Search

Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of neurological disorders caused by immune-mediated inflammatory mechanisms. We herein report a 77-year-old man with CV2/CRMP5-antibody-related PNS associated with a gastrointestinal stromal tumor (GIST). He was admitted for forgetfulness and delusional behavior. His neurological symptoms were subacute, and a whole-body examination revealed a gastric GIST. Serology showed CV2/collapsin response mediator protein (CRMP)-5 antibodies. Partial gastrectomy was performed for the GIST, and the neurological symptoms and serum CV2/CRMP5 antibodies disappeared. No relapse has occurred since the surgery. PNS should be considered in patients with subacute neurological disorders.

A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.

Objective The association between frailty and abdominal symptoms has not been evaluated. Methods We conducted a hospital-based, retrospective cross-sectional study of consecutive outpatients ≥65 years old at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center from 2017 to 2019. Patients were included in the study if all of the following information was available from their medical records: patient's profile, the evaluation of osteoporosis, sarcopenia, frailty, nutritional status, findings of upper gastrointestinal endoscopy, and questionnaire results for abdominal symptoms [Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Constipation Scoring System (CSS)]. We divided the subjects into frailty and non-frailty groups and investigated the risk factors for frailty. Results Of the 313 eligible study subjects [134 men (42.8%) and 179 women (57.2%); mean age, 75.7±6.0 years; mean body mass index, 22.8±3.6 kg/m2], frailty was noted in 71 cases (22.7%). In a univariate analysis, an older age (p

Background Recently, problems associated with proton pump inhibitor (PPI) use have begun to surface. PPIs influence the gut microbiota; therefore, PPI use may increase the risk of enteric infections and cause bacterial translocation. In this study, we investigated fecal microbiota composition, fecal organic acid concentrations and pH, and gut bacteria in the blood of the same patients before and after PPI use. Methods Twenty patients with reflux esophagitis based on endoscopic examination received 8 weeks of treatment with PPIs. To analyze fecal microbiota composition and gut bacteria in blood and organic acid concentrations, 16S and 23S rRNA-targeted quantitative RT-PCR and high-performance liquid chromatography were conducted. Results Lactobacillus species were significantly increased at both 4 and 8 weeks after PPI treatment compared with bacterial counts before treatment (P = 0.011 and P = 0.002, respectively). Among Lactobacillus spp., counts of the L. gasseri subgroup, L. fermentum, the L. reuteri subgroup, and the L. ruminis subgroup were significantly increased at 4 and 8 weeks after treatment compared with counts before treatment. Streptococcus species were also significantly increased at 4 and 8 weeks after PPI treatment compared with counts before treatment (P

Background/Aims: Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL). Methods: Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated. Results: DL (–) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (–) cases had tub1-low or NE at the tumor border. Conclusion: ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication.

BACKGROUND Cold polypectomy (CP) and hot polypectomy (HP) are both accepted methods for polypectomy. In recent years, the use of CP has increased for reasons of safety. However, there have been few investigations of conditions at follow-up early after resection. This prospective study from a single center aimed to compare colonic mucosal healing at 1 week following HP vs CP of benign colonic polyps

Background/Aims: Acotiamide, a prokinetic drug, is used to treat functional dyspepsia (FD), especially postprandial distress syndrome (PDS). However, a treatment for FD patients with PDS and/or epigastric pain syndrome (EPS) has not been established. We investigated the efficacy of famotidine in combination with acotiamide for FD. Methods: Fifty blindly randomized FD patients received placebo with acotiamide, or famotidine with acotiamide, for 4 weeks. Treatment efficacy was assessed by overall treatment effects (OTE), total, PDS and EPS symptom scores, and impairment of quality of life (QOL). Results: After OTE assessment, patients who felt affected by treatment comprised 40.9 and 57.9% of famotidine and placebo groups, respectively, after 4 weeks' treatment, with no significant difference between groups. A significant decrease was seen in total, PDS, and EPS symptom scores, and in QOL impairment, after 4 weeks' treatment compared with pretreatment scores for famotidine and placebo groups, but was not observed between groups. The proportion of patients showing a ≥50% decrease in EPS symptom scores was greater in the famotidine than that in the placebo group for every observation point, with the greatest difference observed after 2 weeks' treatment. Conclusion: The effectiveness of famotidine and acotiamide combination therapy in FD was similar to the effectiveness of acotiamide therapy alone.

The aim of the present study was to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). A hospital-based, retrospective study of outpatients in our department (Department of Gastroenterology, University of Juntendo, Tokyo, Japan) between March 2015 and August 2016 was performed. The patients who were experiencing heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the global overall symptom (GOS) scale to determine their symptom severity at baseline and after the 4 week treatment period. The proportions of patients with RE, NERD, and FD achieving improvement of their symptoms, defined as a GOS scale score of 1 (‘no problem’) or 2 (‘minimal problem’), were evaluated. During 4 weeks of VPZ therapy, changes in the gastroesophageal reflux disease (GERD) score, which was defined as the total points for heartburn and acid regurgitation on the GOS scale in patients with RE and NERD, and in the FD score, which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in patients with FD, were also evaluated. A total of 88 eligible cases were included in the present study, comprising 20 patients with RE, 25 patients with NERD, and 43 patients with FD. The rates of symptomatic improvement in patients with RE, NERD, and FD were 75.0, 60.0, and 48.8%, respectively. For the patients who were first administered VPZ, the rates of symptomatic improvement were 90.9, 66.7, and 58.8% in patients with RE, NERD, and FD, respectively. For those patients who were resistant to 8 weeks of proton pump inhibitor therapy, the rates of symptomatic improvement were 55.6, 53.8, and 42.3% in patients with RE, NERD, and FD, respectively. The GERD score in patients with RE and NERD, and the FD score in FD patients, were decreased after 4 weeks of VPZ therapy (P

The aim of the present study was to evaluate symptomatic reflux esophagitis (RE) in proton pump inhibitor (PPI) users. The present study conducted a hospital-based, retrospective cross-sectional study of consecutive RE cases in PPI users at Juntendo University Hospital recruited between 2008 and 2016. Eligible patients were PPI users with a complete patient profile, who completed the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) questionnaire, and who underwent upper gastrointestinal endoscopy for the examination of RE, hiatal hernia (HH) and endoscopic gastric mucosal atrophy (EGA). The patients with RE who were administered PPIs were divided into two groups: Those with symptomatic RE (FSSG≥8) and those with non-symptomatic RE (FSSG

Daisuke Asaoka,1 Akihito Nagahara,2 Mariko Hojo,1 Kenshi Matsumoto,1 Hiroya Ueyama,1 Kohei Matsumoto,1 Kentaro Izumi,1 Tsutomu Takeda,1 Hiroyuki Komori,1 Yoichi Akazawa,1 Yuji Shimada,2 Taro Osada,1 Sumio Watanabe1 1Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, 2Department of Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, Japan Background: Because of a change in lifestyle, especially adoption of westernized eating habits, lifestyle-related diseases have become increasingly prevalent. The aim of this study was to investigate the association of medications for lifestyle-related diseases with reflux esophagitis (RE).Methods: We conducted a hospital-based, cross-sectional retrospective study of consecutive outpatients who received an upper gastrointestinal endoscopy in our department from February 2008 to November 2014, which was performed by one specialist who was a member of the Japan Gastroenterological Endoscopy Society. We investigated the patient profile, Helicobacter pylori (H. pylori) infection status, medications for lifestyle-related diseases (including calcium channel blockers, statins, and bisphosphonates), and upper gastrointestinal endoscopic findings (RE, hiatal hernia, Barrett’s mucosa, and endoscopic gastric mucosal atrophy [EGA]). Patients with gastrectomy, peptic ulcer disease, gastric or esophageal malignant disease, and those who used proton pump inhibitors or histamine-2 receptor antagonists were excluded. We divided the subjects into a group without RE (RE(–)) and a RE (RE(+)) group as judged by endoscopy, and investigated the risk factors for RE.Results: Of 1,744 consecutive cases, 590 cases (300 males and 290 females; mean age 60.5±13.2 years) were eligible. RE(–) and RE(+) cases numbered 507 and 83, respectively. Bivariate analysis showed significant positive associations of RE with male sex, body mass index (BMI), calcium channel blockers, Barrett’s mucosa, hiatal hernia and negative associations of RE with H. pylori positivity, EGA. Multivariate analysis showed significant positive associations of RE with BMI (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.10–1.29), use of calcium channel blockers (OR: 2.12, 95% CI: 1.16–3.87), Barrett’s mucosa (OR: 2.97, 95% CI: 01.64–5.38), hiatal hernia (OR: 3.13, 95% CI: 1.79–5.47) and negative associations of RE with H. pylori positivity (OR: 0.20, 95% CI: 0.07–0.57), use of statins (OR: 0.42, 95% CI: 0.18–0.96), and EGA (OR: 0.83, 95% CI: 0.70–0.98).Conclusion: Calcium channel blockers were positively associated with RE and statins were negatively associated with RE, while bisphosphonates were not associated with RE. Keywords: reflux esophagitis, calcium channel blockers, statins, bisphosphonates, H. pylori, hiatal hernia, Barrett’s mucosa, endoscopic gastric mucosal atrophy

The aim of the present study was to investigate the association between the severity of constipation and sarcopenia in elderly adults. We conducted a single-center university hospital-based, retrospective cross-sectional study of consecutive outpatients aged ≥65 years from 2017 to 2020. Patients were included in the study if all of the following information were available from medical records: Patient's profile (age, sex, body mass index), laxative/prokinetics use, evaluation of sarcopenia, nutritional status, and questionnaires concerning the severity of constipation [Constipation Scoring System (CSS)], abdominal symptom-related quality of life (QOL) (Izumo scale) and stool shape [Bristol Stool Form Scale (BSFS)]. Multiple regression analysis of risk factors for high CSS score was performed. The results revealed that of the 310 eligible study subjects, [149 men (48.1%) and 161 women (51.9%); mean age, 75.7±6.1 years; mean body mass index, 23.0±3.6 kg/m2], sarcopenia was noted in 83 cases (26.8%). The CSS score was significantly higher in the sarcopenia group than that noted in the non-sarcopenia group (4.9±4.9 vs. 3.6±3.6, P=0.009). The CSS score was significantly associated with the albumin level (r=-0.148), lymphocyte count (r=-0.118), CONUT score (r=0.130), reflux-related QOL score (r=0.155), upper abdominal pain-related QOL score (r=0.171), fullness-related QOL score (r=0.299), constipation-related QOL score (r=0.615), diarrhea-related QOL score (r=0.235) and BSFS score (r=-0.114). In multiple regression analysis, independent predictors for CSS score were sarcopenia [standardized partial regression coefficient (β)=0.107, P=0.032], constipation-related QOL score (β=0.537, P

Background and Aim: Inhibition of gastric acid secretion is important for eradicating Helicobacter pylori. Vonoprazan (VPZ) is a strong, long-lasting inhibitor of gastric acid secretion. Studies that examined the effectiveness of VPZ-based triple therapy in second-line treatment have been performed. However, there have been no randomized controlled studies to compare the effect between VPZ-based triple therapy and proton pump inhibitor (PPI)-based triple therapy in second-line treatment, and it is not known which is more effective between VPZ-based and PPI-based therapies. This study aimed to compare the effectiveness of second-line triple therapies including VPZ or rabeprazole (RPZ) as the PPI. Methods: Eligible patients with H. pylori infection who failed first-line triple therapy were assigned randomly to the VPZ [VPZ40 mg/day, amoxicillin (AMPC) 1500 mg/day, metronidazole (MNZ) 500 mg/day] or RPZ (RPZ20 mg/day, AMPC1500 mg/day, MNZ500 mg/day) group. A 13C-urea breath test result of less than 2.5% was considered as successful eradication. Results: In total, 46 and 41 patients were analyzed as intention to treat (ITT) and per protocol (PP), respectively. Eradication rates in the VPZ and RPZ groups were 73.9% [95% confidence interval (CI) 51.6–89.8%] and 82.6% (95% CI 61.2–95.0%) based on ITT analysis, respectively ( p = 0.72). Based on PP analysis, the eradication rates in the VPZ and RPZ groups were 89.5% (95% CI 66.9–98.7%) and 86.4% (95% CI 65.1–97.1%), respectively ( p = 1.00). Two patients in the VPZ group and one in the RPZ group discontinued treatment due to side effects ( p = 1.00). Conclusion: There were no significant differences in efficacy and safety between second-line therapies including VPZ or RPZ.

Background.Endoscopic submucosal dissection (ESD) of esophageal tumors can cause stenosis, yet the effect of esophageal ESD on motility remains unclarified. This study aimed to compare esophageal motility and symptoms, before and after ESD, using high-resolution manometry (HRM) and symptom scoring.Methods.Twenty-eight patients with 35 cT1a cancers were prospectively enrolled between December 2014 and February 2016. Pre- and post-ESD symptom score and HRM were recorded. Based on circumferential resection (CR), patients were divided into group A (n=17, n=11, 2/3 CR or greater). HRM parameters evaluated were distal contractile integral (DCI), contractile front velocity (CFV), intrabolus pressure, integrated relaxation pressure, distal latency, and peristaltic breaks.Results.Symptom scores worsened after ESD in 8/11 patients in group B, and 0/17 patients in group A. There was no significant difference in any HRM parameter after ESD in the whole study group but mean DCI tended to increase (p=0.07). In group B, DCI increased significantly after ESD (p=0.04), and CFV tended to decrease after ESD (p=0.08).Conclusions.DCI tended to increase after esophageal ESD. ESD affected the symptom score and esophageal motility in cases with 2/3 CR or greater. This trial is registered withUMIN000015829.

Background Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori-infected gastric mucosa of children. Methods Gastric mucosal samples were obtained from 24 patients (12 adults and 12 children) who had undergone endoscopic evaluation of chronic abdominal complaints and were examined by the adult and pediatric gastroenterologists at Juntendo University Hospital. Six adult and pediatric patients with and six without H. pylori infection were enrolled. Their gastric mucosal samples obtained from the antrum and corpus were used for microarray, real-time polymerase chain reaction, and immunohistochemical analyses to examine the expression of inflammatory carcinogenic molecules. Results The expression of inflammatory molecules was upregulated in the H. pylori-infected gastric mucosa from both adults and children. The expression of olfactomedin-4 was only upregulated in adult patients, while that of pim-2, regenerating islet-derived 3 alpha, lipocalin-2, and C-X-C motif chemokine ligand 13 was equally upregulated in the infected gastric mucosa of both adults and children. Conclusions Because several carcinogenic molecules are upregulated in H. pylori-infected gastric mucosa even in children, early eradication therapy from childhood may be beneficial to decrease the incidence of gastric cancer. Although increased expression of olfactomedin-4 can be important in suppressing gastric cancer in adults, the increase was not detected in children.

Background and Aim This prospective pilot study investigated whether it is possible to predict the therapeutic response in both the early phase (1 week) and sustained phase (4 weeks) before starting proton pump inhibitor (PPI) therapy for functional dyspepsia (FD) or non-erosive reflux disease (NERD). Methods We administered rabeprazole 10 mg for 4 weeks to NERD/FD patients, who also answered a modified version of the Frequency Scale for Symptoms of gastroesophageal reflux disease (GERD) (FSSG), which added a pain score to the FSSG. Total score (TS), reflux score (RS), dysmotility score (DS), and pain score (PS) were analyzed. Symptom improvement was defined as ≥ 50% improvement in each score. Results We enrolled 83 patients (age [mean ± SD] 50.8 ± 15.8 years, 29 males, 54 females), of whom 62 could be classified into four groups: achieved symptom improvement within 1 week and maintained it for 4 weeks (Early-R, 40.3%); achieved symptom improvement within 1 week but lost it after 4 weeks (Temp-R, 9.7%); did not achieve symptom improvement within 1 week but did after 4 weeks (Late-R, 9.7%); and no improvement (Non-R, 40.3%). Mean TS, RS, DS, and PS in the Non-R group were significantly higher than in the Early-R group (23.9, 10.5, 11.0, and 2.4 vs 14.3, 6.8, 6.4, and 1.2). However, the Temp-R, Late-R, and Non-R groups could not be distinguished by TS, RS, or DS. Conclusion The magnitude of the pretreatment modified FSSG score seemed to be associated with the response at 1 week and 4 weeks.

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.

Laryngopharyngeal reflux (LPR) is an extraesophageal manifestation of gastroesophageal reflux disease (GERD). With the increase of GERD patients, the importance of LPR is acknowledged widely. However, the pathophysiology of LPR is not understood completely and the diagnostic criteria for LPR remain controversial. Unfortunately, a gold standard diagnostic test for reflux laryngitis is not available. Recently, an experimental animal model for reflux laryngitis was developed to investigate the pathophysiology of reflux laryngitis. An empirical trial of lifestyle modification and proton pump inhibitor therapy is a reasonable approach for LPR symptoms. Alternatives after failure with aggressive medical treatment are limited and multichannel intraluminal impedance and pH monitoring is currently the best alternative to detect nonacid reflux. Additional prospective and evidence-based research is anticipated.

Aim To assess the efficacy of continuous therapy (cont) and on-demand therapy (on-demand) as maintenance therapy for gastroesophageal reflux disease (GERD). Methods Patients with upper GI endoscopy (EGD)-proven GERD who completed 8 weeks of initial therapy were randomized to cont (omeprazole 20 mg od) or on-demand (omeprazole 20 mg on-demand) group. Assessments by the Global Overall Symptom (GOS) scale at baseline (at the start of maintenance therapy) and at 8-week, 16–week, and 24-week visits were made and EGD was performed at 24 weeks. Symptom relief was defined as percentages of patients whose GOS score of 1 or 2. Results Of the 117 enrolled patients, cont/on-demand was 59/58 and nonerosive reflux disease (NERD)/reflux esophagitis (RE) before the initial therapy was 35/82. Symptom relief in cont/on-demand were 57.6%/48.3% at baseline (n.s.), 66.7%/54.7% at 8 week (n.s.), 64.6%/54.7% at 16 weeks (n.s.), and 66.7%/74.0% at 24 weeks (n.s.). When subjects were divided into NERD and RE, symptom relief in cont/on-demand were 33.3%/41.2% at baseline (n.s.), 43.8%/64.3% at 8 weeks (n.s.), 50.0%/42.9% at 16 weeks (n.s.), and 50.0%/69.2% at 24 weeks (n.s.) in NERD, while those were 68.3%/51.2% at baseline (n.s.), 76.3%/51.3% at 8 weeks (p < 0.05), 70.6%/59.0% at 16 weeks (n.s.), and 72.7%/75.7% at 24 weeks (n.s.) in RE, respectively. At 24-week EGD, all patients in NERD remained as NERD but number of healed patients was significantly higher in cont (85.3%) than in on-demand (44.4%) (p < 0.01) in RE. Conclusions Since NERD is defined by symptoms, as a result of the limited efficacy of continuous therapy, on-demand therapy would be sufficient as maintenance therapy in NERD patients. Regarding RE, continuous therapy would be recommended in terms of reduced symptoms and maintaining mucosal healing.

The difference in gastro-esophageal reflux disease (GERD) symptoms between elderly and younger GERD patients has not been fully studied. Our aim was to examine if there was any difference in the degree of GERD symptoms between elderly and younger patients with reflux esophagitis. Patients who were diagnosed by endoscopic examination as having reflux esophagitis and who answered the questionnaire on the frequency scale for the symptoms of GERD (FSSG) were included. Elderly and younger adult patients were defined as patients aged 65 and over or less than 65, respectively. 596 subjects were included. 184 subjects (mean 71.1 years; 114 males) were classified into the Elderly group, and 412 subjects (mean 51.2 years; 307 males) into the Younger group. The mean FSSG score of the Elderly and Younger groups was 6.7 and 8.4, respectively (p = 0.0024). Among those with severe esophagitis, the mean FSSG score of the Elderly and Younger groups was 8.5 and 8.7, respectively (p = 0.58). Although elderly patients tended to have less degree of GERD symptoms than younger patients, these findings suggest that there may be no significant age-related difference in complaints of GERD symptoms among severe reflux esophagitis patients.

We report a rare case of hemorrhagic gastric polyps resulting in anemia during long-term proton pump inhibitor (PPI) administration that endoscopically looked like a fundic gland polyp (FGP). A 44-year-old man presented complaining of anemia and tarry stools. Esophagogastroduodenoscopy (EGD) demonstrated multiple white edematous polyps in the corpus and antrum, which were considered to be FGPs. We attempted endoscopic hemostasis but hemorrhaging increased because of hemorrhagic polyps and vulnerable gastric mucosa. Re-bleeding occurred several times. Polyp resection was performed at 24 polyp sites. We also ceased the administration of PPI. Microscopically, polyps showed characteristics of hyperplasia in the foveolar epithelium, extensions of fundic glands, and edema of the stroma. The proliferation of parietal and chief cells was also observed. Immunohistochemically, aquaporin-4 (AQP4) and KCNQ1-positive parietal cells and dilated mucous glands were found from the basal side to the apical side of the mucosa. These findings were compatible with the development of lesions associated with the long-term administration of PPI. EGD revealed an improvement in the vulnerability of gastric mucosa and the development of polyps, with no further gastric polyps observed 1 year after discharge. Bleeding from polyps resembling FGPs is generally rare, with indications that long-term PPI administration may induce such bleeding.

Background and Aim: Prevalence of gastroesophageal reflux disease (GERD) varies in regions, but few reports on clinical features and quality of life (QOL) of asymptomatic GERD exist in Japan. Methods: Endoscopy was performed in our department between April 2008 and September 2010. Among 6409 cases answering Frequency of Scale for the Symptoms of GERD (FSSG) and SF8 QOL (PCS: physical component summary; MCS: mental component summary), proton pump inhibitor or histamine 2 receptor antagonist users were excluded, and 388 cases diagnosed as reflux esophagitis (RE) (Los Angeles Classification grade A, B, C, D) were analyzed. Asymptomatic cases with FSSG total score = 0 were defined as asymptomatic RE (AsymRE) and FSSG total score ≥ 1 as symptomatic RE (SymRE). Each clinical feature was analyzed. Results: The frequency of AsymRE was 11.6% of RE (AsymRE, n = 45; SymRE, n = 343). Patient characteristics in AsymRE, SymRE were male/female = 35/10; 239/104 (not significant), mean age (year) = 63.5 ± 14.3; 58.3 ± 12.7 (P

Nonalcoholic steatohepatitis (NASH), unlike simple steatosis, is a potentially progressive disease. Various types of drugs have been explored for the treatment of NASH. We reviewed the various therapies available, with particular emphasis on their efficacy for the improvement of hepatic fibrosis. Treatments for NASH included lipase-inhibiting agents, drugs that target components of metabolic syndrome, antioxidants, liver cytoprotectants, and suppressors of inflammatory cytokines. Alanine transaminase levels were significantly decreased and the grade of histologic features other than fibrosis was significantly improved in more than 75% of treatment arms across studies, yet the stage of liver fibrosis was significantly improved in less than 30% of treatment arms. Recently, drugs such as peroxisome proliferator-activated receptor-γ agonists have received attention for their anti-fibrotic effect. However, due to a lack of large-scale, high quality, long-term clinical trials, the utility of any particular treatment for NASH is not yet clear. Further clinical studies are needed to evaluate the efficacy and safety of individual drugs.

Background Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants in the world. Recent studies, however, have raised the concern that SSRIs increase the risk of gastrointestinal dysfunction. Therefore, we conducted a case-control study on gastrointestinal symptoms and endoscopic findings in patients who were taking SSRIs in Japan. Methods Forty-one patients who were taking SSRIs (SSRI-treated group) and 82 age- and sex-matched patients who were not taking antidepressants (control group) were selected from the population of patients who underwent endoscopic examination from January 1, 2005 to March 31, 2010 in our institution, and their subjective symptoms and endoscopic findings were analyzed. Patients who were taking proton pump inhibitors (PPIs) and/or histamine H2-receptor antagonists (H2RAs) were excluded from this study. Results The chief complaints at the endoscopic examination were classified into the following 4 categories: reflux symptoms, dysmotility symptoms, ulcer-like symptoms, and no upper abdominal symptoms. No significant difference was found in the complaint rate of each category between the SSRI-treated and the control groups. No significant differences were found between the groups in endoscopic findings, the LANZA score and the rate of chief complaints in patient classes stratified by the endoscopic finding. Conclusion It was not evident that SSRIs induced mucosal damage of the upper gastrointestinal tract. And, it is considered that SSRIs do not increase the risk of upper gastrointestinal symptoms in patients treated with SSRIs for 1 month or longer. The present study suggests that SSRI medication does not have a bad influence on gastrointestinal symptoms and gastrointestinal organic diseases.

Background: Smoking is considered to be risk factors of gastroesophageal reflux disease (GERD). The present study aimed to reveal whether quit smoking improves GERD symptoms and QOL of patients. Methods: In this prospective study, 33 patients who participated in a 12-week quit smoking program filled out the Frequency Scale for the Symptoms of GERD (FSSG) questionnaire, and SF8 QOL questionnaire. Patients filled out the questionnaires at baseline and during the program at 2 weeks, 4 weeks, 8 weeks and 12 weeks. In the FSSG, the responses were scored and the reflux score (RS), dysmotility score (DS) and total score (TS) were calculated. Results: There were 22 males and 11 females. Their mean age was 54.8 ± 13.0 (mean ± SD) yr, BMI was 22.9 ± 4.0, and duration of smoking was 33.5 ± 12.5 years. Ten patients belonged to GERD subgroup (baselineFSSGscore ≥ 8). All patients were successful at quit smoking. Scores of TS/RS/DS are 8.6 ± 1.8 (mean ± SE)/4.2 ± 0.9/4.5 ± 0.9 at baseline, 4.7 ± 1.6**/2.5 ± 0.9**/2.3 ± 0.7** at 2 w, 5.7 ± 1.3**/2.6 ± 0.6*/3.0 ± 0.7* at 4 w, 4.5 ± 1.4*/2.2 ± 0.8*/2.3 ± 0.8* at 8 w and 3.7 ± 1.2**/1.7 ± 0.6**/2.0 ± 0.7** at 12 w, respectively (**p < 0.01, *p < 0.05 vs. baseline). Among GERD subgroup, Scores of TS/RS/DS are 18.0 ± 2.9/8.9 ± 1.6/9.1 ± 1.5 at baseline, 8.8 ± 3.0/5.1 ± 1.7/3.7 ± 1.6 at 2 w, 10.8 ± 2.9/5.4 ± 1.6/5.4 ± 1.5 at 4 w, 7.6 ± 2.9*/4.1 ± 1.6/3.5 ± 1.5* at 8 w and 7.1 ± 2.9*/3.2 ± 1.6*/3.9 ± 1.5* at 12w, respectively. Regarding QOL, physical component score has significantly improved at 2, 4, 8 and 12 w and mental component score at 4w, respectively. Conclusions: Quit smoking significantly improved not only GERD symptoms but also QOL, indicating that quit smoking might be an option in the treatment strategy of GERD symptoms.

To investigate the pathophysiology of reflux laryngitis, an experimental model is required. The aim of this study is to establish an animal model of reflux esophago-laryngitis, modifying our previously reported model of chronic acid reflux esophagitis. The modified chronic acid reflux esophagitis (m-RE) group (n = 10), in which the duodenum was wrapped with 2.5 mm of Nelaton catheter, was not treated with any drugs. Also postoperatively, two treatment groups (n = 10 in each) received different dosages of rabeprazole (RPZ): 1.0 mg/kg/day (RPZ 1.0 group) or 10.0 mg/kg/day (RPZ 10.0 group). As a control group (n = 5), other rats underwent sham operation. The esophagus and larynx were resected on day 14 after the operation, and ulcer score of the esophagus was assessed. The epithelial thickness and leukocyte infiltration of the supraglottic and subglottic laryngeal mucosae were investigated. The number of interleukin (IL)-1β-positive cells was also counted and defined as the IL-1β labeling index. In the m-RE group, the epithelial thickness, leukocyte infiltration, and IL-1β labeling index of the supraglottic and subglottic laryngeal mucosae were increased compared with controls (P

Background and Aims: It is still controversial which drugs, proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA), are more effective for dyspepsia in the Japanese population. Methods: Patients with uninvestigated dyspepsia (n = 104; male/female 41/63) were treated with either rabeprazole 10 mg o.d. (n = 62) or lafutidine 10 mg b.i.d. (n = 42) for 4 weeks. Questionnaires (modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease [mFSSG] and quality of life [QOL], SF-8) were administered before and after therapy. The mFSSG was classified into a total score (Q-T), reflux score (Q-R), dyspepsia score (Q-D) and pain score (Q-P). The SF-8 had a physical component summary (PCS) and mental component summary (MCS). The predominant type of symptom was reflux (R-S), pain (P-S) or dysmotility (D-S). Results: R-S was 19.2%, P-S 48.1%, D-S 24.0% and overlap 8.7%. In the R-S, Q-T and Q-R significantly improved with rabeprazole, but neither scale improved with lafutidine. MCS significantly improved with rabeprazole. In P-S, Q-T, Q-R, Q-D and Q-P significantly improved with both drugs. PCS significantly improved with both, whereas the MCS significant improved with rabeprazole. In D-S, Q-R and Q-D significant improved with rabeprazole, but neither improved with lafutidine. QOL did not improve with either. With overlap, neither scale nor the QOL reached a significant difference. Conclusion: Both PPI and H2RA have a positive effect on P-S, but H2RA therapy is limited for R-S and D-S, whereas PPI therapy is generally effective. Therefore, careful prescription based on symptoms is important.

The aims of treatment of gastroesophageal reflux disease (GERD) are to cure mucosal breaks, control symptoms, and prevent complications (e.g. stricture, Barrett's esophagus, and esophageal adenocarcinoma). Proton pump inhibitors (PPIs) are known to be the best drugs to cure esophagitis; however, a highrecurrence rate of about 80% was described after the completion of initial therapy. Regretfully, not so many physicians perform maintenance therapy in clinical practice. Histamine H2 receptor antagonists have an insufficient effect in maintenance therapy compared with PPIs; therefore, they could be prescribed for mild reflux esophagitis. Several clinical trials have been conducted to investigate the efficacy of continuous PPI administration maintenance therapy for GERD. Among these trials, recent large-scale studies showed that esomeprazole was equal to or superior to other kinds of PPIs. On the other hand, on-demand PPI studies have been conducted, mainly in patients with nonerosive reflux disease or uninvestigated GERD;however, this strategy was less effective than continuous therapy in many studies. Because on-demand therapy is less expensive, it is worth confirming this strategy in further studies. Studies of maintenance therapy with investigations conducted for as long a period as 5 years have described that PPI maintenance therapy could be considered as effective, safe, and well tolerated.

Although germ cell tumors are the most common malignancy in young men, extragonadal germ cell tumors are rare. Gastric metastasis presenting initially as upper gastrointestinal hemorrhage is also exceedingly rare. A 27-year-old man presented at our hospital with tarry stool. Gastric fiberscopy images revealed a bleeding gastric polypoid lesion in the anterior wall of the gastric body, from which a biopsy specimen was obtained. Histopathological analysis of the biopsy showed syncytiotrophoblast-like cells with multiple, large nuclei, consistent with choriocarcinoma. Based on these results, our diagnosis was extragonadal retroperitoneal germ cell tumor with gastric metastasis.

A 59-year-old Japanese woman was diagnosed in 1998 with systemic sclerosis (SSc). The patient presented with a one-month history of postprandial vomiting prior to hospitalization. The patient underwent esophago-gastroduodenoscopy which revealed a diaphragm-like stricture in the second part of the duodenum in January 2004. Unexpectedly, the patient had not used NSAIDs for any long period of time. Retrospective endoscopic findings from 2000 showed the presence of duodenal circular erosions at the same site. This is the first report of a patient diagnosed with SSc who also presented with endoscopic evidence of a stricture of the duodenum, unrelated to NSAIDs.

Daisuke Asaoka, Akihito Nagahara, Yuji Shimada, Kenshi Matsumoto, Hiroya Ueyama, Kohei Matsumoto, Yuta Nakagawa, Tsutomu Takeda, Ippei Tanaka, Hitoshi Sasaki, Taro Osada, Mariko Hojo, Sumio Watanabe Department of Gastroenterology, University of Juntendo, School of Medicine, Tokyo, Japan Background: A number of diseases and drugs may influence bone mineral density; however, there are few reports concerning the relationship between lifestyle-related diseases and osteoporosis in Japan as determined by multivariate analysis. The aim of this study was to investigate the risk factors for osteoporosis and whether infection by or eradication of Helicobacter pylori is associated with osteoporosis.Methods: Between February 2008 and November 2014, using a cross-sectional study design, we investigated patient profile (age, sex, BMI, alcohol, smoking), H. pylori infection status, comorbidities, internal medicine therapeutic agents (calcium channel blocker, HMG-CoA reductase inhibitors, proton pump inhibitor), serum parameters (Hb, calcium, ΥGTP), bone turn over markers (bone-specific alkaline phosphatase (BAP) and collagen type I cross-linked N telopeptide (NTX), findings on dual-energy x-ray absorptiometry (DEXA) and upper gastrointestinal endoscopy, and Frequency Scale for the Symptoms of GERD score in consecutive outpatients aged ≥50 years at our hospital. We divided the subjects into an osteoporosis group and a non-osteoporosis group and investigated risk factors for osteoporosis between the two groups by bivariate and multivariate analyses.Results: Of the 255 eligible study subjects, 43 (16.9%) had osteoporosis. Bivariate analysis showed that advanced age, female sex, lower body mass index, lower cumulative alcohol intake, lower Brinkman index, H. pylori positivity, lower hemoglobin, bone-specific alkaline phosphatase, lower prevalence of hiatal hernia, and endoscopic gastric mucosal atrophy were related to osteoporosis. Multivariate analysis showed that advanced age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.07–1.19, P

Background. We investigated the prevalence, symptoms, and QOL impact of esophageal (EI), gastric (GI), and duodenal mucosal injury (DI) individually between low-dose aspirin (LDA) users and nonusers to reveal the clinical features of LDA-related mucosal injury.Methods. Data were extracted from the records of subjects who underwent upper gastrointestinal endoscopy at our department between April 2008 and December 2013. Responses from 3162 elderly patients on Frequency Scale for Symptoms of GERD (FSSG) and SF-8 QOL questionnaires (SF-8) were analyzed. FSSG items were classified into total score (TS), reflux score (RS), and dyspepsia score (DS). The SF-8 questionnaire consisted of the physical component summary (PCS) and mental component summary (MCS).Results. Prevalence among LDA users and nonusers, respectively, was 9.6% and 10.0% (P=0.83) for EI, 35.9% and 27.5% (P=0.0027) for GI, 3.3% and 3.4% (P=0.84) for DI, and 8.2% and 5.2% (P=0.036) for mucosal injury in 2 or more organs. LDA users diagnosed with EI had significantly lower PCS, LDA users diagnosed with GI had significantly lower DS, and LDA users diagnosed with DI had significantly lower RS and significantly lower MCS.Conclusion. These results provide important clinical information indicating that symptom-based management is not appropriate in LDA users regarding upper gastrointestinal mucosal injury.

Summary Background Effects of long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized. Aim To investigate colonoscopic findings and prevalence of adverse events following long-term use of NSAIDs. Methods The study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age- and sex-matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre-endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics. Results The occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1-30 years (mean 7.8). Nine of 13 patients (69.2%) took low-dose aspirin. Conclusion The prevalence of colonic lesions in long-term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non-NSAIDs users. The most common features of NSAIDs-associated colitis were segmental ischeznia.

We report the first case-control study in Japan on the prevalence of non-steroidal anti-inflammatory drug (NSAID)-induced gastroduodenal ulcer and the prophylactic effect of co-administered anti-ulcer drugs in regular NSAID users. The NSAID users were 125 patients with rheumatoid arthritis (RA) and without gastrointestinal symptoms while regularly taking NSAIDs (>1 month). The NSAID non-users were125 age- and sex-matched healthy individuals seen between April 2001 and September 2003. Gastric ulcer prevalence was significantly higher among NSAID users than non-users and the odds ratio was 9.50 (95% CI: 2.21-40.8), while that of duodenal ulcers and reflux esophagitis was similar between users and non-users and the odds ratios were 1.11 (0.45-2.73) and 2.00 (0.68-5.85), respectively. The odds ratios for ulcers with concomitant treatment with a proton pump inhibitor or prostaglandin E1 analogue were 0.12 and 0.72 respectively, and were even lower than H2 receptor antagonist and mucosal-protective drug. In conclusion, gastric ulcer prevalence was significantly higher in Japanese RA patients using NSAIDs than in healthy non-users. Concomitant proton pump inhibitor or prostaglandin therapy was effective in preventing NSAID-induced ulcers.

It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC.Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method.The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial.The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Recent studies have reported that proton pump inhibitor (PPI)/amoxicillin (A) metronidazole (M) therapy for Helicobacter pylori infection provides a sufficient cure rate in Japan in patients who have failed first-line treatment with PPI/amoxicillin and clarithromycin (AC). To validate the efficacy of this regimen as second-line therapy, our experience with second-line treatment using a PPI/AM regimen was reviewed. We analyzed data on 151 patients who had been prescribed a 10-day PPI/AM re-treatment regimen after eradication failure of 1 to 2 weeks’ first-line PPI/AC therapy. The PPI/AM regimen was given according to results of susceptibility testing (S+) in 31 patients. The group that had undergone susceptibility testing was further divided into two subgroups according to dosage: standard dose of omeprazole (O)/AM (n = 11) and double dose of lansoprazole (L)/AM (n = 20). The PPI/AM regimen was given without susceptibility testing (S−) to 120 patients. These patients were also divided into two subgroups according to whether they received omeprazole or lansoprazole: OAM (n = 61) and LAM (n = 59). Cure rates and adverse effects in each group were analyzed. The intention-to-treat (ITT)-based cure rate with/without susceptibility testing was 93.5% (95% confidence interval [CI], 79%–99%) and 87.5% (95% CI, 80%–93%), respectively (not significant [NS]). The ITT-based cure rate in S+/S− for OAM and S+/S− for LAM was 90.9% (95% CI, 59%–100%)/82% (95% CI, 70%–91%), and 95% (95% CI, 75%–100%)/93.2% (95% CI, 84%–98%), respectively (NS). Adverse effects were seen in 26.3% and 32.5% of patients in the OAM group and the LAM group, respectively (NS). The 10-day PPI/AM re-treatment regimen is safe and effective, suggesting its usefulness as second-line treatment in Japan in patients who have failed initial treatment with the PPI/AC regimen.

Background: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. Aim: To investigate oesophageal hypersensitivity in Japanese NERD patients. Patients and methods: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. Results: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 ′ 3.4, 4.4 ′ 3.4, 27.8 ′ 26.7, respectively) were higher than in erosive GERD (3.2 ′ 3.3, 3.0 ′ 3.2, 18.2 ′ 24.8) and Barrett patients (2.5 ′ 4.0, 1.8 ′ 3.3, 15.0 ′ 28.8), and significantly higher than in the control group (1.7 ′ 2.7, 1.1 ′ 2.0, 5.4 ′ 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). Conclusion: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Background: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. Aim: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio. Methods: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System. Results: In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 ′ 20.8 ng/mL, 9.2 ′ 4.2 ng/mL, 6.0 ′ 1.7 and 53.5 ′ 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 ′ 46.6 ng/mL, 25.9 ′ 17.1 ng/mL, 3.4 ′ 1.3 and 131.9 ′ 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months. Conclusion: The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Summary Background: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. Patients and methods: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin–clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. Results: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole–amoxicillin–clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66–92%) and 92.4% (79–98%), respectively, and there was no significant difference between these two groups. Conclusion: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Summary Background : It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. Aim : To clarify the histological changes after the cure of H. pylori infection through a literature survey. Methods : Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. Results : Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Five of 28 studies described significant improvement of intestinal metaplasia. Conclusions : Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

Background and Objective.H. pyloriinfection causes a chronic inflammation in the gastric mucosa. However, this local inflammation may result in extra-digestive conditions. Our aim is to investigate the relationship betweenH. pyloriinfection and osteoporosis in Japan.Methods. This cross-sectional study was conducted among outpatients at the Juntendo University Hospital between 2008 and 2014. Participants for patient profile,H. pyloriinfection status, comorbidity, internal medical therapies, lumbar dual-energy X-ray absorptiometry (DXA), and bone turnover marker were collected and upper gastrointestinal endoscopy for reflux esophagitis, hiatal hernia, peptic ulcer disease (PUD), and endoscopic gastric mucosal atrophy (EGA) was performed. The diagnosis of osteoporosis was performed in accordance with the Japanese criteria. We investigated risk factors of osteoporosis.Results. Of the eligible 200 study subjects, 41 cases were of osteoporosis. Bivariate analysis showed that age, being female, BMI, alcohol, smoking,H. pylori, bone-specific ALP, PUD, and EGA were related to osteoporosis. Multivariate analysis showed that age (OR 1.13; 95%CI 1.07–1.20), being female (OR 4.77; 95%CI 1.78–12.77), BMI (OR 0.79; 95%CI 0.68–0.92),H. pylori(OR 5.33; 95%CI 1.73–16.42), and PUD (OR 4.98; 95%CI 1.51–16.45) were related to osteoporosis.Conclusions.H. pyloriinfection may be a risk factor of osteoporosis in Japan.

Background and Aim: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen. Methods: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80%. As a result, data on 114 patients (83 males and 31 females; mean age 49.1 ± 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation. They had either repeated the PPI/AC regimen (n = 34; 5–14 days), or had been administered the PPI/AM regimen (n = 80; 10 days). The cure rates of the two regimens were compared. Results: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35–70) versus 81.3% (95% CI, 71–89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42–79) versus 91.4% (95% CI, 81–97) by per-protocol analysis (P < 0.01). Conclusion: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.

Background: Some of mucosal defensive agents have anti-Helicobacter pylori activities. However, their effectiveness in eradicating H. pylori infection has not been evaluated. Aim: To assess the additive effect of mucosal defensive agents in eradication regimens using statistical analysis. Methods: Pertinent studies were retrieved using the Medline and the Igaku–chuo–zasshi databases in Japan, reference and congress abstract lists. Studies in which regimens consisted of dual or triple therapy with mucosal defensive agents and without them, were selected from the retrieved studies. Eradication rates were extracted from studies according to intention-to-treat analysis. We evaluated the efficacies of mucosal defensive agents by pooled relative risk of eradication rates and its 95% confidence intervals (95% CI), which were calculated by Mantel–Haenszel method. Heterogeneity among the studies in treatment effect was evaluated by a χ2-test. Results: In dual therapy regimens, mucosal defensive agents demonstrated significant additive effects (pooled relative risk 1.41; 95% CI: 1.24–1.61). In triple therapy regimens, these agents did not provide significant additive effect. The clinical usefulness of specific agents could not be established, when each agent was analysed independently. Conclusions: Mucosal defensive agents improve the cure rate when used with existing dual therapy regimens for eradicating H. pylori infection.

Although there are many reports of the high diagnostic accuracy of commercially available serologic kits for Helicobacter pylori infection in Western countries, they rarely has been investigated in oriental population. Accordingly we examined their usefulness in 492 Japanese patients with dyspeptic symptoms. Diagnostic accuracy of 4 imported serologic kits (HEL-p TEST, HM CAP, G.A.P IgG, Helico G2) was investigated using the (13)C-urea breath test as the gold standard. When intermediate results were excluded, the sensitivity, specificity and accuracy of these serologic tests ranged from 88.6% to 97.8%, 67.9% to 85.9%, and 87.9% to 91.4%, respectively, which were comparable with reported median accuracy in the Western population. However, there were many intermediate results in these tests, ranging from 5.3% to 23.0%. Their usefulness seemed to be limited in our patient population because of the large number of intermediate results.