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DNA methylation has been identified as a hallmark of gastric cancer (GC). Identifying genes that are repressed by DNA promoter methylation is essential in providing insights into the molecular pathogenesis of gastric cancer. Using genome-wide methylation studies, we identified that transcription factor forkhead box F2 (FOXF2) was preferentially methylated in gastric cancer. We then investigated the functional significance and clinical implication of FOXF2 in gastric cancer. FOXF2 was silenced in gastric cancer cell lines and cancer tissues by promoter methylation, which was negatively associated with mRNA expression. Ectopic expression of FOXF2 inhibited proliferation, colony formation, G1–S cell-cycle transition, induced apoptosis of gastric cancer cell lines, and suppressed growth of xenograft tumors in nude mice; knockdown of FOXF2 elicited opposing effects. FOXF2 inhibited Wnt signaling by inducing β-catenin protein ubiquitination and degradation independently of GSK-3β. FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation. Multivariate Cox regression analysis identified FOXF2 hypermethylation as an independent prognostic factor of poor survival in early-stage gastric cancer patients. In conclusion, FOXF2 is a critical tumor suppressor in gastric carcinogenesis whose methylation status serves as an independent prognostic factor for gastric cancer patients.Significance: FOXF2-mediated upregulation of the E3 ligase IRF2BPL drives ubiquitylation and degradation of β-catenin in gastric cancer, blunting Wnt signaling and suppressing carcinogenesis. Cancer Res; 78(7); 1643–56. ©2018 AACR.

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: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the small intestine by causing multiple erosions and ulcers. However, to date, no established therapies and prophylactic agents are available to treat such damages. We reviewed the role of intestinal microbiota in NSAID-induced intestinal damage and identified potential therapeutic candidates. Summary: The composition of the intestinal microbiota is an important factor in the pathophysiology of NSAID-induced small intestinal damage. Once mucosal barrier function is disrupted due to NSAID-induced prostaglandin deficiency and mitochondrial malfunction, lipopolysaccharide from luminal gram-negative bacteria and high mobility group box 1 from the injured epithelial cells activate toll-like receptor 4-signaling pathway and nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome; this leads to the release of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. Proton pump inhibitors (PPIs) are often used for the prevention of NSAID-induced injuries to the upper gastrointestinal tract. However, several studies indicate that PPIs may induce dysbiosis, which may exacerbate the NSAID-induced small intestinal damage. Our recent research suggests that probiotics and rebamipide could be used to prevent NSAID-induced small intestinal damage by regulating the intestinal microbiota. Key Messages: Intestinal microbiota plays a key role in NSAID-induced small intestinal damage, and modulating the composition of the intestinal microbiota could be a new therapeutic strategy for treating this damage.

Objective In symptom-dependent diseases such as functional dyspepsia (FD), matching the pattern of epigastric symptoms, including severity, kind, and perception site, between patients and physicians is critical. Additionally, a comprehensive examination of the stomach, duodenum, and pancreas is important for evaluating the origin of such symptoms. Methods FD-specific symptoms (epigastric pain, epigastric burning, early satiety, and postprandial fullness) and other symptoms (regurgitation, nausea, belching, and abdominal bloating) as well as the perception site of the above symptoms were investigated in healthy subjects using a new questionnaire with an illustration of the human body. A total of 114 patients with treatment-resistant dyspeptic symptoms were evaluated for their pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Results A total of 323 subjects (men:women, 216:107; mean age, 52.1 years old) were initially enrolled. Most of the subjects felt the FD-specific symptoms at the epigastrium, while about 20% felt them at other abdominal sites. About 30% of expressed as epigastric symptoms were FD-nonspecific symptoms. At the epigastrium, epigastric pain and epigastric burning were mainly felt at the upper part, and postprandial fullness and early satiety were felt at the lower part. The prevalence of patients with pancreatic exocrine dysfunction was 71% in the postprandial fullness group, 68% in the epigastric pain group, and 82% in the diarrhea group. Conclusion We observed mismatch in the perception site and expression between the epigastric symptoms of healthy subjects and FD-specific symptoms. Postprandial symptoms were often felt at the lower part of the epigastrium, and pancreatic exocrine dysfunction may be involved in the FD symptoms, especially for treatment-resistant dyspepsia patients.

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)

Although endoscopic submucosal dissection (ESD) for expanded-indication lesions of differentiated-type early gastric cancer (EGC) has been widely accepted, no prospective randomized study has been conducted on this subject. This study aimed to evaluate the long-term outcomes of ESD and surgery for expanded-indication lesions of differentiated-type EGC.Between 1997 and 2012, 1500 consecutive patients with EGC were treated in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated the long-term outcomes, risk factors for mortality, and adverse events for patients with expanded-indication lesions of differentiated-type EGC who underwent ESD or surgical treatments.A total of 308 patients with expanded-indication lesions of differentiated-type EGC confirmed by pathologic examination after ESD or surgery met the eligibility criteria. After matching, the 5-year overall survival rate was higher in the ESD group than in the surgery group (97.1% vs 85.8%; P = .01). We also found that surgery was significantly associated with mortality using both the IPTW method (hazard ratio [HR], 10.89; 95% confidence interval [CI], 1.37-86.6; P .01), and Cox analysis (HR, 8.60; 95% CI, 1.11-66.52; P = .04) after matching. Significantly fewer adverse events were associated with ESD than with surgery (6.8% vs 28.4%; P .01). No cause-specific mortality was observed in either group.Our results indicate that ESD might be an alternative treatment modality for expanded-indication lesions of differentiated-type EGC.

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)

Recently, diagnosis of obscure gastrointestinal bleeding (OGIB) has improved greatly due to introduction of capsule endoscopy (CE) and double balloon enteroscopy (DBE). However, the efficacy of CE over DBE in patients with previous OGIB remains unclear. This study aimed to compare, in terms of diagnostic yield, the efficacy of DBE with that of CE in patients with previous OGIB.We enrolled 223 consecutive patients with previous OGIB who were treated between May 2007 and March 2012. We retrospectively evaluated the respective diagnostic yields of CE and DBE in patients with previous OGIB using propensity score-matching analysis. We compared the diagnostic yield of CE with that of DBE.The diagnostic yields were 41.9% in DBE group and 11.6% in CE group, respectively (p .01). On logistic regression analysis, DBE was significantly superior to CE after matching (Odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43-12.6; p .01), even after adjustment for propensity score (OR, 5.65; 95% CI, 1.56?20.5; p .01).Our results indicate that DBE might be more useful and perhaps safer than CE in achieving a positive diagnosis in patients with previous OGIB.

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.

Background & Aims: Microbial molecular products incite intestinal inflammation by activating Toll-like receptors (TLRs) and inflammasomes of the innate immune system. This systemâs contribution to esophageal inflammation is not known. Gram-negative bacteria, which dominate the esophageal microbiome in reflux esophagitis, produce lipopolysaccharide (LPS), a TLR4 ligand. TLR4 signaling produces pro-interleukin (IL)1β, pro-IL18, and NOD-like receptor protein 3 (NLRP3), which prime the NLRP3 inflammasome. Subsequent NLRP3 inflammasome activation cleaves caspase-1, inducing secretion of proinflammatory cytokines and pyroptosis (inflammatory cell death). We explored LPS effects on NLRP3 inflammasome priming and activation in esophageal cells. Methods: We exposed esophageal squamous and Barrettâs epithelial cells to LPS and measured the following: (1) TLR4, pro-IL1β, pro-IL18, and NLRP3 expression; (2) caspase-1 activity; (3) tumor necrosis factor-α, IL8, IL1β, and IL18 secretion; (4) lactate dehydrogenase (LDH) release (a pyroptosis marker); and (5) mitochondrial reactive oxygen species (ROS). As inhibitors, we used acetyl-Tyr-Val-Ala-Asp-CHO for caspase-1, small interfering RNA for NLRP3, and (2-(2,2,6,6,-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride for mitochondrial ROS. Results: Squamous and Barrettâs cells expressed similar levels of TLR4, but LPS induced TLR4 signaling that increased tumor necrosis factor-α and IL8 secretion only in Barrettâs cells. Barrettâs cells treated with LPS showed increased expression of pro-IL18, pro-IL1β, and NLRP3, and increased mitochondrial ROS levels, caspase-1 activity, IL1β and IL18 secretion, and LDH release. Acetyl-Tyr-Val-Ala-Asp-CHO, NLRP3 small interfering RNA, and Mito-TEMPO all blocked LPS-induced IL1β and IL18 secretion and LDH release. Conclusions: In Barrettâs cells, LPS both primes and activates the NLRP3 inflammasome, causing secretion of proinflammatory cytokines and pyroptosis. By triggering molecular events promoting inflammation, the esophageal microbiome might contribute to inflammation-mediated carcinogenesis in Barrettâs esophagus. Keywords: IL1β, Pyroptosis, Esophageal Squamous Cell, GERD, Cytokine

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.

To elucidate the role of autonomic nervous system in functional dyspepsia patients, we examined 24-h heart rate variability: the basal levels, responses after lunch, cold pressor and mental arithmetic tests, and the efficacy of an autonomic drug (tofisopam). The high-frequency component (HF: 0.15–0.40 Hz) and the ratio of HF to the low-frequency component (LF: 0.04–0.15 Hz; LF/HF ratio) were used as indicators of parasympathetic and sympathetic autonomic nervous system function. The HF component in the 24-h, daytime, and nighttime was low in 86.7%, 97.8%, and 66.7% of patients (n = 45) and the LF/HF ratio was high in 51.1%, 73.3%, and 26.6% of patients. Gastrointestinal symptom tended to be severe in patients with autonomic nervous system disorder (p = 0.085). The abnormal response in HF component after lunch occurred in 38.2% (13/34) of patients who revealed a greater tendency towards in indigestion score (p = 0.061). Delays in recovery to the basal autonomic nervous system level after stimulus of the cold pressor and the mental arithmetic tests occurred in parts of patients. Tofisopam partially improved autonomic nervous system dysfunction and abdominal pain/indigestion. Imbalanced autonomic nervous system function and vulnerability for recovery from external stimuli were observed in functional dyspepsia patients, which was associated with dyspeptic symptoms.

Background: Gastrointestinal endoscopy and Helicobacter pylori(H. pylori) eradication therapy are commonly performed even among the elderly population. The aim of this study was to understand the way endoscopists viewed the application of endoscopy and H. pylori eradication in the elderly of East Asian countries. Methods: Self-administered questionnaires containing 13 questions on endoscopy and H. pylori eradication in the elderly were distributed to major institutions in Japan, South Korea, China, Indonesia, and the Philippines. Results: Two hundred and fifteen endoscopists (111 in Japan, 39 in China, 24 in Korea, 21 in Indonesia, and 20 in the Philippines) participated in this study. In the institutions where these endoscopists were associated, around 50% of patients undergoing endoscopy were above the age of 60 years. The participating endoscopists indicated that the necessity of screening esophagogastroduodenoscopy and colonoscopy was lower in populations aged over 81 than the other age groups. They hesitated to perform therapeutic endoscopy, such as endoscopic submucosal dissection or endoscopic retrograde cholangiopancreatography, more often in patients over 85. They also hesitated to perform H. pylori eradication in patients aged over 81, especially in Japan. Conclusion: Endoscopists had significantly different attitudes regarding the indications for screening or therapeutic endoscopy and H. pylori eradication therapy in younger and elderly populations in East Asian countries.

Gastroesophageal reflux disease(GERD) is strongly associated with sleep disturbances. Several studies have shown that gastroesophageal reflux disease is strongly associated with sleep disturbances. Proton pump inhibitor(PPI) therapy improves subjective sleep parameters in GERD patients; however, the effects of this therapy on objective sleep parameters remain controversial. Numerous factors such as stress, lifestyle, and surrounding circumstances affect sleep status in humans, it is hard to examine the direct effect of acid reflux on sleep in patients with GERD. In this paper, we show that acid reflux directly causes sleep disturbances in rats with chronic esophagitis and esomeprazole significantly improved some objective sleep parameters in Japanese GERD patients.