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Background/Aims The diagnosis of small bowel Crohn’s disease with negative ileocolonoscopic findings has been challenging. Fecal calprotectin (FC) has been used to detect colonic inflammation, but its efficacy for detecting small bowel inflammation is less established. We performed an updated meta-analysis to evaluate the diagnostic accuracy of FC to detect active small bowel inflammation observed during capsule endoscopy. Methods We conducted a systematic literature search for studies that evaluated the correlation between small bowel inflammation and FC in patients with suspected/established Crohn’s disease. We calculated the pooled sensitivity, specificity, and diagnostic odds ratios (DORs) and constructed hierarchical summary receiver operating characteristic curves for FC cutoffs of 50, 100, and 200 µg/g. Results Fourteen studies were eligible for the final analysis. The DORs of all FC cutoffs were significant. The highest DOR was observed at 100 µg/g (sensitivity, 0.73; specificity, 0.73; and DOR, 7.89) and was suggested as the optimal diagnostic cutoff. If we analyzed only studies that included patients with suspected Crohn’s disease, the DOR was 8.96. If we analyzed only studies that included patients with a Lewis score ≥135 as a diagnostic criterion for active disease, the DOR was 10.90. Conclusions FC has significant diagnostic accuracy for detecting small bowel inflammation, and an FC cutoff of 100 µg/g can be used as a tool to screen for small bowel Crohn’s disease. (Gut Liver 2021;15-741)

Duodenal underwater endoscopic mucosal resection (UEMR) has been suggested as a feasible treatment option for superficial non-ampullary duodenal epithelial tumors (SNADETs). However, its efficacy and safety have not been fully established yet. Thus, the objective of this systematic review and meta-analysis was to determine the efficacy and safety of UEMR as compared with conventional endoscopic mucosal resection (CEMR) in the treatment of SNADETs.We conducted a comprehensive literature search in PubMed, EMBASE, the Cochrane Library. Studies comparing CEMR and UEMR for the resection of SNADET were included. Outcomes included en-bloc and complete resection rates, adverse events, and procedure time.A total of six studies with 2454 lesions were included in the quantitative synthesis. En-bloc and complete resection rates were not significantly different between UEMR and CEMR (OR for en-bloc resection: 0.997 [95% CI 0.439-2.266]; OR for complete resection: 0.960 [95% CI 0.628-1.468]). There was no significant risk difference for perforation (risk difference: - 0.002; 95% CI - 0.009 to 0.005) or delayed bleeding (risk difference: - 0.001; 95% CI - 0.014 to 0.011). Procedure time was significantly shorter in the UEMR (standardized mean difference: - 1.294; 95% CI - 2.461 to - 0.127). The risk of recurrence was not significantly different between UEMR and CEMR (risk difference: 0.001; 95% CI - 0.041 to 0.044).Although our results did not show any superiority of UEMR over CEMR in the treatment of SNADETs, UEMR showed equivalent efficacy and safety as compared with CEMR and was associated with a shorter procedure time.

Backgrounds/aims PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Various endoscopic submucosal dissection (ESD) methods for gastric tumors have been tried. However, no studies have yet compared results according to the ESD method for gastric body tumors using a dual knife. The objective of this study was to compare outcomes of two ESD methods for gastric body tumors: the pocket-creation method and conventional method.Patients who underwent ESD for a gastric body tumor were retrospectively reviewed. Patients were divided into two groups according to the ESD method: the conventional method (group I) and pocket-creation method (group II). Characteristics of patients and tumors, hospitalization period, incidence of complications, resection margin status, incidence of surgical operation, procedure time, and laboratory findings were investigated.Of the total of 100 patients, 52 belonged to group I and 48 to group II. All tumors were successfully resectedBoth methods are suitable for treating gastric body tumors with adequate treatment success rates and comparable complication rates.

Linked color imaging (LCI), a novel image-enhanced endoscopy, can make it easy to recognize differences in mucosal color. It may be helpful for diagnosing H. pylori associated gastritis and H. pylo...

Clarithromycin resistance is a main factor for treatment failure in the context ofThis was a multicenter, randomized, controlled trial. A total of 782 patients withThe overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy.Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant

Background/Aims: Metformin has been found to have antineoplastic activity in some cancer cells. This study was performed to determine whether metformin inhibits the proliferation of bile duct cancer cells by inducing apoptosis and its effects on the expression of gene-related proteins involved in cancer growth. Methods: Human extrahepatic bile duct cancer cells (SNU-245 and SNU-1196) were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of metformin on the cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay. Expression levels of various proteins, with or without specific small interfering ribonucleic acid-induced gene disruption, were measured by Western blot analysis. The migratory activity of the cancer cells was evaluated by wound healing assay. Results: Metformin suppressed cell proliferation in bile duct cancer cells by inducing apoptosis. Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172). Hyperglycemia impaired metformin-induced AMPKThr172 activation and enhanced phosphorylation of AMPK at serine-485 (AMPKSer485). Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia. Conclusions: Metformin has antineoplastic effects in bile duct cancer, and hyperglycemic environment interrupts the effect of metformin. In addition, AMPK and IGF-1R play a key role in the proliferation of bile duct cancer cells.

OBJECTIVES Diagnosis of reflux esophagitis according to the Los Angeles classification minimal change (LA-M) has a low inter-observer agreement. We aimed to investigate whether the inter-observer agreement of reflux esophagitis was better when expert endoscopists read the endoscopic images, or when the linked color imaging (LCI) or blue laser imaging (BLI)-bright mode was used. In addition, whether the inclusion of LA-M in the definition of reflux esophagitis affected the consistency of the diagnosis was investigated. METHODS During upper endoscopy, endoscopic images of the gastroesophageal junction were taken using white light imaging (WLI), BLI-bright, and LCI modes. Four expert endoscopists and four trainees reviewed the images to diagnose reflux esophagitis according to the modified LA classification. RESULTS The kappa values for the inter-observer variability for the diagnosis of reflux esophagitis were poor to fair among the experts (κ = 0.22, 0.17, and 0.27 for WLI, BLI-bright, and LCI, respectively) and poor among the trainees (κ = 0.18, 0.08, and 0.14 for WLI, BLI-bright, and LCI). The inter-observer variabilities for the diagnosis of reflux esophagitis excluding LA-M were fair to moderate (κ = 0.42, 0.35, and 0.42 for WLI, BLI-bright, and LCI) among the expert endoscopists and moderate among the trainees (κ = 0.48, 0.43, and 0.51 for WLI, BLI-bright, and LCI). CONCLUSIONS The inter-observer agreement for the diagnosis of reflux esophagitis was very low for both the expert endoscopists and the trainees, even using BLI-bright or LCI mode. However, when reflux esophagitis LA-M was excluded from the diagnosis of esophagitis, the degree of inter-observer agreement increased.

Background: Clarithromycin resistance is a main factor for treatment failure in Helicobacter pylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. Here, we aimed to compare the efficacy and cost-effectiveness of bismuth-based quadruple therapy versus metronidazole-intensified triple therapy with increased the dose and duration for clarithromycin-resistant H. pylori infection. Methods: This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Findings: The overall H. pylori eradication rate was 81.5% in the intention-to-treat analysis. The overall clarithromycin resistance rate was 25.7%. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the ITT analysis (80.4% vs. 69.7%, P =0.079), but was significantly higher than the 14-day metronidazole-intensified triple therapy in the per protocol analysis (95.1% vs. 76.4%, P =0.001). There were no significant differences in the incidence of side effects. Compared with empirical clarithromycin-based triple therapy, the 14-day bismuth-based quadruple therapy is more cost-effective than the 14-day metronidazole-intensified triple therapy. Interpretation: The 14-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the clarithromycin-resistant H. pylori infection. Clinical Trial Registration Details: This study was registered with the Clinical Trials Registry (NCT03431688). Funding Information: Dong-A ST. Declaration of Interests: None. Ethics Approval Statement: The study was approved by the ethics committee of four institutions, and was approved by the ethical guidelines of the Declaration of Helsinki (IRB no. 2018-01-015 for Kangdong Sacred Heart Hospital, 2018-04-007 for Hallym University Sacred Heart Hospital, 2018-04-043 for Chuncheon Sacred Heart Hospital, and 2018-11-009 for Dongtan Sacred Heart Hospital).

Linked color imaging (LCI), a novel image-enhanced endoscopy, can make it easy to recognize differences in mucosal color. It may be helpful for diagnosingUpper endoscopy was performed for 100 patients using white light imaging (WLI) and LCI. During the exam, endoscopic video was recorded. It was then analyzed by four expert endoscopists. They reviewed these videos for endoscopic diagnosis of atrophic gastritis, metaplastic gastritis, nodular gastritis andKappa values for the inter-observer variability among the four endoscopists were fair to moderate under WLI and fair to good under LCI. Sensitivity, specificity, positive predictive value and negative predictive value for diagnosingLCI has better diagnostic accuracy for

Currently, because the population is aging, use of medications has been increasing, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents. This study aims to investigate whether NSAIDs can cause damage to the small bowel (SB) mucosa. Endoscopic videos of subjects who had undergone capsule endoscopy (CE) were evaluated by three experts in order to identify SB injury. All medications taken within 2 weeks from the time of CE were investigated. Cases with a final diagnosis of intestinal tuberculosis, inflammatory bowel disease, Behcet’s disease, Peutz–Jeghers syndrome, small bowel lymphoma, or Henoch–Schonlein purpura were excluded from the analysis. Among the 273 subjects, 125 (45.8%) had SB erosions or ulcers (erosion group) and the remaining 148 (54.2%) did not (no erosion group). SB erosions or ulcers were more common in females, patients aged > 60 years, and subjects taking NSAIDs (p = 0.048, 0.032, and

The optimal treatment regimen or the duration of treatment for an endoscopic submucosal dissection (ESD)-induced gastric ulcer has not been established. The aim of this study was to assess the efficacy of novel proton-pump inhibitor, ilaprazole, for the treatment of ESD-induced gastric ulcer. This was a prospective, open-label, randomized multicenter study. Between June 2015 and March 2018, a total of 176 patients (178 lesions) who underwent ESD for a gastric neoplasm were randomly allocated to receive the oral proton-pump inhibitor ilaprazole 20 mg or rabeprazole 20 mg daily for 8 weeks. The primary outcome was the ulcer healing rate at 4 and 8 weeks. A total of 155 (157 lesions) and 154 patients (156 lesions) were included in the modified intention-to-treat (mITT) and per-protocol analyses, respectively. There was no significant difference in the ulcer healing rate (ilaprazole vs. rabeprazole, 97.4% vs. 97.0 p = 0.78 at 4 weeks, 100% vs. 100%, p = 0.95 at 8 weeks in the mITT analysis) or stage of ulcer (scar stage, 25.6% vs. 17.7%, p = 0.25 at 4 weeks, 92.3% vs. 88.6%, p = 0.59 at 8 weeks in the mITT analysis) between the treatment groups. The quality of ulcer healing was not significantly different between the two groups. No independent predictive factor for higher-quality ulcer healing was found in the multivariate analysis. According to this trial, ilaprazole and rabeprazole showed no significant difference in the healing of artificial gastric ulcers. Most of the ulcers achieved complete healing within 4–8 weeks. Trial registration: ClinicalTrial.gov NCT02638584.

Background and Aims Although a growing body of evidence demonstrates that propofol-induced deep sedation can be effective and performed safely, cardiopulmonary adverse events have been observed frequently. Etomidate is a new emerging drug that provides hemodynamic and respiratory stability, even in high-risk patient groups. The objective of this study was to compare safety and efficacy profiles of etomidate and propofol for endoscopic sedation. Methods A total of 128 patients undergoing EUS were randomized to receive either etomidate or propofol blinded administered by a registered nurse. The primary outcome was the proportion of patients with any cardiopulmonary adverse events. Results Overall cardiopulmonary adverse events were identified in 22 patients (34.38%) of the etomidate group and 33 patients (51.56%) of the propofol group, without significant difference ( P = .074). However, the incidence of oxygen desaturation (4/64 [6.25%] vs 20/64 [31.25%]; P =.001) and respiratory depression (5/64 [7.81%] vs 21/64 [32.81%]; P =.001) was significantly lower in the etomidate group than in the propofol group. The frequency of myoclonus was significantly higher in the etomidate group (22/64 [34.37%]) compared with the propofol group (8/64 [12.50%]) ( P =.012). Repeated measure analysis of variance revealed significant effects of sedation group and time on systolic blood pressure (etomidate group greater than propofol group). Physician satisfaction was greater in the etomidate group than in the propofol group. Conclusions Etomidate administration resulted in fewer respiratory depression events and had a better sedative efficacy than propofol; however, it was more frequently associated with myoclonus and increased blood pressure during endoscopic procedures. (Clinical trial registration number: KCT0001701.)

Acute extensive ischemic gastritis is an extremely rare disease because the stomach has an abundant submucosal vascular plexus with a dual blood supply from the pancreaticoduodenal and gastroduodenal arteries. Smoking, hypertension, and atherosclerotic vascular diseases can be major risk factors for ischemic gastritis. Acute gastric ischemia presents as an acute abdomen with diarrhea or hematemesis that rapidly progresses to acute peritonitis, irreversible septic shock, and death if untreated. We report a case of acute extensive ischemic gastritis combined with tetraplegia due to cervical myelopathy and extensive atherosclerotic changes of the celiac trunk and abdominal aorta.

// Hyun Joo Jang 1 , Eun Mi Hong 1 , Mikang Kim 1 , Jae Hyun Kim 1 , Juah Jang 1 , Se Woo Park 1 , Hyun Wu Byun 2 , Dong Hee Koh 1 , Min Ho Choi 1 , Sea Hyub Kae 1 , Jin Lee 1 1 Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi do, Korea 2 Division of Gastroenterology, Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea Correspondence to: Hyun Joo Jang, email: jhj1229@hallym.or.kr Jin Lee, email: jinlee@hallym.or.kr Keywords: statin, NF-E2-related factor, colon cancer, extracellular-signal-regulated kinase, heme oxygenase-1 Received: March 29, 2016 Accepted: May 29, 2016 Published: June 15, 2016 ABSTRACT Statin has been known not only as their cholesterol-lowering action but also on their pleiotropic effects including anti-inflammatory and anti-oxidant as well as anti-cancer effect. Nrf2 (NF-E2-related factor 2) is a transcription factor to activate cellular antioxidant response to oxidative stress. There are little known whether statins affect activation of Nrf2 and Nrf2 signaling pathway in colon cancer cells. We investigated whether simvastatin stimulates the expression of Nrf2 and nuclear translocation of Nrf2 and which signal pathway is involved in the expression of Nrf2 and antioxidant enzymes. We investigated the effect of simvastatin on the expression of Nrf2 and nuclear translocation of Nrf2 in two human colon cancer cell lines, HT-29 and HCT 116 through cell proliferation assay, Western blotting and immunocytochemical analysis. We evaluated which signal pathway such as ERK or PI3K pathway affect Nrf2 activation and whether simvastatin induces antioxidant enzymes (heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1), γ-glutamate-cysteine ligase catalytic subunit (GCLC)). We demonstrated simvastatin-induced dose-dependent up-regulation of Nrf2 expression and stimulated Nrf2 nuclear translocation in colon cancer cells. We also demonstrated that simvastatin-induced anti-oxidant enzymes (HO-1, NQO1, and GCLC) in HT-29 and HCT 116 cells. PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) suppressed simvastatin-induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells. This study shows that simvastatin induces the activation and nuclear translocation of Nrf2 and the expression of various anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells.

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti-inflammatory or anti-neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF-1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT-29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration-dependent manner. In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin and IGF-1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF-1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer.

Theoretically, use of the stylet during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) will prevent the tip of the needle from being blocked and the sample from being contaminated, improving the quality and diagnostic yield of specimens. This meta-analysis aimed to evaluate any benefit from the use of a stylet during EUS-FNA. MEDLINE, EMBASE, WEB of SCIENCE, and the Cochrane Central Register of Controlled Trials were searched for articles published through October 2015. A fixed-effects model was used to calculate the pooled effects when there is no heterogeneity and a random-effects model was used in situations with significant heterogeneity. Five prospective randomized controlled studies and two retrospective studies of a total of 5491 specimens (2504 specimens in the S+ group and 2987 specimens in the S− group) were included in this study. The pooled analysis demonstrated no significant differences in the adequate sample rate between the S+ group (2135/2504, 85.26 %) and S− group (2609/2987, 87.35 %) [odds ratio 0.94 (95 % confidence interval 0.79–1.11), p = 0.45]. Furthermore, the rate of cellularity > 50 %, the contamination rate, and the blood contamination rate were not significantly superior in the S+ group when compared with the S− group. Whether the use of a stylet improves the proportion of adequate specimens or quality of the specimen is questionable. Our results suggest that the use of a stylet dose not guarantee any advantage during EUS-guided tissue sampling.

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan.Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance.Results. The IC50values of simvastatin alone and irinotecan alone were115.4±0.14 μM (r=0.98) and62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50values of these two drugs were221.9±0.22 μM (r=0.98) and195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at2:1molar ratio showed the best synergistic interaction.Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.

Background/aims Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression. Methods Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis. Results Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation. Conclusions Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer.

Background and Aims Etomidate is a short-acting intravenous hypnotic with a safety profile that is superior to alternative drugs such as propofol. However, there is a lack of evidence on the safety of etomidate in ERCP. The objective of this study was to compare efficacy and safety profiles of etomidate and propofol for endoscopic sedation. Methods This single-center, randomized, double-blind, noninferiority trial included patients with American Society of Anesthesiologists (ASA) physical status I to II who had been scheduled for ERCP. All patients received .05 mg/kg midazolam intravenously as pretreatment before receiving etomidate or propofol. Either etomidate or propofol was then administered according to group allocation. The primary endpoint was an overall respiratory event. A noninferiority margin of 10% was assumed. Results Sixty-three and 64 patients were enrolled in the etomidate and propofol groups, respectively. Respiratory events were identified in 10 patients (15.6%) in the etomidate group and 16 patients (25.4%) on the propofol group, with a rate difference of –9.8% (1-sided 97.5% confidence interval, –∞ to 4.2%). The overall incidence of cardiovascular events tended to be higher in the etomidate group (67.2% vs 50.8%, P = .060). In particular, tachycardia (heart rate > 100 beats/min) was more common in the etomidate group than in the propofol group (64.1% vs 34.9%, P = .001). Transient hypotension tended to be less common in the etomidate group (6.3 vs 15.9%, P = .084). Conclusions Etomidate-based sedation during ERCP was noninferior to propofol-based sedation in terms of the overall incidence of respiratory events in patients with ASA physical status I to II. (International Clinical Trials Registry Platform number: KCT0001926.)

Proton pump inhibitors (PPIs) are the most effective treatment for gastroesophageal reflux disease (GERD); however, a considerable number of patients fail to respond to PPI therapy and complain of nocturnal heartburn and sleep disturbance. The aims of this study are to evaluate the treatment pattern of GERD-related medications and their efficacy in relieving nocturnal heartburn. A total of 334 patients with GERD receiving PPI therapy within 6 months were enrolled in a multihospital questionnaire survey from January, 2014 to March, 2015. GERD symptoms and patients' satisfaction were assessed by patient questionnaires, and treatment patterns of GERD-related medications were assessed by investigators. Among the 334 patients, 95.8% used PPI once daily and 58.6% used a half-dose of PPI. The PPI treatment pattern was changed in 26.6% of all patients, of those, 54% of the patients doubled the PPI dose, and 29.2% of the patients switched to another PPI. Approximately 60.3% of all patients were prescribed more than three GERD-related medications. The overall satisfaction rate was 61.8%, and 32.2% of patients experienced nocturnal heartburn and sleep disturbance. In the extended-release PPI group, there were fewer nocturnal symptoms compared with the conventional PPI group (10% vs. 33.7%, respectively, P = 0.027). The use of more than three medications was inversely associated with patients' satisfaction (OR = 0.355, 95% CI; 0.197-0.642, P = 0.001). Most patients were prescribed adjunctive medications other than PPIs; however, patients' satisfaction was inversely associated with multiple drugs. Patients' satisfaction was superior in extended-release PPIs than conventional PPIs for the relief of nocturnal heartburn in Korean patients.

‡‡ § § † † ‡ § 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)

Summary The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.

Background There has been no consensus regarding the optimal treatment durations and drug regimens in patients with endoscopic submucosal dissection (ESD)–induced ulcers. Objective To assess the efficacy of proton pump inhibitor (PPI) and rebamipide combination therapy compared with PPI monotherapy for ESD-induced ulcer healing. Design Randomized, prospective, controlled study; clinical trial. Setting Five hospitals in a University Medical Center group in Korea. Patients This study involved 290 adults (309 lesions) who underwent ESD for gastric adenoma or early gastric cancer. Intervention PPI and rebamipide combination therapy. Main Outcome Measurements The ulcer healing rate at 4 weeks after ESD. Results The ulcer healing rates at 4 weeks after ESD in the PPI and rebamipide combination therapy group were significantly higher than those in the PPI alone group, both in the full analysis (94.9% vs 89.9%; P P = .020). This combination therapy was an independent predictive factor for a high ulcer healing rate (adjusted odds ratio [OR] 5.572; 95% confidence interval [CI], 2.615-11.876; P = .014). Additionally, the combination therapy group exhibited a higher quality of ulcer healing than the PPI monotherapy group (reviewer 1: P = .027; OR 1.949; 95% CI, 1.077-3.527; reviewer 2: P = .027; OR 1.933; 95% CI, 1.074-3.481). Limitations Open-label study. Conclusion PPI and rebamipide combination therapy had a superior 4-week ESD-induced ulcer healing rate and quality of ulcer healing compared with PPI monotherapy. (Clinical trial registration number: NCT01167101.)

Background/Aims: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). Methods: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). Results: Overall frequency of MC (≥1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72–9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. Conclusions: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

The optimal timing of refeeding after ERCP is unknown. Some practices keep the patient fasting for 24 hours after ERCP, whereas others resume feeding earlier. We aimed to evaluate the risk of post-ERCP pancreatitis (PEP) in patients who initiate early feeding, based on their clinical assessment, including serum amylase testing performed at 4 hours after ERCP.Patients who were scheduled for ERCP were recruited. Patients without abdominal pain and tenderness and a serum amylase level within 1.5-fold the upper limit of normal at 4 hours after ERCP were randomly assigned to either the 4-hour fasting or 24-hour fasting group. Patients from the 4-hour fasting group started oral intake 4 hours after ERCP, whereas those from the 24-hour fasting group fasted for 24 hours after ERCP.Among the 276 enrolled, PEP was identified in 3 (2.2%) from the 4-hour fasting group and in 5 (3.6%) from the 24-hour fasting group, with a rate difference of -1.4% (1-sided 97.5% confidence interval, -∞ to 2.5%). Four-hour fasting was non-inferior to 24-hour fasting in terms of PEP incidence. The total medical costs for treatment-related ERCP were significantly lower in the 4-hour fasting group than in the 24-hour fasting group (1157.20 ± 311.90 vs 1311.20 ± 410.70 U.S. dollars; P = .032).Early feeding in patients without abdominal pain and tenderness and a serum amylase level 1.5-fold the upper limit of normal at 4 hours after ERCP does not increase the incidence of PEP after ERCP and decreases medical costs. (Clinical trial registration number: KCT0002354.).

The preservation of gallbladder function by control of inflammation and elimination of cholesterol accumulation in gallbladder epithelial cells (GBEC) could contribute to the prevention of gallstone formation and cholecystitis. Peroxisome proliferator-activated receptors (PPARs) modulate inflammation and lipid metabolism in various cells and GBEC efflux of excessive amounts of absorbed cholesterol through the ATP-binding cassette transporter A1 (ABCA1)-mediated pathway. The aim of this study was to determine whether ligands of PPARalpha and PPARgamma modulate inflammation and have an effect on ABCA1 expression in GBEC. Canine GBEC were cultured on dishes coated with collagen matrix. We performed Western blot analysis for the expression of specific protein and/or RT-PCR for the expression of specific mRNA. PPARalpha and PPARgamma expression was observed and increased in GBEC treated with WY-14643 (PPARalpha ligand), troglitazone (PPARgamma ligand), and lipopolysaccharide (LPS) compared to the no-treatment control and PPARalpha( antagonist (GW-9662) treatment group. WY-14643, troglitazone, and LPS also induced an increase in the expression of ABCA1 protein and mRNA in cultured GBEC. LPS-induced TNFalpha mRNA expression was suppressed by pretreatment with WY-14643 and troglitazone preceding LPS treatment in GBEC. PPAR ligands, especially PPARgamma, may preserve gallbladder function by suppression of inflammatory reaction and prevention of cholesterol accumulation in GBEC, contributing to the prevention of gallstone formation and progression to cholecystitis.

We investigated early postoperative morbidity, mortality, and long-term outcomes in patients with liver cirrhosis (LC) who had undergone curative surgery for gastric cancer. The medical records of patients with LC who had undergone radical gastrectomy for gastric adenocarcinoma between January 1996 and September 2006 were retrospectively reviewed. A total of 57 patients were enrolled in this study. Forty-six patients (81%) were classified into Child's class A. In 22 patients (39%) postoperative complications developed, the most common being ascites (23%), followed by wound infection and hepatic encephalopathy. Postoperative ascites occurred more frequently in patients with Child's class B or C than in those with class A (63.6% vs 13%, P = 0.001). Massive ascites developed in 4 patients, 3 of whom had Child's class B and underwent D2 lymph node (LN) dissection, and 1 of whom had Child's class C and a D1 LN dissection. Postoperative mortality occurred in 5 patients (9%), with a significantly higher mortality rate for patients with Child's class B or C than for those with class A (27.2% vs 4.3%, P = 0.045). With a median follow-up of 32 months, the estimated 5-year survival rate for all patients was 54%. Regardless of the tumor depth, overall survival was longer for patients with Child's class A than for those with Child's class B or C. These results demonstrated that radical gastrectomy with extended LN dissection is feasible in patients with compensated LC. For patients with moderate to severe hepatic dysfunction, however, D1 or less extensive LN dissection may be the more reasonable surgical procedure.

AIM: To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with undifferentiated-type histology. METHODS: A systematic literature review was conducted using the core databases. Complete resection, curative resection, en bloc resection, recurrence and adverse event rate were extracted and analyzed. A random effect model was applied. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated using a funnel plot, the trim and fill method, Egger’s test, and a rank correlation test. RESULTS: Fourteen retrospective studies between 2009 and 2014 were identified (972 EGC lesions with undifferentiated-type histology). The total en bloc and complete resection rates were estimated as 92.1% (95%CI: 87.4%-95.2%) and 77.5% (95%CI: 69.3%-84%), respectively. The total curative resection rate was 61.4% (95%CI: 44.5%-75.9%). The overall recurrence rate was 7.6% (95%CI: 3.4%-16%). Limited to histologically diagnosed expanded-criteria lesions, the en bloc and complete resection rates were 91.2% and 85.6%, respectively. The curative resection rate was 79.8%. CONCLUSION: In this analysis, ESD is a technically feasible treatment modality for EGC with undifferentiated-type histology. Long-term studies are needed to confirm these therapeutic outcomes.

The recently developed double balloon enteroscopy (DBE) may be useful to evaluate small bowel lesions in patients with suspected Crohn’s disease (CD). We investigated the findings of DBE, small bowel follow-through and abdominal CT in patients with suspected CD who could not be diagnosed with CD using conventional colonoscopy.Thirty patients (27 males, mean age 32.7±9.27 years) with suspected CD were consecutively enrolled in this study. The main symptoms were abdominal pain, chronic diarrhea, weight loss, obscure bleeding, or anemia. These patients were enrolled from May 2006 to January 2007 at 10 tertiary medical centers participating in the Korean Association for the Study of Intestinal Diseases.The DBE demonstrated definite CD in 24 patients (80.0%) and suspected findings of CD in six patients. The pathology results obtained by endoscopic biopsies revealed a granuloma in six patients (23.1%). The DBE identified additional findings not detected by radiology studies in 24 patients (80%) although the small bowel followthrough and the abdominal CT revealed the abnormal findings (73.1% and 64%).DBE may be a promising alternative and useful technique for patients with suspected CD. DBE provides biopsy sampling and more detailed information than radiology studies.

This study investigated the clinical characteristics, survival outcomes of the patients with gastric remnant cancers (GRC) diagnosed after gastric cancer surgery and the need of annual endoscopic surveillance after gastric resection for early detection of GRC.We reviewed the medical records of 30 patients who underwent endoscopy and diagnosed with GRC between 1999 and 2009. We analyzed the clinical features, tumor characteristics, regular endoscopic surveillance, treatment, and survival outcomes.The median time interval between first operation and diagnosis of GRC was 36 months. Fifteen patients (50%) had GRC at non-anastomotic sites. Seventeen patients (56.7%) underwent annual endoscopic surveillance and nine patients (30%) had no symptom at the time of diagnosis of GRC. GRC were detected earlier in patients with annual endoscopic surveillance than those without surveillance (p=0.0014). The median overall survival (OS) after the diagnosis of GRC for all patients was 35.9 months. The median OS of patients with curative resection including endoscopic resection for early gastric cancer was longer than those without resectability (46.3 vs. 13.6 months, p=0.0026).These results suggest that annual endoscopic surveillance program after gastric partial resection would be helpful to detect early cancer of remnant stomach for curative resection.

Familial Mediterranean fever (FMF) is an inherited autosomal recessive disorder, ethnically restricted and commonly found among populations surrounding the Mediterranean Sea. FMF is the most prevalent autoinflammatory disease; is characterized by recurrent, self-limited episodes of fever with serositis; and is caused by Mediterranean fever gene (MEFV) mutations on chromosome 16. We describe a case of adult-onset FMF with complete symptomatic remission during pregnancy, without the use of colchicine. A 25-year-old woman had presented with periodic fever, abdominal pain, and vomiting since she was 21. Her abdominal computed tomography scan showed intestinal nonrotation. She underwent exploratory laparotomy and appendectomy for her symptoms 1 year prior. She had a symptom-free pregnancy period, but abdominal pain and fever recurred after delivery. Mutation analysis of the MEFV gene revealed two point mutations (p.Leu110Pro and p.Glu148Gln). We report an adult female patient with FMF in Korea with complete symptomatic remission during pregnancy.

Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, liver X receptor alpha (LXRalpha), farnesoid X receptor (FXR), ABCG5, ABCG8, and 7alpha-hydroxylase (CYP7A1) which are directly involved in the cholesterol saturation index in bile.Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARalpha and PPARgamma was measured by Western blotting analysis, and the mRNA expression of LXRalpha, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR.In cultured Hep3B cells, pravastatin activated PPARalpha and PPARgamma protein expression, induced stronger expression of PPARgamma than that of PPARalpha, increased LXRalpha mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRalpha, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARgamma and LXRalpha pathways, together or independently.Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRalpha and CYP7A1 in human hepatocytes.

Pneumatosis cystoides intestinalis (PCI), characterized by presence of intramural gas cyst in the intestinal wall is associated with various medical condition. Polymyosistis, however, is rarely associated with PCI. Few cases are reported in the world, and none has not been reported previously in Korea. A 67-year-old woman with polymyositis developed mild abdominal pain and abdominal distension during treatment with steroid and azathioprine. Radiographic findings including CT scan showed intraperitoneal free gas and intramural air, compatible with PCI. The patient’s symptom and clinical findings improved after the treatment with antibiotics and high-dose oxygen therapy. (Korean J Gastroenterol 2011;57:249-252)

Background Our earlier study with cultured gallbladder epithelial cells demonstrated that statins (HMG-CoA reductase inhibitors) activate the expression of PPARα and PPARγ, consequently blocking the production of pro-inflmmatory cytokines. The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγ expression in the liver and gallbladder epithelium, and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. Methods A total of 40 Golden Syrian male hamsters (4 weeks old) were randomly assigned to four groups (basal diet control; basal diet+pavastatin; high cholesterol diet; high cholesterol diet+pravastatin). All hamsters were 11 weeks old at the end of the experiment. The liver, gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARα and PPARγ were performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. Results In the gallbladder and liver of the hamsters, pravastatin activated the PPARα and PPARγ expression of gallbladder epithelial cells and hepatocytes, and particularly the response of PPARγ was much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. Conclusion Pravastatin is an effective medication to activate PPARs (especially PPARγ) in the liver and the gallbladder epithelium of hamsters, and contributes to the prevention of gallstone formation.

Background The incidence of H. pylori-negative, idiopathic peptic ulcer disease (IPUD) seems to be increasing with the changing trends of PUD and H. pylori infection in some developed countries. Aim To investigate the changing trend of PUD and the prevalence of H. pylori infection during the last decade and the prevalence of IPUD in Korea. Methods We prospectively evaluated H. pylori infection and the characteristics of PUD in 895 patients with newly diagnosed PUD from September 2004 to February 2005. Results The H. pylori infection rate in PUD was 72.0% and the proportion of IPUD was 22.2%. The proportion of gastric ulcer (GU) has significantly increased (47.8% vs. 44.3%) and the proportion of duodenal ulcer (DU) has significantly decreased (38.9% vs. 44.9%) compared with ten years ago. The changing trend in the prevalence of H. pylori infection in GU and DU showed an increase in GU (66.1% vs. 73.1%, P = 0.014) and a decrease in DU (79.3% vs. 68.1%, P = 0.001). Conclusion Compared with our results of ten years ago, there has been a significant change in the distribution of PUD and in the prevalence of H. pylori infection in GU and DU. Patients with IPUD are not uncommon in Korea.

Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer.Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication.Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346).One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.