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Background: Delta neutrophil index (DNI) is the ratio of the number of immature granulocytes and the total neutrophil count in peripheral circulation. DNI precedes changes in white blood cell or neutrophil counts due to the course of granular leukocyte differentiation in infectious and inflammatory conditions, beginning with immature granulocyte formation. The role of DNI as a biomarker of various infectious or inflammatory conditions has been reported. However, no studies explored the potential role of DNI as an initial biomarker for predicting disease severity, surgical outcomes, and mortality rates of gastrointestinal diseases with pooled diagnostic test accuracy. This study aims to provide evidence that DNI is a predictor of disease severity, surgical outcomes, and mortality rates in patients with gastrointestinal diseases in emergency medical departments. Methods: MEDLINE, EMBASE, and the Cochrane Library will be searched using common keywords (inception to July 2019) by 2 independent evaluators. Inclusion criteria will be patients with gastrointestinal diseases, DNI measurements performed in the emergency department, indices of diagnostic performance (sensitivity, specificity, predictive values, and likelihood ratios) of DNI for predicting severity, surgical outcomes, and mortality rate of gastrointestinal diseases. True and false positives and negatives will be calculated based on the diagnostic indices of each study. All types of study designs with full-text literature written in English will be included. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Descriptive data synthesis will be conducted and quantitative synthesis (bivariate and hierarchical summary receiver operating characteristic model) will be performed if the included studies are sufficiently homogenous. Meta-regression, sensitivity analysis, publication bias, and Fagan nomogram will be analyzed and described. Results: The pooled synthesis of the diagnostic performance of various gastrointestinal diseases with different cut-off values for DNI may limit the interpretation of uniform diagnostic validity. The authors will contact the corresponding authors for the missing values, requesting the original data in each study. However, if there are no responses from these authors, these studies will be excluded. Conclusion: This study will provide diagnostic validity of DNI as an initial marker for the prediction of severity, surgery, and mortality of gastrointestinal diseases.

Background Visual inspection, lesion detection, and differentiation between malignant and benign features are key aspects of an endoscopist’s role. The use of machine learning for the recognition and differentiation of images has been increasingly adopted in clinical practice. This study aimed to establish convolutional neural network (CNN) models to automatically classify gastric neoplasms based on endoscopic images. Methods Endoscopic white-light images of pathologically confirmed gastric lesions were collected and classified into five categories: advanced gastric cancer, early gastric cancer, high grade dysplasia, low grade dysplasia, and non-neoplasm. Three pretrained CNN models were fine-tuned using a training dataset. The classifying performance of the models was evaluated using a test dataset and a prospective validation dataset. Results A total of 5017 images were collected from 1269 patients, among which 812 images from 212 patients were used as the test dataset. An additional 200 images from 200 patients were collected and used for prospective validation. For the five-category classification, the weighted average accuracy of the Inception-Resnet-v2 model reached 84.6 %. The mean area under the curve (AUC) of the model for differentiating gastric cancer and neoplasm was 0.877 and 0.927, respectively. In prospective validation, the Inception-Resnet-v2 model showed lower performance compared with the endoscopist with the best performance (five-category accuracy 76.4 % vs. 87.6 %; cancer 76.0 % vs. 97.5 %; neoplasm 73.5 % vs. 96.5 %; P Conclusion The evaluated deep-learning models have the potential for clinical application in classifying gastric cancer or neoplasm on endoscopic white-light images.

Background The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. Materials and Methods We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through “on‐line database registry” from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. Results Finally, 6738 patients were analyzed. The overall eradication rate of first‐line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P

Background/Aims Frequent bleeding after endoscopic resection (ER) has been reported in patients with end-stage renal disease (ESRD). We aimed to evaluate the association and clinical significance of bleeding with ER in ESRD patients on dialysis. Methods Between February 2008 and December 2018, 7,571 patients, including 47 ESRD patients on dialysis who underwent ER for gastric neoplasia, were enrolled. A total of 47 ESRD patients on dialysis were propensity score-matched 1:10 to 470 non-ESRD patients, to adjust for between-group differences in variables such as age, sex, comorbidities, anticoagulation use, tumor characteristics, and ER method. Matching was performed using an optimal matching algorithm. For the matched data, clustered comparisons were performed using the generalized estimating equation method. Medical records were retrospectively reviewed. Frequency and outcomes of post-ER bleeding were evaluated. Results Bleeding was more frequent in the ESRD with dialysis group than in the non-ESRD group. ESRD with dialysis conferred a significant risk of post-ER bleeding (odds ratio, 6.1; 95% confidence interval, 2.7–13.6; p

Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic gastritis (CAG) and gastric neoplasms. Although various cut-off values have been suggested, PG I &le, 70 ng/mL and a PG I/PG II ratio of &le, 3 have been proposed. However, previous meta-analyses reported insufficient systematic reviews and only pooled outcomes, which cannot determine the diagnostic validity of sPGA with a cut-off value of PG I &le, 70 ng/mL and/or PG I/PG II ratio &le, 3. We searched the core databases (MEDLINE, Cochrane Library, and Embase) from their inception to April 2018. Fourteen and 43 studies were identified and analyzed for the diagnostic performance in CAG and gastric neoplasms, respectively. Values for sensitivity, specificity, diagnostic odds ratio, and area under the curve with a cut-off value of PG I &le, 70 ng/mL and PG I/PG II ratio &le, 3 to diagnose CAG were 0.59, 0.89, 12, and 0.81, respectively and for diagnosis of gastric cancer (GC) these values were 0.59, 0.73, 4, and 0.7, respectively. Methodological quality and ethnicity of enrolled studies were found to be the reason for the heterogeneity in CAG diagnosis. Considering the high specificity, non-invasiveness, and easily interpretable characteristics, sPGA has potential for screening of CAG or GC.

The gastrointestinal endoscopy unit is frequently exposed to gastrointestinal gas expelled from patients and electrocoagulated tissue through carbonation. This can be potentially harmful to the health of not only the healthcare personnel but also patients who undergo endoscopy. This study aimed to measure the air quality in the endoscopy unit. We measured indoor air quality indices (CO2, total volatile organic compounds (VOCs), PM2.5, NO2, CO, and ozone) using portable passive air quality monitoring sensors in the procedural area, recovery area, and cleansing-of-equipment area, at 1-min intervals for 1 week, and the type and number of endoscopic procedures were recorded. CO2, PM2.5, NO2, and ozone levels were the highest in the cleansing area, followed by the procedural and recovery areas, and VOC level was highest in the procedural area. The proportion of poor-quality level of CO2 and VOCs was highest in the procedural area and that of NO2 was highest in the cleansing area. The proportion of tolerable to poor-quality (exceeding acceptable level) level of CO2 and total VOCs in the procedural area was 26% and 19.2% in all measurement times, respectively. The proportion of tolerable to poor-quality level of NO2 in the cleansing area of the endoscopy unit was 32.1% in all measurement times. Multivariate analyses revealed that tolerable to poor-quality (exceeding acceptable level) level of VOCs was associated with the number of endoscopic procedures (odds ratio, 1.79; 95% confidence interval, 1.42–2.27) and PM2.5 level (1.27, 1.12–1.44). Moreover, tolerable to poor-quality level of CO2 was associated with the number of colonoscopy (5.35, 1.19–24.02), especially with electrocoagulation procedures (24.31, 1.31–452.44) in the procedural area. Healthcare personnel and patients who undergo endoscopy are frequently exposed to ambient air pollution. Health-related protective strategies for ambient air pollution in the endoscopy unit are warranted. NCT03724565.

The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.

Objective: To compare Helicobacter pylori ( H. pylori) eradication rate of type 2 diabetic patients with non-diabetic subjects. Methods: In this multicenter prospective observational study, H. pylori-infected subjects were enrolled from three university-affiliated hospitals. Eradication regimen was triple therapy with standard dose of proton pump inhibitors (b.i.d), amoxicillin (1.0 g b.i.d), and clarithromycin (500 mg b.i.d) for 7 days. Urea breath test was performed 4 weeks after treatment. Various clinical and laboratory data were collected for identification of factors associated with successful eradication. Results: Totally, 144 subjects were enrolled and 119 (85 non-diabetic and 34 diabetic patients) were finally analyzed. Eradication rate was 75.6% and there was no difference between diabetic patients and non-diabetic subjects (73.5% vs 76.5%, p value: 0.814). Adverse drug reactions were reported in 44.5% of patients. In multivariate analysis for predicting H. pylori eradication in diabetic patients, HbA1c (⩾7.5%) was a significant factor affecting eradication rate (adjusted odds ratio: 0.100, 95% confidence interval: 0.011–0.909, p value: 0.041). Conclusion: Diabetes itself is not a major factor affecting H. pylori eradication. However, poor glucose control may harmfully affect H. pylori eradication.

Objective The number of articles that researchers must be familiar with is increasing, along with the importance of selective searching and summarization. This study aimed to assess and characterize the most influential articles in Helicobacter pylori research. Methods We performed a search of the top-100 cited articles using the Web of Science Core Collection (WoSCC) and Google Scholar from their inception to 2018. The top-100 Altmetric Attention Score (AAS) articles based on online media mentions were also searched using the term H pylori. Each article was evaluated for the following characteristics: citation number, title, journal, publication year, and authorship. Results The citation number for the top-100 WoSCC articles ranged from 44 to 367. Gut published the largest number of articles (11%). In the top-100 Google Scholar articles, Lancet had the largest number of articles (13%); however, among the top-1000 cited articles published after 2012, Helicobacter published the largest number (46%). The largest number of top-100 AAS articles was published by PLOS Pathogens (6%). PubMed Central articles' citations in WoSCC or Google Scholar showed significant correlation with those from each metric; however, AAS showed no correlation. The proportion of basic research was 36%-37% in top-cited articles; but, 52% in the top-100 AAS articles. No time trend in the number of publications or citations of basic/clinical research in the top-100 bibliometrics was found. "Meta-analysis/systematic review," "gastric cancer," "eradication," and "association" were the most influential title words. Conclusion This study presents a detailed list of top-100 articles, journals, authors, and topic title words.

Background: Melatonin generated in the gastrointestinal tract has mucosal protective effect with inhibiting gastric acid secretion, while increasing gastrin release, which in turn stimulates the contractility of lower esophageal sphincter. Gastroesophageal reflux disease (GERD) is also known to have association with sleep disturbance. However, melatonin or melatonin receptor agonist has not been included in the treatment of GERD. This study aimed to evaluate the efficacy of melatonin for the treatment of GERD. Methods: We will search the core databases [MEDLINE (through PubMed), the Cochrane Library, and Embase] from their inception to December 2018 by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have GERD, Intervention: melatonin or melatonin receptor agonist treatment, Comparison: patients without melatonin or melatonin receptor agonist treatment, Outcome: clinical indices (or crude number or proportion of improvement) for the evaluation of symptomatic improvement which enable comparison of efficacy between patients with melatonin or melatonin receptor agonist and the control group. All types of study design will be sought with full-text will be included. The risk of bias will be assessed using the ROBINS-I tool. Descriptive data synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous. Publication bias will be assessed with quantitative analyses if more than 10 articles are enrolled. Results: The results will provide evidence for the efficacy of melatonin or melatonin receptor agonist for the treatment of GERD. Conclusion: This study will provide evidence of melatonin or melatonin receptor agonist treatment for GERD.

Background: Endoscopic submucosal dissection (ESD) is a primary treatment for the early gastric cancer (EGC) who has a negligible risk of lymph node metastasis. Papillary adenocarcinoma (PAC) of stomach is a rare histologic variant of gastric cancer and categorized into EGC with differentiated-histology. However, aggressive features such as higher rate of lymphovascular invasion (LVI) or submucosal invasion have been reported, whereas comparable lymph node metastasis (LNM) rate to the lesions meeting the current ESD criteria also has been reported. This study aimed to evaluate the feasibility of ESD for EGC with PAC. Methods: We will search the core databases (MEDLINE (through PubMed), the Cochrane Library, and Embase) from their inception to December 2018 by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have EGC with PAC, Intervention: ESD or surgery, Comparison: none, Outcome: at least one among the rate of complete resection, curative resection, en bloc resection, recurrence, procedure-related adverse event, LVI or LNM that enabled an evaluation of the feasibility of ESD. All types of study design with full text will be sought and included. The risk of bias will be assessed using the ROBINS-I tool. Descriptive data synthesis is planned, and quantitative synthesis will be used if the included studies are sufficiently homogenous. Publication bias will be assessed with quantitative analyses if more than 10 articles are enrolled. Results: The results will provide evidence for efficacy and safety of ESD for EGC with PAC. Conclusion: This study will provide evidence of ESD for EGC with PAC.

Background and Aims Diagnosis of esophageal cancer or precursor lesions by endoscopic imaging depends on endoscopist expertise and is inevitably subject to interobserver variability. Studies on computer-aided diagnosis (CAD) using deep learning or machine learning are on the increase. However, studies with small sample sizes are limited by inadequate statistical strength. Here, we used a meta-analysis to evaluate the diagnostic test accuracy (DTA) of CAD algorithms of esophageal cancers or neoplasms using endoscopic images. Methods Core databases were searched for studies based on endoscopic imaging using CAD algorithms for the diagnosis of esophageal cancer or neoplasms and presenting data on diagnostic performance, and a systematic review and DTA meta-analysis were performed. Results Overall, 21 and 19 studies were included in the systematic review and DTA meta-analysis, respectively. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD algorithms for the diagnosis of esophageal cancer or neoplasms in the image-based analysis were 0.97 (95% confidence interval [CI], 0.95-0.99), 0.94 (95% CI, 0.89-0.96), 0.88 (95% CI, 0.76-0.94), and 108 (95% CI, 43-273), respectively. Meta-regression showed no heterogeneity, and no publication bias was detected. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD algorithms for the diagnosis of esophageal cancer invasion depth were 0.96 (95% CI, 0.86-0.99), 0.90 (95% CI, 0.88-0.92), 0.88 (95% CI, 0.83-0.91), and 138 (95% CI, 12-1569), respectively. Conclusions CAD algorithms showed high accuracy for the automatic endoscopic diagnosis of esophageal cancer and neoplasms. The limitation of a lack in performance in external validation and clinical applications should be overcome.

Background/Aims The purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without Helicobacter pylori. Methods We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a H. pylori-negative group (HP-negative group), and a group of patients with untreated H. pylori (HP noneradicated group). We compared the recurrence rates of PUD in these two groups and analyzed the factors that affected ulcer recurrence. Results Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease. Conclusions The 5-year cumulative probability of PUD recurrence without H. pylori infection after a long-term follow-up was 36.4% and the factors that affected recurrence were elder, male, and comorbid chronic kidney disease.

Background/aims Non-pancreatic elevations of serum lipase have been reported, and differential diagnosis is necessary for clinical practice. This study aimed to evaluate the clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation. Methods Patients who were referred for the serum lipase elevation were prospectively enrolled. Clinical findings and serum lipase subtypes were analyzed and compared by dividing the patients into pancreatitis and non-pancreatitis groups. Results A total of 34 patients (12 pancreatitis vs. 22 non-pancreatitis cases) were enrolled. In univariate analysis, the fraction of pancreatic lipase (FPL) in the total amount of serum lipase subtypes was statistically higher in patients with pancreatitis ([median, 0.004; interquartile range [IQR], 0.003 to 0.011] vs. [median, 0.002; IQR, 0.001 to 0.004], p = 0.04). Based on receiver operating characteristic curve analysis for the prediction of acute pancreatitis, FPL was the most valuable predictor (area under the receiver-operating characteristic curve [AUROC], 0.72; 95% confidence interval [CI], 0.54 to 0.86; sensitivity, 83.3%; specificity, 63.6%; positive predictive value, 55.6%; negative predictive value, 97.5%). In multivariate analysis, a cut-off value higher than 0.0027 for the FPL was associated with acute pancreatitis (odds ratio, 8.3; 95% CI, 1.3 to 51.7; p = 0.02). Conclusions The results did not support that serum lipase subtype analysis could replace standard lipase measurement for the diagnosis of acute pancreatitis. However, the test demonstrated adequate sensitivity for use in triage or as an add-on test for serum lipase elevation.

Background/Aims Eradication of Helicobacter pylori infection with standard triple therapy (TT) has declined primarily because of increased antibiotic resistance. Sequential therapy (ST) has been suggested as an alternative to TT for the first-line treatment of H. pylori. The purpose of this study was to compare the efficacy of ST with TT. Methods This was a multicenter, randomized open-label trial performed at nine centers in Korea. Patients with H. pylori infection were randomly assigned to receive either 7 day TT or 10 day ST. Eradication rates, drug compliance, and adverse events were compared among the two regimens. Results A total of 601 patients were enrolled between March 2011 and September 2014. The intention-to-treat eradication rates were 70.8% for TT and 82.4% for ST (p=0.001). The corresponding per protocol eradication rates were 76.9% and 88.8% for TT and ST, respectively (p=0.000). There were no statistically significant differences between the two regimens with respect to drug compliance and adverse events. Conclusions ST achieved better eradication rates than TT as a first-line therapy for H. pylori eradication in Korea.

Intravesical bacillus Calmette-Guerin (BCG) immunotherapy is a common treatment modality for bladder cancer after transurethral resection of a bladder tumor. This therapy is generally safe, and development of a prostatic abscess with a prostatorectal fistula after intravesical BCG immunotherapy is a very rare complication. This finding was incidentally obtained by the authors, who examined a patient with colonoscopy for evaluation of abdominal pain. The patient was successfully treated with antitubercular drugs. To the authors' knowledge, this is the first report of a patient with a tuberculous prostatic abscess with prostatorectal fistula after BCG immunotherapy in South Korea.

Background Helicobacter pylori plays a central role in the development of gastric cancer, and prediction of H pylori infection by visual inspection of the gastric mucosa is an important function of endoscopy. However, there are currently no established methods of optical diagnosis of H pylori infection using endoscopic images. Definitive diagnosis requires endoscopic biopsy. Artificial intelligence (AI) has been increasingly adopted in clinical practice, especially for image recognition and classification. Objective This study aimed to evaluate the diagnostic test accuracy of AI for the prediction of H pylori infection using endoscopic images. Methods Two independent evaluators searched core databases. The inclusion criteria included studies with endoscopic images of H pylori infection and with application of AI for the prediction of H pylori infection presenting diagnostic performance. Systematic review and diagnostic test accuracy meta-analysis were performed. Results Ultimately, 8 studies were identified. Pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve of AI for the prediction of H pylori infection were 0.87 (95% CI 0.72-0.94), 0.86 (95% CI 0.77-0.92), 40 (95% CI 15-112), and 0.92 (95% CI 0.90-0.94), respectively, in the 1719 patients (385 patients with H pylori infection vs 1334 controls). Meta-regression showed methodological quality and included the number of patients in each study for the purpose of heterogeneity. There was no evidence of publication bias. The accuracy of the AI algorithm reached 82% for discrimination between noninfected images and posteradication images. Conclusions An AI algorithm is a reliable tool for endoscopic diagnosis of H pylori infection. The limitations of lacking external validation performance and being conducted only in Asia should be overcome. Trial Registration PROSPERO CRD42020175957; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=175957

The aims of this study were to demonstrate the trends in seropositivity and the eradication therapy rate for Helicobacter pylori (H. pylori) over an 18-year period in an asymptomatic Korean population and to explore the factors associated with H. pylori seropositivity and its eradication therapy. In total, 23,770 subjects (aged 17–97 years) from a health examination center participated in this cross-sectional study from January 2016 to June 2017. Questionnaires that included questions about the participants’ H. pylori eradication therapy history were collected, and anti-H. pylori IgG antibodies were measured. Among the eligible subjects, the seroprevalence of H. pylori infection was 41.5%. The H. pylori eradication therapy rate increased continuously from 2005 (13.9%) to 2011 (19.3%) and then increased again until the first half of 2017 (23.5%) (P < 0.001). After exclusion of subjects with a history of gastric surgery, gastric cancer, H. pylori eradication therapy, or gastric symptoms, H. pylori seropositivity was 43.9% in 16,885 subjects, which was significantly lower than the seropositivities in 1998 (66.9%), 2005 (59.6%), and 2011 (54.4%). The risk factors associated with H. pylori seropositivity according to multivariable analysis were male sex (odds ratio (OR) 1.34, 95% confidence interval (CI): 1.23–1.46), medium educational level (OR 1.17, 95% CI: 1.05–1.31), medium household income level (OR 1.10, 95% CI: 1.03–1.19), and age of 60–69 years (OR 8.78, 95% CI: 6.41–11.85). The observed downward trend in H. pylori seroprevalence and increase in H. pylori eradication over the 18-year period will affect upper gastrointestinal disorders in South Korea.

The prevalence of upper gastrointestinal disease is expected to change following advances in socioeconomic status and improved hygiene in Korea. The aim of this study was to investigate the recent trends in upper gastrointestinal diseases based on endoscopic findings and Helicobacter pylori (H. pylori) seroprevalence in subjects undergoing health check-up at tertiary centers in Korea.A multicenter cross-sectional study was conducted at nine healthcare centers between September 2016 and June 2017. The subjects were evaluated using questionnaires, upper endoscopy and H. pylori serology tests. The results were compared with previous data in our study group obtained from eight tertiary healthcare centers in 2011 (n = 4023).In total, we prospectively enrolled 2504 subjects undergoing health check-up. The prevalence of reflux esophagitis (RE) was 9.7%, which showed an increasing but insignificant trend since 2011 (8.8%). The prevalence of active and healing-stage benign gastric ulcer and duodenal ulcer (DU) was 1.6% and 1.2%, respectively, which confirmed a significant decrease since 2011 (4.1%; p .001 and 2.2%; p = .005, respectively). The prevalence of gastric cancer was 0.5%, representing an increasing trend since 2011 (0.12%; p = .003). H. pylori seroprevalence was 51.3%, which significantly decreased from 2011 (59.8%; p .001). In multivariate analysis, H. pylori seropositivity was a significant risk factor for DU (p .001), whereas a significant protective factor against RE (p .001).The significant decrease of H. pylori seroprevalence in the past five years altered the incidence of upper gastrointestinal disease.

Background/aims Functional dyspepsia (FD) is one of the most common gastrointestinal disorders, and FD imposes social and economic burden worldwide. The aim of this study is to identify the prevalence and risk factors of FD in health check-up population in tertiary centers in Korea. Methods A nationwide multicenter prospective study was performed at 9 tertiary healthcare centers in Korea between September 2016 and June 2017. A total of 2525 subjects were investigated based on endoscopic findings and questionnaires with the Rome III criteria, and Helicobacter pylori serology (IgG). Results A total of 1714 subjects without organic disease were enrolled. The mean (± SD) age was 51.5 (± 12.7) years, and 917 patients (53.5%) were female. The proportion of H. pylori seropositivity was 51.0% (874/1714). The prevalence of FD was 10.3% (176/1714), and the subtypes of postprandial distress syndrome alone, epigastric pain syndrome alone, and postprandial distress syndrome-epigastric pain syndrome overlap were 4.8%, 3.0%, and 2.5%, respectively. Multivariate analysis showed that female gender (OR, 1.58; 95% CI, 1.14-2.21) and education below college level (OR, 1.45; 95% CI, 1.01-2.07) were related to FD. Multivariate analysis based on age 60 showed female gender as a significant (OR, 2.90; 95% CI, 1.06-7.94) factor in the group ≥ 60 years. Conclusions The prevalence of FD was 10.3% in the health check-up population in Korea. Female sex and education below college level were risk factors for FD. Female sex is a risk factor for FD in old age, underscoring the need for close attention in this age group.

Antibiotic resistance is growing worldwide, and patients who have failed consecutive 1st- and 2nd-lineH. pylorieradication regimens are increasing. Therefore, the role of the bacterial culture with antibiotic susceptibility testing and molecular susceptibility testing is important for avoiding the use of ineffective antibiotics. However, antibiotic susceptibility testing-guided treatment does not necessarily guarantee successful eradication, and there have been mixed results for the effectiveness of a 3rd-line rescue therapy. Therefore, providing patients with pretreatment medication instructions and education is important. It is also crucial to determine the reason of the eradication failure, including host-related factors (poor compliance to eradication regimen, smoking, and cytochrome P450 2C19 genetic polymorphism) or treatment-related factors (inadequate dosage or duration of therapy and gastric acidity), as such factors can be modified for a tailored therapy. Although the indications forH. pylorieradication have widened, patients at a high risk of gastric cancer can gain definitive benefits with a 3rd-line or even 4th-line therapy.

Helicobacter pylori is among the most common bacterial pathogens, but it has not yet been conquered. It is related to various gastrointestinal diseases, including chronic gastritis, peptic ulcer, gastric marginal zone B cell lymphoma, and gastric cancer. The association between Helicobacter pylori infection and functional dyspepsia or gastroesophageal reflux disease is not clear. Numerous factors determine disease course and outcome, such as bacterial virulence, genotype, host immunity, and environmental factors. The eradication of Helicobacter pylori in associated gastrointestinal diseases is important for the treatment and prevention of recurrent or severe outcomes, especially in Korea where gastric cancer is prevalent. (Korean J Med 2015,89:142-148)

Controversies persist regarding the effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer (EGC). The aim of this study was to assess the efficacy of Helicobacter pylori eradication after endoscopic resection of EGC for the prevention of metachronous gastric cancer. A systematic literature review and meta-analysis were conducted using the core databases PubMed, EMBASE, and the Cochrane Library. The rates of development of metachronous gastric cancer between the Helicobacter pylori eradication group vs. the non-eradication group were extracted and analyzed using risk ratios (RRs). A random effect model was applied. The methodological quality of the enrolled studies was assessed by the Risk of Bias table and by the Newcastle-Ottawa Scale. Publication bias was evaluated through the funnel plot with trim and fill method, Egger's test, and by the rank correlation test. Ten studies (2 randomized and 8 non-randomized/5,914 patients with EGC or dysplasia) were identified and analyzed. Overall, the Helicobacter pylori eradication group showed a RR of 0.467 (95% CI: 0.362-0.602, P < 0.001) for the development of metachronous gastric cancer after endoscopic resection of EGC. Subgroup analyses showed consistent results. Publication bias was not detected. Helicobacter pylori eradication after endoscopic resection of EGC reduces the occurrence of metachronous gastric cancer.

Background and Aim Upper gastrointestinal bleeding (UGIB) leads to significant morbidity and mortality in chronic kidney disease (CKD) patients. This study determined the efficacy of using a low-dose proton pump inhibitor (PPI) to reduce the risk of non-variceal UGIB in CKD patients receiving aspirin. Methods We retrospectively reviewed the medical records of 500 CKD patients who received aspirin between January 2008 and March 2013. Cumulative incidence analysis using the Kaplan–Meier method was performed to analyze the rate of non-variceal UGIB and association with the administration of low-dose PPI. Results Of the 500 patients, 191 received low-dose PPI. Over the follow-up period, which lasted 1067 person-years, three patients in the low-dose PPI group (8.9 per 1000 person-years) and 19 patients in the non-PPI group (25.9 per 1000 person-years) developed non-variceal UGIB, respectively (P = 0.113). Low-dose PPI use did not decrease the risk of UGIB in CKD patients, including patients who did not receive dialysis (P = 0.127). However, according to the subgroup analysis of 230 patients who received dialysis, the low-dose PPI group (14.4 per 1000 person-years) demonstrated significantly reduced incidence and risk of non-variceal UGIB in comparison with the non-PPI group (53.8 per 1000 person-years) (P = 0.032). Conclusion Prophylactic low-dose PPI can reduce the risk of non-variceal UGIB in dialysis patients receiving aspirin.

Background aims: Environmental factors and genetic predisposition are thought to play important roles in the pathogenesis of Crohn’s disease [CD]. Although numerous studies have reported the positive association between urban environment and CD development, few studies have compared the clinical outcomes between urban and rural environments. Therefore, this study aimed to compare the clinical characteristics and long-term prognosis between urban and rural populations of patients with CD. Methods: This retrospective multicenter cohort study included 1002 Korean patients diagnosed with CD [743 urban residents and 259 rural residents] between 1982 and 2008 from 32 medical centers. The clinical outcomes of urban versus rural populations were compared using the KaplanMeier method and log-rank test. Results: Disease distribution and behavior of the urban population did not differ from those of the rural population. There were no significant differences in the cumulative probabilities of perianal fistula [ P = 0.086] and intestinal complications such as stricture [ P = 0.109], fistula [ P = 0.952], abscess [ P = 0.227], and perforation [ P = 0.382] between the two groups. In addition, no significant differences were observed between the two groups with regard to the cumulative probabilities of immunosuppressant use [ P = 0.527] and biologic agent use [ P = 0.731]. Although the cumulative probability of surgery in the urban population was significantly higher than that in the rural population [ P = 0.040], this difference was mainly established within the first year from diagnosis [19.1% vs 13.5%, P = 0.042] and observed only among patients diagnosed in 2005–2008 [ P = 0.033]. Conclusions: There were no differences in terms of disease presentation and natural history between urban and rural populations, except for a higher rate of surgery in the urban population who were recently diagnosed with CD.

Background and Aim The aim of this study was to assess the therapeutic effect of mosapride in patients with functional dyspepsia (FD). Methods Randomized controlled trials (RCTs) of mosapride for the treatment of FD performed between 2002 and 2013 were identified from databases. Symptom response rates were extracted and analyzed using risk ratios (RRs). A random effect model was applied based on Higgins I2 tests. Publication bias was evaluated using a funnel plot, Egger's test, trim and fill, and the rank correlation test. Results In total, 13 RCTs, which included 1091 mosapride-treated patients and 1129 control patients (on placebo or other drugs), were identified and analyzed. Overall, mosapride showed an RR of 0.999 (95% confidence interval [CI]: 0.869–1.150, P = 0.992) for improving global efficacy or symptom-based scores. In a sensitivity analysis of the high-quality RCTs, mosapride showed an RR of 1.114 (95% CI: 1.011–1.227, P = 0.029). However, in the studies using the Rome III criteria for the diagnosis of FD, mosapride showed an RR of 0.906 (95% CI: 0.807–1.016, P = 0.092). In the studies having funding source, mosapride showed an RR of 1.131 (95% CI: 1.028–1.244, P = 0.012), whereas an RR of 0.966 (95% CI: 0.896–1.042, P = 0.367) was observed in the studies without funding source. Publication bias was not detected. Conclusion In this analysis, we could not find a significant effect of mosapride on FD. Inconsistent diagnostic criteria for FD and different assessment outcomes are causes of heterogeneity. Further studies using common validated outcomes or questionnaires and high-quality RCTs will elucidate the real effect of this medication on FD.

Background/Aims: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). Methods: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. Results: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were -9.69±6.44 and -10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, -1.75 to 2.41), demonstrating non-inferiority of UI- 05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. Conclusions: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD. (Gut Liver 2018;12:516-522)

The effect of non-alcoholic fatty liver disease (NAFLD) on the occurrences of colorectal neoplasm (CRN) at surveillance colonoscopy is rarely evaluated. We retrospectively reviewed medical records of 1,023 patients who had both index and surveillance colonoscopy at a single institution. The cumulative occurrence rates of overall and advanced CRN at the time of surveillance colonoscopy were compared between patients with and without NAFLD using propensity score matching analysis. In an analysis of matched cohort of 441 patients, the cumulative rates of overall CRN occurrence at 3 and 5 years after index colonoscopy were higher in subjects with NAFLD than in those without NAFLD (9.1% vs. 5.0% & 35.2% vs. 25.3%, P = 0.01). Cox regression analysis showed that NAFLD independently increased the risk of overall CRN occurrence with marginal significance (adjusted hazard ratio [aHR]: 1.31 95% CI: 1.01-1.71, P = 0.05). Additionally, NAFLD was associated with the development of 3 or more adenomas at the time of surveillance colonoscopy (aHR: 2.49, 95% CI: 1.20-5.20, P = 0.02). In subgroup analysis based on index colonoscopy risk categories, the effect of NAFLD on the overall CRN occurrence at the time of surveillance colonoscopy was confined to the normal group (aHR: 1.47, 95% CI: 1.05-2.06, P = 0.02). Regarding advanced CRN occurrences at the time of surveillance colonoscopy, age was the only significant risk factor (aHR: 1.06, 95% CI: 1.02-1.10, P = 0.001). NAFLD was associated with overall CRN occurrence, especially in patients with no adenoma at the index colonoscopy. NAFLD may be considered for the determination of the time-interval for surveillance colonoscopy, especially the patients with negative index colonoscopy findings.

Background/Aims Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. Methods The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. Results In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. Conclusions The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.

Background Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. Methods Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. Results In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27–6.06), mosapride (OR: 1.99, 95% credible interval: 0.87–4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92–4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29–6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43–6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07–1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04–2.18). Conclusions Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0639-0) contains supplementary material, which is available to authorized users.

Gastrocolocutaneous fistula is a rare complication of the percutaneous endoscopic gastrostomy (PEG) procedure. Typical symptoms usually occur in the first few months. We recently encountered 2 patients with 8- and 33-month asymptomatic periods. A 74-year-old man presented with watery diarrhea for 1 month. He had undergone PEG 9 months earlier. During workup, an upper endoscopy and abdominal CT scan revealed the migration of the feeding tube into the transverse colon. He was discharged with a nasogastric tube after treatment. A 77-year-old man presented with sudden loosening of his PEG tube with a duration over 3 days. He had undergone PEG procedure three times until that time. During workup, a gastrocolocutaneous fistula was diagnosed. However, when previous studies were reviewed, an abdominal CT scan, which was done 6 months ago before the third PEG, showed the fistula already existed at that time, suggesting that it was created about 33 months earlier when he underwent the second PEG procedure. The patient died of pneumonia aggravation despite conservative treatment. Both a high index of suspicion and the careful inspection of the upper endoscopy are very important for early diagnosis regardless of symptoms.

The pathophysiology of peptic ulcer disease (PUD) in liver cirrhosis (LC) and chronic hepatitis has not been established. The aim of this study was to assess the role of portal hypertension from PUD in patients with LC and chronic hepatitis.We analyzed the medical records of 455 hepatic vein pressure gradient (HVPG) and esophagogastroduodenoscopy patients who had LC or chronic hepatitis in a single tertiary hospital. The association of PUD with LC and chronic hepatitis was assessed by univariate and multivariate analysis.A total of 72 PUD cases were detected. PUD was associated with LC more than with chronic hepatitis (odds ratio [OR]: 4.13, p = 0.03). In the univariate analysis, taking an ulcerogenic medication was associated with PUD in patients with LC (OR: 4.34, p = 0.04) and smoking was associated with PUD in patients with chronic hepatitis (OR: 3.61, p = 0.04). In the multivariate analysis, taking an ulcerogenic medication was associated with PUD in patients with LC (OR: 2.93, p = 0.04). However, HVPG was not related to PUD in patients with LC or chronic hepatitis.According to the present study, patients with LC have a higher risk of PUD than those with chronic hepatitis. The risk factor was taking ulcerogenic medication. However, HVPG reflecting portal hypertension was not associated with PUD in LC or chronic hepatitis (Clinicaltrial number NCT01944878).

Background and Aim Gastrointestinal carcinoid tumors

Background: Detection rate of precursor lesion of colorectal cancer and early colon cancer have recently been rising because of increased screening endoscopy and increased incidence of colorectal cancer. Endoscopic submucosal dissection (ESD) technique has been reported to be useful in the treatment of such superficial lesions in colon. However, nationwide multicenter study for usefulness and feasibility of colorectal ESD is still limited. Methods: From January 2009 to February 2014, colorectal ESD data performed at nationwide university hospitals were enrolled in retrospective design. Demographic, clinical, technical data, and data of complications were reviewed. Results: A total of 189 patients were included with 191 lesions resected by colorectal ESD. The indications were epithelial lesions (n=120), neuroendocrine tumor (n=25), cancer (n=46). The lesion locations were right colon (n=45), transverse colon (n=17), descending colon (n=8), sigmoid colon (n=33), rectum (n=88). The median size of the lesions was 21.1 mm. En bloc resection rate of the lesion was 83.3%, with complete R0 resection in 73.3%. The median duration of ESD was 53.7 minutes. Factor related to En bloc resection was tumor location (right colon/transverse colon 72.6% vs . other location 89.2%, P=0.004). Factors related complication were tumor location (right colon/transverse colon 12.9% vs . Other location 10.13%, P=0.044) and tumor size (without complication 20.5±10.2 mm vs . with complication 25.9±11.7 mm, P=0.027). The short term morbidity rate was 11.0% including 5 hemorrhages (2.6%) and 16 perforations (8.4%). Conclusions: In this study, ESD shows promise as a useful, potentially feasible procedure in colorectal superficial tumor because of high en bloc resection rate and low morbidity rate, especially in small lesions located from descending colon to rectum.

Background and aim: Although abdominal pain is a common adverse event related to endoscopic submucosal dissection (ESD), it can be sometimes underestimated by endoscopists. There are some endoscopic interventions available for the prevention of post-ESD pain, but their efficacy has not been established. We investigated whether a submucosal injection of bupivacaine (BP) can reduce procedure-related abdominal pain compared with the standard method. Methods: We performed a multicenter, double-blinded, randomized controlled trial of 86 adult patients referred for ESD as treatment for gastric neoplasms. Patients were randomly assigned to either the BP submucosal or conventional solution group. Questionnaires were collected when the study began (baseline) and immediately after ESD, as well as at 6, 12, and 24 hours post-operatively. The primary outcome was indicated by the visual analog scale (VAS) evaluated at 6 hours after procedure. Results: There were no significant differences in primary outcomes between groups and among all time points (immediately, 12, and 24 hours after ESD). The VAS and short-form McGill pain (SF-MP) scores were higher immediately after ESD than at 6, 12, or 24 hours post-operatively. The incidence of abdominal pain immediately after ESD was 94.0% (78/83) for all patients of both groups, and there was no significant difference between the 2 groups in the rate of abdominal pain immediately after ESD (BP group 37/40 [92.5%] versus non-BP group 41/43 [95.3%], P = .934). In univariable and multivariable analyses, BP did not have protective effect on post-ESD abdominal pain. Conclusions: Submucosal BP injection does not promote pain relief or mitigate the effects of post-ESD abdominal pain.

Background: Serum pepsinogen assay (sPGA) combining concentration of pepsinogen I (PG I), and the ratio of PG I/II is the noninvasive biomarker for predicting chronic atrophic gastritis (CAG) and neoplasms reflecting mucosal secretory status. Although various cut-off values have been suggested, PG I ≤70 ng/mL and PG I/II ≤3 have been widely accepted. However, previous studies for diagnostic test accuracy presented only pooled outcomes, which cannot discriminate the diagnostic validity of sPGA with cut-off of PG I ≤70 ng/mL and PG I/II ≤3. Methods: We will search the core databases [MEDLINE (through PubMed), the Cochrane Library, and Embase] from their inception to December 2018 by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have histologically proven CAG or gastric neoplasms, Intervention: sPGA with cut-off of PG I ≤70 ng/mL and/or PG I/II ≤3, Comparison: none, Outcome: diagnostic performance indices of sPGA for CAG and gastric neoplasms (sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) (if, true/false positive, true/false negative values are presented, diagnostic performance indices will be calculated). All types of study design with full text will be sought and included. The risk of bias will be assessed using the QUADAS-2 tool. Descriptive data synthesis is planned and quantitative synthesis (bivariate and HSROC model) will be used if the included studies are sufficiently homogenous. Publication bias will be assessed. Results: The results will provide clinical evidence for diagnostic validity of sPGA. Conclusion: This study will provide evidence of sPGA for predicting CAG and gastric neoplasms.

Background: A gastrointestinal endoscopy unit is frequently exposed to gastrointestinal gas expelled from patients and electrocoagulated tissue through carbonation for the treatment of gastrointestinal neoplasms or hemostasis of gastrointestinal bleeding. This can be potentially harmful to the health of not only the healthcare personnel but also patients who undergo endoscopic examinations. However, there has been scarce data on air quality in the endoscopy unit. This study aimed to measure the air quality in the gastrointestinal endoscopy unit. Methods: This is a prospective study using conventional portable passive air quality monitoring sensors in the gastrointestinal endoscopy unit. We will check the 6 main indoor air quality indices, as well as the atmospheric temperature, pressure, and humidity in the endoscopy unit of a single hospital in Korea. These indices are as follows: carbon dioxide (CO2), total volatile organic compounds (VOCs), particulate matter that has a diameter of

Background: Endoscopic submucosal dissection (ESD) is a primary treatment for the early gastric cancer (EGC) who have a negligible risk of lymph node metastasis satisfying specific criteria. These criteria are histologically categorized by EGC with differentiated-type histology (EGC-DH) and undifferentiated-type histology (EGC-UH). However, gastric cancer is histologically heterogenous and there has been no specific criteria for EGC with mixed-type histology (EGC-MH). Moreover, therapeutic outcomes of ESD for EGC-MH have not been clearly described. Methods: We will search the core databases (MEDLINE (through PubMed), the Cochrane Library, and Embase) from their inception to November 2018 using pre-established searching strategy by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have EGC-MH, Intervention: ESD, Comparison: none, Outcome: at least one among the rate of complete resection, curative resection, en bloc resection, recurrence or procedure-related adverse event that enabled an evaluation of feasibility of ESD. All types of study design will be sought and publications in English with full-text will be included. The risk of bias will be assessed using the ROBINS-I tool. Descriptive data synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous (pooled therapeutic outcomes data with 95% confidence intervals). Publication bias will be assessed with quantitative analyses if more than 10 articles are enrolled. Results: The results will provide evidence for validity of current ESD criteria in addition to the technical feasibility of ESD for EGC-MH. Conclusion: This study will provide evidence of ESD for EGC-MH.

See Article on Page 801-807 Helicobacter pylori is still prevalent in Korea, although the prevalence has decreased from 66.9% in 1998 to 54.4% in 2013 [1-5]. Sanitary improvements and wide application of eradication therapy have contributed to this. However, it is still a great socioeconomic and national healthcare burden [6]. This bacterial pathogen is involved in various gastrointestinal diseases, including gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer [7,8]. Although only 1% to 15% of patients with H. pylorii infection develop the clinical disease, even asymptomatic H. pylorii gastritis should be considered an infectious disease and treated to prevent severe complications, such as gastric cancer, as reported by the Kyoto Global Consensus conference [4]. This suggests a paradigm shift in the eradication of H. pylorii from treatment to prevention [4]. Standard triple therapy (standard dose proton pump inhibitor, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 to 14 days) is the recommended first-line regimen for eradication of H. pylorii in Korea [9]. Over the past decade, studies of the trend in H. pylorii eradication rates in Korea have shown a constant or decreasing trend [10]. Concerns about changing the first-line regimen have been growing, because studies indicating a constant trend also showed eradication rates below 90% in per-protocol analyses [10]. Particularly, a recent meta-analysis revealed a decreasing trend in the eradication rate (from 1998 to 2013) in Korea, which has an overall eradication rate of 74.6% (95% confidence interval [CI], 72.1 to 77.2) with intention-to-treat and 82.0% (95% CI, 80.8 to 83.2) by per-protocol analysis [11]. In this issue, Kim et al. [12] reported a trend in the H. pylorii eradication rate using first-line triple therapy in Metropolitan Busan, which is the second largest city in Korea after Seoul. This retrospective study included 1,413 patients who were treated with the standard triple regimen for 7 days between 2003 and 2012 [12]. The overall eradication rate was 84.9% (per-protocol analysis), which is an unacceptable level for the currently recommended regimen. Moreover, the most recent eradication rate was 78.8% in 2012, which has decreased significantly during the last 10 years [12]. These results are consistent with those of the recent meta-analysis and indicate the need for a novel therapeutic regimen in Korea. If the treatment duration had been extended to 14 days, the expected improvement in the eradication rate would have been approximately 5%, which is still an unacceptable level [13]. High clarithromycin resistance in Korea is suspected to be a cause of treatment failure. Although data are scarce, the clarithromycin resistance rate was estimated to be 17.2% to 23.7% in 2012 [14]. Another study reported a resistance rate of 38.5% in 2009, which falls into the category of high clarithromycin resistance [13,15]. The Korean guideline recommends a bismuth-containing quadruple regimen (standard dose proton pump inhibitor twice daily, metronidazole 500 mg three times daily, and bismuth 120 mg and tetracycline 500 mg four times daily for 7 to 14 days) in areas where clarithromycin resistance is high [9]. It is difficult to determine when to change the first-line regimen in an area, because only a few studies have reported data on antibiotic resistance in H. pylorii eradication. However, time trend data continuously indicate the need for a novel regimen. If possible, a susceptibility test-based combination of drugs is the ideal regimen for eradication of an infectious pathogen. However, it is nearly impossible to perform culture and susceptibility tests for H. pylorii in hospitals. With the increase in geographical antibiotic resistance data, it should be possible to determine the preferred regimen among the potential candidates according to the geographic area. Kim et al. [12] also reported that smoking and female gender are associated with treatment failure. Smoking is a well-known risk factor for treatment failure. As the authors described, a reduction in antibiotic delivery due to decreased gastric blood flow is suspected to be the main mechanism [13]. However, it is not clear why female gender is associated with treatment failure. The high prevalence of H. pylorii infection in carriers of the A2143G mutation in 23S rRNA, which is associated with treatment failure, is presumed to be a possible cause [12,16]. However, another Korean study did not show a preponderance of the A2143G mutation in women [17]. In brief, time trend data indicate decreasing efficacy of standard triple therapy in the eradication of H. pylorii. However, no superior regimen has been found to be more effective than standard triple therapy in Korea. The combination of existing drugs, based on the results of antibiotic susceptibility tests, is the ideal method. Without geographic antibiotic resistance data, it is impossible to compare or interpret the clinical trials of novel regimens [18]. In the setting of a culture and susceptibility test-based regimen choice or with the accumulation of local antibiotic resistance data, it may be possible to determine the best regimen or find novel therapies.

Background/Aims Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions. Methods In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured. Results The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively). Conclusions A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.

Background/Aims Researches on the potential risk factors for the development of erosive esophagitis have been conducted extensively, however, the results are conflicting. The aim of this multicenter study was to identify the prevalence rate and risk factors of erosive esophagitis and their interactions with residency status. Methods A total of 4,023 eligible subjects at 8 tertiary health care centers were evaluated using questionnaires, laboratory tests and endoscopy. Univariate and multivariate analyses were conducted to identify independent risk factors for erosive esophagitis. Results The prevalence rate of reflux esophagitis was 8.8%. Los Angeles grade A was common type of erosive esophagitis. Residence in a large urban areas was negatively associated with the development of erosive esophagitis (OR, 0.60; 95% CI, 0.40-0.90). The high body mass index (≥ 25 kg/m2) was more frequent in residents of small and medium-sized cities than those in big cities (38.8% and 26.9%, respectively; P < 0.001). Seronegativity of Helicobacter pylori was associated with increased erosive esophagitis (OR, 1.91; 95% CI, 1.48-2.46). Triglyceride ≥ 150 mg/dL (OR, 1.65; 95% CI, 1.08-2.07), fasting glucose level ≥ 126 mg/dL (OR, 1.73; 95% CI, 1.06-2.81), and hiatal hernia (OR, 3.11; 95% CI, 1.87-5.16) were also associated with erosive esophagitis. Conclusions The prevalence rate of erosive esophagitis and its risk factors in this study were similar to the result of 8.0% of nationwide study in 2006. Residency and obesity are more important independent risk factors than H. pylori infection status for development of erosive esophagitis in Korea. These results suggest that the prevalence rate of erosive esophagitis in Korea might not increase as in the Western countries.

Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients.Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (6HVPG≤10), HS-3 (10HVPG≤12), HS-4 (12HVPG≤20), and HS-5 (20HVPG). CS was classified as follows: CS-0 (no cirrhosis), CS-1 (cirrhosis without varix), CS-2 (cirrhosis with varix), CS-3 (varix bleeding without other complications), CS-4 (first nonbleeding decompensating event), and CS-5 (any second decompensating event). The HCC development and risk factors for HCC were evaluated in all patients and patients with cirrhosis, respectively.HCC developed in 53 patients (6.6%). The incidence densities of HCC according to HS-1 to HS-5 and CS-0 to CS-5 were 4, 16, 36, 45, and 49/1000 person years and 0, 15, 25, 33, 36, and 53/1000 person years of observation, respectively. Ascites aggravation [P=0.008, odd ratio (OR)=2.33], HVPG12 mm Hg (P=0.033, OR=2.17), CS2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG12 mm Hg (OR=2.46), and CS2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively.HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Background : /Aims: In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. Methods : : A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. Results : : A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). Conclusion : s: In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness. (Korean J Gastroenterol 2016;68:16-22)

GOALS We evaluated the efficacy of initial and follow-up hepatic venous pressure gradient (HVPG), models of end-stage liver disease (MELD), and MELD-Na for predicting the survival of patients with decompensated liver cirrhosis (LC). BACKGROUND MELD with/without Na score and HVPG have been important predictors of mortality in patients with LC. STUDY Between January 2006 and 2011, a total of 57 patients with decompensated LC, all of whom underwent >2 HVPG measurements for the confirmation of propranolol dosing, were enrolled. MELD and MELD-Na scores were calculated on the day of HVPG measurement. The prognostic accuracy of the initial and follow-up HVPG, MELD, and MELD-Na were analyzed, and independent factors for mortality were evaluated. RESULTS Ten patients (17.5%) died from LC. Initial HVPG (0.883), initial MELD-Na (0.877), follow-up HVPG (0.829), and follow-up MELD-Na (0.802) showed good area under the receiver operating characteristic curve scores in predicting 1-year mortality. In predicting 2-year mortality, only follow-up HVPG (0.821, cut-off value 18 mm Hg) showed good score. Overall area under the receiver operating characteristic curves (initial and follow-up) were 0.843 and 0.864 in HVPG, 0.721 and 0.674 in MELD, and 0.762 and 0.715 in MELD-Na, respectively. In the Cox regression analysis, only follow-up HVPG (P=0.02; odds ratio, 1.11) was associated with mortality. CONCLUSIONS The efficacy of HVPG for predicting mortality is excellent compared with that of MELD or MELD-Na. Therefore, aside from the confirmation of adequate propranolol dosing, HVPG may be needed for predicting the survival of patients with decompensated LC.

‡‡ § § † † ‡ § Background/Aims: First-line therapies against Helicobacter pylori, including proton pump inhibitors (PPIs) plus two antibiotics, may fail in up to 20% of patients. ‘Rescue’ therapy is usually needed for patients who failed the firstline treatment. This study evaluated the eradication rate of bismuth-containing quadruple rescue therapy over a 1- or 2-week period. Methods: We prospectively investigated 169 patients with a persistent H. pylori infection after the first-line triple therapy, which was administered from October 2008 to March 2010. The patients were randomized to receive a 1- or 2-week quadruple rescue therapy (pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.). After the ‘rescue’ therapy, the eradication rate, compliance, and adverse events were evaluated. Results: The 1-week group achieved 83.5% (71/85) and 87.7% (71/81) eradication rates in the intention to treat (ITT) and per-protocol (PP) analyses, respectively. The 2-week group obtained 87.7% (72/84) and 88.9% (72/81) eradication rate in the ITT and PP analyses, respectively. There was no significant difference in the eradication rate, patient compliance or rate of adverse events between the two groups. Conclusions: One-week bismuth-containing quadruple therapy can be as effective as a 2-week therapy after the failure of the first-line eradication therapy. (Gut Liver 2012;6:434-439)