Abstract

Background: More than 50% of non-erosive gastroesophageal reflux disease (NERD) patients have a poor response to proton pump inhibitors (PPIs) treatment. Recently, it was reported that esophageal motility disorder involving a decline in esophageal clearance contributes to refractory for PPIs. However, there was few reports focused to esophageal motility of patients with NERD refractory for PPIs and there is no established strategy for treatment of refractory NERD. Aims: To clarify the characteristic of patients with refractory NERD, we investigated the esophageal function using MII-EM. In addition, we also evaluated the efficacy of rikkunshito which is a gastrointestinal prokinetic agent. Methods: In this study, 24 NERD patients including 15 patients with NERD refractory for PPIs treatment. Refractory NERD was defined as a score of more than 6 points in the QUEST questionnaire after PPI treatment for over than 4 weeks. After wash-out of gastrointestinal-related drugs, all enrolled patients underwent the examinations using MII-EM and then started oral administration of rikkunshito (7.5 g/ day). After rikkunshito treatment for 8 weeks, the examinations using MII-EM was performed again. Also, symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before and 4 weeks / 8 weeks after starting the rikkunshito treatment. Results: At first examination using MII-EM, 71.4% of the refractory NERD patients had peristaltic contraction rate (PC rate) deviating from the standard value (≧80%) and 85.7% of them had a complete bolus transit rate (CBT rate) deviating from the standard value (≧75%). On the other hand, in the 9 patients other than the refractory NERD, the rate of patients with such deviation was 25.0% and 50.0%, respectively. The rate of patients with a resting LES pressure deviating from the standard value was comparable between the two patient groups. Next, we also evaluated the efficacy of rikkunshito in the refractory NERD. Rikkunshito significantly improved the LES residual pressure during swallow from 7.2 ± 5.1 mmHg to 5.2 ± 4.1 mmHg, PC rate from 52.4 ± 34.6% to 75.5 ± 31.1% and CBT rate from 51.5 ± 27.4% to 81.8 ± 16.0%. In assesment of symptoms with GSRS, rikkunshito significantly improved score of acid reflux symptoms, dyspepsia-like symptoms and total gastrointestinal symptoms. Conclusion: These results suggested that the refractory NERD patients had a disorder of esophageal motility and that rikkunshito ameliorated the gastrointestinal symptoms through improvement of the esophageal and LES motility disorder. We propose the application of rikkunshito as a strategy to treat patients with NERD refractory for PPIs.

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