Kang Moon Lee

Development and Validation of Novel Diagnostic Criteria for Intestinal Behçet's Disease in Korean Patients With Ileocolonic Ulcers

OBJECTIVES:It is difficult to diagnose intestinal Behçets disease (BD) due to various extraintestinal manifestations emerging at different time points in the disease course and a lack of reliable diagnostic criteria. We conducted this study to develop and validate novel diagnostic criteria for intestinal BD.METHODS:Experts from three universities generated the preliminary diagnostic criteria for intestinal BD, and a consensus was reached using a modified Delphi method with 13 gastroenterologists participating. To validate the criteria, we recruited 12,850 consecutive patients who underwent colonoscopic examinations between January 2000 and December 2006 at Severance Hospital, Yonsei University, Seoul, Korea.RESULTS:The novel diagnostic criteria were developed on the basis of two aspects: colonoscopic findings and extraintestinal manifestations. Of the 12,850 patients, 280 with ileocolonic ulcers were enrolled for validation. At the time of initial colonoscopic examinations, patients were categorized for BD status into 4 groups: definite (84 patients), probable (67), suspected (15), and nondiagnostic (114). At the end of the follow-up period (mean, 50.9±25.7 months), intestinal BD was confirmed in 145 patients (51.8%)—84 (100%) from the definite group, 49 (73.1%) from the probable group, 10 (66.7%) from the suspected group, and 2 (1.8%) from the nondiagnostic group. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the diagnosis probability of these criteria were 98.6, 83.0, 86.1, 98.2, and 91.1%, respectively.CONCLUSIONS:These newly proposed, simple criteria might be useful in diagnosing intestinal BD, especially in patients with ileocolonic ulcers who do not fully satisfy the diagnostic criteria of systemic BD.

Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: A Korean multicenter retrospective study

Infliximab is currently used for the treatment of moderate‐to‐severe ulcerative colitis (UC) with an inadequate response to conventional agents. The efficacy and safety of infliximab in Korean patients with UC were assessed.

Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study

The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Efficacy of infliximab in intestinal Behçet's disease: A Korean multicenter retrospective study

Background:Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet’s disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustained treatment response following infliximab treatment. Methods:This study was conducted using a retrospective noncontrolled review of medical records from 8 tertiary hospitals in Korea. We collected clinical, demographic, and laboratory data for patients with 28 patients with intestinal BD who received at least 1 dose of infliximab. Response rates of infliximab at 2, 4, 30, and 54 weeks for each patient and factors predictive of sustained response were investigated. Adverse events were also identified. Results:The median duration of follow-up after initial infliximab infusion was of 29.5 months. The clinical response rates at 2, 4, 30, and 54 weeks were 75%, 64.3%, 50%, and 39.1%, respectively, with clinical remission rates of 32.1%, 28.6%, 46.2%, and 39.1%, respectively. After multivariate analysis, older age at diagnosis (≥40 yr), female sex, a longer disease duration (≥5 yr), concomitant immunomodulator use, and achievement of remission at week 4 were found to be predictive factors of sustained response. There was 1 serious infection but no malignancies or deaths in this study. Conclusions:Infliximab was a well-tolerated and effective therapy for patients with moderate-to-severe intestinal BD. Moreover, we found 5 predictive factors associated with sustained response, which might assist in optimal patient selection for infliximab treatment.

Comparison of a newly designed double-layered combination covered stent and D-weave uncovered stent for decompression of obstructive colorectal cancer: a prospective multicenter study.

PURPOSE: Stent reocclusion and migration are the most important complications after stent insertion. To overcome both problems, a double-layered combination covered stent was developed. Our purpose was to compare the efficacy and safety of the newly designed double-layered combination covered stent (Niti-S enteral colonic stent, Comvi type) and the double-wire woven uncovered stent (Niti-S enteral colonic stent, D-type) in the treatment of malignant colorectal obstructions. METHODS: Sixty-eight patients with obstructive colorectal cancer underwent stent placement for preoperative decompression (n = 30) or palliative purpose (n = 38) at 6 medical centers. Combination covered stents were used in 31 patients and uncovered stents were used in 37 patients. RESULTS: There were no significant differences between both stents in terms of technical and clinical success rates. Regarding complications after stent insertion, there was no significant difference in early stent occlusion and migration rate between the combination covered stents and the uncovered stents. Despite a trend toward lower rates of late stent occlusion in the combination covered stent group, there was no significant difference in the rate of late stent occlusion by tumor ingrowth between the 2 groups (0% vs 20%, respectively; P = .107), and late stent migration occurred significantly more often with the combination covered stent (22.2% vs 0%, respectively; P = .041). However, we observed no significant difference in the overall late-complication rates and stent patency duration between the 2 groups. CONCLUSIONS: In our study, we could not prove that the newly designed double-layered combination covered stents have preventive advantages in stent migration compared with the uncovered stent.

Outcome and safety of self-expandable metallic stents for malignant colon obstruction: a Korean multicenter randomized prospective study

BackgroundNewly developed uncovered stents are designed to have varied radial force and high conformability to improve clinical outcome and safety. This study aimed to determine and compare the clinical outcome and safety of the Taewoong D-type uncovered stent and the Boston Scientific Wallfex stent.MethodsPatients with acute malignant colonic obstruction were treated with a colonic stent. For the purpose of palliation, patients were randomly allocated. For the purpose of bridging, the type of stent was determined by the discretion of the individual doctors. Technical and clinical success and complication occurrence were measured as primary outcomes.ResultsFrom 12 university hospitals, 123 patients with malignant colonic obstruction were enrolled. Of these 123 patients, 58 were treated with colonic stents for palliative purposes. The technical and clinical success rate was 100xa0% for both stents in the palliative group. Perforation occurred for one patient (3.6xa0%) in the Wallflex stent group (nxa0=xa028) on day 5 and for no patients in the D-type stent group (nxa0=xa030). Two cases of migration occurred: one with the Wallflex stent and one with the D-type stent. Stent restenosis occurred for one patient with the Wallflex stent. Preoperative bridging stents were placed in 65 patients. The median time to surgery was 10xa0days. The technical success rate was 93.4xa0%, and clinical success was achieved for 86.2xa0% of the patients. Perforation occurred for five patients: four with the Wallflex stent and one with the D-type stent. The efficacy and safety of the two stents did not differ statistically.ConclusionsThe D-type colonic uncovered stent and the Wallflex colonic uncovered stent are effective and safe for both palliative and preoperative bridging therapy used to treat acute malignant colonic obstruction.

Clinical Outcome of Self-Expandable Metal Stent Placement in the Management of Malignant Proximal Colon Obstruction

Background/Aims There are limited data regarding the clinical outcomes of self-expandable metal stents in the treatment of proximal colon obstruction. We compared the clinical outcomes of stent placement in patients with malignant proximal to distal colon obstructions. Methods We reviewed medical records from 37 consecutive patients from three institutions (19 men; mean age, 72 years) who underwent endoscopic stent placement at a malignant obstruction of the proximal colon. We also examined the records from 99 patients (50 men; mean age, 65 years) who underwent endoscopic stent placement for a distal colon obstruction. Technical success, clinical improvements, complications and stent patency were compared between treatments. Results The technical success rate tended to be lower in stents inserted to treat proximal colon obstructions than in those used to treat distal colon obstructions (86% vs 97%, p=0.06). Clinical improvement was achieved in 78% of patients (29/37) with proximal colonic stenting and in 91% of patients (90/99) with distal colonic stenting (p=0.08). Complications (24% vs 27%), stent migration (8% vs 8%) and stent reocclusion rates (11% vs 17%) did not differ significantly between groups. Two cases of bowel perforation related to stenting (5%) occurred in patients with proximal colonic stenting. Conclusions The technical success and clinical improvement associated with self-expandable metal stents used to treat proximal colon obstruction tend to be lower than cases of distal colon obstruction. Technical failure is an important cause of poor clinical improvement in patients with proximal colon stenting. Complication rates and stent patency appear to be similar in both groups.

P53 genetic polymorphism of gastric cancer in Korea.

Background/Aims Deletion or functional loss of the p53 tumor suppression gene plays a role in oncogenic transformation. The codon 72 polymorphism on exon 4 in the p53 gene produces variant proteins with either arginine (Arg) or proline (Pro), and is associated with an increased susceptibility of cancers of the lung, esophagus, breast, cervix and nasopharynx on a genetic basis. We designed this study to evaluate the influence of the p53 codon 72 polymorphism on gastric cancer in Korea. Methods We extracted the peripheral blood samples in 84 patients with gastric cancer, 66 patients with H. pylori-associated chronic gastritis and 43 controls without H. pylori infection. PCR-RFLP analysis was performed to detect p53 codon 72 polymorphism in these patients. Results There was no specific genotype of p53 polymorphism in the gastric cancer group compared to the other groups and no difference in genotypes by histologic subtypes. Classified by tumor location, Pro/Pro genotype was associated with an increase in proximal cancer and Arg/Arg genotype with distal cancer. As the frequency of p53 Arg allele increased, the cancer was of a more poorly differentiated type. Conclusions The specific genotype of p53 polymorphism seems to correlate with tumor location. Increased frequency of p53 Arg allele is associated with more poorly differentiated cancers.

Patients with Crohn's disease on anti-tumor necrosis factor therapy are at significant risk of inadequate response to the 23-valent pneumococcal polysaccharide vaccine

BACKGROUND/AIMSnThe effect of immunosuppressants on the efficacy of a variety of vaccines is a controversial issue in patients with inflammatory bowel disease (IBD). In this study we determined whether specific immunosuppressants impair the serological response to the standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) in a large cohort of patients with Crohns disease (CD).nnnMETHODSnThis was a multi-center, prospective observational study of adult patients with CD at 15 academic teaching hospitals in Korea. The study population received one intramuscular injection of PPSV23. Anti-pneumococcal IgG antibody titers were measured by immunoassay prior to and 4weeks after vaccination. All vaccination-related adverse events and the effect of the vaccine on disease activity were also evaluated.nnnRESULTSnThe overall serological response rate was 67.5% (133/197). The serological response rate was significantly lower in patients on anti-tumor necrosis factor (anti-TNF) therapy (50.0% on anti-TNF alone; 58.0% on anti-TNF combined with an immunomodulator, IM) than patients on 5-aminosalicylate (78.4%; all P-values vs. 5-aminosalicylate<0.05); 45.6% (41/90) of patients on anti-TNF therapy were not protected against PPSV23. IM did not affect the immunologic response to the vaccine. Female gender and anti-TNF therapy were significant predictors of non-response to the vaccine (odds ratio [OR] 2.316, P=0.015; OR 2.582, P=0.048, respectively). Vaccination was generally safe and tolerated by all patients.nnnCONCLUSIONSnPatients with CD on anti-TNF therapy are at significant risk of an inadequate response to PPSV23. The pneumococcal vaccination strategy should be optimized for patients with CD on anti-TNF therapy.

Crohn's Disease Clinical Network and Cohort (CONNECT) Study: The First Step Toward Nationwide Multicenter Research of Crohn's Disease in Korea

Crohns disease (CD) is a chronic, relapsing immune-mediated inflammatory disorder of the intestine with unknown causes. Both genetic and environmental factors are known to be involved in the pathogenesis of the disease.1 The incidence and prevalence of CD have recently been increasing in Korea, probably secondary to environmental changes.2 To address this challenge, we need to understand the specific clinical and therapeutic characteristics of CD in Korean patients. It has been widely accepted that the phenotypes of IBD differ considerably between East Asians and Caucasians.3,4 Thus, the management strategies used for patients with CD in Western countries may not be appropriate for those in Korea. Therefore, it is crucial to understand the natural history and clinical characteristics of this disease in Korean patients, which are largely unknown due to the lack of population-based cohort studies. Most of the currently available data comes from single-center, hospital-based studies. Several important cohort studies conducted in Western Europe and America have described the clinical course of CD.5,6,7 But there have been no well-designed cohort studies in Korea. Consequently, investigators are becoming aware of the need for a cohort study of CD in Korea. Moreover, genetic or biomarker studies need blood or tissue specimens from a large number of patients, which should be collected together with accurate, matched clinical data. This highlights the urgent need for a nationwide collection of well-defined clinical characteristics of Korean CD patients and their biological specimens. n nAttempts to comprehensively understand the epidemiologic, clinical, and genetic characteristics of Korean CD patients started in 2008. Won Ho Kim at Yonsei University, President of the Korean Association for the Study of Intestinal Diseases (KASID) at that time, obtained a national grant, the Research Network for Crohns Disease. The four major aims of the study were as follows: (1) understand the epidemiologic and clinical characteristics by establishing a registered database of CD patients; (2) establish a genetic research management system and a genetic biobank by obtaining blood specimens and clinical data from CD patients; (3) establish a network of doctors specialized in CD treatment and patients with CD as a private non-profit organization; and (4) develop specific Korean diagnostic and therapeutic guidelines for CD. During the study period, clinical data from nearly 2,000 blood specimens (both genomic DNA and sera) of 1,316 Korean CD patients were collected and stored at the Korean Green Cross Corporation. Active translational research by basic and clinical researchers is now underway using these samples.8,9 In addition, this study team established a nationwide doctor-patient network by hosting educational workshops for patients and symposiums for clinicians via the regional society meetings every year (Seoul, Gyunggi, Daegu, and Daejeon). These provided disease information, life style education, counseling, and various programs for patients and their families, including one ensuring patients rights. This study team also established and published the Korean diagnostic and therapeutic guidelines for CD with the help of the IBD Study Group of KASID10,11 that published the diagnostic guidelines for intestinal tuberculosis, a disease often misdiagnosed as CD, in the same year.12 Through an e-mail survey, the IBD Study Group of KASID monitored the effectiveness of the diagnostic guidelines in clinical practice, investigated clinician satisfaction with the guidelines, and collected feedback on ways to improve the guidelines.13 At that time, the chair of IBD study group was Professor Joo Sung Kim at Seoul National University. n nAfter the nationally funded Research Network for Crohns Disease study ended, a better-designed cohort study involving prospective collection of clinical data was planned. The Korea Eisai Company sponsored a two-year educational grant for this CD cohort study. This study followed the Research Network for Crohns Disease study and was named Establishment of Crohns disease in Korea and characterization of clinical features with long-term follow-up, and was conducted from January 2012 to December 2013. This study team was led by Dong Soo Han, a Professor at the Hanyang University and the current vice president of KASID. Retrospective clinical data (for patients enrolled before 2009) and prospective clinical data (for patients enrolled during and after 2009) were collected in this study. The prospective patients were enrolled using a novel web-based eCRF system (www.cdcohort.org). Data for 1,388 retrospective patients and 890 prospective patients were collected and analyzed. A study coordinator monitored submission and quality of eCRF data. Blood specimens were collected from 635 of the prospective patients and stored in a deep freezer at -80℃. During this study, the IBD study group chair was Professor Young Ho Kim at the Sungkyunkwan University, who organized the clinical and translational studies that utilized these data. This study was registered at www.clinicaltrials.gov. The first results using the prospective data were presented during the 2014 regular meeting of the European Crohns and Colitis Organization in Copenhagen, Denmark. The most important and innovative outcomes from this study were the establishment of a novel eCRF system to collect well-recorded, high-quality prospective data and the development of the associated data input protocol (the latter of which was led by Professor Byong Duk Ye). n nIn 2012, the Cardiovascular and Rare Disease Section, Korea Centers for Disease Control and Prevention (www.cdc.go.kr) solicited grant applications for a 6-month demonstration project aimed at establishing a CD network (to run from August 2012 to December 2012). The KASID obtained this grant, and in 2012, for a 3-year national grant from the Korea Centers for Disease Control and Prevention. The new study funded by these grants was named Establishment and Management of Crohns Disease Research Network. The principal aim of this study was to broaden the pool of study subjects by recruiting additional investigators throughout Korea. Consequently, 28 institutions were recruited to participate in this study. Currently, Professor Joo Sung Kim at the Seoul National University is in charge of the study. The current chair of the IBD study group is Professor Kang Moon Lee at the Catholic University, and he is currently supervising the investigators and study projects working with the collected data. n nRecently, the latter two studies discussed above were integrated into a single study referred to as the Crohns Disease Clinical Network and Cohort (CONNECT) study (Fig. 1). A total of 34 institutions are now participating in this study, and 1,900 blood specimens have been collected. Four abstracts were presented at the regular KASID meeting in April 2014. From the CONNECT study, investigators anticipate that the typical clinical characteristics and genetic causes of CD in Korean patients will be elucidated. Additional diagnosis and treatment guidelines and therapeutic agents for Korean CD patients will be developed based on these data. Additionally, we anticipate that after analysis, the collected data will be presented at international symposiums and the papers published. By following up with the registered patients, long-term clinical characteristics and accuracy of initial diagnosis can also be investigated. Long-term follow-up results from the CONNECT study should help clinicians and researchers more accurately define CD prognosis in Korea, provide specific health care planning and education, and identify causative factors for CD in Korea, where the incidence of CD is rapidly increasing. n n n nFig. 1 n nThe progress of 3 studies integrated into the Crohns Disease Clinical Network and Cohort (CONNECT) study. KASID, Korean Association for the Study of Intestinal Diseases.