteristics and the health-related quality of life (HR-QOL) of Japanese IBD patients with or without sleep disturbances, and to investigate the risk factors for disease flare in these patients. Methods IBD patients were asked to complete a self-administered questionnaire including the Pittsburg sleep quality index and the 8-item short-form health survey. The information about disease flare within 1 year from enrollment in the study was analyzed with a multiple logistic regression model to identify risk factors for IBD flare-ups. Results The prevalence of sleep disturbances was 44.1 % (60 out of 136 IBD patients). Use of sleep medications was significantly higher in IBD patients with sleep disturbances whereas use of immuno modulators was significantly higher in IBD patients without sleep disturbances. The scores from all HR-QOL domains were significantly lower in patients with sleep disturbances than in patients without sleep disturbances. Fifty-one patients (37.5 %) had disease flare within 1 year from enrollment in the study and sleep disturbances were identified as a significant risk factor for disease flare (OR 3.09, 95 % CI 1.47–6.43). Conclusions Our results indicate that sleep disturbances are common in Japanese IBD patients and are associated with poorer HR-QOL. Since the presence of sleep disturbances is a significant risk factor for IBD flare-ups, we encourage physicians to perform a careful examination of sleep disturbances in IBD patients.

Background and study aim: The incidence of stricture formation caused by endoscopic submucosal dissection (ESD) for widespread lesions is high, and stricture formation can reduce quality of life. We evaluated the prophylactic efficacy of hybrid therapy using a locoregional steroid injection and polyglycolic acid (PGA) sheets with fibrin glue to prevent stricture formation after esophageal ESD in high risk patients in whom we predicted stricture formation would be difficult to prevent with a single prophylactic steroid injection. Methods: Ten patients who underwent esophageal ESD were enrolled (entire-circumference: n = 6; sub-circumference, more than 5/6 of the circumference: n = 4). A single locoregional steroid injection and PGA sheets with fibrin glue were used after ESD. We evaluated the incidence of stricture formation, the number of endoscopic balloon dilation (EBD) procedures needed to treat the stricture formation, and adverse events of the therapy. Results: Esophageal stricture formation occurred in 50.0 % of patients (5/10) (median EBD sessions 0.5, range 0 – 16). Subanalysis showed that stricture formation occurred in 37.5 % of patients (3/8) excluded the lesions located near a previous scar from ESD or surgical anastomosis site (median EBD sessions 0, range 0 – 4). Conclusion: Hybrid therapy using a locoregional steroid injection and PGA sheets with fibrin glue may have the potential to prevent esophageal stricture formation after esophageal ESD in high risk patients.

Background & Aims It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. Methods We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. Results During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%–5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%–8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%–14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%–20.4%) (P = .26). Conclusions In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.