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Background/Aims: Gastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC). Methods: Patients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status. Results: In total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylorieradicated group than in the persistent group during followup (p=0.029). In patients <70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development. Conclusions: H. pylori eradication might prevent the development of metachronous cancer in patients <70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to evaluate the clinical characteristics and prognosis of Crohn's disease (CD) in patients who showed proximal small bowel involvement using a nationwide Korean CD cohort. Methods: We reviewed the data from a cohort of patients diagnosed with CD. The clinical outcomes of patients were evaluated according to the presence of proximal small bowel involvement. Results: Among 1,329 patients with CD for whom complete disease location data were available, 222 patients (16.7%) showed involvement of the proximal small bowel. Compared to patients without proximal small bowel involvement, those with small bowel involvement were more likely to display stricturing behavior (19.8% vs 12.7%, p=0.020). The surgery-free survival of patients who showed proximal small bowel involvement was inferior to that of patients without proximal small bowel involvement (10-year surgery-free survival: 58.4% vs 67.7%, respectively, p<0.001). Additionally, upper gastrointestinal involvement was more common in patients with proximal small bowel involvement than in those without involvement (odds ratio, 1.643; 95% confidence interval, 1.008 to 2.677). Conclusions: Proximal small bowel involvement is a poor prognostic factor for the surgery-free survival of Korean patients with CD. Proximal small bowel involvement should be evaluated in patients with CD for predicting long-term clinical outcomes. (Gut Liver 2018;12:67-72) [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. Methods: We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pyloripositive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori -positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. Results: In gastric cancer cell line, miR-34b/c and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR133a showed serial increase of promoter methylation in order of C, H, and T (all, p<0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p<0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p<0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. Conclusions: This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis. (Gut Liver 2018;12:58-66) [ABSTRACT FROM AUTHOR]

Current-induced domain wall motion has drawn great attention in recent decades as the key operational principle of emerging magnetic memory devices. As the major driving force of the motion, the spin-orbit torque on chiral domain walls has been proposed and is currently extensively studied. However, we demonstrate here that there exists another driving force, which is larger than the spin-orbit torque in atomically thin Co films. Moreover, the direction of the present force is found to be the opposite of the prediction of the standard spin-transfer torque, resulting in the domain wall motion along the current direction. The symmetry of the force and its peculiar dependence on the domain wall structure suggest that the present force is, most likely, attributed to considerable enhancement of a negative nonadiabatic spin-transfer torque in ultranarrow domain walls. Careful measurements of the giant magnetoresistance manifest a negative spin polarization in the atomically thin Co films which might be responsible for the negative spin-transfer torque. [ABSTRACT FROM AUTHOR]

Background/Aims Unregulated activation of nuclear factor-κB (NF-κB) plays a critical role in the pathogenesis of Crohn's disease. In this study, we investigated the clinical characteristics and disease outcome of Crohn's disease patients with varying levels of the NF-κB activation. Methods Crohn's disease patients who underwent surgical bowel resection were divided into two groups, based on the activation status of NF-κB. NF-κB activation was assessed by the immunoreactivity of nuclear NF-κB during immunohistochemical staining of bowel resection specimens. We compared the demographic, clinical and histologic characteristics between groups. Furthermore, the occurrence of reoperation, readmission, and medication change due to disease flare-up were investigated according to NF-κB activation status. Results Among 83 Crohn's disease patients, 47 (56%) showed high NF-κB activity and 36 (44%) showed low NF-κB activity. Patients with high NF-κB activity had higher frequency of ileocolonic involvement (P = 0.028) and lower frequency of perianal involvement (P = 0.042) relative to those with low NF-κB activity. Total histologic scores were significantly higher in patients with high NF-κB activity than those with low NF-κB activity (P = 0.044). There was no significant difference in the frequency of reoperation, readmission, and medication change in relation to NF-κB activation status. Conclusions Crohn's disease patients with high NF-κB activation showed specific clinical manifestations of higher frequency of ileocolonic involvement and lower frequency of perianal involvement relative to those with low NF-κB activation. High NF-κB activity was associated with higher histologic scores. However, the NF-κB activity did not affect the outcome and disease course after surgery. [ABSTRACT FROM AUTHOR]

Background: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis.Methods: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255.Findings: Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (-1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug.Interpretation: PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Background/Aims: Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. Methods: We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. Results: Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn’s disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency. Conclusions: Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients. [ABSTRACT FROM AUTHOR]

Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. Methods: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). Results: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole- treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. Conclusions: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum. [ABSTRACT FROM AUTHOR]

Background/Aims: A percutaneous gastrostomy can be placed either endoscopically (percutaneous endoscopic gastrostomy, PEG) or radiologically (radiologically-inserted gastrostomy, RIG). However, there is no consistent evidence of the safety and efficacy of PEG compared to RIG. Recently, 30-day mortality has become considered as the most important surrogate index for evaluating the safety and efficacy of percutaneous gastrostomy. The aim of this meta-analysis was to compare the 30- day mortality rates between PEG and RIG. Methods: Major electronic databases (MEDLINE, Embase, Scopus, and Cochrane library) were queried for comparative studies on the two insertion techniques of gastrostomy among adults with swallowing disturbance. The primary outcome was the 30-day mortality rate after gastrostomy insertion. Forest and funnel plots were generated for outcomes using STATA version 14.0. Results: Fifteen studies (n=2,183) met the inclusion criteria. PEG was associated with a lower risk of 30-day mortality after tube placement compared with RIG (odds ratio, 0.60; 95% confidence interval [CI], 0.38-0.94; P =0.026). The pooled prevalence of 30-day mortality of PEG was 5.5% (95% CI, 4.0%-6.9%) and that of RIG was 10.5% (95% CI, 6.8%-14.3%). No publication bias was noted. Conclusions: The present meta-analysis demonstrated that PEG is associated with a lower probability of 30-day mortality compared to RIG, suggesting that PEG should be considered as the first choice for long-term enteral tube feeding. Further prospective randomized studies are needed to evaluate and compare the safety of these two different methods of gastrostomy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the effect of a prior gastrectomy on the difficulty of subsequent colonoscopy, and to identify the surgical factors related to difficult colonoscopies. Materials and Methods: Patients with a prior gastrectomy who had undergone a colonoscopy between 2011 and 2014 (n=482) were matched (1:6) to patients with no history of gastrectomy (n=2,892). Cecal insertion time, intubation failure, and bowel clearance score were compared between the gastrectomy and control groups, as was a newly generated comprehensive parameter for a difficult/incomplete colonoscopy (cecal intubation failure, cecal insertion time >12.9 minutes, or very poor bowel preparation scale). Surgical factors including surgical approach, extent of gastrectomy, extent of lymph node dissection, and reconstruction type, were analyzed to identify risk factors for colonoscopy performance. Results: A history of gastrectomy was associated with prolonged cecal insertion time (8.7±6.4 vs. 9.7±6.5 minutes; P=0.002), an increased intubation failure rate (0.1% vs. 1.9%; P<0.001), and a poor bowel preparation rate (24.7 vs. 29.0; P=0.047). Age and total gastrectomy (vs. partial gastrectomy) were found to be independent risk factors for increased insertion time, which slowly increased throughout the postoperative duration (0.35 min/yr). Total gastrectomy was the only independent risk factor for the comprehensive parameter of difficult/incomplete colonoscopy. Conclusions: History of gastrectomy is related to difficult/incomplete colonoscopy performance, especially in cases of total gastrectomy. In any case, it may be that a pre-operative colonoscopy is desirable in selected patients scheduled for gastrectomy; however, it should be performed by an expert endoscopist each time. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a medical case of cytomegalovirus-associated multiple gastric ulcers in ulcerative colitis.

Background/Aims: The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. Methods: Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. Results: Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P <0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. Conclusions: Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy. [ABSTRACT FROM AUTHOR]

Background/Aims: C-reactive protein (CRP) is an easily measured index of disease activity, but its ability to predict clinical course is controversial. We therefore designed a study to determine whether the CRP level at Crohn's disease (CD) diagnosis is a valuable indicator of the disease phenotype, activity, and clinical course. Methods: We retrospectively analyzed 705 CD patients from 32 institutions. The patients were classified into two groups according to CRP level. The patients' demographic and clinical characteristics and their use of immunosuppressive or biological agents were recorded. Disease location and behavior, hospitalization, and surgery were analyzed. Results: A high CRP was associated with younger age, steroid use, colonic or ileocolonic location, high CD activity index, and active inflammation at colonoscopy (p<0.001). As the disease progressed, patients with high CRP were more likely to exhibit strictures (p=0.027). There were significant differences in the use of 5-aminosalicylic acid, antibiotics, corticosteroids, azathioprine, and infliximab (p<0.001, p<0.001, p<0.001, p<0.001, and p=0.023, respectively). Hospitalization was also more frequent in patients with high CRP. Conclusions: The CRP level at diagnosis is useful for evaluating the phenotype, activity, and clinical course of CD. Closer follow-up strategies, with early aggressive treatment, could be considered for patients with high CRP. [ABSTRACT FROM AUTHOR]

Background/Aims: The optimal route for iron administration in anemic patients with inflammatory bowel disease (IBD) has not been determined. The aim of this study was to compare the efficacies of parenteral and oral iron therapy in IBD patients in Korea. Methods: A retrospective multicenter study was performed. Patients who had been administered parenteral iron were matched to the controls with oral iron at a 1:1 ratio according to age, sex, and type of IBD. Results: Patients that received parenteral iron exhibited increases in hemoglobin levels of ≥20% from the baseline at lower doses and in shorter durations (p=0.034 and p=0.046, respectively). In the multivariate analysis, parenteral iron therapy appeared to be more efficient than oral iron therapy, but this difference was not statistically significant (hazard ratio [HR], 1.552; 95% confidence interval [CI], 0.844 to 2.851; p=0.157). Patients with ulcerative colitis responded better to iron therapy than those with Crohn's disease (HR, 3.415; 95% CI, 1.808 to 6.450; p<0.001). Patients with an initial hemoglobin level of 10 g/dL or higher responded poorly to iron therapy (HR, 0.345; 95% CI, 0.177 to 0.671; p=0.002). Conclusions: Parenteral iron therapy appears to be more efficient than oral iron therapy. Physicians should focus on the iron deficiency of IBD patients and consider parenteral iron supplements in appropriate patient groups. [ABSTRACT FROM AUTHOR]

Background/Aims: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. Methods: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. Results: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 highgrade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). Conclusions: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms. [ABSTRACT FROM AUTHOR]

Angiodysplasia (AD) is increasingly being recognized as a major cause of gastrointestinal bleeding. Morphologically flat lesions are common types of AD, whereas the polypoid types are rare. We report a case of multiple polypoid AD in the small bowel causing severe anemia and requiring surgical treatment. A 60-year-old male patient visited our hospital with dyspnea and hematochezia. He had a history of myocardial infarction and was taking both aspirin and clopidogrel. Capsule endoscopy, enteroscopy, computed tomography, and angiography revealed multifocal vascular lesions with a polypoid shape in the jejunum. Surgical resection was performed because endoscopic treatment was considered impossible with the number and the location of lesions. The risk of recurrent bleeding related to the use of antiplatelet agents also contributed to the decision to perform surgery. AD was histologically diagnosed from the surgical specimen. He resumed taking both aspirin and clopidogrel after surgery. He fully recovered and has been doing well during the several months of follow-up. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastric pathology and Helicobacter pylori (H. pylori) infection among Asian patients with Crohn's disease (CD) are still unclear. We evaluated gastric histologic features and frequency of H. pylori infection in Korean patients with CD. Methods: Among 492 patients with CD receiving upper gastrointestinal (GI) endoscopic evaluation in 19 Korean hospitals, we evaluated the endoscopic findings and gastric histopathologic features of 47 patients for our study. Histopathologic classification was performed using gastric biopsy tissues, and H. pylori infection was determined using the rapid urease test and histology. Results: There were 36 men (76.6%), and the median age of patients at the time of upper GI endoscopy was 23.8 years (range, 14.2-60.5). For CD phenotype, ileocolonic disease was observed in 38 patients (80.9%), and non-stricturing, nonpenetrating disease in 31 patients (66.0%). Twenty-eight patients (59.6%) complained of upper GI symptoms. Erosive gastritis was the most common gross gastric feature (66.0%). Histopathologically, H. pylori -negative chronic active gastritis (38.3%) was the most frequent finding. H. pylori testing was positive in 11 patients (23.4%), and gastric noncaseating granulomata were detected in 4 patients (8.5%). Gastric noncaseating granuloma showed a statistically significant association with perianal abscess/ fistula (P =0.0496). Conclusions: H. pylori -negative chronic active gastritis appears to be frequent among Korean patients with CD. The frequency of H. pylori infection was comparable with previous studies. An association with perianal complications suggests a prognostic value for gastric noncaseating granuloma in patients with CD. [ABSTRACT FROM AUTHOR]

Background and study aims: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. Patients and methods: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4 %) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. Results: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5 %), pathology overestimation in 5 (9.6 %), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8 %). The mean length and surface area of the non-neoplastic lesions were 9.2±2.6mm and 49.6±23.6mm2, respectively. Mean sampling ratios were 3.0±1.5mm/fragment and 16.3±10.0mm2/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (P<0.001 for all). Conclusions: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for nonneoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is defined as a chronic and relapsing inflammatory disorder of the intestine. Intestinal inflammation in IBD has been proposed to be attributable to the interplay between microbial, genetic, environmental, and immunological factors. The incidence and prevalence rates of IBD are rapidly increasing apparently in other parts of the world, with dramatic increases especially in East Asia. Generally, cohort studies are useful for estimating the incidence, prevalence, natural course, prognosis, and risk factors of diseases. In particular, cohort studies performed in Western countries have well described the prevalence, risk factors, and natural course of IBD and investigated its genetic pathophysiology. However, the outcomes of IBD cohort studies performed in Korea are not as persuasive as those of Western studies because of the relatively low prevalence of IBD and short follow-up periods of the cohorts in Korea. Despite this critical limitation, members of the Korean Association for the Study of Intestinal Diseases have demonstrated outstanding results. Some unique features of IBD patients in Korea are well demonstrated, such as thiopurine-induced leukopenia or risks of opportunistic tuberculosis infection in patients receiving tumor necrosis factor-α inhibitors. In this review, the present authors summarized the key points of the results of the cohort studies performed in Korea and explored future perspectives. [ABSTRACT FROM AUTHOR]

We know little concerning the expression of transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-β1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-β1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-β1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-β1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways. [ABSTRACT FROM AUTHOR]

Background: Free perforation is the most severe and debilitating complication associated with Crohn's disease (CD), and it usually requires emergency surgery. The aim of this study was to evaluate the incidence of free perforation among Korean patients with CD. Methods: The CrOhn's disease cliNical NEtwork and CohorT (CONNECT) study was conducted nationwide in Korea, and patients who were diagnosed with CD between 1982 and 2008 were included in this retrospective study. We investigated the incidence of free perforation among these patients and their clinical characteristics. Results: A total of 1346 patients were analyzed and 88 patients (6.5%) were identified with free perforation in CD. The mean age of the free perforation group was 31.8 ± 13.0 years, which was significantly higher than that of the non-perforated group (27.5 ± 12.1 years) (p = 0.004). Free perforation was the presenting sign of CD in 46 patients (52%). Of the 94 perforations that were present in 88 patients, 81 involved the ileum. Multivariate logistic regression analysis determined that free perforation was significantly associated with being aged ⩾ 30 years at diagnosis (OR 2.082, p = 0.002) and bowel strictures (OR 1.982, p = 0.004). The mortality rate in the free perforation group was significantly higher (4.5%) than that in the non-perforated group (0.6%) (p < 0.001). Conclusion: The incidence of free perforation in Korean patients with CD was 6.5%. Being aged ⩾ 30 years at CD diagnosis and bowel strictures were significant risk factors associated with free perforation. [ABSTRACT FROM AUTHOR]

Background/Aims: Patients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC. Methods: We retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2x105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration. Results: A total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025). Conclusions: The CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia. (Intest Res 2015;13:50-59) [ABSTRACT FROM AUTHOR]

Aims Ursolic acid (UA), a natural pentacyclic triterpenoid acid, has been reported to show immunomodulatory activity. This study investigated the effects of UA on nuclear factor-kappa B (NF-κB) signaling in cells and experimental murine colitis. Main methods Human intestinal epithelial cells (IECs) COLO 205 and peritoneal macrophages from IL-10-deficient (IL-10-/-) mice were pretreated with UA and then stimulated with tumor necrosis factor-ɑ(TNF-ɑ(LPS), respectively. The expression of pro-inflammatory cytokines was determined by real-time RT-PCR and ELISA. The effect of UA on NF-κB signaling was examined by immunoblot analysis to detect IκBɑphosphorylation/degradation and electrophoretic mobility shift assay to assess the DNA binding activity of NF-κB. For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10-/- mice were treated with or without UA. Colitis was quantified by histopathologic evaluation. Immunohistochemical staining for phosphorylated IκBɑwas performed in the colonic tissue. Key findings UA significantly inhibited the production of pro-inflammatory cytokines, IκBɑphosphorylation/degradation and NF-κB DNA binding activity in both IEC and IL-10-/- peritoneal macrophages stimulated with TNF-ɑand LPS, respectively. UA significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histopathology. UA also significantly ameliorated the severity of colitis in IL-10-/- mice. Furthermore, UA suppressed IκBɑphosphorylation in the colonic tissue. Significance UA inhibits NF-κB activation in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that UA is a potential therapeutic agent for inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background/Aims: Few studies have investigated the prognosis of non-gastric gastrointestinal stromal tumors (GISTs) under the modified National Institutes of Health (NIH) consensus criteria in Korea. This study aims to clarify the clinical usefulness of the modified NIH criteria for risk stratification. Methods: From January 2000 through October 2012, 88 patients who underwent curative resection for primary GISTs were included in this study. The enrolled patients were stratified to predict recurrence by the original NIH criteria and modified NIH criteria. Results: In all, 88 patients had non-gastric GISTs, including 82 and 6 patients with GISTs of the small intestine and colorectum, respectively. The mean age was 57.3±13.0 years, and the median follow-up duration was 3.40 years (range, 0.02-12.76 years). All patients who were placed in the intermediate-risk category according to the original NIH criteria were reclassified into the high-risk category according to the modified NIH criteria. Therefore, the proportion of cases in the intermediate-risk category declined to 0.0% from 25.0% (22/88), and the proportion of cases in the high-risk category increased to 43.2% (38/88) from 18.2% (16/88) under the modified NIH criteria. Among the 22 reclassified patients, 6 (27.3%) suffered a recurrence during the observational period, and the recurrence rate of high-risk category patients was 36.8% (14/38). Conclusions: Patients in the high-risk category according to the modified NIH criteria had a high GIST recurrence rate. Therefore, the modified NIH criteria are clinically useful in selecting patients who need imatinib adjuvant chemotherapy after curative surgical resection. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the effect of screening by using endoscopy on the diagnosis and treatment of gastric cancer. Materials and Methods: The clinicopathologic characteristics of gastric cancer were compared in individuals who underwent an endoscopy because of symptoms (non-screening group) or for screening purposes (screening group). The distributions of gastric cancer stages and treatment modalities in 2006 and 2011 were compared. Results: The proportion of patients in the screening group increased from 45.1% in 2006 to 65.4% in 2011 (P<0.001). The proportion of stage I cancers in the entire patient sample also increased (from 60.5% in 2006 to 70.6% in 2011; P=0.029). In 2011, the percentages of patients with cancer stages I, II, III, and IV were 79.9%, 8.2%, 10.9%, and 1.1%, respectively, in the screening group, and 47.9%, 10.8%, 29.8%, and 11.5%, respectively, in the non-screening group. The proportion of laparoscopic and robotic surgeries increased from 9.6% in 2006 to 48.3% in 2011 (P<0.001), and endoscopic submucosal dissection increased from 9.8% in 2006 to 19.1% 2011 (P<0.001). Conclusions: The proportion of patients diagnosed with gastric cancer by using the screening program increased between 2006 and 2011. This increase was associated with a high proportion of early-stage cancer diagnoses and increased use of minimally invasive treatments. [ABSTRACT FROM AUTHOR]

Objective Virtual chromoendoscopy (CE) is expected to enhance adenoma yield and reduce variation in performance between colonoscopists. This study aimed to compare the efficacy of narrow band imaging (NBI), flexible spectral imaging CE (FICE) and white light (WL) colonoscopy and their impact for less experienced endoscopists. Methods We performed a randomised tandem colonoscopy trial controlling for withdrawal time and bowel preparation. Average-risk adults undergoing screening colonoscopy were enrolled and randomly assigned to first withdrawal with one of the three imaging modalities (NBI (NBI-WL group), FICE (FICE-WL group) and WL (WL-WL group)). Eight colonoscopists were categorised into expert and non-expert subgroups. Results 1650 subjects (mean age 51.4 years, 63.9% men) were included (550 in each group). Compared with WL, neither NBI nor FICE increased the mean number of adenomas detected per patient (0.37 vs 0.35 and 0.36; p=0.591) or the percentage of patients with adenoma (25.3% vs 24.5% and 23.6%; p=0.753). For all three modalities, expert subgroups had higher yields of adenomas than non-expert subgroups. Learning curves were observed only for non-expert subgroups with all three modalities. The percentage of missed adenomas did not differ between the three groups (20.8% by WL vs 22.9% by NBI and 26.0% by FICE, p=0.300) and was not affected by endoscopists' expertise. Conclusions Neither NBI nor FICE improved adenoma detection or miss rates, with no difference in diagnostic efficacy between the two systems. Virtual CE had no additional benefits over WL for non-experts. Clinical trial registration number: KCT0000570. [ABSTRACT FROM AUTHOR]

Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and L-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOSimmunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the agingassociated colonic dysmotility. [ABSTRACT FROM AUTHOR]

Background/Aims: The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. Methods: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. Results: A total of 75 patients were enrolled. The mean tumor size was 3.43±0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. Conclusions: Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiology, associated with extraintestinal manifestations, including the rarely reported immune thrombocytopenic purpura. Here, we present a case of immune thrombocytopenic purpura associated with preexisting ulcerative colitis. The patient was diagnosed with ulcerative colitis 13 years ago. Two years after diagnosis, he presented with hematochezia and active ulcerative colitis. Despite steroid use, the platelet count gradually decreased to 21,000/mm3. Hematochezia and the platelet count recovered after the administration of cyclosporine, and ulcerative colitis was in near complete remission for 11 years. However, the patient was re-admitted for hematochezia and thrombocytopenia persisting over a month. Medical management including increased doses of steroids in combination with cyclosporin failed to control hematochezia and thrombocytopenia. Immune thrombocytopenic purpura was suspected on the basis of normocellular marrow with a normal number of megakaryocytes. To treat uncontrolled colitis and steroid-refractory thrombocytopenia, total proctocolectomy with ileal pouch-anal anastomosis and splenectomy were performed. The patient was followed up for 10 months after surgery and was found to be in good health with a normal platelet count. Therefore, colectomy alone or in combination with splenectomy should be considered in cases of life-threatening ulcerative colitis complicated with steroid-refractory immune thrombocytopenic purpura. [ABSTRACT FROM AUTHOR]

Background/Aims: Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway. Methods: The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-β (TGF-β) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 μmol/L). Results: H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3β (p=0.029) by Western blot analysis. Conclusions: H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors.Methods: This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated.Results: After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area.Conclusions: A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis. [ABSTRACT FROM AUTHOR]

Crohn's disease is a chronic inflammatory disease that can involve the entire gastrointestinal tract. Several studies indicate that Crohn's patients with long disease duration have an increased risk of small bowel or colorectal cancer. In Korea, only a few cases of Crohn's disease-related small bowel or colorectal cancer have been reported. Here, we described 3 cases of colorectal cancer and 2 cases of small bowel cancer in patients with Crohn's disease. Among 5 patients, 3 had Crohn's disease-related lower gastrointestinal malignancy and the other 2 had sporadic lower gastrointestinal malignancies. Since the diagnosis of Crohn's disease-related lower gastrointestinal malignancy tends to be delayed, the development of malignancy should be considered in patients with long duration of Crohn's disease if patients have refractory symptoms despite intensive medical treatment. Surgical consultation should not be delayed. [ABSTRACT FROM AUTHOR]

Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dosedependent manner. Pretreatment with GG-52 suppressed TNF-α- induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent. [ABSTRACT FROM AUTHOR]

A response from Hae Yeon Kang and colleagues to a letter to the editor on their article about endoscopic resection for undifferentiated early gastric cancer, in a previous issue is presented.

Objective Postpolypectomy surveillance guidelines for colorectal cancer introduced the concept of 'risk stratification'; however, few studies have been conducted for validation of its usefulness. The aim of this study was to assess the 5-year incidence of advanced neoplasia recurrence based on the risk stratification scheme of the guidelines and to identify its risk factors. Methods A prospective study of surveillance colonoscopy after screening colonoscopy was carried out at the Seoul National University Hospital Healthcare System Gangnam Center. 3803 asymptomatic Koreans aged 50-69 were enrolled prospectively and 5-year cumulative adenoma rates were analysed according to three risk groups: normal (no baseline adenoma), low-risk (1-2 adenomas <10 mm) and high-risk (an advanced adenoma or ≥3 adenomas) groups. The RR was computed by HR using Cox proportional regression after multivariate adjustments. The primary outcome was the 5-year cumulative rate of recurrent advanced adenoma in each risk category and the secondary outcome was its predictive factors. Results Among 3803 subjects enrolled between 2003 and 2005, 2452 were followed-up within 5 years: 1242, 671 and 539 in the normal, low-risk and high-risk groups, respectively. Compared with the normal group, the low-risk group had a sufficiently low 5-year incidence and did not show an increased risk for subsequent advanced adenoma (2.4% vs 2.0%, HR=1.14, 95% CI 0.61 to 2.17). Conversely, a significantly higher 5-year rate (12.2%) and early recurrence (4.6, 7.4 and 9.6% at 1, 2 and 3 years) of advanced adenoma were revealed in the high-risk group. Among various patients and adenoma characteristics, only high-risk adenoma (HR=5.95, 95% CI 3.66 to 9.68) along with a number of ≥3 (HR=3.06, 95% CI 1.51 to 6.57) and size ≥10 mm (HR=3.02, 95% CI 1.80 to 5.06) were independent predictors. Conclusions The surveillance interval for low-risk patients could be extended beyond 5 years. Colonoscopic surveillance should be targeted to high-risk patients, and 3-year follow-up after initial polypectomy may be appropriate. INSET: Significance of this study. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori ( H. pylori) antigen in stool by determination of the optimal cut-off value in the screening population. A consecutive 515 patients undergoing a routine health check-up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, C-urea breath test, and serology) were positive. A stool antigen test (EZ-STEP H. pylori) was performed for the detection of H. pylori. The optimal cut-off value was determined by the receiver-operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and theC-urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6-95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM. [ABSTRACT FROM AUTHOR]

To determine genome-wide DNA methylation profiles induced by Helicobacter pylori ( H. pylori) infection and to identify methylation markers in H. pylori-induced gastric carcinogenesis. Gastric mucosae obtained from controls (n = 20) and patients with gastric cancer (n = 28) were included. A wide panel of CpG sites in cancer-related genes (1505 CpG sites in 807 genes) was analyzed using Illumina bead array technology. Validation of the results of Illumina bead array technique was performed using methylation-specific PCR method for four genes ( MOS, DCC, CRK, and PTPN6). The Illumina bead array showed that a total of 359 CpG sites (269 genes) were identified as differentially methylated by H. pylori infection ( p < .0001). The correlation between methylation-specific PCR and bead array analysis was significant ( p < .0001, Spearman coefficient = 0.5054). Methylation profiles in noncancerous gastric mucosae of the patients with gastric cancer showed quite distinct patterns according to the presence or absence of the current H. pylori infection; however, 10 CpG sites were identified to be hypermethylated and three hypomethylated in association with the presence of gastric cancer regardless of H. pylori infection ( p < .01). Genome-wide methylation profiles showed a number of genes differentially methylated by H. pylori infection. Methylation profiles in noncancerous gastric mucosae from the patients with gastric cancer can be affected by H. pylori-induced gastritis. Differentially methylated CpG sites in this study needs to be validated in a larger population using quantitative methylation-specific PCR method. [ABSTRACT FROM AUTHOR]

Background: Endoscopic resection as curative treatment of early gastric cancer (EGC) requires accurate staging for depth of invasion (T) before therapy. This study aimed to compare T staging of EGC using a miniprobe with that of conventional endoscopy (CE). Methods: A total of 388 patients with suspected of EGC by CE were prospectively enrolled in the study. After miniprobe staging by an experienced endosonographer, CE staging was performed by another endoscopist who was blinded to the miniprobe assessment. Patients underwent either endoscopic resection ( n = 325) or surgery (=63) according to staging results. Results of each method were compared with the histology of the resected specimen. Clinicopathological factors affecting accuracy of each test were also evaluated. Results: Overall accuracy of miniprobe and CE staging was 78.9% (306/388) and 81.4% (316/388), respectively ( p = 0.052). Sensitivity for T1m was more than 95% (miniprobe 98.7%, CE 97.7%), whereas sensitivity for T1sm was lower at 6.6% for miniprobe and 23.7% for CE ( p = 0.002). Among nine lesions identically considered submucosal invasion by both methods, three were T1sm cancer. Diagnostic accuracy of the miniprobe was lower than that of CE with respect to lesions located in the lower third of the stomach, differentiated histology, or massive submucosal invasion. Conclusions: Overall accuracy of the miniprobe and CE for T staging in EGC was approximately 80% with no significant difference. Accurate prediction of both techniques for submucosal invasion was poor, even by using a combination of the two methods. The use of the miniprobe may not increase the positive predictive value for T staging over the use of CE alone. [ABSTRACT FROM AUTHOR]

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging. [ABSTRACT FROM AUTHOR]

Background and Aim: Colorectal cancer screening is recommended for average-risk persons beginning at age 50. However, information about the incidence and risk factors of precursor adenoma in preceding decades is limited. The aim of this study was to determine the prevalence and risk factors of colorectal adenoma in persons aged 40–49 years and to compare the data with those aged 30–39 years and 50–59 years. Methods: A cross-sectional study of 5254 asymptomatic subjects who underwent screening colonoscopy was conducted. Data were stratified by age into three groups: 608 aged 30–39 years, 1930 aged 40–49 years, and 2716 aged 50–59 years. Results: Prevalence of overall adenomas was 10.4% in the 30–39 years age group, 22.2% in the 40–49 years age group, and 32.8% in the 50–59 years age group. Advanced adenoma was found in 0.7% of the 30–39 years age group, 2.7% of the 40–49 years age group, and 4.1% of the 50–59 years age group. In the 40–49 years age group, male sex and current smoking habits showed associations with low-risk adenoma after multiple adjustments. Moreover, male sex (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.02–3.23), current smoking (OR = 1.58, 95%CI: 1.06–3.50), and family history of colorectal cancer (OR = 2.54, 95%CI: 1.16–5.56) were independent predictors of advanced adenoma in this age group. Conclusions: Prevalence of adenoma in subjects aged 40–49 years was higher than in previous studies. Male sex and current smoking habits along with a family history of colorectal cancer were associated with advanced adenoma in this age group. [ABSTRACT FROM AUTHOR]

The p53 gene has been referred to as 'the guardian of the genome' because it controls apoptosis and cell cycle arrest. The purpose of this study was to evaluate the association of p53 codon 72 genetic polymorphism and the p53 immunohistochemistry with Helicobacter pylori-associated gastroduodenal diseases, including gastric cancer. This study included 1,852 subjects: controls and patients with gastric cancer, dysplasia, benign gastric ulcers, and duodenal ulcers (DU). Biallelic polymorphism was genotyped by restriction fragment length polymorphism. Immunohistochemical analysis for the detection of mutant type p53 expression was performed. The frequency of the Pro/Pro allele of the p53 codon 72 was higher in the patients with H. pylori-positive dysplasia than in controls (OR: 2.3, 95% CI: 1.3-4.3), but it was less frequent among patients with a H. pylori-positive DU (OR: 0.5, 95% CI: 0.3-0.8). However, there was no significant association with gastric cancer, including the location, stage, or histological type of gastric cancer. Expression of a mutant type of p53 protein was detected in 6.3% of dysplastic tissues and 26.5% of cancerous tissues compared 0% in the controls. Positive expression was higher in the intestinal type of cancer (34.9%) than in the diffuse type (15.0%; P = 0.001). These results suggest that genetic polymorphism of p53 codon 72 played a role in the determination of H. pylori-associated gastroduodenal diseases, but p53 immunostaining did not correlate with those of the p53 genetic polymorphism analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Colorectal adenoma is known to be associated with obesity, but the association between colorectal adenoma and visceral adipose tissue (VAT) area measured by abdominal computed tomography (CT) has not been documented clearly. In addition, the relationship between insulin resistance and colorectal adenomas, which underlies the mechanism that links obesity and colorectal adenoma, has not been studied extensively. The aim of this study was to examine VAT area and insulin resistance as risk factors of colorectal adenoma.METHODS:A cross-sectional, case–control study was conducted in Koreans that presented for health check-ups. Subjects underwent various laboratory tests, abdominal CT, and colonoscopy. VAT, subcutaneous adipose tissue (SAT), and homeostatic metabolic assessment (HOMA) index were evaluated as potential risk factors of colorectal adenoma in 2,244 age- and sex-matched subjects.RESULTS:According to univariate analysis, the prevalences of smoking, hypertension, metabolic syndrome, and family history of colorectal cancer were higher in the adenoma group than in the normal control group. In addition, body mass index, waist circumference, triglyceride, high-density lipoprotein cholesterol, and VAT and SAT areas were significantly different in the two groups. According to the multivariate analysis adjusted for multiple confounders, VAT area was independently associated with the risk of colorectal adenoma (odds ratio (OR)=3.09, 95% confidence interval (CI): 2.19–4.36, highest quintile vs. lowest quintile). Mean HOMA index was higher in the adenoma group than in the control group (OR=1.99, 95% CI: 1.35–2.92, highest vs. lowest quintile).CONCLUSIONS:Visceral obesity was found to be an independent risk factor of colorectal adenoma, and insulin resistance was associated with the presence of colorectal adenoma. [ABSTRACT FROM AUTHOR]

Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels.N(G)-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, downregulating cPLA(2), 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10. [ABSTRACT FROM AUTHOR]

Background and Aim: Proton pump inhibitors (PPI) are mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. We investigated whether the CYP2C19 genotype plays a role in the eradication rate of Helicobacter pylori ( H. pylori) infection in patients receiving pantoprazole- or esomeprazole-based triple therapy. Methods: A total of 327 patients infected with H. pylori were treated with either pantoprazole or esomeprazole, plus amoxicillin and clarithromycin for 7 days. The presence of the CYP2C19 genotype was determined by pyrosequencing. Results: The overall H. pylori eradication rate was 85%; 82.6% for the PAC regimen, and 88.3% for the EAC regimen; the differences were not statistically significant. The overall eradication rate in the poor metabolizer groups (PM) was significantly higher than in the extensive metabolizer groups (EM) (97.4% vs 83.3%; P = 0.016). The eradication rates in the EM and PM groups were 80.8% and 95.7% for the PAC regimen and 86.8% and 100% for the EAC regimen, respectively. Conclusion: The results of this study suggest that the CYP2C19 genotype status may play a role in the H. pylori eradication rate in patients receiving pantoprazole or esomeprazole-based triple therapy. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)-based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty-seven H. pylori-infected patients were randomized into a triple-plus-yogurt group (yogurt group, n = 168) or a triple-only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B-1. 13C-urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention-to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) ( p = .124). However, by per-protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) ( p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) ( p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups ( p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side-effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field. [ABSTRACT FROM AUTHOR]

Background and Aim: Interactions between released proteins by Helicobacter pylori ( H. pylori) and the cells of gastric epithelium to which it adheres may contribute to gastric inflammation and epithelial damage. The present study was performed to evaluate the gene expression of AGS gastric cancer cells stimulated with released proteins by H. pylori. Methods: Gene expression of AGS cells to the stimulation by H. pylori-released proteins (G27 strain) were monitored using oligonucleotide microarrays. Results: Eighty-eight genes (0.88%) and eight genes (0.08%) were up- or downregulated, respectively, by treating AGS cells with H. pylori-released proteins but not by H. pylori adhesion after 12 h of coculture. Out of the selected 40 up- and five downregulated genes, 29 upregulated genes classified as general RNA polymerase II transcription factor activity ( GTF2B, PPARGC1A), SH3/ SH2 adaptor activity ( CRKL), transferase activity ( ACLY, CRKL, PIGC, PLK4), and oxidoreductase activity ( IDH1) were confirmed to be upregulated by released proteins and not by H. pylori adhesion by real-time reverse transcription–polymerase chain reaction. When the concentrated H. pylori-cultured supernatant prepared by our protocol was treated by boiling, the upregulations of 26 of these 29 genes (89.7%) except for CD160, ZNF268, and PSAT1 disappeared. This confirmed that most of these upregulations were caused by released proteins. Conclusion: Host genes involving transcription, signaling and stress are significantly modulated by the proteins released by H. pylori. This might strengthen the gastroduodenal pathogenesis induced by H. pylori. [ABSTRACT FROM AUTHOR]

Background and Aim: This study was performed to determine whether serum pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in Korea. Methods: Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and gastrin levels were measured in 1006 patients with gastroduodenal diseases including cancer. Follow-up tests were performed 1 year after Helicobacter pylori eradication. Results: sPGI and sPGII levels increased and PG I/II ratios decreased in line with the severity of activity, chronic inflammation, and the presence of H. pylori ( p < .01). In contrast, sPGI levels and PG I/II ratios decreased in proportion with the severity of atrophic gastritis (AG)/intestinal metaplasia ( p < .01). Gastrin levels were found to be correlated with chronic inflammation negatively in the antrum but positively in the corpus. H. pylori eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios to the levels of H. pylori-negative patients, and was found to be correlated with reductions in activity and chronic inflammation of gastritis. The sensitivity and specificity of a PG I/II ratio of ≤ 3.0 for the detection of dysplasia or cancer were 55.8–62.3% and 61%, respectively. In addition, sPGI and sPGII levels of intestinal-type cancer were significantly lower than those of the diffuse type, respectively ( p = .008 and p = .05, respectively). Gastric cancer risk was highest in the H. pylori-positive, low PGI/II ratio (≤ 3.0) group with an odds ratio of 5.52 (confidence interval: 2.83–10.77). Conclusion: PG I/II ratio (≤ 3.0) was found to be a reliable marker for the detection of dysplasia or gastric cancer, especially of the intestinal type. This detection power of PG I/II ratio (≤ 3.0) significantly increased in the presence of H. pylori, and thus, provides a means of selecting those at high risk of developing gastric cancer in Korea. [ABSTRACT FROM AUTHOR]

Background and aim: The aim of this study was to test the efficacy of 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy for the second-line treatment of Helicobacter pylori infection. Methods: One hundred and ninety-two patients who had failed previous H. pylori eradication on standard triple therapy were randomized to one of two regimens: 1, moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.) for 10 days (the 10MEA group), or 2, esomeprazole (20 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.) for 14 days (the 14EBMT group). The eradication rates, drug compliances, and side-effect rates of these two regimens were compared. Results: Eradication rates by intention-to-treat and per-protocol analyses in the 10MEA and 14EMBT groups were 71.9% and 82.6%, and 71.7% and 90.5% ( p = .973 and .321), respectively. The 10MEA group was significantly superior to the 14EMBT group in terms of side-effect rates (12.2% vs. 39.6%, p = .001), and discontinuation rates due to side-effects were lower in the 10MEA group than in the 14EMBT group (0.7% vs. 13.2%, p < .001). Moreover, compliance was higher in the 10MEA group (94.2% (131/139)) than in the 14EBMT group (83.0% (44/53)) ( p = .014). Conclusion: The 10-day moxifloxacin-based triple therapy was found to have a high eradication rate with few side-effects and good drug compliance. These findings suggest that this regimen is a safe and effective second-line treatment option for H. pylori infection in Korea. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether or not genetic polymorphism of IL-1B, IL-1RN, and TNF-Α is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection. Methods: This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first-degree gastric cancer relative (GCR). IL-1Β-511 and TNF-A-308 biallelic polymorphism were genotyped by 5′ nuclease polymerase chain reaction (PCR) assays, and PCR-restriction fragment length polymorphism (PCR-RFLP). IL-1RN penta-allelic variable number of tandem repeats was genotyped by PCR. Results: There was no difference in the genetic polymorphism of IL-1Β-511, IL-1RN and TNF-A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL-1B-511 C/T (OR: 0.5, 95% CI: 0.3–0.7) and T carrier (OR: 0.6, 95% CI: 0.4–0.8) were lower in the H. pylori-positive BGU patients. The IL-1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1–28.5) in the H. pylori-positive GCR. There was no significance in the polymorphism of TNF-Α-308 regardless of H. pylori-induced gastroduodenal diseases. Conclusions: The IL-1Β-511 T-carrier polymorphism has a negative effect on the development of H. pylori-positive BGU, and high frequency of IL-1RN 2/2 was found in the H. pylori-positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori-induced gastroduodenal diseases in Korea. [ABSTRACT FROM AUTHOR]