Hee Jung Son

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)

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.

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.

Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density.

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 ± 54.2) than those of the negative maspin expression groups (256.1 ± 75.4, P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvesel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.

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.

Increased risk of peristomal wound infection after percutaneous endoscopic gastrostomy in patients with diabetes mellitus.

BACKGROUND Results of prospective studies on the effect of prophylactic antibiotics before percutaneous endoscopic gastrostomy are conflicting. Factors for increased risk of peristomal wound infection have not been clearly identified. AIM To evaluate the incidence of complications of percutaneous endoscopic gastrostomy and to determine the predictors of wound infection. PATIENTS AND METHODS Percutaneous endoscopic gastrostomy was performed on 134 patients in different disease groups between January 1996 and June 2000. Medical records were carefully reviewed for demographic data, indications for percutaneous endoscopic gastrostomy, use of prophylactic antibiotics, complications and comorbid conditions predisposing to wound infection. RESULTS Of 134 patients, 22 (16.4%) developed complications after percutaneous endoscopic gastrostomy Wound infection, the most common complication, occurred in 19 patients (14.2%) and Pseudomonas aeruginosa was the most frequently isolated microorganism. In univariate analysis, non-malignant disease and diabetes mellitus were significantly associated with peristomal wound infection after percutaneous endoscopic gastrostomy. In multivariate analysis, only diabetes mellitus was an independent risk factor for the development of peristomal wound infection after percutaneous endoscopic gastrostomy (p = 0.035) CONCLUSIONS Patients with diabetes mellitus have a higher risk of peristomal wound infection after percutaneous endoscopic gastrostomy.

Prevalence and risk factors of Barrett's esophagus in Korea.

Background and Aim:  Barrett’s esophagus (BE) is diagnosed when specialized intestinal metaplasia (SIM) is detected histologically in endoscopically suspected columnar‐lined esophagus (CLE). It is a premalignant condition and plays a pivotal role in the development of esophageal adenocarcinoma. It has traditionally been believed to affect Asians less frequently. The aim of this study was to determine the prevalence of BE and possible associated risk factors in Korea.

Lack of association of Helicobacter pylori infection with gastric hypersensitivity or delayed gastric emptying in functional dyspepsia

Objective:We evaluated the relationship between Helicobacter pylori (H. pylori) infection and gastric sensitivity to distention or gastric emptying rate to define the role of H. pylori in the pathogenesis of functional dyspepsia.Methods:Gastric barostat, gastric emptying scintigraphy, and 13C urea breath test were performed in 34 consecutive patients with functional dyspepsia.Results:Between H. pylori-positive and -negative patients with functional dyspepsia, there were no significant differences in basal tone (57.2 ± 15.0 ml vs 66.8 ± 18.3 ml), compliance (41.0 ± 11.2 ml/mm Hg vs 38.2 ± 11.8 ml/mm Hg), threshold of first sense (3.6 ± 2.7 mm Hg vs 2.3 ± 1.5 mm Hg), threshold of abdominal discomfort (9.4 ± 4.0 mm Hg vs 7.3 ± 1.9 mm Hg), and postprandial receptive relaxation (115.4 ± 89.7 ml vs 99.0 ± 88.7 ml), measured by gastric barostat. Half gastric emptying time (88.6 ± 24.5 min vs 91.4 ± 21.6 min) and retention rate at 120 min (32.8 ± 17.8%vs 41.9 ± 20.1%) were also similar between the two groups.Conclusion:H. pylori infection was not associated with gastric hypersensitivity to distention or delayed gastric emptying.

Clinical diagnosis of primary epiploic appendagitis: Differentiation from acute diverticulitis

Background Primary epiploic appendagitis (PEA) is an uncommon cause of abdominal pain that occurs either from appendageal torsion or spontaneous thrombosis of an appendageal draining vein. Primary epiploic appendagitis is frequently misdiagnosed as either appendicitis or diverticulitis, depending on its location. Study Clinical and radiologic characteristics of 8 patients with PEA were retrospectively reviewed and compared with 18 patients with acute diverticulitis. Results Patients with PEA presented with lower abdominal pain of recent onset that was localized to the left (seven cases) and right (one case) lower quadrants. Well-localized tenderness without peritoneal irritation sign was usually the only physical finding. Blood tests were not significant. In acute diverticulitis, the pain was more evenly distributed throughout the lower abdomen and findings like nausea, fever, and leukocytosis were more frequently associated than in PEA. Computed tomography findings, such as pedunculated oval fatty mass with streaky densities connected to the serosal surface of the adjacent colon, can lead to the diagnosis of PEA. Symptoms of PEA were resolved within 1 week (mean, 4.7 days) without surgery. Conclusions When patients with very localized lower abdominal pain and tenderness do not have associated symptoms or laboratory abnormalities, a high index of suspicion for PEA and early radiologic examinations are required.

Analysis of pacemaker activity in the human stomach

Non‐technical summary  What is known about gastric electrophysiology and used in motility clinics throughout the world is mostly deduced from animal studies and extracellular recordings from human patients. Extracellular recording from gastrointestinal muscles, however, is prone to extensive motion artifact, and it is not clear that animal models can be translated directly to human physiology. Therefore, we have performed a detailed analysis of electrical activity from carefully mapped specimens of gastric muscle removed from humans during surgery for gastric cancers. Our data show several important differences in electrical activity recorded with intracellular microelectrodes and accepted gastric electrophysiological dogma. We observed ongoing electrical slow wave activity in the gastric fundus; we also found no evidence for a slow wave frequency gradient. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution of pacemaker cells.