Factors Associated with Overlap between Functional Dyspepsia and Nonerosive Reflux Disease in Endoscopy-based Helicobacter pylori-uninfected Japanese Health Checkup Participants: A Prospective, Multicenter Cross-sectional Study.

Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.

Histopathologic diagnosis of ultra-early autoimmune gastritis: A case report.

We describe an ultra-early stage of autoimmune gastritis (AIG) that occurs prior to the well-known early-stage AIG. The key pathology is the shortening of the second layer with degenerated parietal cells. In the management of patients with autoimmune diseases, AIG should be considered even if the endoscopy findings are normal.

Development of serological assays to identify Helicobacter suis and H. pylori infections.

Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H. suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H. suis urease activity often yield negative results, and there is no reliable method for diagnosing H. suis infection in clinical practice without gastric biopsy specimens. This study presents the world's first use of whole-bacterial cell ELISA to simultaneously assess H. suis and H. pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H. suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H. pylori test.

Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan.

The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.

Incisura angularis belongs to fundic or transitional gland regions in Helicobacter pylori-naïve normal stomach: Sub-analysis of the prospective multi-center study.

OBJECTIVE: Incisura angularis is one of the important parts for evaluating mucosal atrophy and cancer risk. We determined the type of mucosa at incisura angularis in Helicobacter pylori-naïve normal stomach. METHODS: Subjects aged 40 years or older who underwent esophagogastroduodenoscopy for dyspepsia or a routine health checkup were recruited in 24 facilities between March 2008 and February 2009. Serum antibody to H. pylori was measured. Endoscopic atrophy was evaluated according to Updated Kimura-Takemoto classification. Five biopsy specimens were taken from the incisura angularis and greater and lesser curvatures of the antrum and corpus. These specimens were histologically classified as fundic, pyloric or transitional. H. pylori-naïve normal stomach was defined with the strictest criterion among various combinations of histological, endoscopic and serum findings. We determined histological type of mucosa at incisura angularis in H. pylori-naïve normal stomach. RESULTS: A total of 270 subjects (122 men, mean 64.6 yo) were analyzed. The strictest criterion consists of serum antibody ≤ 3.0 U/mL, endoscopic atrophy C-1 and histological grade 0 in all of the five items in Updated Sydney System. The numbers having fundic, transitional and pyloric mucosa at incisura angularis under the strictest criterion were 13 (50%), 13 (50%) and 0, respectively. The probability that the type of mucosa at incisura angularis would be pyloric was almost zero (97.5% confidence interval 0-0.132). CONCLUSIONS: Incisura angularis of the stomach may not belong to pyloric, but fundic or transitional mucosa in H. pylori-naïve normal stomach. UMIN000018218.

Influence of sex on the association between body mass index and frequency of upper gastrointestinal symptoms.

BACKGROUND AND AIM: Upper gastrointestinal symptoms (UGSs), including reflux and dyspeptic symptoms (postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), affect health-related quality of life. However, the influence of sex on the relationship between body mass index (BMI) and UGSs remains controversial. This study investigates the influence of sex on this association in healthy subjects. METHODS AND RESULTS: We utilized the database of a prospective, multicenter, cohort study of 7112 subjects who underwent upper endoscopy for health screening. A multivariable logistic regression analysis was conducted to assess the association between BMI and UGSs stratified by sex, adjusting for clinical features. The influence of sex on the association between the overlapping of UGSs and BMI in symptomatic subjects was also investigated. Reflux symptoms were significantly associated with high BMI (multivariable odds ratio [OR] 1.36; 95% confidence interval [CI] 1.10-1.67, P = 0.004). PDS symptoms were significantly associated with low BMI (OR 2.37; 95% CI 1.70-3.25; P < 0.0001), but EPS symptoms were not associated with BMI. The association between reflux symptoms and higher BMI was limited to men (men: OR 1.40; 95% CI 1.10-1.77; P = 0.005, women: P = 0.40). sex did not influence the association between the presence of PDS symptoms and lower BMI. The percentage of overlapping of all three symptoms (reflux, PDS, and EPS) was higher in women than in men (19.9% [58/292] vs 10.5% [49/468], P = 0.0002). CONCLUSIONS: The influence of BMI on the presence of UGSs was significantly different according to sex in this large-scale cohort.

Multicenter study of autoimmune gastritis in Japan: Clinical and endoscopic characteristics.

BACKGROUND AND AIM: In Japan, the prevalence of autoimmune gastritis (AIG) is assumed to be very low. With the recent rapid decrease in Helicobacter pylori (Hp) prevalence, reports on AIG are increasing. This multicenter registry study aimed to clarify the characteristics of AIG, especially its endoscopic appearance. METHODS: A total of 245 patients with AIG from 11 institutions in Japan from January 2010 to October 2016 were included, and their clinical and endoscopic findings were evaluated. RESULTS: Mean age was 67.2 ± 11.4 years, and 63.7% of the participants were women. The most common approach to diagnose AIG was endoscopic examination. Repeated incorrect treatment for Hp infection, due to a false-positive result in 13 C-urea breath test, ranked third among the basis for diagnosis of AIG. Associated gastric lesions were type 1 neuroendocrine tumor (11.4%), adenocarcinoma (9.8%), and hyperplastic polyps (21.1%). Corpus pan-atrophy was the most common appearance (90.1%); however, remnant oxyntic mucosa was found in 31.5% of the patients (flat, localized type, 48.6%). Sticky adherent dense mucus and scattered minute whitish protrusions were also observed in approximately 30% of the patients. Despite the prevailing presumption of the antral mucosa remaining normal, 42.3% of the patients presented with various extents of atrophy, and patchy redness and circular wrinkle-like patterns were both observed in approximately 20% of the patients. CONCLUSIONS: The present study showed some prominent clinical characteristics and endoscopic findings of AIG. We believe that our study will facilitate the diagnosis of potential AIG.

Factors associated with the presentation of erosive esophagitis symptoms in health checkup subjects: A prospective, multicenter cohort study.

BACKGROUND: We aimed to clarify the factors associated with the presentation of erosive esophagitis (EE) symptoms in subjects undergoing health checkups. METHODS: We utilized baseline data from 7,552 subjects who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The subjects were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Based on the heartburn and/or acid regurgitation frequency, the EE subjects were stratified into the following three groups: (1) at least one day a week (symptomatic EE [sEE]), (2) less than one day a week (mild symptomatic EE [msEE]), and (3) never (asymptomatic EE [aEE]). Postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. RESULTS: Of the 1,262 (16.7%) subjects (male 83.8%, mean age 52.6 years) with EE, the proportions of sEE, msEE and aEE were 15.0%, 37.2% and 47.9%, respectively. The sEE group showed significant associations with overlapping EPS (OR: 58.4, 95% CI: 25.2-160.0), overlapping PDS (OR: 9.96, 95% CI: 3.91-26.8), severe hiatal hernia (OR: 2.43, 95% CI: 1.43-4.05), experiencing high levels of stress (OR: 2.20, 95% CI: 1.43-3.40), atrophic gastritis (OR: 1.57, 95% CI: 1.03-2.36) and Los Angeles (LA) grade B or worse (OR: 1.72, 95% CI: 1.12-2.60) in the multivariate analysis. CONCLUSIONS: Approximately one-sixth of EE subjects were symptomatic. A multifactorial etiology, including factors unrelated to gastric acid secretion, was associated with the symptom presentation of EE subjects.

Influence of hiatal hernia and male sex on the relationship between alcohol intake and occurrence of Barrett's esophagus.

BACKGROUND: The association of alcohol intake with the incidence of Barrett's esophagus (BE) has been inconsistent. Although hiatal hernia and male sex are well-known risk factors of BE, its effect on the association of alcohol intake with the incidence of BE remains unknown. AIM: To investigate whether the influence of alcohol intake on the occurrence of BE might differ depending on male sex and presence of hiatal hernia. METHODS: We utilized a database of 8031 patients that underwent upper endoscopy for health screening in a prospective, multicenter, cohort study (the Upper Gastro Intestinal Disease study). The incidence of endoscopic columnar-lined esophagus (eCLE; endoscopically diagnosed BE) was the outcome variable. Multivariable logistic regression analysis was conducted to assess the association between alcohol intake and eCLE stratified by male sex and hiatal hernia, adjusting for clinical features and other potential confounders. RESULTS: Alcohol intake (≥20 g/day) showed a marginally significant association with the incidence of eCLE in participants without hiatal hernia (0 vs. ≥20 g/day; odds ratio [OR], 1.62; 95% confidence interval [CI], 0.92-2.85, P = 0.09) but not in participants with hiatal hernia (0 vs. ≥20/day; OR, 0.99; 95% CI, 0.59-1.65; P = 0.95). Furthermore, alcohol intake (≥20 g/day) was significantly associated with the incidence of eCLE in male participants without hiatal hernia (0 vs. ≥20 g/day; OR, 1.98; 95% CI, 1.04-4.03; P = 0.04) but not in female participants without hiatal hernia (0 vs. ≥20 g/day; OR, 0.47; 95% CI, 0.03-2.37; P = 0.42). CONCLUSIONS: The effect of alcohol intake on the incidence of eCLE might be associated with hiatal hernia status and male sex.

Atypical symptoms and health-related quality of life of patients with asymptomatic reflux esophagitis.

BACKGROUND AND AIM: Asymptomatic reflux esophagitis (RE) is simply regarded as RE without the typical reflux symptoms, but it is unknown whether patients with asymptomatic RE have atypical symptoms. The aim of this study was to examine the clinical characteristics and health-related quality of life (HRQOL) of patients with asymptomatic RE. PATIENTS AND METHODS: Consecutive patients with RE were enrolled during January 2010 to August 2012, and of them, 41 who had taken acid-suppressing drugs were excluded, leaving 280 patients as the study group. The patients' symptoms were evaluated using a self-completed questionnaire (modified Frequency Scale for the Symptoms of gastroesophageal reflux disease [FSSG]), as well as an HRQOL questionnaire (SF-8). We defined the typical symptoms of RE as heartburn and regurgitation. Asymptomatic RE was defined if the total symptom score was 0 or the minimum (1 point) for typical reflux symptoms in the modified FSSG. RESULTS: Of the 280 RE patients, 71.8% (n = 201) were symptomatic and 28.2% (n = 79) were asymptomatic. The atypical symptom scores were significantly lower in asymptomatic RE (2.2 ± 2.2) than in symptomatic RE patients (6.9 ± 5.2) (P < 0.0001), and the HRQOL scores were significantly higher in asymptomatic RE than in symptomatic RE (P < 0.0001). Sleep was significantly less disturbed and chronic cough less frequent in asymptomatic RE than in symptomatic RE. CONCLUSION: Frequency and severity of atypical symptoms in patients with asymptomatic RE were significantly less than in patients with symptomatic RE, and the HRQOL score was significantly higher in those patients. These observations suggest a specific patient cohort that is truly unlikely to manifest symptoms.

Endoscopic diagnosis of gastric mucosal atrophy: multicenter prospective study.

BACKGROUND AND AIM: Gastric atrophy is one of the important pathological states that cause gastric cancer. As atrophic gastritis is related to the risk of gastric cancer, it is important to diagnose atrophic gastritis. In the present study, we tried to establish endoscopic criteria for atrophic gastritis. METHODS: A multicenter study of prospectively collected patients was conducted in 24 participating facilities. Two hundred and seventy-five patients received endoscopic examination and 15 endoscopic features, including diffuse redness, swelling of areae gastrica, and mucosal swelling, were evaluated. Biopsy specimens were taken from five points recommended by the Updated Sydney System, and evaluated by a single pathologist for atrophy. Sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve (AUC/ROC) of each endoscopic finding to histological atrophy were calculated. Pepsinogen I/II ratios of these patients were measured and compared to the endoscopic features. RESULTS: There was no single endoscopic feature that is highly specific for histological atrophy. In the corpus, the combination of visibility of vascular pattern and swelling of areae gastrica by indigocarmine chromoendoscopy showed the highest AUC/ROC (0.83). In the antrum, the combination of visibility of vascular pattern and mucosal swelling showed the highest AUC/ROC (0.70). These endoscopic findings correlated very well to the pepsinogen I/II ratio. CONCLUSIONS: Combination of endoscopic findings can improve diagnostic accuracy, and endoscopic diagnosis of atrophy is improved especially with new endoscopic criteria, such as swelling of areae gastrica or mucosal swelling.

Endoscopic diagnosis of gastric mucosal activity and inflammation.

AIM: Gastritis is an important pathological state that causes gastric atrophy and cancer. The Sydney System is a well-used classification for histological evaluation for gastritis. However, there is no concordance with endoscopic findings. In the present study, we tried to establish endoscopic criteria and diagnosis for the inflammation activity of gastric mucosa. METHODS: A prospective multicenter study was conducted and 24 facilities participated. Two hundred and seventy patients received endoscopic examinations and 15 endoscopic features were evaluated. Biopsy specimens were taken from five points, and evaluated by a single pathologist for mononuclear cell infiltration and polymorphonuclear cell infiltration. Sensitivity, specificity, positive predictive value, negative predictive value, area under curve of receiver operating characteristics (AUC/ROC) of each endoscopic finding to histological gastritis were calculated. RESULTS: There was no single endoscopic finding that was highly specific for mononuclear cell infiltration and polymorphonuclear cell infiltration. In the corpus, the combination of swelling of areae gastrica by the indigo carmine contrast method (IC method) and lack of a regular arrangement of collecting venules (RAC) in angle for mononuclear cell infiltration (0.887), and the combination of swelling of areae gastrica by the IC method and diffuse redness for polymorphonuclear cell infiltration (0.851) showed the highest AUC/ROC. In the antrum, the combination of diffuse redness and visibility of a vascular pattern for mononuclear cell infiltration (0.780), and the combination of visibility of vascular pattern and swelling of areae gastrica by the IC method for polymorphonuclear cell infiltration (0.795) showed the highest AUC/ROC. CONCLUSION: Combination of endoscopic findings can improve diagnostic accuracy, and sensitivity of examination for inflammation.

Changes in endoscopic findings of gastritis after cure of H. pylori infection: multicenter prospective trial.

BACKGROUND AND AIM: Successful eradication of H. pylori changes pathological findings of gastritis dramatically. However, change of endoscopic mucosal findings is not fully understood. To clarify the short-term changes of endoscopic mucosal findings after cure of H. pylori infection, a multicenter prospective trial was conducted. METHODS: One hundred and forty-seven patients with H. pylori infection from 12 institutions were enrolled into this prospective cohort trial. Nineteen endoscopic findings using high-resolution white light electronic endoscopy were assessed before and 2-4 months after eradication treatment of H. pylori. H. pylori infection was diagnosed by pathology of three stomach sites using hematoxylin-eosin stain or H. pylori-specific immunostaining. Endoscopic features of the successful eradication group and the failed eradication group were compared. The change of severity of endoscopic features before and after H. pylori eradication were compared between successful eradication and failed eradication. RESULTS: One hundred and twenty-six patients were analyzed. Eradication rate was 81% (102/126). Non-transparency of gastric juice, diffuse redness of fundic mucosa, enlarged fold, spotty redness of fundic mucosa, flat erosion of stomach, and hemoglobin index of fundic mucosa were significantly different between the successful eradication group and the failed eradication group. Gastric flat erosion was of higher frequency in the successful eradication group. When eradication was successful, spotty redness of fundic gland improved significantly. CONCLUSION: Assessment of endoscopic findings of spotty redness after eradication treatment is useful in the diagnosis of H. pylori eradication.

Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial.

BACKGROUND: Patients using low-dose aspirin (LDA) have an increased risk of gastroduodenal mucosal lesions and upper gastrointestinal symptoms. We aimed to clarify the efficacy of rabeprazole for preventing peptic ulcer, esophagitis, and gastrointestinal symptoms associated with LDA. METHODS: Patients with a history of peptic ulcers who were receiving LDA for cardiovascular or cerebrovascular disease were randomly assigned to receive rabeprazole at 10 mg daily, rabeprazole at 20 mg daily, or gefarnate (a cytoprotective anti-ulcer agent) at 50 mg twice daily. The primary endpoint was the development of gastric and/or duodenal ulcer at 12 weeks. The modified Lanza score (MLS) and gastrointestinal symptoms were evaluated at baseline and at 12 weeks. RESULTS: The full analysis set comprised 261 patients (rabeprazole 10 mg: n = 87, rabeprazole 20 mg: n = 89, gefarnate 100 mg: n = 85). The cumulative incidences of gastroduodenal ulcers at 12 weeks in the 10 mg rabeprazole group, 20 mg rabeprazole group, and gefarnate group were 7.4, 3.7, and 26.7 %, respectively (rabeprazole group 5.5 % vs. gefarnate group 26.7 %, hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.082-0.394; p < 0.0001). The proportions of patients with an MLS of ≥1 and erosive esophagitis were significantly lower in the rabeprazole group than in the gefarnate group at 12 weeks (gastric lesions 33.5 vs. 62.4 %, p < 0.0001; duodenal lesions 5.7 vs. 24.7 %, p < 0.0001; erosive esophagitis 5.8 vs. 19.4 %, p < 0.0001). Rabeprazole was significantly more effective than gefarnate for the resolution and prevention of gastrointestinal symptoms (resolution 53.6 vs. 25.0 %, p = 0.017; occurrence 9.2 vs. 28.3 %, p = 0.0026). CONCLUSIONS: Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.

Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis.

BACKGROUND AND AIM: Immunosuppressive drugs are recommended for use as replacements of steroid therapy in sustaining remission of steroid-dependent ulcerative colitis (UC). However, discontinuation of these therapeutic agents leads to a high relapse, and their long-term administration has not been proven safe. A newly introduced antibiotic combination therapy led to improvement and remission of active UC. The aim of this study is to examine whether this new therapy can replace immunosuppressive agents and allow discontinuation of steroids in steroid-dependent UC remission. METHODS: 48 patients with steroid-dependent UC were recruited for a 2-week treatment with amoxicillin, tetracycline, and metronidazole (ATM). Examination of clinical symptoms, endoscopy, and histological evaluation were performed before and 6 and 12 months after treatment. RESULTS: The proportion of patients who showed clinical improvement at 6 and 12 months after treatment was 54.2% (26/48) and 75.0% (36/48), respectively. The rate of clinical remission at 6 and 12 months was 31.3% (15/48) and 37.5% (18/48), respectively. Steroid withdrawal was attained in 64.6% (31/48) and 70.8% (34/48) of patients at 6 and 12 months, respectively. Endoscopic improvement was detected in 56.3% (27/48), and histological improvement was detected in 52.1% (25/48) at the final observation point for each patient. CONCLUSION: The triple antibiotic therapy resulted in improvement, remission, and steroid withdrawal in steroid-dependent UC patients.

Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial.

OBJECTIVES: Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC. METHODS: Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred. CONCLUSIONS: The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial.

BACKGROUND: The relation between Helicobacter pylori infection and gastric cancer has been proven in epidemiological studies and animal experiments. Our aim was to investigate the prophylactic effect of H pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer. METHODS: In this multi-centre, open-label, randomised controlled trial, 544 patients with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment or in post-resection follow-up after endoscopic treatment, were randomly assigned to receive an H pylori eradication regimen (n=272) or control (n=272). Randomisation was done by a computer-generated randomisation list and was stratified by whether the patient was newly diagnosed or post-resection. Patients in the eradication group received lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week; those in the control group received standard care, but no treatment for H pylori. Patients were examined endoscopically at 6, 12, 24, and 36 months after allocation. The primary endpoint was diagnosis of new carcinoma at another site in the stomach. Analyses were by intention to treat. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001169. FINDINGS: At 3-year follow-up, metachronous gastric carcinoma had developed in nine patients in the eradication group and 24 in the control group. In the full intention-to-treat population, including all patients irrespective of length of follow-up (272 patients in each group), the odds ratio for metachronous gastric carcinoma was 0.353 (95% CI 0.161-0.775; p=0.009); in the modified intention-to-treat population, including patients with at least one post-randomisation assessment of tumour status and adjusting for loss to follow-up (255 patients in the eradication group, 250 in the control group), the hazard ratio for metachronous gastric carcinoma was 0.339 (95% CI 0.157-0.729; p=0.003). In the eradication group, 19 (7%) patients had diarrhoea and 32 (12%) had soft stools. INTERPRETATION: Prophylactic eradication of H pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. FUNDING: Hiroshima Cancer Seminar Foundation.