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Background: The prevalence of gastroesophageal reflux disease (GERD) has increased in Japan since the end of the 20th century due to changes in environmental factors, such as a decreased infection rate of Helicobacter pylori and increased ability of acid secretion in the Japanese population. In 2013, the Japanese health insurance system started to cover eradication treatment for all patients infected with H. pylori to prevent gastric cancer, suggesting we may soon be able to completely eradicate this infection in Japan. Re-clarification of the clinical characteristics of GERD in Japan is therefore required in time covering the eradication for all patients infected with H. pylori., Summary: In Japan, more than half of GERD patients exhibit non-erosive reflux disease, and a majority of erosive esophagitis (RE) cases have mild severity of GERD (Los Angeles classification of grades A and B). The prevalence of RE in H. pylori-positive patients is relatively low (4.1%) compared to the general Japanese population (7.6-10.6%). In multivariate analysis to evaluate a risk of RE development, a risk in H. pylori-positive patients is elevated in those with mild gastric mucosal atrophy (C-I and C-II according to the Kimura-Takemoto classification, OR 12.14, 95% CI 1.28-115.26, p = 0.03) or with hiatal hernia (OR 5.24, 95% CI 1.80-15.22, p < 0.01). Here, we provide a comprehensive review of GERD in Japan, including associations between GERD and H. pylori infection, low-dose-aspirin-induced GERD, and pharmacological treatment for GERD., Key Messages: The recent decrease in the rate of H. pylori infection and increase in the proportion of elderly persons might have increased the prevalence of GERD in Japan., (© 2016 S. Karger AG, Basel.)

Background and Aim: Spinal kyphotic deformity occasionally results in gastroesophageal reflux disease (GERD). The effects of acid reflux on the esophagus in kyphotic patients are unclear, however, and it is unknown whether acid reflux, endoscopic GERD, and reflux-related symptoms improve following surgical spinal correction in these patients. Herein, we investigated the characteristics of GERD in kyphotic patients and the improvement in GERD following surgical correction., Methods: In 48 patients with severe kyphotic deformity scheduled for surgical spinal correction, we conducted esophagogastroduodenoscopy, 24-h pH monitoring and three questionnaire surveys, including the frequency scale for the symptoms of GERD (FSSG). We repeated these measurements after surgical correction and compared pre- and post-surgery values., Results: Of 48 patients, 70.8% [95% CI: 55.9-83.0%, 34/48] had endoscopically evaluated esophageal mucosal injury. Regarding pH before surgery, 64.9% (CI: 47.5-79.8%, 24/37) had abnormal acid reflux (intraesophageal pH < 4 more than 5% of the time). FSSG score was significantly associated with the severity of GERD, and the positive rate was 52.6% (CI: 35.8-69.0%, 20/38). Following surgical correction, esophageal mucosal injury improved endoscopically in 90% of patients, and median total FSSG score significantly decreased from 8 (0-30) to 5 (0-19) (P = 0.005). Regarding pH after surgery, prevalence of abnormal acid reflux decreased from 66.7% (95% CI: 41.0-86.7%) to 33.3% (95% CI: 13.3-59.0%) (P = 0.045)., Conclusion: Surgical spinal correction in kyphosis patients improves not only kyphotic deformity-related disorders but also esophageal mucosal injury, abnormal acid reflux, and reflux-related symptoms., (© 2015 Japan Gastroenterological Endoscopy Society.)

Background: When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition., Methods: In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens., Results: Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384)., Conclusion: Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.

Background: In esophagus whether antiplatelet drugs, such as low-dose aspirin (LDA) and clopidogrel, induce mucosal injury by pH changes or by acid reflux is unclear. We designed to clarify which mechanism was responsible., Methods: In study 1, 80 patients taking LDA and 80 age- and sex-matched subjects who underwent endoscopy for dyspeptic symptoms or for a health check-up were evaluated the endoscopic incidence of esophageal mucosal injury and severity. In study 2, 35 healthy subjects were treated with LDA 100 mg (regimen A), and then 20 randomly selected subjects were dosed clopidogrel 75 mg (regimen C), LDA/clopidogrel (regimen AC), or LDA/clopidogrel/rabeprazole 10 mg for 7 days. Subjects underwent endoscopy and 24-hour pH measurements on day 7., Results: In study 1, the prevalence of esophageal injury in LDA patients was 40.0%, significantly higher than in non-LDA subjects (25.0%, p = 0.042). In study 2, significant increases in incidence of injury were observed with regimens A (45.8%) and AC (50.0%), but not with C (20.0%), on day 7. Among subjects in whom pH was >5.0 and <4.0 for less than 40% of time, none developed esophageal injury., Conclusions: LDA caused esophageal injury in half of patients and volunteers. Acid-inhibitory drugs effectively prevented the development of LDA-induced, not clopidogrel, esophageal injury., (Copyright © 2013 S. Karger AG, Basel.)

Background and Aim: Aspirin enjoys widespread use as an antithrombotic drug, but such ubiquity also increases the risk of gastrointestinal mucosal injury. Recent studies have shown that aspirin can also induce esophageal mucosal injury. We resolved to determine the intragastric pH value necessary to prevent aspirin-induced esophageal mucosal injury., Methods: 15 healthy Japanese volunteers were dosed for 7 days in a four-way random crossover trial with 100 mg entero-coated type aspirin only once daily, 100 mg aspirin + 20 mg famotidine twice daily, 15 mg lansoprazole once daily, or 10 mg rabeprazole once daily. All subjects underwent endoscopy and intragastric pH monitoring on day 7., Results: 7 individuals (46.7%) developed esophageal mucosal injury when ingesting aspirin alone. The incidence of esophageal mucosal injury was reduced however with concomitant dosing of aspirin and famotidine (26.6%; p = 0.193), lansoprazole (0%; p = 0.004), and rabeprazole (6.7%; p = 0.019). Among individuals for whom mean 24-h pH was >5.0 and who experienced pH <4.0 less than 40% of the time, none developed aspirin-induced esophageal mucosal injury., Conclusion: Acid inhibition achieved with a half-dose of a proton pump inhibitor effectively prevented development of aspirin-induced esophageal mucosal injury, whereas a standard dose of a histamine-2-receptor antagonist failed to achieve the same results., (Copyright © 2011 S. Karger AG, Basel.)

Aim: To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment., Methods: We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ: 10 mg or 20 mg od, 20 mg bid, or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14., Results: With increased dosages and frequency of administration of RPZ, median intragastric pH significantly increased, and FSSG scores significantly decreased. With RPZ 10 mg qid, potent acid inhibition was attained throughout 24 h. However, five subjects were refractory to RPZ 10 mg qid, although the median intragastric pH in these subjects (6.6, range: 6.2-7.1) was similar to that in the remaining five responsive subjects (6.5, range: 5.3-7.3). With baseline RPZ 10 mg od, FSSG scores in responsive patients improved by > 30%, whereas there was no significant decrease in the resistant group., Conclusion: NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

Background: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels. Methods: Eleven healthy volunteers were subjected to 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75 mg alone, vonoprazan 10 mg alone, and vonoprazan 10 mg plus pirenzepine 75 mg administered in a randomized crossover fashion. Results: Median pH 4 holding time ratios (range) achieved with pirenzepine 75 mg, vonoprazan 10 mg, and vonoprazan 10 mg plus pirenzepine 75 mg were 6.9% (2.4–32.8%), 88.4% (54.6–100%), and 84.2% (40.3–100%), respectively. Respective serum gastrin levels were 79 (75–210) pg/ml, 310 (110–870) pg/ml, and 170 (140–930) pg/ml. In cases with hypergastrinemia (gastrin ≥ 200 pg/ml) induced by vonoprazan 10 mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370 to 180 pg/ml (P = 0.028). Conclusion: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (HRA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. Aims: The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. Methods: Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. Results: Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. Conclusion: Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels. [ABSTRACT FROM AUTHOR]