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Summary Background Tegoprazan is a novel, fast‐ and long‐acting potassium‐competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non‐erosive reflux disease (NERD), a type of gastroesophageal reflux disease. Aim To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD. Methods In this phase 3, double‐blind, placebo‐controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4‐week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated. Results Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn‐free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P, Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with non‐erosive reflux disease.

Background/Aims Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD. Methods In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed. Results The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: -10.04 ± 4.45 and -10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, -1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events. Conclusion In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile. (J Neurogastroenterol Motil 2021;27:87-96)

Background and aim The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD. Methods This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups. Results In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis. Conclusion Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders.

The prevalence of obesity and functional gastrointestinal disorders (FGIDs) is increasing worldwide. Obesity has been linked to gastroesophageal reflux disease, irritable bowel syndrome, functional dyspepsia, and various FGIDs. However, the relationship between obesity and FGIDs remains unclear. The purpose of this paper is to evaluate the published studies on this topic and clarify the relationship between obesity and the pathophysiology of various FGIDs. (Korean J Med 2019;94:425-430)

Background/Aims Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. Methods In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. Results There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. Conclusions The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Background/Aims: The diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB.Methods: A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports.Results: The mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Background/Aims In spite of increased concerns about the overlaps among the various functional gastrointestinal disorders (FGIDs), studies for the overlap between constipation and other common FGIDs are rare. Therefore, we investigated the patterns of overlaps between constipation and other common FGIDs. Methods This study was designed as a prospective nationwide multi-center questionnaire study using Rome III questionnaires for functional dyspepsia (FD), irritable bowel syndrome (IBS), and functional constipation (FC), as well as various questionnaires about patients' information, degree of symptoms, and quality of life. For the evaluation of gastroesophageal reflux disease (GERD), GERD-Q was used. Results From 19 centers, 759 patients with constipation were enrolled. The proportions of FC and IBS subtypes of constipation (IBS-C) were 59.4% and 40.6%, respectively. Among them, 492 (64.8%) showed no overlap. One hundred and thirty-six patients (17.9%) presented overlapping GERD, and 80 patients (10.5%) presented overlapping FD. Fifty one (6.7%) of patients were overlapped by both GERD and FD. Coincidental herniated nucleus pulposus (HNP) (P = 0.026) or pulmonary diseases (P = 0.034), reduced fiber intake (P = 0.013), and laxative use (P < 0.001) independently affected the rate of overlaps. These overlapping conditions negatively affected the constipation-associated quality of life, general quality of life, and degree of constipation. Conclusions The overlap of GERD or FD was common in patients with constipation. Coincidental HNP or pulmonary diseases, reduced fiber intake, and laxatives use were found to be independent associated factors for overlapping common FGIDs in Korean patients with constipation.

Background/Aims We aim to evaluate the efficacy and safety of combination therapy in erosive reflux disease (ERD) patients by comparing endoscopic healing rates according to the Los Angeles classification for esomeprazole alone, and esomeprazole plus mosapride. Methods A total of 116 ERD patients were randomized to receive esomeprazole 40 mg once daily plus mosapride 5 mg 3 times daily (E+M group), or esomeprazole plus placebo (E only group) for 8 weeks. Patients recorded gastroesophageal reflux disease (GERD) symptom questionnaire at weeks 4 and 8. The primary endpoint was the endoscopic healing rate of ERD after 8 weeks of treatment. Results Endoscopic healing rates according to the Los Angeles classification was 32 (66.7%) in the E+M group and 26 (60.5%) in the E only group, but there was no statistically significant difference between the groups. Only at 4 weeks, the total GERD symptom score changes relative to the baseline significantly improved in the E+M group than that of the E only group (-13.4 ± 14.7 vs -8.0 ± 12.3, P = 0.041), and upper abdominal pain and belching score changes showed significantly improved in the E+M group than that of the E only group (P = 0.018 and P = 0.013, respectively). Conclusions The combination of a proton pump inhibitor with mosapride shows a tendency for upper abdominal pain, belching, and total GERD symptoms scores to improve more rapidly. This suggests that combination therapy with esomeprazole and mosapride will be useful for rapid improvement of specific GERD symptoms, such as upper abdominal pain and belching in ERD patients. (J Neurogastroenterol Motil 2017;23:218-228)

Background/Aims The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. Methods In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. Results The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. Conclusions DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD.

Although the mortality rates for non-variceal upper gastrointestinal bleeding (NVUGIB) have recently decreased, it remains a significant medical problem. The main aim of this prospective multicenter database study was to construct a clinically useful predictive scoring system by using our predictors and compare its prognostic accuracy with that of the Rockall scoring system. Data were collected from consecutive patients with NVUGIB. Logistic regression analysis was performed to identify the independent predictors of 30-day mortality. Each independent predictor was assigned an integral point proportional to the odds ratio (OR) and we used the area under the curve to compare the discrimination ability between the new predictive model and the Rockall score. The independent predictors of mortality included age >65 years [OR 2.627; 95 % confidence interval (CI) 1.298–5.318], hemodynamic instability (OR 2.217; 95 % CI 1.069–4.597), serum blood urea nitrogen level >40 mg/dL (OR 1.895; 95 % CI 1.029–3.490), active bleeding at endoscopy (OR 2.434; 95 % CI 1.283–4.616), transfusions (OR 3.811; 95 % CI 1.640–8.857), comorbidities (OR 3.481; 95 % CI 1.405–8.624), and rebleeding (OR 10.581; 95 % CI 5.590–20.030). The new predictive model showed a high discrimination capability and was significantly superior to the Rockall score in predicting the risk of death (OR 0.837;95 % CI 0.818–0.855 vs. 0.761; 0.739–0.782; P = 0.0123). The new predictive score was significantly more accurate than the Rockall score in predicting death in NVUGIB patients. We need to prospectively validate the accuracy of this score for predicting mortality in NVUGIB patients.

Using data from the real world to solve clinical questions that cannot be answered using data from clinical trials is attracting more attention. Clinical outcomes for patients with esophageal cancer in a real-world setting might be different from data in randomized controlled trials. This study aimed to provide real world data on treatment and prognosis in Korean patients with esophageal cancer. This retrospective cancer cohort included newly diagnosed cases of esophageal cancer at 19 tertiary hospitals between January 1, 2005 and December 31, 2017. Cancer staging was defined according to the 7th edition of the American Joint Committee on Cancer criteria. We identified 6,354 patients with newly diagnosed esophageal cancer (mean age: 64.9 ± 9.0 years, 96.9% squamous cell carcinoma). The proportion of early esophageal cancer increased from 24.7% in 2005 to 37.2% in 2015 (p

Background and Aims This study aimed to validate the equivalence of first-line concomitant and hybrid regimens for Helicobacter pylori infection in an era of increasing antibiotic resistance. The study also aimed to assess regimen compliance. Methods H. pylori-infected patients from six hospitals in Korea were randomly assigned to either concomitant or hybrid regimens. The concomitant regimen consisted of 20 mg of esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg metronidazole, twice daily for 10 days. The hybrid regimen consisted of a 5-day dual therapy (20 mg of esomeprazole and 1 g of amoxicillin, twice daily) followed by a 5-day quadruple therapy (20 mg of esomeprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily). Results Eradication rates for concomitant and hybrid therapy were 78.6% (187/238) and 78.8% (190/241) in the intention-to-treat analysis, and 89.8% (176/196) and 89.6% (181/202) in the per protocol analysis. For both analyses, 95% confidence intervals fell within the ± 8% equivalence margin. Adherence was better in the hybrid group (95.0%) than in the concomitant group (90.1%), a difference that was borderline significant (P = 0.051). Adverse event rates were higher in the concomitant group than in the hybrid group for nausea (15.8% vs 8.8%; P = 0.028) and regurgitation (17.6% vs 10.7%; P = 0.040). Conclusion As compared with concomitant therapy, hybrid therapy offered similar efficacy, better compliance, and fewer adverse events. Hybrid therapy could be a reasonable first-line treatment option for H. pylori in areas with high antibiotics resistance.

Background Probiotics can be beneficial in irritable bowel syndrome (IBS). Mosapride citrate, a selective 5-HT4 receptor agonist, stimulates gastrointestinal motility. We investigated the efficacy of combination therapy with probiotics and mosapride for non-diarrheal-type IBS. Methods Two hundred and eighty-five IBS patients were randomly assigned to either a combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at one of four different doses or a placebo for 4 weeks. The primary outcome was the proportion of patients experiencing adequate relief (AR) of global IBS symptoms at week 4. The secondary outcomes included subject's global assessment (SGA) of IBS symptom relief, individual symptoms, stool parameters, and IBS-quality of life. Key Results The proportion of AR at week 4 was significantly higher in all treatment groups compared to the placebo group (53.7% in group 1, 55.0% in group 2, 55.2% in group 3, 53.6% in group 4 [the highest dose], and 35.1% in placebo group, respectively, p

‡§ § § � � � ¶ ¶ † ‡ § � ¶ Background/Aims: Advances in endoscopic submucosal dissection (ESD) techniques have led to the development of expanded criteria for endoscopic resection of early gastric cancer (EGC). The aim of this study was to evaluate the short- and long-term outcomes for ESD using indication criteria. Methods: A total of 1,105 patients underwent ESD for EGC at six medical centers. The patients were classified into the following two groups based on the lesion size, presence of ulceration and pathological review: an absolute criteria group (n=517) and an expanded criteria group (n=588). Results: The curative resection rates (91.1% vs 91.3%, p=0.896) were similar in the absolute criteria group and the expanded criteria group. The en bloc resection rates (93.4% and 92.3%, respectively; p=0.488) and complete resection rates (98.3% and 97.4%, respectively; p=0.357) did not differ between the groups. The cumulative disease-free survival rates and the overall survival rates were similar between the groups (p=0.778 and p=0.654, respectively). Independent factors for the curative resection of EGC included tumor location (upper vs middle and lower, 2.632 [1.128-6.144] vs 3.497 [1.560-7.842], respectively) and en bloc resection rate 12.576 [7.442-21.250]. Conclusions: The expanded criteria for ESD in cases of EGC is comparable with the widely accepted pre-existing criteria. (Gut Liver, 2015;9:181-187)

Background/aims Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10(-/-)) mice. Methods Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. Results The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10(-/-) mice compared to IL-10(+/+) mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10(-/-) mice compared to IL-10(+/+) mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10(-/-) mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10(-/-) mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. Conclusions These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

Background/Aims Bacillus Licheniformis, a probiotic used in the treatment of diarrhea, has been shown to suppress the growth of pathologic bacteria. This study was performed to assess the therapeutic efficacy and safety of Zhengchangsheng® (Bacillus Licheniformis) in comparison with another probiotic, Bioflor® (Saccharomyces Boulardii) for the treatment of diarrhea. Methods Patients with diarrhea (n=158) were randomized to receive Zhengchangsheng® or Bioflor® for 5 days. The existence or non-existence of formed feces, changes in daily stool frequency, improvement of subjective symptoms, and changes in the severity of diarrhea were compared. Results Of the 158 full analysis set (FAS) patient population, 151 patients comprised the per protocol (PP) analysis. The rates of recovered to formed feces in the Bacillus and Saccharomyces groups were 91.0% vs. 95.0% in the FAS (P=0.326) and 90.5% vs. 96.1% in the PP analysis (P=0.169), respectively. The mean duration of diarrhea changing to formed feces was 3.15±1.10 days in the Bacillus group and 3.22±1.01 in the Saccharomyces group (P=0.695, FAS). The frequency of defecation, subjective symptoms, and degree of severe diarrhea were improved in both groups, however, there were no statistically significant differences between the 2 groups. Analysis of the 95% confidence intervals for the differences in the rate of recovery to formed feces between the 2 groups met the criteria for non-inferiority of Bacillus compared to Saccharomyces. No significant adverse events were observed during the study period. Conclusions Zhengchangsheng® is not inferior to Bioflor® in therapeutic efficacy and is a safe and useful therapeutic agent for the treatment of diarrhea.

Background/aims Smoking and alcohol intake are two wellknown risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis. Methods In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking. Results The median duration of followup was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008). Conclusions Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis.

Aliment Pharmacol Ther 2012; 35: 56–65 Summary Background The eradication rates following standard triple therapy for Helicobacter pylori infection are declining worldwide. Recent studies have shown that sequential therapy for H. pylori infection yields high cure rates. Aim To compare the efficacy and tolerability of a sequential regimen as first-line treatment of H. pylori infection with a standard triple regimen. Methods A total of 348 naive H. pylori-infected patients from six hospitals in Korea were assigned randomly to standard triple or sequential therapy groups. Standard triple therapy consisted of 20 mg of rabeprazole, 1 g of amoxicillin and 500 mg of clarithromycin, twice daily for 7 days. Sequential therapy consisted of a 5-day dual therapy (20 mg of rabeprazole and 1 g of amoxicillin, twice daily) followed by a 5-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily). Results The intention-to-treat (ITT) and per-protocol (PP) eradication rates were 62.2% (95% CI 54.8–69.6%) and 76.0% (95% CI 68.5–83.5%) in the standard triple group, and 77.8% (95% CI 71.4–84.2%) and 87.9% (95% CI 82.3–93.5%) in the sequential group, respectively. The eradication rate was significantly higher in the sequential group compared with the standard triple group in both the ITT and PP populations (P = 0.002 and P = 0.013 respectively), whereas the incidence of adverse events was similar. Conclusions Ten-day sequential therapy is more effective and equally tolerated for eradication of H. pylori infection compared with standard triple therapy. Sequential therapy may have a role as first-line treatment for H. pylori infection.

∥¶ † ‡ § ∥ ¶ Background/Aims: The diagnostic proton pump inhibitor test (PPI test) is a method used in diagnosing gastroesophageal reflux disease (GERD). This study aimed to determine the appropriate dose of lansoprazole for use in the diagnostic test for GERD. Methods: This study was a randomized, controlled, multicenter trial in the Daegu-Gyeongbuk area. Patients with typical refl ux symptoms such as regurgitation and heartburn for at least three months were enrolled in this study. Patients were divided into two groups, the erosive refl ux disease (ERD) group and the non-erosive refl ux disease (NERD) group, and randomized to 14 days of treatment with lansoprazole at a dose of 15 mg, 30 mg or 60 mg once daily. The PPI test was considered positive if the patient’s symptoms improved by more than 50%. Results: A total of 218 patients were enrolled, and analysis was performed on the 188 patients who completed the study. The PPI test was positive in 93.2% of the ERD group and 87.2% of the NERD group. A positive PPI test was observed in 91.7%, 89.4%, and 87.2% of the 15 mg, 30 mg, and 60 mg groups, respectively. Signifi cant symptom score changes were observed starting on day 8 for the 15 mg, 30 mg, and 60 mg groups. Conclusions: In this multicenter, randomized study of Korean patients, the standard dose of lansoprazole was as effective as a high dose of lansoprazole in relieving the symptoms of GERD, regardless of the presence of ERD, by day 14 of treatment. (Gut Liver 2011;5:302-307)

Background The endoscopic submucosal dissection (ESD) technique has been gaining popularity, with continued advances in this treatment approach. However, ESD still is associated with potential complications such as severe bleeding and perforation. Methods This study was performed to compare the clinical outcomes for macro- and microperforations with ESD procedures and to determine the short-term prognosis after ESD. A macroperforation was defined as a gross perforation that occurred during an ESD procedure, and a microperforation was defined by free air observed on simple radiography after the procedure. Immediate closure of macroperforations was performed using endoclips. From July 2003 through May 2008, 1,711 patients underwent ESD for gastric lesions such as dysplasia, early cancer, and subepithelial lesions. Results Among 39 perforation cases (2.3%), macroperforations occurred for 26 patients (67%) and microperforations for 13 patients (33%). All the patients except one who underwent emergency surgery because of severe bleeding and perforation during ESD were managed successfully by intravenous antibiotics and no oral intake. The clinical prognosis and endoscopic characteristics of the patients with macroperforations did not differ from those of the patients with microperforations. Conclusions Perforations associated with ESD could be managed safely and successfully by nonsurgical methods. The clinical prognoses for macro- and microperforations were favorable and comparable.

Background/aims The optimal management of bleeding peptic ulcer with adherent clot remains controversial. The purpose of this study was to compare clinical outcome between endoscopic therapy and medical therapy. We also evaluated the risk factors of rebleeding in Forrest type IIB peptic ulcer. Methods Upper gastrointestinal (UGI) bleeding registry data from 8 hospitals in Korea between February 2011 and December 2013 were reviewed and categorized according to the Forrest classification. Patients with acute UGI bleeding from peptic ulcer with adherent clots were enrolled. Results Among a total of 1,101 patients diagnosed with peptic ulcer bleeding, 126 bleedings (11.4%) were classified as Forrest type IIB. Of the 126 patients with adherent clots, 84 (66.7%) received endoscopic therapy and 42 (33.3%) were managed with medical therapy alone. The baseline characteristics of patients in two groups were similar except for higher Glasgow Blatchford Score and pre-endoscopic Rockall score in medical therapy group. Bleeding related mortality (1.2% vs.10%; p=0.018) and all cause mortality (3.7% vs. 20.0%; p=0.005) were significantly lower in the endoscopic therapy group. However, there was no difference between endoscopic therapy and medical therapy regarding rebleeding (7.1% vs. 9.5%; p=0.641). In multivariate analysis, independent risk factors of rebleeding were previous medication with aspirin and/or NSAID (OR, 13.1; p=0.025). Conclusions In patients with Forrest type IIB peptic ulcer bleeding, endoscopic therapy was associated with a significant reduction in bleeding related mortality and all cause mortality compared with medical therapy alone. Important risk factor of rebleeding was use of aspirin and/or NSAID.

Background As a result of increased resistance to antibiotics, Helicobacter pylori eradication rates using standard triple therapy have been declining. Aim To validate the efficacy and tolerability of a concomitant regimen as a first-line treatment for H. pylori infection. Methods A total of 348 naive H. pylori-infected patients from six hospitals in Korea were randomly assigned to concomitant therapy and standard triple therapy groups. The concomitant regimen consisted of 30 mg of lansoprazole, 1 g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen consisted of 30 mg of lansoprazole, 1 g of amoxicillin, and 500 mg of clarithromycin, twice daily for 10 days. Results Concomitant and standard eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat (p = 0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p = 0.016), respectively. The two groups were similar with regard to the incidence of adverse events. Conclusions Although 10-day concomitant therapy was validated as a suboptimal treatment option for the treatment of H. pylori infection, this regimen is expected to be a promising starting point in the development of an optimal treatment regimen for H. pylori infection.

Endoscopic submucosal desection (ESD) is an effective treatment for selected patients with early gastric cancer (EGC). The purpose of this study was to examine the short-term and long-term outcomes of ESD of undifferentiated early gastric cancer. Data for 1,241 patients who underwent ESD for treatment of EGC between February 2003 and May 2010 were collected. We performed a retrospective analysis of the medical records of 74 patients diagnosed with undifferentiated EGC. We divided the enrolled cases into two groups: the expanded-criteria group (EC group) versus the non-EC group, according to lesion size, presence of ulceration, and pathologic review. Of a total of 74 lesions with undifferentiated EGC, as a result of pathologic examination the EC group included 29 cases and the non-EC group included 45 cases. The mean diameter of lesions was 19.86 ± 12.5 mm. The overall rates of en bloc resection and complete resection were 90.5 % (67/74) and 73 % (54/74), respectively. The curative resection rate was low at 31.1 %. If limited to the pathologically diagnosed EC group, the curative resection rate was 79.3 % (23/29). During median follow-up periods of 34 months (range 7–81), local recurrences were observed in 5.5 % (4/74) of patients. All of these were in the non-EC group and all underwent noncurative resection. There was no mortality related to ESD for treatment of EGC during follow-up. ESD may be a feasible treatment for selected patients with undifferentiated EGC; this should be validated by development of new criteria for ESD for treatment of EGC.

AIM To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus (DM). METHODS Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson’s Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), neurokinin-1 (NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha, (PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also conducted. RESULTS Twenty-six controls and 35 diabetic patients (21 short-duration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index (BMI) (higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group (P < 0.01). On immunohistochemical staining, c-Kit- and PDGFRα-positive immunoreactivity were significantly decreased in the DM group compared with the control group (P < 0.05). There were no statistically significant differences in PGP9.5, nNOS, VIP, and neurokinin 1 expression. On immunofluorescent staining, cellularity of interstitial cells of Cajal (ICC) was observed to decrease with increasing duration of DM. CONCLUSION Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

In adults, most intussusceptions develop from a lesion, usually a benign or malignant neoplasm, and can occur at any site in the gastrointestinal tract. Intussusception in the proximal gastrointestinal tract is uncommon, and gastro-gastric intussusception is extremely rare. We present a case of gastro-gastric intussusception secondary to a primary gastric lymphoma. An 82-year-old female patient presented with acute onset chest pain and vomiting. Abdominal CT revealed a gastro-gastric intussusception. We performed upper gastrointestinal endoscopy, revealing a large gastric mass invaginated into the gastric lumen and distorting the distal stomach. Uncomplicated gastric reposition was achieved with endoscopy of the distal stomach. Histological evaluation of the gastric mass revealed a diffuse large B cell lymphoma that was treated with chemotherapy. (Korean J Gastroenterol 2016;68:40-44)

BACKGROUNDS/AIMS: In spite of several case reports about gastrointestinal stromal tumor (GIST) complicated with hemorrhage, study regarding the risk factors of bleeding in this tumor is scanty. Therefore, we analyzed the clinical characteristics of bled GISTs and tried to find risk factors of bleeding by comparing with non-bled cases. METHODOLOGY: Medical records of 49 bled GIST cases from 5 university hospitals in Korea between year 2001 to 2010 were compared with 96 non-bled cases. Whole pathological slides were reviewed by an experienced pathologist. RESULTS: Female predominance (58.6%) was noted and the mean age of the included patients was 58.4±13.1 years. In univariate analysis, location of jejunum, prolonged prothrombin time, presence of surface dimpling in CT, cellular pleomorphism and positivity of S100 was significantly dominant in the bled cases. Multivariate analysis showed significant differences in the location of jejunum (p=0.004, OR=3.533), prolonged prothrombin time (p=0003, OR=19.643), presence of surface dimpling (p=0.026, OR=6.250) in CT, and positivity of S100 (p=0.001, OR=12.941). CONCLUSIONS: Location of jejunum, prolonged prothrombin time, presence of surface dimpling in CT, and positivity of S100 are independent risk factors associated with bleeding in GI GIST patients.

Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 µg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 µM), N(ω)-Nitro-L-arginine methyl ester hydrochloride (100 µM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 µM), ryanodine (10 µM) and phentolamine (10 µM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 µM). Furthermore, the β-adrenergic receptor antagonist, propranolol (10 µM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via â-adrenergic receptors and sarcoplasmic reticulum Ca(2+) ATPase.

BACKGROUND/AIMS Dysfunction of the gastrointestinal tract occurs in about 76% of patients who are diabetic for more than 10 years. Although diabetes-related dysfunctions of the stomach such as gastroparesis have been extensively studied over the recent years, studies about the mechanism underlying colonic symptoms in long-term diabetes models are rare. Therefore, the goal of our study was to clarify the nature of colonic dysfunction in a long-term diabetic rat model. METHODS The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats. RESULTS Spontaneous contractility of the proximal colon was significantly decreased in the diabetic rats compared to the controls, while the spontaneous contractility of the distal colon was not. The number of interstitial cells of Cajal networks in the proximal colon was greatly decreased in diabetic rats compared to the controls. Contractility of the proximal colon in response to carbachol, an acetylcholine receptor agonist, was significantly weaker in the diabetic rats. In addition, the degree of relaxation in response to nitric oxide in the proximal colon of diabetic rats also appeared to be attenuated. CONCLUSIONS The results from our study suggest that the decrease of interstitial cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase in the proximal colon plays important roles in diabetes-related dysfunction of colon.

Traditional symptom-based therapies of irritable bowel syndrome (IBS) are directed at the relief of individual IBS symptoms, but they are often of limited efficacy in addressing the entire symptom complex. Combinations of drugs to target bothersome symptoms are suggested as the first-line pharmacologic treatment. Increasing knowledge of the pathophysiology and molecular mechanisms of IBS has resulted in the development of several new therapeutic approaches. Thirteen consensus statements for the treatment of IBS were developed using the modified Delphi approach. Exclusion diets have modest efficacy in improving symptoms in some IBS patients. Symptom-based therapies with dietary fiber, bulking agents, laxatives, antispasmodics and laxatives are effective in the improvement of some individual symptoms, e.g. dietary fiber and bulking agents for constipation, laxatives for constipation, antispasmodics for abdominal pain and discomfort, antidiarrheals for diarrhea. 5HT3 receptor antagonists and 5HT((4)) receptor agonists are effective in the relief of global IBS symptoms and individual symptoms such as abdominal pain and abnormal bowel habits. A short term course of nonabsorbable antibiotics may improve global IBS symptoms, particularly in patients with diarrhea- predominant IBS. Some probiotics appear to have the potential benefit in improving global IBS symptoms. Selective C-2 chloride channel activator is more effective than placebo at relieving global IBS symptoms in patients with constipation-predominant IBS. Both tricyclic antidepressants and selective serotonin reuptake inhibitors are equally effective in relieving global IBS symptoms, and have some benefits in treating abdominal pain. Certain types of psychologic therapy may be effective in improving global symptoms in some IBS patients. Further studies are strongly needed to develop better treatment strategies for Korean patients with IBS.

Background/Aims: Obesity is associated with gastroesophageal reflux disease (GERD). Leptin is a hormone which controls appetite and energy homeostasis. Alterations of its level in humans have been linked with obesity and related carcinogenesis. We postulated that the leptin level in plasma or tissues might be different according to the phenotype of GERD. We evaluated this hormone in patients with non-erosive reflux disease (NERD) and reflux esophagitis (RE) with demographic characteristics to confirm the postulation. Methods: The patients with typical GERD symptoms such as acid regurgitation and heartburn were prospectively enrolled and evaluated. The demo- graphic data included body mass index, waist circumference, smoking, and the consumption of coffee. Rapid ure- ase test was done to evaluate the status of Helicobacter pylori infection. We measured plasma leptin level along with the tissue level, which was obtained from the fundus of stomach. Results: A total of 44 patients were eval- uated (RE 20 cases, NERD 24 cases). No demographic data was dif ferent between the two groups, except waist circumference (mean 88.6 cm in RE, 80.9 cm in NERD, p=0.006), smoking (45% in RE, 12.5% in NERD, p=0.021) and coffee consumption (85% in RE, 50% in NERD, p=0.025). The level of plasma leptin was not dif- ferent between the two groups. The level of tissue leptin was also not different between the two groups with an increasing tendency in RE (mean 32.5 ng/mL vs. 28.0 ng/mL in NERD). Conclusions: We could not find any association between plasma and tissue leptin levels and the phenotype of GERD. However, increasing tendency in RE could afford to further studies in near future. (Korean J Gastroenterol 2010;56:15-19)

Brush cytology during ERCP can provide a pathologic diagnosis in malignant biliary obstruction. K-ras and p53 mutations are commonly found in biliary and pancreatic cancers. We evaluated the diagnostic yield of brush cytology and the changes obtained by adding p53 and K-ras staining.One hundred and forty patients with biliary obstruction who underwent ERCP with brush cytology during a 7-year period were included. The sensitivity and specificity of brush cytology only and with the addition of p53 and K-ras staining were obtained.Malignant biliary obstruction was confirmed in 119 patients. The sensitivity and specificity of brush cytology were 78.2% and 90.5%, respectively. The sensitivity of cytology was 77.3% at the ampulla-distal common bile duct (CBD), 92.6% at the mid common hepatic duct (CHD), and 94.7% at the proximal CBD-CHD (p0.05); these values did not differ with the degree or the length of the obstruction. In the 97 patients who received additional p53 and K-ras staining, the sensitivity of cytology plus p53 was 88.2%, cytology plus K-ras was 84.0%, and cytology plus p53 and K-ras was 88.2%. The sensitivity of cytology plus p53 was higher than that of brush cytology only (95% confidence interval: 83.69-92.78 vs 72.65-83.65) but not that of cytology plus K-ras.Brush cytology for malignant biliary obstruction has a high diagnostic accuracy. Adding p53 staining can further improve the diagnostic yield, whereas K-ras staining does not.

Background: Acute upper gastrointestinal bleeding (UGIB) is a common medical emergency resulting in significant morbidity, mortality and cost of care. Whilst red blood cell (RBC) transfusion may be life-saving in massive UGIB, recent controlled trials suggest that a liberal transfusion practice is associated with increased re-bleeding rates and reduced survival after UGIB. 1 Aim: To determine the association between transfusion and rebleeding, mortality at 30 days and at one year after acute non-variceal UGIB. Methods: A retrospective, cohort study of patients who underwent endoscopy at three Western Australian tertiary hospitals for a suspected acute non-variceal UGIB in the period 2008-2010. A detailed chart review and linkage to hospital morbidity, emergency department, death registration and patient blood management data was performed. Logistic regression models were used to investigate factors associated with odds of an early rebleed. Cox models were used to identify factors associated with mortality outcomes. Results: There were 2,238 individuals with a total of 2,370 UGIB admission records. The median age at presentation for first UGIB was 70 years (range 19 to 99 years) and 63% of the cohort was male. Increasing volumes of early RBC transfusion was associated with increased odds of an early rebleed in a dose response trend but only in patients who presented with an Hb >90g/dl (OR 1.5; 95% CI 1.3-1.8; p=0.001). 30-day mortality was 4.9% (n=109). An increased rate of 30 day mortality was observed with increasing number of units of FFP (HR 2.3; 95% CI 1.1-4.6; p=0.02) and platelets (HR 3.7; 95% CI 1.8-7.7; p=0.001) transfused during the UGIB admission after adjusting for other patient and treatment related covariates. There were a further 200 deaths (9%) that occurred after 30 days but within one year of UGIB admission. Transfusion of greater than five units of FFP during the UGIB admission was associated with increased one year mortality (HR 6.7; 95% CI 3.3-13.4; p=0.001) but only for patients who had an INR 150,000 and after adjusting for other covariates. RBC transfusion was not associated with mortality outcomes. Conclusion: In this large, multicentre study, early RBC transfusion was associated with increased rebleeding in patients who presented with Hb > 90g/dl. FFP transfusion and not RBC transfusion was associated with increased mortality outcomes for patients, particularly those with a normal coagulation profile. Reference: 1. Villanueva et al, NEJM 2013; 368: 11-21.

Background Clarithromycin-based standard triple therapy for the first-line treatment of Helicobacter pylori (H. pyloi) has not achieved acceptable eradication rates in some parts of the world, especially in China. This is driven, in part, by clarithromycin resistance. The plant alkaloid berberine and allicin were known to significantly inhibit proliferation of H. pylori in vitro. Moreover, they also seemed to be potentially effective agent for H. pylori eradication in vivo. Whether berberine or allicin treatment could replace clarithromycin as the first-line treatment for Helicobacter pylori infection is unknown. We compared the efficacy of berberine-, allicinor clarithromycin-based triple therapy for 14 days in first-line treatment. Methods For this single-center, randomized trial, we recruited 336 patients (≥18 years old) with H pylori infection from PLA General Hospital between April and December, 2013. Using a permuted block randomization with a block size of six, we randomly allocated eligible patients to receive one of the following regimens (1:1:1): standard triple regimen of clarithromycin 500 mg, omeprazole 20 mg and amoxicillin 1000 mg taken twice a day for 14 days; berberine-based triple regimen of berberine, 300mg 3 times a day and omeprazole 20 mg, amoxicillin 1000 mg twice a day for 14 days; or allicin-based regimen of allicin 8 mg 3 times a day and omeprazole 20 mg, amoxicillin 1000 mg twice a day for 14 days. Investigators were mask to treatment allocation. Eradication was assessed by 13C urea breath test at least 1 month after the treatment. Our primary outcome was probablity of H pylori eradication. The prior patients' consent and approval were obtained from Institutional Review Board of the Chinese PLA General Hospital (Number 2013FC-TSYS-1009). Results We enrolled a total of 336 participants: 112 to each group. In the intention-to-treat population, H. pylori eradication rate was higher with berberine-based therapy (80.4%, 95% CI 73.087.7) than with standard-based therapy (67.0%, 95% CI 58.3-75.7) and allicin-based therapy(65.2%, 95% CI 56.4-74.0). In the per-protocol population, eradication rate was 70.8% (95% CI 62.1-79.4; 75 of 106 patients) in standard triple therapy, 84.1% (95% CI 77.291.0; 90 of 107 patients) in berberine-based therapy, and 73% (95% CI 64.3-81.7; 73 of 100 patients) in allicin-based therapy. Safety profiles for each treatments was similar andmain adverse events were gastrointestinal disorders. Conclusion Berberine-based triple regimen (berberine, amoxicillin and PPI) can achieve a > 80% ITT success rate with similar safety and tolerability to standard regimen for first-line treatment of H. pylori infection.