Jae J. Kim

Is Metabolic Syndrome A Risk Factor for Colorectal Adenoma

Background and Aims: Epidemiologic studies provide evidence for a link between obesity or diabetes and the risk for colorectal cancer. However, there is a lack of information about the relationship between metabolic syndrome and colorectal adenoma. Therefore, we investigated whether metabolic syndrome is a risk factor for colorectal adenoma. Methods: We did a study for consecutive subjects who underwent colonoscopy as a screening exam at the Center for Health Promotion, Samsung Medical Center, from March 2004 to December 2005. According to the modified ATP III criteria, metabolic syndrome was diagnosed. We classified a total of 2,531 subjects into the adenoma group (n = 731) and the control group (n = 1,800), including normal colonoscopic finding, nonpolyp benign lesions, or histologically confirmed hyperplastic polyp. Results: The prevalence for metabolic syndrome was 17% in the adenoma group and 11% in the control group. On the multiple logistic regression analyses, metabolic syndrome was found to be associated with an increased risk of colorectal adenoma (odds ratio, 1.51; 95% confidence interval, 1.18-1.93). Also, waist circumference among the individual components of metabolic syndrome was an independent risk factor for colorectal adenoma. An increased risk for metabolic syndrome was more evident for proximal than distal colon, for multiple (≥3), and for advanced adenoma in the adenoma group. Conclusion: Metabolic syndrome was associated with colorectal adenoma. Abdominal obesity of the individual components of metabolic syndrome was an important risk factor for colorectal adenoma. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1543–6)

Microsatellite Instability in Gastric Intestinal Metaplasia in Patients with and without Gastric Cancer

The role and significance of microsatellite instability (MSI) in gastric carcinogenesis remain unknown. This study determined the chronology of MSI in gastric carcinogenesis by examining intestinal metaplasia (IM) from patients with and without gastric cancer. DNA was obtained from gastric specimens of 75 patients with gastric IM (30 cancer, 26 peptic ulcer, and 19 chronic gastritis patients) and was amplified with a set of eight microsatellite markers. Eight (26. 7%) tumors and seven (9.3%) IM samples (three from cancer-free patients) displayed high-level MSI (three or more loci altered). Low-level MSI (one or two loci altered) was detected in 50% of the tumors, in 40% of IM samples coexisting with cancer, and in 38% of IM tissues of cancer-free individuals. Among the 30 cancer patients, microsatellites were more frequently altered in IM coexisting with tumors that showed MSI (P = 0.003). In addition, patients with low-level MSI in the tumor tissues were more likely to have active Helicobacter pylori infection than those with stable tumors (P = 0.02). In conclusion, this study indicates that MSI occurs not only in gastric IM of patients with gastric carcinoma, but also in IM of cancer-free individuals. These data suggest that the progressive accumulation of MSI in areas of IM may contribute to gastric cancer development, representing an important molecular event in the multistep gastric carcinogenesis cascade.

Epigenomic Analysis of Aberrantly Methylated Genes in Colorectal Cancer Identifies Genes Commonly Affected by Epigenetic Alterations

BackgroundDetermination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC.Materials and MethodsWe analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa with bead-chip array-based technology.ResultsWe identified 621 CpG sites located in promoter regions and CpG islands that were greatly hypermethylated in CRC compared to normal mucosa. The genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. Compared to the genome-wide expression array, mRNA expression was more likely to be downregulated in the genes demonstrating promoter hypermethylation, even though this was not statistically significant. We validated ten CpG sites that were hypermethylated (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylation (MAEL, SFT2D3) in CRC compared to the normal mucosa in the array studies using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data.ConclusionsMethylation profiling based on bead-chip arrays is an effective method for screening aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.

Regional Differences in Metronidazole Resistance and Increasing Clarithromycin Resistance among Helicobacter pylori Isolates from Japan

ABSTRACT The patterns of antibiotic resistance in Helicobacter pylori were assessed in two different regions in Japan. Overall, prevalences of resistance to metronidazole and clarithromycin were 12.4 and 12.9%, respectively. While there was no difference in clarithromycin resistance, the prevalence of metronidazole resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From 1996 to 1999, the prevalence of metronidazole resistance did not change but the prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%).

Efficacy and tolerability of split-dose magnesium citrate: low-volume (2 liters) polyethylene glycol vs. single- or split-dose polyethylene glycol bowel preparation for morning colonoscopy.

OBJECTIVES:Preparation regimens for morning colonoscopy are suboptimal. The aim of this study was to test the efficacy and tolerance of a split-dose magnesium citrate–low-volume (2 liters) polyethylene glycol (PEG) regimen for morning colonoscopy.METHODS:A total of 232 patients were randomly assigned to receive 4 liters PEG (day before procedure; group 1, n=79), 2 liters PEG (day before procedure) followed by another 2 liters PEG (day of procedure; group 2, n=80), or magnesium citrate (250 ml, day before procedure) followed by 2 liters PEG (day of procedure; group 3, n=73). The quality of bowel cleansing, tolerability, and adverse effects in group 3 were compared with those in groups 1 and 2.RESULTS:Satisfactory bowel preparation was more frequently reported for group 3 than for group 1 (75% vs. 51%, P=0.001) and was similar to that for group 2 (75% vs. 76%, P=0.896). A significantly greater proportion of patients in group 3 graded their overall satisfaction as satisfactory compared with group 1 (43% vs. 23%, P=0.010), and the proportion was similar to that in group 2 (43% vs. 35%, P=0.133). Patients in group 3 were more willing to repeat the same preparation regimen, if necessary, than those in group 1 (93% vs. 48%, P<0.001) or group 2 (93% vs. 62%, P<0.001).CONCLUSIONS:The split-dose magnesium citrate–low-volume (2 liters) PEG regimen was more efficient than and preferred to the conventional regimen of 4 liters of PEG, and it was equally efficient as, but, again, preferred to the split-dose (2+2 liters) regimen for morning colonoscopy.

Comparison of 7-day and 14-day proton pump inhibitor-containing triple therapy for Helicobacter pylori eradication: Neither treatment duration provides acceptable eradication rate in Korea

Background and Aims:  Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first‐line anti‐Helicobacter pylori treatment, there are still debates on the ideal duration of treatment. The aim of this study was to compare the efficacies of 7‐day and 14‐day PPI‐containing triple therapy.

Mixed-infection of antibiotic susceptible and resistant Helicobacter pylori isolates in a single patient and underestimation of antimicrobial susceptibility testing

Antibiotic resistance among Helicobacter pylori has been increasing worldwide and has begun to affect the overall efficacy of current antibiotic regimens adversely. We examined 220 pairs of H. pylori isolates obtained from both the antrum and corpus of separate patients; 109 (50%) harbored antibiotic‐resistant H. pylori: amoxicillin (0.5%), clarithromycin (5.9%), furazolidone (1.4%), metronidazole (45.5%), nitrofurantoin (1.4%), and tetracycline (6.8%). Heteroresistance among the two biopsy sites from each patient was present in 41 of the 109 patients (38%) with antibiotic resistant H. pylori (e.g. 34% with resistant strains would be misclassified as susceptible if a biopsy of the antrum alone used for antimicrobial susceptibility testing). DNA fingerprinting genotype analysis was carried out on the 41 pairs of isolates with heteroresistance. While different patients had different fingerprinting patterns, each pair of isolates showed identical or similar fingerprinting patterns. These results suggest that antibiotic‐resistant H. pylori typically develop from pre‐existing susceptible strain rather than coinfection with a different strain. The minor differences in genotype (degeneration of genotype) seen reflect one of the processes for development of genetic diversity in H. pylori. No biopsy single site can be considered representative for antimicrobial susceptibility testing.

CpG methylation and reduced expression of O6-methylguanine DNA methyltransferase is associated with Helicobacter pylori infection.

BACKGROUND & AIMS The gastric epithelium genome undergoes extensive epigenetic alterations during Helicobacter pylori-induced gastritis. Expression of the gene encoding the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) might be reduced via hypermethylation of its promoter in patients with H pylori gastritis. We characterized expression of MGMT and its epigenetic regulation via CpG methylation in gastric tissue from patients with H pylori gastritis and investigated the effects of H pylori infection eradication on MGMT expression. METHODS Gastric biopsy samples were collected from patients with H pylori gastritis before and after eradication and from H pylori-negative control subjects. AGS cells were cocultured with H pylori to study the effects of H pylori infection on MGMT RNA, protein expression, and CpG methylation. RESULTS CpG methylation of MGMT was more frequent in the gastric mucosa of patients with H pylori gastritis (69.7%) than in those without (28.6%, P = .022). MGMT methylation was significantly reduced after H pylori eradication (from 70% to 48% of cases, P = .039), and mean levels of CpG methylation decreased from 12.6% to 5.7% (P = .025), increasing MGMT expression. MGMT methylation was significantly associated with CagA-positive H pylori (P = .035). H pylori reduced MGMT protein and RNA levels and induced MGMT CpG methylation in gastric AGS cells. CONCLUSIONS H pylori gastritis, particularly in patients infected with H pylori CagA-positive strains, is associated with hypermethylation of MGMT and reduced levels of MGMT in the gastric epithelium. MGMT promoter methylation is partially reversible after eradication of H pylori infection. These data indicate that DNA repair is disrupted during H pylori gastritis, increasing mutagenesis in H pylori-infected gastric mucosa.

Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: A randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVES:Esophageal hypersensitivity is currently believed to have a crucial role in the pathogenesis of functional chest pain (FCP). The aim of this study was to evaluate the clinical efficacy of venlafaxine, a serotonin–norepinephrine reuptake inhibitor (SNRI), for FCP in young adult patients.METHODS:Patients diagnosed with FCP were randomized to either an extended-release formulation of venlafaxine (75 mg hora somni) or a placebo for 4 weeks. After a washout period of 2 weeks, patients crossed over to the other arm of the study. The primary efficacy variable was the number of patients with >50% improvement in symptom scores. The secondary efficacy variables were (i) the symptom intensity score during each week, (ii) quality of life (QOL), (iii) the Beck Depression Inventory (BDI) score, and (iv) side effects.RESULTS:A total of 43 patients (37 men, mean age 23.5±1.9 years) completed the study. A positive response was observed in 52.0% of patients during venlafaxine treatment; 4.0% had a positive response with placebo treatment as assessed by the intention-to-treat analysis (venlafaxine vs. placebo: odds ratio 26.0; 95% confidence interval 5.7–118.8; P<0.001). Results of Short-Form 36 (SF-36) indicated that patients who received venlafaxine treatment had a significantly greater improvement in body pain and emotional role compared with those who received placebo treatment (P=0.002 and P=0.002, respectively). No significant change was noted in the depression score after venalafaxine or placebo treatment. One patient withdrew from the study because of sleep disturbance and loss of appetite while receiving venlafaxine.CONCLUSIONS:Venlafaxine, an SNRI antidepressant, significantly improved symptoms in young adult patients with FCP.

Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole.

BACKGROUND Although EMR-induced ulcers heal faster and recur less often than noniatrogenic gastric ulcers, there is no consensus regarding the duration of therapy for these ulcers. This study prospectively evaluated healing of EMR-induced ulcers according to the duration of omeprazole therapy. METHODS A total of 69 patients were randomly assigned, after EMR, to treatment with omeprazole (20 mg per day) for 7 days (1-week group) or with omeprazole (20 mg per day) for 28 days (4-week group). Four weeks after EMR, ulcer size and stage were compared with those of the initial EMR-induced ulcer. Each patient kept a daily diary of drugs consumed and ulcer-related symptoms during the 4-week period after EMR. RESULTS Thirty-four patients were randomized to the 4-week group, and 26 were randomized to the 1-week group. No significant differences were observed between the two groups at 4 weeks after EMR in terms of ulcer reduction ratio (p=0.29) or stage (p=0.11). In addition, no difference was observed between the two groups with respect to ulcer-related symptoms or use of additional gastric-coating medication (p=0.48). CONCLUSIONS For EMR-induced ulcer, treatment with omeprazole for 1 week is equivalent to treatment for 4 weeks. Short-term therapy with omeprazole can be considered for EMR-induced ulcer.