Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Effects of Rikkunshito (TJ-43) on Esophageal Motor Function and Gastroesophageal Reflux.

BACKGROUND/AIMS: Rikkunshito (TJ-43), an herbal medicine, has been demonstrated to relieve gastroesophageal reflux symptoms. However, the effects of TJ-43 on esophageal motor functions have not been fully determined. This double-blind crossover study was performed to investigate the effects of TJ-43 on esophageal motor functions and gastroesophageal reflux. METHODS: The subjects were 10 normal male volunteers. Lower esophageal sphincter pressure and esophageal body peristaltic contractions with and without 1-week administration of TJ-43 were examined in a crossover fashion. Post-prandial gastroesophageal reflux was also determined using a multi-channel impedance pH dual monitor. RESULTS: TJ-43 at a standard dose of 7.5 g/day did not significantly augment esophageal peristaltic contraction pressure measured in the proximal, middle and distal segments of the esophagus, whereas increment of resting lower esophageal sphincter pressure was observed in a supine position. In addition, TJ-43 administration did not decrease post-prandial gastroesophageal acid, non-acid reflux events or accelerate esophageal clearance time. CONCLUSIONS: TJ-43 at a standard dose did not have a significant effect on esophageal motor activity or gastroesophageal reflux in healthy adults.

Efficacy of prokinetic agents in improving bowel preparation for colonoscopy.

BACKGROUND AND AIM: Colonoscopy plays an important role in the diagnosis and treatment of gastrointestinal illness in both Western countries and Japan. However, preparative bowel cleansing for colonoscopy is frequently troublesome for elderly and/or constipated patients, since they must drink larger volumes of lavage solution for adequate cleansing. We investigated the use of prokinetic agents for improving the efficacy and tolerability of bowel cleansing prior to colonoscopy. METHODS: 613 patients were divided into two groups according to oral lavage solution used (polyethylene glycol or magnesium citrate), and were further randomized to receive either vehicle (100 ml water) alone, vehicle with 5 mg mosapride citrate, or vehicle with 50 mg itopride hydrochloride 30 min before administration of lavage solution. Experimental parameters included bowel cleansing quality, times to first defecation and completion of bowel cleansing, and incidence of uncomfortable abdominal symptoms during colonoscopy preparation. RESULTS: Administration of mosapride citrate or itopride hydrochloride prior to oral lavage solution did not significantly improve bowel cleansing quality. However, statistically significantly fewer uncomfortable abdominal symptoms were found in patients who received mosapride citrate or itopride hydrochloride versus vehicle alone. CONCLUSION: Prokinetic agents effectively decreased the incidence of uncomfortable abdominal symptoms experienced during colonoscopy preparation.

Ferucarbotran expands area treated by radiofrequency ablation in rabbit livers.

BACKGROUND AND AIM: Several studies have examined the factors involved with expansion of the coagulation volume following radiofrequency ablation (RFA). Ferucarbotran contains superparamagnetic iron oxide that generates heat in a radiofrequency electric field and may have an effect on the area affected by RFA. We attempted to determine whether ferucarbotran administration expands radiofrequency-ablated volume using a rabbit model. METHODS: A total of 15 male Japanese white rabbits (16 weeks old) were used and divided into three groups of five each. A 1-mL saline solution was given intravenously into a dorsal ear vein in the control group, whereas 1 mL ferucarbotran solution (0.016 mL/kg bodyweight) was given to the common-dose group and 1 mL of a twofold concentrated ferucarbotran solution (0.032 mL/kg bodyweight) was given to the high-dose group. RFA was performed with a cool-tip electrode 4 h after the administration and immediately thereafter the rabbits were killed, and the volume of the ablated area measured using magnetic resonance imaging (MRI). Following the MRI analysis, the rabbit's livers were resected, and the maximum short axis diameter of the ablated area in each was measured. RESULTS: None of the rabbits died during the RFA procedure. The volume of the ablated area estimated on MR images in the ferucarbotran-administered groups was larger than that in the control group. Further, our macroscopic assessment showed that the maximum short axis diameter had a tendency to increase with ferucarbotran administration. CONCLUSION: Ferucarbotran may expand the area treated by RFA.

Nocturnal gastric acid breakthrough during the administration of rabeprazole and ranitidine in Helicobacter pylori-negative subjects: effects of different regimens.

BACKGROUND: Nocturnal gastric acid breakthrough (NAB) is defined as nocturnal intragastric pH less than 4 for more than 1 h during proton pump inhibitor (PPI) administration. A bedtime dose of an H2 receptor antagonist (H2RA) inhibites NAB, but the efficacy of the H2RA decreases with continuous administration. We carried out the present study to investigate the effect of 14-day H2RA administration on NAB. METHODS: Ten male volunteers without Helicobacter pylori infection received four different 14-day regimens of rabeprazole and ranitidine (study a, morning dose of 20 mg rabeprazole; study b, morning dose of 20 mg rabeprazole with a single bedtime dose of 150 mg ranitidine only on the last day; study c, continuous 20 mg morning dose of rabeprazole and 150 mg at bedtime; study d, morning and evening doses of 10 mg rabeprazole). Ambulatory 24-h gastric pH monitoring was conducted on the last day of each regimen. RESULTS: NAB in studies a, b, c, and d was observed in 9, 1, 4, and 4 subjects, respectively, and the longest periods of nocturnal gastric pH at less than 4.0 were 102.5, 14.0, 37.5, and 52.5 min, respectively (study b vs study c, P<0.05). CONCLUSIONS: The continuous inhibitory effect of ranitidine combined with rabeprazole on nocturnal gastric acid secretion declined during 14-day-long administration in H. pylori-negative subjects. Split dosing of rabeprazole was more effective than the single morning dose for inhibiting nocturnal gastric acid secretion.