Search

Background/Aims: Colonoscopic perforations have been managed with exploratory laparotomy, and have resulted in some morbidity and mortality. Recently, laparoscopic surgery is commonly performed for this purpose. The aim of this study was to compare the outcomes of several management strategies for iatrogenic colonoscopic perforations. Methods: We retrospectively reviewed the medical records of patients who had been treated for colonoscopic perforation between January 2004 and April 2013 at CHA Bundang Medical Center in Korea. Results: A total of 41 patients with colonoscopic perforation were enrolled. Twenty patients underwent conservative management with a success rate of 90%. Surgical management was performed in 23 patients including two patients who were converted to surgical management after the failure of the initial conservative management. Among 14 patients who underwent surgery at 8 hours after the perforation, there was no considerable difference in adverse outcomes between the laparotomy group and the laparoscopic surgery group. The medical costs and claim rate were 1.45 and 1.87 times greater in the exploratory laparotomy group, respectively. Conclusions: Conservative management of colonoscopic perforation could be an option for patients without overt symptoms of peritonitis or with a small defect size. If surgical management is required, laparoscopic surgery may be considered as the initial procedure even with a delayed diagnosis.

Esophageal duplication (ED) is rarely diagnosed in adults and is usually asymptomatic. Especially, ED that is connected to the esophagus through a tubular communication and combined with bronchoesophageal fistula (BEF) is extremely rare and has never been reported in the English literature. This condition is very difficult to diagnose. Although some combinations of several modalities, such as upper gastrointestinal endoscopy, esophagography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, can be used for the diagnosis, the results might be inconclusive. Here, we report on a patient with communicating tubular ED that was incidentally diagnosed on the basis of endoscopy and esophagography during the postoperational evaluation of BEF.

The natural history of hepatitis B virus (HBV) infection is probably related to host immune factors. Interferon-gamma (IFN-gamma) plays significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of IFN-gamma, IFN-gamma receptor (IFNGR)-1 and 2, and interferon regulatory factor (IRF)-1 genes. Between March 2002 and December 2002, 614 Korean patients were enrolled in two different groups: an HBV clearance group (n = 201), who were hepatitis B surface antigen (HBsAg) negative with antibodies to HBsAg and hepatitis B core antigen, and an HBV persistence group (n = 413), who were repeatedly HBsAg positive. We assessed polymorphisms in the IFN-gamma gene at position +874, in the IFNGR-1 gene at positions -56 and +95, in the IFNGR-2 gene at the second position of codon 64 (Gln64Arg), and in the IRF-1 gene promoter (-410, -388), and the genotype distributions of the HBV clearance and persistence groups were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-gamma, IFNGR-1 and 2, and IRF-1 gene polymorphisms under the codominant, dominant, and recessive models.

The H+/K+-ATPase of gastric parietal cell exchanges luminal K+ for cytoplasmic H+, of which outcome is gastric acidification with outflux of hydronium ion (H3O+). Secretion of gastric acid from the H+/K+-ATPase is stimulated by neuronal sensing and elaborately regulated various neuronal transmitters and hormones, consequently resulting in anchoring of the H+/K+-ATPase in canaliculi membrane of gastric parietal cell. Since hypersecretion of gastric acid or a defect of its barrier function is considered as a principal casual factor in the acid-related diseases such as duodenal and gastric ulcer, reflux esophagitis, and some types of gastritis, the development of anti-secretory agents including PPIs (proton pump inhibitors) and H2-RAs (histamine type 2 receptor antagonists) has revolutionized during the second millennium. Similar considerations applying to design of compounds substituting K+ led to the development of acid pump antagonists (APAs), of which advantages are independent of secretory status, no lag time required, reversible in actions allowing “on-demand dosage”. Our recent studies revealed that these inhibitors of H+/K+-ATPase could be extensively applied for the selective induction of cancer cell apoptosis, a significant anti-inflammatory and gastroprotective action far beyond acid suppression. In the current review, we described the mechanistic regulation of gastric acid secretion with pump inhibitor, the difference and characteristics between PPI and APA based on the molecular mechanism, and their new applications beyond acid suppression.

Background: Quality of life (QOL) in patients with functional dyspepsia in South Korea has never been studied, mostly due to the lack of a psychometrically validated disease-specific instrument for measuring the QOL. The aim of the present study was to develop and validate a QOL scale for patients with functional dyspepsia. Methods: A Functional Dyspepsia-Related QOL (FD-QOL) scale was developed and validated as follows: item generation, pilot test, and psychometric test. Patients with functional dyspepsia (n = 220) were recruited from seven university hospitals. The participants were asked to complete the preliminary item-generated FD-QOL, the Short Form-36 (SF-36), and the Index of Dyspepsia Symptoms-Korean (IDS-K). The data were analyzed using factor analysis, correlation, anova, and Cronbach’s alpha. Results: Twenty-three items were generated based upon content validity. Factor analysis extracted a four-factor solution, and two items were deleted because they were not loaded significantly on any factor. The FD-QOL was correlated with the SF-36 subscales, of which scores were differentiated according to the levels of dyspepsia symptoms. Cronbach’s alpha of the FD-QOL was 0.94. Conclusions: The FD-QOL scale is a rapid and easily applicable instrument with excellent psychometric properties of content, factorial, convergent, and known-groups validity, and internal consistency reliability in Korean patients with functional dyspepsia.

RETRACTED PUBLICATIONRetracted publication: Marie Yeo, Tae Young Oh, Yong Seok Kim, Young Mi Won, Sung Whan Ahn, Jin Kim, Soon Ki Chung, Myung Hee Chung, Sung Uk Han and Ki-Baik Hahm: Journal of Clinical Biochemistry and Nutrition, 38(2), 77-93(2006). "Identification of Molecular Targets Associated with Augmented Gastric Mucosal Damages after Stress in the Presence of Helicobacter Pylori Using High Throughput Analysis of cDNA Microarray and Proteomics" (Received 11 October 2005, Accepted 22 November 2006)This article was withdrawn by the request of the authors on September 22, 2006.

Helicobacter pylori has been known to provoke gastric inflammation, ulceration, and DNA damage, based on which WHO defined H. pylori as a class I carcinogen. Although ginseng, the root of Panax ginseng C.A. Meyer, has been reported to possess antiadhesion or antimicrobial activity against H. pylori, in this study, we examined the protective effect of red ginseng extracts (RGE) against H. pylori-induced cytotoxicity and DNA damage. RGE significantly attenuated both H. pylori-induced DNA damage assessed by comet assay and apoptosis measured by DNA fragmentation. Inactivation of ERK1/2 signaling and attenuation of caspase-3 activation and PARP cleavage were revealed with RGE against H. pylori infection. RGE decreased H. pylori-stimulated IL-8 gene expression, which resulted from the transcriptional regression of NF-kappaB. In conclusion, RGE showed significant gastroprotective effects against H. pylori-associated gastric mucosal cell damage, suggesting that red ginseng could be used as a medicinal phytonutrient against H. pylori infection.

Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.

Mannose-binding lectin (MBL) plays an important role in immune defense. This study was undertaken to investigate the association between hepatitis B virus infection and polymorphisms of MBL gene. We assessed the single nucleotide polymorphism at codon 54 in exon 1 of MBL in patients with hepatitis B virus infection and HBsAg negative controls in Korean population. A total of 498 enrolled subjects was classified into four groups. Group 1; Clearance, Group 2; Inactive healthy carrier, Group 3; Chronic hepatitis, Group 4; Liver cirrhosis. MBL gene polymorphisms at codon 54 led to three genotypes (G/G, G/A, A/A). When we divided subjects into clearance group (group 1) and persistence group (group 2-4), G/G genotype and A-allele carrier were observed in 55.6% and 44.4% in clearance group, 64.8% and 35.2% in persistence group (p=0.081), respectively. When hepatitis B virus persistent cases were divided into inactive healthy carrier (group 2) and disease progression group (group 3 and 4), MBL gene polymorphisms at codon 54 were not related to disease progression (p=0.166). MBL gene polymorphism at codon 54 was not associated with the clearance of hepatitis B virus infection nor progression of disease in chronic hepatitis B virus infection.

Purpose: Helicobacter pylori infection can lead to gastric cancer, and cyclooxygenase-2 (COX-2) is overexpressed in the stomach during H. pylori infection. Therefore, we investigated whether nonsteroidal anti-inflammatory drugs might protect against this form of cancer. Specifically, we examined the chemopreventive effect of the COX-2 inhibitor nimesulide on H. pylori-associated gastric carcinogenesis in mice. Experimental Design: C57BL/6 mice were treated with the carcinogen N-methyl-N-nitrosourea (MNU) and/or H. pylori. To determine the effect of COX-2 inhibition, nimesulide was mixed with feed pellets and administered for the duration of the experiment. All of the mice were sacrificed 50 weeks after the start of the experiment. Histopathology, immunohistochemistry, and Western blotting for COX-2, Bax and Bcl-2 were performed in stomach tissues. In vitro experiments with the human gastric cancer cell line AGS were also performed to identify mechanisms underlying cancer chemoprevention by nimesulide. Results: Gastric tumors developed in 68.8% of mice that were given both MNU and H. pylori, whereas less than 10% developed gastric tumors when given either MNU or H. pylori alone. These findings indicate that H. pylori promotes carcinogen-induced gastric tumorigenesis. In mice treated with both MNU and H. pylori, nimesulide administration substantially reduced H. pylori-associated gastric tumorigenesis, whereas substantial inductions of apoptosis were observed. In vitro studies demonstrated that nimesulide and H. pylori when combined acted synergistically to induce more apoptosis than either alone. Conclusions: Our data show that nimesulide prevents H. pylori-associated gastric carcinogenesis, and suggest that COX-2 may be a target for chemoprevention of gastric cancer.

Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in Helicobacter pylori induced gastritis. The purpose of this study was to examine the role of iNOS in H pylori associated gastric carcinogenesis.Two types of mice were used in this study: iNOS deficient mice (iNOS-/-) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising N-methyl-N-nitrosourea administration and H pylori infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine.The overall incidence of gastric cancer at week 50 was significantly lower in iNOS-/- compared with iNOS wild-type mice (p0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS-/- compared with iNOS wild-type mice (p0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues.These findings suggest that iNOS contributes to H pylori associated gastric carcinogenesis in mice.

The gastric inflammatory response provoked by Helicobacter pylori (H. pylori) consists of infiltrations by neutrophils, lymphocytes, and macrophages, resulting in varying degrees of epithelial cell damage. H. pylori-associated inflammation not only activates various oxidant-producing enzymes such as NADPH oxidase and inducible nitric oxide synthase, but also lowers the antioxidant ascorbic acid in the stomach. Reactive oxygen metabolites and nitrogen metabolites generated by these enzymes react with each other to generate new or more potent reactive species. The specific types of cellular damage resulting from reactive oxygen metabolites include lipid peroxidation, protein oxidation, and oxidative DNA damage. All of these oxidative products can result in biochemical changes leading to cancer. A positive association has been demonstrated between H. pylori infection and gastric adenocarcinoma with increased oxidative stress. Therefore, appropriate treatment to reduce oxidative stress would be expected to prevent subsequent gastric carcinogenesis through lessening of H. pylori-associated inflammation. This review will provide evidence that antiinflammatory regimens can decrease the development of tumors and the amelioration of gastric inflammation might lead to chemoprevention strategies by the attenuation of oxidative stress.

Background: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immuno-inflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1β, TNF-α, IFN-γ and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-KB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). Results: Serum levels of IL-1β, IFN-γ and TNF-α, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-KB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-y, RANTES, TNF-A, TNFR p75. IL-1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However, long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. Conclusion: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.

Background: Long-term evaluation of gastric pathology after H. pylori infection is very important in order to reveal its clinical implications, since debate still exists on the gastric carcinogenesis provoked by H. pylori infection in animal models. Aim: Either to evaluate the long-term outcome of H. pylori infection or to determine how H. pylori could provoke gastric cancer in the mice model. Methods: Four-week-old specific pathogen free C57BL/6 mice (n = 115) were infected with SS1. the mouse-adapted H. pylori strain. After 4, 8, 16, 24, 36, 50 and 80 weeks of bacterial infection, the H. pylori-infected mice were sacrificed. Results: After 80 weeks of infection, almost all the H. pylori-infected mice developed hyperplastic gastritis. but did not show any evidence of gastric adenoma, dysplasia or carcinoma. PCNA positive cells were most abundant after 50 weeks and tended to decrease thereafter up to 80 weeks, whereas apoptosis began to be noted 8 weeks after H. pylori infection, showing 7-8 apoptotic cells/high power field, and tending to increase as time passed. Normally observed neutral mucin decreased during the experiment, showing the most marked decrease 50 weeks after H. pylori infection. In contrast, acidic mucin was noted from 50 weeks after infection. Conclusion: The SS1-infected mouse seems to be a suitable animal model for H. pylori-related research. and H. pylori itself does not induce gastric cancer in normal wild-type mouse model following long-term exposure, which could be explained by the balance that exists between cell proliferation and apoptosis.

Background/Aims: A previous study showed that dietary intervention with Artemisia and green tea extracts, i.e., SD1003F, relieved Helicobacter pylori-associated chronic atrophic gastritis in a mouse model. We continue the research through the current randomized double-blind clinical trial to evaluate the efficacy and safety of the intervention for H. pylori-associated gastric discomfort. Materials and Methods: Forty-nine volunteers who tested positive for H. pylori infection received either placebo or SD1003F for 10 weeks and their functional dyspepsia-related quality of life (QOL) was evaluated. H. pylori infection using a urea breath test (UBT), measurement of pepsinogen level using GastroPanel. Adverse effects with biochemical changes were also evaluated. Results: SD1003F administration significantly improved health related-QOL, including dietary intake, emotional stability, life pattern, and social factors relevant to gastric discomfort, in comparison to the control (P＜0.05). The mean UBT measurement significantly decreased in the SD1003F group (P＜0.05). In 2 of the 24 volunteers, SD1003F alone eradicated H. pylori infection, with significant improvements in endoscopic findings. GastroPanel analysis revealed significant improvements that reflect rejuvenation of gastric atrophy in the SD1003F group. No significant side effect was observed in any participant. Conclusions: SD1003F (Artemisia and green tea extract), is a potential phytochemical to improve H. pylori-associated gastric discomfort.

Aim: Sociocultural factors are important because their different effects on the features of irritable bowel syndrome (IBS) between countries will provide clues towards solving this problem. The aims of this study were to depict the clinical realities of IBS in East Asian countries and test the hypothesis that the diagnosis and treatment of IBS differ between countries. Subjects and Methods: Study participants were 251 physicians involved in the clinical practice of IBS at major institutions in Japan, South Korea, China, the Philippines, Indonesia and Singapore. The questionnaire contained 45 questions focused on the clinical practice of IBS. Results: Subjects in Japan, South Korea, China, Indonesia, the Philippines and Singapore accounted for 55.4, 17.9, 8.8, 8.0, 6.4 and 3.6% of the study cohort, respectively. Amongst East Asian physicians, the most important symptom was considered to be abdominal pain by 33.4%, whilst 24.3% regarded alternating diarrhea and constipation to be the most important symptoms. Total colonoscopy and histopathology use showed no difference among countries. Prescriptions given for mild (p < 0.0001), moderate (p < 0.0001), severe (p < 0.0001), intractable (p = 0.002), diarrheal (p < 0.0001) and constipating (p < 0.0001) patients with IBS significantly differed between the countries. Except for several minor points, IBS specialists showed no significant difference in their diagnosis and treatment of IBS when compared to nonspecialists. Conclusion: This survey provided data on the clinical treatment of IBS among East Asian countries. The results supported the hypothesis that the diagnosis and treatment of IBS differs between countries.

Based on the unexpected Middle East respiratory syndrome (MERS) outbreak in Korea, it was established that the virus can spread easily, MERS exposure in hospitals carries an extreme risk for infection as well as mortality, and the sharing of information was essential for infection control. Although the incidence of exogenous infections related to contaminated endoscopes is very low, the majority of published outbreaks have been caused by various shortcomings in reprocessing procedures, including insufficient training or awareness. Ever since the inauguration of "Clinical Endoscopy" as an English-language journal of the Korean Society of Gastrointestinal Endoscopy in 2011, it has published several articles on disinfection of the endoscope and its accessories. Many Science Citation Index journals have also emphasized high-level disinfection of the gastrointestinal endoscope. Many papers have been produced specifically, since the outbreak of carbapenem-resistant Enterobacteriaceae in 2013. The recent review papers concluded that quality control is the most important issue among all the aspects of procedural care, including the efficiency of the gastrointestinal endoscopy unit and reprocessing room. Thorough reprocessing of endoscopes using high-level disinfection and sterilization methods may be essential for reducing the risk of infection.

Background: Downregulation of TGF-β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF-β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis. Methods: We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF-β type II receptor was expressed under the control of tissue-specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF-β signalling in gastrointestinal carcinogenesis. Results: Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild-type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen-labelling index when infected with H.pylori than wild-type littermates (P

Background and Aim: Debate that Helicobacter pylori might play a causative role in gastric carcinogenesis still exists in spite of the World Health Organization’s definition of H. pylori as a class I carcinogen. In order to define the exact role of H. pylori infection in gastric carcinogenesis, we established a mice model of H. pylori infection. Methods: One hundred and forty-four female C57BL/6 mice were divided into nine groups according to N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the 50th or 80th week after treatment, and their histopathological changes were evaluated according to group. Results: The incidence of gastric adenocarcinoma at the 50th week was 80% in mice treated with both MNU 240 μg/L and H. pylori infection, whereas the incidence was only 27% in mice treated with only MNU 240 μg/L. Although H. pylori caused marked expansion of the proliferative zone at the surface epithelium, H. pylori infection alone caused only chronic atrophic gastritis without any evidence of carcinomas until 80 weeks. The combination of MNU and H. pylori infection also resulted in a significantly higher incidence of gastric adenoma and adenocarcinoma. Significantly higher expressions of proliferating cell nuclear antigen were noted in the gastric mucosa infected with H. pylori compared to controls. Conclusions: These results clearly demonstrated the role of H. pylori infection, rather than direct carcinogens, in promoting gastric carcinogenesis in a mice model. © 2002 Blackwell Science Asia Pty Ltd

Nonsteroidal anti-inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, are associated with gastric mucosal damages including ulcer directly or indirectly. This study was aimed to document the preventive effects of an organosulfur constituent of garlic, S-allyl cysteine (SAC), against NSAIDs-induced gastric damages, as well the elucidation of its pharmacological actions, such as anti-inflammatory, anti-oxidative, and cytoprotective actions.Different doses of SAC were administrated intragastrically before the indomethacin administration. After killing, in addition to gross and pathological evaluations of ulcer, the expressions of inflammatory mediators, including cyclooxygenase-2, prostaglandin E2 , IL-1β, tumor necrosis factor-α, IL-6, and anti-oxidant capacity, were analyzed by Western blot analysis or ELISA, respectively. Transferase deoxytidyl uridine end labeling assay, periodic acid and Schiff staining, F4/80 staining, and CD31 staining were compared among doses of SAC. Detailed documentation of in vitro biological actions of SAC, including NF-κB, histone deacetylator inhibition, phase 2 enzyme, and MAPKs, was performed.SAC was very effective in preventing indomethacin-induced gastric damages in a low dose through significant decreases in macrophage infiltration as well as restorative action. Indomethacin-induced expressions of inflammatory mediators were all significantly attenuated with SAC in accordance with histone deacetylator inhibition. In addition, SAC significantly increased the total anti-oxidant concentration and mucus secretion, and allows for a significant induction of HO-1. However, these preventive effects of SAC were dependent on dosage of SAC; higher dose above 10 μM paradoxically aggravated NSAID-induced inflammation.Synthetic SAC can be promising therapeutics agent to provide potent anti-inflammatory, anti-oxidative, and mucosa protective effects against NSAID-induced damages.

Cellular quiescence is defined with reversible nonproliferating state and featured with a low metabolic state such as decreased glycolysis, reduced translation rates, and activation of autophagy. As signal for quiescence or dormancy, reduced cell growth and biosynthesis inactivating the TOR kinase are essential, but cellular quiescence is not always associated with reduced metabolism since it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis, and flux through central carbon metabolism are not reduced. However, in contrast to normal cells, cancer cells, especially cancer stem or dormancy cells, intrinsic and acquired resistance led to resistance to cancer therapeutics, but can be reversed with the acquisition of chemoquiescence. The development of new drug combinations or strategy to treat the highly aggressive and metastatic cancers including relapsed leukemias, melanoma, and head and neck, brain, lung, breast, ovary, prostate, pancreas as well as gastrointestinal cancers can be feasible with the combination of chemoquiescence agent, in which cancer stem cells (CSCs) or tumor dormancy can be possibly eradicated or removed. Therefore, active investigations of metformin or chloroquine as well as other drugs under revisited study, such as potassium channel-inhibiting acid pump antagonist, sonic hedgehog inhibitors, and Akt inhibitor, are actively performing under the hopeful vision of chemoquiescence, aiming at achieving complete cancer cure as well as prevention of cancer recurrence far beyond the scope of current chemotherapy or chemoprevention. In this chapter, the evolving concept of chemoquiescence or cancer dormancy will be introduced accompanied by introduction of some novel drug development targeted for chemoquiescence. Now, we should seize as well as eradicate rotten root of cancer for cure.

Since the discovery of Helicobacter pylori (H. pylori) infection as the major cause of gastroduodenal disorders including acute and chronic gastritis, gastroduodenal ulcer, chronic atrophic gastritis, and gastric cancer almost three decades ago, the possibility of preventing these clinical diseases through eradicating H. pylori has been the focus of active research, but soon debate in the scientific community, though eradication opens the feasibility of cancer prevention and the removal of bacteria significantly prevents development or recurrence of peptic ulcer diseases and some clinical diseases, was proposed due to uncertainty in either achievement of complete eradication or inefficacy in cancer prevention with eradication alone. Still its linkage to gastric cancer is incontestable. Since the multiple combination of bacterial factors, environmental insults, and the host immune response that drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer is intervened, simple eradication deemed the feasibility of cancer prevention. Therefore, our group open strong hypothesis that non-microbial, dietary approach might be the alternate, for which several interventions of nutritional components can highlight rejuvenation of chronic atrophic gastritis as well as amelioration of H. pylori-associated procarcinogenic inflammation. In this review article, the experience and outcome regarding nutritional application to rejuvenate gastric atrophy will be introduced, using Korean red ginseng, garlic extracts, cancer preventive Korea kimchi, n-3 polyunsaturated fatty acids (PUFA), special form of licorice, and probiotics. The detailed influence of dietary intervention and bacterial eradication therapy on disease progression and reversibility of premalignant lesions are discussed.

Nonsteroidal anti-inflammat ory drugs (NSAIDs) are one of the drug types frequently prescribed for their analgesic, anti-inflammatory, and antithrombotic actions, but carry a risk of major gastroduodenal damage from mild erosive changes to serious ulceration leading to fatal outcomes. From the long history of willow tree bark and its extracts being applied for the relief of pain and fever, the synthesis of acetylsalicylic acid, the development of selective cyclooxygenase 2 inhibitors (coxibs), and the identification of a G-protein-coupled receptor for prostaglandin, the popular combination regimen of an NSAID and a proton pump inhibitor was invented, but development was continued for further improvement. With regard to major NSAID adverse effects, gastrointestinal (GI) and cardiovascular (CV) risks still remained as problems to be solved. In this review, it is shown that n-3 polyunsaturated fatty acid (PUFA) based NSAIDs can be an angelus custos, supported with facts that an intake of essential n-3 PUFAs orchestrates concerted protective actions against two notorious side effects of NSAIDs, the aforementioned GI risk and CV risk of NSAIDs. Since pills containing n-3 PUFAs, omega-3-acid ethyl ester capsules (Lovaza, Omarcor), have already been safely prescribed to prevent atherosclerosis through lessening lipid burdening, the introduction of a drug delivery system such as a gastroretentive form of n-3 PUFA based NSAIDs will highlight newer hope for GI safety under the guarantee of reduced CV risk. Because n-3 PUFAs have been proven to attenuate cytotoxicity, inhibit lipid-raft-associated harmful signaling, and relieve oxidative stress relevant to NSAIDs, n-3 PUFA based NSAIDs will be next-generation GI-safe NSAIDs.

Background Various bio-sheet grafts have been attempted either to accelerate healing of artificial ulcers or to prevent adverse events after endoscopic submucosal dissection (ESD), but neither prospective nor mechanistic studies were available. Objective To evaluate the substantial effect of a bio-sheet graft on artificial ulcer healing and its feasibility as an endoscopic treatment modality. Design Preclinical, in vivo animal experiment and proof-of-concept study. Setting Animal laboratory. Subjects Three mini-pigs, Sus scrofa , mean age 14 months. Intervention Multiple ulcers sized 2.5 cm in diameter were generated by ESD in 3 mini-pigs and were assigned randomly into the following 3 groups; control group, bio-sheet group, or combination (bio-sheet plus drug) group. Bio-sheet grafts or bio-sheet plus drug combinations were applied on the artificial ulcers immediately after the ESD. Main Outcome Measurements Feasibility and efficacy of endoscopic bio-sheet graft therapy for the management of artificial ulcers and the evaluation of healing conditions based on histology changes in the remaining gastric bed tissues harvested from the stomachs. Results Thirty-three ESD specimens were obtained. On an image analysis of the ratio of healed area in the remaining gastric bed tissue compared with the matched dissected gastric mucosa, the control group showed the most significant improvement in healing activity among the 3 groups ( P P Limitations Animal model. Conclusion Although the bio-sheet grafts provided physical protection from gastric acid attack as reflected in the attenuated inflammation on the ulcer beds, unexpected delayed ulcer healing was noted in the bio-sheet graft group because of its physical hindrance of the healing process.

The guideline of the Korean College of Helicobacter and Upper Gastrointestinal Research group for Helicobacter pylori infection was first produced in 1998, when definite indication for H. pylori eradication is early gastric cancer in addition to the previous indications of peptic ulcer (PUD) including scar lesion and marginal zone B cell lymphoma (MALT type). Though treatment is recommended for the relatives of a patient with gastric cancer, unexplained iron deficiency anemia, and chronic idiopathic thrombocytopenic purpura, a consensus treatment guideline is the treatment of PUD, MALToma, and gastric cancer in Korea. One- or 2-week treatment with proton pump inhibitor (PPI)-based triple therapy consisting of one PPI and 2 antibiotics, clarithromycin and amoxicillin, is recommended as the first-line treatment regimen. In the case of treatment failure, one or 2 weeks of quadruple therapy (PPI + metronidazole + tetracycline + bismuth) is recommended, whose eradication regimen was not different between Korea and Japan. Though the treatment regimen was similar between two nations, the Japanese government declared the inclusion of H. pylori eradication in patients with H. pylori-associated chronic gastritis, reaching the conclusion that the treatment guideline became quite different between Korea and Japan from February 21, 2013. The prime rationale of the Japanese extended treatment guideline for H. pylori infection was based on the drastic intention to prevent gastric cancer as well as the improvement of chronic gastritis-associated functional dyspepsia based on their findings that H. pylori eradication might decrease gastric cancer incidence as well as mortality. In this review, the discrepancy between the Korean and Japanese treatment guidelines will be explained; why and how?

Objective In spite of cytoprotective and anti-inflammatory actions, conventional licorice extracts (c-lico) were limitedly used due to serious side effects of glycyrrhizin. As our group had successfully isolated special licorice extracts (s-lico) lowering troublesome glycyrrhizin, but increasing licochalcone A, we have compared anti-inflammatory, antioxidative, and cytoprotective actions of s-lico and c-lico against either in vitro or in vivo Helicobacter pylori infection. Methods RT-PCR and Western blot were performed to check anti-inflammatory action and electron spin resonance (ESR) and DCFDA spectroscopy to check antioxidative action. s-lico or c-lico was pretreated 1 hours before H. pylori infection on AGS cells. Interleukin-10 deficient mice inoculated H. pylori and followed with high salt containing pallet diets to produce H. pylori-associated chronic atrophic gastritis and gastric tumors, during which s-lico or c-lico-containing pellet diets were administered up to 24 weeks. Results s-lico had fabulous efficacy on scavenging ROS which was further confirmed by DCFDA study and ESR measurement. The expressions of COX-2, iNOS, VEGF, and IL-8 were increased after H. pylori infection, of which levels were significantly decreased with s-lico in a dose-dependent manner. s-lico significantly ameliorated hypoxia-induced or H. pylori-induced angiogenic activities. s-lico significantly ameliorated H. pylori-induced gastric damages as well as gastritis. Our animal model showed significant development of gastric tumors including adenoma and dysplasia relevant to H. pylori infection, and s-lico administration significantly attenuated incidence of H. pylori-induced gastric tumorigenesis. Conclusions Special licorice extracts can be anticipating substance afforded significant attenuation of either H. pylori-induced gastritis or tumorigenesis based on potent antioxidative, anti-inflammatory, and antimutagenic actions.

BACKGROUND—Although antisecretory medications such as histamine type II receptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete mucosal healing or suffer from either sustained symptoms or ensuing complications, suggesting other damaging factors or impaired mucosal resistance are also involved in the pathogenesis of reflux oesophagitis. AIMS—The present study was designed to evaluate oxidative stress as the major pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis. MATERIALS AND METHODS—Reflux oesophagitis was induced by insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats. RESULTS—DA-9601, a novel antioxidant substance, significantly attenuated the gross and histopathological scores of reflux oesophagitis compared with those treated with ranitidine alone or reflux oesophagitis controls in a dose dependent manner. Only scattered erosions were observed in the antioxidant pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amounts of malondialdehyde (MDA), increased nuclear factor κB (NFκB) activation, and depletion of reduced glutathione (GSH) were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal GSH levels and decreased MDA formation significantly. DA-9601 treatment caused significant reductions in activation of NFκB transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NFκB expression. CONCLUSION—Reflux oesophagitis caused considerable levels of oxidative stress in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophagitis with acid suppression. Keywords: reflux oesophagitis; antioxidants; oxidative stress; rat

BACKGROUNDInflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents.AIMGiven the effects of transforming growth factor β1 (TGF-β1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-β signalling in intestinal epithelial cells may play an important role in the development of IBD.METHODSTGF-β signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-β type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-β signalling in the pathogenesis of IBD.RESULTSTransgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS.CONCLUSIONSDeficiency of TGF-β signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-β signalling may be important in regulating immune homeostasis in the intestine

The goals in developing animal models of inflammatory bowel disease (IBD) are to determine the underlying mechanisms and the action of currently available drugs and to evaluate the value of new therapeutic approaches. Because of the difficulty in determining the severity of colitis in living animals, it has been necessary to kill the experimental animals at varying stages in the studies. If colonoscopic evaluation or endoscopic biopsy is feasible in these experimental animals, continuous observations could be possible, thus avoiding the need to kill them. The aims of the current study were to assess the efficacy of endoscopic examination as a monitoring tool for the severity of colitis in rats and to the efficacy of DA-9601, an extract from Artemisia asiatica which has both antioxidative and cytoprotective actions, on dextran sulfate sodium induced ulcerative colitis in rats endoscopically. Sprague-Dawley rats received 4% DSS in drinking water for 5 consecutive days. Either DA-9601 or sulfasalazine was administered twice a day for 8 days, starting 3 days before DSS administration. After the colonoscopic evaluations on days 2, 4, and 5 after DSS administration the rats were also killed for gross and histopathological evaluations. Simultaneous measurements of malondialdehyde (MDA) and myeloperoxidase (MPO) activities were performed. There was a statistically significant correlation between the scores evaluated by the gross examination and colonoscopic scores, between the colonoscopic scores and the levels of MDA or mucosal MPO activities, and between colonoscopic scores and histopathological activity index. DA-9601 showed excellent improvement in gross lesion scores, decreased MDA amounts and MPO activities compared to sulfasalazine. In conclusion, the introduction of appropriate colonoscopic examination in animal models of IBD could avoid the sacrifice of experimental animals for interim evaluation and provide the valuable information on the course and efficacy of treatment. The potential usefulness of antioxidants in treating IBD is very promising based on the colonoscopic intervention of IBD.

The effect of lamivudine administration on the evolution of precore/core promoter mutation is unknown. The aim of this study was to determine the changes of precore/core promoter sequences in chronic type B hepatitis patients treated with lamivudine. Serial sera were obtained from 11 patients before, at the beginning of, and during therapy. Serum samples were polymerase chain reaction-amplified, and nucleotide sequences of hepatitis B virus (HBV) were analyzed. At baseline, precore and core promoter mutations were found in 6 and 4 of 11 patients, respectively. A precore stop codon mutant was replaced by a wild-type virus in all 6 patients infected with precore mutant at a median treatment of 12 months (vs. before therapy; P = .011). Mutations in the core promoter appeared in only 1 of 10 patients (vs. before therapy; P = .021). However, precore and core promoter mutations appeared in 5 and 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had hepatitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeAg-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene deletions are not eliminated completely during prolonged therapy in 2 patients in whom the HBV genomes had core gene deletions at baseline. In conclusion, lamivudine therapy resulted in reversion from precore/core promoter mutants to wild-type. However, mutations in the precore and core promoter region reappeared during prolonged therapy. HBeAg-negative wild-type precore hepatitis B virus could be selected after lamivudine withdrawal in patients who had HBeAg loss or seroconversion.

Recent observations suggest that immune response is involved in the development of pancreatitis. However, the exact pathogenesis underlying this immune-mediated response is still under debate. TGF-beta has been known to be an important regulating factor in maintaining immune homeostasis. To determine the role of TGF-beta in the initiation or progression of pancreatitis, TGF-beta signaling was inactivated in mouse pancreata by overexpressing a dominant-negative mutant form of TGF-beta type II receptor in the pancreas, under control of the pS2 mouse trefoil peptide promoter. Transgenic mice showed marked increases in MHC class II molecules and matrix metalloproteinase expression in pancreatic acinar cells. These mice also showed increased susceptibility to cerulein-induced pancreatitis. This pancreatitis was characterized by severe pancreatic edema, inflammatory cell infiltration, T- and B-cell hyperactivation, IgG-type autoantibodies against pancreatic acinar cells, and IgM-type autoantibodies against pancreatic ductal epithelial cells. Therefore, TGF-beta signaling seems to be essential either in maintaining the normal immune homeostasis and suppressing autoimmunity or in preserving the integrity of pancreatic acinar cells.

Chromosomal translocations resulting in the expression of chimaeric transcription factors are frequently observed in tumour cells, and have been suggested to be a common mechanism in human carcinogenesis. Ewing sarcoma and related peripheral primitive neuroectodermal tumours share recurrent translocations that fuse the gene EWSR1 (formerly EWS) from 22q-12 to FLI1 and genes encoding other ETS transcription factors (which bind DNA through the conserved ETS domain). It has been shown that transduction of the gene EWSR1-FLI1 (encoding EWS-FLI1 protein) can transform NIH3T3 cells, and that mutants containing a deletion in either the EWS domain or the DNA-binding domain in FLI1 lose this ability. This indicates that the EWS-FLI1 fusion protein may act as an aberrant transcription factor, but the exact mechanism of oncogenesis remains unknown. Because ETS transcription factors regulate expression of TGFBR2 (encoding the TGF-beta type II receptor, TGF-beta RII; Refs 9,14), a putative tumour suppressor gene, we hypothesized that TGFBR2 may be a target of the EWS-FLI1 fusion protein. We show here that Ewing sarcoma [corrected] (ES) cell lines with the EWSR1-FLI1 fusion have reduced TGF-beta sensitivity, and that fusion-positive ES cells and primary tumours both express low or undetectable levels of TGFBR2 mRNA and protein product. Co-transfection of FLI1 and the TGFBR2 promoter induces promoter activity, whereas EWSR1-FLI1 leads to suppression of TGFBR2 promoter activity and FLI1-induced promoter activity. Introduction of EWSR1-FLI1 into cells lacking the EWSR1-FLI1 fusion suppresses TGF-beta RII expression, whereas antisense to EWSR1-FLI1 in ES cell lines positive for this gene fusion restores TGF-beta RII expression. Furthermore, introduction of normal TGF-beta RII into ES cell lines restores TGF-beta sensitivity and blocks tumorigenicity. Our results implicate TGF-beta RII as a direct target of EWS-FLI1.

The aim of this study was to investigate the effect of interferon-α (IFN-α) on the occurrence of mutations in the precore region of the hepatitis B virus (HBV). We studied 24 patients with chronic hepatitis B; 11 were non-responders to IFN therapy and 13 were untreated patients. After HBV DNA extraction from serum, nested PCR of the precore region and direct sequencing was performed. Among the baseline sera of 24 patients, three types of mutation G to A at nucleotide 1896 (A1896), 1899 (A1899), and A to T at nucleotide 1846(T1846) were found in 12 patients. The prevalence of A1896 was 45.8% (11/24), A1899 8.3% (2/24), and T1846 12.5% (3/24), respectively. A1896 was found in six out of 18 HBeAg-positive patients and in five out of six anti-HBE-positive patients. During the 1 year follow-up period, sequence changes were found in five out of 13 untreated patients: A wild-type strain was replaced by a mutant A1896 strain in two patients; mixed viral populations of wild-type strains and mutant A1896 strains were replaced by a mutant A1896 strain in one patient; and a mutant A1896 strain was replaced by a wild-type strain in two patients. In contrast, ten out of 11 non-responders had no changes in the precore region after therapy during follow-up period. A shift from predominantly wild-type strains to predominantly mutant A1896 strains was found in the remaining one non-responder. In conclusion, sequence changes in the precore region occur frequently during the course of chronic hepatitis B virus infection. IFN-α therapy may decrease the appearance of mutations in the precore region in non-responders.

A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene.

The aim of the present study was to determinethe efficacy of a new combination regimen including anantioxidant, a proton pump inhibitor, and antibioticsagainst Helicobacter pylori and to document the changes of oxidative stress and cytokinesinvolved in H. pylori-associated gastric inflammation.From 57 patients with endoscopically diagnosed gastricand/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimenswere taken for the diagnosis of H. pylori and for theexperimental measures. The patients were then treatedeither with lansoprazole 30 mg + amoxicillin 1.5 g (LAgroup; 21 patients) or lansoprazole 30 mg amoxicillin1.5 g + rebamipide 300 mg (LAM group; 36 patients) fortwo weeks. Four weeks after the initiation of treatment,the patients were endoscoped again and biopsy specimens were obtained. Mucosalmalondialdehyde (MDA) levels; myeloperoxidase (MPO)activities; superoxide dismutase; catalase; glutathioneperoxidase; cytokines IL-1, IL-6, TNF-α; andchemokines IL-8, GRO-α, RANTES (regulated onactivation normal T expressed and secreted) weremeasured. Using paraffin-embedded tissue sections, insitu terminal deoxyribonucleotide transferase (TdT)mediated dUTP nick end labeling (TUNEL) for apoptosisand immunohistochemical staining for inducible nitricoxide synthase (iNOS) were performed. Two weeks oftreatment with the LA regimen resulted in 57.4%eradication rates of H. pylori, whereas two weeks oftreatment with the LAM regimen resulted in 75.0%eradication rates. Eradication rates between these twogroups were statistically significantly different (P< 0.05). Mucosal MDA levels and MPO activities weresignificantly lower in the LAM group than the LA group.Mucosal levels of cytokines IL-1, IL-6, and TNF-αand of chemokines IL-8, GRO-α, and RANTES were all significantly decreased after the treatmentof H. pylori, especially so in the LAM group. Theapoptotic index and iNOS score were significantlyreduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradicationregimen against H. pylori has advantages either inaugmenting the eradication rates of H. pylori or indecreasing the oxidative stress and cytokines levelsgenerated by H. pylori infection.

Background and Aim: The prevalence and incidence of inflammatory bowel disease (IBD) are lower in East Asia than in Western countries; however, marked increases have recently been reported. The clinical diagnosis and medical management of IBD in East Asia differ from those in Western countries. A questionnaire-based survey was performed to gather physicians' current opinions on IBD in different East Asian countries. Methods: Representative International Gastrointestinal Consensus Symposium (IGICS) committee members provided a questionnaire to physicians in each East Asian country studied. The questionnaire mainly focused on the diagnosis and management of IBD. Results: There were 19 respondents from Japan, 10 from South Korea, 9 from the Philippines, 6 from China and 4 from Indonesia. Colonoscopy (100%) and histopathology (63%) were commonly used for the diagnosis in ulcerative colitis (UC). Conventional small bowel enteroclysis was still the most common diagnostic tool for assessing small bowel lesions in Crohn's disease (CD) in East Asia. The percentage of physicians who investigated the reactivation of Cytomegalovirus in severe or refractory patients with UC ranged from 0% in the Philippines and Indonesia to 100% in Japan and Korea. Most physicians in Korea, the Philippines, China and Indonesia chose thiopurines or anti-TNF therapy as the second-line treatment in severe refractory UC, whereas Japanese physicians preferred to use tacrolimus or leukocyte apheresis. Physicians in the Philippines and Indonesia preferred to use oral 5-aminosalicylic acid for newly diagnosed severe ileocecal CD. In contrast, Korean physicians chose oral steroids and most physicians in China and Japan preferred to use anti-TNF. Nutritional therapy to induce or maintain remission in patients with CD was commonly used in Indonesia, Japan and China. Targeted biopsies by conventional colonoscopy were the most preferred strategy for cancer surveillance in long-standing UC over random biopsies in this region. Conclusions: The present survey found that current diagnostic approaches and clinical management of IBD vary within East Asian countries.

Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis (SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected, an early endoscopic retrograde cholangiopancreatography is recommended. However, practice guidelines regarding the treatment of pancreatitis are suboptimal. In chronic pancreatitis, conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation. Recently, attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies. Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis, antioxidants alone or combined with conventional therapy may improve oxidative-stress-induced organ damage. Interest in phytoceuticals stems from their potential use as simple, accurate tools for pancreatitis prognostication that could replace older and more tedious methods. Therefore, the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis. In this review article, recent advances in the understanding of the pathogenesis of pancreatitis are discussed and the paradigm shift underway to develop phytoceuticals and antioxidants to treat it is introduced. Despite the promise of studies evaluating the effects of antioxidants/phytoceuticals in pancreatitis, translation to the clinic has thus far been disappointing. However, it is expected that continued research will provide solid evidence to justify the use of antioxidative phytoceuticals in the treatment of pancreatitis.

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent fromArtemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostaglandin E(2) (PGE(2)) and prostaglandin F(1alpha) (PGF(1alpha)) levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion, of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

Recent advances in genomic medicine have opened up the possibility of tailored medicine that may eventually replace traditional “one-size-fits all” approaches to the treatment of inflammatory bowel disease (IBD). In addition to exploring the interactions between hosts and microbes, referred to as the microbiome, a variety of strategies that can be tailored to an individual in the coming era of personalized medicine in the treatment of IBD are being investigated. These include prompt genomic screening of patients at risk of developing IBD, the utility of molecular discrimination of IBD subtypes among patients diagnosed with IBD, and the discovery of proteome biomarkers to diagnose or predict cancer risks. Host genetic factors influence the etiology of IBD, as do microbial ecosystems in the human bowel, which are not uniform, but instead represent many different microhabitats that can be influenced by diet and might affect processes essential to bowel metabolism. Further advances in basic research regarding intestinal inflammation may reveal new insights into the role of inflammatory mediators, referred to as the inflammasome, and the macromolecular complex of metabolites formed by intestinal bacteria. Collectively, knowledge of the inflammasome and metagenomics will lead to the development of biomarkers for IBD that target specific pathogenic mechanisms involved in the spontaneous progress of IBD. In this review article, our recent results regarding the discovery of potential proteomic biomarkers using a label-free quantification technique are introduced and on-going projects contributing to either the discrimination of IBD subtypes or to the prediction of cancer risks are accompanied by updated information from IBD biomarker research.

See "Diagnostic Yield and Therapeutic Impact of Rectal Retroflexion: A Prospective, Single-Blind Study Conducted in Three Centers" by Felix Tellez-Avila, Josue Barahona-Garrido, Sandra Garcia-Osogobio, et al., on page 79-83 Rectal retroflexion (RR) is performed after initial examination in the forward view to observe the entire rectum at the end of the colonoscopy. The endoscope shaft is positioned with most or all of the bending section just inside the anus, by which the endoscope tip achieves maximum retroflexion by flexing in both an up or down direction and a right or left direction simultaneously. This advantage makes retroflexion a better visualization technique than the traditional forward antegrade viewing, for which RR does not take a long time and does not add any cost. The mean time taken to successfully complete the RR maneuver seems to be approximately 10 to 20 seconds.1 The first study evaluating the utility of RR in rectum examination was by Grobe et al.2 in 1982. It proved to be a useful adjunct to the standard forward view of the rectum in the evaluation of internal hemorrhoids and in the detection of small perirectal polyps, inflammatory bowel disease in the anus or rectum, and anal cancers.2 In detail, RR increases the detection of flat adenomas, including invasive cancer, that can be missed with antegrade viewing.1,3-6 It showed how easily an early-stage cancer in a diminutive colonic polyp can be missed when in difficult areas of straight view.3 However, there stands a controversy that RR has a low yield for adenoma detection, causing the risks to surpass the benefits.7,8 For instance, Quallick and Brown9 reported four cases of rectal perforation in the rectum during RR. Rectal perforation occurs at a rate of 1.02 per 10,000 RR procedures, and even if the perforation rate is relatively low, those who perform RR should always be cautious of these rare, unexpected risks of perforation or anal tearing/bleeding during colonoscopy. The endoscope tip should not be deflected when resistance to tip deflection is apparent or when resistance to advancement and torque is felt. If the rectal lumen is very narrow, RR may not be feasible with every trial. RR should be immediately terminated if any resistance occurs during retroflexion.9 Therefore, RR should be performed on a lumen with a fully inflated state after insufflating sufficient air into the rectal lumen. The utility of RR for the aforementioned dual purpose is controversial because of varying advocated2 or questioned opinions.7 Varadarajulu and Ramsey1 found that RR increased rectal polyp detection rates by 53.2%, affording significant additional information compared with the standard forward view of the rectum, and Saad and Rex8 reported similarly that RR increased rectal polyp detection rates by 17%. In their study, RR increased rectal adenomatous polyp detection rates by 3%.8 Meanwhile, because retroflexion has risks and may cause discomfort, routine retroflexion should be used at the discretion of the endoscopist.8 Cutler and Pop7 reported that RR did not produce additional information, insisting that endoscopists who do not perform RR in their patients should ensure confidence that no pathologies were missed. Taken together, considering that colonoscopy is conventionally used in the diagnosis and removal of premalignant lesions, as well as early colorectal cancer, a recent report10 recommends that RR be frequently used to avoid missing anorectal adenomas and cancers; on the contrary, the most common reason endoscopists do not perform RR is their personal experience that it does not increase adenoma or cancer detection rates. In this issue of Clinical Endoscopy, Tellez-Avila et al.11 conducted a prospective single-blind study in three centers to evaluate the diagnostic yield and therapeutic impact of RR compared with those of either digital rectal exploration or the straight view. They evaluated the therapeutic impact and diagnostic yield of RR during colonoscopy to elucidate whether RR can serve as a bridge over troubled water. RR was successful in 917 of 934 cases (98.2%), and 32 patients (3.4%) had distinct lesions in the anorectal area, of which 10 (1%) were identified only on retroflexion. There were three cases of hyperplastic polyp, three cases of tubular adenoma, one case of tubulovillous adenoma, two cases of angiodysplasia, and one case of flat lesion that benefited from RR. An additional therapeutic benefit was feasible with RR. The authors concluded that RR had little diagnostic yield and therapeutic impact in their cases. In the present study, RR was a bridge over troubled water because its application was associated with low rates of major complications while detecting lesions that might not have been seen by straight viewing. In conclusion, we recommend performing RR after straight view examination of the anorectal area and suggest the additional feasibility of the therapeutic approach. With further advancement of endoscopic instrumentation, the possibility of perforation can be further evaluated. However, endoscopists should be alert that there might be a possibility of a booby trap even looking easy.

Epithelial-mesenchymal transition (EMT) is an important factor in cancer invasiveness and metastatic progression. During EMT, cancer cells acquire stem cell properties. The role of EMT and stemness in colon cancer has not been fully understood. We aimed to demonstrate the clinical significance of EMT and the stem cell phenotype in colorectal cancer. Two hundred and thirty-one surgically resected colon cancer cases were included in the present study. mRNAs of E-cadherin, TWIST1 and SNAI1 were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) (n=109). Immunohistochemical staining was performed for six markers (ALDH1, TGF-β1, E-cadherin, β-catenin, TWSIT1 and SNAI1) (n=231). We assessed clinicopathological characteristics according to the expression of the stem cell phenotype and EMT markers. Based on the results of qRT-PCR, TWIST1 and SNAI1 significantly influenced node metastasis (P=0.04 and P=0.02, respectively). High TWIST1 and SNAI1 mRNA expression was associated with poor overall survival according to the univariate analysis (P

Imaging mass spectrometry (IMS) is currently receiving large attention from the mass spectrometric community, although its use is not yet well known in the clinic. As matrix-assisted laser desorption/ionization time-of-flight (MALDI)-IMS can show the biomolecular changes in cells as well as tissues, it can be an ideal tool for biomedical diagnostics as well as the molecular diagnosis of clinical specimens, especially aimed at the prompt detection of premalignant lesions much earlier before overt mass formation, or for obtaining histologic clues from endoscopic biopsy. Besides its use for pathologic diagnosis, MALDI-IMS is also a powerful tool for the detection and localization of drugs, proteins, and lipids in tissue. Measurement of parameters that define and control the implications, challenges, and opportunities associated with the application of IMS to biomedical tissue studies might be feasible through a deep understanding of mass spectrometry. In this focused review series, new insights into the molecular processes relevant to IMS as well as other field applications are introduced.

Though long-term administration of proton pump inhibitor (PPI) imposed the risk of gastrointestinal track tumorigenesis by accompanied hypergastrinemia, no overt increases of colon cancer risk were witnessed after a long-term cohort study. Our recent investigation revealed that PPI prevented colitis-associated carcinogenesis through anti-inflammatory, anti-oxidative, and anti-mutagenic mechanisms in spite of hypergastrinemia. Therefore, we hypothesized that PPI might either antagonize the trophic action of gastrin on gastrointestinal tumorigenesis or synergize to exert augmented anti-tumorigenic actions. We challenged APCMin/+ mice with gastrin, PPI, PPI and gastrin together for 10 weeks and counted intestinal polyposis accompanied with molecular changes. Gastrin significantly increased intestinal polyposis, but combination of PPI and gastrin markedly attenuated intestinal polyposis compared to gastrin-promoted APCMin/+ mice (P < .001), in which significant β-catenin phosphorylation and inhibition of β-catenin nuclear translocation were observed with PPI alone or combination of PPI and gastrin, whereas gastrin treatment significantly increased β-catenin nuclear translocation. Significant footprints of apoptosis, G0/G1 accumulation, inactivation of p38 and extracellular signal-regulated kinase, decreased expressions of CD31, and inhibition of tumor necrosis factor-α and cyclooxygenase-2 were noted in the combination group. In vitro investigations were similar to in vivo findings as shown that PPI treatment inhibited the binding of gastrin to its receptor, inactivated β-catenin-associated signaling including Tcf/Lef and glycogen synthase kinase β, and paradoxically inhibited β-catenin-associated proliferative activities. Our investigations explain why colon cancer risk has not increased despite long-term use of PPIs and provide a rationale for using PPI to achieve anti-tumorigenesis beyond acid suppression.

Although the International Agency for Research on Cancer declared Helicobacter pylori (H. pylori) as a definite human carcinogen in 1994, the Japanese Society for Helicobacter Research only recently (February 2013) adopted the position that H. pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality. Japanese researchers have found that H. pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer. However, those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer. Because chronic perpetuated progression of H. pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis, a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity. This non-microbial approach might represent a new form of prerequisite “rescue” therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication.

This special May issue of Clinical Endoscopy discusses the tutorial contents dealing with either the diagnostic or therapeutic gastrointestinal (GI) endoscopy that contain very fundamental and essential points in this filed. The seminar of Korean Society of Gastrointestinal Endoscopy (KSGE) had positioned as one of prime educational seminars covering the very beginner to advanced experts of GI endoscopy. Besides of four rooms allocated for each lecture, two additional rooms were open for either live demonstration or hands-on course, covering totally 20 sessions including one special lecture. Among these prestigious lectures, 12 lectures were selected for the current review articles in this special issue of Clinical Endoscopy journal. Basic course for beginner to advanced tips to expert were all covered in this seminar. This introductory review prepared by four associated editors of Clinical Endoscopy contained core contents divided into four sessions-upper gut, lower gut, pancreaticobiliary, and specialized topic session part-to enhance understandings not covered by enlisted review articles in this issue.