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A 60-year-old man with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor was referred to our hospital because of his refractory watery diarrhea. Ileocolonoscopy revealed increased capillary growth, fine granular mucosa, and longitudinal mucosal tears mainly in the left side of the colon. A bioptic examination revealed thickened subepithelial collagen bands, thus confirming the diagnosis of collagenous colitis. Systemic steroid therapy was initiated, but his symptoms recurred when tapering the steroid. However, withdrawal of the DPP-4 inhibitor was successful even after the cessation of steroid therapy. We therefore considered his collagenous colitis to have been caused by the DPP-4 inhibitor.

The virtual scale endoscope (VSE) is a new endoscope that helps estimate the size of neoplasms in the gastrointestinal tract. We compared the accuracy of polyp size estimation by VSE with that of visual estimation. A dual center prospective study was conducted in two Japanese academic endoscopy units. Ten endoscopists (five trainees and five experts) estimated the size of 20 simulated polyps in four colon phantoms during colonoscopy by two methods: conventional visual estimation and estimation by VSE. The primary endpoint was the relative accuracy in relation to true polyp size according to visual estimation and VSE estimation during colonoscopy. The secondary endpoint was the required time (the time needed to measure in each procedure). The mean values of the primary end-point were 62.5% for visual estimation and 84.0% for VSE estimation; hence the result differed significantly (95% confidence interval 18.3-24.7; P 0.001). The mean of required times was significantly longer for estimation by VSE (6.4 min) than that by visual estimation (2.9 min; P 0.001). The accuracy of colorectal polyp size estimation was superior with VSE than with visual estimation during colonoscopy. In the future, VSE should be evaluated in actual clinical settings, including the time required for size estimation.

The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI).The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI.A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI.Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility.

The Colonoscopy Screening and Surveillance Guidelines were developed by the Japan Gastroenterological Endoscopy Society as basic guidelines based on the scientific methods. The importance of endoscopic screening and surveillance for both detection and post-treatment follow-up of colorectal cancer has been recognized as essential to reduce disease mortality. There is limited high-level evidence in this field; therefore, we had to focus on the consensus of experts. These clinical practice guidelines consist of 20 clinical questions and eight background knowledge topics that have been determined as the current guiding principles.

Background Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color. Objective To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract. Design A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863). Setting 16 university hospitals and 3 tertiary care hospitals in Japan. Patients 1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer. Intervention WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group). Measurements Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome). Results 752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50; P = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]). Limitation Endoscopists were not blinded. Conclusion LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach. Primary funding source Fujifilm Corporation.

This study was to examine the recent trends in upper gastrointestinal bleeding in Japan using a large-scale real-world database. The incidence of upper gastrointestinal bleeding was evaluated in the Japan Medical Data Center claims database of 13,019,713 patients aged 20 to 74 years with traceability for 3 months from 2009 to 2014. The incidence was compared with peptic ulcers and gastroesophageal reflux disease. The prescription of medications was also evaluated. The incidence of bleeding was 0.137%, 0.121%, 0.113%, 0.106%, 0.099%, and 0.105% during 2009 to 2014 with a time-dependent decline (p10 times higher than the incidence of bleeding) decreased with time (p

We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study.We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative,2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C).Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS.ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Objective: The aim of this study was to determine the characteristics of patients without Helicobacter pylori infection who were prescribed antacid medications (potassium-competitive acid blockers, proton pump inhibitors, and/or H2 receptor antagonist) and had no upper gastrointestinal lesions detected by endoscopy. Methods: This cross-sectional study included the patients who underwent upper gastrointestinal endoscopy in our institution between August 2017 and July 2018. They were aged from 55 to 89 years, had no upper gastrointestinal lesions detected by endoscopy, and no H. pylori infection. Exclusion criteria comprised low-dose aspirin and/or nonsteroidal anti-inflammatory drugs. The subjects were allocated to middle-aged (55–69 years) and older age groups (70–89 years). The relationships between antacid medications and patient lifestyle and comorbidities were evaluated by multivariate analyses. Results: Of the 420 patients, 272 were in the middle-aged group and 148 patients in the older age group. Age was found to be a risk factor for antacid medications in both groups (p = 0.002, p = 0.007). No other lifestyle related factors were risk factors. As to comorbidities, hiatal hernia was positively associated with antacid medications in the middle-aged group (p = 0.002). Hypertension and Ca-blockers were positively associated with prescription of antacids in the older age group (p = 0.013); this association was not significant in the middle-aged group. Conclusions: Three lifestyle-related and/or comorbidity-associated factors known to exacerbate gastroesophageal reflux, namely, age, hiatus hernia, and Ca-blockers, were associated with prescription of antacid medications, even in patients without endoscopic reflux esophagitis.

Background: In both Western countries and in Japan, the incidence of colonic diverticular bleeding has increased with increased use of antithrombotic and nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the Japan Gastroenterological Association issued guidelines for colonic diverticular bleeding and colonic diverticulitis in Japanese in 2017 and in English in 2019. However, the guidelines contain unresolved problems. Herein, we review the recent treatment trends for colonic diverticular bleeding in Japan. Summary: Colonic diverticular bleeding necessitates frequent blood transfusions due to rebleeding, and patients require prolonged hospitalization. Endoscopic treatment plays an important role in treating diverticular bleeding. Currently, endoscopic band ligation (EBL) and endoscopic clipping are used in Japan for diverticular hemorrhage when the source of the hemorrhage is identified. EBL results in significantly lower early (Key Messages: EBL is superior to endoscopic clipping regarding short- and long-term rebleeding rates and the rate of transition to surgery and embolization. Methods for preventing diverticular hemorrhage have not been established, but NSAIDs should be discontinued if possible. Prevention strategies for diverticular bleeding need to be evaluated in studies with large sample sizes.

When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM). This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC. This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients. The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p

Background/Aims: Proton pump inhibitors (PPIs) are widely used for the management of acid-related diseases. This study aimed to clarify the status of PPI use in hospitalized patients. Method: A retrospective observational study was performed. We analyzed PPI prescription data for the past 8 years (2009–2016) using Diagnosis Procedure Combination survey data from approximately 10,000 patients per year at Saga University Hospital. We investigated the trend in the number of hospitalized patients who were prescribed PPI for the past 8 years and the changes in patient characteristics. Results: We identified 11,009 patients using PPIs throughout the study period. PPI prescription proportions significantly increased over the study period. The use of PPIs increased steadily with increasing age. The proportion of PPIs prescribed was 1.3-times higher among men than compared with women. In most clinical departments, the number of patients prescribed PPIs was up to 3 times higher in the second half of the period (2013–2016) compared with the first half of the period (2009–2012). The number of patients taking concomitant PPIs and anticoagulants or dual antithrombotic combination therapy increased. Conclusion: PPI use has increased substantially in hospitalized patients. The prevalence of PPI prescription by doctors other than gastroenterologists also increased.

Objective This historical control study was performed to evaluate i) the rebleeding rate of bleeding colon diverticula treated with endoscopic band ligation (EBL) versus endoscopic clipping (EC) and ii) risk factors for rebleeding of diverticula initially treated by endoscopic hemostasis. Methods From January 2010 to December 2012, 68 patients were treated with EC, and from January 2013 to August 2016, 67 patients were treated with EBL. All patients in each group were followed up for one year to check for rebleeding. Results The rebleeding rate was lower in the EBL group (7 of 67, 10%) than in the EC group (21 of 68, 31%; p

Background and aim Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG-Asc) solution versus the combination of sodium picosulfate and 1-L PEG-Asc solution as bowel preparation for colonoscopy. Methods This multi-center, randomized, observer-blinded, non-inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1-L PEG-Asc group (group A) or the sodium picosulfate plus 1-L PEG-Asc group (group B). The quality of the bowel cleansing level was assessed by the Boston Bowel Preparation Scale (BBPS) and compared the bowel cleansing level between the groups. Data regarding bowel preparation time, patients' tolerability, and adverse events were also analyzed. Results Data for 196 patients (99 in group A and 97 in group B) were analyzed finally. BBPS was comparable between group A and B (8.3 ± 0.9 vs. 8.3 ± 0.7; P = 0.88). Consequently, the adequate bowel preparation rate in groups A and B was 95.0% and 99.0%, respectively (-4.0%, 95% CI -9.3 to 1.5). Bowel preparation time in group A was similar to that in group B (348.2 ± 79.8 min vs. 330.8 ± 82.5 min; P = 0.13), whereas, sleep disturbance was significantly less frequent in group A than in group B (10.2% vs. 22.7%; P = 0.02). Conclusions The combination of elobixibat and 1-L PEG-Asc can be considered an alternative bowel preparation for colonoscopy considering the equivalent bowel cleansing effect and less frequent sleep disturbance. The Japan Registry of Clinical Trials (jRCTs41180026).

Aims: The influence of lifestyle-related factors, including smoking and drinking, was evaluated for Helicobacter pylori eradication therapy with vonoprazan or proton pump inhibitors (PPIs). Methods: Between 2012 and 2016, the medical records of 620 patients receiving H. pylori eradication therapy at Saiseikai Karatsu Hospital were evaluated. Patients had received vonoprazan (20 mg) or PPIs with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 days. The influence of lifestyle-related factors on eradication failure was determined in the 2 groups. Results: The eradication rates for vonoprazan and lansoprazole, rabeprazole, and esomeprazole were, respectively, 91.0, 73.8, 72.0, and 84.6%. The vonoprazan eradication rate was significantly higher than those for the PPIs (p < 0.01). Habitual smoking and drinking did not increase eradication failure, and smoking and drinking during the eradication period did not reduce the eradication rate. Metabolic syndrome-related factors including obesity, hypertension, and diabetes mellitus had no negative influence on the eradication rate. Eradication with vonoprazan was more effective compared with that achieved through the use of PPIs. Conclusion: Lifestyle-related factors including smoking and drinking did not exacerbate the H. pylori eradication failure, and vonoprazan was more effective than the PPIs.

Objective The aim of this study was to clarify the safety of colorectal endoscopic submucosal dissection (ESD) during the era of health insurance coverage starting from April 2012 in Japan. Methods Between April 2012 and May 2016, ESD was applied to 398 lesions in 373 patients. Risk factors for serious complications of colorectal ESD, perforation and post-ESD bleeding, were evaluated focusing on the resected specimen size, location, growth pattern, invasion depth, histopathology, postoperative clipping, and procedure time. In addition, the relationship between serious complications and patients' background characteristics was analyzed. Results Among 373 patients, perforation occurred in 12 patients and post-ESD bleeding in 19 patients. A univariate analysis showed that the risk factors for perforation were the lesion size, the resected specimen size, and a long operation time. A multivariate analysis showed that a long operation time was a risk factor for perforation during colorectal ESD. A univariate analysis indicated that significant risk factors for postoperative bleeding were a long operation time, rectal lesion, and cancer. All patients with serious complications were treated by an endoscopic procedure without blood transfusion or the need to convert to open surgery. Conclusion The present study suggests that colorectal ESD may be accepted with relative safety in Japan as a common therapeutic approach for early colorectal cancer.

Background and Aims No reports have described the immunogenicity and boosting effect of the quadrivalent inactivated influenza vaccine (QIV) in adults with inflammatory bowel disease. Methods Adults with Crohn’s disease or ulcerative colitis were randomly assigned to a single vaccination group or booster group, and a QIV was administered subcutaneously. Serum samples were collected before vaccination, 4 weeks after vaccination, and after the influenza season in the single vaccination group. In the booster group, serum samples were taken before vaccination, 4 weeks after the first vaccination, 4 weeks after the second vaccination, and after the influenza season. We measured hemagglutination inhibition antibody (HAI) titer and calculated the geometric mean titer ratio (GMTR), seroprotection rate, and seroconversion rate. Results In total, 132 patients were enrolled. Twenty-two patients received immunomodulatory monotherapy and 16 received anti-tumor necrosis factor-α (anti-TNF-α) single-agent therapy. Fifteen patients received combination therapy comprising an immunosuppressant and anti-TNF-α agent. Each vaccine strain showed immunogenicity satisfying the European Medicines Agency criteria with a single inoculation. The booster influenza vaccination did not induce additional response. In patients administered infliximab, the seroprotection rate and seroconversion rate tended to be lower in patients who maintained blood concentrations [seroprotection rate: H1N1: OR, 0.37 (95% CI, 0.11–1.21); H3N2: 0.22 (0.07–0.68); seroconversion rate: H1N1: 0.23 (0.06–0.91); H3N2: 0.19 (0.06–0.56)]. Conclusion Single dose QIV showed sufficient immunogenicity in patients with inflammatory bowel disease, and a boost in immunization by additional vaccination was not obtained. Additionally, immunogenicity was low in patients receiving infliximab therapy.

Background/Aims: The role of an undifferentiated component in submucosal invasion and submucosal invasion depth (SID) for lymph node metastasis (LNM) of early gastric cancer (EGC) with deep submucosal invasion (SID ≥500 μm from the muscularis mucosa) after endoscopic submucosal dissection (ESD) has not been fully understood. This study aimed to clarify the risk factors (RFs), including these factors, for LNM in such patients. Methods: We enrolled 513 patients who underwent radical surgery after ESD for EGC with deep submucosal invasion. We evaluated RFs for LNM, including an undifferentiated component in submucosal invasion and the SID, which was subdivided into 500–999, 1,000–1,499, 1,500–1,999, and ≥2,000 µm. Results: LNM was detected in 7.6% of patients. Multivariate analysis revealed that an undifferentiated component in submucosal invasion (OR 2.22), in addition to tumor size >30 mm (OR 2.51) and lymphatic invasion (OR 3.07), were the independent RFs for LNM. However, the SID was not significantly associated with LNM. Conclusion: An undifferentiated component in submucosal invasion was one of the RFs for LNM, in contrast to SID, in patients who underwent ESD for EGC with deep submucosal invasion. This insight would be helpful in managing such patients.

Background The aim of this study was to evaluate the differences in upper gastrointestinal symptoms between generations and genders in relatively healthy Japanese subjects. Methods Altogether, 4086 healthy Japanese male and female (M/F) adults (M/F: 2244/1842) were analyzed. Among them, 3505 subjects (M/F: 1922/1583) were underwent a routine medical checkup at one of five hospitals in Saga, Japan from January 2013 to December 2013. The others were 581 (M/F: 322/259) healthy young volunteers at the Saga Medical School from April 2007 to March 2013. The participants were asked to complete the frequency scale for the symptoms of gastroesophageal reflex disease (FSSG) questionnaire, undergo upper gastrointestinal endoscopy, and submit to a rapid urease test to diagnose Helicobacter pylori infection. Among the 4086 subjects, the 2414 who had no H. pylori infection and no positive endoscopic findings were enrolled in the study. Results Subjects’ average age was 46.9 ± 12.2 years, with males’ and females’ ages being almost equivalent. The total FSSG score were high in females compared to males (P

Sufficient information is not available on the extent to which lymph node metastasis (LNM) and prognosis are affected by submucosal manipulation during endoscopic submucosal dissection (ESD) for submucosal invasive gastric cancer (SMGC). We aimed to identify the effects of submucosal manipulation during ESD on LNM and prognosis in patients with SMGC. From 19 institutions in Japan, 2526 patients who failed to meet the current curative criteria for ESD between 2000 and 2011 were recruited. After exclusion, 1969 patients were remained. Based on the treatment strategy after ESD, 1064 patients underwent additional radical surgery. A total of 890 of 1064 patients with SMGC, LNM and cancer recurrence, and prognosis were retrospectively reviewed. The median follow-up duration was 67 months. A total of 214 patients had SM1 (depth of tumor invasion from the muscularis mucosae

Background: Bleeding from a colonic diverticulum is serious in aged patients. The aim of this study was to determine the risk factors for high-cost hospitalization of colonic diverticular bleeding using the diagnosis procedure combination (DPC) data. Methods: From January 2009 to December 2015, 78 patients with colonic diverticular bleeding were identified by DPC data in Saga Medical School Hospital. All patients underwent colonic endoscopy within 3 days. The patients were divided into 2 groups: the low-cost group (DPC cost of 500,000 yen). Results: Univariate analysis revealed that aging, hypertension, rebleeding, a low hemoglobin concentration at admission, and blood transfusion were risk factors for high hospitalization cost. Multivariate analysis revealed that rebleeding (OR 5.3; 95% CI 1.3-21.3; p = 0.017) and blood transfusion (OR 3.8; 95% CI 1.01-14.2; p = 0.048) were definite risk factors for high hospitalization cost. Conclusion: Rebleeding and blood transfusion were related to high hospitalization cost for colonic diverticular bleeding.

Objective The aim of this study was to determine the prevalence and risk factors of reflux esophagitis and Helicobacter pylori (H.pylori) infection and their interrelationship in healthy young Japanese volunteers. Methods Between 2010 and 2016, 550 fifth-year medical students at Saga Medical School, aged 22 to 30 years, underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease). H. pylori infection was determined by detecting urinary immunoglobulin G antibodies. Results H. pylori antibodies were detected in 45 of the 550 subjects (8.2%). Endoscopic reflux esophagitis was detected in 38 out of 550 (6.9%): grade A in 37 subjects (97.3%) and grade B in 1. Most subjects with reflux esophagitis were H. pylori-negative (35/37). Nodular gastritis was observed in 33.3% (15/45) of H. pylori-positive subjects. The risk factors for H. pylori infection were drinking well water in childhood, nodular gastritis, and duodenal ulcer scars. The risk factors for endoscopic reflux esophagitis were male gender and obesity (body mass index ≥25). Conclusion This study describes the risk factors for H. pylori infection and reflux esophagitis in healthy young Japanese subjects. The prevalence of reflux esophagitis was relatively high, and the infection rate of H. pylori was low compared with the aged Japanese population.

Rationale: Helicobacter pylori infection causes atrophic gastritis in childhood, but atrophic gastritis due to H pylori infection is extremely rare in infancy. The relationship between H pylori infection and chronic diarrhea without protein leakage remains controversial. Patient concerns: An 8-month-old male infant presented to our hospital with severe watery diarrhea, erythema, and failure to thrive from approximately 1 month after birth. Blood, stool, esophagogastroduodenoscopy, total colonoscopy, and H pylori urease analysis results were positive, thereby suggesting atrophic gastritis. Diagnoses: Atrophic gastritis and chronic diarrhea due to H pylori infection. Interventions: We performed H pylori eradication therapy using triple therapy with vonoprazan (6 mg/kg), amoxicillin (300 mg/d), and clarithromycin (120 mg/kg) for 7 days. Outcomes: From approximately 1 week after the H pylori eradication therapy, the frequency of defecation had decreased, stool shape had improved, and body weight had gradually increased. Lessons: H pylori infection can cause atrophic gastritis and chronic diarrhea even in infancy. Early eradication therapy for H pylori infection may be useful for prevention of gastric cancer and improvement in growth disorders.

The aim of this study was to determine the characteristics of patients without Helicobacter pylori infection who were prescribed antacid medications (potassium-competitive acid blockers, proton pump inhibitors, and/or H2 receptor antagonist) and had no upper gastrointestinal lesions detected by endoscopy.This cross-sectional study included the patients who underwent upper gastrointestinal endoscopy in our institution between August 2017 and July 2018. They were aged from 55 to 89 years, had no upper gastrointestinal lesions detected by endoscopy, and no H. pylori infection. Exclusion criteria comprised low-dose aspirin and/or nonsteroidal anti-inflammatory drugs. The subjects were allocated to middle-aged (55-69 years) and older age groups (70-89 years). The relationships between antacid medications and patient lifestyle and comorbidities were evaluated by multivariate analyses.Of the 420 patients, 272 were in the middle-aged group and 148 patients in the older age group. Age was found to be a risk factor for antacid medications in both groups (p = 0.002, p = 0.007). No other lifestyle related factors were risk factors. As to comorbidities, hiatal hernia was positively associated with antacid medications in the middle-aged group (p = 0.002). Hypertension and Ca-blockers were positively associated with prescription of antacids in the older age group (p = 0.013); this association was not significant in the middle-aged group.Three lifestyle-related and/or comorbidity-associated factors known to exacerbate gastroesophageal reflux, namely, age, hiatus hernia, and Ca-blockers, were associated with prescription of antacid medications, even in patients without endoscopic reflux esophagitis.

Up until now, the main driving force for the semiconductor industry is the continual shrinkage of device feature sizes, thereby incorporating more devices per unit area, reducing manufacturing cost and enhancing their performance have been achieved. However, the shrinkage of feature size leads to a reduction of process window imposing an extremely tight requirement for parameters such as critical dimension (CD), edge and width roughness of spaces/trenches, contacts, lines, and tip to tip (T2T) values. At sub 14 nm technology nodes these parameters have a significant influence on the overall device performance. With EUV based pattering becoming the sole option at these advanced nodes, a thorough characterization of the patterning process is of utmost importance before it can be a high-volume manufacturing solution. In this work, we show how e-beam inspection has been used to characterize a single exposure EUV M2 (Metal 2 layer, BEoL) to have an understanding of the different hotspots and intra-field signatures present. Design Based Metrology (DBM) with wide SEM image was employed to measure CD distribution and Edge Placement Error (EPE) distribution of metal layer pattern on the 10nm logic wafer.

Background/Aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study. Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients. Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively. Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.

Background: Additional surgery is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer due to the risk of lymph node metastasis. However, age may affect the clinical management of these patients. Objectives: The aim of our retrospective multicenter study was to clarify whether age affects decision-making after noncurative ESD and if the decision affects long-term outcomes. Methods: Age was classified as follows: non-elderly, n = 811); elderly, 70–79 years (n= 760); and super-elderly, ≥80 years (n = 398). Age associations with the selection for additional surgery were evaluated using logistic regression analysis. Long-term outcomes were also evaluated in each age group. Results: Age was inversely related to the rate of additional surgery, which ranged from 70.0% in the non-elderly group to 20.1% in the super-elderly group (p < 0.001). On multivariate analysis, age p< 0.001), whereas the difference was not significant in the super-elderly group (p = 0.23). Conclusions: Despite the fact that almost 80% of super-elderly patients did not undergo additional surgery, the difference of OS between patients with and without additional surgery was not significant only in patients ≥80 years. Therefore, establishment of criteria for selecting treatment methods after noncurative ESD in elderly patients is required.

Background and study aims The aim of the present study was to determine whether blue-laser imaging (BLI) reduced the miss rate of colon adenomatous lesions compared with conventional white-light imaging (WLI). Patients and methods This was a prospective randomized study of patients undergoing screening and/or surveillance colonoscopy at Saga Medical School, Japan. A total of 127 patients were randomized to tandem colonoscopy with BLI followed by WLI (BLI-WLI group) or WLI followed by WLI (WLI-WLI group). The main outcome measure was the adenoma miss rate. Results The proportion of patients with adenomatous lesions was 62.5 % (40 /64) in the BLI-WLI group and 63.5 % (40 /63) in the WLI-WLI group. The total number of adenomatous lesions detected in the first inspection of the BLI-WLI and WLI-WLI groups was 179 and 108, respectively, compared with 182 and 120 in the second inspection, respectively. The miss rate in the BLI-WLI group was (1.6 %), which was significantly less than that in the WLI-WLI group (10.0 %, P = 0.001). Conclusions Colonoscopy using BLI resulted in a lower colon adenoma miss rate than WLI. Trial registration UMIN 000015677.

Although radical surgery is routinely performed for patients who do not meet the curative criteria for endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM), this standard therapeutic option may be excessive given the lower number of patients with LNM. Therefore, we aimed to investigate long-term outcomes and validate risk factors predicting recurrence after ESD. Of 15,785 patients who underwent ESD for EGC at 19 institutions between 2000 and 2011, 1969 patients not meeting the curative criteria were included in this multi-center study. Based on the treatment strategy after ESD, patients were divided into radical surgery (n = 1064) and follow-up (no additional treatment, n = 905) groups. Overall survival (OS) and disease-specific survival (DSS) were significantly higher in the radical surgery group than in the follow-up group (p

Background/Aims Upper gastrointestinal symptoms are more frequent and severe in female than in male outpatients in Japan. This study compared the upper gastrointestinal symptoms between healthy male and female young adult volunteers using a questionnaire. Methods In total, 581 third-grade medical students at Saga Medical School aged 22 to 30 years underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease) from 2007 to 2013. Of these 581 students, 298 who were negative for Helicobacter pylori infection and had no particular lesions on endoscopic examination were enrolled in the present evaluation. A symptom was defined as positive when the subject evaluated the frequency of the symptom as sometimes, often, or always. Results The subjects comprised of 163 males (average age, 23.7 years) and 135 females (average age, 23.1 years). Upper gastrointestinal symptoms were more frequent in the females (75 of 135, 55.6%) than males (69 of 163, 42.3%; P < 0.05), with a high score for 4 symptoms (bloated stomach, heavy feeling in the stomach after meals, subconscious rubbing of the chest with the hand, and feeling of fullness while eating meals). Of the 144 subjects (69 males and 75 females) who complained of these symptoms, the females complained of dysmotility symptoms more often than did the males, but this was not true for reflux symptoms. Conclusions This study suggests that females develop upper gastrointestinal symptoms more frequently than do males among the young healthy Japanese population.

A 67-year-old woman with recurrent gastrointestinal bleeding and aortic valve stenosis presented with spurting bleeding from angiodysplasia of the upper jejunum. As electrophoresis revealed decreased levels of high-molecular-weight (HMW) von Willebrand factor (VWF) multimers, she was diagnosed with Heyde's syndrome. After aortic valve replacement, her HMW VWF levels quickly recovered to normal, and the gastrointestinal bleeding ceased. However, capsule endoscopy still revealed gastrointestinal angiodysplasia six months later. This case shows that minute analyses of VWF multimers enable the diagnosis and confirmation of the resolution of Heyde's syndrome, and implies that gastrointestinal angiodysplasia can be attributed to unknown factors other than decreased VWF multimers.

There is a lack of data regarding the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) without curative resection, and the relationship of these outcomes with hospital volumes remains unclear. This study evaluated long-term outcomes of patients who underwent ESD for EGC without curative resection according to hospital volumes in Japan. This multicenter retrospective study evaluated 1,969 patients who did not meet the criteria of the Japanese Gastric Cancer Association for curative resection between January 2000 and August 2011. Hospitals were classified according to the annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). Clinicopathological features, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared across groups after a generalized propensity score matching analysis. In 495 pairs of generalized propensity score-matched patients, the 5-year OS, DSS, and RFS rates were 81.5%, 97.9%, and 97.6% for LMVG; 86.9%, 98.2%, and 97.0% for HVG; and 85.4%, 98.5%, and 97.6% for VHVG, respectively. The 5-year DSS and RFS rates did not significantly differ among the three groups. However, 5-year OS was significantly worse in the LMVG than in the HVG and VHVG (P

Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age.

Background No reports have described the immunogenicity and boosting effect of the quadrivalent influenza vaccine in adults-patients with inflammatory bowel disease (IBD). Methods Adults with Crohn’s disease or ulcerative colitis were randomly assigned to a single vaccination group or booster group, and a quadrivalent influenza vaccine was administered subcutaneously. Serum samples were collected before vaccination, 4 weeks after vaccination and after the influenza season in the single vaccination group and before vaccination, 4 weeks after the first vaccination, 4 weeks after the second vaccination, and after the influenza season in the booster group. We measured hemagglutination inhibition antibody titer and calculated the geometric mean titer ratio, seroprotection rate, and seroconversion rate. Results Totally, 132 patients were enrolled. Twenty-two patients received immunomodulatory monotherapy and 16 received anti-TNF-α single-agent therapy. Fifteen patients received combination therapy comprising an immunosuppressant and anti-TNF-α agent. Each vaccine strain showed immunogenicity satisfying the European Medicines Agency criteria with a single inoculation. The booster influenza vaccination did not induce an additional response. In patients administered infliximab, the seroprotection rate and seroconversion rate tended to be lower in patients who maintained blood concentrations (seroprotection rate: H1N1: OR, 0.37 (95% CI, 0.11–1.21); H3N2: 0.22 (0.07–0.68); seroconversion rate: H1N1: 0.23 (0.06–0.91); H3N2: 0.19 (0.06–0.56)). Conclusions Although single-dose quadrivalent influenza vaccine showed sufficient immunogenicity in the patients with inflammatory bowel disease, the immunogenicity of patients receiving infliximab therapy was low.

Background In Japan, the amount of usage of proton pump inhibitors (PPIs) has been increasing as the indications extended to maintenance treatment of reflux esophagitis and prevention of ulcer recurrence in patients receiving non-steroidal anti-inflammatory agents (NSAIDs) and low-dose aspirins, in addition to the treatment of peptic ulcer. This study aimed to clarify the status of use of PPIs in hospitalised patients with Diagnosis Procedure Combination (DPC) data. Methods A retrospective observational study was carried out. We analysed the PPI prescription data for past 8 years (2009–2016) using the DPC survey data of approximately ten thousand patients a year in Saga university hospital. The primary objective is to investigate the trend of a number of hospitalised patients who were prescribed PPI for the past 8 years. The secondary objective is to investigate the changes in the characteristics of patients (age, indication, concomitant medication, and clinical department that follows a patient). Lists of proton pump inhibitors subjected to the survey are omeprazole, esomeprazole, lansoprazole, rabeprazole and vonoprazan. Results We identified 11 009 patients using PPIs throughout the study period. Prevalence of PPI use was higher among male than female, approximately 1.3 times. The average age of PPI users was 67.8 years. The number of PPI users increased 1.5 times during the study period, from 1071 (10.5% of inpatients) in 2009 to 1581 (12.3% of inpatients) in 2016. Lansoprazole was the most commonly used agent (30.7%–50.5%) during the study period, followed by rabeprazole (29.3%–48.6%) and esomeprazole. A newer agent, vonoprazan exhibited substantial growth in prescription rates (2.4% in 2015 and 13.8% in 2016). In most of the clinical departments, especially emergency and critical care medicine, neurology, cardiovascular surgery and nephrology, the number of patients prescribed PPIs was up to 3 times higher in the second half of the period (2013–2016) than in the first half of the period (2009–2012). Patients received PPIs concomitantly with NSAIDs and antithrombotic agents has been increased. Conclusions The use of PPIs, as well as the approved indications for PPIs, has increased substantially in hospitalised patients. The prevalence of PPI prescription by doctors other than gastroenterologists also increased.

Background: The term “acute esophageal mucosal lesion (AEML)” includes black esophagitis, and non-black esophagitis characterized by diffuse circumferential erosions without black-appearing mucosa. Black esophagitis is easily diagnosed, whereas non-black esophagitis is often misdiagnosed as severe reflux esophagitis (sRE). The aim of this study was to determine differences in clinical characteristics of patients with AEML and those with sRE. Methods: Thirty-nine patients with sRE and 32 patients with AEML were diagnosed on the basis of endoscopic findings from 2009 to 2016. Characteristics assessed included age, sex, medication use, coexisting endoscopic finding, comorbidities, laboratory tests results, and chief complaints. Results: In contrast with sRE, male sex, need for emergency endoscopy, presence of duodenal lesions, hypertension, and renal dysfunction were positively associated with AEML. Analysis of associations between laboratory data and AEML showed that high white blood cell count, blood urea nitrogen, and blood glucose were significantly associated with an increase OR for AEML. Conclusions: We showed that AEML differed from sRE regarding both endoscopic findings and clinicopathological features. AEML has not been widely recognized, but it should be defined as a distinct inflammatory disease of the esophagus consisting of both black and non-black esophagitis.

We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case-control study using a large-scale medical database in Japan.We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month.The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia.This case-control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.

The influence of lifestyle-related factors, including smoking and drinking, was evaluated for Helicobacter pylori eradication therapy with vonoprazan or proton pump inhibitors (PPIs).Between 2012 and 2016, the medical records of 620 patients receiving H. pylori eradication therapy at Saiseikai Karatsu Hospital were evaluated. Patients had received vonoprazan (20 mg) or PPIs with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 days. The influence of lifestyle-related factors on eradication failure was determined in the 2 groups.The eradication rates for vonoprazan and lansoprazole, rabeprazole, and esomeprazole were, respectively, 91.0, 73.8, 72.0, and 84.6%. The vonoprazan eradication rate was significantly higher than those for the PPIs (p0.01). Habitual smoking and drinking did not increase eradication failure, and smoking and drinking during the eradication period did not reduce the eradication rate. Metabolic syndrome-related factors including obesity, hypertension, and diabetes mellitus had no negative influence on the eradication rate. Eradication with vonoprazan was more effective compared with that achieved through the use of PPIs.Lifestyle-related factors including smoking and drinking did not exacerbate the H. pylori eradication failure, and vonoprazan was more effective than the PPIs.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy produces noise at a level such that patients often complain. However, the noise level has not been measured digitally. METHODS: We evaluated 3 types of HFNCs without filters and 2 types with filters attached for noise reduction. Optiflow (with and without a filter), MaxVenturi (with and without a filter) and AIRVO2 (without a filter only) were positioned at the center of a hospital room. We measured the noise levels at the distance of 1 m from the equipment at various total flows (30, 40, 50, 60 L/min) and F IO 2 (0.40, 0.60, and 0.90). RESULTS: Noise levels were increased with the AIRVO2 and MaxVenturi when total flow and F IO 2 were increased. Noise levels decreased with the MaxVenturi when a filter was used. The noise level did not change with the Optiflow when total flow and F IO 2 were increased. The noise level decreased in the groups with AIRVO2 and Optiflow compared with MaxVenturi without a filter. CONCLUSIONS: The findings in this study show that the noise level of HFNC/Venturi could be reduced by attaching an intake filter. However, the noise level of HFNC/blender and HFNC/turbine decreased in comparison with HFNC/Venturi without an intake filter

Background: The aim of the present study was to determine differences in the prognosis of patients in Japan who underwent emergency endoscopic hemostasis (i) during regular hours versus off hours and (ii) as outpatients versus hospitalized patients. Methods: The present retrospective study included 443 patients who underwent emergency endoscopic hemostasis for non-variceal upper gastrointestinal bleeding from January 2008 to December 2014. These patients were classified into 2 groups: hospitalized patients and outpatients. The outpatients were further subclassified into those who visited the hospital during regular hours and those who visited during off hours. Results: The outcomes of outpatients who underwent emergency hemostasis during off hours did not differ from patients treated during regular hours. Multivariate analysis revealed that outcomes of hospitalized patients, including mortality, need for blood transfusion and length of hospitalization, were worse than those of outpatients; it also revealed that patient age, malnutrition rate and prevalence of diabetes and neoplasms were higher among hospitalized patients than those in outpatients. Conclusions: The clinical outcomes of patients who underwent emergency endoscopic hemostasis for upper gastrointestinal bleeding during off hours did not differ from those of patients treated during regular hours. Outcomes were worse among hospitalized patients, mainly because of their bad general condition.

At each of the 89th to the 92nd congresses of the Japan Gastroenterological Endoscopy Society, a series of featured discussion sessions concerning advanced diagnostic endoscopy in the lower gastrointestinal tract were presented. In total, 45 lectures were presented in this subject area. It was shown that, in recent years, several convenient and less invasive colonoscopic modalities have been developed. This review article summarizes these core sessions and the efficacy of the techniques discussed.