Changes in the Long-term Prognosis of Crohn’s Disease between 1986 and 2015: The Population-Based Songpa-Kangdong Inflammatory Bowel Disease Cohort Study

Ye Byong Duk,Hong Sung Noh,Seo Seung In,Kim Ye-Jee,Cha Jae Myung,Rhee Kyoung Hoon,Yoon Hyuk,Kim Young-Ho,Kim Kyung Ho,Kim Kyung Ho,Jeong Seung Kyu,Lee Ji Hyun,Park Hyunju,Kim Joo Sung,Im Jong Pil,Kim 거트앤리버 소화기연관학회협의회 2022 Gut and Liver Vol.16 No.2

Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.

EDITORIAL : Could Early Anti-Tumor Necrosis Factor Therapy Change the Prognosis of Crohn`s Disease?

( Byong Duk Ye ) 대한장연구학회 2014 Intestinal Research Vol.12 No.4

Long-Term Clinical Outcomes of Korean Patient With Crohn’s Disease Following Early Use of Infliximab (Intest Res 2014;12:281-286)

Disorders of Small and Large Intestine : Clinical Course Of Submucosal Colorectal Cancers Treated By Endoscopic Mucosal Resection

( Byong Duk Ye ),( Jeong Sik Byeon ),( Seung Hyun Kwon ),( Benjamin Kim ),( Seung Jae Myung ),( Suk Kyun Yang ),( Jin Ho Kim ) 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: Although the risk of lymph node metastasis is known to be increased in deep submucosal invasion, some submucosal colorectal cancers (CRCs) with negligible risk of lymph node metastases can be cured by endoscopic mucosal resection (EMR). The purpose of this study was to investigate the clinical course of submucosal CRC treated by EMR. Methods: We retrospectively reviewed the medical records of patients who underwent EMR for colorectal polyps. Pathologically proven submucosal CRC cases were enrolled in the analysis. Results: A total of 52 patients (32 men, mean age 62 years) were enrolled between March 2001 and February 2007. In one patient, two submucosal CRCs were identified. Forty seven lesions were located in left side colon and majority of lesions (n=44) were protruded types. EMR was performed for 47 lesions and endoscopic submucosal dissection (ESD) for 6 lesions. Mean long diameter of resected specimens was 17.8±8.3 mm. Histologic examination showed moderately-differentiated adenocarcinoma in 35 lesions, and well-differentiated in 18 lesions. Complete resection rate was 79.2%. Among 52 patients, 22 patients underwent additional surgery and 1 patient underwent radiation therapy due to one or more following poor prognostic factors: involvement of resection margin, poor differentiation, deep submucosal tumor invasion, and lymphovascular tumor emboli. For the 25 tumors that were treated by radical endoscopic resection and followed-up by endoscopy, no local tumor recurrence was found after a mean endoscopic follow-up period of 18.0 months (range 2.1-53.3 months) with a mean of 2.4 follow-up endoscopies (range 1-5). Hepatic metastasis was identified in one patient who rejected additional surgery despite positive resection margin 26 months after EMR. Minor bleeding and perforation developed in 10 and 1 during 53 procedures, respectively. Perforation was successfully managed with endoscopic clipping. Conclusions: Endoscopic resection seems to be feasible for the treatment of selected cases of submucosal colorectal cancers. Long-term follow-up with larger number of subjects is needed for elucidating the role of endoseopic treatment for submucosal colorectal cancers.

Identification of Ten Additional Susceptibility Loci for Ulcerative Colitis Through Immunochip Analysis in Koreans :

Ye, Byong Duk,Choi, Hyunchul,Hong, Myunghee,Yun, Woo Jin,Low, Hui-Qi,Haritunians, Talin,Kim, Kyung-Jo,Park, Sang Hyoung,Lee, Inchul,Bang, So-Young,Kim, Tae-Hwan,Shin, Hyoung Doo,Kang, Daehee,Youn, Hee Oxford University Press 2016 Inflammatory bowel diseases Vol.22 No.1

크론병 치료 가이드라인

예병덕 ( Byong Duk Ye ),양석균 ( Suk Kyun Yang ),신성재 ( Sung Jae Shin ),이강문 ( Kang Moon Lee ),장병익 ( Byung Ik Jang ),천재희 ( Jae Hee Cheon ),최창환 ( Chang Hwan Choi ),김영호 ( Young Ho Kim ),이희영 ( Heeyoung Lee ) 대한장연구학회 2012 Intestinal Research Vol.10 No.1

Crohn`s disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD caninvolve any site of gastrointestinal tract from the mouth to anus and is associated with serious complications suchas bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are stilllower than those of Western countries, but have been rapidly increasing during the past decades. Although thereare no definitive curative modalities for CD, various medical and surgical therapies are currently applied for diverseclinical situations of CD. However, a lot of decisions on the management of CD are made depending on the personalexperiences and personal dicision of physicians. To suggest preferable approaches to diverse problems of CD andto minimize the variations according to physicians, guidelines for the management of CD are needed. Therefore,IBD Study Group of the Korean Association for the Study of the Intestinal Diseases has set out to develop theguidelines for the management of CD in Korea. These guidelines were developed using the adaptation methodsand encompass the treatment of inflammatory disease, stricturing disease, and penetrating disease. The guidelinesalso cover the indication of surgery, prevention of recurrence after surgery, and CD in pregnancy and lactation. These are the first Korean guidelines for the management of CD and the update with further scientific data andevidences is needed. (Intest Res 2012;10:26-66)

한국인에서 크론병과 Toll-Like Receptor 유전자의 연관성

예병덕 ( Byong Duk Ye ),양석균 ( Suk Kyun Yang ),송규영 ( Kyu Young Song ),양동훈 ( Dong Hoon Yang ),윤순만 ( Soon Man Yoon ),김경조 ( Kyung Jo Kim ),변정식 ( Jeong Sik Byeon ),명승재 ( Seung Jae Myung ),김진호 ( Jin Ho Kim ) 대한소화기학회 2009 대한소화기학회지 Vol.54 No.6

목적: Toll-like receptor (TLR)는 병원균의 특정한 분자 패턴을 인지하는 패턴 인지 수용체로 작용하여 친염증성 사이토카인 분비를 매개한다. 최근 서구에서 수행된 몇몇 연구들에서 TLR이 크론병의 감수성 유전자로 밝혀졌다. 이에 연구자들은 한국인에서 크론병과 TLR4 및 TLR9 유전자 변이의 관계를 규명하고자 하였다. 대상 및 방법: 380명의 크론병 환자와 380명의 대조군에서 TLR4 Asp299Gly (rs4986790), Thr399Ile (rs4986791) 및 TLR9 -1237T/C (rs5743836) 유전자형을 분석, 양 군 간에 비교하였다. 결과: TLR4 Asp299Gly 및 TLR9 -1237T/C 유전자형 분석을 시행한 크론병 환자 중 유전자 변이를 보인 환자는 없었다. 또한 TLR4 Thr399Ile 유전자형 분석을 시행한 모든 피험자에서도 유전자 변이는 확인되지 않았다. 결론: 이 연구 결과는 한국인에서 TLR4 및 TLR9의 주요 유전자 변이는 드물고, 또한 크론병 감수성과도 연관성이 없음을 시사한다. Background/Aims: Toll-like receptors (TLRs) serve as pattern recognition receptors that recognize specific molecular patterns of pathogens and can mediate the production of proinflammatory cytokines. Recently, TLRs have been identified as susceptibility genes for Crohn`s disease (CD) in several studies from Western populations. We investigated the association of genetic variations in TLR4 and TLR9 with CD in Korean population. Methods: In 380 CD cases and 380 healthy controls, we performed genotyping for TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791). The genetic variations in the TLR9-1237T/C (rs5743836) were also examined. Results: Among CD patients genotyped for TLR4 Asp299Gly and TLR9-1237T/C, none had variant alleles. Similarly, none of the subjects genotyped for TLR4 Thr399Ile showed genetic variations. Conclusions: Our results indicate that the major genetic variations in TLR4 and TLR9 are rare and may not be associated with susceptibility to CD in Koreans. (Korean J Gastroenterol 2009;54:377-383)

기획소화기 질환에서의 정맥영양공급

예병덕 ( Byong Duk Ye ) 대한소화기학회 2015 대한소화기학회지 Vol.65 No.6

Protein-calorie malnutrition and deficiencies of specific nutrients could commonly occur in various types of gastrointestinal diseases. These nutritional problems could delay recovery from diseases, resulting in increased morbidity and mortality, and impairment of quality of life. Parenteral nutrition (PN) is one of the methods of nutritional support through which macronutrients (glucose, amino acids, and triglycerides), micronutrients (vitamins and trace elements), water, and electrolytes are administered via peripheral or central venous route. PN could play an important role for patients for whom enteral/oral feeding is contraindicated or cannot meet the patients’ requirement for adequate nutrition due to anatomical and/or functional problems. Since insufficient and excessive PN supplement could both be harmful for patients, it is very important to adhere to correct indication, optimal timing, and dosage/composition of PN. In this article, the current role of PN for various gastrointestinal diseases will be reviewed and discussed. (Korean J Gastroenterol 2015;65:346-353)

크론병 치료 가이드라인

예병덕 ( Byong Duk Ye ),양석균 ( Suk Kyun Yang ),신성재 ( Sung Jae Shin ),이강문 ( Kang Moon Lee ),장병익 ( Byung Ik Jang ),천재희 ( Jae Hee Cheon ),최창환 ( Chang Hwan Choi ),김영호 ( Young Ho Kim ),이희영 ( Hee Young Lee ) 대한소화기학회 2012 대한소화기학회지 Vol.59 No.2

Crohn`s disease (CD) is a chronic inflammatory bowel disease (IBD) with uncertain etiopathogenesis. CD can involve any site of gastrointestinal tract from the mouth to anus and is associated with serious complications such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies are currently applied for diverse clinical situations of CD. However, a lot of decisions on the management of CD are made depending on the personal experiences and choices of physicians. To suggest preferable approaches to diverse problems of CD and to minimize the variations according to physicians, guidelines for the management of CD are needed. Therefore, IBD Study Group of the Korean Association for the Study of the Intestinal Diseases has set out to develop the guidelines for the management of CD in Korea. These guidelines were developed using the adaptation methods and encompass the treatment of inflammatory disease, stricturing disease, and penetrating disease. The guidelines also cover the indication of surgery, prevention of recurrence after surgery, and CD in pregnancy and lactation. These are the first Korean guidelines for the management of CD and the update with further scientific data and evidences is needed.

최신 연구 소개 : 염증성 장질환 환자에서 임신 중 Thiopurine 치료의 안전성

예병덕 ( Byong Duk Ye ) 대한소화기학회 2011 대한소화기학회지 Vol.58 No.1

Thiopurine은 염증성 장질환에 효과적이며 특히 스테로이드 투여 없이 장기 관해를 유지하고, 재발을 억제하는 효과가 있다. 임신 중 약물에의 노출은 저체중아, 선천성 기형 등의 우려를 낳게 하지만, 염증성 장질환 환자에서는 임신 중에도 thiopurine 등 적절한 약물 치료로 관해를 유지해야 염증성 장질환의 활성화로 인한 환자와 태아에의 악영향을 방지할 수 있다. 이전 동물 실험에서는 인체 투여량의 4-13배 thiopurine을 투여한 경우 태아의 선천성 기형이 증가하였지만, 인체 투여량 이내에서는 선천성 기형이 증가하지 않음을 보였다. 덴마크의 한 연구에서는 크론병 환자에서 thiopurine을 투여한 경우 선천성 기형이 9.7% 증가하였으나, 통계적으로 유의하지는 않았다고 보고된 바 있다. 그러나, 아직 임신 중 thiopurine의 안전성에 대한 증거는 부족한 실정이다. 이번 연구는 프랑스의 19,486명의 염증성 장질환 환자를 대상으로한 CESAME (Cancers Et Surrisque Associeaux Maladies inflammatoires intestinales En France) 연구 코호트 중 임신에 초점을 둔 코호트 내 연구(nested study)로, 204명 환자에서의 215번의 임신 결과를 평가하였다. 자료는 2005-2007년에 걸쳐 수집(2005년의 자료는 후향적 수집, 그 이후는 전향적 수집), 분석되었고, 204명 중 크론병이 155명(76%), 궤양성 대장염이 44명(21.5%), 미분류 염증성 장질환(IBD unclassified)이 5명(2.5%)이었으며, 대상군을 임신 중 thiopurine을 복용한 군(A군), 임신 중 thiopurine 이외의 약제를 투여 받은 군(B군), 및 임신 중 약제를 투여 받지 않은 군(C군)으로 분류하였다. 환자들의 임신 당시의 평균 연령은 28.3세였고, 평균 유병 기간은 6.7년이었다. 215회의 임신 중 138회의 생존 출산(live birth) (64.2%), 142명의 신생아(4명의 쌍생아 포함)가 있었고, 평균 체중은 3,135 g이었다. A, B, C 세군에서 생존 출산율(각각 64%, 66.6%, 60%), 조산(prematurity)율(21.8%, 16%, 14.8%), 신생아 평균 체중(3,114, 3,088, 3,289 g), 2,500 g 미만 저체중아 출산율(15.8%, 13.8%, 7.4%)은 차이가 없었다. 또한 선천성 기형 발생 빈도 역시 A, B, C군에서 각각 3.6% (2예 - bilateral cataract 1예, cervical angioma 1예), 7.1% (4예 - partial syndactyly 1예, Pierre Robin syndrome 1예, complex cardiac malformation 1예, omphalocele 1예) 및 0%로 차이를 보이지 않았다. 총 11예의 임신 관련 합병증(aspiration of meconium, umbilical artery thrombosis 등)이 발생하였고, A, B, C 각 군에서 각각 3, 5, 3예로 군 간 차이가 없었다. Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME study (Gut 2011;60:198-203)

점막하 종양의 형태로 나타난 식도결핵 1 예

예병덕(Byong Duk Ye),곽금연(Geum Youn Gwak),김원(Won Kim),박수철(Su Cheol Park),우열근(Yeol Keun Woo),이상협(Sang Hyub Lee),김병관(Byeong Gwan Kim),정현채(Hyun Chae Jung),송인성(In Sung Song),김우호(Woo Ho Kim) 대한소화기학회 2001 대한소화기학회지 Vol.38 No.3

Esophageal involvement of tuberculosis is rare. It is usually secondary to tuberculous infection of contiguous organs and most commonly presented as ulcerative lesion in esophagoscopy. This report describes the case of a 62-year-old woman who complained of dysphagia and left chest discomfort on swallowing foods. Initial esophagoscopy revealed submucosal tumor of esophagus, and surgical management was planned. But surgery was delayed, and in the meantime, the enlargement of left submandibular lymph node was detected. The aspiration cytology of lymph node revealed chronic granulomatous inflammation. Subsequently, standard anti-tuberculous drug therapy was started. Follow-up esophagoscopy showed decreased size of submucosal mass and the histologic examination of the lesion revealed chronic granulomatous inflammation. Based on this clinical course, the diagnosis of esophageal tuberculosis presented as submucosal tumor with tuberculous submandibular lymphadenopathy was made. We think that in the differential diagnosis of submucosal tumor of esophagus, tuberculous lesion should be included. (Korean J Gastroenterol 2001;38:203-206)