Jai Hyun Choi

Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations

Objective Crohns disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. Methods We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. Results We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10−14), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10−10) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10−9), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10−12) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10−5)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. Conclusions Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.

Comparison of the characteristics of submucosal injection solutions used in endoscopic mucosal resection

OBJECTIVE Submucosal injection is used to prevent complications, such as perforation, during endoscopic mucosal resection (EMR). Since injection of normal saline produces mucosal elevation of short duration, repeated injection is needed for extensive resection. To overcome this limitation, various submucosal injection solutions have been developed but there are few data comparing their efficacy. This study was therefore conducted to compare the physical and chemical properties and the duration of mucosal elevation of various submucosal injection solutions. MATERIAL AND METHODS A fresh transverse colon specimen acquired from a mongrel was used. Experiments were repeated four times. To compare the efficacy of mucosal elevation, 1 ml of each solution was injected into the submucosa: 0.9% NaCl, 20% mannitol, 0.1% sodium hyaluronate, 0.3% hydroxypropyl methylcellulose (HPMC), and 2% fibrinogen. Physical and chemical properties such as viscosity and osmolarity were compared. RESULTS The heights of initial mucosal elevations were 6.52+/-0.26 mm, 6.87+/-0.05 mm, 6.92+/-0.09 mm, 6.90+/-0.08 mm, and 6.90+/-0.08 mm for normal saline, mannitol, sodium hyaluronate, HPMC, and fibrinogen, respectively. Whereas injection of normal saline took about 20 min and mannitol about 30 min for the initial elevation to be reduced to more than half the initial height, it took more than 60 min for all the other agents. A correlation was found between the duration of mucosal elevation and viscosity but not with osmolarity. CONCLUSIONS The mucosal elevation lasted longer with sodium hyaluronate, HPMC, and fibrinogen than with mannitol or normal saline, and this seems to be due to the viscosity rather than the osmolarity of each solution.Objective. Submucosal injection is used to prevent complications, such as perforation, during endoscopic mucosal resection (EMR). Since injection of normal saline produces mucosal elevation of short duration, repeated injection is needed for extensive resection. To overcome this limitation, various submucosal injection solutions have been developed but there are few data comparing their efficacy. This study was therefore conducted to compare the physical and chemical properties and the duration of mucosal elevation of various submucosal injection solutions. bA fresh transverse colon specimen acquired from a mongrel was used. Experiments were repeated four times. To compare the efficacy of mucosal elevation, 1 ml of each solution was injected into the submucosa: 0.9% NaCl, 20% mannitol, 0.1% sodium hyaluronate, 0.3% hydroxypropyl methylcellulose (HPMC), and 2% fibrinogen. Physical and chemical properties such as viscosity and osmolarity were compared. b The heights of initial mucosal elevations were 6.52±0.26 mm, 6.87±0.05 mm, 6.92±0.09 mm, 6.90±0.08 mm, and 6.90±0.08 mm for normal saline, mannitol, sodium hyaluronate, HPMC, and fibrinogen, respectively. Whereas injection of normal saline took about 20 min and mannitol about 30 min for the initial elevation to be reduced to more than half the initial height, it took more than 60 min for all the other agents. A correlation was found between the duration of mucosal elevation and viscosity but not with osmolarity. Conclusions. The mucosal elevation lasted longer with sodium hyaluronate, HPMC, and fibrinogen than with mannitol or normal saline, and this seems to be due to the viscosity rather than the osmolarity of each solution.

Comparative study of helicobacter pylori eradication rates with 5-day quadruple concomitant therapy and 7-day standard triple therapy

Background: Several studies have shown the superiority of concomitant quadruple therapy containing 3 antibiotics over triple therapy for Helicobacter pylori infection. The aim of this study was to compare concomitant quadruple therapy with standard triple therapy for first-line H. pylori eradication. Methods: A total of 270 patients with proven H. pylori infection were randomly assigned to one of 2 regimens: amoxicillin 1000 mg with clarithromycin 500 mg and lansoprazole 30 mg twice daily for 7 days (triple therapy) or amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice daily for 5 days (concomitant therapy). The success of eradication was evaluated 4 to 5 weeks after completion of treatment. Results: Eradication rates were 86.1% in the triple therapy and 91.4% in the concomitant therapy (per protocol), but the difference was not statistically significant. Mild adverse events were more frequently reported in the concomitant-therapy group (35.6%) than in the triple-therapy group (25.2%) (P=0.09). Conclusions: Five-day quadruple concomitant therapy eradicated H. pylori in over 90% of patients. Accordingly, concomitant therapy is thought to be a promising alternative to triple therapy as a first-line treatment regimen for H. pylori eradication.

Colorectal Neoplasm in Asymptomatic Average-risk Koreans: The KASID Prospective Multicenter Colonoscopy Survey

BACKGROUND/AIMS The incidence of colorectal cancer is increasing in Korea, but the epidemiology of colorectal neoplasm is not clearly defined. We aimed to elucidate the prevalence of colorectal neoplasm in average-risk Koreans and explore the underlying risk factors. METHODS A large-scale, multicenter, prospective study was conducted. Of the 19,460 subjects who underwent colonoscopy at 11 university hospitals, we analyzed 3,951 consecutive asymptomatic adults with no risk factors for colorectal cancer. RESULTS The subjects were aged 52.1+/-11.6 years (mean+/-SD) and 60.1% of them were men. The prevalences of colorectal neoplasm and advanced neoplasm were 33.3% and 2.2%, respectively. The prevalence of a neoplasm increased with age (trend: p<0.001) and was higher in males (p<0.001). The prevalence of a proximal neoplasm was higher in subjects with a distal neoplasm than in those without a distal neoplasm (11.9% vs. 5.4%, p<0.001). However, 150 (52.1%) of the 288 subjects with a proximal neoplasm had no distal neoplasm. CONCLUSIONS The overall prevalence of colorectal neoplasm in asymptomatic average-risk Koreans is comparable with that in Western countries. Being male and older are associated with a higher risk of colorectal neoplasm. Over half of proximal neoplasms are not associated with any distal sentinel lesions.

Immunochip Analysis Identification of 6 Additional Susceptibility Loci for Crohn's Disease in Koreans

Background:Crohns disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population. Methods:Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls. Results:We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10−11, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10−9, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10−7, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10−8, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10−8, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10−7, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans. Conclusions:Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

Prospective evaluation of the clinical utility of interferon-γ assay in the differential diagnosis of intestinal tuberculosis and Crohn's disease

Background: Distinguishing intestinal tuberculosis (ITB) from Crohns disease (CD) is challenging. This study prospectively evaluated the clinical utility of the QuantiFERON‐TB gold test (QFT) in the differential diagnosis of ITB and CD, and compared it with the clinical utility of the tuberculin skin test (TST). Methods: Patients with suspected ITB or CD on colonoscopic findings were enrolled from 13 hospitals in Korea between June 2007 and November 2008. A QFT and TST were performed. When the initial diagnosis was not confirmed, 2‐3 months of empiric antituberculous therapy was administered. Results: In all, 128 patients were analyzed; 64 patients had ITB and 64 patients had CD. The median age of patients with ITB was greater than the patients with CD (47 years versus 31 years, P < 0.001). The positive rate for the QFT and TST (≥10 mm) in patients with ITB was significantly higher than patients with CD (67% versus 9% and 69% versus 16%, respectively; P < 0.001). The QFT and TST had good agreement (&kgr; = 0.724, P < 0.001). The diagnostic validity of QFT in ITB had a 67% sensitivity, 90% specificity, 87% positive predictive value, and 73% negative predictive value. There was no difference in these parameters between the QFT and TST. The likelihood ratio for a positive QFT was higher than a positive TST in the diagnosis of ITB (7.1 and 4.4, respectively). Conclusions: The QFT is a limited but useful diagnostic aid in combination with the TST in the diagnosis of ITB. (Inflamm Bowel Dis 2011;)

Clinical significance of variceal hemorrhage in recent years in patients with liver cirrhosis and esophageal varices

Background and Aims:  Recent progress in the treatment of variceal bleeding might have reduced the impact of variceal bleeding on survival in patients with esophageal varices. We conducted a retrospective cohort study in an attempt to re‐evaluate the clinical significance of variceal bleeding.

Endovascular Management for Isolated Spontaneous Dissection of the Superior Mesenteric Artery: Report of Two Cases and Literature Review

The clinical course and treatment strategies of isolated superior mesenteric artery (SMA) dissection have not been fully investigated. Two cases of uncontrolled abdominal pain caused by isolated SMA dissection were successfully treated with percutaneous endovascular stent placement. At follow-up 6 months later, computed tomography confirmed that the lesions had stabilized. The patients remained symptom free at 14- and 13-month follow-up, respectively. The present report describes these two cases of isolated SMA dissection treated successfully with percutaneous endovascular stent placement, along with a review of the related literature.

Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy

Purpose Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea. Materials and Methods We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected. Results A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohns disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results. Conclusion Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.

Effectiveness of three times daily lansoprazole/amoxicillin dual therapy for Helicobacter pylori infection in Korea.

AIM We compared three times daily dual therapy with standard triple therapy for effectiveness and safety in H. pylori infection. METHODS Two hundred and four H. pylori positive patients with peptic ulcer were randomly assigned to one of two regimens: (i) triple therapy with amoxicillin, clarithromycin and lansoprazole twice daily for 2 weeks or (ii) dual therapy with amoxicillin and lansoprazole three times daily for 2 weeks. The success of eradication was evaluated 4 to 5 weeks after completing treatment. RESULTS The eradication rate was 82.8% in the triple therapy group and 78.4% in the dual therapy group by per protocol analysis. This difference was not significant (P= 0.573). Adverse events were more frequent in the triple therapy group than in the dual therapy group (P= 0.002). CONCLUSIONS Because dual therapy had fewer side effects than triple therapy and a similar eradication rate, dual therapy may provide an acceptable alternative first line therapy for H. pylori eradication in Korea.