Masahito Aimi

Case-control study of association of eosinophilic gastrointestinal disorders with Helicobacter pylori infection in Japan

Recent studies have suggested that decrease in Helicobacter pylori infection may predispose to allergic diseases. However, there are few reports of the relationships of eosinophilic gastrointestinal disorders (EGIDs), especially eosinophilic gastroenteritis (EGE), with H. pylori infection. We investigated the possible influence of H. pylori infection on EGIDs in Japanese patients. We performed a case-control study to investigate the prevalence of H. pylori infection in patients with EGIDs. Eighteen with eosinophilic esophagitis (EoE) and 22 with EGE were enrolled. For each patient, 3 age- and gender-matched normal controls (n = 120) were randomly selected from a population who received a medical check-up between April 2010 and December 2011 at the Shimane Institute of Health Science. The mean ages of the EoE and EGE patients were 50.9 ± 17 and 49.2 ± 20 years, respectively. Males were more frequently seen in the EoE group, while there was no significant gender difference in regard to EGE. Of the patients with EoE, 22.3% were infected with H. pylori, as compared to 55.5% of their age- and sex-matched normal controls. The odds ratio for EoE patients to have an H. pylori infection was 0.22 (p<0.05). In addition, 22.7% of the patients with EGE and 48.5% of their matched controls were infected with H. pylori, with odds ratio for EGE patients to have an H. pylori infection shown to be 0.31 (p<0.05). In conclusion, the prevalence of H. pylori infection was significantly lower in EGE and EoE patients in Japan as compared to normal control subjects.

Prevalence of gastroesophageal reflux disease in children, adults, and elderly in the same community.

The prevalence of gastroesophageal reflux disease (GERD) in adults is increasing in Japan as well as worldwide likely due to increasing obesity and the decreasing rate of Helicobacter pylori infection. However, data regarding the prevalence of GERD in children and adolescents in Japan are lacking. We investigated the prevalence of GERD in children, adults, and elderly living in the same community.

Clinical features of eosinophilic esophagitis: differences between Asian and Western populations.

The prevalence and incidence of eosinophilic esophagitis (EoE) have been rapidly increasing in Western countries. It is thought to be more common among Caucasians than other racial or ethnic groups, but epidemiological studies have not been fully evaluated in Asian populations, and its clinical manifestation is rarely documented. In this review, recent reports regarding EoE in Asian countries have been collected, and differences in the clinical features, including symptoms and endoscopic findings, between Asian and Western populations have been evaluated. In Asia, EoE is still much less prevalent than in Western countries. Baseline values for average age, male/female ratio, and personal history of allergic disease were comparable to those in Western populations. Predominant symptoms were dysphagia, and food impaction was extremely rare among Asian patients. Although the frequency of abnormal endoscopic findings varies among studies, over 90% of patients with EoE have shown abnormal findings such as linear furrow, which is the most common findings, in recent prospective studies in Asia. There are few reports regarding the treatment of EoE and no prospective studies evaluating drugs or elimination diet in patient with EoE have been reported in Asia. Overall, EoE had similar clinical characteristics in Asian populations. Because the incidence of EoE could increase in the future with the increase in allergic disorders in Asian countries, large‐scale, nationwide prospective studies should be performed to more fully understand the epidemiology and pathophysiology of EoE in Asian populations.

Specific locations of linear furrows in patients with esophageal eosinophilia

Linear furrows are the most frequently found endoscopic abnormality in patients with esophageal eosinophilia (EE); however, the precise endoscopic features remain to be fully elucidated. Here, we aimed to clarify the endoscopic features of EE, essential for the diagnosis of eosinophilic esophagitis (EoE), by focusing on the specific locations of linear furrows in a Japanese population.

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett’s esophagus

Crosstalk between the Notch signaling pathway and Caudal-related homeobox 2 (Cdx2) has important roles in the development of Barrett’s esophagus (BE). We investigated the expression and function of the Notch signaling ligand Delta-like 1 (Dll1) during the development of BE. We determined the expression levels of Dll1 and intracellular signaling molecules related to Notch signaling ((Notch1, Hairy/enhancer of split 1 (Hes1), and Atonal homolog 1 (ATOH1)) in human esophageal squamous and Barrett’s epithelium samples. Next, those expression levels in esophageal squamous cells (Het-1A) and Barrett’s esophageal cells (CP-A and BAR-T) following stimulation with either bile acids or gamma-secretase inhibitor were investigated. Finally, changes in those expression levels following transfection of a Cdx2 or Dll1 expression vector into Het-1A cells were examined. In addition, changes in those expression levels following knockdown of Cdx2 or Dll1 in CP-A cells were also examined. Dll1 was found to be upregulated and localized in the cell membrane and cytoplasm in BE. Bile acids enhanced cytoplasmic expression of Dll1 in CP-A cells, while cleaved Notch1 expression did not change, suggesting lack of a Dll1 agonistic effect on Notch signaling. Cells transfected with Cdx2 revealed significantly enhanced Dll1, while forced expression of Dll1 enhanced ATOH1, Cdx2, and MUC2 expression levels. Nevertheless, enhanced Dll1 did not induce Hes1 expression, suggesting that Dll1 may primarily function as an intracellular signaling molecule and not a Notch agonistic ligand in the canonical pathway. In addition, knockdown of Cdx2 completely abrogated any increase in Dll1 expression upon treatment with bile acids. Our results revealed a novel function of Dll1: facilitation of intestinal metaplasia in conjunction with Cdx2 expression. Furthermore, they suggest that intracellular induction of Dll1 expression in esophageal epithelial cells due to Cdx2 induction in response to bile acids has important roles in BE development.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.

Intra-gastric pH following single oral administrations of rabeprazole and esomeprazole: double-blind cross-over comparison

Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.

Effect of Timing of Proton Pump Inhibitor Administration on Acid Suppression.

Background: Esomeprazole has been reported to show a strong acid suppression following preprandial as compared to postprandial administration, though no known study has compared the acid suppressing effects of other proton pump inhibitors between those administrations. The aim of this study was to compare intragastric pH levels following pre- and postprandial administrations of rabeprazole and esomeprazole. Methods: In 15 Helicobacter pylori-negative healthy volunteers, we measured intragastric pH after 7 days of pre- and postprandial administrations of rabeprazole (10 mg) or esomeprazole (20 mg) using a 5-way crossover design. Results: Preprandial administration of esomeprazole showed stronger acid suppression than postprandial administration. The values for percent time at pH >4.0 over a 24-hour period increased from 45.3% with postprandial administration of esomeprazole to 54.4% with preprandial administration, while the percent time at pH >4.0 during daytime was increased to a greater extent from 51.4 to 66.5% with preprandial administration (p = 0.05). On the other hand, the acid suppressing effect of rabeprazole was not influenced by the timing of administration. Conclusions: The acid suppressing effect of esomeprazole is influenced by administration timing. In contrast, the acid suppressing effect of rabeprazole is not augmented by preprandial administration.

Pathophysiology of Barrett's Esophagus-Associated Neoplasia: Circumferential Spatial Predilection

The prevalence rates of Barretts esophagus (BE) and esophageal adenocarcinoma (EAC) arising from BE show striking geographic patterns as they are much more common in Western as compared with Asian countries. However, recent epidemiological studies indicate that the number of patients with BE and EAC are gradually increasing in Asia including Japan, corresponding to the increase in prevalence of gastroesophageal reflux disease (GERD). Because the prognosis of patients with advanced-stage EAC remains poor, early detection of neoplastic lesion in those with BE has led to recent interest in effective treatment. Several promising studies have revealed that early neoplasia in BE is mainly located in the right anterior wall of the distal esophagus. Interestingly, this endoscopic characteristic has been found in both Western and Japanese populations. Potential pathophysiologic explanations underlying the circumferential distribution of neoplasia in BE include a nonuniform asymmetric distribution of esophageal acid exposure, with a tendency toward mucosal acid-related injury on the right side of the esophageal wall in patients with GERD, and the functional structure of the lower esophageal sphincter. Findings of the present study should improve lesion detection and aid in developing a target biopsy protocol for surveillance of BE.

Isolated Superior Mesenteric Artery Dissection with Small Intestine Ischemia

Superior mesenteric artery (SMA) dissection without aortic dissection is a rare condition, and its diagnosis is considered to be difficult. Intestinal infarction is a severe complication of the disease, which may require resection of the intestine. We present a case of isolated SMA dissection. A 53-year-old man experienced sudden pain in the abdomen while playing Japanese pinball and was admitted to our hospital due to acute abdominal symptoms of uncertain cause. Enhanced CT revealed a defect of the root of the SMA, while angiography and intravascular ultrasound findings showed dissection of the SMA wall. Conservative treatment was chosen at the time, while a part of the small intestine was eventually resected because of progressive ischemia. Although SMA dissection is a rare occurrence in cases with acute abdominal symptoms, awareness of the condition is important for differential diagnosis.