Hiun-Suk Chae

Expression of Viral MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma

ABSTRACT Epstein-Barr virus (EBV) is associated with about 6 to 16% of gastric carcinoma cases worldwide. Expression of the EBV microRNAs (miRNAs) was observed in B cells and nasopharyngeal carcinoma cells infected with EBV. However, it is not clear if the EBV miRNAs are expressed in EBV-associated gastric carcinomas (EBVaGCs). We found that BART miRNAs but not BHRF1 miRNAs were expressed in EBV-infected gastric carcinoma cell lines and the tumor tissues from patients as well as the animal model. The expression of viral miRNAs in EBVaGCs suggests that these EBV miRNAs may play important roles in the tumorigenesis of EBVaGCs.

LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells

BackgroundAs EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A) in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY), a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719.MethodsAfter single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT.ResultsWhen 5-FU was sequentially combined with LY, the combination index (CI) value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NFκB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NFκB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (%) increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone.ConclusionThese data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance of 5-FU via downregulation of activated p-AKT and mitochondria-dependent apoptosis in EBV gastric cancer cell line, SNU-719.

Diagnostic Yield of Tissue Sampling Using a Bite-On-Bite Technique for Incidental Subepithelial Lesions

Background/Aims Techniques for endoscopic evaluation of gastrointestinal subepithelial lesions include conventional endoscopy, jumbo biopsy, endoscopic ultrasonogrphy (EUS), EUS-guided fine needle aspiration, and endoscopic submucosal resection. However, these procedures have many limitations, such as low diagnostic yields and high complication rates. We therefore evaluated the diagnostic yield for tissue sampling of incidental subepithelial lesions using the bite-on-bite technique. Methods One hundred and forty subepithelial lesions were found in 129 patients during conventional diagnostic esophagogastroduodenoscopy by one examiner from October 2003 to November 2004. Bite-on-bite biopsies with conventional-sized forceps were taken from 36 patients having 37 lesions that did not appear to be hypervascular or to have a thick overlying epithelium. Two to eight bites were performed to obtain submucosal tissue for one lesion. Results The bite-on-bite technique was diagnostic in 14 of the 37 lesions (38%). Blood oozing for more than 30 seconds occurred in five cases, but was easily controlled by epinephrine injection (2 cases) or hemoclip (3 cases). The diagnostic yield tended to be higher in the esophagus than in the stomach and duodenum (54% vs. 28%, p=0.109). Conclusions The bite-on-bite technique for subepithelial lesions is an effective and safe method in selected cases. This technique may be useful for incidental subepithelial lesions, especially those of the esophagus, except for ones with a high risk of bleeding or thick overlying epithelium.

Usefulness of the Bedside Index for severity in acute pancreatitis in the early prediction of severity and mortality in acute pancreatitis.

Objectives The aim of this study was to evaluate the usefulness of the Bedside Index for Severity in Acute Pancreatitis (BISAP) in the early prediction of severity and mortality in AP. Methods The medical records of all patients with acute pancreatitis (AP) admitted to our institution between January 2008 and July 2010 were reviewed retrospectively. Severe AP was defined as the persistence of organ failure for more than 48 hours. The capacity of the BISAP score to predict severity and death was evaluated using linear-by-linear association. The predictive accuracy of the BISAP and Ranson score was measured as the area under the receiver operating characteristic curve (AUC). Results Of 299 consecutive patients, 22 (7.4%) were classified as having severe AP, and 8 (2.7%) died. There were statistically significant trends for increasing severity (P < 0.001) and mortality (P < 0.001) with increasing BISAP. The AUC for severity predicted by BISAP was 0.762 (95% confidence interval, 0.631–0.893) and by Ranson score was 0.804 (0.717–0.892). The AUC for mortality predicted by BISAP was 0.940 (0.863–1.018) and by Ranson score was 0.861 (0.734–0.988). Conclusions We confirmed that BISAP is an accurate means of risk stratification in AP within 24 hours of presentation.

Clinical trial: Inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects

Background and Aim:  Revaprazan is a novel acid pump antagonist. The aim of this study was to investigate the inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects.

Acute Appendicitis Caused by Colonoscopy

A 48-year-old woman who was without any abnormal past medical history underwent colonoscopy as a screening procedure for colorectal disease. The procedure was uneventful and there was no sign of inflammation around the appendicular orifice or the luminal surface of the cecum. The patient did not complain of pain or significant discomfort throughout the procedure. She then developed pain in the right lower quadrant of the abdomen that evening and this persisted for four days. She visited the outpatient department and underwent abdominal ultrasonography, which showed a swollen appendix with a collection of pericecal fluid. Surgical exploration and appendectomy were performed; the final diagnosis was acute suppurative appendicitis. Colonoscopists should be aware of this rare complication and consider it when making the differential diagnosis of post-colonoscopy abdominal pain.

Hemoclip placement through a forward-viewing endoscope for a Dieulafoy-like lesion in a duodenal diverticulum

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Intestinal Helminthic Infections Diagnosed by Colonoscopy in a Regional Hospital during 2001-2008

The present study investigated characteristics of 24 parasite infection cases detected during colonoscopy in a regional hospital from January 2001 to December 2008. Sixteen patients were confirmed with Trichuris trichiura infection, 6 patients were with Ascaris lumbricoides infection, 1 patient with Enterobius vermicularis infection, and 1 patient with Anisakis infection. Among them, 7 patients (43.8%) were asymptomatic. Colonoscopy findings were normal in 18 patients (75.0%). Among the patients with T. trichiura infection, colonoscopy showed several erosions in 2 patients (8.3%) and non-specific inflammation of the affected segment of the colon in 3 patients (12.5%). In 1 patient with anisakiasis, colonoscopy revealed a markedly swollen colonic wall. Stool examinations were performed before treatment in 7 patients (29.2%) and were all negative for parasite eggs or worms. These results suggest that colonoscopy is a useful diagnostic approach for parasitic infections even for asymptomatic patients and for patients with negative stool examinations.

Antimigration property of a newly designed covered metal stent for esophageal stricture: an in vivo animal study.

BACKGROUND Covered self-expandable metal stents (SEMSs) are associated with a higher migration rate than uncovered SEMSs. OBJECTIVE The antimigration property of a novel covered SEMS was investigated in a canine esophageal stricture model. DESIGN The new stent (80 mm in length, 20 or 24 mm in diameter) has multiple protuberances on its body that were designed to be separated from the inner silicone membrane so that they could be embedded into the mucosa after deployment. Twenty-two beagle dogs were subjected to circumferential EMR in the middle esophagus for stricture formation. After 2 weeks, conventional covered stents were inserted in a control group (n = 11), and the newly designed covered SEMSs were inserted in a study group (n = 11). SETTING Animal laboratory. INTERVENTIONS Circumferential EMR of the middle esophagus for stricture formation, followed by endoscopic placement of a conventional or newly designed stent. MAIN OUTCOME MEASUREMENTS Migration, complications, survival, and esophageal histopathology. RESULTS There was no significant difference in the diameter of the esophageal stricture between the control and study groups (10 mm vs 11 mm, P = .52). Within 3 days, all stents in the control group had migrated, whereas 6 had migrated in the study group (100% vs 55%, P = .035). There were no significant complications directly associated with stent insertion. LIMITATIONS Complications, survival, and esophageal histopathology could not be compared because all of the conventional stents migrated in the control group within 3 days. CONCLUSIONS The newly designed covered SEMS is more resistant to migration than the conventional covered SEMS.

Comparison of the 13C-urea breath test and the endoscopic phenol red mucosal pH test in the quantification of Helicobacter pylori infection loading.

Background/Aims The 13C-urea breath test (UBT) is a semiquantitative test for measuring Helicobacter pylori infection loading. H. pylori produces ammonia, which elevates the pH of the gastric mucosa and is detectable via endoscopy using a phenol red indicator. We evaluated whether this test could be used to diagnose H. pylori infection and whether phenol red staining was correlated with 13C-UBT results. Methods One hundred and twenty-three patients participated. The UBT was performed after ingestion of a capsule containing urea. A change in 13C-UBT >2‰ was selected as the cutoff value for diagnosing infection. After spraying evenly with a 0.1% phenol red solution, the pH of the gastric mucosal surface was measured using an antimony electrode through the biopsy channel. Results The pH of stained mucosa (6.9±0.4) was significantly higher than that of unstained mucosa (1.9±0.8; p<0.001), and the H. pylori detection rate confirmed via histology was higher in stained versus unstained mucosa (p<0.01). Extensive mucosal staining resulted in a higher detection rate (p<0.001). The UBT produced results were very similar to those obtained via histological detection in stained mucosa (p<0.001). The extent of staining, expressed as a staining score, was positively correlated with the change in 13C-UBT (r=0.426, p<0.001). A significant correlation was also observed between the histologically determined H. pylori density and 13C-UBT results (r=0.674, p<0.001). Conclusions H. pylori infection elevates gastric mucosal surface pH, and endoscopic phenol red staining may be an alternative method for the diagnosis of H. pylori infection.