Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value ≥ 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care.

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 mm(2)/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. CONCLUSIONS: Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.

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.

Circumferential distribution and location of Mallory-Weiss tears: recent trends.

BACKGROUND AND STUDY AIMS: Mallory-Weiss tears (MWTs) are not only a common cause of acute nonvariceal gastrointestinal bleeding but also an iatrogenic adverse event related to endoscopic procedures. However, changes in the clinical characteristics and endoscopic features of MWTs over the past decade have not been reported. The aim of this study was to investigate recent trends in the etiology and endoscopic features of MWTs. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with a diagnosis of MWT at our university hospital between August 2003 and September 2013. The information regarding etiology, clinical parameters, endoscopic findings, therapeutic interventions, and outcome was reviewed. RESULTS: A total of 190 patients with MWTs were evaluated. More than half (n = 100) of the cases occurred during endoscopic procedures; cases related to alcohol consumption were less frequent (n = 13). MWTs were most frequently located in the lesser curvature of the stomach and right lateral wall (2 - to 4-o'clock position) of the esophagus, irrespective of the cause. The condition of more than 90 % of the patients (n = 179) was improved by conservative or endoscopic treatment, whereas 11 patients (5.8 %) required blood transfusion. Risk factors for blood transfusion were a longer laceration (odds ratio [OR] 2.3) and a location extending from the esophagus to the stomach (OR 5.3). CONCLUSIONS: MWTs were frequently found on the right lateral wall (2 - to 4-o'clock position) of the esophagus aligned with the lesser curvature of the stomach, irrespective of etiology. Longer lacerations extending from the esophagus to the gastric cardia were associated with an elevated risk for bleeding and requirement for blood transfusion.

Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux. METHODS: Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer. RESULTS: Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time. CONCLUSIONS: Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance. TRIAL REGISTRATION: This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260.

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.

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

BACKGROUND AND AIM: 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. METHODS: We surveyed employees of Shimane University Hospital and a related facility and their families using the Gastroesophageal Reflux Disease Questionnaire (GerdQ) and Izumo Scale instruments with demographic information (age, sex, body height, and body weight) and information regarding concurrent medication being taken for GERD. The presence of GERD was defined as a GerdQ score of ≥ 8. RESULTS: A total of 1859 subjects (771 males, 1088 females; 6-96 years old) were eligible for assessment. The prevalence of GERD in those under 20 years old was 4.4%, which was approximately one third of the rate in adults (11.6%). GERD prevalence was closely associated with obesity in adults, but not in subjects under 20 years old. GERD and other gastrointestinal symptoms frequently overlapped in both adults and younger subjects. CONCLUSION: We found that the prevalence of GERD in subjects under 20 years of age was lower than that in adults and not associated with obesity. Nevertheless, it is important to be aware of symptoms such as heartburn and/or regurgitation when children and adolescents seek routine clinical care.

Association between sleep disturbances and abdominal symptoms.

OBJECTIVE: Although gastroesophageal reflux disease (GERD) is known to cause sleep disturbances, the relationships between other abdominal symptoms and sleep disorders have not been clarified. In the present study, we examined the relationships between daytime sleepiness and various abdominal symptoms in a non-clinical population. METHODS: We enrolled 2,936 subjects who visited Matsue Red Cross Hospital for an annual health check examination during a 10-month consecutive period after excluding those with organic gastrointestinal diseases. The Izumo scale abdominal symptom and Epworth Sleepiness Scale (ESS) questionnaires were employed to evaluate the presence of abdominal symptoms and daytime sleepiness. RESULTS: Among the 2,936 subjects, 233 (7.9%), 254 (8.6%) and 528 (18%) had GERD-like, functional dyspepsia (FD)-like and irritable bowel syndrome (IBS)-like symptoms, respectively. The ESS scores in the subjects with GERD-, FD- and IBS-like symptoms were significantly higher than those observed in the asymptomatic subjects. The subjects with multiple abdominal symptoms tended to have higher ESS scores than those with single symptoms. A multiple logistic regression analysis revealed a younger age and the presence of FD- and IBS-like symptoms to be significant influencing factors for sleep disturbances. CONCLUSION: The presence of FD and IBS symptoms in addition to GERD symptoms exhibits a strong relationship with sleep disturbances from the viewpoint of daytime sleepiness.

Reliability of symptoms and endoscopic findings for diagnosis of esophageal eosinophilia in a Japanese population.

BACKGROUND/AIMS: The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. METHODS: We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. RESULTS: A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). CONCLUSION: EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive.

Effects of mosapride on esophageal motor activity and esophagogastric junction compliance in healthy volunteers.

BACKGROUND: The effects of the prokinetic drug mosapride on esophageal motor activity vary at standard doses. In addition to esophageal motor activities, compliance of the esophagogastric junction (EGJ) is important for prevention of gastroesophageal reflux. However, the effects of mosapride on EGJ compliance have not been reported. Here, we investigated the effects of high-dose mosapride on esophageal motor activities and EGJ compliance. METHODS: Nine healthy volunteers were enrolled in the study. Peristaltic esophageal contraction and lower esophageal sphincter pressures before and after administration of 40 mg mosapride were examined by high resolution esophageal manometry. Esophageal compliance was also investigated by intra-esophageal impedance planimetry (EndoFLIP(®)). RESULTS: High-dose mosapride augmented peristaltic contractions, especially in the distal esophageal segments (P < 0.05). The mean resting lower esophageal sphincter pressure was elevated from 25.0 mmHg before administration to 28.9 mmHg after (P < 0.05). In addition, mosapride significantly reduced EGJ compliance (P < 0.05). CONCLUSIONS: Mosapride at 40 mg augmented esophageal motor activities and reduced EGJ compliance in healthy volunteers.

Continuous imaging of esophagogastric junction in patients with reflux esophagitis using 320-row area detector CT: a feasibility study.

BACKGROUND AND AIM: The function of the lower esophageal sphincter (LES) is evaluated using an esophageal manometric study. However, information regarding the surrounding organs is difficult to obtain with use of a sensor catheter. We investigated the utility of 320-row area detector computed tomography (CT) to evaluate morphological changes of the esophagogastric junction and surrounding organs. METHODS: The study subjects were 18 healthy volunteers and 29 patients with reflux esophagitis (RE). Immediately after swallowing a diluted contrast agent, continuous imaging of the esophagogastric junctional area was performed for 15 s. Using CT images, the presence or absence of esophageal hiatal hernia, His angle before and after swallowing, size of the diaphragmatic hiatus, morphologically identified-LES (MI-LES) length, intraluminal horizontal area of MI-LES during relaxation phase, MI-LES thickness, abdominal esophagus length, subcutaneous fat area, visceral fat area, and esophagogastric junction fat area were evaluated. RESULTS: Analysis of CT images showed more frequent occurrence of hiatal hernia, greater His angle, and a larger diaphragmatic hiatus in patients with severe RE, while the lengths of MI-LES and abdominal esophagus were shorter in those patients. Visceral and esophagogastric junction fat areas tended to be greater in patients with RE. In all subjects, the posterior wall of the MI-LES was thicker than the anterior wall. CONCLUSION: Continuous imaging with 320-row area detector CT is useful to evaluate morphological changes in the esophagogastric junction area in both normal individuals and patients with reflux esophagitis.

Efficacy of pectin solution for preventing gastro-esophageal reflux events in patients with percutaneous endoscopic gastrostomy.

The aim of this study was to determine the efficacy of pectin solution, which increases the viscosity of liquid nutrient, for prevention of gastro-esophageal reflux in comparison with half-solid nutrient. The subjects were 10 elderly patients undergoing percutaneous endoscopic gastrostomy feeding. Twenty-four-hour esophageal multichannel intraluminal impedance and pH testing was performed during intake of half-solid nutrient and a combination of pectin solution and liquid nutrient. During 4 h after delivery, there was no significant difference in the total number of gastro-esophageal reflux events between the feeding of the half-solid nutrient and the combination of pectin solution and liquid nutrient (5.7 ± 1.2 vs 5.3 ± 1.0/4 h). Acidic reflux after delivery of the half-solid nutrient was significantly more frequent than that after delivery of the combination of pectin solution and liquid nutrient (80.7% vs 60.4%, p = 0.018). The incidence of gastro-esophageal reflux reaching the upper portion of the esophagus tended to be higher during delivery of the half-solid nutrient than during delivery of the combination of pectin solution and liquid nutrient (47.4% vs 34.0%, p = 0.153). In conclusion, the usage of pectin solution combined with liquid nutrient is effective for preventing acidic gastro-esophageal reflux and gastro-esophageal reflux reaching the upper portion of the esophagus.

Radially asymmetric gastroesophageal acid reflux in the distal esophagus: examinations with novel pH sensor catheter equipped with 8 pH sensors.

BACKGROUND: Esophageal mucosal breaks in patients with Los Angeles (LA) grade A or B esophagitis are mainly found in the right anterior wall of the distal esophagus. The aim of this study was to reveal radial acid exposure in the distal esophagus and determine whether radial asymmetry of acid exposure is a possible cause of radially asymmetric distribution of the lesions. METHODS: We developed a novel pH sensor catheter using a polyvinyl chloride catheter equipped with 8 antimony pH sensors radially arrayed at the same level. Four healthy volunteers, 5 patients with non-erosive reflux disease (NERD), and 10 with LA grade A or B esophagitis were enrolled. The sensors were set 2 cm above the upper limit of the lower esophageal sphincter, and post-prandial gastroesophageal acid reflux was monitored for 3 h with the subjects in a sitting position. RESULTS: We successfully examined radial acid exposure in the distal esophagus in all subjects using our novel pH sensor catheter. Radial variations of acid exposure in the distal esophagus were not observed in the healthy subjects. In contrast, the patients with NERD and those with reflux esophagitis had radial asymmetric acid exposure that was predominant on the right wall of the distal esophagus. In the majority of patients with reflux esophagitis, the directions of longer acid exposure coincided with the locations of mucosal breaks. CONCLUSIONS: Radial acid exposure could be examined using our novel 8-channel pH sensor catheter. We found that the directions of longer acid exposure were associated with the locations of mucosal breaks.

Influence of Full-body Water Immersion on Esophageal Motor Function and Intragastric Pressure.

BACKGROUND/AIMS: In Japan, it is customary to take a daily bath during which the body is immersed in water to the neck. During full-body immersion, hydrostatic pressure is thought to compress the chest and abdomen, which might influence esophageal motor function and intra-gastric pressure. However, whether water immersion has a significant influence on esophageal motor function or intragastric pressure has not been shown. The aim of this study was to clarify the influence of full-body water immersion on esophageal motor function and intragastric pressure. METHODS: Nine healthy male volunteers (mean age 40.1 ± 2.8 years) were enrolled in this study. Esophageal motor function and intragastric pressure were investigated using a high-resolution 36-channel manometry device. RESULTS: All subjects completed the study protocol. Intragastric pressure increased significantly from 4.2 ± 1.1 to 20.6 ± 1.4 mmHg with full-body water immersion, while the lower esophageal high pressure zone (LEHPZ) value also increased from 20.5 ± 2.2 to 40.4 ± 3.6 mmHg, with the latter being observed regardless of dietary condition. In addition, peak esophageal peristaltic pressure was higher when immersed as compared to standing out of water. CONCLUSIONS: Esophageal motor function and intragastric pressure were altered by full-body water immersion. Furthermore, the pressure gradient between LEHPZ and intragastric pressures was maintained at a high level, and esophageal peristaltic pressure was elevated with immersion.

Diarrhea caused by proton pump inhibitor administration: comparisons among lansoprazole, rabeprazole, and omeprazole.

BACKGROUND: The number of patients who require treatment with proton pump inhibitors (PPIs) is increasing in Japan. One of their adverse effects is diarrhea. OBJECTIVES: We investigated the incidence of diarrhea caused by 3 different PPIs: lansoprazole, rabeprazole, and omeprazole. METHODS: Patients using PPIs for >1 month were enrolled. Enrolled patients recorded daily stool frequency, stool consistency using the Bristol Stool Scale Form, and impaired quality of life caused by diarrhea for 1 month. Their attending physicians described the types and dosages, and duration of PPI administration, as well as other necessary information. RESULTS: A total of 255 patients participated. Mean age of the patients was 70.7 years old. During the 1-month observation period, 3.5% of the patients complained of diarrhea. There was no significant difference for the incidence of diarrhea among the 3 types of PPIs. Furthermore, no correlations between diarrhea and length and dosage of PPI administration were found. CONCLUSIONS: The incidence of diarrhea in patients receiving long-term therapy did not differ among 3 different PPIs. ClinicalTrials.gov identifier: UMIN ID 000005300.