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Hiroto Miwa,
Kaiyo Takubo,
Tomohiko Shimatani,
Takahisa Furuta,
Tadayuki Oshima,
Junji Tanaka,
Junko Aida,
Masanori Ito,
Susumu Kurosawa,
Takashi Joh,
Tsuneya Wada,
Yasuki Habu,
Yusuke Watanabe, Michio Hongo,
Tsutomu Chiba,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND/AIMS: To examine the differences in esophageal histopathology between non-erosive reflux disease (NERD) and reflux esophagitis (RE), and to investigate whether baseline esophageal histopathology can predict the therapeutic response to proton pump inhibitors (PPIs). METHODS: The subjects comprised 94 patients with NERD (n=71) or mild RE (n=23). Tissue was biopsied from 5 cm above the squamo-columnar junction, and the degree or presence of 9 histopathological markers was assessed. The patients were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. If complete heartburn relief was not achieved, RPZ was increased to 10 mg twice daily for another 2 weeks, and then to 20 mg twice daily for another 2 weeks if heartburn remained. RESULTS: Features of esophageal histopathology 5 cm above the SCJ differed between NERD and RE patients. The esophageal histopathology in patients unresponsive to RPZ was characterized by Protein Gene Product (PGP) 9.5 negativity in those with NERD, and intraepithelial bleeding in those with RE. In addition, the combination of dilated intercellular spaces (DIS) (+)/PGP 9.5(-) was indicative of strong resistance to PPI therapy in NERD patients. CONCLUSIONS: The therapeutic efficacy of PPI can be predicted from the features of biopsied esophageal tissue. Factors predictive of resistance to treatment with PPI are negativity for PGP9.5 in NERD patients and intraepithelial bleeding in RE patients.
Journal of Gastroenterology and Hepatology 09/2012; · 2.87 Impact Factor
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Nihon Naika Gakkai Zasshi 09/2012; 101(9):2690-7.
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Emiko Aizawa,
Yasuhiro Sato,
Takanori Kochiyama,
Naohiro Saito,
Masahiro Izumiyama,
Joe Morishita,
Motoyori Kanazawa,
Keisetsu Shima,
Hajime Mushiake, Michio Hongo,
Shin Fukudo
[show abstract]
[hide abstract]
ABSTRACT: Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions.
We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling.
Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann's area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre-supplementary motor area in subjects with IBS, compared with controls (P = .012).
Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre-supplementary motor area.
Gastroenterology 07/2012; 143(5):1188-98. · 11.68 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: BackgroundSeveral studies have described factors associated with the failure of proton pump inhibitors (PPIs) to effect endoscopic healing
of reflux esophagitis (RE), but few studies have addressed factors promoting PPI-based endoscopic healing. We performed post
hoc analysis of a multicenter prospective cohort of RE patients to identify factors encouraging endoscopic healing of this
disorder.
MethodsPatients with RE received 10 or 20mg rabeprazole for 8weeks, and endoscopic findings before and after treatment were studied.
To evaluate the effects of patient background factors on endoscopic healing, we performed multiple logistic regression analysis
and determined the respective odds ratios (ORs) and 95% confidence intervals (CIs).
ResultsA total of 454 patients who underwent endoscopy at baseline and again at week 8 were included in the analysis. After 8weeks
of treatment, improvement in endoscopic findings was observed in 94.1% (427/454) of patients, and endoscopic healing was seen
in 76.7% (348/454). Multiple logistic regression analysis revealed that a combination of angiotensin II receptor blockers
(ARBs) had a significant positive impact on endoscopic healing (OR 3.9, 95% CI 1.411–10.903), but no significant positive
relationship was seen for other concomitant drugs such as nonsteroidal anti-inflammatory drugs and calcium channel blockers.
Severe RE at baseline (OR 0.365, 95% CI 0.281–0.475) and PPI therapy prior to enrollment (OR 0.154, 95% CI 0.052–0.453) were
found to have significant negative effects on endoscopic healing.
ConclusionsConcomitant use of ARBs may promote endoscopic healing of RE treated with PPIs.
KeywordsReflux esophagitis–Proton pump inhibitor–Angiotensin II receptor blockers–Endoscopic findings
Journal of Gastroenterology 04/2012; 47(3):249-255. · 4.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: BackgroundDespite low gastric acid secretion levels among elderly people and Helicobacter pylori-positive individuals in Japan, many patients suffer from endoscopic relapse of erosive gastroesophageal reflux disease (GERD)
during standard-dose proton pump inhibitor (PPI) maintenance therapy. We aimed to investigate the relapse rate and risk factors
for relapse during long-term PPI therapy in a prospective multicenter study.
MethodsPatients diagnosed endoscopically as having erosive GERD according to the Los Angeles (LA) classification, with remission
under PPI medication, and without mucosal damage in the esophagus, were enrolled and took rabeprazole 10mg/day, the standard
dose in Japan, for up to 104weeks, with endoscopy at weeks 24, 52, 76, and 104; erosive GERD with LA classification grade
A, B, C, or D was defined as relapse.
ResultsThe baseline status of the 191 cases analyzed was: female (34.6%), ≥65years old (50.8%), H. pylori-positive (40.8%), body mass index (BMI) ≥25kg/m2 (35.6%), and hiatus hernia (79.6%). Relapse occurred by week 104 in 21 cases (11%; 12 females, 9 males). Risk factors were
hiatus hernia; severe past erosive GERD (grade C or D); H. pylori-negative; no mucosal atrophy; nonsmoking; and being female and <150cm in height.
ConclusionsThis study revealed the significant risk factors that might be monitored during long-term maintenance therapy to prevent relapse
of GERD.
KeywordsReflux esophagitis-Hiatus hernia-
Helicobacter pylori
-Los Angeles classification
Journal of Gastroenterology 04/2012; 45(12):1193-1200. · 4.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: GoalTo investigate the development of fundic gland polyp (FGP) and gastric hyperplastic polyp (HPP) during long-term proton pump
inhibitor (PPI) therapy and risk factors of each polyp via patient status in a multicenter prospective study.
BackgroundThe risk of developing FGP may increase during long-term PPI therapy. However, the association with PPI-induced hypergastrinemia
is unclear. Helicobacter pylori (Hp) infection (which there is a high rate of in Japan) may influence the development of HPP.
MethodsReflux esophagitis patients on PPI maintenance therapy were enrolled. At baseline, the presence of protruding lesion (gastric
polyps) and mucosal atrophy was examined endoscopically. The serum gastrin level (SGL) and Hp infection status were noted. The patients took rabeprazole 10mg/day for 104weeks and endoscopy was performed at weeks 24,
52, 76, and 104 to check for newly developed FGPs and HPPs. The hazard ratios (HRs) of risk factors were calculated.
Results191 patients were analyzed. The distribution of patients with baseline SGLs (pg/mL) of <200, ≥200 to <400, and ≥400 was 118
(61.8%), 51 (26.7%), and 22 (11.5%), respectively. 78 (40.8%) patients were Hp-positive, and gastric polyps were found in 70 (36.6%) patients. By the end of rabeprazole therapy, 26 (13.6%) and 17 (8.9%)
patients had developed new FGPs and HPPs. In terms of risk factors, Hp-positive was significantly lower (HR=0.288; 95% CI, 0.108–0.764) for FGP while SGL ≥400pg/mL was significantly higher
(HR=4.923; 95% CI, 1.486–16.31) for HPP.
ConclusionDuring long-term PPI therapy, FGP development was associated with absence of Hp infection. Meanwhile, Hp infection and high SGL may influence HPP development.
KeywordsFundic gland polyp-Hyperplastic polyp-Long-term proton pump inhibitor therapy
Journal of Gastroenterology 04/2012; 45(6):618-624. · 4.16 Impact Factor
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[show abstract]
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ABSTRACT: Many questionnaires that assess subjective symptoms or health-related quality of life (HRQOL) have been developed to confirm the efficacy of treatment in patients with gastroesophageal reflux disease (GERD). However, few reports have correlated early improvements in scale scores with predictions of subsequent therapeutic responses. Our aim was to investigate the appropriate timing for evaluating therapeutic response and subsequent changes in symptoms and HRQOL.
This was a post hoc analysis of a multicenter prospective cohort study. A total of 5,279 GERD patients with Frequency Scale for the Symptoms of GERD (FSSG) scores ≥ 8 points at baseline were analyzed. Correlations between HRQOL and FSSG were investigated and logistic regression analysis was performed.
The FSSG scores and HRQOL improvements in responders were significantly greater than in non-responders. Positive correlation between FSSG and HRQOL was observed. Based on the analysis, severity of esophagitis at baseline, complications of hypertension, higher HRQOL mental score at baseline, and higher FSSG score at baseline were predictors of responders. Gastrectomy, complication of insomnia, and prior medication with proton pump inhibitors were predictors of non-responders.
Evaluating patients' symptoms during the fourth week of rabeprazole therapy allows predictions of subsequent changes in subjective symptoms and HRQOL.
Digestion 04/2012; 85(4):282-7. · 2.05 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: BackgroundDespite many reports from Western nations describing endoscopic and symptomatic improvements in patients with reflux esophagitis
(RE) using proton pump inhibitors (PPI), PPI effects on the health-related quality of life (HRQOL), particularly for a dose
duration of less than 8weeks, have not been sufficiently clarified in Japanese RE patients.
MethodsRE patients (n=9,029) in general practice settings took rabeprazole once daily for 8weeks. HRQOL, using the 8-item Short-Form Health
Survey (SF-8™), and symptoms, using a frequency scale for the symptoms of gastroesophageal reflux disease (GERD), were evaluated
at the initiation of therapy (0W), week 4 (4W), and week 8 (8W). Endoscopy was performed at 0 and 8W where possible.
ResultsIn efficacy analysis (n=6,839), the mean±SD values for the physical component summary of the SF-8™ at 0, 4, and 8W were 45.005±7.534, 48.517±6.336,
and 49.328±6.207, respectively, while those for the mental component summary were 46.465±7.743, 49.460±6.470, and 50.388±6.049,
respectively. Significant improvements, compared to 0W, were observed in eight domains and two summary scores at 4W (P<0.001), and further QOL score elevations were seen by 8W. Regarding symptoms, the mean total frequency scale for the symptoms
of GERD (FSSG) scores at 0, 4, and 8W were 16.4±9.8, 7.8±7.4, and 6.0±6.8, respectively. Significant improvements,
compared to 0W, were seen in the total, reflux, and dysmotility scores and in the scores for all 12 items at 4W (P<0.001).
ConclusionsThe score for the HRQOL of RE patients before rabeprazole therapy was below 50 points (the national mean for the general Japanese
population), indicating harmed QOL. Rabeprazole markedly improved the HRQOL at 4W, with recovery to the national mean by
8W. Symptoms had also improved significantly at 4W, with further improvements observed at 8W.
KeywordsRabeprazole–Reflux esophagitis–Quality of life–Symptoms
Journal of Gastroenterology 04/2012; 46(3):297-304. · 4.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: BackgroundAcid suppression induced by rabeprazole 5mg in patients with NERD has not been reported in the literature.
AimsThe objective of this study was to investigate gastroesophageal acid suppression in NERD patients by rabeprazole 5mg and
10mg/day.
MethodsSubjects were grade M (minimal changes) NERD patients. Twenty-two patients not responding to open label antacid therapy entered
a double-blind treatment phase in which rabeprazole 5mg or 10mg/day for four weeks were compared. Twenty-four-hour esophageal
pH monitoring was performed before and on treatment (at week 4) to assess the pharmacodynamic effect of these doses of rabeprazole.
ResultsThe frequency of heartburn episodes and the number of acid reflux episodes in the esophagus corresponded well in grade M NERD
patients (r=0.44, P=0.042). Median percentage of time at pH<4 was 4.3% before treatment and 1.1% on treatment with rabeprazole 5mg (change
from baseline; −2.5%), whereas the median percentage of time at pH<4 in the rabeprazole 10mg group was 7.4% before treatment
and 0.5% on treatment (change from baseline; −6.6%). Likewise, treatment-related changes of median number of reflux episodes
were −18.0 with rabeprazole 5mg and −44.0 with rabeprazole 10mg. For each esophageal pH data, no significant differences
were observed between the two groups (P=0.377, P=0.077).
ConclusionsAdministration of 5 mg and 10mg rabeprazole sufficiently inhibited pathological gastroesophageal acid reflux and relieved
heartburn episodes in NERD patients who did not respond to an antacid. Further investigation would be necessary to determine
proper usage of the two doses.
Keywords24-hour esophageal pH monitoring–Rabeprazole–Nonerosive reflux disease–Minimal changes
Digestive Diseases and Sciences 04/2012; 56(8):2333-2342. · 2.12 Impact Factor
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Hiroto Miwa,
Uday C Ghoshal,
Sutep Gonlachanvit,
Kok-Ann Gwee,
Tiing-Leong Ang,
Full-Young Chang,
Kwong Ming Fock, Michio Hongo,
Xiaohua Hou,
Udom Kachintorn, [......],
Kwang Jae Lee,
Ching-Liang Lu,
Sanjiv Mahadeva,
Soichiro Miura,
Hyojin Park,
Poong-Lyul Rhee,
Kentaro Sugano,
Ratha-Korn Vilaichone,
Benjamin Cy Wong,
Young-Tae Bak
[show abstract]
[hide abstract]
ABSTRACT: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia.
Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group.
Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added.
This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.
Journal of neurogastroenterology and motility 04/2012; 18(2):150-68.
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[show abstract]
[hide abstract]
ABSTRACT: Approximately 10% of patients with reflux esophagitis (RE) are not cured with the standard 8-week q.d. regimen with a proton pump inhibitor (PPI). Thus, b.i.d. dosing is often used in refractory RE (rRE) patients, although there has been no report of endoscopically confirmed healing with b.i.d. dosing of PPIs. This study aimed to assess the efficacy and safety of 8-week therapy with rabeprazole (RPZ) sodium at 20 mg b.i.d. or 10 mg b.i.d. as compared with RPZ at 20 mg q.d. in patients with RE refractory to the standard PPI regimen in Japan.
Endoscopically confirmed rRE patients (Los Angeles grade A-D) who had received a standard PPI regimen for at least 8 weeks were randomized in a double-blind manner into groups receiving RPZ at 20 and 10 mg b.i.d. or 20 mg q.d. (control) daily for up to 8 weeks. The primary efficacy endpoint was the rate of endoscopically confirmed healing after week 8.
A total of 337 rRE patients treated at 71 sites were randomized. The rate of endoscopically confirmed healing after 8 weeks was significantly higher in those who received RPZ at 20 mg b.i.d. (77.0%, P = 0.003) and 10 mg b.i.d. (78.4%, P = 0.001) as compared with 20 mg q.d. (58.8%), and the rates of resolution of heartburn after week 8 were 80.0%, 74.0%, and 56.4%, respectively. All treatment regimens were well tolerated.
Regimens of RPZ at 20 and 10 mg b.i.d. for 8 weeks were more effective than 20 mg q.d. with regard to endoscopically confirmed healing and symptom resolution of RE refractory to a standard PPI regimen.
The American Journal of Gastroenterology 03/2012; 107(4):522-30. · 7.28 Impact Factor
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2012; 109(5):703-9.
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[show abstract]
[hide abstract]
ABSTRACT: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD.
Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated.
Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication.
Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.
Journal of Gastroenterology and Hepatology 01/2012; 27(1):62-8. · 2.87 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To determine the efficacy of acotiamide, an acetylcholinesterase inhibitor, in patients with functional dyspepsia (FD) in a 4-week trial.
A multicentre, randomised, placebo-controlled, parallel-group, phase III trial was carried out, in which patients with FD received 100 mg of acotiamide or placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The primary efficacy end points were global assessment of overall treatment efficacy (OTE) and elimination rate of all three meal-related symptoms (postprandial fullness, upper abdominal bloating and early satiation), as derived from daily diaries. Secondary efficacy end points were individual symptom scores and quality of life. Adverse events were monitored.
52.2% of those receiving acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders according to a global assessment of OTE. Over 4 weeks, the elimination rate for all three meal-related symptoms was 15.3% among patients receiving acotiamide compared with 9.0% in the placebo group (p=0.004). The significant benefit of acotiamide over placebo in OTE and elimination rate was maintained during the 4 week post-treatment follow-up. All other secondary efficacy end points, including quality of life, were significantly improved with 100 mg of acotiamide as compared with placebo. The number needed to treat was 6 for OTE and 16 for symptom elimination rate. The incidence of adverse events was similar between the acotiamide group and placebo group and no significant cardiovascular effects due to treatment were seen.
Over 4 weeks, acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD.
http://ClinicalTrials.gov number, NCT00761358.
Gut 12/2011; 61(6):821-8. · 10.11 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: A correlation to obesity has been reported in patients with gastroesophageal reflux disease (GERD). However, insufficient data have been obtained regarding underweight GERD patients. Post hoc analysis of a multicenter prospective cohort study was conducted to evaluate subjective symptoms and health-related quality of life (HRQOL) in underweight GERD patients (body mass index [BMI] < 18.5) and to evaluate therapeutic response to proton pump inhibitors.
A total of 2646 patients who underwent endoscopy were classified by BMI and analyzed. Rabeprazole was administered for 8 weeks. Subjective symptoms and HRQOL were assessed using questionnaires (F-Scale and SF-8™).
Baseline endoscopy revealed 29.2% of patients had non-erosive reflux disease (NERD). Underweight status was identified in 5.8% of GERD patients, and mean baseline symptoms score and SF-8 physical component summary (PCS) score were 18.6 and 42.4, respectively, reflecting greater impairment compared with the values of 15.4 and 45.6 in normal-weight patients (BMI ≥ 22 but < 25). Treatment with rabeprazole resulted in a decrease from 18.6 at baseline to 6.7 at week 8 in underweight reflux esophagitis subjects, and from 15.0 to 6.3 in underweight NERD patients. PCS score improved in underweight patients. These changes were about the same as in normal-weight or obese patients.
Japanese GERD patients are often obese, as reported previously, but some GERD patients are underweight. Baseline symptoms and QOL in underweight GERD patients tended to be more severe than in normal-weight patients, but therapeutic response with proton pump inhibitors was about the same as in normal-weight or obese patients.
Journal of Gastroenterology and Hepatology 12/2011; 27(5):913-8. · 2.87 Impact Factor
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Hiroto Miwa,
Uday Chand Ghoshal,
Kwong Ming Fock,
Sutep Gonlachanvit,
Kok-Ann Gwee,
Tiing-Leong Ang,
Full-Young Chang, Michio Hongo,
Xiaohua Hou,
Udom Kachintorn, [......],
Kwang Jae Lee,
Ching-Liang Lu,
Sanjiv Mahadeva,
Soichiro Miura,
Hyojin Park,
Poong-Lyul Rhee,
Kentaro Sugano,
Ratha-korn Vilaichone,
Benjamin C Y Wong,
Young-Tae Bak
[show abstract]
[hide abstract]
ABSTRACT: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia.
Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group.
Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. Conclusions: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.
Journal of Gastroenterology and Hepatology 12/2011; 27(4):626-41. · 2.87 Impact Factor
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Tomohiko Shimatani,
Mitsushige Sugimoto,
Masafumi Nishino,
Kyoichi Adachi,
Kenji Furuta,
Masanori Ito,
Susumu Kurosawa,
Noriaki Manabe,
Kotaro Mannen, Michio Hongo,
Tsutomu Chiba,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: We aimed to determine whether reflux- and symptom-related parameters can predict the efficacy of proton pump inhibitors (PPI) in non-erosive reflux disease (NERD).
Twenty-seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks.
Univariate analysis demonstrated no significant associations between any reflux- or symptom-related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post-hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037).
Pre-therapeutic pH monitoring in the lower and mid-esophagus is useful for predicting the efficacy of PPI in NERD patients.
Journal of Gastroenterology and Hepatology 11/2011; 27(5):899-906. · 2.87 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Several studies have described factors associated with the failure of proton pump inhibitors (PPIs) to effect endoscopic healing of reflux esophagitis (RE), but few studies have addressed factors promoting PPI-based endoscopic healing. We performed post hoc analysis of a multicenter prospective cohort of RE patients to identify factors encouraging endoscopic healing of this disorder.
Patients with RE received 10 or 20 mg rabeprazole for 8 weeks, and endoscopic findings before and after treatment were studied. To evaluate the effects of patient background factors on endoscopic healing, we performed multiple logistic regression analysis and determined the respective odds ratios (ORs) and 95% confidence intervals (CIs).
A total of 454 patients who underwent endoscopy at baseline and again at week 8 were included in the analysis. After 8 weeks of treatment, improvement in endoscopic findings was observed in 94.1% (427/454) of patients, and endoscopic healing was seen in 76.7% (348/454). Multiple logistic regression analysis revealed that a combination of angiotensin II receptor blockers (ARBs) had a significant positive impact on endoscopic healing (OR 3.9, 95% CI 1.411-10.903), but no significant positive relationship was seen for other concomitant drugs such as nonsteroidal anti-inflammatory drugs and calcium channel blockers. Severe RE at baseline (OR 0.365, 95% CI 0.281-0.475) and PPI therapy prior to enrollment (OR 0.154, 95% CI 0.052-0.453) were found to have significant negative effects on endoscopic healing.
Concomitant use of ARBs may promote endoscopic healing of RE treated with PPIs.
Journal of Gastroenterology 11/2011; 47(3):249-55. · 4.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Some non-erosive reflux disease (NERD) and reflux esophagitis (RE) patients are unresponsive to a proton pump inhibitor (PPI) at standard dose. We investigated the predictive marker of the efficacy of PPI for GERD patients including NERD and RE treated with standard and increased doses of a PPI.
Patients with symptomatic gastroesophageal reflux disease (GERD) (NERD and RE) were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. The RPZ dosage was increased to 10 mg twice daily for an additional 2 weeks and again to 20 mg twice daily for another 2 weeks if heartburn was not relieved. Baseline characteristics and efficacy of RPZ were assessed on the basis of a heartburn diary and frequency scale for symptoms of GERD (FSSG).
Complete heartburn relief rates after 4 weeks were 42.5% (31/73) and 67.9% (19/28) in NERD and RE groups, respectively, which rose to 68.9 and 91.7% after dose escalation. Multivariate analysis revealed that parameters associated with resistance to RPZ 10 mg once daily were female, non-smoking, frequent heartburn, low score for question 4 (Q4) of the FSSG (subconsciously rubbing the chest), and high scores for Q3 (heavy stomach after meal) and Q7 (unusual sensation in the throat). Frequent heartburn and a high score for Q7 were associated with resistance to RPZ 20 mg twice daily. FSSG scores of patients resistant to RPZ were significantly higher in comparison with responders before and during treatment.
FSSG could predict response to a PPI for symptomatic GERD. Increase of RPZ dose is useful for treatment of GERD refractory to the standard dose of RPZ.
Journal of Gastroenterology 08/2011; 46(11):1273-83. · 4.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Epidemiological studies of gastroesophageal reflux disease (GERD) in Japan vary in design. This systematic review examines the prevalence of GERD in Japan, distinguishing between study methodologies, and reports on changes over time and factors potentially associated with GERD.
PubMed and Embase searches identified studies reporting the prevalence of GERD in the general population, primary care patients, and individuals undergoing routine health checks.
Of the twenty eligible studies, half excluded individuals taking acid-suppressive medication, so these studies would have been likely to have underestimated the prevalence by 2-3%. Nine studies reported the prevalence of at least weekly reflux symptoms (the definition closest to the Montreal definition): in seven studies this was 6.5-9.5%, but in two studies that included individuals who underwent upper gastrointestinal endoscopy the prevalence was 19.0 and 21.8%. Eight studies used symptom scores: prevalence estimates ranged from 10.2 to 29.0% in five studies using the Carlsson-Dent self-administered questionnaire (QUEST), and from 27.0 to 37.6% in three studies using the frequency scale for the symptoms of GERD. Prevalence estimates were 15.1-24.3% in three studies that reported the presence of reflux symptoms of undefined frequency. Six studies reported the prevalence of reflux esophagitis as 4.9-8.2%. Changes in prevalence over time and factors associated with reflux symptoms were inconsistent.
Few studies have reported the prevalence of GERD in Japan using standardized criteria. Thus, prevalence estimates vary substantially, reflecting differences in study populations and GERD definitions. However, seven studies reported that the prevalence of at least weekly symptoms was 6.5-9.5%, a finding which approaches that reported in Western populations (10-20%).
Journal of Gastroenterology 06/2011; 46(9):1092-103. · 4.16 Impact Factor
