Seung Joo Kang

Effect of annual endoscopic screening on clinicopathologic characteristics and treatment modality of gastric cancer in a high‐incidence region of Korea

We investigated risk factors for gastric cancer (GC) and effect of annual endoscopic screening on detection and treatment modality of GC. Asymptomatic adults who underwent upper endoscopy during health checkups at Seoul National University Hospital Healthcare System Gangnam Center were enrolled. We compared clinicopathologic characteristics of GC according to screening interval (repeated vs. infrequent, annual vs. biennial). After age‐ and sex‐matching, relative risk was computed by hazard ratio (HR) using Cox proportional regression with multivariate adjustment. Of the 58,849 subjects who received screening endoscopy, 277 (0.47%) were found to have GC. Intestinal type comprised 55.4% (102/184) followed by diffuse type (n = 65, 35.3%). Age ≥50 years, family history and smoking independently increased the risk of GC for both types, whereas male gender [HR = 4.81, 95% confidence interval (CI): 2.72–8.03] and intestinal metaplasia (IM) (HR = 10.87, 95% CI: 3.36–22.30) were significant predictors for intestinal type only. Proportion of early gastric cancer (EGC) was 98.6% (71/72) in annual screening group and 80.7% (46/57) in biennial screening group (p < 0.01). In the former, tumor size was smaller (1.7 ± 1.3 vs. 2.3 ± 1.8 cm; p < 0.01] and proportion of intramucosal cancer was larger (75.0 vs. 56.1%; p = 0.04). Endoscopic resection was performed more frequently in annual screening group (56.9 vs. 33.3%; p = 0.02). IM along with male gender and older age was a strong risk factor for intestinal type GC. Annual screening group improved detection of early‐stage and endoscopically treatable GC suggesting that intensive screening and surveillance may be useful for high‐risk subpopulations with epidemiologic risk factors or premalignant lesions such as IM.

Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

Background/Aims Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD. Methods A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day. Results The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001). Conclusions Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.

Effects of serum bilirubin on atherosclerotic processes.

Abstract This review highlights the protective roles of bilirubin against the atherosclerotic process. Bilirubin belongs to the superfamily of tetrapyrrolic compounds formed during heme catabolism. Although for decades bilirubin was considered to be a harmful waste product, recent epidemiologic studies have shown that serum bilirubin levels have consistently been inversely associated with cardiovascular disease (CVD), as well as cardiovascular risk factors such as metabolic syndrome and diabetes. These clinical studies are supported by in vitro and in vivo experimental data and have demonstrated that bilirubin not only has an ability to scavenge overproduced reactive oxygen species and inhibit vascular smooth muscle cell proliferation but, additionally, has anti-inflammatory effects. In this review, we will discuss the inverse association of serum bilirubin and CVD and cardiovascular risk factors established in various clinical studies. We also review detailed experimental studies about the effect of bilirubin on atherosclerotic processes. In vitro, animal and human studies have proved that bilirubin inhibits oxidation of cholesterol which is an important step of atherosclerosis. Bilirubin attenuates chemotactic activity of monocytes and strongly inhibits adhesion of leukocytes to venule and production of pro-inflammatory cytokines. Bilirubin has inhibited serum-driven smooth muscle cell cycle progression at the G1 phase. Lastly, we will discuss briefly the influence of bilirubin on lipoprotein composition and endothelial dysfunction.

Association between Helicobacter pylori Seropositivity and the Coronary Artery Calcium Score in a Screening Population

Background/Aims Helicobacter pylori causes numerous extragastric manifestations, including coronary heart disease. The coronary artery calcification (CAC) score, measured using computed tomography (CT) has been used as a screening test for coronary atherosclerosis. This study investigated the association between H. pylori seropositivity and CAC scores in a screening population. Methods Patients who underwent a health checkup between October 2003 and July 2007 and who did not have a history of ischemic heart disease were enrolled in the study. Subjects were screened with a multidetector CT scan to determine the CAC score and for anti-H. pylori antibody immunoglobulin G; traditional risks for coronary heart disease were evaluated using a structured questionnaire, anthropometric measurements, and laboratory tests. Results Of the 2,029 subjects enrolled (1,295 males), 1,214 (59.8%) subjects were H. pylori positive and 815 were H. pylori negative. There were no significant differences in the baseline characteristics of the seropositive and seronegative patients. When the CAC presence or absence scores were considered, multivariate analysis revealed that H. pylori seropositivity was statistically associated with the presence of CAC and that this association was stronger in the mild CAC score category. Conclusions H. pylori seropositive patients are at a higher risk for coronary atherosclerosis regardless of traditional cardiovascular risk factors. This association is particularly applicable for early coronary atherosclerosis.

Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria

AIM To investigate the relationship between Helicobacter pylori (H. pylori) seropositivity and the presence of microalbuminuria. METHODS Between December 2003 and February 2010, asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H. pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio (UACR) were included. All study subjects completed a structured questionnaire, anthropometric measurements and laboratory tests. Anti-H. pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit. A random single-void urine sample, collected using a clean-catch technique, was obtained to determine the UACR. The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg. The presence of diabetes mellitus (DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication. Multiple logistic regression analysis was performed to identify the risk factors. The dependent variable was microalbuminuria, and the independent variables were the other study variables. RESULTS A total of 2716 subjects (male, 71.8%; mean age, 54.9 years) were included. Among them, 224 subjects (8.2%) had microalbuminuria and 324 subjects (11.9%) had been diagnosed with DM. Subjects with microalbuminuria had a significantly higher H. pylori seropositivity rate than subjects without microalbuminuria (60.7% vs 52.8%, P = 0.024). Multivariate analysis after adjustment for age, body mass index (BMI), waist circumference, and glucose and triglyceride levels showed that H. pylori seropositivity was significantly associated with microalbuminuria [odds ratio (OR), 1.40, 95% CI, 1.05-1.89, P = 0.024]. After the data were stratified into cohorts by glucose levels (≤ 100 mg/dL, 100 mg/dL < glucose < 126 mg/dL, and ≥ 126 mg/dL or history of DM), H. pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age, BMI and serum creatinine level (OR, 2.21, 95% CI, 1.20-4.08, P = 0.011). In addition, the subjects were divided into five groups. Those without microalbuminuria (an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values, and subjects with microalbuminuria comprised their own group. Notably, H. pylori seropositivity gradually increased with an increase in UACR (P = 0.001) and was highest in subjects with microalbuminuria (OR, 2.41, 95% CI, 1.14-5.11). This suggests that H. pylori seropositivity is positively associated with microalbuminuria in diabetic subjects. CONCLUSION H. pylori seropositivity was independently associated with microalbuminuria, and the prevalence of H. pylori seropositivity was associated with the severity of UACR in diabetic subjects.

Role of ascites adenosine deaminase in differentiating between tuberculous peritonitis and peritoneal carcinomatosis

AIM To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC). METHODS A retrospective analysis of data was performed on consecutive patients who underwent peritoneoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS Serum c-reactive protein (7.88 ± 6.62 mg/dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serum-ascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.

Visceral adipose tissue area is associated with coronary stenosis and noncalcified plaques.

Objective:Few studies have investigated the relationships between visceral adipose tissue (VAT) and coronary stenosis and noncalcified plaques at the subclinical stage. The aim of this study was to investigate relationship between VAT and coronary lesions assessed by coronary computed tomography (CT) in an apparently healthy population.Design:Retrospective cross-sectional study.Subjects:One thousand six hundred and fifty-eight subjects free of cardiovascular disease underwent coronary CT and abdominal fat CT as part of a routine medical examination.Measurement:VAT area was measured at the level of the umbilicus using CT. Coronary stenoses and plaques were evaluated using coronary CT.Results:The mean age of the study population was 55.9±8.0 years, and 1198 (72.3%) subjects were men. There were 201 subjects (12.1%) with coronary stenosis <50% and 144 (8.7%) had significant stenosis. Noncalcified plaques were observed in 108 (6.5%) subjects. Coronary stenosis <50% and noncalcified plaques increased steadily as the VAT area increased (P<0.001). The 4th quartile of VAT area was significantly associated with prevalence of coronary stenosis <50% and the presence of noncalcified plaques when compared with the first through third VAT quartiles in the cardiovascular risk factor-adjusted model (odds ratio (OR): 1.58, 95% confidence interval (CI): 1.09–2.30 and OR: 1.66; 95% CI: 1.02–2.68, respectively).Conclusion:Excess VAT area was associated with coronary stenosis <50% and noncalcified plaques, independent of traditional cardiovascular risk factors, in an asymptomatic population without a history of coronary artery disease.

The effect of intestinal alkaline phosphatase on intestinal epithelial cells, macrophages and chronic colitis in mice

AIMS Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that is shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10(-/-)) mice. MAIN METHODS Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10(-/-) mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-κB and IκBα phosphorylation/degradation was evaluated by immunoblot assay in COLO 205. For the in vivo study, colitis was induced in IL-10(-/-) mice with piroxicam, the mice were then treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry. KEY FINDINGS IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10(-/-) mice. SIGNIFICANCE IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease.

Prediction of Risk of Malignancy of Gastrointestinal Stromal Tumors by Endoscopic Ultrasonography

Background/Aims The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. Methods Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. Results A total of 75 patients were enrolled. The mean tumor size was 3.43±0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. Conclusions Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy.

The Relationship Between Colonoscopy Procedure Order and Adenoma Detection Rates: A Prospective Study.

Goals: The aim of this study was to prospectively assess the effects of the order of colonoscopic procedures and other possible factors on the adenoma detection rate (ADR). Background: There have been conflicting studies regarding the timing or order of a colonoscopy and its ability to detect adenomas. Study: Between March 2011 and July 2011, consecutive colonoscopies were prospectively performed by 7 board-certified staff endoscopists at the Seoul National University Hospital Healthcare System Gangnam Center. The primary outcome was the overall ADR according to the procedure order of the colonoscopies, and the secondary outcome was the identification of other possible factors influencing the ADR. Results: A total of 1908 colonoscopies were analyzed. The detection rate was 56.5% for all polyps and 37.3% for adenomas. The ADR increased as the performance order of the colonoscopy increased and was highest for the third procedure (43.4%). However, the ADR of the remaining procedures, including later procedures, was similar throughout the workday. In the multivariable analysis, the ADR was significantly associated with older age, male sex, high body mass index, personal history of colorectal polyps, long withdrawal time, and an experienced endoscopist. However, the colonoscopy procedure order was not significantly associated with the ADR. Conclusions: The ADR was stable according to the procedure order for the later procedures of the workday in a setting of moderate daily procedure volumes. The withdrawal time and experience level of the endoscopist were more important than the procedure order in detecting adenomas by colonoscopy.