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Context: Plasma liver-specific mRNAs are useful biomarkers of hepatotoxicity in rats. Objective: To investigate the potential application of liver-specific mRNAs as biomarkers for liver injury in humans. Methods: We determined the plasma levels of liver-specific mRNAs by real-time qRT-PCR in healthy donors and patients with liver injury. Results: Plasma levels of albumin (ALB) and apolipoprotein H (APOH) mRNAs increased in patients with elevated serum alanine aminotransferase. These mRNAs also increased in plasma after transcatheter arterial chemoembolization, which induces specific injury to liver. Conclusions: We demonstrated the potential application of plasma ALB and APOH mRNAs as clinical biomarkers for liver injury. [ABSTRACT FROM PUBLISHER]

Background: Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. Methods: This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily ( n = 185) or gefarnate 50 mg twice daily ( n = 181) and followed up for 12 months or longer prospectively. Results: The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. Conclusion: Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy. [ABSTRACT FROM AUTHOR]

Background and aims: The results of a phase III, placebo-controlled study demonstrated that endoscopic direct spraying of l-menthol onto the gastric mucosa effectively suppressed gastric peristalsis in the study patients. The aim of the study reported here was to determine whether the anti-peristaltic effect of an l-menthol preparation facilitates endoscopic examinations in a clinical setting. Methods: This was a multicenter, open-label, single-arm trial in which the study cohort comprised patients in whom l-menthol was likely to be used to facilitate endoscopic examination in clinical settings. The primary outcome was the proportion of subjects with no peristalsis (Grade 1) after treatment and at the end of endoscopy (defined as the complete suppression of gastric peristalsis). This variable was assessed according to the level of anti- Helicobacter pylori immunoglobulin G (IgG) antibody, pepsinogen test results, whether sedation was performed, and whether subjects were considered unsuitable for the use of conventional antispasmodics. Results: Of the 119 enrolled subjects, data from 112 were included in the primary efficacy analysis. Gastric peristalsis was completely suppressed in 37.5% of the patients [42/112 patients; 95% confidence interval (CI) 28.5-47.1]. Subgroup analyses revealed that the rate of peristalsis suppression was significantly higher in patients with elevated levels of anti- H. pylori IgG antibody (26/44, 59.1%; 95% CI 43.2-73.7); P < 0.001] and positive pepsinogen test results (21/35, 65.6%; 95% CI 46.8-81.4; P < 0.001]. There was no significant difference according to sedation (17/52, 32.7%; 95% CI 20.3-47.1; P = 0.434) or whether subjects were considered unsuitable for use of conventional antispasmodic agents (14/28, 50.0%; 95% CI 30.6-69.4; P = 0.12]. Conclusion: These findings are comparable to those of the phase III placebo-controlled study and provide further evidence that endoscopic direct spraying of l-menthol effectively suppresses gastric peristalsis during upper gastrointestinal endoscopy. [ABSTRACT FROM AUTHOR]

Background: The efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers. Methods: Patients were randomized to receive lansoprazole 15 mg daily ( n = 226) or gefarnate 50 mg twice daily ( n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease. Results: The primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P < 0.001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042-0.230). Conclusion: Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD.METHODS:In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals.RESULTS:Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms.CONCLUSIONS:Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores. [ABSTRACT FROM AUTHOR]

Patients with reflux esophagitis (RE) in Western countries have impaired health-related quality of life (HRQOL). However, few data are available concerning HRQOL in Asian patients with RE. To determine the demographic characteristics, HRQOL, and the impact of lansoprazole treatment in a large cohort of RE patients in Japan. Patients with RE were enrolled. Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after 4 and 8 weeks of treatment. Among enrolled patients, 2320 patients with the Los Angeles classification grade A to D esophagitis at enrollment to the study were analyzed. A higher proportion of older women was observed (in the group of patients aged ≥60 years, 61.3% were women). Prevalence of obesity was 4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the Japanese general population in all domains of the SF-8. After 8 weeks of treatment with lansoprazole, these scores significantly improved to the levels of the general population ( P < 0.01). Scores of RESQ also significantly improved ( P < 0.01). Demographically, RE patients in Japan differ from those in Western countries with an increased proportion in older women and lower prevalence of obesity. RE has a marked negative impact on HRQOL, which is significantly improved by treatment with lansoprazole. [ABSTRACT FROM AUTHOR]

Background. In Europe and the United States, it is known that obesity, which is increasing, is closely associated with gastroesophageal reflux disease (GERD), but in Japan no definite consensus has been reached on this relationship. Clarification of the relationship between the two is an important issue. Methods. After screening, gastrointestinal endoscopic examinations were conducted on 1813 subjects who were surveyed using a questionnaire in which they recorded body weight, height, weight loss or gain, chief complaints, and underlying disease to prospectively examine the relationship between obesity and GERD. Differences in GERD prevalence and esophageal hiatal hernia prevalence in thin (body mass index less than 18.5 kg/m2), normal (18.5 to 25.0), and obese (greater than 25.0) subjects were examined, and the differences in GERD prevalence in patients with weight loss or gain were also investigated. Results. GERD prevalence was 20.96% in the thin group, 24.42% in the normal group, and 31.86% in the obese group, indicating a significantly higher prevalence in the obese group compared with the other groups. The prevalence of hernia was also significantly higher in the obese group. GERD prevalence in the weight gain group was significantly higher than in the unchanged weight group and weight loss group. Conclusions. Both GERD prevalence and the prevalence of hernia were significantly higher in obese subjects, and the prevalence of GERD in subjects who had gained weight was also significantly higher. From these results, it was concluded that obesity is a risk factor for GERD in Japan. [ABSTRACT FROM AUTHOR]

Background. To evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20mg once daily in patients with nonerosive reflux disease (NERD) in Japan. Methods. A total of 37 patients were randomized to omeprazole 10mg or omeprazole 20mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshihara's modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment. Results. Both omeprazole 10mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported. Conclusions. Omeprazole 10mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patient's endoscopic classification. [ABSTRACT FROM AUTHOR]

We investigated the peptic ulcer recurrence rates during maintenance therapy with H2-receptor antagonists (H2RAs) following first-line therapy with a proton pump inhibitor (PPI). Patients with gastric ulcer (GU) or duodenal ulcer (DU) were enrolled in this study; 583 eligible patients (GU, 325; DU, 258) were administered lansoprazole (30 mg/day for 8 weeks for GU, and the same dosage for 6 weeks for DU) as first-line therapy, and a half dose of H2RA as maintenance therapy for 12 months. Endoscopic photographs were taken before administration and after 8 (GU) and 6 (DU) weeks of lansoprazole administration. Ulcer stage was evaluated using the classification of Sakita and Miwa. Endoscopic examinations were performed 6 months or 12 months after the start of maintenance therapy or when a recurrence was suspected because of the appearance of subjective symptoms. The healing rates for GU and DU patients after completion of lansoprazole therapy were 79% in both groups, while the S2-stage healing rates were 18% and 31%, respectively. At 1 year after the start of maintenance therapy, the recurrence rates were 25% for GU and 39% for DU patients. In DU patients, the recurrence rates from S1-stage and S2-stage were 49% and 20%, respectively (P = 0.004), but no significant difference was found between these rates in GU patients. The recurrence rates in H. pylori-positive patients before lansoprazole administration were 27% for GU and 43% for DU patients. We concluded that the maintenance therapy with a half-dose of H2RA following PPI therapy was insufficient to prevent recurrences of GU and DU. [ABSTRACT FROM AUTHOR]

Background : The safety and effectiveness of vonoprazan-based Helicobacter pylori ( H. pylori ) eradication therapy in routine clinical practice, and patient characteristics that influence safety and effectiveness, have not been well investigated. Methods : H. pylori -positive patients with gastric ulcer, duodenal ulcer, idiopathic thrombocytopenic purpura, history of endoscopic treatment of early gastric cancer, and gastritis were enrolled. Patients received vonoprazan 20 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200-400 mg twice daily for 7 days for the first-line eradication. For the second-line eradication, vonoprazan, AMPC, and metronidazole (MTZ) 250 mg were administered. The incidence of adverse drug reactions (ADRs) and eradication rates were evaluated. Results : The incidences of ADRs with vonoprazan/AMPC/CAM and vonoprazan/AMPC/MTZ were 3.22% (16/497) and 1.89% (1/53), respectively. Commonly reported ADRs were diarrhea, nausea, dysgeusia, feces soft, and rash. The eradication rates of the first-line therapy and the second-line therapy were 91.24% (427/468) and 95.45% (42/44), respectively. No notable differences in ADRs and eradication rates were observed when stratified by patient demographic characteristics. Conclusion : No new safety concerns were observed, and the effectiveness of vonoprazan-based triple therapy was confirmed in routine clinical practice. Trial registration : This study is registered at the Japan Pharmaceutical Information Center Clinical Trials Information (JapicCTI-153003).

Objectives: To assess the efficacy and safety of vonoprazan on heartburn symptoms in patients with nonerosive reflux disease (NERD) (ClinicalTrials.gov: NCT02954848)., Methods: This phase 3, double-blind, placebo-controlled study included Japanese patients aged 20 years and older with grade N/M NERD and recurrent heartburn. Patients received placebo (n = 245) or vonoprazan 10 mg (n = 238) for 4 weeks. The primary efficacy outcome was frequency of heartburn experienced by patients during the treatment period (proportion of days without heartburn). Other outcomes included cumulative improvement rates of heartburn, proportion of patients with complete heartburn resolution in the fourth week of treatment, and safety., Results: Compared with placebo, the proportion of days without heartburn was not significantly higher in the vonoprazan group in the full analysis (primary end point, 72.55% vs 61.50%, vonoprazan vs placebo, P = 0.0643) but was significantly higher in the per-protocol-set sensitivity analysis (P = 0.0341). Early onset of response and significantly greater cumulative improvement rates of heartburn were observed in the vonoprazan group (P = 0.0003). In a post hoc analysis, a greater proportion of patients with complete heartburn resolution in the fourth week of treatment were reported in the vonoprazan group (P = 0.0023). Incidence of treatment-emergent adverse events was similar between treatment groups (23.5% vs 23.3%); most treatment-emergent adverse events were mild in severity., Discussion: Although vonoprazan 10 mg was not superior to placebo with respect to proportion of days without heartburn in Japanese patients with NERD, vonoprazan had a significantly higher cumulative rate of heartburn resolution and was well tolerated.

Aim: To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE)., Methods: A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg ( n = 201), vonoprazan 10 mg ( n = 202), or vonoprazan 20 mg ( n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results., Results: Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg ( P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan ( P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively., Conclusion: Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE., Competing Interests: Conflict-of-interest statement: Kiyoshi Ashida has received fees and honoraria from Takeda Pharmaceutical Company Limited and Otsuka Pharmaceutical Company Limited; Katsuhiko Iwakiri has received grants, fees, and honoraria from Takeda Pharmaceutical Company Limited, and fees from Otsuka Pharmaceutical Company Limited; Yuuichi Sakurai, Tetsuharu Hori, Kentarou Kudou, and Akira Nishimura are full-time employees of Takeda Pharmaceutical Company Limited; Naoki Hiramatsu and Eiji Umegaki have no conflicts of interest to declare.

Background: Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE., Methods: This randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint. Following a 7 to 14-day run-in period (lansoprazole 30 mg treatment), patients with endoscopically confirmed PPI-resistant EE received vonoprazan 20 mg or 40 mg for 8 weeks., Results: Patients were randomized to receive vonoprazan 20 mg ( n = 9) or 40 mg ( n = 10). Over a 24-hour period; both groups showed a significant increase from baseline in the percentage of time gastric pH ≥ 4, referred to as pH 4 holding time ratio (HTR): an increase from 73.21% to 96.46% in the 20 mg group, and from 69.97% to 100.00% in the 40 mg group. Increases from baseline in esophageal pH 4 HTRs were not significant. The 40 mg group showed greater increases in gastric and esophageal pH 4 HTRs compared with the 20 mg group, but differences between groups were not significant. After 8 weeks' treatment, the healing rate in subjects with baseline EE grades A-D was 60.0% (3/5 patients) in the 20 mg group and 71.4% (5/7 patients) in the 40 mg group. Vonoprazan was generally well tolerated. One patient (40 mg group) experienced four treatment-emergent adverse events (TEAEs) (unrelated to study drug), leading to study discontinuation., Conclusions: Vonoprazan 20 mg and 40 mg effectively inhibited gastric acid secretion over a 24-hour period with significantly increased gastric pH 4 HTR, and resulted in an EE healing rate > 60.0% in this study. Vonoprazan treatment may be valuable for patients with PPI-resistant EE., Competing Interests: Conflict of interest statement: YS, MS, HO, KK, and AN are employees of Takeda Pharmaceutical Company Limited. KI, NH, EU, and KA are all paid consultants for Takeda Pharmaceutical Company Limited. Takeda Pharmaceutical Company Limited was involved in the study design, data collection, data analysis and preparation of the manuscript.

Objectives: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects., Methods: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1-120 mg in Japan and 1-40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH)., Results: Plasma concentration-time profiles of TAK-438 at all dose levels showed rapid absorption (median Tmax up to 2 h). Estimated mean elimination half-life was up to 9 h. Exposure was slightly greater than dose proportional. No clear difference in TAK-438 pharmacokinetics was observed between Japanese and non-Japanese subjects. Acid suppression was dose dependent and similar in both studies. The 24-h intragastric pH ≥4 holding time ratio with 40 mg TAK-438 was 92% in Japan and 87% in the UK. TAK-438 was well tolerated, with no adverse events reported in Japanese subjects; 10 of 63 UK subjects experienced 12 treatment-emergent adverse events (non-serious). Increases in serum gastrin and pepsinogen I and II concentrations were observed at doses ≥10 mg, but there were no changes in alanine aminotransferase concentrations., Conclusions: Single oral doses of TAK-438 20-120 mg caused rapid, profound, and 24-h suppression of gastric acid secretion in healthy male subjects, regardless of geographical region, and TAK-438 was well tolerated at all doses studied, making it a potential alternative to proton pump inhibitors for the treatment of acid-related disorders.

Background and Aim: Cytomegalovirus (CMV) exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. The conditions under which CMV reactivation occurs in patients with UC, however, is unclear. In addition, the diagnostic and treatment strategies for UC positive for CMV have not been established. Granulocyte and monocyte adsorptive apheresis (GMAA) is natural biological therapy for UC in which the granulocytes/macrophages producing inflammatory cytokines are removed. We investigated the rate of colonic CMV reactivation and the efficacy of GMAA in active UC patients positive for CMV without concomitant corticosteroid (CS) therapy., Methods: Fifty-one active UC patients without concomitant CS therapy were enrolled. Colonic CMV reactivation was examined by real-time polymerase chain reaction (PCR) using biopsy specimen and/or histological examination. All patients were treated with intensive GMAA (twice per week). Rates of clinical remission and mucosal healing were compared between UC patients positive and negative for CMV., Results: Of 51 patients, 15 (29.4%) were diagnosed as CMV positive. The clinical remission rates following intensive GMAA did not differ between UC patients positive and negative for CMV (73.3% vs 69.4%, p=0.781). Proportion of patients achieving mucosal healing was also similar between these two groups. CMV-DNA became negative in all UC patients positive for CMV who achieved clinical remission 1 week after completion of intensive GMAA., Conclusions: Intestinal inflammation might trigger CMV reactivation in a subpopulation of active UC patients without CS treatment. GMAA could be a promising option for active UC positive for CMV., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background/aims: To compare the endoscopic features of LDA-induced ulcers developing during secondary prophylaxis with lansoprazole (LPZ) and gefarnate (GFN)., Methodology: All ulcers that had developed during prophylaxis with LPZ (15mg once daily) and GFN (50mg twice daily) in a prospective, randomized, double-blind trial, were reviewed and compared by a panel of expert endoscopists, based on endoscopic images available from the trial, to provide evidence for efficacy of LPZ versus GFN in secondary prophylaxis in patients with endoscopically confirmed ulcer scars., Results: A total of 6 and 53 patients had developed gastric or duodenal ulcers during prophylaxis with LPZ and GFN, respectively. Six gastric ulcers seen in those given LPZ were "small" and "shallow", while, of the 38 gastric ulcers seen those given GFN, 44.7% and 55.3% were "medium" or "large" and "small", respectively. Ulcers associated with blood coagula were seen only in those given GFN. Duodenal ulcers developed in 15 and 0 patients given GFN and LPZ, respectively., Conclusions: The ulcers developing during prophylaxis with GFN and LPZ varied in their features. The study findings may be useful when devising a strategy for prophylaxis of ulcers in high-risk patients receiving LDA therapy in a routine clinical setting.

Aim: To compare efficacy of proton pump inhibitors (PPIs) with H(2)-receptor antagonists (H(2)RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD)., Methods: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment., Results: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%., Conclusion: PPI monotherapy improves dysmotility-like symptoms significantly better than H(2)RAs plus Proks, and should be the treatment of first choice for Japanese FD.

Background: Acid suppression induced by rabeprazole 5 mg in patients with NERD has not been reported in the literature., Aims: The objective of this study was to investigate gastroesophageal acid suppression in NERD patients by rabeprazole 5 mg and 10 mg/day., Methods: Subjects 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 5 mg or 10 mg/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., Results: The 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 5 mg (change from baseline; -2.5%), whereas the median percentage of time at pH<4 in the rabeprazole 10 mg 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 5 mg and -44.0 with rabeprazole 10 mg. For each esophageal pH data, no significant differences were observed between the two groups (P=0.377, P=0.077)., Conclusions: Administration of 5 mg and 10 mg 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.

It is well known that gastric ulcers are most often found at anglus and upper corpus in the elderly. The number of gastric ulcer found at upper corpus hold half of all cases in the elderly patients with bleeding ulcer. Sixty percent of the elderly patients with bleeding ulcer took NSAIDs including low-dose aspirin in authors' hospital. Now it is easy to treat and cure bleeding ulcers due to development of endoscopic hemostasis and antiulcer drugs such as proton pump inhibitor(PPI). However, the elderly patients sometimes result in fatal outcome on bleeding from gastric ulcer. Therefore, it is important to prevent ulcer complications by PPI for the high-risk group such as elderly patients taking NSAIDs.

Objectives: Although lifestyle modification involving diet, exercise, cessation of smoking, etc. is generally advised for patients with reflux esophagitis (RE), few data that show its clinical benefits are available. We analyzed whether lifestyle modification improves health-related quality of life (HRQOL) in Japanese patients with RE receiving the proton pump inhibitor (PPI) lansoprazole as a post hoc analysis of an observational study that investigated the effect of lansoprazole on HRQOL., Methods: Patients with RE received lansoprazole for 8 weeks. HRQOL was assessed using the 8-Item Short-Form Health Survey (SF-8) and RE-specific HRQOL questionnaires at baseline and after 4 and 8 weeks of treatment. Physical and mental component summaries (PCS, MCS) and RE-specific summary (RES) scores were calculated., Results: Of the 8,757 patients analyzed, 40.8% were advised regarding new lifestyle at the start of lansoprazole treatment (Group A), 33.3% were advised to continue the lifestyle as advised previously (Group B), and 25.9% did not receive any advice (Group C). The change in PCS from baseline at week 8 for Group A was 5.7 +/- 8.1, and this was significantly greater (P < 0.001) than the increases achieved in Groups B (4.3 +/- 7.5) and C (4.0 +/- 7.6). The changes in MCS and RES were also significantly greater in Group A than in the other groups. The changes in HRQOL scores from baseline were significantly greater in Group A than in the other groups, irrespective of baseline patient characteristics., Conclusions: Lifestyle modification may be clinically beneficial in terms of improving HRQOL in Japanese patients with RE who are receiving treatment with a PPI.

A 57-year-old man presented with chief complaints of right hypochondrial pain and fever. Laboratory tests revealed severe inflammatory reactions. Abdominal ultrasonography disclosed a mass with non-homogeneous internal echoes suggesting hepatic abscess. Percutaneous liver biopsy revealed a lump of actinomycetes, allowing a diagnosis of hepatic actinomycosis. The abscess disappeared following long-term treatment with penicillin antibiotics. Actinomycosis developing primarily in the liver is very rare. This condition needs to be distinguished from tumorous lesions of the liver, including malignancy. It seems noteworthy that the diagnosis of this condition was possible on the basis of percutaneous liver biopsy.

Background: Whether or not the eradication of Helicobacter pylori is a risk factor for reflux esophagitis (RE) is a question at issue. To find an answer, it is necessary to clarify the influence of H. pylori eradication on the mechanism of RE., Methods: The authors investigated the influence of H. pylori eradication on gastric acidity and gastroesophageal reflux in ten gastric ulcer (GU) patients and ten duodenal ulcer (DU) patients by 24-h simultaneous determination of pH in the stomach and esophagus., Results: Though the results indicated enhanced gastric acidity in GU patients at night after H. pylori eradication, no such influence was observed in DU patients. No significant changes in gastroesophageal reflux occurred in GU or DU patients before and after H. pylori eradication. RE after H. pylori eradication occurred in only one patient, with GU. This patient had several risk factors for RE, such as obesity, male sex, and dietary habits to add to the increase in gastric acidity at night that occurred after H. pylori eradication. No increase in gastroesophageal reflux occurred in any DU patients or in the other GU patients that demonstrated enhanced gastric acidity at night after H. pylori eradication., Conclusions: The cure of H. pylori infection does not, by itself, cause RE in patients who have few other risk factors for RE.

A 64-year-old man developed progressive dementia and altered consciousness with myoclonus over 2 months. Neurological examination revealed mild dysphagia and negative myoclonus of both hands. Electroencephalography (EEG) showed continuous periodic synchronous discharge (PSD) of 1 Hz, although his EEG abnormality was not similar to that usually observed in Creutzfeldt-Jakob disease (CJD). Magnetic resonance imaging (MRI) of the brain revealed only few lacunes. Laboratory data were also normal. Since his consciousness level fluctuated and the PSD were spiky, we came to a diagnosis of nonconvulsive status epilepticus (NCSE). After administering the valproic acid, his symptoms and EEG finding improved. Nine months after the onset, despite his continued valproic acid, the patient had recurrent NCSE and PSD of 1 Hz. Diffusion-weighted MRI showed a T2-hyperintense lesion in the right parietal lobe, where SPECT scans showed hyperperfusion. After adding zonisamide, he improved slowly. The follow-up MRI and SPECT showed a disappearance of the previous lesion. Now CT scans of the abdomen showed enlarged periaortic lymph node and endoscopic ultrasonography disclosed a submucosal tumor of the stomach. Biopsy of the periaortic lymph node by laparotomy revealed undifferentiated adenocarcinoma with its origin being unclear. Chemotherapy didn't work well for the tumor and the patient underwent a downhill course, although his mental and neurological manifestation were mostly unremarkable. Two years and four months after the onset, he died in emaciation. Autopsy confirmed small cell carcinoma originating in the stomach and metastases in the liver and lungs. Neuropathological examination revealed only mild scattered gliosis. This case was unique in the prolonged CJD-like manifestations, which turned out to be due to NCSE. Despite anti-neuronal antibodies were not detected, we suspect yet another paraneoplastic brain syndrome in this patient.