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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.

SUMMARYHelicobacter suishosted by hogs is the most prevalent gastric non-Helicobacter pylori Helicobacterspecies found in humans. Recent studies suggest that theH. suisinfection has already induced many cases of gastric disease. However, the infection period and route ofH. suisfrom hogs remain unclear. Because diagnostic methods based on the urease activity ofH. suisoften yield negative judgments, there is no reliable method for diagnosingH. suisinfection in clinical practice without gastric biopsy specimens. We developed the world’s first ELISA to simultaneously diagnoseH. suisandH. pyloriinfection in a single test. The area under the ROC curve was 0.9648 or 0.9200 for identifyingH. suisorH. pyloriinfection, respectively. The sensitivity, specificity, and positive and negative predictive values for identifyingH. suisinfection were 100%, 92.6%, 76.9%, and 100%, and those for identifyingH. pyloriinfection were 88.2%, 87.5%, 65.2%, and 96.6%, respectively. (150 words)

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, This study aimed to investigate the influence of sex on the association between body mass index (BMI) and the presence of upper gastrointestinal symptoms using healthy check‐up subjects. The association between reflux symptoms and higher BMI was limited to males, although sex did not influence the association between the presence of functional dyspepsia (FD) symptoms and lower BMI. The percentage of overlapping of reflux and FD symptoms was higher in women than men.

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±11.4years, 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., 著者最終稿（査読済み）, © 2019 Japan Gastroenterological Endoscopy Society.

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-naive 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-naive 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-naive 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-naive normal stomach. UMIN000018218.

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

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.

Summary Background We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Aim To assess whether antibiotic combination therapy is effective for active UC refractory to or dependent on steroids in a multicentre, open-label trial. Methods We enrolled 30 patients with steroid-refractory and 64 with steroid-dependent active UC. These patients received three-times-daily by mouth amoxicillin 500 mg, tetracycline 500 mg and metronidazole 250 mg, for two weeks, as well as conventional treatment. Symptom assessment and colonoscopic evaluation were performed before enrolment and at 3 and 12 months after treatment completion. Clinical response was defined as a Lichtiger symptom score decrease in ≥3 points and clinical remission as a score ≤4. Results Nineteen of the 30 steroid-refractory (63.3%) and 47 of the 64 steroid-dependent (73.4%) patients showed a clinical response within 2 weeks. At 3 and 12 months, 60% and 66.6% of steroid-refractory patients, and 56.3% and 51.6% of steroid-dependent patients, respectively, achieved clinical remission. In the steroid-dependent group, 39 of the 64 patients (60.9%) were able to stop steroid therapy and remained in remission for 3 months. Three (10%) steroid-refractory and four (6.3%) steroid-dependent patients underwent colectomy. Conclusions This multicentre, long-term follow-up study suggests 2 week antibiotic combination therapy to be effective and safe in patients with active UC refractory to or dependent on steroids.

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.

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.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.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; p0.0001). 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 %, p0.0001; duodenal lesions 5.7 vs. 24.7 %, p0.0001; erosive esophagitis 5.8 vs. 19.4 %, p0.0001). 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).Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.

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.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.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, P0.0001). 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.The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

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.

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.

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.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.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.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.

Summary Aim This large-scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan. Methods This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow-up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection. Results Three-thousand twenty-one patients were enrolled. The median follow-up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62). Conclusion This large-scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.

Summary Aim To conduct a retrospective multicentre study at 31 medical centres in Japan, to investigate the association between the eradication of Helicobacter pylori and the development of new gastric cancer after endoscopic mucosal resection (EMR) for early gastric cancer. Methods Patients included those in whom early gastric cancer had been removed by EMR, and who had received follow-up endoscopic treatment. All patients underwent follow-up endoscopic treatment at least once a year after the initial EMR. The rate of new gastric cancer development was compared among those patients for whom H. pylori had been successfully eradicated and those with persistent H. pylori infection. Results The study included 2835 patients with a median follow-up period of 2 years (range 0.5–12 years). Helicobacter pylori was eradicated in 356 patients (13%). Metachronous gastric cancers developed in eight (2%) patients among those who had been successfully treated for H. pylori, compared with 129 patients (5%) among those with persistent H. pylori infection (P = 0.021; OR = 0.42; 95% CI = 0.20–0.86). Conclusion Although longer term, prospective randomized controlled trials are needed to better estimate the extent and sustainability of possible benefits, this study suggests that the eradication of H. pylori may help reduce the incidence of metachronous gastric cancer.

Tetanic stimulation of high-threshold primary afferent fibers in the dorsal root was found to elicit intrinsic optical signals (IOSs) in transverse slices of 11- to 20-day-old rat spinal cords. The IOS, lasting for 30 s or longer, was most prominent in the lamina II of the dorsal horn. Treatment with a Na+-K+-2Cl- co-transport blocker, furosemide, abolished the IOS, suggesting that the origin of the IOS is the cellular swelling due to an activity-dependent rise in extracellular K+. Substance P antagonist spantide, glutamate antagonists 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, and the mu-opioid agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin suppressed IOSs. Thus, IOSs represent at least in part the slow excitatory response that is known to be generated in dorsal horn neurons after tetanic activation of unmyelinated afferent fibers.

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.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.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.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.

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.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.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.Assessment of endoscopic findings of spotty redness after eradication treatment is useful in the diagnosis of H. pylori eradication.

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.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.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.Combination of endoscopic findings can improve diagnostic accuracy, and sensitivity of examination for inflammation.

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.

Summary 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.

skin, gastrointestinal and genitourinary tracts, cardiac, smooth and skeletal muscle and immune cells (lymphocytes, mast cells and eosinophils). Dysregulation of NGF expression and signalling have been described in allergy, asthma, inflammation in the gut, chronic constipation, coronary artery disease and some cancers. In prostate cancer NGF stimulates tumour cell growth and metastasis and may drive nerve sprouting and infiltration. Inhibiting NGF by using blocking antibodies has a significant analgesic effect and is proposed to decrease metastatic cancer pain. Aim: ProNGF expression has not been previously described in tumours of the gastrointestinal tract. Materials and Methods: The expression of proNGF was examined by immunocytochemistry of esophageal squamous cancer (SCC) (15 cases), gastric adenocarcinoma (10 cases) and colorectal adenocarcinoma (12 cases) and corresponding normal adjacent tissues in the gut in tumour microarrays (Figure 1). Sections were scored for site of cytoplasmic staining in esophagus and cancer grade. Results: All gut epithelial tissue expressed pro-NGF. In normal oesophageal squamous epithelium expression site was diffuse, superficial or basal (Figure 2), in squamous carcinoma, staining was intense and diffuse. In adenocarcinomas (stomach and colon) staining was diffuse, and in intestinal metaplasia (IM) in the stomach, staining was more intense compared to adjacent gastric epithelium. There was no significant difference in intensity of staining by grade of cancer. Conclusions: There is significant expression of pro-NGF in squamous oesophageal and gastrointestinal columnar epithelium in both normal tissue and cancer. Pro-NGF may be therefore be a target of interest in biomarker exploration and therapeutic development for inhibition of cancer growth and cancer pain.

An incremental approach is used to develop the control system of an autonomous robot to approach toward the target object by avoiding obstacles in an environment. The approach consists of two-stage evolution. In the first-stage, controllers are evolved to avoid obstacles in an environment. The final population of the first-stage evolution is then used as the initial population for the second-stage evolution. Controllers are evolved in the second-stage to approach toward the target object by avoiding obstacles in the environment. We compare the performance of the incremental approach with that of conventional approach, an onestage evolutionary approach. It is found that the performance of incremental approach is better than that of conventional approach.

The choice of a fittness function in artificial evolution has strong consequences on the evolvability of robots, dynamics of the evolutionary process, and ultimately on the outcome of the evolutionary process. In this paper, the effect of fitness functions for the evolution of autonomous robots to navigate in an open-environment by avoiding obstacles is studied. It is found that both the number and description of components of a fitness function affect the convergence of the evolutionary process. However, the performance of evolved robots in an unknown environment is greatly dependent on the description of components of a fitness function.