In-Sik Chung

Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric Cancer

ABSTRACT Helicobacter pylori causes diseases ranging from gastritis to peptic ulcer disease to gastric cancer. Geographically, areas with high incidences of H. pylori infection often overlap with areas with high incidences of gastric cancer, which remains one of the leading causes of cancer-related deaths worldwide. Strains of H. pylori that carry the virulence factor cytotoxin-associated gene A (cagA) are much more likely to be associated with the development of gastric cancer. Moreover, particular C-terminal polymorphisms in CagA vary by geography and have been suggested to influence disease development. We conducted a large-scale molecular epidemiologic analysis of South Korean strains and herein report a statistical link between the East Asian CagA EPIYA-ABD genotype and the development of gastric cancer. Characterization of a subset of the Korean isolates showed that all strains from cancer patients expressed and delivered phosphorylatable CagA to host cells, whereas the presence of the cagA gene did not strictly correlate to expression and delivery of CagA in all noncancer strains.

Anxiety, depression and quality of life in patients with irritable bowel syndrome.

BACKGROUND/AIMS There have been few Asian studies regarding anxiety and depression associated with irritable bowel syndrome (IBS). The aim of this study was to evaluate the frequency and importance of anxiety and depression in Korean patients with IBS. METHODS A total of 124 IBS patients and 91 healthy subjects were enrolled consecutively. All participants were asked to complete self-administered questionnaires: one addressing symptom severity, the Short Form 36, and the Hospital Anxiety and Depression Scale (HADS). The patients were also asked to complete the IBS-specifi c quality of life (IBS-QOL) questionnaire. RESULTS Anxiety and depression were observed in 38.6% and 38.6% of IBS patients, respectively, and in 24.2% and 16.5% of healthy subjects, respectively (p<0.05 for both). The mean HADS scores for anxiety and depression in IBS patients were 6.8±4.5 and 7.1±4.4, respectively. Both anxiety and depression were associated with self-reported symptom severity (p<0.012 and p<0.001, respectively). As determined by multivariate analysis, symptom severity was the most important factor in the prediction of anxiety and depression. Self-reported symptom severity and depression were clearly and independently associated with the overall IBS-QOL score. CONCLUSIONS Anxiety and depression were frequently observed in Korean IBS patients and were related to the severity of their symptoms and the impairment of the patients QOL. Our data suggest that assessing anxiety and depression is important when evaluating IBS patients.

Triterpenoids from the Flower of Campsis grandiflora K. Schum. as Human Acyl-CoA: Cholesterol Acyltransferase Inhibitors

The flower of Campsis grandiflora K. Schum. was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H2O. From the EtOAc fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico-chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3β-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3β-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3β-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2α,3β-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2α,3β-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3β,23-dihydroxyurs-12-en-28-oic acid (23-hydroxyursolic acid, 6) and 2α,3β,23-thhydroxyolean-12-en-28-oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2±1.1, 46.7±0.9, 41.5±1.3 and 60.8±1.1% at the concentration of 100 μg/mL, respectively.

Polyps in the gastrointestinal tract: discrepancy between endoscopic forceps biopsies and resected specimens

Background and Aim An endoscopic forceps biopsy (EFB) carries the risk of missing the neoplastic foci within a polyp as only a small portion of the lesion is sampled using this technique. Accordingly, the histological examination of specimens obtained by an EFB is of limited accuracy and patient management based on the histological findings is controversial. The aim of this prospective study was to determine the diagnostic concordance between an EFB and resected tissues of gastric and colon polyps. Methods Between January 2006 and October 2007, 1312 gastrointestinal polyps from 896 patients were resected in our hospital. Patients with polyps of epithelial origin of at least 8 mm in diameter and not associated with polyposis syndromes were included in the study. Polyps of nonepithelial origin were excluded. One thousand two hundred and sixty-four polyps of epithelial origin [gastric polyps (n=268) and colon polyps (n=996)] obtained from 813 patients met the inclusion criteria. All patients underwent an EFB and resection of the polyp by endoscopic mucosal resection and endoscopic submucosal dissection. Results Multiple polyps existed in 31.6% of the patients. The pathological diagnoses of resected gastric polyps were as follows: adenomas with low-grade dysplasia, 46 (17.2%); adenomas with high-grade dysplasia, 42 (15.7%); hyperplastic polyps, 126 (47.0%); chronic inflammatory polyps, 29 (10.8%); and adenocarcinomas, 25 (9.3%). The discrepancy rate between an EFB and the pathology of the resected gastric polyps was 39.2% (the Kendalls tau-b and the κ coefficient for agreement between the EFB and resected specimens of gastric polyps were 0.577 and 0.472, respectively; P value <0.001). No relationship between the size of the gastric polyp and the concordance rate was observed. The pathological diagnoses of the resected colon polyps were as follows: adenomas with low-grade dysplasia, 559 (56.1%); adenomas with high-grade dysplasia, 229 (23.0%); hyperplastic polyps, 44 (4.4%); adenocarcinomas, 53 (5.3%); and inflammatory polyps, 111 (11.1%). The discrepancy rate between the EFB and the pathology of the resected colon polyps was 39.8%. (the Kendalls tau-b and the κ coefficient for agreement between the EFB and the resected specimens of the colon polyps were 0.479 and 0.293, respectively; P value <0.001). No relationship between the size of the colon polyp and the concordance rate was observed. Conclusion Considerable discrepancies were observed in histological findings between the EFB and the resected specimens. Therefore, complete removal of the entire polyp is recommended to confirm the diagnosis, to remove precancerous lesions, and to develop an optimal management plan.

Lignans from the fruits of cornus kousa burg. and their cytotoxic effects on human cancer cell lines

The fruits of Cornus kousa Burg. were extracted with 80% aqueous MeOH, and the concentrated extract partitioned with EtOAc, n-BuOH and H2O. Six lignans were isolated from the EtOAc fraction through repeated silica gel, ODS and Sephadex LH-20 column chromatographies. From the physico-chemical data, including NMR, MS and IR, the chemical structures of the compounds were determined to be (+)-pinoresinol (1), (-)-balanophonin (2), (+)-laricresinol (3), erythro-guaiacylglycerol-β-coniferyl aldehyde ether (4), threo-guaiacylglycerol-β-coniferyl aldehyde ether (5) and dihydrodehydrodiconiferyl alcohol (6), which were isolated for the first time from this plant. Most of these compounds showed cytotoxicity against human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HepG2) cell lines in vitro, with IC50 values ranging from 19.1 to 71.3 μg/mL.

Improved menthol production from chitosan-elicited suspension culture of Mentha piperita

The optimum concentration of chitosan to menthol production by Mentha piperita cells cultured in shake flasks was 200 mg/l, which gave 166 mg menthol/l after 12 days. Chitosan elicitation may activate the conversion of pulegone to menthol.

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.

Cannabinoid Receptor 1 Gene Polymorphism and Irritable Bowel Syndrome in the Korean Population: A Hypothesis-generating Study

Objective The cannabinoids affect gastrointestinal function and are thought to be involved in the pathogenesis of irritable bowel syndrome (IBS). We hypothesized that genetic variants of the cannabinoid receptor 1 gene (CNR1) might be associated with IBS. Methods One hundred sixty-two IBS patients, who met the Rome II criteria, and 423 healthy controls were subjected to genotyping of polymorphic triplet AAT repeats located in the 3-flanking region of the CNR1 gene. Results Allele frequencies of AAT triplet repeats in the CNR1 gene differed markedly between the controls and IBS patients (P<0.01). Controls had a lower frequency of distribution of 10 alleles or more. We divided the alleles into 2 groups (⩽10 and >10), and 3 genotypes ⩽10/⩽10, heterozygote, and >10/>10. The CNR1 having>10/>10 AAT triplet repeats occurred with greater frequency in IBS patients than in the controls (P<0.01). A strong genotype association was observed between the CNR1 >10/>10 genotype and all IBS subtypes compared with controls (P<0.01 for each). The allele frequencies and the CNR1 genotypes did not differ between the 3 IBS subtypes. Symptom scores for abdominal discomfort or pain were higher in patients with the CNR1 >10/>10 genotype than in patients with the other genotypes (P<0.05). Conclusions We found a different distribution of allelic frequency of AAT repeats in the CNR1 gene in healthy controls and IBS patients, and a significant association between the CNR1 >10/>10 genotype and IBS. These results suggest that the CNR1 gene is a potential candidate gene involved in IBS in Korea.

The Prevalence of Gastrointestinal Symptoms in Patients with Non-Insulin Dependent Diabetes Mellitus

Background/Aims Gastrointestinal (GI) symptoms are common among patients with non-insulin dependent diabetes mellitus (NIDDM). Our aim was to investigate the frequency of chronic GI symptoms in Korean patients with NIDDM. Methods A cross-sectional survey, using a reliable and valid questionnaire, was performed in diabetes clinics from seven hospitals of the Catholic University of Korea. Results A total of 608 patients (249 males and 359 females, mean age 53.7±10.9 years) were investigated. The frequencies of weekly heartburn and acid regurgitation (esophageal symptoms) were 7.1% (95% confidence interval [CI], 5.0 to 9.2) and 4.4% (95% CI, 2.8 to 6.1), respectively. The frequency of dyspepsia was 13.2% (95% CI, 10.5 to 15.8). The frequencies of constipation and diarrhea were 15.0% (95% CI, 12.2 to 18.0) and 5.3% (95% CI, 3.5 to 7.1), respectively. Nausea and the use of manual maneuvers to facilitate defecation were more prevalent in women than in men. Constipation and fecal incontinence were more common in diabetes patients with long duration (>10 years). Fecal incontinence and using laxatives were more frequent in the complicated diabetes group. Using laxatives was more frequent in the uncontrolled diabetes group. Conclusions Two-thirds of diabetic patients experienced GI symptoms. The prevalence of GI symptoms was more common in patients who had diabetic complications and a long duration of diabetes.

Is it reasonable to treat early gastric cancer with signet ring cell histology by endoscopic resection? Analysis of factors related to lymph-node metastasis.

Background/aim Early gastric cancer (EGC) with signet ring cell histology has a more favorable prognosis than other undifferentiated gastric adenocarcinomas. The presence of lymph-node metastasis is the most important factor in treating EGC by endoscopic resection. The aim of this study was to identify the factors predicting successful endoscopic treatment of EGC with signet ring cell histology. Methods Data from 215 patients who had undergone gastrectomy with D2 lymph-node dissection for EGC with signet ring cell histology between January 1999 and December 2007 were retrospectively reviewed. Associations between various clinicopathological factors and the presence of lymph-node metastasis were analyzed to identify factors predictive of lymph-node metastasis. Results The overall incidence of lymph-node metastasis was 7.9%: 1.9% with intramucosal cancer and 6% with submucosal cancer. Univariate analysis identified the depth of tumor invasion to the submucosa and positive lymphatic–vascular involvement as associated with lymph-node metastasis (both P<0.01). On multivariate analysis, positive lymphatic–vascular involvement was the most significant factor related to lymph-node metastasis (odds ratio: 43.7; 95% confidence interval: 8.7–220.9), followed by the depth of invasion (odds ratio: 4.87; 95% confidence interval: 1.02–23.21). Patients with EGC with signet ring cell histology and a diameter of less than 25 mm, invasion within the sm2 layer, and no lymphatic–vascular involvement had no lymph-node metastasis. Conclusion EGC with signet ring cell histology can be treated by endoscopic mucosal resection, if it is smaller than 25 mm, limited within the sm2 layer, and does not involve the lymphatic–vascular structure. More extensive prospective data are required to confirm definitive guidelines for the endoscopic treatment of patients with EGC with signet ring cell histology.