program (Abstract Book) - The 6th Korea

Transcription

Contents
Welcome Message
1
General Information
2
Organizing Committees
3
Invited Speakers and Chairpersons
4
Floor Plan
8
Scientific Program
10
Poster Round
12
Contents
18
Session1~7
31
Poster
61
Welcome Message
Dear Colleagues,
It is our great pleasure to announce the 6th Korea-Japan IBD Symposium on behalf of Japanese
Society for Inflammatory Bowel Disease (JSIBD) in Japan and Korean Association for the Study of Intestinal
Diseases (KASID) in Korea, which leads basic and clinical research in the field of IBD. As quite recent
memories, the 1st – 5th Japan-Korea IBD Symposiums have achieved serial great successes and contributed
not only to scientific progress in IBD but also to make a close relationship between the two countries.
The main theme of the 6th meeting is “Future for Lifelong Managment”, which intends to spread
updated knowledge in basic and clinical science of IBD. The scientific program will provide important aspect
to promote the pathophysiology and the new therapeutic strategy including surgical approach of IBD in the
oral and poster session. Thus we would strongly like to encourage young researchers to submit their recent
works and participate to the meeting, and to make fruitful discussion each other. Furthermore, as the first-time
experiment, this meeting will give another session to seek and discuss the best direction expanding to other
Asian countries.
We trust that you will find the science to be outstanding and the fellowship among the IBD community
strong in the meeting. The organizing committee has been seeking for opportunity to expand this meeting to
Asia. We believe this new change will further advance IBD society.
Looking forward to seeing you in Tokyo.
Sincerely yours,
Hyo Jong Kim, M.D.
Mamoru Watanabe, M.D.
President of KASID
President of the 6th KJIBD
1
The 6th Korea-Japan
IBD Symposium
General Information
■Title
The 6th Korea-Japan IBD Symposium
■DATE
Saturday, January 28, 2012
■VENUE
Keio Plaza Hotel Tokyo
2-2-1 Nishi-Shinjuku, Shinjuku-Ku, Tokyo, 160-8330 Japan
Tel: +81-3-3344-0111
URL: http://www.keioplaza.co.jp/
■LANGUAGE
Simultaneous translation for the Japanese and Korean languages
will be provided throughout the symposium sessions. All printed and
presentation materials will be in English.
■REGISTRATION
US$140.oo- or JPY10,000Registration fees must be paid in U.S. dollar or Japanese yen only on site.
Payments are made by accepted cash only. Credit cards are not accepted.
■ORGANIZED BY
Korean Association for the Study of Intestinal Diseases(KASID)
Japanese Society for Inflammatory Bowel Disease(JSIBD)
■SECRETARIAT
Makoto Naganuma, M.D., Ph.D
Division of Gastroenterology, School of Medicine
Tokyo Medical and Dental University
1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
TEL: +81-3-5803-5877 FAX: +81-3-5803-0268
e-mail: [email protected]
2
Organizing Committees
Korean Association for the
Study of Intestinal Diseases
Japanese Society for
Inflammatory Bowel Disease
President
Hyo Jong Kim
Toshifumi Hibi
Vice President
Suk-Kyun Yang
Geun Am Song
Mamoru Watanabe
Honorary Members
In Sung Song
Jin Hai Hyun
Kyu Yong Choi
Jin-Ho Kim
Won Ho Kim
Jae Hyun Choi
Hidenobu Watanabe
Hitoshi Asakura
Tetsuichiro Muto
Tsuneyoshi Yao
Secretary General
Joo Sung Kim
Takanori Kanai
Organizing Committee
Dong Soo Han
Yoon Tae Jeen
Hyun Soo Kim
Dong Il Park
Kyu Chan Huh
Hwang Choi
Sung-Ae Jung
Seung-Jae Myung
Cha Jae Myung
Toshiyuki Matsui
Takayuki Matsumoto
Haruhiko Ogata
Akira Sugita
Soichiro Miura
Iwao Sasaki
3
The 6th Korea-Japan
IBD Symposium
Invited Speakers and Chairpersons
■ Korea
Byong Duk Ye
University of Ulsan
Chang Hwan Choi
Chung-Ang University
Dong Il Park
Sung Kyun Kwan University
Geom-Seog Seo
Wonkwang University
Geun Am Song
Pusan National University
Hwang Choi
The Catholic University of
Korea
Hyo Jong Kim
Kyunghee University
Hyun Soo Kim
Chonnam National University
Jae Hee Cheon
Yonsei University
Jai Hyun Choi
Korea University
Jin-Ho Kim
University of Ulsan
Joo Sung Kim
Seoul National University
Kang-Moon Lee
Korea
Kyu Chan Huh
Konyang University
Kyu Joo Park
Seoul National University
College of Medicine
Kyu Yong Choi
Korea
Seung Jae Myung
University of Ulsan
Soohyun Kim
Konkuk University
Suk-Kyun Yang
University of Ulsan
Sung Ae Jung
Ewha Womans University
Won Ho Kim
Yonsei University
4
Young Ho Kim
Sungkyunkwan University
Young Sook Park
Eulji University
5
The 6th Korea-Japan
IBD Symposium
■ Japan
Akira Andoh
Shiga University of Medical
Science
Akira Sugita
Yokohama Municipal Hospital
Fumihito Hirai
Fukuoka University Chikushi
Hospital
Haruhiko Ogata
Keio University
Hideki Iijima
Osaka University
Hiroki Ikeuchci
Hyogo College of Medicine
Hiroshi Nakase
Kyoto University
Iwao Sasaki
Tohoku Graduate School of
Medicine
Kanna Nagaishi
Sapporo Medical University
Katsuyoshi Matsuoka
Keio University
Kazuichi Okazaki
Kansai Medical University
Kenji Watanabe
Osaka City University
Kiichiro Tsuchiya
Tokyo Medical and Dental
University
Kiyonori Kobayashi
Kitasato University
East Hospital
Mamoru Watanabe
University
Satoshi Motoya
Sapporo Kosei General
Hospital
Soichiro Miura
National Defense Medical
College
Takayuki Matsumoto
Hyogo College of Medicine
Takayuki Matsumoto
Kyushu University
Tetsuya Nakamura
University
Toshifumi Hibi
Keio University
6
Toshiyuki Matsui
Fukuoka University Chikushi
Hopsital
Yasuo Suzuki
Toho University Sakura
Hospital
Yutaka Kohgo
Asahikawa Medical University
■ Germany
Stefan Schreiber
Christian-Albrechts-University
7
Yoshihide Fujiyama
Shiga University of Medical
Science
The 6th Korea-Japan
IBD Symposium
Floor Plan
4F
調整室
なつめ
DR･B
かつら
みずき
キッチン
倉庫
花
クローク
クローク
宴会サロン
Ｇ
化粧室
Ｌ
Nishiki
キッチン
錦
January 27(Fri)
Welcome Party
化粧室
Ｌ
Ｇ
グ
ラ
ス
シ
ェ
ル
も
み
じ
けやき
かえで
扇
リ
フ
ト
カリヨン
5F
January 28 (Sat)
Poster Exhibition
Registration Desk
Head Office
リフト
化粧室
Ｇ
キッチン
コンコードボールルーム
Ｌ
Dahlia
ダリア
Concord
Ballroom
C
キッチン
クローク
化粧室
Ｌ
January 28(Sat)
Symposium
化粧室
Ｇ
Ｇ
Ｌ
エミネンスホール
カトレア
コスモス
ﾌﾟﾗｻﾞﾁｬﾍﾟﾙ
Eminence
Hall
アゼリア
リ
フ
ト
8
PC
Registration Desk
43F
クローク
スバル
コメット
Subaru
Commet
Cloak
化粧室
Rest room
Gents
Ladies
スターライト
Star
Light
Star light
Elevator
E le v a t o r
Elevator
ムーンライト
Moon light
January 28 (Sat)
Farewell Party
オリオン
Orion
9
The 6th Korea-Japan
IBD Symposium
Scientific Program
07:00 ~
08:00 - 08:10
Registration
Opening Remarks
Mamoru Watanabe (Tokyo Medical and Dental University)
Session 1. Topics for recent progress of basic research in IBD
Soichiro Miura (National Defense Medical College)
Chaired by
Won Ho Kim (Yonsei University)
08:10 - 08:30
Epithelial regeneration by cultured colonic cells expanded from a single adult Lgr5+ stem cell
Tetsuya Nakamura (Tokyo Medical and Dental University)
08:30 - 08:50
Paradoxical effects of human IL-32γ in transgenic mice during experimental colitis
Soohyun Kim (Konkuk University)
08:50 - 09:10
The role of oligosaccharide alterations in immunoglobulins of inflammatory bowel diseases
Hideki Iijima (Osaka University Graduate School of Medicine)
09:10 - 09:30
The effect of sleep deprivation and melatonin treatment on inflammatory bowel disease
Young Sook Park (Eulji University)
Session 2. Lymphoproliferative disorders in IBD
Yutaka Kohgo (Asahikawa Medical University)
Chaired by
Geun Am Song (Pusan National University)
09:30 - 09:50
Lymphoproliferative disorders in the Japanese patients with inflammatory bowel disease
Kazuichi Okazaki (Kansai Medical University)
09:50 - 10:10
Inflammatory bowel disease and limphoproliferative disorders: a Korean multicenter expericne
Byong Duk Ye (University of Ulsan College of Medicine)
Session 3. How to use new devices for diagnose in IBD
Toshiyuki Matsui (Fukuoka University Chikushi Hopsital)
Chaired by
Jin-Ho Kim (University of Ulsan)
10:10 - 10:30
How to use new devices for the diagnosis and treatment of IBD
Takayuki Matsumoto(Kyushu University)
10:30 - 10:50
Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)
Expression and Endoscopic Activity in Inflammatory Bowel Diseases
Jae Hee Cheon (Yonsei University College of Medicine)
Session 4. Recent progress of Surgical Treatment in IBD
Iwao Sasaki (Tohoku Graduate School of Medicine)
Chaired by
Kyu Yong Choi (The Catholic University of Korea)
10:50 - 11:10
Surgery for gastroduodenal Crohn’s disease
Akira Sugita (Yokohama Municipal Hospital)
11:10 - 11:30
Ileal Pouch Anal Anastomosis for Ulcerative Colitis: Management of Complications Related
to Surgery and the Pouch
Kyu Joo Park (Seoul National University College of Medicine)
Session 5. Best Poster Presentation & Poster Round
Yoshihide Fujiyama (Shiga University of Medical Science)
Chaired by
Jai Hyun Choi (Korea University)
11:30 - 11:45
Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells
Kanna Nagaishi (Sapporo Medical University)
11:45 - 12:00
Promoter polymorphism of the EED gene is associated with the susceptibility to ulcerative colitis
Geom-Seog Seo (Wonkwang University)
10
12:00 - 12:50
Chaird by
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
Group 7
Group 8
Group 9
Group 10
Group 11
Group 12
Group 13
Group 14
Group 15
Haruhiko Ogata (Keio University)
Hwang Choi
(The Catholic University of Korea)
Sung Ae Jung (Ewha Womans University)
Satoshi Motoya (Sapporo Kosei General Hospital)
Hyun Soo Kim (Chonnam National University)
Kyu Chan Huh (Konyang University)
Hiroki Ikeuchci (Hyogo College of Medicine)
Fumihito Hirai (Fukuoka University Chikushi Hospital)
Dong Il Park
(Sung Kyun Kwan University)
Kenji Watanabe (Osaka City University)
Kiyonori Kobayashi (Kitasato University East Hospital)
Seung Jae Myung (University of Ulsan)
Akira Andoh (Shiga University of Medical Science)
Joo Sung Kim (Seoul National University)
Kiichiro Tsuchiya (Tokyo Medical and Dental University)
Luncheon Satellite Symposium
Chaired by
Mamoru Watanabe (Tokyo Medical and Dental University)
12:50 - 13:45
New treatments for IBD after anti-TNF
Stefan Schreiber (Christian-Albrechts-University)
Session 6. Recent trends of medical treatments in Japan and Korea
Yasuo Suzuki (Toho University Sakura Hospital)
Chaired by
Suk-Kyun Yang (University of Ulsan)
Key lecture
13:45 - 14:05
Use of Tacrolimus and Infliximab for Refractory Ulcerative Colitis.
Hiroshi Nakase (Kyoto University)
14:05 - 14:25
The efficacy and safety of infliximab therapy in Korean patients with crohn's diseases: a
retrospective, multicenter study
Chang Hwan Choi (Chung-Ang University College of Medicine)
Case-presentation
Management of post-operative Crohn's disease.
14:25 - 14:50
Katsuyoshi Matsuoka (Keio University)
14:50 - 15:15
A case of acute severe ulcerative colitis
Kang-Moon Lee (The Catholic University of Korea)
Session 7. How to establish Asian consensus and guideline in IBD ?
Toshifumi Hibi (Keio University)
Chaired by
Hyo Jong Kim (Kyunghee University)
15:15 - 15:30
How to establish Asian consensus and guideline in IBD ?
Takayuki Matsumoto (Hyogo College of Medicine)
15:30 - 15:45
Young Ho Kim (Sungkyunkwan University)
15:45 - 16:00
Discussion
16:00 - 16:10
Closing Remarks
Hyo Jong Kim (President of KASID)
11
The 6th Korea-Japan
IBD Symposium
Poster Round
Group 1. Clinical 1
Chaired by
Haruhiko Ogata (Keio University)
Poster No.
1
2
3
Efficacy of the first infliximab administration predicts long-term prognosis in refractory
ulcerative colitis
Hiroki Tanaka (Sapporo Kosei General Hospital)
Therapeutic efficacy of infliximab in the treatment of steroid-resistant or -dependent
ulcerative colitis
Motochika Yasaka (Fukuoka University Chikushi Hospital)
Efficacy of Infliximab Rescue Therapy in Hospitalized Patients with Steroid-Refractory
Ulcerative Colitis: Single Center Experience
Choul Ki Park (Kyung Hee University School of Medicine)
4 The experience of infliximab for Ulcerative colitis in Korea.
Hyun Il Seo (Sungkyunkwan University School of Medicine)
5
6
A case of new-onset ulcerative colitis in a patient with ankylosing spondylitis during
infliximab treatment; paradoxical reaction of anti-TNF α or not?
Yong Sung Choi (Daehang Hospital)
Efficacy of a probiotic preparation(VSL#3) in the patients with ulcerative colitis and its
effect on the cytokines
Gyoo Moon (Hanam Song Do Colorectal Hospital)
Group 2. Clinical 2
Chaired by
Hwang Choi (The Catholic University of Korea)
Poster No.
7
Safety and feasibility of daily granulocyte and monocyte apheresis in patients with active
ulcerative colitis: a prospective study
Takayuki Yamamoto (Yokkaichi Social Insurance Hospital)
Safety and efficacy of high-dose, 4.0 g/day mesalazine therapy for patients with ulcerative
8 colitis who relapsed under low-dose, 1.5-2.25 g/day maintenance therapy: a prospective
study
9
10
11
Mucosal healing in patients with active ulcerative colitis during granulocyte and monocyte
apheresis therapy: a prospective cohort study
Intensive, Daily Granulocyte and Monocyte Adsorptive Apheresis in Patients with Active
Ulcerative Colitis.
Aki Aisaka (Tokyo Women's Medical University Hospital)
Pneumocystis jiroveci pneumonia after initiation of infliximab therapy in a patient with
ulcerative colitis
Bo Sung Kwon (Korea University College of Medicine)
Group 3. Clinical 3
Chaired by
Sung Ae Jung (Ewha Womans University)
Poster No.
12
13
Anti-viral therapy is not necessarily indicated in ulcerative colitis patients with
cytomegalovirus infection detected by immunohistochemistry
Yuriko Maruyama (Keio University)
Appendiceal orifice inflammation may precede development of ulcerative colitis: Analysis
of 20 patients
Sang Hyoung Park (University of Ulsan College of Medicine)
12
14
Clinical courses of chronic hepatitis B virus infection and inflammatory bowel disease in
patients with both diseases
Sang Hyoung Park (University of Ulsan College of Medicine)
15 A Case of Pustular Psoriasis Induced by Infliximab Treatment for Ulcerative Colitis
Kyoung-Joo Kwon (Ewha Womans University School of Medicine)
16
A Case of squamous cell carcinoma of the breast in a patient with Crohn’s disease taking
azathioprine
Kyoung Chan Park (Catholic University of Daegu)
Group 4. Clinical 4
Chaired by
Satoshi Motoya (Sapporo Kosei General Hospital)
Poster No.
17
Improvement of bowel stenosis in Crohn’s disease after treatment with steroid combined
infliximab
Keisuke Hasui (Hirosaki University Granduate School of Medice)
18 Clinical and endoscopic efficacy of Adalimumab in patients with Crohn’s Disease
Noriko Kamata (Osaka City University Graduate School of Medicine)
19 Infliximab for Steroid-Dependent Hemorrhagic Crohn’s Disease
Jae Myung Cha (Kyung Hee University Hospital)
20
The immunoassay for the accurate determination of antibodies to infliximab in Crohn’s
Disease.
Hirotsugu Imaeda (Shiga University of Medical Science)
21 Clinical usefulness of serum IL-32 in Crohn's disease: preliminary results
Eun Ran Kim (Sungkyunkwan University)
22 A case of the fistulizing enterovesical Crohn’s disease treated with Infliximab
Hoon Sup Koo (Konyang University Hospital)
Group 5. Clinical 5
Chaired by
Hyun Soo Kim (Chonnam National University)
Poster No.
23
24
25
26
27
Monitoring 6-thioguanine nucleotide concentrations in Japanese children and adolescents
with inflammatory bowel disease
Yoshikazu Ohtsuka (Juntendo University Graduate School of Medicine)
Can a gradual dose increment policy reduce azathioprine-induced bone marrow toxicity? :
A multicenter retrospective analysis
Suck-Ho Lee (Soonchunhyang University)
Acute myelomonocytic leukemia following treatment of Crohn’s disease with
6-mercaptopurine: a case report
Hee Jae Hyun (Kyung Hee University School of Medicine)
Increased rates of early adverse reaction to azathioprine in patients with inflammatory
bowel disease compared to autoimmune hepatitis
Dong Choon Kim (Keimyung University School of Medicine)
Incidence of Extraintestinal Malignancies in a Single-Center Inflammatory Bowel Disease
Population in Korea
Soo-Kyung Park (University of Ulsan College of Medicine)
28 Extensive Arterial and Venous Thrombosis in Patient with Ulcerative Colitis
Hyun-Soo Kim (Chonnam National University Medical School)
13
Group 6. Clinical 6
Chaired by
Kyu Chan Huh (Konyang University)
Poster No.
29
Development of liver cirrhosis and massive variceal bleeding in a patient with refractory
Crohn’s disease
Kyoung Sup Hong (Seoul National University College of Medicine)
30 Portal pylephlebitis as a complication of paediatric Crohn’s disease: a case report
Eun Yeong Kim (Kyung Hee University School of Medicine)
31
Hemophagocytic lymphohistiocytosis in a Crohn’s disease patient who recovered by IV
gamma-immunoglobulin.
Hyo Keun Jeon (Yonsei University Wonju College of Medicine)
32 EBV-associated lymphoproliferative disorders misdiagnosed with Crohn’s disease
Hee Kyong Na (University of Ulsan College of Medicine)
33
34
Clinical characteristics of the cancer patients who occurred the rectum and anal canal
associated with Crohn’s disease in Japanese cases
Takeshi Ueda (Nara Medical University)
A case of Crohn’s colitis-associated rectal cancer following after sporadic adenocarcinoma
in adenoma.
Hiroshi Takeyama (Osaka University Graduate School of Medicine)
Group 7. Clinical7
Chaired by
Hiroki Ikeuchci (Hyogo College of Medicine)
Poster No.
35 Surgery for ulcerative colitis in elderly patients.
Hiroki Ikeuchi (Hyogo College of Medicine)
36
37
Impact of level of mucosal proctectomy on outcome of ileal pouch–anal anastomosis for
ulcerative colitis
Toshimitsu Araki (Mie University Graduate School of Medicine)
The impact of Anti TNF-α Agents with Operative Treatment for Crohn’s Anorectal Fistula
–Aim to introduce the deep remission of fistulaNaoto Saigusa (Yokoyama Hospital )
38 A case of an ulcerative colitis patient with enterocutaneous fistula and abscess
You Sun Kim (Inje University College of Medicine)
39
The value of concomitant endoscopic balloon dilation for intestinal stricture during long term infliximab therapy in patients with Crohn’s disease
Yoichiro Ono (Fukuoka University Chikushi Hospital)
Group 8. Clinical 8
Chaired by
Fumihito Hirai (Fukuoka University Chikushi Hospital)
Poster No.
40
41
42
Emerging trends in the incidence and prevalence of inflammatory bowel disease:
experience from a single center
Haruhiko Takahashi (Fukuoka University Chikushi Hospital)
Clinical Significance of Fecal Leukocyte, Lactoferrin, and Calprotectin in Moderate to
Severe Acute Diarrhea
Hae Mi Lee (The Catholic University of Korea)
The Usefulness of C-reactive Protein as a Disease Activity Marker in Crohn’s Disease
According to the Location of Disease
Dong-Hoon Yang (University of Ulsan College of Medicine)
43 Long-term prognosis of jejunal involvement of Crohn’s disease
Soo-Kyung Park (University of Ulsan College of Medicine)
14
44
Increased risk of gallstone disease among people with inflammatory bowel disease: a
population-based retrospective cohort study
Chien-Chang Liao (Taipei Medical University)
45 CANCEL
Group 9. Clinical 9
Chaired by
Dong Il Park (Sung Kyun Kwan University)
Poster No.
46 Growth disturbance in Japanese children with IBD
Toshiaki Shimizu (Juntendo University Graduate School of Medicine)
47 Increased Risk of Hip Fracture in People With Inflammatory Bowel Disease
Yi-Chun Chou (China Medical University Hospital)
48
49
50
51
The Seasonality in Flares of Korean Patients with Inflammatory Bowel Disease: a
Multicenter Study
Dong Il Park (Sungkyunkwan University School of Medicine)
Comorbidity of depression and anxiety in inflammatory bowel disease and its relationship
with disease status in Korea
Chang Sup Lim (Kosin University College of Medicine)
How are thiopurines dosed in Crohn’s disease? : A novel strategy, maximum dose-titration
based on the lower limit of leukocyte count and tolerability
Importance of early inflammatory bowel disease: long diagnostic time lag and prior
frequent operation in tuberculosis-high risk country
Group 10. Clinical 10
Chaired by
Kenji Watanabe (Osaka City University)
Poster No.
52
53
54
55
56
Questions about Crohn’s Disease by Patients: Survey of the Question and Answer in the
Homepage of Crohns’ Disease Fellow Asociation
Kyeong Ok Kim (Yeungnam University College of Medicine)
The Change of the Diagnosis in Crohn’s Disease and Intestinal Tuberculosis According to
the Endoscopic Scoring System and Short Term anti-tuberculosis Medication Challenge.
Kyeong Ok Kim (Yeungnam University College of Medicine)
Diagnostic role of CT enterography differentiating Crohn’s disease from intestinal
tuberculosis
Yoon Hea Park (Yonsei University College of Medicine)
Crohn’s Disease and Intestinal Behcet’s Disease: A Comparison of the Long-term Clinical
Outcomes
Yoon Suk Jung (Yonsei University College of Medicine)
Correlations between endoscopic severity and the clinical disease activity index in
intestinal Behcet’s disease
Hyun Jung Lee (Yonsei University College of Medicine)
57 Ulcerative colitis patients should be instructed to conceive while in remission.
Masaki Ujihara (Nagoya University Graduate School of Medicine)
Group 11. Clinical 11
Chaired by
Kiyonori Kobayashi (Kitasato University East Hospital)
Poster No.
58 Treatment Outcomes of Tacrolimus in Patients with Ulcerative Colitis
Miyuki Mukae (Kitasato University East Hospital)
59 Efficacy of oral tacrolimus and infliximab in the treatment of active ulcerative colitis.
Kouichi Asano (Kyushu University Hospital)
15
60 Nutritional Status Assessment of Newly-diagnosed Inflammatory Bowel Disease patients
Min Ji Lee (Sungkyunkwan University School of Medicine)
61
62
The Cap Assisted Technique Enhances the Colonoscopy Training; Prospective Randomised
Study of Six Trainees.
Sang Man Park (Kyungpook National University School of Medicine)
A Case of Soft Tissue Abscess Caused by Salmonella Serotype D in a Patient Presenting
As Acute Colitis
Eun Mi Song (Ewha Womans University School of Medicine)
63 The outcome and interval between colonoscopy after a negative colonoscopy
Won Kyung Yoon (Kyungpook National University Hospital)
Group 12. Basic 1
Chaired by
Seung Jae Myung (University of Ulsan)
Poster No.
64
65
66
67
Autophagy upregulates CXCL10 in primary intestinal epithelial cells stimulated by Flagellin
via TLR5 on basolateral membrane.
Xiu Zheng (Tokyo Medical and Dental University)
Hes1 promotes IL-22-mediated epithelial regeneration through enhancement of STAT3dependent transcription in human intestinal epithelial cells.
Tatsuro Murano (Tokyo Medical and Dental University)
Notch-Hes1 pathway and TNF-α synergistically up-regulates OLFM4 expression in the
inflamed mucosa of the human intestine
Ryuichi Okamoto (Tokyo Medical and Dental University)
Overexpression of Smad2/3, phosphorylated at specific linker threonine residues, in the
murine model of Dextran Sodium Sulfate-Induced Colitis
Masanobu Kishimoto (Kansai Medical University)
68 The novel host-probiotics interaction through activation of intestinal epithelial autophagy
Yuhei Inaba (Asahikawa Medical College)
69 A protective effect of vitamin C on DSS-induced colitis
Jong Pil Im (Seoul National University College of Medicine)
Group 13. Basic 2
Chaired by
Akira Andoh (Shiga University of Medical Science)
Poster No.
70
71
Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran
sodium sulfate induced colitis
Akiko Kurishima (Kansai Medical University)
Intestinal CXCR4+IgG+ Immature Plasma Cells Contribute to the Pathogenesis of Ulcerative
Colitis through IgG-Immune Complex-FcγR Signaling
Tadakazu Hisamatsu (Keio University School of Medicine)
72 Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells
Kanna Nagaishi (Sapporo Medical University)
73
74
Association between red cell distribution width and disease activity in patients with
inflammatory bowel disease
Chang Seok Song (Sungkyunkwan University School of Medicine)
Novel Guggulsterone Derivative GG-52 Inhibits NF-κB Signaling in Bone Marrow-Derived
Dendritic Cells and Attenuates Colitis in IL-10 Deficient Mice
Seung Joo Kang (Seoul National University College of Medicine)
75 Adipose Tissue-Derived Stem Cell Attenuate Colitis in Interleukin-10 Knockout Mice.
Byung Ik Jang (Yeungnam University College of Medicine)
16
Group 14. Basic 3
Chaired by
Joo Sung Kim (Seoul National University)
Poster No.
76
77
78
Intravital assessment of infliximab efficacy in murine ulcerative colitis model using two
photon laser scanning microscopy
Kohei Matsushita (Mie University Graduate School of Medicine)
Glutamine induces intestinal epithelial heat shock response via HSF-1 activation by
polyamines
Toshio Sakiyama (Kagoshima University Graduate School of Medical and Dental Sciences)
Macrophages pre-exposed to heat-killed feces show hyporesponsiveness to mRNA
expression of inflammatory cytokines induced by fatty acids exposure.
Chie Kurihara (National Defense Medical College)
79 Are PPIs Associated with Increased Intraepithelial Lymphocytes in the Colon?
Yeon Hwa Yu (Hanyang University College of Medicine)
80 Restraint Stress Induces and Exacerbates Intestinal Inflammation in IL-10 Deficient Mice
Seong-Joon Koh (Seoul National University College of Medicine)
81
Glutinous rice extract suppresses LPS-induced proinflammatory mediator expression via
blockage of NF-κB activation in intestinal epithelial cells
Young-Eun Joo (Chonnam National University Medical School)
Group 15. Basic 4
Chaired by
Kiichiro Tsuchiya (Tokyo Medical and Dental University)
Poster No.
82
The role of SERPINB1 (monocyte neutrophil elastase inhibitor) in the pathogenesis of
ulcerative colitis
Kazuhiro Kamada (Kyoto Prefectural University of Medicine)
83 Aberrant DNA methylation of FBN2 and TCERG1L genes in Ulcerative Colitis Patients
Tae-Oh Kim (Inje University Colledgel of Medicine)
84
85
86
Promoter polymorphism of the EED gene is associated with the susceptibility to ulcerative
colitis
Geom-Seog Seo (Wonkwang University)
Terminal restriction fragment length polymorphism analysis of the diversity of fecal
microbiota in patients with inflammatory bowel disease and irritable bowel syndrome
Bong Ki Cha (Chung-Ang University College of Medicine)
The Study of Gene Expression Induced by Sleep Deprivation and Melatonin Treatment on
DSS Induced Colitis Mice.
Sang Soo Kim (Eulji University)
17
The 6th Korea-Japan
IBD Symposium
Contents
■ SESSION
Session 1 Topics for recent progress of basic research in IBD
1 Epithelial regeneration by cultured colonic cells expanded from a single adult Lgr5+ stem cell
Tetsuya Nakamura M.D., Ph.D.
33
2 Paradoxical effects of human IL-32γ in transgenic mice during experimental colitis
34
3 The role of oligosaccharide alterations in immunoglobulins of inflammatory bowel diseases
36
4 The effect of sleep deprivation and melatonin treatment on inflammatory bowel disease
38
Session 2 Lymphoproliferative disorders in IBD
1 Lymphoproliferative disorders in the Japanese patients with inflammatory bowel disease
40
Soohyun Kim PhD.
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology,
Konkuk University, Seoul, 143-701 Korea;
Hideki Iijima, MD, PhD, Assistant professor
Department of Gastroenterology and Hepatology,
Osaka University Graduate School of Medicine, Suita, Osaka, Japan
YOUNG SOOK PARK
Department of Gastroenterology, Eulji University, Eulji Medical Center, Seoul, Korea
Kazuichi Okazaki, Norimasa Fukata
Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
2 Inflammatory bowel disease and limphoproliferative disorders: a Korean multicenter expericne
Byong Duk Ye, M.D., Ph.D.
Department of Gastroenterology, University of Ulsan College of Medicine,
Asan Medical Center, Seoul, Korea
Session 3 How to use new devices for diagnose in IBD
1 How to use new devices for the diagnosis and treatment of IBD
Takayuki Matsumoto
Department of Medicine and Clinical Science, Graduate School of Medical Sciences,
Kyushu University
2 Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)
Expression and Endoscopic Activity in Inflammatory Bowel Diseases
Jae Hee Cheon MD., PhD.
Department of Internal Medicine and Institute of Gastroenterology,
Yonsei University College of Medicine, Seoul, Korea
Session 4 Recent progress of Surgical Treatment in IBD
1 Surgery for gastroduodenal Crohn’s disease
Akira Sugita*, Kazutaka Koganei*, Kenji Tatsumi*, Ryo Futatsuki*, Hirosuke Kuroki*,
Sayumi Nakao*, Katsuhiko Arai*, Hideaki Kimura**, Fumihiko Kito*, Tsuneo Fukushima***
Department of Surgery, Yokohama Municipal Hospital*
Inflammatory Bowel Center, Yokohama City University Hospital**
Matsushima Clinic***
2 Ileal Pouch Anal Anastomosis for Ulcerative Colitis: Management of Complications Related to
Surgery and the Pouch
Kyu Joo Park, M.D.
Division of Colorectal Surgery
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
18
42
43
44
45
46
Session 5 Best Poster Presentation
1 Pleiotropic Action1 of Gut Tropic Factors
Derived from 3Conditioned Mesenchymal
Stem Cells2
2
2
48
2 Promoter polymorphism of the EED gene is associated with the susceptibility to ulcerative
colitis
49
Kanna Nagaishi , Shuhei Watanabe , Yasuyoshi Naishiro , Kentaro Yamashita , Yoshiaki Arimura ,
Mineko Fujimiya1, Yasuhisa Shinomura2, Kohzoh Imai4
1
Second Department of Anatomy, Sapporo Medical University
2
First Department of Internal Medicine, Sapporo Medical University
3
Department of Educational Development, Sapporo Medical University
4
Division of Novel Therapy for Cancer, Advanced Clinical Research Center, Institute of Medical
Science, University of Tokyo
Geom-Seog Seo,* Suck-Chei Choi,* Ki-Jung Yun,† Soo-Cheon Chae† *†Digestive Disease Research Institute, Department of Internal Medicine,* Pathology,† School of
Medicine, Wonkwang University, Iksan, Chonbuk 570-749, South Korea Luncheon Satellite Symposium
1 New treatments for IBD after anti-TNF
50
Session 6 Recent trends of medical treatments in Japan and Korea
1 Use of Tacrolimus and Infliximab for Refractory Ulcerative Colitis.
52
Stefan Schreiber
Christian-Albrechts-University, Kiel
Hiroshi Nakase, Tsutomu Chiba
Department of Gastroenterology and Hepatology, Endoscopic Medicine, Kyoto University.
2 The efficacy and safety of infliximab therapy in Korean patients with crohn’s diseases:
a retrospective, multicenter study
54
3 Management of post-operative Crohn's disease.
56
4 A case of acute severe ulcerative colitis
57
Chang Hwan Choi, M.D., In Do Song, M.D., Se Kyung Chang, M.D., Young Ho Kim, M.D.*,
Won Ho Kim, M.D.**, IBD study group of the Korean Association for the Study of the Intestinal
Diseases
Department of Internal Medicine, Chung-Ang University College of Medicine, *Sungkyunkwan
University College of Medicine, **Yonsei University College of Medicine, Seoul, Republic of Korea
Katsuyoshi Matsuoka, M.D., Ph.D.
Div. of Gastroenterology and Hepatology,
Dept. of Internal Medicine, School of Medicine Keio University
Kang-Moon Lee, M.D.
Department of Internal Medicine, College of Medicine, The Catholic University of Korea
Session 7 How to establish Asian consensus and guideline in IBD ?
1 How to establish Asian consensus and guideline in IBD ?
58
2 How to establish Asian consensus and guideline in IBD ?
59
Takayuki Matsumoto
Department of Lower Gastroenterology, Hyogo College of Medicine.
Young-Ho Kim
Division of Gastroenterology, Samsung Medical Center,
Sungkyunkwan University School of Medicine
19
The 6th Korea-Japan
IBD Symposium
■ POSTER
P-1 Efficacy of the first infliximab administration predicts long-term prognosis in refractory
ulcerative colitis
63
P-2 Therapeutic efficacy of infliximab in the treatment of steroid-resistant or -dependent
ulcerative colitis
64
P-3 Efficacy of Infliximab Rescue Therapy in Hospitalized Patients with Steroid-Refractory
Ulcerative Colitis: Single Center Experience
65
P-4 The experience of infliximab for Ulcerative colitis in Korea
66
P-5 A case of new-onset ulcerative colitis in a patient with ankylosing spondylitis during
infliximab treatment; paradoxical reaction of anti-TNF α or not?
67
P-6 Efficacy of a probiotic preparation(VSL#3) in the patients with ulcerative colitis and its
effect on the cytokines
1
2
2
2
68
P-7 Safety and feasibility of daily granulocyte and monocyte apheresis in patients with active
ulcerative colitis: a prospective study
69
P-8 Safety and efficacy of high-dose, 4.0 g/day mesalazine therapy for patients with ulcerative
colitis who relapsed under low-dose, 1.5-2.25 g/day maintenance therapy:
a prospective study
70
P-9 Mucosal healing in patients with active ulcerative colitis during granulocyte and
monocyte apheresis therapy: a prospective cohort study
71
Hiroki Tanaka, Satoshi Motoya, Masaki Yamashita, Akimichi Imamura
Inflammatory Bowel Disease Center, Sapporo Kosei General Hospital, Sapporo, Japan
Motochika Yasaka, Fumihito Hirai, Noritaka Takatsu, Takashi Hisabe, Toshiyuki Matsui
Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
Choul Ki Park, MD, Hee Jae Hyun, MD, Eun Yeong Kim, MD, Chang Kyun Lee, MD,
Hyo Jong Kim, MD
Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University School
of Medicine, Seoul, Korea
Hyun Il Seo MD, Dong Il Park PhD
Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Yong Sung Choi M.D., Jong Kyu Kim M.D., Jung Pil Suh M.D., Suk Hee Lee M.D.**,
In Taek Lee M.D. *,
Department of Gastroenterology, Department of Surgery*, Department of Pathology**,
Daehang Hospital, Seoul, Korea
Gyoo Moon, M.D. ; Ji Hyun Lee, M.D. ; Hyeok Jin,Kwon, M.D. ; Woo Jin Jung, M.D. ;
Pyoung Ju Seo, M.D.2; Lee, Ju Hyeong3
1
Department of Gastroenterology, Hanam Song Do Colorectal Hospital, Hanam, Korea,
Republic of.
2
Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea, Republic of.
3
Songdo Biocell Research institute, Seoul, Korea, Republic of.
Takayuki Yamamoto, Satoru Umegae, Koichi Matsumoto
Inflammatory Bowel Disease Center, Yokkaichi Social Insurance Hospital
20
P-10 Intensive, Daily Granulocyte and Monocyte Adsorptive Apheresis in Patients with Active
Ulcerative Colitis.
72
P-11 Pneumocystis jiroveci pneumonia after initiation of infliximab therapy in a patient with
ulcerative colitis 1
1
1
1
1
73
P-12 Anti-viral therapy is not necessarily indicated in ulcerative colitis patients with
cytomegalovirus infection
detected by immunohistochemistry
1)
1)
2)
1)
74
P-13 Appendiceal orifice inflammation may precede development of ulcerative colitis:
Analysis of 20 patients
‡
75
P-14 Clinical courses of chronic hepatitis B virus infection and inflammatory bowel disease in
patients with both diseases
76
P-15 A Case of Pustular Psoriasis Induced by Infliximab Treatment for Ulcerative Colitis
77
P-16 A Case of squamous cell carcinoma of the breast in a patient with Crohn’s disease taking
azathioprine
78
Aisaka Aki, Iiduka Bunei, Ayumi Ito, Emiko Nakao, Teppei Omori, Maria Yonezawa,
Shiratori Keiko
IBD Center of Tokyo Women’s Medical University Hospital, Tokyo, Japan.
Bo Sung Kwon , Ja Seol Koo , Jae-Won Yun , Jong Jin Hyun , Sung Woo Jung ,
Dae Won Park2, Hyung Joon Yim1, Sang Woo Lee1, Jai Hyun Choi1
1
Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
2
Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
Yuriko Maruyama , Katsuyoshi Matsuoka , Yasushi Iwao , Tomoharu Yajima ,
Nagamu Inoue1), Tadakazu Hisamatsu1), Tomohisa Sujino1), Kaoru Takabayashi1),
Kazuaki Yoneno1), Yohei Mikami1), Jun Miyoshi1), Shinta Mizuno1), Kayoko Kimura1),
Takanori Kanai1), Haruhiko Ogata3), Makio Mukai4), Toshifumi Hibi1)
1)
Division of Gastoenterology, Department of Internal Medicine, School of Medicine,
Keio University, Tokyo
2)
Center for Preventive medicine, Keio University Hospital, Tokyo
3)
Center for Endoscopic examination, Keio University Hospital, Tokyo
4)
Division of Diagnostic Pathology, Keio University Hospital, Tokyo
Sang Hyoung Park, MD,* Suk-Kyun Yang, MD,* Mi-Jung Kim, MD,
Dong-Hoon Yang, MD,*Kee Wook Jung, MD,* Kyung Jo Kim, MD,* Byong Duk Ye, MD,*
Jeong-Sik Byeon, MD,* Seung-Jae Myung, MD,* Jin-Ho Kim MD*, Yun Kyung Cho, RN*
*Department of Gastroenterology,
‡Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, Korea
Sang Hyoung Park, MD, Suk-Kyun Yang, MD, Young-Suk Lim, MD, Ju Hyun Shim, MD,
Dong-Hoon Yang, MD, Kee Wook Jung, MD, Kyung Jo Kim, MD, Byong Duk Ye, MD,
Jeong-Sik Byeon, MD, Seung-Jae Myung, MD, Jin-Ho Kim MD, Eun Ja Kwon, RN,
Ji Young Park, RN
Kyoung-Joo Kwon, Sung-Ae Jung, Seong-Eun Kim, Ki-Nam Shim, Hye-Won Kang,
Eun-Mi Song,Ju-Young Choi, Hye-Kyung Jung, Tae-Hun Kim, Kwon Yoo, Il-Hwan Moon
Department of Internal Medicine, Ewha Medical Research Institute,
Ewha Womans University School of Medicine, Seoul, Korea
Kyoung Chan Park, Kyung Ho Ha, Jin Tae Jung, Joong Goo Kwon, Eun Young Kim.
Departments of Internal Medicine, Catholic University of Daegu, School of Medicine,
Daegu, Korea
21
P-17 Improvement of bowel stenosis in Crohn’s disease after treatment with steroid combined
infliximab
79
P-18 Clinical and endoscopic efficacy
of Adalimumab in patients
with Crohn’s Disease
1
1
80
P-19 Infliximab for Steroid-Dependent Hemorrhagic Crohn’s Disease
81
P-20 The immunoassay for the accurate determination of antibodies to infliximab in Crohn’s
Disease.
*
**
*
*
*
82
P-21 Clinical usefulness of serum IL-32 in Crohn's disease: preliminary results
83
P-22 A case of the fistulizing enterovesical Crohn’s disease treated with Infliximab
84
P-23 Monitoring 6-thioguanine nucleotide concentrations in Japanese children and
adolescents with inflammatory
bowel2disease 1
1
1
1
85
P-24 Can a gradual dose increment policy reduce azathioprine-induced bone marrow
toxicity? : A multicenter
retrospective analysis
1
2
3
86
KEISUKE HASUI, YOH ISHIGURO, HIROTAKE SAKURABA, SHINSAKU FUKUDA,
DEPARTMENT OF GASTROENTEROLOGY AND HEMATOLOGY
HIROSAKI UNIVERSITY GRADUATE SCHOOL OF MEDICINE, HIROSAKI, JAPAN
Noriko Kamata, M.D., Ph.D. , Kenji Watanabe, M.D., Ph.D. , Hisotsugu Imaeda, M.D., Ph.D.2,
Akira Andoh, M.D., Ph.D.2, Kenichi Morimoto, M.D., Ph.D.1, Atsushi Noguchi, M.D., Ph.D.1,
Mitsue Sogawa, M.D., Ph.D.1, Hirokazu Yamagami, M.D., Ph.D.1,
Tetsuo Arakawa, M.D., Ph.D.1
Department of Gastroenterology
1
Osaka City University Graduate School of Medicine, Japan,Department of Medicine,
2
Shiga University of Medical Science, Japan
Jae Myung Cha, Joung Il Lee, Kwang Ro Joo, Hyun Phil Shin, Jae Jun Park, Jung Won Jeon,
Jun Uk Lim, Kyuseong Lym
Department of Gastroenterology, Kyung Hee University Hospital at Gang Dong,
149 Sangil-dong, Gangdong-gu, Seoul 134-727,Republic of Korea
Hirotsugu Imaeda , Akira Andoh , Hiromitsu Ban , Shigeki Bamba , Masaya Sasaki ,
Tomoyuki Tsujikawa* and Yoshihide Fujiyama*
*
Division of Gastroenterology, Shiga University of Medical Science,
**
Division of Mucosal Immunology, Graduate School of Medicine,
Shiga University of Medical Science, Otsu, Japan.
Eun Ran Kim, Sung Noh Hong*, Soo-Hyun Kim**, Young-Ho Kim,
KASID IBD Study Group***
Department of Internal Medicine, Sungkyunkwan University, School of Medicine,
Seoul, Korea
*Department of Internal Medicine, Konkuk University, School of Medicine, Seoul, Korea
**Department of Biomedical Science and Technology, Konkuk University, Seoul, Korea
Hoon Sup Koo, Kyu Chan Huh
Department of Gastroenterology, Konyang University Hospital, Daejeon, Korea
Yoshikazu Ohtsuka , Katsuhiro Arai, Yo Aoyagi , Tohru Fujii , Tamaki Ikuse ,
Takahiro Kudo1, Toshiaki Shimizu1
1
Department of Pediatrics, Juntendo University Graduate School of Medicine, Tokyo, Japan
2
Division of Gastroenterology, Department of Medical Specialties,
National Center for Child Health and Development, Tokyo,Japan
Suck-Ho Lee, MD , Dong Il Park, MD , Chang Kyun Lee, MD , Jeong Eun Shin, MD4,
Chang Soo Eun, MD5, Kyu Chan Huh, MD6,
1
Soonchunhyang University (Cheonan Hosp) ,
2
Sungkyunkwan University (Kangbook Samsung Hosp) ,
3
Kyung Hee University College of Medicine ,
4
Dankook University,
5
Hanyang University (Kuri Hops) ,
6
Konyang University College of Medicine,
22
P-25 Acute myelomonocytic leukemia following treatment of Crohn’s disease with
6-mercaptopurine: a case report
Hee Jae Hyun, MD, Eun Yeong Kim, MD, Choul Ki Park, MD,
Chang Kyun Lee, MD, Hyo Jong Kim, MD
Division of Gastroenterology, Department of Internal Medicine,
Kyung Hee University School of Medicine, Seoul, Korea
P-26 Increased rates of early adverse reaction to azathioprine in patients with inflammatory
bowel disease compared to autoimmune hepatitis
87
88
Dong Choon Kim, Eun Soo Kim, Yun Jung Kim, Kyung Sik Park, Kwang Bum Cho
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
P-27 Incidence of Extraintestinal Malignancies in a Single-Center Inflammatory Bowel Disease
Population in Korea
89
P-28 Extensive Arterial and Venous Thrombosis in Patient with Ulcerative Colitis
90
P-29 Development of liver cirrhosis and massive variceal bleeding in a patient with refractory
Crohn’s disease
91
P-30 Portal pylephlebitis as a complication of paediatric Crohn’s disease: a case report
92
P-31 Hemophagocytic lymphohistiocytosis in a Crohn’s disease patient who recovered by IV
gamma-immunoglobulin.
93
P-32 EBV-associated lymphoproliferative disorders misdiagnosed with Crohn’s disease
94
P-33 Clinical characteristics of the cancer patients who occurred the rectum and anal canal
associated with 1Crohn’s disease
in Japanese cases
2
2
1
1
95
Soo-Kyung Park, Byong Duk Ye, Suk-Kyun Yang, Dong-Hoon Yang,
Kee Wook Jung, Kyung-Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, and Jin-Ho Kim
Hyun-Soo Kim, Young-Eun Joo
Department of Gastroenterology, Chonnam National University Medical School,
Gwangju, South Korea
Kyoung Sup Hong, Jong Pil Im, Joo Sung Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Eun Yeong Kim, MD., Hee Jae Hyun, MD., Choul Ki Park, M.D., Chang Kyun Lee, MD.,
Hyo Jong Kim, MD.
Hyo Keun Jeon, So Yeon Park, Hong Jun Park, Hyun Soo Kim
Yonsei University Wonju College of Medicine
Hee Kyong Na, MD, Byong Duk Ye, MD, Suk-Kyun Yang, MD,Dong-Hoon Yang, MD,
Kee Wook Jung, MD, Kyung-Jo Kim, MD,Jeong-Sik Byeon, MD,
Seung-Jae Myung, MD and Jin-Ho Kim, MD
Takeshi Ueda , Hisao Fujii , Fumikazu Koyama , Tadashi Nakagawa , Shinji Nakamura ,
Naoto Nishigori1, Takashi Inoue1, Keijirou Kawasaki1, Shinsaku Obara1,
Yoshiyuki Nakajima1
1
Department of Surgery, Nara Medical University, Nara, Japan
2
Department of Endoscopy and Ultrasound, Nara Medical University, Nara, Japan
23
P-34 A case of Crohn’s colitis-associated rectal cancer following after sporadic
adenocarcinoma in adenoma.
96
P-35 Surgery for ulcerative
colitis in *elderly patients.
*
97
P-36 Impact of level of mucosal proctectomy on outcome of ileal pouch-anal anastomosis for
ulcerative colitis
98
P-37 The impact of Anti TNF-α Agents with Operative Treatment for Crohn’s Anorectal
Fistula -Aim to introduce the deep remission of fistula-
99
P-38 A case of an ulcerative colitis patient with enterocutaneous fistula and abscess
100
P-39 The value of concomitant endoscopic balloon dilation for intestinal stricture during
long - term infliximab
therapy in1 patients with Crohn’s
disease 1
1
1
1
101
P-40 Emerging trends in the incidence and prevalence of inflammatory bowel disease:
experience from a single center
102
P-41 Clinical Significance of Fecal Leukocyte, Lactoferrin, and Calprotectin in Moderate to
Severe Acute Diarrhea
1
1
2
1
1
1
103
P-42 The Usefulness of C-reactive Protein as a Disease Activity Marker in Crohn’s Disease
According to the Location of Disease
104
Takeyama Hiroshi, Tsunekazu Mizushima, Kiyokazu Nakajima, Hidekazu Takahashi,
Junichi Nishimura, Ichiro Takemasa, Masataka Ikeda, Hirofumi Yamamoto,
Mitsugu Sekimoto, Riichiro Nezu*, Toshinori Ito, Yuichiro Doki and Masaki Mori
Department of Gastroenterological Surgery,
Osaka University Graduate School of Medicine, Department of Surgery,
Osaka Rosai Hospital*
Hiroki Ikeuchi , Motoi Uchino , Hiroki Matsuoka*, Toshihiro Bando*, Akihiro Hirata*,
Yoshio Takesue**, Naohiro Tomita***, Takayuki Matsumoto*
*
Inflammatory Bowel Disease Center, Hyogo College of Medicine
**
Department of Infection Control and Prevention, Hyogo College of Medicine
***
Department of Surgery, Hyogo College of Medicine
Toshimitsu Araki, Yooshimi Okita, Hiroyuki Fujikawa Inoue, Koji Tanaka. Yasuhiro Inoue,
Yasuhiko Mohri, Keiichi Uchida, Masato Kusunoki
Department of Gastrointestinal and Pediatric Surgery,
Mie University Graduate School of Medicine, Tsu, Mie, Japan
Naoto Saigusa, Tadashi Yokoyama, Manabu Kikuchi and Yasuhisa Yokoyama
Yokoyama Hospital for Gastroenterology
You Sun Kim¹, Seong Yeon Jeong¹, Sun Ok Kwon¹, Jeong Seop Moon¹, Yun Kyung Kang²,
Seong Woo Hong³
Departments of ¹Internal Medicine, ²Pathology and ³General Surgery, Seoul Paik Hospital,
Inje University College of Medicine,Seoul, Korea
Yoichiro Ono , Fumihito Hirai , Toshiyuki Matsui , Takahiro Beppu , Yutaka Yano ,
Noritaka Takatsu1, Daijiro Higashi2, Kitaro Futami2
1
Department of Gastroenterology, Fukuoka University Chikushi Hospital
2
Department of Surgery, Fukuoka University Chikushi Hospital
Haruhiko Takahashi, Takashi Hisabe, Fuminito Hirai, Toshiyuki Matsui
Department of Gastroenterology, Fukuoka University Chikushi Hospital,
Chikushino, Fukuoka, Japan
Hae Mi Lee , Bo-In Lee , Seungok Lee , Joo-Yong Song , Hye-Jung Choi , Bong Koo Kang ,
Eun Joo Im1, Joon Sung Kim1,, Jong In Kim1, Byung-Wook Kim1, Hwang Choi1
Department of 1Internal Medicine,
2
Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
Dong-Hoon Yang, Suk-Kyun Yang, Sang Hyoung Park, Sun-Jin Boo, Jae-Ho Park,
Soo Young Na, Kee Wook Jung, Kyung Jo Kim, Byong Duk Ye, Jeong-Sik Byeon,
Seung-Jae Myung, Jin-Ho Kim
Department of Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of Korea.
24
P-43 Long-term prognosis of jejunal involvement of Crohn’s disease
105
P-44 Increased risk of gallstone disease among people with inflammatory bowel disease:
a population-based retrospective cohort study
106
Soo-Kyung Park, Suk-Kyun Yang, Byong Duk Ye, Dong-Hoon Yang,
Kee Wook Jung, Kyung Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, and Jin-Ho Kim
Department of gastroenterology, University of Ulsan College of Medicine,
Asan Medical Center, Seoul, Republic of Korea
Chien-Chang Liao, PhD, MPH (Assistant Professor); Ta-Liang Chen, MD, PhD (Professor)
School of Medicine, Taipei Medical University, Taipei 110, Taiwan
Department of Anesthesiology, Taipei Medical University, Taipei 110, Taiwan
P-45 CANCEL
P-46 Growth disturbance in Japanese children with IBD
107
P-47 Increased Risk of Hip 1Fracture in People With
Inflammatory Bowel Disease
2,3
108
P-48 The Seasonality in Flares of Korean Patients with Inflammatory Bowel Disease:
a Multicenter Study 1
1
2
109
P-49 Comorbidity of depression and anxiety in inflammatory bowel disease and its
relationship with disease
status
in Korea 1
1
1
1
1
110
P-50 How are thiopurines dosed in Crohn’s disease? : A novel strategy, maximum
dose-titration based
on the lower
limit of leukocyte
count1 and tolerability 1
1
1
1
111
Toshiaki Shimizu , Tetsuo Shono, Yo Aoyagi, Tohru Fujii, Takahiro Kudo, Yoshikazu Ohtsuka.
Department of Pediatrics, Juntendo University Graduate School of Medicine
Yi-Chun Chou, MD ; Ta-Liang Chen, MD , PhD; Chien-Chang Liao, PhD, MPH2,3
1
Department of Physical Medicine and Rehabilitation,
China Medical University Hospital, Taichung 404, Taiwan
2
3
Department of Anesthesiology, Taipei Medical University Hospital, Taipei 110, Taiwan
Dong Il Park, M.D., Chang Seok Song, M.D., Jae Myung Cha, M.D., Jae Hak Kim, M.D.,3
Suck Ho Lee, M.D.,4 Chang Soo Eun, M.D., 5 Dong Soo Han, M.D., 5 Eun Ran Kim, M.D.,6
Young Ho Kim, M.D.6
1
Department of Internal Medicine, Kangbuk Samsung Hospital,
Sungkyunkwan University School of Medicine, Seoul, Korea
2
Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
3
Department of Internal Medicine, Dongguk University Ilsan Hospital, Seoul, Korea.
4
Department of Internal Medicine, Soonchunhyang University College of Medicine,
Cheonan, Korea
5
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea
6
Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang Sup Lim , Won Moon , Seun Ja Park , Moo In Park , Hyung Hun Kim ,
Eun Soo Kim2,Seok Reyol Choi3
1
Crohn’s Disease and Ulcerative Colitis Clinic,Department of Internal Medicine,
Kosin University College of Medicine, Busan, Korea,
2
Division of Gastroenterology and Hepatology,Department of Internal Medicine,
Keimyung University school of Medicine, Daegu, Korea
3
Dong-A University school of Medicine, Busan, Korea
1
2
3
25
P-51 Importance of early inflammatory bowel disease: long diagnostic time lag and prior
frequent operation1 in tuberculosis-high
risk1 country
1
1
1
112
P-52 Questions about Crohn’s Disease by Patients: Survey of the Question and Answer in the
Homepage of Crohns’ Disease Fellow Asociation
113
P-53 The Change of the Diagnosis in Crohn’s Disease and Intestinal Tuberculosis According to
the Endoscopic Scoring System and Short Term anti-tuberculosis Medication Challenge.
114
P-54 Diagnostic role of CT enterography differentiating Crohn’s disease from intestinal
tuberculosis
1
2
1
1
1
115
P-55 Crohn’s Disease and Intestinal Behcet’s Disease: A Comparison of the Long-term
Clinical Outcomes
116
P-56 Correlations between endoscopic severity and the clinical disease activity index in
intestinal Behcet’s disease
117
P-57 Ulcerative colitis patients should be instructed to conceive while in remission.
118
P-58 Treatment Outcomes of Tacrolimus in Patients with Ulcerative Colitis
119
1
2
3
Kyeong Ok Kim, Byung Ik Jang, Yu Kyung Park, Jae Hong Yang
Yeungnam University College of Medicine
Kyeong Ok Kim, Byung Ik Jang, Sung Ho Chun.
Division of Gastroenterology,
Department of Internal Medicine Yeungnam University College of Medicine
Yoon Hea Park , Joon Seok Lim , Jae Hee Cheon , Tae Il Kim , Won Ho Kim , Sung Pil Hong1
1
2
Radiology Yonsei University College of Medicine, Seoul, Korea
Yoon Suk Jung, Jae Hee Cheon, Soo Jung Park, Sung Pil Hong, Tae Il Kim, and Won Ho Kim
Hyun Jung Lee, M.D.,* Hui Won Jang, M.D.,* Han Ho Jeon, M.D., * Eun Suk Jung, M.D.,*
Soo Jung Park, M.D., Ph.D.,* Sung Pil Hong, M.D., Ph.D.,* Tae Il Kim, M.D., Ph.D.,*
Won Ho Kim, M.D,Ph.D.,*, † Chung Mo Nam, Ph.D., ‡ Youn Nam Kim, MS., ‡‡
Jae Hee Cheon, M.D, Ph.D.*, †
*Department of Internal Medicine and Institute of Gastroenterology,
Yonsei University College of Medicine, Seoul,Republic of Korea;
†Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine,
Seoul, Republic of Korea;
‡Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea;
‡‡Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea.
Masaki Ujihara, Takafumi Ando, Kazuhiro Ishiguro, Osamu Watanabe, Osamu Maeda,
Satoshi Hibi, Toru Kamiya, Shunya Mimura, Yutaka Hirayama, Kazuhiro Morise,
Ryoji Miyahara, Naoki Omiya, Hidemi Goto
Nagoya University Graduate School of Medicine
Miyuki Mukae, Kiyonori Kobayashi, Taishi Ogawa, Kaoru Yokoyama,
Miwa Sada, and Wasaburo Koizumi
Department of Gastroenterology, Kitasato University East Hospital
26
P-59 Efficacy of oral tacrolimus
and2 infliximab in the treatment
of active ulcerative
colitis.
1
2
2
120
P-60 Nutritional Status Assessment of Newly-diagnosed Inflammatory Bowel Disease patients
121
P-61 The Cap Assisted Technique Enhances the Colonoscopy Training; Prospective
Randomised Study of Six Trainees.
122
P-62 A Case of Soft Tissue Abscess Caused by Salmonella Serotype D in a Patient
Presenting As Acute Colitis
123
P-63 The outcome and interval between colonoscopy after a negative colonoscopy
124
P-64 Autophagy upregulates CXCL10 in primary intestinal epithelial cells stimulated by
Flagellin via TLR5 on basolateral membrane.
125
P-65 Hes1 promotes IL-22-mediated epithelial regeneration through enhancement of
STAT3-dependent transcription in human intestinal epithelial cells.
126
P-66 Notch-Hes1 pathway and TNF-α synergistically up-regulates OLFM4 expression in the
inflamed mucosa of the human intestine
127
Kouichi Asano , Junji Umeno , Tomohiko Moriyama , Motohiro Esaki , Shotaro Nakamura2,
and Takayuki Matsumoto2
1
Department of endoscopic diagnosis and diagnosis, Kyushu University Hospital,
Fukuoka, Japan,
2
Department of Medicine and Clinical Science Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
Min Ji Lee, Sung Hye Kim*, Mi Yong Rha*, Young Yun Cho*, Byung-Hoon Min,
Jun Haeng Lee, Dong Kyung Chang , Young-Ho Kim, Poong-Lyul Rhee, Jae J. Kim,
Jong Chul Rhee, Jin Yong Kim
Department of Medicine,
*Department of Dietetics, Samsung Medical Center,
Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
Sang Man Park, M.D., Soon Hak Lee, M.D., Keun Young Shin, M.D., Jun Heo, M.D.,
Sang Hoon Sung, M.D., Soon Hong Park, M.D., So Young Choi, M.D., Dong Wook Lee, M.D.,
Hyun Gu Park, M.D., Hyun Seok Lee, M.D., Seong Woo Jeon M.D., Ph.D.,
Sung Kook Kim M.D., Ph.D., Min Kyu Jung, M.D., Ph.D.
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Kyungpook National University School of Medicine, 50, Samduk-Dong 2 Ga, Junggu, Daegu,
700-721, South Korea
Eun Mi Song, Sung-Ae Jung, Seong-Eun Kim, Kyoung Joo Kwon, Hye Won Kang,
Ju Young Choi, Ki-Nam Shim, Hye-Kyung Jung, Tae Hun Kim, Kwon Yoo, Il Hwan Moon
Won Kyung Yoon, Min Kyu Jung, Min Kim, Keun Young Shin, Jun Heo, Seong Woo Jeon.
Internal Medicine Gastroenterology and Hepatology,
Kyungpook National University Hospital, Republic of Korea
Xiu Zheng, Kiichiro Tsuchiya, Yoshihito Kano, Nobukatsu Horita, Ryuichi Okamoto,
Tetsuya Nakamura and Mamoru Watanabe
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University
Tatsuro Murano, Ryuichi Okamoto, Hiromichi Shimizu, Go Ito, Kiichiro Tsuchiya,
Tetsuya Nakamura, Mamoru Watanabe
Ryuichi Okamoto, Junko Akiyama, Hiromichi Shimizu, Tatsuro Murano, Go Ito,
Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe
27
P-67 Overexpression of Smad2/3, phosphorylated at specific linker threonine residues, in the
murine model of Dextran Sodium Sulfate-Induced Colitis
128
P-68 The novel host-probiotics
interaction
through activation
of intestinal
epithelial autophagy
1
1
1
2
1
129
P-69 A protective effect
of vitamin2 C on DSS-induced
colitis
1
2
130
P-70 Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran
sodium sulfate induced
colitis 2
1
1
1
1
131
P-71 Intestinal CXCR4+IgG+ Immature Plasma Cells Contribute to the Pathogenesis of
Ulcerative Colitis through
IgG-Immune
Complex-FcγR
Signaling 1
1
1
1
132
P-72 Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal
Stem Cells
1
2
3
2
133
P-73 Association between red cell distribution width and disease activity in patients with
134
P-74 Novel Guggulsterone Derivative GG-52 Inhibits NF-κB Signaling in Bone Marrow-Derived
Dendritic Cells and Attenuates Colitis in IL-10 Deficient Mice
135
Masanobu Kishimoto , Toshiro Fukui , Yu Takahashi , Atsushi Nakajima , Yutaku Sakaguchi ,
Kazushige Uchida , Akiyoshi Nishio , Koichi Matsuzaki , Kazuichi Okazaki
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Yuhei Inaba , Mikihiro Fujiya , Nobuhiro Ueno , Eugene B Chang and Yutaka Kohgo
1
Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan
2
Department of Medicine, University of Chicago, Chicago, Illinois, USA
Jong Pil Im , Hyemin Kim , Hang Rae Kim , Young Il Hwang2, Jae Seung Kang2,
Wang Jae Lee2 and Joo Sung Kim1
Department of
1
Internal Medicine and Liver Research Institute,
2
Anatomy and Tumor Immunity Medical Research Center,
Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu,
Seoul 110-799, Korea
Akiko Kurishima , Muneo Inaba , Yutaku Sakaguchi , Toshiro Fukui , Kazushige Uchida ,
Akiyoshi Nishio1, Shosaku Nomura2, Kazuichi Okazaki1
1
Kansai Medical University,Osaka, Japan.
2
First Department of Internal Medicine, Kansai Medical University, Osaka,Japan
Tadakazu Hisamatsu , Michihide Uo , Jun Miyoshi , Kazuaki Yoneno ,
Katsuyoshi Matsuoka1,Takanori Kanai1, Haruhiko Ogata2, and Toshifumi Hibi1
1
Keio University School of Medicine, Tokyo, Japan.
2
Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University
Kanna Nagaishi , Shuhei Watanabe , Yasuyoshi Naishiro , Kentaro Yamashita ,
Yoshiaki Arimura2, Mineko Fujimiya1, Yasuhisa Shinomura2, Kohzoh Imai4
1
2
3
4
Division of Novel Therapy for Cancer, Advanced Clinical Research Center,
Institute of Medical Science, University of Tokyo
Chang Seok Song, M.D., Dong Il Park, M.D.
Seung Joo Kang, Seong-Joon Koh, Joo Sung Kim
Department of Internal Medicine and Liver Research Institute,Seoul National University
College of Medicine, Seoul, KOREA
28
P-75 Adipose Tissue-Derived
Stem Cell
Attenuate Colitis
in Interleukin-10
Knockout Mice.
1
2
1
3
136
P-76 Intravital assessment of infliximab efficacy in murine ulcerative colitis model using two
photon laser scanning
microscopy
1
1
1
1
1
137
P-77 Glutamine induces intestinal epithelial heat shock response via HSF-1 activation by
polyamines
1
1
1
1
1
138
P-78 Macrophages pre-exposed to heat-killed feces show hyporesponsiveness to mRNA
expression of inflammatory cytokines induced by fatty acids exposure.
139
P-79 Are PPIs Associated with Increased Intraepithelial Lymphocytes in the Colon?
140
P-80 Restraint Stress Induces
and Exacerbates
Intestinal
Inflammation
in IL-10 Deficient
Mice
1
1
2
1
1
141
P-81 Glutinous rice extract suppresses LPS-induced proinflammatory mediator expression
via blockage of NF-κB activation in intestinal epithelial cells
142
P-82 The role of SERPINB1 (monocyte neutrophil elastase inhibitor) in the pathogenesis of
ulcerative colitis
143
Byung Ik Jang , In-Hwan Song ,, Kyeong Ok Kim , Chang Hun Yang
Division of Gastroenterology, Department of Internal Medicine1, Anatomy2 , Yeungnam
University College of Medicine, Daegu,Division of Gastroenterology, Department of Internal
Medicine, Dongkuk Unversity College of Medicine, Kyeong Ju3, Korea
Kohei Matsushita , Koji Tanaka , Yuhki Morimoto , Masato Okigami , Mikio Kawamura ,
Kiyosi Hashimoto1, Susumu Saigusa1, Yuji Toiyama1, Yuuki Koike1, Yoshinaga Okugawa1,
Yasuhiro Inoue1, Toshimitsu Araki1, Keiichi Uchida1, Yasuhiko Mohri1,
Akira Mizoguchi2, and Masato Kusunoki1
Departments of 1Gastrointestinal and Pediatric Surgery, and 2Neural Regeneration and Cell
Communication, Mie University
Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507
Toshio Sakiyama , Yuji Iwashita , Takuro Maeda , Yuga Komaki , Hiroki Taguchi ,
Masatsugu Numata1, Hiroshi Fujita1, Mark W. Musch2, Eugene B. Chang2, Hirohito Tsubouchi1
1
Department of Digestive and Life-style related Diseases,
Kagoshima University Graduate School of Medical and Dental Sciences,
Kagoshima, Japan and2Department of Medicine, University of Chicago, Chicago, Illinois.
Chie Kurihara, Ryota Hokari, Toshihide Ueda, Shingo Sato, Hideaki Hozumi, Hirokazu Sato,
Kazuyuki Narimatsu, Yoshikiyo Okada, Chikako Watanabe, Kengo Tomita, Shunsuke Komoto,
Astushi Kawaguchi, Shigeaki Nagao, Soichiro Miura
Department of Internal Medicine, National Defense Medical College,
Tokorozawa, Saitama Japan
Yeon Hwa Yu, M.D., Dong Soo Han, M.D., Hyen Soo Kim. M.D., Eun Kyung Kim. M.D.,
Chang Soo Eun, M.D.,Ju Yeon Pyo, M.D. *
Department of Internal Medicine and Pathology*,
Hanyang University College of Medicine, Guri, Korea
Seong-Joon Koh , Jong Pil Im , Ji Won Kim , Hyun Chae Jung , and Joo Sung Kim
1
Department of Internal Medicine and Liver Research Institute,
Seoul National University College of Medicine, Seoul, Korea
2
Department of Internal Medicine, Seoul National University Boramae Hospital,
Seoul National University College of Medicine, Seoul, Korea.
Young-Eun Joo, Young-Lan Park, Seon-Young Park, Sung-Bum Cho,Chang-Hwan Park,
Hyun-Soo Kim, Sung-Kyu Choi, Jong-Sun Rew
Department of Internal Medicine, Chonnam National University Medical School,
8 Hak-Dong, Dong-ku, Gwangju 501-757, Korea
Kazuhiro Kamada, Yuji Naito, Kazuhiko Uchiyama, Tomohisa Takagi, Katsura Mizusima,
Yasuko Hirai, Kazuhiro Katada, Osamu Handa, Nobuaki Yagi, Toshikazu Yoshikawa
Kyoto Prefectural University of Medicine
29
P-83 Aberrant DNA methylation of FBN2 and TCERG1L genes in Ulcerative Colitis Patients
144
P-84 Promoter polymorphism of the EED gene is associated with the susceptibility to
ulcerative colitis
145
P-85 Terminal restriction fragment length polymorphism analysis of the diversity of fecal
microbiota in patients
with inflammatory
bowel disease
and irritable
bowel syndrome
1
1
1
2
3
146
P-86 The Study of Gene Expression Induced by Sleep Deprivation and Melatonin Treatment on
DSS Induced Colitis
Mice.
1
2
3
3
4
147
TAE-OH KIM, JOO MI YI, HEUI SOO KIM
Department of Internal Medicine, Haeundae Paik Hospital,
Inje University Colledgel of Medicine
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS)
Division of Biological Sciences, College of Natural Sciences, Pusan National University
Geom-Seog Seo,* Suck-Chei Choi,* Ki-Jung Yun, † Soo-Cheon Chae †
*†Digestive Disease Research Institute, Department of Internal Medicine,* Pathology,†
School of Medicine, Wonkwang University, Iksan, Chonbuk 570-749, South Korea
Bong Ki Cha, Chang Hwan Choi, Se Kyung Chang, Kijeong Kim, Byung Chang Kim,
Sung-Ae Jung4
Department of Internal Medicine1 and Microbiology, 2
Chung-Ang University College of Medicine,1, 2 Department of Internal Medicine,
National Cancer Center, 3 Department of Internal Medicine,
Ewha Womans University School of Medicine, 4 Seoul,Republic of Korea
Sang Soo Kim , Sook Hee Jung , Jae-Ho Shin , Jin-Hyun Jun ,Haeng Woon Baek ,
Young-Sook Park1, 5
1
Eulji Bio-medical Research Institute, Eulji University, Seongnam, Korea.
2
Dept. of Gastroenterology, Severance Hospital, Yonsei University, Seoul, Korea.
3
Dept. of Biomedical Laboratory Sciences College of Health Science, Eulji University,
Seongnam, Korea
4
Dept. of Biomedical Laboratory Sciences, School of Medicine, Eulji University, Daejon ,
Korea
5
Dept. of Internal Medicine, Eulji general hospital, Seoul, Korea
30
Session
Session 1 Topics for recent progress of basic research in IBD
Session 2 Lymphoproliferative disorders in IBD
Session 3 How to use new devices for diagnose in IBD
Session 4 Recent progress of Surgical Treatment in IBD
Session 5 Best Poster Presentation
Session 6 Recent trends of medical treatments in Japan and Korea
Session 7 How to establish Asian consensus and guideline in IBD ?
31
Session1-1
Epithelial regeneration by cultured colonic cells
expanded from a single adult Lgr5+ stem cell
Tetsuya Nakamura M.D., Ph.D.
Research on intestinal epithelial stem cells has flourished in the last few years since their specific
molecular markers were identified. In particular, advancement in culture method to grow normal
intestinal stem cells in vitro is expected to open up new avenues for the use of these adult stem
cells in the treatment of gastrointestinal diseases. However, in order to exploit the potentials of
cultured stem cells as a source for regenerative medicine, further refinement of culture technologies
and validation of their tissue regeneration capacity would be essential. To address this, we have
developed a novel method for long-term culture of colonic epithelial cells that are capable of selfrenewal and multilineage differentiation in vitro (TMDU method). The colonic cells obtained
from adult mice were shown to grow as round cystic organoids under serum- and mesenchymefree conditions. The expression of Lgr5, a specific marker for colonic epithelial stem cells, was
maintained over a prolonged period, and the dynamic expansion of Lgr5+ cells in growing organoids
could be visualized in real time. In order to test whether the cultured colonic cells could regenerate
functional epithelium in vivo, GFP+ colon organoids were re-introduced into the lumen of mouse
colon superficially damaged by Dextran Sodium Sulfate (DSS) treatment. The transplanted donor
cells readily integrated into the recipients' colon, covering the area that lacked epithelium. At 4
weeks post-transplantation, the donor-derived cells constituted single-layered epithelium forming
self-renewing crypts that were histologically and functionally normal. Moreover, long-term (> 6
months) engraftment was observed with transplantation of organoids that were derived from a single
Lgr5+ colon stem cell after extensive in vitro expansion. These data for the first time demonstrate the
feasibility of colon stem cell therapy based on in vitro expansion of a single adult colonic stem cell.
33
Session1-2
Paradoxical effects of human IL-32γin transgenic mice during
experimental colitis
Soohyun Kim PhD.
Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology,
Konkuk University, Seoul, 143-701 Korea;
Abstract
Background/aims: Inflammatory cytokines mediate inflammatory bowel diseases (IBD) and
cytokine blocking therapies often ameliorate the disease severity. IL-32 was first reported as an
inducer of TNFa1 and IL-32γwas the most active isoform inducing proinflammatory cytokines and
chemokines including IL-1b, IL-6, and MIP-22. In addition, IL-32 is present in the intestinal tissue
of patients with CD3 or UC4. Here, we investigated the role of IL-32 in intestinal inflammation with
human IL-32γtransgenic mouse (IL-32γTG).
Methods: We generated transgenic mice in which human IL-32γwas driven by the chicken betaactin promoter in order to express IL-32γin all tissues. IL-32γTG mice and WT mice were fed a 3.5%
solution of DSS in the drinking water for 5 days and observed for 14 days.
Results: Although IL-32γTG mice are healthy, constitutive serum and colonic tissue levels of TNFa
are elevated. Compared to wild type (WT) mice, IL-32γTG mice exhibited a modestly exacerbated
acute inflammation early following the initiation of dextran sodium sulfate (DSS)-induced colitis.
However, there was less colonic inflammation, reduced tissue loss and improved survival rate
compared to WT mice. Associated with attenuated tissue damage, colonic levels of TNFa and IL-6
were significantly reduced in the IL-32γ TG mice whereas IL-10 was elevated, particularly in the
rectum.
Conclusions: Our study provides evidence that the more aggressive defense in IL-32γ TG mice
results in a rapid recovery and return to intestinal homeostasis. Consequently these followed that
DSS-treated IL-32γ TG mice were protected from irreversible colon damage leading to improve
survival rate during recovery from colitis and promote remission of inflammation.
Keywords: Interleukin-32, Inflammatory cytokine, Dextran sodium sulfate (DSS)-induced colitis,
Human IL-32γtransgenic mouse (IL-32γTG), Inflammatory bowel diseases (IBD).
References
1. Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA. Interleukin-32: a cytokine and inducer of
TNFalpha. Immunity 2005;22:131-42.
2. Choi JD, Bae SY, Hong JW, Azam T, Dinarello CA, Her E, Choi WS, Kim BK, Lee CK, Yoon
DY, Kim SJ, Kim SH. Identification of the most active interleukin-32 isoform. Immunology
2009;126:535-42.
3. Netea MG, Azam T, Ferwerda G, Girardin SE, Walsh M, Park JS, Abraham E, Kim JM,
Yoon DY, Dinarello CA, Kim SH. IL-32 synergizes with nucleotide oligomerization domain
(NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent
mechanism. Proc Natl Acad Sci U S A 2005;102:16309-14.
34
4.
Shioya M, Nishida A, Yagi Y, Ogawa A, Tsujikawa T, Kim-Mitsuyama S, Takayanagi A,
Shimizu N, Fujiyama Y, Andoh A. Epithelial overexpression of interleukin-32alpha in
inflammatory bowel disease. Clin Exp Immunol 2007;149:480-6.
35
Session1-3
The role of oligosaccharide alterations in immunoglobulins of
inflammatory bowel diseases
Hideki Iijima, MD, PhD, Assistant professor
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine,
Suita, Osaka, Japan
Ideal biomarkers are required to be developed for the diagnosis and prediction of the treatment
efficacy of inflammatory bowel diseases (IBD). To date, there are no serologic markers with
sensitivity and specificity high enough to diagnose IBD. We recently reported that alteration of
N-linked oligosaccharides of immunoglobulin (Ig) G is a novel diagnostic marker of IBD1. The ratio
of galactose-deficient and galactose-sufficient fraction in fucosylated IgG oligosaccharides (G0F/
G2F) was significantly increased in patients with IBD in comparison to healthy volunteers. G0F/
G2F was significantly correlated with disease severity in IBD patients, and had higher sensitivity to
diagnose IBD compared with anti-Saccharomyces cerevisiae antibody (ASCA). Moreover, G0F/G2F
was associated with disease prognosis of IBD.
In order to investigate the role of agalactosyl oligosaccharide modification in the pathogenesis of
IBD, we used beta-1,4-galactosyltransferase I (B4galt1)-deficient mice. Severity of dextran sodium
sulfate and trinitrobenzene sulfonic acid-induced colitis was ameliorated in B4galt1+/- mice, which
have galactose deficiency in IgG oligosaccharides similar to that of patients with Crohn's disease,
compared with B4galt1+/+ mice. Amelioration of colitis was associated with an increased interleukin
(IL)-10 production from macrophages in B4galt1+/- mice. In vitro experiments revealed IL-10 was
produced from macrophages via direct interaction with B4galt1+/- B cells. We then analyzed the
phagocytic activity of human monocyte-derived dendritic cells by antigen-captured agalactosyl
and non-agalactosyl IgG antibody. Phagocytic activity was significantly increased in the presence
of agalactosyl IgG compared to non-agalactosyl IgG2. These results indicate that oligosaccharide
alterations of IgG are not only a marker of IBD but also functionally modulate immune function of
IBD.
In addition to the changes in IgG oligosaccharides, we found that IgA oligosaccharides are
altered in IBD patients. IgG has N-linked oligosaccharides alone, while IgA has N- and O-linked
oligosaccharides. Although N-linked oligosaccharides of IgA were not different between IBD and
HV, the number of N-acetylgalactosamines per hinge glycopeptide (GalNAc/HP) in the O-linked
oligosaccharides of IgA was significantly decreased in CD compared to UC and HV. GalNAc/
HP had higher sensitivity and specificity for discriminating between CD and HV when compared
with ASCA. Lower GalNAc/HP was associated with more severe disease activity of CD. In CD
patients whose disease activity was improved after the introduction of infliximab, GalNAc/HP was
significantly increased compared to the pretreatment levels.
Alterations of oligosaccharides in IgG and IgA are novel diagnostic and prognostic markers of IBD.
In addition to the role of oligosaccharides as a marker, altered oligosaccharide structures on immune
cells can modulate mucosal immune function and would be a potential therapeutic target for IBD.
REFERENCES
36
1.
2.
Shinzaki S, Iijima H, Nakagawa T, et al. IgG oligosaccharide alterations are a novel diagnostic
marker for disease activity and the clinical course of inflammatory bowel disease. Am J
Gastroenterol 2008;103:1173-81.
Nakajima S, Iijima H, Shinzaki S, et al. Functional analysis of agalactosyl IgG in inflammatory
bowel disease patients. Inflammatory bowel diseases 2011;17:927-36.
37
Session1-4
The effect of sleep deprivation and melatonin treatment on
YOUNG SOOK PARK
Department of Gastroenterology, Eulji University, Eulji Medical Center, Seoul, Korea
Backgrounds & Aims : Inflammatory bowel disease is waxing and waning disease which results in
poor quality of life. Advances in the molecular machinery of the circadian clock, and the discovery
of clock genes in the GI tract help to upgrade researches for a role of sleep in IBD. Altering circadian
rhythm significantly worsens the development of colitis in animal models, and preliminary human
studies have shown that patients with IBD are at increased risk for sleep disruption. Melatonin,
a hormone and marker of the central circadian clock, has been shown to be protective in animal
models of colitis.
Stressful condition has reported aggravation or reactivation of inflammatory bowel disease. Thus,
we tried to investigate the effect of stress caused by sleep deprivation on DSS induced colitis model.
Also, we designed to evaluate protective effect of melatonin on such condition.
Materials and Methods : We used the 5 groups of C57BL/6 mice. Group I: control, Group II: 2%
DSS induced colitis for 7days, Group III: 2% DSS induced colitis and melatonin treatment, Group
IV: 2% DSS induced colitis with sleep deprivation(SD, 20hr/d) and Group V: 2% DSS induced
colitis with SD and melatonin treatment. Specially designed modified multiple platform water baths
for sleep deprivation were used. Melatonin(10mg/kg) or saline was injected daily by intraperitoneal
route. The mice were sacrificed after finishing administration of melatonin or saline for 4 days.
We checked body weight and stool color daily. Degree of colitis was evaluated after H&E stain. Also
proinflammatory cytokines from serum were checked using Bio-Plex Pro Mouse Cytokine assay
kit (Bio-Rad, Hercules, CA, USA). RNA was isolated from the colon of mice in each group and
collected to analyze by microarray and ontology. We confirmed significant changes of expression of
important genes by RT-PCR.
Results : Sleep deprivation worsens body weight reduction of mice and exacerbate the severity of
colonic inflammation. Administration of melatonin reduced the rate of weight loss and severity of
mucosa injury compared with saline injection group. Increased expression of pro-inflammatory
cytokines such as IL-6, TNF-α, IFN-γ was significantly reduced with melatonin supplementation.
Gene expression of TGFβ1 and Bcl2 like 1 (Bcl2l1) was significantly changed by 2% DSS, sleep
deprivation and melatonin in microarray. In RT-PCR sleep deprivation increased mRNA of prkcz,
calm3 and decreased that of iNOS, wnt5a. Melatonin increased mRNA of TGFβ1, ccl5, iNOS, wnt5a
and bcl2l1 and decreased that of prkcz and calm3.
Conclusions : Sleep deprivation acts as an aggravating factor and delays recovery from active
inflammation, whereas melatonin acts as an improving factor by reducing expression of proinflammatory cytokines. Genetic study showed melatonin and sleep deprivation may regulate
38
metabolism, gene expression, cell growth and apoptosis in process of inflammatory bowel disease.
This result may help management of IBD in the aspect of stress and sleep problems.
REFERENCES
1. Sonnenberg A: Occupational distribution of inflammatory bowel disease among german
employees. Gut 1990;31:1037-1040.
2. Swanson GR, Burgess HJ, Keshavarzian A. Sleep disturbances and inflammatory bowel disease: a
potential trigger for disease flare?. Exper Rev. Cli. Immunol 2011;7:29-36.
3. Green CB, Takahashi JS, Bass J. The meter of metabolism. Cell 2008;134:728-742
4. Sl dek M, Rybov M, Jindr kov Z et al. Insight into the circadian clock within rat colonic epitherial
cells. Gastroenterology 2007;133:1240-1249.
5. Burgess HJ, Revell VL, Molina TA, Eastman CI. Human phase response curves to three days of
daily melatonin: 0.5mg versus 3.0mg. J. Clin. Endocrinol. Metab. 2010;95:3325-3331.
6. Lange T, Dimitov S, Born J. Effects of sleep and circadian rhythm on the human immune system.
Ann. NYAcad. Sci. 2010;1193:48-59.
7. Keefer L, Stepanski E, Ranjbaran Z, Benson LM, Keshavarzian A. An initial report of sleep
disturbance in inactive inflammaoty bowel disease. J Clin Sleep Med 2006;2:409-416.
8. Ranjbaran Z, Keefer L, et al. Impact of sleep disturbances in inflammatory bowel disease. J
Gastroenterol Hepatol 2007; 22:1748-1753.
9. Tang Y, Preuss F, et al. Sleep deprivation worsens inflammation and delays recovery in a mouse
model of colitis. Sleep Med 2009;10:597-603.
10. MY Jung, YS Park, HW Paik, et al. The effects of sleep deprivation and melatonin
supplementation in recovery of DSS induced colitis. Intest Res 2010;8(Supp1):79
11. Bubenik GA. Thirty four years since the discovery of gastrointestinal melatonin. J Phsiol
Pharmacol 2008;59:33-51.
12. Li JH, Yu JP, et al. Melatonin reduces inflammatory injury through inhibiting NF-kappaB
activation in rats with colitis. Mediators Inflamm 2005;4: 185-193.
13. Necefli A, Tulumoglu B, et al. The effect of melatonin on TNBS-induced colitis. Dig Dis Sci
2006;51(9): 1538-1545.
14. Akcan A, Kucuk C, Sozuer E, et al. Melatonin reduces bacterial translocation and apoptosis in
trinitrobenzene sulphonic acid-induced colitis of rats. World J Gastroenterol. 2008;14:918-924.
15. Nosal'ova, V, M. Zeman, et al. Protective effect of melatonin in acetic acid induced colitis in rats.
J Pineal Res 2007; 42(4): 364-370.
16. Terry PD, Villinger F, Bubenik GA, Sitaraman SV. Melatonin and Ulcerative Colitis: Evidence,
Biological Mechanisms, and Future Research. Inflamm Bowel Dis 2009;15:134-140.
39
Session2-1
Lymphoproliferative disorders in the Japanese patients with
Kazuichi Okazaki, Norimasa Fukata
Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
Background and aims;
Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are
useful for inducing and maintaining remissions in most patients with inflammatory bowel disease
(IBD). However, it has been reported that their use may be a risk factor of the development of
lymphoproliferative disorder (LPD). The aim of the present study was to estimate the relative risk of
LPD in the Japanese patients with IBD.
Methods;
Questionaires about LPD patients associated with IBD were mailed to 70 hospitals, the members of
the Japanese Intractable IBD Committee supported by the program for Intractable Disease from the
Ministry of the Health, Labor and Welfare of Japan. The clinical data of LPD patients associated
IBD were analyzed and compared with the standard data of LPD in the Japanese general population.
Results;
1) Totally, 36,939 IBD patients (22,947 patients with ulcerative colitis (UC) (62.1%) and 13,992
with Crohn's disease (CD) (37.9%)) were collected. Among them, 46 cases of LPD (12 cases of
malignant lymphoma (ML), 12 of leukemia, 8 of multiple myeloma (MM), 4 of MALT lymphoma)
were found. The morbidity rate of LPD (125.8), ML (33.5), leukemia (33.5) and MM (22.4) per
each 100,000 cases of IBD were higher compared with those of LPD (125.8), ML (13.3), leukemia
(7.1) and MM (4.3) in 100,000 of the Japanese general population.
2) LPD associated with UC.
Eleven (male/female; 5/6) of 22,947 UC patients developed LPD with 7 of total colitis, 2 of leftsided, one of proctitis, and one of unknown sites. Ten of 11 UC patients were observed in repeated
remission/recurrence states and one in a stable remission state. Seven ML and 4 MM patients with
UC showed the relative risk of 1.96 for ML and 3.45 for MM. The mean age at the onset of UC
and LPD was 38.72 yr and 54.27 yr, respectively, with 15.82 years of the mean suffering duration
period from the onset of UC to LPD. Out of 11 UC patients with LPD, 10 were treated with 5-ASA
and 7 with steroid. Only 2 (18%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP).
Among 9,950 UC patients in the present study, 1,252 (13.1%) patients had exposure to AZA/6-MP.
There were no significant differences in the development of LPD between exposure (2 of 1252;
0.16%) and non-exposure (9 of 8298; 0.11%) to AZA/6-MP.
3) LPD associated with Crohn's disease (CD)
Nineteen (9 of leukemia, 6 ML and 4 MM) of 13,992 CD cases developed LPD with the relative
risk of 1.79 for ML and 3.45 for MM. with mean age at the onset of CD (26.58 yr,) and LPD (42.17
yr), suffering duration period from CD to LPD (15.64 yrs). Eight of 12 CD cases showed remission
40
~ recurrent type. Sites of the lesions are small intestine in 2 and both small and large intestine in
10. Out of 12 CD patients with LPD, 10 patients were treated with elemental diet, 7 with 5-ASA
and 6 with steroid. Four (33%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP) and 5
(42%) to infliximab. Among 6,070 CD patients, 1,470 (24.22%) patients were exposure to AZA/6MP. Exposure to immunosuppressive agents may be higher risk in the development of LPD (4 of
1,470; 0.27%) compared with non-exposure (8 of 4,600; 0.17%) to AZA/6-MP.
Conclusions:
This nationwide study suggested an overall increased risk for LPD in Japanese patients with IBD.
Exposure to immunosuppressive agents may be a risk factor in the development of LPD in CD, but
not in UC.
41
Session2-2
Inflammatory bowel disease and limphoproliferative disorders:
a Korean multicenter expericne
Byong Duk Ye, M.D., Ph.D.
Lymphoproliferative disorders (LPDs) are malignancies resulting from neoplastic transformation
of lymphoid cells and encompass non-Hodgkin lymphoma and Hodgkin lymphoma. The risk of
LPDs has been reported to be increased in various immunodeficiencies, autoimmune diseases and
chronic inflammatory diseases. Similar to other chronic inflammatory diseases such as rheumatoid
arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD).
Generally, in the Western IBD patients, the risk of LPDs appears to be similar with or slightly higher
than the risk in the general population. Although thiopurine was reported to be related with increased
risk of Epstein-Barr virus-associated LPD in post-transplant patients, the role of therapeutic agents
for the risk of LPDs is difficult to evaluate due to multiple other factors potentially involved and
co-treatment with other agents. To date, concordant data suggest that thiopurine is associated with
a moderately increased risk of LPDs in Western patients with IBD. Evidence regarding the risk of
LPDs in Western IBD patients using methotrexate is not sufficient, but the risk seems to be low. The
possible responsibility of anti-TNF-α agents on the risk of LPDs is difficult to determine, because
most of IBD patients are co-treated with thiopurines. However, more attention should be given to
the risk of hepatosplenic T cell lymphoma in young male patients treated with thiopurines and antiTNF-α agents.
Although there are multiple studies on the risk of LPDs in Western IBD patients, the reports on
Asian IBD patients are lacking. In this lecture, the results of a Korean multicenter study on the risk
of LPDs in IBD patients will be presented.
Key Words: Inflammatory bowel disease; Lymphoproliferative disorder; Thiopurine; Anti-TNF-α
agent
References
1 Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving
thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet
2009;374:1617-1625.
2. Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE. Risk of lymphoma associated with
combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's
disease: a meta-analysis. Clin Gastroenterol Hepatol 2009;7:874-881.
3. Sokol H, Beaugerie L. Inflammatory bowel disease and lymphoproliferative disorders: the dust is
starting to settle. Gut 2009;58:1427-1436.
42
Session3-1
How to use new devices for the diagnosis and treatment of IBD
Takayuki Matsumoto
Department of Medicine and Clinical Science, Graduate School of Medical Sciences,
Kyushu University
Recent development of enteroscopy and CT contributed to a great advance in the diagnosis and the
treatment of IBD. In this session, the role of capsule endoscopy (CE), balloon-assisted enteroscopy
(BAE) and CT enteroscopy (CTE) for Crohn’s disease (CD) will be discussed.
European Crohn’s Colitis Organization (ECCO) and Organization Mondiale d’Endoscopie Digestive
(OMED) have reported on international consensus for the use of CE. In that consensus, it has been
stated that CE is superior to the detection of small bowel lesions in patients with CD, but that the
potential significance of the superiority of CE needs to be defined. In our multicenter analysis of
patients examined by CE, it was evident that CE contributed to the detection of diminutive small
bowel lesions, and it was especially the case for patients suspected of having CD. However, the
rate of capsule retention in those patients (6.0%) were no different from that noted in patients with
the established diagnosis of CD (7.4%). From this observation, CE seems to be a procedure, which
should be carefully applied for the diagnosis of CD.
BAE, initially developed in Japan, has significant roles for the endoscopic and histologic diagnosis
of CD. With the application of endoscopic balloon dilatation (EBD), BAE also contributes to the
management of structuring CD. It has been suggested that EBD should be indicated for symptomatic
small bowel strictures with less than 5cm in length with neither deep ulcer nor fistula formation. A
Japanese multicenter survey for the application of EBD for small bowel CD has shown that shortterm efficacy was 75%.
In Western countries, CTE has been regarded as a promising procedure for the diagnosis of
small bowel lesions in CD. While there have been various types of contrast material for CTE,
active and acute lesions are depicted as mural hyperenhancement, mural stratification, bowel wall
thickening and increased attenuation of mesenteric fat. In addition, chronic lesions can be detected
as sacculations of antimesenteric wall and fibrofatty proliferation. It has been suggested that the
appropriate use of CTE would be valuable for the effect of therapy in small bowel CD. Images of
actual CTE findings will be demonstrated.
43
Session3-2
Correlation between Soluble Triggering Receptor Expressed on
Myeloid Cells-1 (sTREM-1) Expression and Endoscopic Activity in
Inflammatory Bowel Diseases
Jae Hee Cheon MD., PhD.
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of
Medicine, Seoul, Korea
Abstract
Background/aims: Recently, a triggering receptor expressed on myeloid cells-1 (TREM-1) was
shown to be upregulated in the intestines of pateints with inflammatory bowel diseases (IBD) and
also found to correlate with disease activity. However, data correlating the serum-soluble TREM-1
(sTREM-1) level with the IBD endoscopic activity are not currently available. As such, this study was
conducted to determine if the sTREM-1 expression level is able to be used as a biological marker in
assessing IBD endoscopic activity.
Methods: A total of 85 patients with ulcerative colitis (UC) and 34 patients with Crohn's disease
(CD) were prospectively enrolled. The relative IBD endoscopic activity was then assessed in this
population using the Mayo score (for UC) and the Simplified Endoscopic Activity Score for Crohn's
disease (SES-CD) (for CD) and compared with the sTREM-1 level from that time.
Results: In UC, sTREM-1 level correlated more strongly with the endoscopic activity (r = 0.498)
than the CRP level (r = 0.386) or ESR (r = 0.236), though was not superior to the partial Mayo score (r
= 0.611). Moreover, only sTREM-1 correlated significantly with the endoscopic activity irrespective
of the disease extent. In CD, the SES-CD correlated with both the CRP (r = 0.585) and ESR (r = 0.474)
levels, but not with sTREM-1 (r = 0.097).
Conclusions: In UC, sTREM-1 level correlated most closely with the endoscopic activity among
all serum biomarkers, but was not superior to the clinical activity index. Our results suggest that the
sTREM-1 level may represent a complementary marker for the assessment of the endoscopic activity
in UC but CD.
Keywords: Triggering Receptor Expressed on Myeloid Cells-1, C-reactive Protein, Erythrocyte
Sedimentation Rate, Ulcerative Colitis, Crohn's disease, Endoscopic Activity, Clinical Activity
References
1. Park JJ, Cheon JH, Kim BY, et al. Correlation of serum-soluble triggering receptor expressed
on myeloid cells-1 with clinical disease activity in inflammatory bowel disease. Dig Dis Sci.
2009;54:1525-1531.
2. Jung YS, Kim SW, Yoon JY, et al. Expression of a soluble triggering receptor expressed on
myeloid cells-1 (sTREM-1) correlates with clinical disease activity in intestinal Behcet's disease.
Inflamm Bowel Dis. 2011;17:2130-2137.
3. Schenk M, Bouchon A, Seibold F, et al. TREM-1-expressing intestinal macrophages crucially
amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. J Clin
Invest. 2007;117:3097-3106.
44
Session4-1
Surgery for gastroduodenal Crohn's disease
Akira Sugita1, Kazutaka Koganei1, Kenji Tatsumi1, Ryo Futatsuki1,
Hirosuke Kuroki1, Sayumi Nakao1, Katsuhiko Arai1, Hideaki Kimura2,
Fumihiko Kito1, Tsuneo Fukushima3
1
Department of Surgery, Yokohama Municipal Hospital,
Inflammatory Bowel Center, Yokohama City University Hospital
3
Matsushima Clinic
2
Gastroduodenal lesions are relatively rare complications in Crohn's disease. However, severe
stricture or fistula in stomach or duodenum which deteriorate patients' QOL are required to be
treated by surgery.
The incidence of surgical treatment for gastroduodenal Crohn's disease was 7% which was 26 of 374
cases with intestinal surgery in our institute. Seventy percent of these lesions were secondary lesion
which came from primary Crohn's disease in small intestine or colon.
Three lesions in stomach were gastrocolonic fistulas which was treated by wedge resection of
stomach with resection of diseased colon. Long duodenal stricture was found in 7 cases, which was
treated gastrojejunostomy. In 17 cases with duodenal fistula, simple closure underwent for the fistula
with small size and duodenojejunostomy was performed for duodenal defect with large size, which
showed low incidence of complications with good functiuon.
Gastroduodenal Crohn's disease with stricture or fistula which include primary and secondary lesion
should be treated by adequate surgical procedure without any delay.
45
Session4-2
Ileal Pouch Anal Anastomosis for Ulcerative Colitis:
Management of Complications Related to Surgery and the Pouch
Kyu Joo Park, M.D.
Division of Colorectal Surgery
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
Up to 20~30% of patients ulcerative colitis (UC) patients eventually undergo surgical treatment.1
Since AG Parks and RJ Nicholls introduced ileal pouch anal anastomosis (IPAA) for avoiding
permanent ileostomy in 1978 2, it has been a standard surgical procedure for ulcerative colitis, and
currently, IPAA is accepted as safe procedure with good functional results and improvement of
quality of life.3-6
But, there are many complications after IPAA and many reports still presented significant rates of
morbidity and mortality.7, 8 Early postoperative complications, such as small bowel obstruction, pouch
bleeding, leakage and pelvic sepsis, are especially more detrimental to the patients who have been
taking long-term anti-inflammatory drugs. Furthermore, late complications, such as pouchitis, fistula,
stricture and incontinence are often troublesome and sometimes deteriorate satisfactions on surgical
treatment. These complications are difficult to manage and the treatment would be complex as being
combined with medical and surgical methods. When the problem could not be resolved, pouch
failure would develop as the most serious result of the IPAA procedure.9
Recently in Korea and Japan, the incidence of UC has been increasing and the surgical treatment
might also have increased.10 But, the reports concerning the long-term outcomes of treatment
for complications after IPAA in Asian UC patients are rare. We have looked into early and late
complications related to IPAA for UC performed at our institution, and the outcomes of treatment on
these complications.
Between March 1998 and February 2010, 61 consecutive patients underwent IPAA for UC by a
surgeon who has been serving in colorectal division at Seoul National University Hospital. The
patients were registered prospectively and analyzed retrospectively.
Sixty-two cases of IPAA were performed, including one re-pouch procedure. Elective operations
were performed in 54 (87.1%), and emergent operations were in 8 (12.9%). Double stapling technique
was performed in 58 (93.5%), and hand sewing in 4 (6.5%). Protective loop ileostomy was made in
61 (98.4%). These were taken down in 60 patients (96.8%) after the median of 4.4 months.
Twenty-five (40.3%) had early postoperative complications and 11 (17.7%) of these were related
to pouch, including pouch bleeding, anastomosis rupture and pelvic abscess. Most of the patients
were successfully managed conservatively, except for one patient in whom surgical drainage of
pelvic abscess was needed. Seventeen patients (28.3%) had complications related to ileostomy takedown. Twenty-six (41.6%) had late complications during follow-up, and in 20 (32.3%) patients,
complications were related to the pouch. All patients with pouchitis (N=16, 25.8%) were managed
medically, but surgical treatment was necessary for pouch vaginal fistula, peranal abscess or fistula,
46
and anastomosis stricture. One patient with recurrent fistula, who had received repeated local repairs,
eventually underwent pouch removal and re-pouch procedure. Pouch failure developed in 2 patients
(3.2%). Emergency operation was the significant risk factor of the early complications, and pouchitis
was related to the early and late complications. The early and late complication did not affect on the
pouch function of stool frequency.
Our results indicate that IPAA procedure for UC is a safe and successful procedure despite
substantial complication rates. Continuous follow-up examinations and aggressive management for
the pouch related complications are critical for the lower rate of pouch failure and good functional
outcomes.
Reference
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Cottone M, Scimeca D, Mocciaro F, et al. Clinical course of ulcerative colitis Dig Liver Dis
2008: 40 Suppl 2; S247-252
Parks AG, Nicholls RJ Proctocolectomy without ileostomy for ulcerative colitis Br Med J
1978: 2; 85-88
Utsunomiya J, Iwama T, Imajo M, et al. Total colectomy, mucosal proctectomy, and ileoanal
anastomosis Dis Colon Rectum 1980: 23; 459-466
Meagher AP, Farouk R, Dozois RR, et al. J ileal pouch-anal anastomosis for chronic
ulcerative colitis: complications and long-term outcome in 1310 patients Br J Surg 1998: 85;
800-803
Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function
in 1005 patients Ann Surg 1995: 222; 120-127
Park KJ, Park G Analysis of the Results of Surgical Treatment Options for Ulcerative Colitis
J Korean Soc Coloproctol 1997: 13; 77-96
El-Raouf AA, Hak NG, Fathy O, et al. Outcome of pouch surgery for ulcerative colitis: single
center experience Hepatogastroenterology 2008: 55; 2130-2134
Hueting WE, Buskens E, van der Tweel I, et al. Results and complications after ileal pouch
anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients Dig
Surg 2005: 22; 69-79
Bach SP, Mortensen NJ Revolution and evolution: 30 years of ileoanal pouch surgery
Inflamm Bowel Dis 2006: 12; 131-145
Yang SK, Hong WS, Min YI, et al. Incidence and prevalence of ulcerative colitis in the
Songpa-Kangdong District, Seoul, Korea, 1986-1997 J Gastroenterol Hepatol 2000: 15; 10371042
47
Session5-1
Pleiotropic Action of Gut Tropic Factors Derived from Conditioned
Mesenchymal Stem Cells
Kanna Nagaishi1, Shuhei Watanabe2, Yasuyoshi Naishiro3, Kentaro Yamashita2, Yoshiaki Arimura2,
Mineko Fujimiya1, Yasuhisa Shinomura2, Kohzoh Imai4
1
3
4
2
Background/Aims: Although mounting evidence implicates mesenchymal stem cells (MSCs)
in intestinal tissue repair, the mechanism of action remains uncertain. Therefore, we focused on
humoral gut tropic factors derived from conditioned MSCs and their therapeutic effects through
paracrine interactions for achieving definitive repair.
Methods: Rat bone marrow MSCs were exposed to INFg (designated as γCM), normoxia (norCM)
or hypoxia (hypoCM) to explore the optimal MSC-conditioned medium (MSC-CM). DSS colitis and
TNBS colitis was induced in Lewis rats and C57BL/6 mice, respectively. MSC-CM was systemically
administrated for five days after inducing colitis. The effects of MSC-CM on rat intestinal epithelial
cell (IEC-6) viability, mobility, apoptosis and cell cycle were assessed by MTT, scratch assay,
TUNEL reaction and FACS, respectively. Immunologic modulation of MSC-CM was evaluated on
cytokine production in both laminar propria lymphocytes (LPL) isolated from TNBS colitis-induced
mice and murine macrophage cell line (RAW264.7) stimulated with LPS. The contents of MSC-CM
were estimated using rat cytokines antibody array and MALDI-TOF/MS analysis.
Results: MSC-CM enhanced recovery from DSS colitis in rats and significantly alleviated TNBS
colitis in mice. Body weight restoration and disease activity index were significantly improved in the
group administrated MSC-CM. Strong driving force for the epithelial cell proliferation was revealed
by the Ki-67 labeling index. The effect to cell survival, migration and suppression of apoptosis in
IEC-6 were significantly superior in hypoCM to γCM and norCM treatment through the activation
of the PI3K-Akt pathway. IL-2, IFNg and IL-17A secretions in LPL and TNFa and IL-6 secretions in
RAW cells were down-regulated with MSC-CM treatment while IL-10 secretion was up-regulated.
MSC-CM contains pleiotropic factors promoting anti-inflammatory, proliferative, and remodeling
phase in the wound healing machinery.
Conclusion: Optimization of pleiotropic gut tropic factors in MSC-CM is urgent as opening a new
avenue for drug discovery or basis for cell-based therapy for IBD.
48
Session5-2
Promoter polymorphism of the EED gene is associated with the
susceptibility to ulcerative colitis
Geom-Seog Seo,* Suck-Chei Choi,* Ki-Jung Yun,†Soo-Cheon Chae†
*†Digestive Disease Research Institute, Department of Internal Medicine,* Pathology,† School of
Medicine, Wonkwang University, Iksan, Chonbuk 570-749, South Korea
Backgrounds: Embryonic ectoderm development (EED) protein is involved in multiple cellular
protein complexes. EED mediates the repression of gene activity through histone deacetylation, and
it may act as a specific regulator of integrin's function. This gene was identified as a candidate gene
for the susceptibility to IBD by our previous cDNA microarray analysis.
Aim: The present study aimed to validate the expression level of the EED gene in patients with
IBD by performing RT-PCR, and we investigated whether the polymorphisms in the EED gene are
associated with the susceptibility to UC, and whether a functional EED promoter polymorphism is
related to UC.
Methods: Genotype analysis of the EED SNPs was performed by single-base extension (SBE)
analysis. The haplotype frequencies of the EED gene for multiple loci were estimated using the
expectation maximization (EM) algorithm. The promoter region of the human EED gene, including
the g.-1850G>C allele, was isolated by PCR. The amplified PCR products were inserted into the
pGL3-basic vector and the luciferase activity was analyzed.
Results: The expression level of the EED gene was significantly decreased in both the UC and CD
patients and it was significantly higher in the liver and ileum than in the other tissues of the human
digestive system. The genotype and allele frequencies of the g.-1850G>C polymorphism of the EED
gene in the UC patients were significantly different from those of the healthy controls (P = 0.018 and
0.017, respectively). The luciferase activity assay showed that the promoter activity was decreased
about 2-fold in the construct containing the g.-1850G allele compared with that of the construct
containing the g.-1850C allele, which means that the allele G could produce less EED mRNA.
Conclusion: These results suggest that the g.-1850G>C polymorphism in the EED gene might be
associated with the susceptibility to UC by the change of the EED expression level.
Keywords: EED . WAIT-1 . promoter assay . Haplotype . IBD
49
New treatments for IBD after anti-TNF
Stefan Schreiber
Christian-Albrechts-University, Kiel
Crohn’s disease represents a life-long condition that is characterized by chronic progression with
development of non-inflammatory complications (e.g. stenoses, fistula, abscesses). Only few patients
present with uncomplicated courses in which phases of symptomatic activity intervene with a
complete remission. Most patients develop an ongoing, chronic inflammatory activity (as defined on
the level of the immune system) which persists even if a symptomatic remission can be induced and
maintained by therapy. Anti-TNF therapies have been demonstrated to alter the course of disease
(i.e. induce mucosal healing and reduce CD-specific hospitalizations and surgeries). However, these
agents are often used late in the disease career and therefore in patients who have already developed
some non-inflammatory complications. The course of ulcerative colitis is less well analyzed.
However, in main aspects these observations in Crohn’s disease can be transferred to patients with
ulcerative colitis.
Several novel anti-inflammatory therapies have successfully completed the first stages of clinical
development. The most promising strategies comprise the blockade of adhesion molecules (mainly
the alpha4-beta7 – MadCam complex), blockade of interleukin-6 and inhibition of cytokine-receptor
associated janus kinases. In particular, the blockade of IL-6 which was first introduced by T.
Kishimoto and co-workers appears to be promising. The dissection between trans-signaling and
classical signaling offers a strategy that could lead to elimination of chronic inflammatory activity
without the side effects of systemic immune suppression. In contrast, strategies that specifically
inhibit T-cells have failed development.
However, before embarking on novel therapies, the present use of anti-TNF for the therapy of IBD
should be optimized. Anti-TNF therapy is often used too late in the course of disease to still avoid
the formation of anatomical damages. Secondary failures to anti-TNF have to be analyzed to
decide whether a dose increase or intensification, a switch between anti-TNF agents or a change in
the substance class for therapy is more beneficial to the patient. For this, we have to divide patients
in two groups (i) those who show persisting symptoms despite of anti-TNF use but no signs of
inflammatory activity and (ii) patients in which anti-TNF therapy is not stopping the inflammatory
pathophysiology.
50
Session6-1
Use of Tacrolimus and Infliximab for Refractory Ulcerative Colitis.
Hiroshi Nakase, Tsutomu Chiba
Department of Gastroenterology and Hepatology, Endoscopic Medicine, Kyoto University.
Ulcerative colitis (UC) is a chronic disease featuring recurrent inflammation of the colonic
mucosa. The treatment of patients with UC is dependent on several important factors, including the
anatomical extent of disease, the severity of disease, disease chronicity, and disease complication.
Recent development of new drugs and biological agents has altered the therapeutic possibilities for
patients with UC. Generally, the majority of active UC patients respond to treatment with oral and
local 5-aminosalicylic acids (5-ASA) and corticosteroid. Some UC patients do not respond to it and
become steroid-dependent or steroid-refractory condition. Thiopurine analogs have an established
role as mainstay therapy for such refractory cases of UC. However, a substantial proportion of
patients does not tolerate, or fail to respond to thiopurines. In such circumstances, treatment with
tacrolimus or infliximab (IFX) has been considered to induce and/or maintain remission. We
herein report the efficacy of tacrolimus and IFX in patients with refractory UC in a prospective,
uncontrolled, open-label study.
Efficacy of Tacrolimus in refractory UC
Between April 2001 and September 2010, 44 patients with refractory UC (Gender 26 male, 18
female; Age 15~78) were enrolled. Initially, tacrolimus was administered orally to aim for serum
trough level of 10~15ng/ml. After patients achieved their clinical remission, tacrolimus was tapered
to the serum trough level 5~10ng/ml. Disease activity was defined as Modified Truelove-Witts
severity index (MTWSI) score (severe category: more than twelve). Clinical response and remission
was defined as a drop of the score by more than 4 points from baseline and the score 4 or less,
respectively. According to this definition, 14 of 44 patients were defined as severe. Thirty-one and 13
patients had pancolitis and left sided colitis, respectively. Of 44 patients, 32 (72.7%) achieved clinical
remission within 30 days. The median MTWSI score decreased from 11 at the initiation to 3.0 at
30 days after the start of treatment. None of the patients underwent colectomy in 30 days. Based on
Kaplan-Meier survival analysis, the overall cumulative colectomy-free survival was estimated to be
63.6% at 67 months.
Efficacy of IFX in refractory UC
Between November 2005 and September 2010, 21 patients with refractory UC (Gender 8 male, 13
female; Age 18~69) received intravenous infusion of IFX at a dose of 5mg/kg. We evaluated their
disease activity and therapeutic response in the same definition in tacrolimus treatment. Fifteen and
6 patients had pancolitis and left sided colitis, respectively. The proportion of patients who were in
clinical remission at week 2 and week 8 was 47.6% (10 of 21) and 57.1% (12 / 21), respectively. The
overall cumulative colectomy-free survival was estimated to be 66.9% at 54.3months.
Our data strongly indicates that tacrolimus and IFX are generally well tolerated and can be
52
considered alternative options in patients with refractory UC. However, we still have following
questions; (1) Which should be firstly administered for cases of refractory UC, tacrolimus or
IFX? (2) Should IFX be kept in stable long term remission of UC? (3) Can tacrolimus be used
as a maintenance therapy for patients with UC who are intolerant or refractory to conventional
immuomodulators? To answer these questions, further clinical trial and long-term data on patients
treated with tacrolimus or IFX are needed.
53
Session6-2
The efficacy and safety of infliximab therapy in Korean patients with
crohn's diseases: a retrospective, multicenter study
Chang Hwan Choi, M.D., In Do Song, M.D., Se Kyung Chang, M.D.,
Young Ho Kim, M.D.*, Won Ho Kim, M.D.**, IBD study group of the Korean Association for the
Study of the Intestinal Diseases
Department of Internal Medicine, Chung-Ang University College of Medicine,
*Sungkyunkwan University College of Medicine,
**Yonsei University College of Medicine, Seoul, Republic of Korea
Background & Aims: The aim of this study was to evaluate the efficacy and safety of infliximab in
Korean patients with inflammatory and fistulizing Crohn's disease (CD).
Methods: A total of 218 patients with refractory luminal CD (n=140) and fistulizing CD (n=58) or
both of them (n=20) between 2007 and 2011 were reviewed retrospectively in 28 Korean referral
centers. Patients received 5 mg/kg of infliximab intravenously on week 0, 2, 6 and then every 8
weeks thereafter. Clinical response was classified as complete response (CR), partial response (PR),
and non-response (NR). In luminal CD, CR was defined as a decrease of CDAI score to less than 150
points and PR as a decrease in CDAI score of 70 points or more from the baseline value and at least
a 25% reduction in the total score. The benefit of infliximab maintenance treatment was assessed in
patients with initial early (2 weeks) responses to single infliximab infusion. In fistulizing CD, CR
was defined as the absence of draining fistulas and PR as a reduction of at least 50 percent from base
line in the number or size of draining fistulas. The benefit of maintenance treatment was assessed in
patients with responses at week 14.
Results: The total patients were comprised of 147 (67.4%) men and 71 (32.6%) women with a median
age of 30 years (17-81). The patients received a median of 7 infusions (1-31) and had a median followup period of 15 months (1-104). At week 2, the response rate (CR + PR) in luminal CD was 141/160
(88.1%); CR 57/160 (35.6%) and PR 84/160 (52.5%). At week 6, the response rate was 137/160 (85.6%);
CR 80/160 (50%) and PR 57/160 (35.6%). Among week-2 responders, the response and CR rates were
86/104 (82.7%) and 60/104 (57.7%) at week 30, respectively. At week 54, those were 56/74 (75.7%)
and 37/74 (50%), respectively. The response rates at week 30 and 54 were greater in patients who
received infliximab earlier (diagnosis to 1st infliximab < 5 years) and combined with azathioprine. In
patients with fistulizing diseases, the response rate was 66/78 (84.6%) at week 14; CR 28/78 (35.9%)
and PR 38/78 (48.7%). Among week-14 responders, the response and CR rates were 47/51 (92.2%)
and 27/51 (53%) at week 30, respectively. At week 54, those were 33/37 (89.2%) and 19/37 (51%),
respectively. The response rate was greater in perianal fistulas than in the others. Twenty two patients
(10.1%) experienced adverse events. Serious adverse events were developed in 8 (3.7%) patients
and then infliximab infusion was stopped; 3 had acute infusion reaction, 2 had serum sickness-like
syndrome and 3 had infectious diseases (reactivation of tuberculosis, necrotizing pancreatitis).
Conclusions: Infliximab induction and maintenance therapies were effective and safe in Korean
patients with refractory luminal and fistulizing CD. In luminal CD, the efficacy of maintenance
therapy was superior in patients who received infliximab earlier and combined with azathioprine. In
54
fistulizing CD, infliximab was most effective in perianal fistulas. However, clinicians must be careful
for the occurrence of rare but critical adverse event.
Keywords: Crohn's disease, Infliximab
55
Session6-3
Management of post-operative Crohn's disease.
Katsuyoshi Matsuoka, M.D., Ph.D.
Div. of Gastroenterology and Hepatology,
Dept. of Internal Medicine, School of Medicine Keio University
56
Session6-4
A case of acute severe ulcerative colitis
Kang-Moon Lee, M.D.
Department of Internal Medicine, College of Medicine, The Catholic University of Korea
Abstract
- 41 year-old UC female patients
- She had been in remission on 5-ASA for 3 years after diagnosis.
- She complained of frequent bloody diarrhea since 2 months ago and recently, her symptoms were
rapidly aggravated.
- She was admitted and treated with i.v. corticosteroid.
How do we treat for acute severe ulcerative colitis?
Which is the best treatment option in case of intravenous-steroid resistant UC?
In this case, treatment strategy for intravenous steroid refractory UC will be discussed.
57
Session7-1
Takayuki Matsumoto
Department of Lower Gastroenterology, Hyogo College of Medicine.
Abstract:
Although the etiology of IBD still remains unclear, recent advances in modulating immunological
abnormalities in IBD have brought us major improvement in the outcome of medical treatment.
In ulcerative colitis (UC) and Crohn's disease (CD), new therapeutic approaches with biologics,
immunomodulators and cytapheresis have introduced in theses ten years. However, it is still not
clear to select and manipulate one from these options to a particular status of the patients.
Currently, guidelines for IBD treatment are available from ECCO and ACG. As published in the
various journals, genetic aspects of IBD in Asia including Korea, China and Japan are different from
those in the western world. For example, 3 SNPs in the NOD2 are not observed in Asian population.
Therefore, it is very important to establish treatment guidelines for IBD patients common to Asian
population. Although there are some differences in the drugs and treatment strategies even in these
three countries, it is essential to make a group to discuss further agreements in establishing those
guidelines.
In the lecture, Japanese outline of guidelines for UC and CD are summarized as one of the examples
which could be a base to discuss for Asian guidelines.
58
Session7-2
How to establish Asian consensus and guideline in IBD?
Young-Ho Kim
Division of Gastroenterology, Samsung Medical Center,
Sungkyunkwan University School of Medicine
The prevalence and incidence of inflammatory bowel disease (IBD) differs between Asian and
Western countries. The incidence of IBD has the tendency to increase in Asia in recent years
although Asia is a very diverse continent and marked geographic and ethnic differences have been
reported within Asia. In addition to epidemiology, clinical manifestation, diagnosis, and treatment
of IBD in Asian region are somewhat different from those in Western countries. Differences in
the environmental and genetic background of the population in a particular geographic location
contribute to this variance. For example, Asian studies have shown the absence of the NOD2/
CARD15 gene mutation, well-known genetic susceptibility to Crohn's disease. In Asia, men appear
to be at greater risk for Crohn's disease and perianal disease is generally less common. And, IBD
seems to have good long-term prognosis. In point of clinical practice, infectious diseases, especially
intestinal tuberculosis and other intestinal infections, are common in this region; they added to the
complexity in the diagnosis and treatment of patients with IBD. Also, the high endemic rates of
hepatitis B virus infection require stringent screening before initiating immune-suppressive agents.
In addition, leukocytapheresis and nutritional therapy are treatment options in some Asian countries.
Recognition of these differences has raised the need for development of Asia-specific guidelines for
diagnosis and treatment of IBD. Beside the diagnosis and treatment of IBD in different situations,
the guidelines also included service delivery, patient perspective, and associated aspects of IBD
diagnosis and treatment.
The major limitation of development of Asian guideline is a paucity of studies performed in Asian
countries. That means development of Asian guidelines will depend on making a consensus such
as Delphi approach, although evidence-based approach is essential. And, there will be substantial
variations in medical and socioeconomic aspects in various ethnic groups in Asia, which will make it
difficult to develop uniform guidelines. During this process, we can know what studies are necessary
and have the chances to plan multi-national studies to make Asia-specific guidelines.
59
Session0-0
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60
Poster
Group 1 Clinical 1
Group 2 Clinical 2
Group 3 Clinical 3
Group 4 Clinical 4
Group 5 Clinical 5
Group 6 Clinical 6
Group 7 Clinical 7
Group 8 Clinical 8
Group 9 Clinical 9
Group 10 Clinical 10
Group 11 Clinical 11
Group 12 Basic 1
Group 13 Basic 2
Group 14 Basic 3
Group 15 Basic 4
61
P-1
Efficacy of the first infliximab administration predicts long-term
prognosis in refractory ulcerative colitis
Hiroki Tanaka, Satoshi Motoya, Masaki Yamashita, Akimichi Imamura
Inflammatory Bowel Disease Center, Sapporo Kosei General Hospital, Sapporo, Japan
Background/Aims
Infliximab (IFX) has developed into a useful treatment option in Japan for patients diagnosed with
refractory ulcerative colitis (UC). However, the long-term outcome of IFX treatment remains unclear.
We analyzed the influence of the efficacy of the first IFX administration for refractory UC on the
long-term prognosis.
Methods
Retrospective data was collected from 60 UC patients who were treated with IFX at Sapporo Kosei
General Hospital from July 2005 to May 2011. The efficacy of IFX treatment was evaluated based on
the decrease in the Lichtiger’s Clinical Activity Index (CAI). Response was defined as a decrease in
the CAI by at least 5 points from the baseline value, whereas remission was defined as a CAI score
of ≤4. The CAI scores were evaluated at baseline and at 2 and 6 weeks following IFX infusion. The
cumulative colectomy rate following IFX administration was estimated by using the Kaplan–Meier
method.
Results
Of the 60 patients, 28 were females. The mean age of the patients was 37.3 ± 15.2 years, the mean
duration of the disease was 5.3 ± 4.8 years, and the mean CAI score was 9.5 ± 2.5. Two weeks after
IFX administration, 55% patients showed a response and 47% patients had achieved remission. Of
the 33 patients who showed a positive response to treatment (responders) at week 2, 29 achieved
remission by week 6. Of the 27 patients that did not respond to treatment (non-responders) at week 2,
only 5 achieved remission by week 6. The cumulative colectomy rate following IFX administration
was significantly higher in the non-responders (63%) as compared to that in the responders (8%).
Conclusions
The patients that were determined as non-responders 2 weeks following the first IFX infusion were
apparently unable to achieve remission and required colectomy within a period of 5 years.
63
P-2
Therapeutic efficacy of infliximab in the treatment of steroid-resistant
or -dependent ulcerative colitis
Motochika Yasaka, Fumihito Hirai, Noritaka Takatsu, Takashi Hisabe,
Toshiyuki Matsui
Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
Objective: The objective of the study was to determine the efficacy of infliximab (IFX) in remission
induction for ulcerative colitis (UC) resistant to conventional treatments. Patients: Included in the
study were UC patients that was steroid-resistant or -dependent and had moderate or greater severity.
The study population comprised 19 patients with IFX in the clinic between 2006 and 2011.
Methods: The patients were to receive 3 doses of 5 mg/kg of IFX at Weeks 0, 2, and 6 with
subsequent maintenance therapy once every 8 weeks. The following 3 endpoints were evaluated: 1)
short-term outcome after 6-10 weeks; 2) long-term outcome after 30 weeks; 3) short-term outcome
for the 6 patients receiving tacrolimus in the clinic as prior therapy.
Results: 1) Short-term outcome: The clinical response rate was 57.8% (11 of 19 patients), and the
remission rate was 36.8% (7 of 19 patients). The endoscopic response rate among the 15 patients with
endoscopic data available for Weeks 2-10 was 46.7% (7 of 15 patients), and the endoscopic remission
rate was 33.4% (5 of 15 patients). 2) Long-term outcome: The clinical response rate in the 14 patients
observed to Week 30 or beyond was 50.0% (7 of 14 patients), and the remission rate was 35.7% (5 of
14 patients). Two of the 7 patients with no response were treated surgically. 3) The clinical response
rate among the 6 patients who received tacrolimus as prior therapy was 66.6% (4 of 6 patients), and
the remission rate was 33.3% (2 of 6 patients).
Conclusions: The study revealed that IFX for the treatment of refractory UC had a short-term
efficacy of about 60% and a long-term efficacy of about 50%. Therefore
we concluded that IFX is a efficious treatment for refractory UC.
64
P-3
Efficacy of Infliximab Rescue Therapy in Hospitalized Patients with
Steroid-Refractory Ulcerative Colitis: Single Center Experience
Choul Ki Park, MD, Hee Jae Hyun, MD, Eun Yeong Kim, MD,
Background/Aims: In hospitalized patients with acute steroid-refractory ulcerative colitis (UC),
infliximab has been demonstrated to be one of medical rescue therapies to avoid colectomy. We
report the result of a retrospective observational study to find the efficacy and safety of infliximab as
rescue therapy in our hospital. Methods: Between January 2007 and January 2010, nine hospitalized
patients with steroid-refractory UC were selected to receive three infusions of infliximab (5 mg/kg)
at weeks 0, 2, and 6. Efficacy of treatment was evaluated at 8 weeks after the first infliximab infusion
and at the end of follow-up period. Adverse events related to infliximab rescue therapy were also
collected. Results: Seven patients (77.8%) had completed three infusions of infliximab and achieved
clinical response at 8 weeks after the first infliximab infusion. Clinical remission rate and the rate of
mucosal healing at 8 weeks were 57.1% (4/7) and 71.4% (5/7), respectively. They were followed up
for mean duration of 801 days (median 698 days, range 547-1502). One patient underwent emergency
colectomy at weeks 2 because of colon perforation. Another one patient discontinued infliximab
treatment at weeks 4, because of Clostridium difficile-associated colitis. Finally, colectomy was
avoided in 88.9% (8/9) of cases. There was no mortality. Conclusions: Rescue therapy with
infliximab has a sustained clinical benefit in 88.9% of our hospitalized patients with acute steroidrefractory UC. Future prospective and long-term follow-up trials with a large number of patients are
needed to confirm the efficacy and safety of the treatment.
Key Words: Ulcerative Colitis; Steroid-refractory; Infliximab; Rescue Therapy
65
P-4
The experience of infliximab for Ulcerative colitis in Korea.
Hyun Il Seo MD, Dong Il Park PhD
Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Background : Recently, a chimeric immunoglobulin G1 monoclonal antibody to tumor necrosis
factor, infliximab has been used as rescure therapy for refractory ulcerative colitis (UC) in Korea.
But there was no data about safety and efficacy of infliximab on Korean UC patients.
Method : Multicenter, retrospective review of medical records of patients who treated with infliximab
for UC. The severity and response to treatment were measured using modified (partial) Mayo score
(Mayo score without endoscopy). Clinical remission was defined as a modified Mayo score of 2
points or lower, with no individual subscore exceeding 1 point. The score was assessed at every visit
for infusion of infliximab. Cummulative rates of remission and adverse events were calculated.
Results : Twenty eight patients (men=22) were enrolled. The indications for infliximab treatment 27
patients were as followed (multiple-choice); Steroid 1. dependence (n=17) or 2. refractoriness (n=10),
Immune-modulator 3. refractoriness (n=9) or 4. intolerance (n=4). The rest one by patient requiring
(n=1). The baseline median Mayo score and modified Mayo score were 11 (interquartile range :
10~11) and 8 (interquartile range : 7~8) respectively. Median numbers of infusion was 4 (interquartile
range : 3~7).
After first infliximab infusion, twenty seven patients were followed and 48.1 % (13/27) of
patients achieved remission. After 4th infliximab infusion, 13 patients were followed and 61.5%
(8/13) achiedved remission. And after 8th infusion, 66.6%(2/3) achieved remission. Total adverse
event occurred in 4 patients. They were pneumonia, rhabdomyolysis, fever of unkown origin
and pancreatitis. And (n=10) patient stopped because of follow up loss (n=4), side effects (n=2),
ineffectiveness (n=2) and exacerbation after remission.
Conclusion : Infliximab infusion therapy for refractory UC was relatively safe and effective
treatment. For make fine indication for infliximab in UC, further large scaled long term study are
needed
Key Words: Ulcerative Colitis; Infliximab; Rescue Therapy
66
P-5
A case of new-onset ulcerative colitis in a patient with ankylosing
spondylitis during infliximab treatment; paradoxical reaction of
anti-TNF α or not?
Yong Sung Choi M.D., Jong Kyu Kim M.D., Jung Pil Suh M.D.,
Suk Hee Lee M.D.**, In Taek Lee M.D.*,
Department of Gastroenterology, Department of Surgery*, Department of Pathology**,
Daehang Hospital, Seoul, Korea
Background; Infliximab, a monoclonal antibody to tumor necrosis factor-α, is known to be effective
in patients with ankylosing spondylitis (AS), inflammatory bowel disease, rheumatoid arthritis and
psoriasis, who have not responded to conventional therapy. However, there has been a series of the
literature about paradoxical inflammation such as psoriasis, uveitis and ulcerative colitis in patients
who had been given anti-TNF α due to its complex immune regulatory function.
We describe a case of new-onset ulcerative colitis (UC) in a patient with AS during remission
induction therapy with infliximab. We cannot exclude UC as linked to AS since there appears to
be an association between them. However, it is unlike that the UC arises when joint disease is wellcontrolled with infliximab therapy.
Case; A 35-year-old patient presented with bloody and mucoid diarrhea accompanied by lower
abdominal discomfort for 3 weeks. He had a history of ankylosing spondylitis for which he had
been started on intravenous infliximab (Remicade) at a dose of 5 mg/kg at 0, 2 and 6-week in a
rheumatologic clinic six weeks ago. His joint symptoms improved. About three week after the first
dose of infliximab infusion, bloody diarrhea occurred and he visited our GI clinic. Colonoscopy
demonstrated continuous mucopurulent hyperemic inflammation with mucosal friability on the
sigmoid colon and rectum. Histology of the colonic mucosa revealed acute and chronic inflammation
with cryptic abscesses and basal lymphoplastomacytosis. Stool culture was negative for bacterial and
parasitic infections. A diagnosis of distal ulcerative colitis was made and oral and local mesalamine
was started daily. His symptoms improved promptly and he has been free of symptom for 8 months.
Conclusion; Our case would seem to support the hypothetical paradoxical effect of anti-TNF α,
and further study is necessary to investigate its immunodysregulatory mechanism to understand the
pathophysiology of ulcerative colitis.
67
P-6
Efficacy of a probiotic preparation(VSL#3) in the patients with
ulcerative colitis and its effect on the cytokines
Gyoo Moon, M.D.1; Ji Hyun Lee, M.D.2; Hyeok Jin,Kwon, M.D.2;
Woo Jin Jung, M.D.2; Pyoung Ju Seo, M.D.2; Lee, Ju Hyeong3
1
Department of Gastroenterology, Hanam Song Do Colorectal Hospital,
Hanam, Korea, Republic of.
2
Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea, Republic of.
3
Songdo Biocell Research institute, Seoul, Korea, Republic of.
Background & Aims : Ulcerative colitis is a chronic inflammatory bowel disease that has periods
of exacerbated symptoms and periods that are symptom-free. Probiotics could possibly induce
remission in the treatment of active UC. We evaluated the clinical efficacy of probiotic preparation
VSL#3 and assessed cytokine concentration changes in the treatment of mild to moderate UC
patients.
Methods: Thirteen eligible patients with mild to moderate UC between the ages of 20 to 70 received
VSL#3 4 sachets daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3
therapy was assessed by Mayo ulcerative colitis endoscopic score; colonic tissue cytokine profiling
done at baseline and at week 8.
Results: Thirteen patients (8 males and 5 females) with a mean age of 45.5 were enrolled in the
open-label VSL#3 study and completed 8 weeks of VSL#3 treatment. VSL#3 treatment outcome
demonstrated remission (defined as UCDAI ≤3) in 61.5% of subjects(n= 8); response (decrease in
UCDAI ≥2) in 15.3 %(n= 2); no change or worse in 23.1 % (n=3). A significant decrease (p=0.004)
in UCDAI from baseline 6.15±1.77 to study completion 1.15±0.69 was observed. The levels of proinflammatory cytokines TNF-α(162.8±211.1 pg/ml to 34.7±42. pg/ml, p=0.011) , IFN-γ(721.4±541.3
pg/ml to 324.0±470.2 pg/ml, p>0.05), and IL-12 (61.6±47.7 pg/ml to 39.2±123.2 pg/ml, p=0.039) were
all dropped after VSL#3 therapy. And the anti-inflammatory cytokine IL-10 level (102.8±118.1 pg/ml
to 109.9±267.7 pg/ml, p>0.05) was increased after VSL#3 therapy.
Conclusions: Our study demonstrated that using VSL#3 in the treatment of mild to moderate UC
is effective in induction of remission and response. Those who responded to VSL#3 treatment had a
significant decrease in their UCDAI scores and colonic tissue pro-inflammatory cytokines level.
68
P-7
Safety and feasibility of daily granulocyte and monocyte apheresis in
patients with active ulcerative colitis: a prospective study
Background/Aim: Previous studies comparing efficacy of weekly and twice-a-week granulocyte and
monocyte apheresis (GMA) therapy for active ulcerative colitis (UC) found that the rate of clinical
remission was higher, and the mean time to remission was shorter in the twice-a-week treatment
group. We were interested to see safety and efficacy of a more intensive GMA treatment frequency
like daily regimen. This prospective study was to assess safety and efficacy of daily GMA therapy
for patients with active UC.
Methods: Thirty consecutive patients with moderately or severely active UC received daily GMA
treatment (5 sessions over 5 consecutive days) with the Adacolumn. Adverse event (AE), patient
tolerability and clinical symptoms were monitored daily.
Results: Sixteen patients (53%) experienced AE during at least one GMA session. The most
frequent AE was mild headache followed by fatigue and fever. None of the AE was serious, all
patients completed the 5 consecutive GMA sessions. Clinical symptoms (stool frequency and/or
rectal bleeding) were improved in 21 patients (70%) during the course of GMA therapy. Clinical
remission defined as normal stool frequency and no rectal bleeding was achieved in 7 patients (23%)
after 5 GMA sessions. Seven of 20 patients (35%) with moderately active disease achieved clinical
remission, whereas none of the 10 patients with severely active disease achieved clinical remission.
Total and differential leukocyte counts, platelet count and hemoglobin level did not significantly
change, but C-reactive protein level significantly decreased during the course of GMA therapy.
Conclusions: This is the first report on daily GMA in the treatment of patients with UC. Daily
GMA was safe and well-tolerated without serious AE. Further, daily GMA was associated with rapid
improvement of clinical symptoms in patients with moderately active UC. However, controlled trials
are warranted to assess a definite efficacy for daily GMA therapy.
69
P-8
Safety and efficacy of high-dose, 4.0 g/day mesalazine therapy for
patients with ulcerative colitis who relapsed under low-dose,
1.5-2.25 g/day maintenance therapy: a prospective study
Background/Aim: Mesalazine has shown efficacy for both inducing and maintaining clinical
remission in patients with mildly and moderately active ulcerative colitis (UC). However, the optimal
dose of mesalazine for the treatment of UC needs further investigation. Safety and efficacy of
increasing the dose of oral Pentasa up to 4.0 g/day for patients who relapse during treatment with
lower doses have not been investigated. This prospective study was to investigate whether increasing
the dose of oral Pentasa up to 4.0 g/day is safe and effective for patients who relapse under the lowdose, 1.5-2.25 g/day maintenance therapy.
Methods: Ninety consecutive patients who relapsed during maintenance therapy with oral Pentasa
at 1.5-2.25 g/day were included. All patients had mildly or moderately active UC at entry, and were
treated with oral Pentasa at 4.0 g/day for the following 8 weeks. During the study, corticosteroids,
immunosuppressants or tumor necrosis factor-α blocking agents were not given unless patients
developed severely worsening symptoms. At entry and week 8, endoscopic examinations were
carried out to assess the severity of endoscopic inflammation. The primary as well as the secondary
endpoints were clinical and endoscopic improvements at week 8.
Results: No patient experienced any serious side effect, and the treatment with 4.0 g/day Pentasa
over the 8 week period was well tolerated by all patients. Fifty-nine patients (66%) achieved
clinical improvement in stool frequency and/or rectal bleeding including 40 (44%) with clinical
remission (normal stool frequency and no rectal bleeding). Forty-three patients (48%) showed
endoscopic improvement including 25 (28%) with endoscopic remission. Patients with clinically and
endoscopically mild UC showed significantly higher remission rate as compared with patients with
moderate UC.
Conclusions: Increasing the dose of Pentasa up to 4.0 g/day appeared to be safe and effective for
patients who relapsed under low-dose, 1.5-2.25 g/day maintenance therapy.
70
P-9
Mucosal healing in patients with active ulcerative colitis during
granulocyte and monocyte apheresis therapy: a prospective cohort
study
Background/Aim: The impact of granulocyte and monocyte apheresis (GMA) therapy on mucosal
inflammation in patients with active ulcerative colitis (UC) has not yet been fully reported. The
primary objective of this study was to investigate the incidence of mucosal healing (MH) following a
course of GMA and the impact of MH on the maintenance rate of clinical remission in patients who
responded to this therapy. We were also interested in the predictive factors of MH during the course
of GMA therapy as well as clinical efficacy and safety of this treatment.
Methods: One hundred and twenty-four patients with clinically and endoscopically active UC
received 5 or 10 GMA sessions at one or two sessions/week. The endoscopic severity of mucosal
inflammation at entry and one week after the last GMA session were scored as follows: 0 = normal
mucosa and inactive disease; 1 = mild inflammation; 2 = moderate inflammation; 3 = severe
inflammation. MH was defined as score 0 or 1 at post GMA course.
Results: At entry, the endoscopic severity of the mucosal inflammation was score 2 in 100 patients
(81%) and 3 in 24 patients (19%). Following the course of GMA, 56 patients (45%) achieved clinical
remission (normal stool frequency and no rectal bleeding). Thirty-four of these 56 responders
achieved MH; 32 (94%) of the 34 patients with MH had an endoscopic score of 2 (moderate
inflammation) at entry. The maintained clinical remission rate was significantly higher in the 34
patients who achieved MH as compared with 22 patients who achieved clinical remission without
MH (P=0.0005).
Conclusions: MH is achieved more frequently in patients with moderate than with severe endoscopic
severity at entry. Further, patients with MH have a reduced risk of future clinical relapse as compared
with patients who achieve remission without MH.
71
P-10
Intensive, Daily Granulocyte and Monocyte Adsorptive Apheresis in
Patients with Active Ulcerative Colitis.
Aisaka Aki, Iiduka Bunei, Ayumi Ito, Emiko Nakao, Teppei Omori, Maria Yonezawa, Shiratori Keiko
IBD Center of Tokyo Women's Medical University Hospital, Tokyo, Japan.
BACKGROUND: Weekly adsorptive granulocyte/monocytes apheresis (GMA) with an Adacolumn
has been accepted as one therapeutic option in Japan for ulcerative colitis (UC) patients. Further,
more frequent GMA involving two sessions per week have been associated with a higher efficacy
rate in a shorter time as compared with weekly GMA.
METHODS: In an inpatient setting, 17 patients with moderately active UC dependent to prednisolone
(PSL) received 5 GMA sessions over 5 consecutive days per week for one week or two weeks.
Efficacy was evaluated by measuring the clinical activity index (Lichtiger’s CAI) and the endoscopic
activity index (Iizuka’s CSAI) at entry and within two weeks after the final session, while endoscopy
was performed at entry and within two weeks following the last session. Of the variables were
factored to see patients’ response to GMA.
RESULTS: Six of 17 patients had a marked improvement in the CSAI, 9 were poor responders
and in 2 pregnant patients endoscopy was not done. CAI score was improved in 64.7% of patients
(P<0.0001). An improvement in the CAI score was observed after the 2nd GMA session in most
patients. The CAI score after the 2nd GMA session appeared to be valuable for predicting the clinical
response to the subsequent GMA sessions. In the non-responders or poor responders, UC duration
was longer, the cumulative dosage of PSL was larger, and the patients’ past relapses were more
frequent as compared with patients who responded well.
CONCLUSIONS: Daily GMA was safe, and well tolerated. Short duration of UC, and less exposure
to corticosteroids were associated with good clinical and endoscopic response to GMA. We could
decide to start combination therapy or switch to an alternative treatment for non-responder after
three GMA sessions (just 3days).
72
P-11
Pneumocystis jiroveci pneumonia after initiation of infliximab therapy
in a patient with ulcerative colitis
Bo Sung Kwon1, Ja Seol Koo1, Jae-Won Yun1, Jong Jin Hyun1, Sung Woo Jung1,
Dae Won Park2, Hyung Joon Yim1, Sang Woo Lee1, Jai Hyun Choi1
1
Korea University College of Medicine, Seoul, Korea
2
Division of Infectious Diseases, Department of Internal Medicine,
Korea University College of Medicine, Seoul, Korea
Infliximab, a monoclonal antibody to tumor necrosis factor-alpha (TNFα), is used to treat patients
with moderate-to-severe Crohn’s disease. The application of infliximab has been extended to the
treatment of ulcerative colitis (UC) in patients who fail to respond to conventional therapy. However,
serious adverse events can occur as a result of anti-TNFα therapy. We present a case of a 30-yrold man with life-threatening Pneumocystis jiroveci pneumonia that developed after the initiation
of infliximab for the treatment of severe UC. Fortunately, the patient recovered completely after
treatment with trimethoprim-sulfamethoxazole and prednisolone. Later on, the patient did receive
infliximab therapy with antibiotic prophylaxis, without further complications. It is still unclear
whether prophylactic antibiotics against P. jiroveci pneumonia should be given to patients receiving
infliximab therapy. However, with the increase of infliximab therapy for inflammatory bowel disease,
practitioners should consider prophylactic treatment in patients on infliximab, along with other
immunosuppressants.
73
P-12
Anti-viral therapy is not necessarily indicated in ulcerative
colitis patients with cytomegalovirus infection detected by
immunohistochemistry
Yuriko Maruyama1), Katsuyoshi Matsuoka1), Yasushi Iwao2), Tomoharu Yajima1), Nagamu Inoue1),
Tadakazu Hisamatsu1), Tomohisa Sujino1), Kaoru Takabayashi1), Kazuaki Yoneno1), Yohei Mikami1),
Jun Miyoshi1), Shinta Mizuno1), Kayoko Kimura1), Takanori Kanai1), Haruhiko Ogata3),
Makio Mukai4), Toshifumi Hibi1)
1)
Division of Gastoenterology, Department of Internal Medicine,
School of Medicine, Keio University, Tokyo
2)
Center for Preventive medicine, Keio University Hospital, Tokyo
3)
Center for Endoscopic examination, Keio University Hospital, Tokyo
4)
Division of Diagnostic Pathology, Keio University Hospital, Tokyo
Background and aims: Cytomegalovirus (CMV) infection is considered to be an exacerbating factor
in ulcerative colitis (UC) patients. However, there are no specific tests to determine whether CMV
is a pathogenic or an innocent by-stander in the colon in UC. At this point, immunohistochemistry
(IHC) for CMV in biopsy specimens is one of the most specific tests to indicate antiviral therapy.
The aim of this study is to evaluate the clinical significance of CMV-IHC in UC by analyzing the
clinical course of patients with positive CMV-IHC staining. Methods: A total of 86 hospitalized UC
patients with moderate to severe activity between July 2009 and November 2011 were retrospectively
analyzed. CMV infection in the colon was evaluated by IHC in biopsy specimens. Results: Serum
CMV IgG was positive in 64 patients (74%) and negative in 22 patients (26%). Sixteen patients
(25%) out of the 64 CMV seropositive patients showed positive CMV-IHC staining. . Punchedout ulcers, which were reported to be a characteristic endoscopic feature of CMV, were observed
at a similar rate in CMV seronegative patients (7/22; 31.8%) and CMV-IHC positive patients
(4/15; 26.7%). Most importantly, 12 out of the 16 CMV-IHC positive patients (75.0%) responded to
conventional immunosuppressive therapies without administration of antiviral agents and showed
clinical improvement. Ganciclovir was administrated to four CMV-IHC positive patients and only
one patient avoided colectomy. Conclusions: During moderate to severe flare-up, one-fourth of
CMV seropositive patients have reactivation of CMV in the colon if assessed by IHC. There is no
difference on endoscopic severity or features between CMV-IHC positive and CMV-seronegative
patients. The most important finding n this study is that most CMV-IHC positive patients responded
to conventional immunosuppressive therapies, suggesting that positive CMV-IHC is not necessarily
an indicator for anti-viral therapy in UC patients.
74
P-13
Appendiceal orifice inflammation may precede development of
ulcerative colitis: Analysis of 20 patients
Sang Hyoung Park, MD,* Suk-Kyun Yang, MD,* Mi-Jung Kim, MD,‡
Dong-Hoon Yang, MD,* Kee Wook Jung, MD,* Kyung Jo Kim, MD,*
Byong Duk Ye, MD,* Jeong-Sik Byeon, MD,* Seung-Jae Myung, MD,*
Jin-Ho Kim MD*, Yun Kyung Cho, RN*
*Department of Gastroenterology, ‡Department of Pathology,
University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Abstract
BACKGROUND: Appendiceal orifice inflammation (AOI) is considered as a distinct skip lesion of
ulcerative colitis (UC). In previous studies on AOI as a skip lesion of UC, the AOI was found together
with the main UC lesion. However, it does not necessarily mean that AOI develops concomitant with
the main UC lesion. Therefore, we performed this study to investigate the possibility of AOI as a
preceding lesion in the development of UC.
PATIENTS AND METHODS: A total of 20 patients with UC-like inflammatory lesions at the
appendiceal orifice, without concomitant typical features of UC, such as diffuse rectal involvement,
were identified at the Asan Medical Center between January 2001 and December 2009. The
subsequent clinical courses and endoscopic findings of all patients were analyzed.
RESULTS: A total of 20 patients (mean age 41.2 years; 11 males) met our inclusion criteria. Nineteen
patients were followed up endoscopically for a mean duration of 18.4 months (range, 2-84 months).
Typical UC (proctitis in four patients, extensive colitis in one patient) developed in five patients (25%)
in a mean time of 18.4 months (range, 2-36 months). Negative conversion of all inflammatory lesions
occurred in seven patients (35%) after a mean follow-up time of 20 months (range, 3-84 months).
In the remaining seven patients (35%), the initial lesions did not progress to UC and did not go into
remission during the mean follow-up time of 16.9 months (range, 2-42 months).
CONCLUSIONS: Our results suggest that, at least in some occasions, AOI precedes development of
UC, and indicate that the appendix may play a role in the pathogenesis of UC.
KEYWORDS: ulcerative colitis; appendiceal orifice inflammation, precedent lesion.
75
P-14
Clinical courses of chronic hepatitis B virus infection and
inflammatory bowel disease in patients with both diseases
Sang Hyoung Park, MD, Suk-Kyun Yang, MD, Young-Suk Lim, MD,
Ju Hyun Shim, MD, Dong-Hoon Yang, MD, Kee Wook Jung, MD,
Kyung Jo Kim, MD, Byong Duk Ye, MD, Jeong-Sik Byeon, MD,
Seung-Jae Myung, MD, Jin-Ho Kim MD, Eun Ja Kwon, RN, Ji Young Park, RN
Abstract
BACKGROUND&AIM: Little is known about the clinical features of hepatitis B virus (HBV)
infection in patients with inflammatory bowel disease (IBD). We therefore evaluated the influence
of immunosuppressive treatment for IBD on the course of HBV infection and the effect of HBV
infection on the therapeutic strategy and clinical course of IBD patients.
METHODS: We retrospectively evaluated the incidence of and risk factors for liver dysfunction in
hepatitis B surface antigen (HBsAg)-positive IBD patients. Also, the clinical course of IBD patients
with HBV infection was compared with matched IBD controls without HBV infection.
RESULTS: Of 4,153 patients diagnosed with IBD between July 1989 and May 2011, 134 were
HBsAg-positive, including 54 with Crohn’s disease (CD) and 80 with ulcerative colitis (UC).
Liver dysfunction was observed in 23 of the 134 (17.2%) HBsAg-positive patients. Prolonged
immunosuppression (> 3 months) was an independent predictor of liver dysfunction (OR 3.06;
95% CI 1.02-9.16). The rate of use of immunosuppressants, including corticosteroids (p = 0.005),
azathioprine/6-mercaptopurine (p < 0.001), and infliximab (p = 0.026), was significantly lower in
HBsAg-positive than HBsAg-negative IBD patients. Clinical outcomes, including admission rate,
mean number of admissions, total proctocolectomy in UC patients and mortality, were worse in
HBsAg-positive than HBsAg-negative IBD patients during the follow-up period.
CONCLUSION: Liver dysfunction in HBsAg-positive IBD patients was more frequent in those with
prolonged immunosuppression. IBD patients with chronic HBV infection used immunosuppressants
less frequently and had a worse prognosis than those without it.
KEYWORDS: Chronic hepatitis B, inflammatory bowel disease, reactivation, outcome
76
P-15
A Case of Pustular Psoriasis Induced by Infliximab Treatment for
Ulcerative Colitis
Kyoung-Joo Kwon, Sung-Ae Jung, Seong-Eun Kim, Ki-Nam Shim, Hye-Won Kang, Eun-Mi Song,
Ju-Young Choi, Hye-Kyung Jung, Tae-Hun Kim, Kwon Yoo,
Il-Hwan Moon
Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University
School of Medicine, Seoul, Korea
Background: Infliximab, TNF-α antagonist, has been used to treat patients with moderately to
severely active ulcerative colitis (UC) who have had an inadequate response to conventional
therapy. Its use in Korea has increased rapidly since the allowance of insurance coverage by the
national health insurance in 2010. The adverse drug reactions related to TNF-α antagonist, including
infusion-related reactions, opportunistic infections, reactivation of tuberculosis, neurologic disorders,
and autoimmune reactions, also have increased. The most commonly observed cutaneous side effects
were skin eruptions including psoriasiform eruptions. It is surprising because TNF-α antagonist
has been successfully used in the treatment of psoriasis. A possible explanation is that excessive
TNF inhibition may cause the activation of autoreactive T cells which result in autoimmune tissue
damage. These skin eruptions may respond to topical or oral steroids, antihistamines, emollients, and
phototherapy without discontinuation of anti-TNF drug.
Case: A 42-year-old female visited our outpatient clinic because of whole body rash with itching
sense which started 15 days ago. She was diagnosed with UC 5 years ago. She has maintained the
disease with 5-aminosalicylic acid or azathioprine and intermittently used steroids for flare-up. She
started anti-TNF treatment after 4 years from diagnosis due to steroid-refractory condition. After
three i.v. infusions of infliximab (5mg/kg), clinical response and remission induction were obtained,
but on 15th day after third infusion, she had an itching sense on whole body with 2-3mm sized skin
eruptions. She was diagnosed with pustular psoriasis by experienced dermatologist after skin biopsy.
Anti-histamines and topical steroids were tried for 10 days but the skin condition did not improve.
After using oral steroids for 27 days, the lesion showed improvement and we could taper-off the
steroid. Infliximab was restarted after 2 months from the last infusion. Skin lesion did not recur until
she finishes 8 cycles of infliximab therapy.
77
P-16
A Case of squamous cell carcinoma of the breast in a patient with
Crohn’s disease taking azathioprine
Kyoung Chan Park, Kyung Ho Ha, Jin Tae Jung,
Joong Goo Kwon, Eun Young Kim.
Departments of Internal Medicine, Catholic University of Daegu,
School of Medicine, Daegu, Korea
Background: Azathioprine (AZA) treatment in transplant or autoimmune patients and subsequent
appearance of lymphomas or squamous cell carcinomas at various sites, particularly skin and cervix,
have shown a close relationship. However, it remains uncertain whether this is true for the patients
with Crohn’s disease. We report a case of squamous cell carcinoma of the breast occurred in a young
patient with Crohn’s disease who has received AZA.
Case: A 35-year-old female visited breast cancer clinic in our hospital due to incidentally found
right breast mass. She was first diagnosed with Crohn’s disease 10 years ago and has taken AZA
with 5-ASA on regular follow up in GI department of our hospital for 9 years. She had no family
history of breast cancer. A mastectomy on right breast was performed and 6.3 cm x 5.5 cm mass
was removed. The mass was microscopically proven to be poorly differentiated squamous cell
carcinoma with focal keratin pearl formation. No definite lymph node metastasis was noted. At age
of 25, she was first diagnosed with active Crohn’s disease. At that time, 5-ASA and corticosteroid
induced remission. 3 years later, symptom aggravated and she started taking AZA together with
corticosteroid. After remission induction, steroid was tapered off and AZA was maintained at 1
mg/kg due to leukopenia at higher dose. She stopped taking AZA at her discretion during her two
pregnancies and reported total of 67 months of AZA medication on her breast cancer diagnosis.
After mastectomy, she got radiotherapy in combination with chemotherapy and AZA was taken off.
Currently, her Crohn’s disease is in remission with 5-ASA for about 1 year.
78
P-17
Improvement of bowel stenosis in Crohn’s disease after treatment
with steroid combined infliximab
KEISUKE HASUI, YOH ISHIGURO, HIROTAKE SAKURABA, SHINSAKU FUKUDA,
DEPARTMENT OF GASTROENTEROLOGY AND HEMATOLOGY
HIROSAKI UNIVERSITY GRADUATE SCHOOL OF MEDICINE, HIROSAKI, JAPAN
AIM: To assess prospectively bowel stenosis in Crohn’s disease (CD) patients treated with steroid (SH)
combined infliximab (IFX) analyzing double contrast barium examination.
METHOD: Fourteen patients (6 female/8 male [43%/57%]; mean age 27.5(22-50) years) who showed
obstructive symptoms indicating the presence of small or large bowel stenosis and were SH naïve
treated with infliximab (5 mg/kg at wk 0, 2, 6 and 5 mg/kg every 8 wk thereafter) combined with
SH. Double-contrast barium examination was performed at the induction phase and at regular time
intervals during the follow-up period (24 ± 2.5 mo, range 4 - 35 mo). Primary end point of this trial
was proportion of patients with significant improvement of stenosis at 4 weeks, defined as a diameter
Results: After the first 2 induction infusions there was significant improvement of diameter of the
stenotic lesion (9.5 mm ± 0.9 mm) as compared with those of untreated baseline (5.9 mm ± 1.9 mm)
(P<0.0001). In no case was progression of stenosis or the appearance of new ones seen. Of the 14
patients with stenosis treated with SH combined IFX, one stopped treatment after the induction
phase (because of no response) and referred surgery.
Conclusion: The favorable response was obtained after treatment with SH combined IFX for severe
stenotic lesions in CD patients. Initial responder (diameter > 8.5 mm at primary end point) might
avoid surgery for 2 yrs. Definition of failure at primary end point based on a luminal diameter after
IFX plus SH treatment might be helpful to optimize surgical treatment.
79
P-18
Clinical and endoscopic efficacy of Adalimumab in patients with
Crohn’s Disease
Noriko Kamata, M.D., Ph.D.1, Kenji Watanabe, M.D., Ph.D.1,
Hisotsugu Imaeda, M.D., Ph.D.2, Akira Andoh, M.D., Ph.D.2,
Kenichi Morimoto, M.D., Ph.D.1, Atsushi Noguchi, M.D., Ph.D.1,
Mitsue Sogawa, M.D., Ph.D.1, Hirokazu Yamagami, M.D., Ph.D.1,
Tetsuo Arakawa, M.D., Ph.D.1
1
Department of Gastroenterology
Osaka City University Graduate School of Medicine, Japan,
2
Department of Medicine,
Shiga University of Medical Science, Japan
Background/Aims; Adalimumab (ADA) has approved for Crohn’s Disease (CD) in Japan in 2010.
We investigated the clinical and endoscopic efficacy of ADA in patients with CD prospectively.
Methods; Suitable endoscopic examination (ileocolonoscopy or balloon enteroscopy) was performed
to assess the most inflamed lesion before and after 28 weeks for ADA treatment. We evaluated the
efficacy according to Harvey-Bradshaw Index (HBI: remission < 4) or CRP, endoscopic efficacy
according to simple endoscopic score for Crohn’s disease (SES-CD). The primary endpoint is
remission induction at 28 weeks. We also investigated the correlation with efficacy and serum ADA
trough level.
Results; Sixty-three CD (mean age: 35.0 year, Female: 16, L1/L2/L3=18/7/38) cases were enrolled.
Most patients (98.4%: 62/63) could perform self-injection of ADA. Anti-TNFα agent naïve patients
(N group) was 21 cases (33.3%), and switched cases from Infliximab (IFX) to ADA (S group) was
42 cases (66.7%). Loss of response for IFX was 28 cases (shortened injection interval was 23 cases:
11 cases were clinical active and 12 cases were endoscopic active with every 8 weeks IFX injection),
and intolerant for IFX was 12 cases. Remission induction was tend to higher in N group (83.3%)
than S group (66.7%) at 28 weeks, and CRP (mg/dl) was tend to lower in N group (0.13) than S group
(0.71) at 28 weeks. CRP was dropped down after 2 weeks of ADA administration in 40 cases (p<0.05).
Endoscopic efficacy according to SES-CD was 59.5% (22/37, N group: 9, S group: 28), especially
significant improvement was shown in N group (p=0.0074). ADA trough level was seemed to be
correlated with efficacy (n=19: N group 7, S group 12).
Conclusion; ADA is effective not only anti-TNFα agent naïve patients but switched cases from IFX
clinically and endoscopically in patients with CD.
80
P-19
Infliximab for Steroid-Dependent Hemorrhagic Crohn’s Disease
Jae Myung Cha, Joung Il Lee, Kwang Ro Joo, Hyun Phil Shin, Jae Jun Park, Jung Won Jeon,
Jun Uk Lim, Kyuseong Lym
Department of Gastroenterology, Kyung Hee University Hospital at Gang Dong, 149 Sangil-dong,
Gangdong-gu, Seoul 134-727, Republic of Korea
Background/Aims: Infliximab has been recommended for moderate to severe inflammatory Crohn’s
disease (CD) or fistulizing CD, however, other potential uses of infliximab in different CD settings,
such as hemorrhagic CD, deserves special mention. Herein we report the effects of infliximab on
hemorrhagic CD.
Methods: A 43-year old female without previous medical history presented with acute recurrent
hematochezia. She had 12 months history of recurrent abdominal pain and diarrhea. Two months
ago, she underwent upper endoscopy and colonoscopy at other hospital for hematochezia, however,
bleeding focus was not identified. Capsule endoscopy was recommended, however, was not
performed as hematochezia was self-limited. On this admission, laboratory investigations showed
hemoglobin of 11.5 g/dL, hematocrit of 34.0%, serum iron 15 ug/dl, and ferritin 5.3 ng/ml. Upper
endoscopy showed non-specific findings. At colonoscopy, the entire colon appeared normal up to
the cecum, however, discrete longitudinal ulcers with oozing bleeding were noted at 20cm proximal
ileum from ileocecal valve (Fig. 1). Endoscopic biopsy showed non-caseous granuloma. Small bowel
follow-through demonstrated linear ulcers at mesenteric border of distal ileum. She was diagnosed
as active CD with bleeding, and her bleeding decreased with intravenous steroid. She was discharged
with oral steroid, however, recurrent heamtochezia was developed for two times during tapering of
steroid. Her recurrent hematochezia was persisted at trial of steroid tapering and her clinical course
was not improved with addition of mesalamine and azathioprine.
Results: A 5 mg/kg infliximab infusion was given at 0, 2, and 6 weeks interval. At follow-up
colonoscopy at 8 weeks after the first infliximab infusion, the size and number of ileal ulcer was
decreased, and most ulcers were healed without stricture (Fig. 2).
Conclusion: Infliximab appears to be an appropriate agent for the treatment of hemorrhagic CD,
especially in steroid-dependent conditions.
DISCLOSURE: None of these authors has a financial relationship to disclose relevant to this abstract.
81
P-20
The immunoassay for the accurate determination of antibodies to
infliximab in Crohn’s Disease.
Hirotsugu Imaeda*, Akira Andoh**, Hiromitsu Ban*, Shigeki Bamba*,
Masaya Sasaki*, Tomoyuki Tsujikawa* and Yoshihide Fujiyama*
*Division of Gastroenterology, Shiga University of Medical Science,
** Division of Mucosal Immunology, Graduate School of Medicine,
Shiga University of Medical Science, Otsu, Japan.
[Background/Aim] The formation of antibodies to infliximab (ATIs) is closely associated with the
loss of a response to infliximab in patients with Crohn’s disease (CD). But the conventional method
to measure ATI is including that many patients are diagnosed to false negative, because much of
them are saturated by serum free infliximab. We evaluated the clinical utility of a novel method to
measure serum ATI levels in the presence of infliximab.
[Methods] 58 patients with CD under infliximab maintenance therapy were evaluated. ATI levels
were measured by a novel method of immunoassay with protein A. The serum infliximab trough
levels were determined by enzyme-linked immunosorbent assay.
[Results] ATIs were detected in 16 out of 58 patients (27.6%). Patients positive for ATIs had
significantly lower serum trough levels of infliximab, and significantly higher clinical activity scores
and higher laboratory markers for inflammation (CRP and ESR) as compared to patients negative for
ATI.
The existence of ATI infliximab administrated CD cause loss of the effect of infliximab. So we
established the strategy for second failure to infliximab, patients whose serum infliximab levels are
high, it does not seem to be caused by TNF-α, they could be administrated of another medication
like immunomodulator or prebiotics. Some of patients whose serum infliximab levels are low and
whose ATI levels are high, must be changed to adalimumab. The others whose ATI levels are low
should be increased the dosage of infliximab.
[Conclusion] This method makes it possible to measure serum ATI levels in the presence of
infliximab, and seems to be useful for deciding the optimal management strategies for CD patients
with a loss of response to infliximab.
82
P-21
Clinical usefulness of serum IL-32 in Crohn's disease: preliminary
results
Eun Ran Kim, Sung Noh Hong*, Soo-Hyun Kim**,
Young-Ho Kim, KASID IBD Study Group***
Department of Internal Medicine, Sungkyunkwan University, School of Medicine, Seoul, Korea
*Department of Internal Medicine, Konkuk University, School of Medicine, Seoul, Korea
**Department of Biomedical Science and Technology, Konkuk University, Seoul, Korea
Backgroud/Aims: IL-32 is a newly discovered cytokine and induces other proinflammatory
cytokines including IL-1β, IL-6, TNF-α, and chemokines. Recent study demonstrated that IL32 is overexpressed markedly in the inflamed tissues from patients with Crohn’s disease (CD).
We investigated the association with serum IL-32 titer and clinical manifestation of patients with
CD, and identify whether serum IL-32 test is helpful in the differential diagnosis between CD and
intestinal tuberculosis (ITB).
Methods: Serum samples from 48 patients with CD, 46 patients with ITB and 20 normal control
were collected. Serum IL-32 γ (most active isoform of IL-32) titer was measured by IL-32 γ specific
sandwich ELISA.
Results: Serum IL-32 γ titer in patients with CD was significantly elevated compared with patients
with ITB and normal control (p<0.01). Between patients with ITB and normal control, serum IL-32 γ
titers were not significantly different. In patients with CD, serum IL-32 γ titer tended to be increased
patients with clinical symptoms such as weight loss, abdominal pain and hematochezia, and patients
with lesion involved small bowel and anorectal area (p>0.05). In patients with CD, serum IL-32
γ titer of normal CRP group was higher than elevated CRP group, but there was no significant
difference between two groups (p=0.068).
The sensitivity, specificity, positive predictive value and negative predictive value of serum IL-32 γ
titier for diagnosis of CD were 64.6%, 73.9%, 45.7% and 54.3%, respectively.
Conclusion: Serum IL-32γ titer can represent CD activity and be helpful in the differential diagnosis
between CD and ITB. However, prospective large studies are needed to verify the clinical usefulness
of serum IL-32γ titer in diagnosis and monitoring of CD.
※ Key words : serum IL-32, Crohn's disease, intestinal tucerculosis
83
P-22
A case of the fistulizing enterovesical Crohn’s disease treated with
Infliximab
Hoon Sup Koo, Kyu Chan Huh
Department of Gastroenterology, Konyang University Hospital, Daejeon, Korea
An enterovesical fistula is an uncommon complication of Crohn’s disease. Confirmation of its
presence generally depends on clinical findings, such as fecaluria and pneumaturia. This fistula is
very difficult to be treated by nonsurgical means, although the resulting cystitis may be controlled
with antibiotics. We present here the case of a 31-year-old woman admitted with facaluria and
pneumaturia. She had previously been diagnosed with Crohn’s disease, confirmed by colonoscopy
with biopsies, and has been taking 3.2g of mesalazine, 50mg of azathioprine and 500mg of
ciprofloxacin daily. Investigations classified the patient as a moderate Crohn’s Disease Activity Index
(CDAI 256). She presented mild abdominal pain with diarrhea five times a day, but no pathological
findings of the perianal region. Laboratory findings revealed no abnormality except elevated
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Urinalysis showed pyuria and
microscopic hematuria, and urine cultures showed Escherichia coli. Abdominopelvic CT showed
air-fluid level in the bladder and enterovesical fistular tract. Cystoscopy revealed erythematous
edema with bleeding in an area of the right lateral bladder. We diagnosed the enterovesical fistular
tract by confirming the leakage of contrast enhanced dyes from the bladder to the intestine. Although
surgical management is the treatment of choice, we decided to choose medical therapy (biologic
agent) to treat this patient because surgical therapy may negatively affect the quality of life of patient
and she had abdominal pain with diarrhea. Therefore, we initiated Infliximab therapy. She received
a 5mg/kg infliximab induction regimen at weeks 0, 2, and 6, with mesalazine and ciprofloxacin. The
urinary symptoms rapidly disappeared and the fistula closed after 2 weeks of therapy. She received
an infliximab 5mg/kg maintenance treatment every 8 weeks with having no recurrence of the fistula.
It is very rare to treat enterovesical fistular of Crohn’s disease by medical therapy successfully. We
experienced the fistulizing enterovesical Crohn’s disease treated with Infliximab.
84
P-23
Monitoring 6-thioguanine nucleotide concentrations in Japanese
children and adolescents with inflammatory bowel disease
Yoshikazu Ohtsuka1, Katsuhiro Arai,2 Yo Aoyagi1, Tohru Fujii1, Tamaki Ikuse1,
Takahiro Kudo1, Toshiaki Shimizu1
1
Department of Pediatrics, Juntendo University Graduate School of Medicine, Tokyo, Japan
2
Division of Gastroenterology, Department of Medical Specialties,
National Center for Child Health and Development, Tokyo, Japan
Background / Aim: 6-Mercaptopurine (6-MP) and azathioprine (AZA) are widely used as
maintenance therapy in children with inflammatory bowel disease (IBD). However, proper
6-thioguanine nucleotide (6-TGN) concentrations in Japanese children with IBD have not been
reported.
Methods: This retrospective review examines 32 ulcerative colitis (UC) patients and 19 Crohn's
disease (CD) patients (12.87 ± 3.56years) who required 6-MP or AZA to maintain disease remission.
All patients were treated with 6-MP or AZA for at least 3 weeks prior to this study in addition to
previous treatment. 6-MP dose, 6-TGN levels, assayed by high-performance liquid chromatography,
as well as laboratory data were evaluated.
Results: Thirty-five children were successfully kept in remission with 6-MP and AZA therapy
after weaning off corticosteroids. Overall, 123 measurements (59 active disease, 64 in remission)
were analyzed. The mean 6-TGN concentration of the entire study population was 499.61 ± 249.35
pmol/8×108 RBC. The mean 6-MP dose in patients with active disease (0.910 ± 0.326 mg/kg/day)
was significantly higher than for patients in remission (0.749 ± 0.225) (p=0.0016). A significant
inverse correlation was found between WBC counts and 6-TGN concentrations (r= 0.275, p<0.002).
Two patients experienced leukopenia with alopecia, and 4 transiently experienced increased serum
levels of pancreatic enzymes, although no thiopurine S-methyl transferase mutations were confirmed.
Conclusion: The doses of 6-MP or AZA needed to maintain remission in Japanese children with
IBD are lower than those reported in Western countries. However, 6-TGN concentrations in this
population are higher than previously reported.
85
P-24
Can a gradual dose increment policy reduce azathioprine-induced
bone marrow toxicity?: A multicenter retrospective analysis
Suck-Ho Lee, MD1, Dong Il Park, MD2, Chang Kyun Lee, MD3,
Jeong Eun Shin, MD4, Chang Soo Eun, MD5, Kyu Chan Huh, MD6,
1
2
Soonchunhyang University (Cheonan Hosp) ,
Sungkyunkwan University (Kangbook Samsung Hosp) ,
3
Kyung Hee University College of Medicine ,
4
Dankook University,
5
Hanyang University (Kuri Hops) ,
6
Konyang University College of Medicine,
Background/Aims: The most important adverse effect of azathioprine (AZA) is bone marrow
toxicity (BMT). Many physicians have preferred a gradual dose increment (GDI) policy for the
prevention of BMT. The aim of this study was to evaluate the efficacy of GDI for the prevention of
AZA-induced BMT in inflammatory bowel disease (IBD) patients.
Methods: The medical records of IBD patients who received AZA in six university hospitals were
reviewed. The patients were divided into two groups: the GDI group (initial dose < 1.5 mg/kg,
gradually increased to a therapeutic dose) and the non-GDI group (initial therapeutic dose ≥ 2 mg/
kg).
Results: A total of 308 patients were enrolled (male to female ratio: 1:2.3; mean age: 34.91 ±
14.19; ulcerative colitis: 43.5%; Crohn's disease: 55.2%; and intermediate colitis: 1.3%). The overall
incidence of BMT was 16.2% (50/308). BMT developed most frequently between four to eight
weeks (26%, 13/50). The following demographics did not differ between the two groups: sex, age,
body weight, type of IBD, indication for AZA (e.g., steroid-dependent, steroid-resistant), concurrent
medication (e.g., mesalamine, steroid, infliximab), and other adverse effects (e.g., GI trouble,
hepatotoxicity). The rate of BMT of the non-GDI group was significantly higher than that of the GDI
group (27.5%, 11/40 vs. 14.6%, 39/268, P = 0.038). A multivariate analysis showed that the only factor
related to BMT was a non-GDI policy (P = 0.036; OR, 2.41; 95% CI, 1.06–5.49). The main limitation
of this study was the lack of measurement of the thiopurine methyltransferase genotype or activity.
Conclusion: A GDI policy could be useful for reducing AZA-induced BMT in Korean IBD patients.
86
P-25
Acute myelomonocytic leukemia following treatment of Crohn’s
disease with 6-mercaptopurine: a case report
Hee Jae Hyun, MD, Eun Yeong Kim, MD, Choul Ki Park, MD,
Abstract
Background: Crohn's disease is an inflammatory bowel disease (IBD) characterized by
inflammatory, ulcerative bowel lesions and frequent association with systemic manifestations.
Recent studies suggest that incidence of leukemia is higher in patients with IBD than in the normal
population and an association may exist between IBD and leukemia. The association seems to
be related to several factors, including genetic susceptibility, exposure to environmental toxic
agents, autoimmune diseases or exposure to diagnostic or therapeutic radiation, and assumption
of drugs as immunosuppressants. We present a patient with Crohn’s disease who developed acute
myelomonocytic leukemia after 18 months of 6-mercaptopurine (6-MP) therapy. Case description:
A 63-year-old woman with Crohn’s disease was admitted to our gastroenterology unit for the
occurrence of general weakness. Crohn’s disease was diagnosed 5 years ago, according to standard
endoscopic and histological criteria. She was referred to our gastroenterology unit for the recurrence
of Crohn’s disease 2 years ago. Thereafter, stable remission of the disease had been maintained for
18 months with 5-aminosalicylic acid and 6-MP (cumulative dose 5.3g) after induction treatment
with steroid. The laboratory findings revealed severe anemia (serum hemoglobin 8.0 g/dL), increased
WBC count (35,370/mm3), low platelets counts (113x103/dL). Morphological evaluation of peripheral
blood revealed the presence of immature cells of the granulocyte. Biopsy of bone marrow revealed
that blasts with high N/C ratio are counted up to 86.6% and confirmed the diagnosis of acute
myelomonocytic leukemia without cytogenetic abnormality. Conclusion: This case suggests that a
possible relationship between 6-MP and leukemia persists in Crohn’s disease. Additional studies are
warranted to clarify the role of immunosuppressants in patients with Crohn’s disease complicated
with leukemia.
Key Words: Acute myelomonocytic leukemia; Crohn’s disease; 6-mercaptopurine
87
P-26
Increased rates of early adverse reaction to azathioprine in patients
with inflammatory bowel disease compared to autoimmune hepatitis
Dong Choon Kim, Eun Soo Kim, Yun Jung Kim, Kyung Sik Park, Kwang Bum Cho
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
Background/Aims: Immunomodulation with azathioprine (AZA)/6-MP has been used in the
maintenance therapy of chronic inflammatory disease including Crohn’s disease (CD) and
autoimmune hepatitis (AIH). There is a lack of research comparing the adverse effects of AZA/6-MP
in Korean patients between two groups. This study aimed to compare the adverse reaction of AZA in
patients of Korean between inflammatory bowel disease (IBD) and autoimmune disease (AID).
Methods: Medical records of 139 patients with IBD and 55 with AID in whom thiopurine
treatment was indicated at a tertiary single hospital between January 2000 and March 2011 were
retrospectively analyzed. We compared the clinical characteristics and adverse effects of AZA/6-MP
between two groups.
Results: Overall, 30 (21.6%) of 139 IBD and 8 (14.5%) of 55 AID patients using AZA/6-MP
experienced adverse effects of drug (p=0.319). Adverse effects included leucopenia, pancreatitis,
nausea/vomiting, liver enzyme rising, and skin rash. Among them, leucopenia was more observed in
IBD patients than AID (15.1% vs. 3.6%, p=0.027).
Conclusion: Overall adverse effects of AZA/6-MP were comparable between patients with IBD and
AID. More attention should be paid for WBC count monitoring when IBD patients are treated with
thiopurine.
88
P-27
Incidence of Extraintestinal Malignancies
in a Single-Center Inflammatory Bowel Disease Population in Korea
Soo-Kyung Park, Byong Duk Ye, Suk-Kyun Yang, Dong-Hoon Yang,
Kee Wook Jung, Kyung-Jo Kim, Jeong-Sik Byeon,
Seung-Jae Myung, and Jin-Ho Kim
BACKGROUND: Limited data are available regarding the incidence of extraintestinal malignancies
in Asian inflammatory bowel disease (IBD) patients. The objective of this study was to investigate
the incidence of extraintestinal malignancies in Korean IBD patients.
METHODS: Patients diagnosed with malignancies were identified from a single-center IBD
database from the Asan Medical Center, Seoul, Korea. For patients with IBD, we included patients
diagnosed with ulcerative colitis or Crohn’s disease, who were followed at our center for more
than one year. Colorectal adenocarcinoma and small bowel adenocarcinoma were excluded. The
standardized incidence ratio (SIR) of extraintestinal malignancies was estimated using data from the
Korea Central Cancer Registry (KCCR) of the National Cancer Center.
RESULTS: Out of 3,292 patients, 57 patients (1.7%) were diagnosed with 59 extraintestinal
malignancies (two patients with double cancers). Seven patients who were diagnosed with cancer
before the diagnosis of IBD were excluded. Twenty five out of remaining 50 patients (50.0%) were
male and 39 patients (78.0%) had ulcerative colitis. The median age at diagnosis of cancer was 52
years (range, 24-75 years) and median duration of IBD at diagnosis of cancer was 77 months (range
1-242 months). There were 6 cases of lymphoma and the SIR for lymphoma was 4.0 (95% confidence
interval 1.5-8.7). However, the SIR for other extraintestinal malignancies (bladder, brain, breast,
esophagus, gallbladder, kidney, leukemia, liver, lung, multiple myeloma, prostate, stomach, thyroid,
and uterine cervix) was not increased.
CONCLUSIONS: Our single center study suggests the increased risk of lymphoma among Korean
IBD patients. However, further larger scaled population-based studies are required to determine the
incidence of extraintestinal malignancies in Asian IBD patients.
89
P-28
Extensive Arterial and Venous Thrombosis in Patient with Ulcerative
Colitis
Hyun-Soo Kim, Young-Eun Joo
Department of Gastroenterology, Chonnam National University Medical School,
Gwangju, South Korea
Vascular thrombosis is a rare but well-recognized extraintestinal manifestation of ulcerative colitis
(UC). Thrombosis usually involves the peripheral veins and less commonly the arterial system. We
report herein the rare case of UC complicated with both extensive arterial and venous thrombosis.
A 42-year-old man with severe chronically active UC developed both lower leg pain and weakness.
UC had been diagnosed 4 years previously. Abdominal and lower leg CT angiography revealed
extensive thrombosis in right portal vein, long segment of lower abdominal aorta, internal and
external iliac artery and femoral artery, popliteal artery, tibial artery of both lower legs. Because
catheter embolectomy was insufficient, he underwent repetitive transcatheter thrombolytic therapy
and percutaneous transluminal angioplasty (PTA) with stent replacement and artificial graft bypass
operation. And the patient subsequently underwent total proctocolectomy with end ileostomy for
treatment of refractory ulcerative colitis with severe bloody diarrhea. The small bowel did not appear
ischemic. Histopathologic examination of the specimen was consistent with ulcerative colitis. The
patient has received anticoagulation therapy with warfarin and is not observed worsening although
has remained extensive thrombosis of abdomen and low extremity.
90
P-29
Development of liver cirrhosis and massive variceal bleeding in a
patient with refractory Crohn’s disease
Kyoung Sup Hong, Jong Pil Im, Joo Sung Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Asymptomatic and mild elevations of liver biochemical tests often are seen in Crohn’s disease, but
few of these patients are known to develop into clinically evident liver cirrhosis. We report a case of
a 26-year-old man presenting with a massive hematochezia from stoma and rectal varices, who was
diagnosed a Crohn’s colitis with anal fistula and abscess 13 years ago. He underwent colostomy 7
years ago due to recurrent and refractory anal fistula. His symptoms had responded to infliximab,
but recently were refractory to infliximab. Adalimumab has shown a marginal response to clinical
activity. Portal angiography demonstrated engorged variceal veins with ongoing active bleeding in
the colostomy stoma and rectum. There has been no recurrent bleeding since embolization was done
for the varices and administration of propranolol. Although meticulous work-up was performed to
find any cause of liver cirrhosis in this patient, there was no evidence of viral hepatitis, primary
sclerosing cholangitis, or autoimmune hepatitis.
91
P-30
Portal pylephlebitis as a complication of paediatric Crohn’s disease:
a case report
Eun Yeong Kim, MD., Hee Jae Hyun, MD., Choul Ki Park, M.D.,
Chang Kyun Lee, MD., Hyo Jong Kim, MD.
Background: Vascular thromboembolism is a known extraintestinal manifestation of inflammatory
bowel disease (IBD) but infrequent, especially in young IBD patients. Deep vein thrombosis (DVT)
and pulmonary embolus are the most common types of thromboembolic events, on the other hand
portal vein is one of unusual sites of venous thrombosis in IBD. Thrombosis of the portal venous
system (PVS) has been commonly described in the portal vein (PV) and superior mesenteric vein
(SMV). Thrombosis of PVS is occasionally related with sepsis (portal pylephlebitis), normally arising
from ascending infection from the gastrointestinal tract into the portal vein. Although rare, this event
may occur in association with IBD and can be often a fatal complication.
Case description: We present a 17-year old boy, 3 months previously diagnosed with Crohn’s
disease, admitted with fever, abdominal pain. He has been treated with azathioprine, 5-aminosalicylic
acid (5-ASA) and prednisolone, which have adequately controlled his symptoms. The laboratory
findings revealed mild liver function abnormalities, highly elevated C-reactive protein (29.07 mg/
dL). Abdominal computerised tomography (CT) showed multiple thrombosis in right, left, main
portal vein and superior mesenteric vein. Blood cultures were positive for Streptococcus viridians.
Intravenous antibiotic therapy combined with anticoagulation led to resolution of clinical symptoms.
Within 2 months, CT showed improved thrombosis of the portal venous system.
Conclustion: To our knowledge, this is the first report of thrombosis of PVS with sepsis (portal
pylephlebitis) in a adolescent with Crohn’s disease in Korea. This case demonstrates the need to be
aware of possibility of portal pylephlebitis in IBD patients with unknown origin of fever, abdominal
pain, even though the degree of bowel disease activity is low.
Key Words: Thromboembolism; Inflammatory bowel disease; Portal thrombosis; Sepsis
92
P-31
Hemophagocytic lymphohistiocytosis in a Crohn’s disease patient
who recovered by IV gamma-immunoglobulin.
Hyo Keun Jeon, So Yeon Park, Hong Jun Park, Hyun Soo Kim
Yonsei University Wonju College of Medicine
Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, severe condition of
hyperinflammation caused by the uncontrolled proliferation of activated lymphocytes and histiocytes
secreting high amounts of inflammatory cytokines. It is important to evaluate the patients with
inflammatory bowel disease receiving immunosuppressive therapy presenting with unexplained
fever, cytopenia, progression of organomegaly and biochemical changes for the investigation of HLH
for diagnosis and treatment.
Here we present 46-years-old man was diagnosed Crohn’s disease seven months ago and received
immunosuppressive therapy such as azathioprine and mesalazine (5-aminosalicylic acid). He
was admitted to hospital due to poor oral intake and fever for seven days. He presented with
splenomegaly, anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia. However, he was
not associated with any infection or malignancy. As the pancytopenia progressed, the hematologist
recommended bone marrow biopsy. Bone marrow biopsy showed hemophagocytosis, and the HLH
was diagnosed. We stopped azathioprine first and used intravenous (IV) immunoglobulin for the
treatment of HLH. He was gradually improved in clinical signs and laboratory findings after 3 days
of IV gamma-immunoglobulin. In an IBD patient on immunomodulator presented with unexplained
pancytopenia and progression of organomegaly, not only azathioprine induced leukopenia but also
HLH should be excluded by bone marrow biopsy for prompt diagnosis and treatment.
93
P-32
EBV-associated lymphoproliferative disorders misdiagnosed with
Crohn’s disease
Hee Kyong Na, MD, Byong Duk Ye, MD, Suk-Kyun Yang, MD,
Dong-Hoon Yang, MD, Kee Wook Jung, MD, Kyung-Jo Kim, MD,
Jeong-Sik Byeon, MD, Seung-Jae Myung, MD and Jin-Ho Kim, MD
Background: Epstein-Barr virus (EBV) has an etiologic role in various diseases. EBV-associated
lymphoproliferative disorder (LPD) is usually observed in individuals with congenital or acquired
immune deficiencies. However, it also recently has been reported in non-immunocompromised
individuals. We describe here two cases of immunocompetent patients with EBV-associated T cell
LPD of the small bowel and colon, who were misdiagnosed with Crohn’s disease (CD) initially.
Case 1: A previously healthy, 50-year-old man presented with loose stool for 8 years. He had been
diagnosed and treated with intestinal tuberculosis and CD at other hospital. Endoscopic examination
revealed multiple discrete ulcers from jejunum to rectum. Histologic examination of colonoscopic
biopsy specimens made a diagnosis of EBV-associated T cell LPD. During hospitalization, he
underwent an emergency small bowel resection due to perforation. Eight months after the diagnosis,
he died of septic shock caused by small bowel perforation during the third cycle of chemotherapy.
Case 2: A 49-year-old woman presented with recurrent hematochezia. She had been diagnosed with
CD nine months earlier at other hospital and treated with prednisolone, azathioprine and 3 cycles
of infliximab. Double balloon enteroscopy showed multiple well demarcated circumferential or
geographic deep ulcers in ileum. Pathologic evaluation of biopsy specimen revealed peripheral T cell
lymphoma and the result of staging work-up was IVME. One month later, she underwent ileocecal
resection due to bowel perforation and surgical specimens showed EBV-associated T cell LPD. After
that, she underwent repeated angiographic embolizations and near total small bowel resection for
recurrent small bowel bleeding. To date, she is receiving chemotherapy.
Conclusion: EBV-associated T cell LPD with primary gastrointestinal tract involvement can
manifest as multiple discrete ulcers of small and/or large bowel. The presence of multiple ulcers not
typical of CD or intestinal tuberculosis and unusual clinical course can suggest the possibility of
EBV-associated LPD.
Key Words: Lymphoproliferative disorders, Epstein-Barr virus, Crohn’s disease
94
P-33
Clinical characteristics of the cancer patients who occurred the
rectum and anal canal associated with Crohn’s disease in Japanese
cases
Takeshi Ueda1, Hisao Fujii2, Fumikazu Koyama2, Tadashi Nakagawa1,
Shinji Nakamura1, Naoto Nishigori1, Takashi Inoue1, Keijirou Kawasaki1,
Shinsaku Obara1, Yoshiyuki Nakajima1
1
Department of Surgery, Nara Medical University, Nara, Japan
Department of Endoscopy and Ultrasound, Nara Medical University, Nara, Japan
2
Background: Patients of Crohn’s disease are known to be at an increased risk of cancers. In Japan,
there are many patients diagnosed with cancers in the rectum or anal canal. However, the risk of
cancer is not well defined.
Aim: The aim of this study was to investigate the clinical characteristics of cancer patients who
occurred the rectum and anal canal associated with Crohn’s disease.
Methods: Four cases who were treated in our institution and ninety-seven cases who were reported
by articles in Japan between 1995 and 2010, were analyzed about clinical characteristics such as
symptom, age at cancer diagnosis, duration of cancer diagnosis, duration of anal fistula and TMN
stage.
Result: Almost all of patients had anal symptoms such as anal pain, anal stenosis and increase of
mucus discharge before diagnosis of cancer. Median age at cancer diagnosis was 42.5±12.3 years old,
it was the tendency that was younger than conventional colorectal cancer. Median duration of cancer
diagnosis from onset of Crohn’s disease was 16.7±6.3 years. Median duration of cancer diagnosis
from onset of anal fistula was 12.2±9.9 years. Preoperative diagnosis was possible in 78 cases (86.8%).
In 67 cases who identified the stage, there were 15 patients with StageⅣ,22 with StageⅢ, 21 with
StageⅡ, 1 with StageⅠ, and 8 with Stage0.
Conclusion: The differentiation of inflammation and cancer associated with Crohn’s disease is
difficult for the rectum and anal canal. It is often with advanced cancer at the time of the diagnosis, it
is necessary to establish a surveillance method immediately.
95
P-34
A case of Crohn’s colitis-associated rectal cancer following after
sporadic adenocarcinoma in adenoma.
Takeyama Hiroshi, Tsunekazu Mizushima, Kiyokazu Nakajima,
Hidekazu Takahashi, Junichi Nishimura, Ichiro Takemasa, Masataka Ikeda, Hirofumi Yamamoto,
Mitsugu Sekimoto, Riichiro Nezu*, Toshinori Ito,
Yuichiro Doki and Masaki Mori
Department of Gastroenterological Surgery,
Osaka University Graduate School of Medicine, Department of Surgery,
Osaka Rosai Hospital*
Background/Aims: Recently, the prevalence and incidence rates of CD have been increasing in
Japan, as in Western countries. However colorectal cancer associated with Crohn’s disease is still
rare in Japan. We report a case of Crohn’s colitis-associated rectal cancer following after sporadic
adenocarcinoma in adenoma.
Case Report: Patient is a 51-year old man with Crohn’s disease who was initially diagnosed at 23
years old. He underwent ileocecal resection due to the stricture of terminal ileum at 36 years old. He
was followed with 5-ASA and home parenteral nuturition after initial operation. He felt something
strange with his anus and consulted us in August 2008. Rectal polyp 4 cm in diameter was
detected and he underwent transanal resection of the polyp. Histologically, we diagnosed sporadic
adenocarcinoma in adenoma rather than colitis-associated cancer because of the lack of dysplasia
in rectal mucosa. After three years, follow-up colonoscopy revealed reddish elevated lesion in his
rectum, which was located in different site from initial lesion. Signet ring cell carcinoma was seen on
colonoscopic biopsy. He underwent abdominoperineal resection of rectum and bilateral pelvic lymph
node dissection. Postoperative histological examination revealed mucinous adenocarcinoma with
signet ring cell carcinoma with lymph node metastasis. Dysplasia was detected in rectal mucosa.
Iimmunohistochemically, basement menbrane was strongly stained by Ki67 and crypt base was
stained by p53 that was consistent with pattern of colitis-associated colorectal cancer in ulcerative
colitis patients.
Summary: Colorectal cancer associated with Crohn’s disease is still rare in Japan, however
Longstanding Crohn's disease patients should receive cancer surveillance as well as ulcerative colitis
patients.
96
P-35
Surgery for ulcerative colitis in elderly patients.
Hiroki Ikeuchi*, Motoi Uchino*, Hiroki Matsuoka*, Toshihiro Bando*, Akihiro Hirata*,
Yoshio Takesue**, Naohiro Tomita***, Takayuki Matsumoto*
*Inflammatory Bowel Disease Center, Hyogo College of Medicine
**Department of Infection Control and Prevention, Hyogo College of Medicine
***Department of Surgery, Hyogo College of Medicine
Background/Aims: Since 2000, the number of elderly ulcerative colitis (UC) patients over 60 years
old has been rapidly increasing. We reviewed our surgical experience with elderly patients suffering
from UC treated at our hospital. Methods: Patients 60 years old or more at the time of surgery were
defined as elderly. Mortality was defined as death within 30 days of or directly related to the surgical
procedure. An operation was defined as ‘elective’ if the decision to operate on the UC patient was
made prior to admission to the hospital, while ‘emergency’ colectomy cases were decided during or
after admission (e.g. acute complications or refractory to in-hospital intensive medical management).
The medical records of all elderly patients who underwent surgery for UC during a 26-year period
were retrospectively analyzed. Results: From 1984 to 1999, 18 (5.5%) of 330 patients underwent
surgery at the age of 60 years or older, while from 2000 to 2010, 126 (13.3%) of 945 patients were
elderly. The prognosis for elderly patients who underwent emergency surgery was extremely poor, as
8 (26.7%) of 30 such emergency cases died within 30 days of the operation, while only 1 (0.88%) of
114 died within 30 days of elective surgery. In those who underwent emergency surgery, respiratory
tract infection and sepsis resulting from MRSA or mycotic infection were frequently noted as the
cause of death. Conclusion: A current issue under discussion is whether medical therapy should be
performed for elderly patients with severe or fulminating UC in the same manner as for younger
patients. Since the prognosis of patients undergoing emergency surgery is very poor, physicians and
surgeons should collaborate to treat severe and fulminant cases, so as to not error in the timing of
surgery.
97
P-36
Impact of level of mucosal proctectomy on outcome of ileal pouch–
anal anastomosis for ulcerative colitis
Toshimitsu Araki, Yooshimi Okita, Hiroyuki Fujikawa Inoue, Koji Tanaka. Yasuhiro Inoue,
Yasuhiko Mohri, Keiichi Uchida, Masato Kusunoki
Department of Gastrointestinal and Pediatric Surgery,
Mie University Graduate School of Medicine, Tsu, Mie, Japan
Background: Long-term functional results of ileal pouch–anal anastomosis (IPAA) with mucosal
proctectomy (MP) for ulcerative colitis (UC) are satisfactory, but may be compromised by certain
perianal septic complications.
Methods: We analysed preoperative status and the impact of the level of MP above or below the
dentate line on the risk of perianal fistula in 150 patients undergoing IPAA for UC.
Results: Postoperative perianal sepsis occurred in 14 patients (10 with MP above the dentate line and
four below). Anal fistulae were identified in eight patients and vaginal fistulae in seven. Risk factors
for postoperative perianal sepsis were preoperative vaginal fistula (odds ratio (OR) 38·4, P = 0·0068)
and MP above the dentate line (OR 6·1, P = 0·013). With regard to postoperative anal fistula, only MP
above the dentate line was a significant risk factor (OR 14·9, P = 0·019). Preoperative vaginal fistula
was a risk factor for postoperative vaginal fistula (OR 43·3, P = 0·0034). Survival analysis showed
that MP below the dentate line reduced the risk of postoperative anal fistula (hazard ratio 0·2, 95 per
cent confidence interval 0·05–0·84, P = 0·048), but did not affect perianal sepsis or vaginal fistula.
Postoperative daily stool frequency or nocturnal soiling and manometric parameters in 136 patients
without postoperative perianal sepsis were not influenced by MP procedure.
Conclusion: Total removal of the dentate line, including the cryptoglandular epithelium, might
reduce the risk of postoperative anal but not vaginal fistula. This technique could affect anal function
after IPAA for UC.
98
P-37
The impact of Anti TNF-α Agents with Operative Treatment for
Crohn’s Anorectal Fistula –Aim to introduce the deep remission of
fistulaNaoto Saigusa, Tadashi Yokoyama, Manabu Kikuchi and Yasuhisa Yokoyama
Yokoyama Hospital for Gastroenterology
[Backgrounds/Aim] Anorectal fistula is frequently complicated with Crohn’s disease (CD) and often
refractory. We examined the outcome of treatment for anorectal fistula from the standpoint of use
of anti TNF-α agents and surgery. [Patients and method] Except 16 patients who had a diverting
stoma amongst 198 CD patients we experienced, 46 of them with anorectal fistula who received
anti TNF-α agents at least three infusions were enrolled. Gender, age, initial presentation site of
the disease (anorectal fistula or intestinal lesion), disease duration, type of intestinal disease, rectal
lesion, interval between onset and anti TNF-α agents introduction, intestinal mucosal healing and
outcome of anorectal fistula were investigated. We evaluated the outcome of fistula in three stages;
1)remission: none of following three symptoms; discharge from secondary opening with gentle
compression, pain, swelling, 2)complete healing: clinically complete disappearance of fistula and 3)
symptomatic: at least one of three symptoms mentioned above was demonstrated. [Results] The ratio
of men: women was 34: 12. The number of patients whose CD diagnosis was based on anorectal
fistula: intestinal lesion was 28: 18. The mean age of onset was 22 (range, 14-36) years. The mean
duration of CD was 10.7 (range, 0.4-30) years. Twenty-six patients (57%)resulted in remission,18
(39%)healed and 2 (4%) were symptomatic. Active proctitis before treatment was seen in 26(57%)
patients. Thirteen of 14 patients who showed proximal mucosal healing resulted in remission of
anorectal fistula, and 6 of them achieved complete healing. Thirty-five patients (76%) had operative
treatment. All of 18 patients who showed complete healing received operative treatment (fistulotomy/
fistulectomy; 11 and seton placement; 7). [Conclusion] Outcome of anorectal fistula is associated with
intestinal mucosal healing. Although anti TNF-α agents are effective for fistula remission, surgical
intervention is required to achieve complete healing.
99
P-38
A case of an ulcerative colitis patient with enterocutaneous fistula and
abscess
You Sun Kim¹, Seong Yeon Jeong¹, Sun Ok Kwon¹, Jeong Seop Moon¹,
Yun Kyung Kang², Seong Woo Hong³
Departments of ¹Internal Medicine, ²Pathology and ³General Surgery, Seoul Paik Hospital,
Inje University College of Medicine, Seoul, Korea
Case: A 49-year-old female was presented with a left flank pain and fever that had begun two weeks
before. She had received a diagnosis of Ulcerative colitis (UC) 20 years ago, however, she arbitrarily
stopped visiting the hospital and relied on home remedies. The vital signs; BP 130/80 mmHg, HR
110/min, BT 38.1℃. A tender mass accompanied by a hot sensation and redness in her left flank.
A laboratory exam: Hb 5.0 g/dL, WBC 16,100 /mm3, and ESR 70 mm/hr, CRP 6.7 mg/dL. An
abdominopelvic CT scan revealed luminal narrowing and extra-peritoneal fistula formation in the
descending colon. Fistula was connected with a subcutaneous abscess in the left flank. The patient
was started on intravenous antibiotics and the abscess was drained percutaneously. A colonoscopy
showed remarkable shortening of the colon and severe stricture. She underwent total proctocolectomy
with ileoanal anastomosis. Pathological findings showed that there were no malignant cells and no
granulomatous lesions. This finding appears to be a typical long standing UC with benign strictures.
Discussion: Complications of UC include stricture, colorectal cancer, and toxic colitis. UC patients
rarely present with a stricture or fistula, and strictures develop in less than 5% of patients with
UC. The pathogenesis of a benign stricture formation in patients with UC remains uncertain.
However, fibrosis, contraction, and hypertrophy of the muscularis mucosae are a major cause of
stricture. Benign strictures in UC should be differentiated from malignant strictures. In our case,
severe stricture caused an enterocutaneous fistula and resulted in the development of abscess. We
believed that our case did not receive proper treatment for UC, which has thus led to these serious
complications. It cannot be emphasized enough that the correct therapeutic approach and an
appropriate follow-up schedule are very important among patients with UC.
100
P-39
The value of concomitant endoscopic balloon dilation for intestinal
stricture during long - term infliximab therapy in patients with
Crohn’s disease
Yoichiro Ono 1, Fumihito Hirai 1, Toshiyuki Matsui 1, Takahiro Beppu 1,
Yutaka Yano 1, Noritaka Takatsu 1, Daijiro Higashi 2, Kitaro Futami 2
1
Department of Gastroenterology, Fukuoka University Chikushi Hospital
2
Department of Surgery, Fukuoka University Chikushi Hospital
Aim: We aimed to assess the long-term outcome of infliximab (IFX) therapy in patients with Crohn’s
disease (CD) and to investigate the efficacy of concomitant endoscopic balloon dilation (EBD) for
intestinal stricture during treatment.
Methods: The effectiveness of maintenance therapy with IFX was retrospectively evaluated
in 185 patients with CD in a single center (median observation period, 24 months). IFX effectiveness
with and without immunomodulators (IMMs) and enteral nutrition (EN) was also compared, as well
as cumulative rate surgery-free in the maintenance, non-responder, and/or episodic administration
group. Adverse effects and efficacy of concomitant EBD in patients with obstructive symptoms and
high-level stricture were evaluated.
Results: In 185 patients in the maintenance group, the long-term efficacy rate was 84.9% at 24
months and 79.0% at 48 months. The cumulative surgery-free rate was significantly higher in
the maintenance group (p<0.001). Concomitant IMMs and EN did not significantly affect the
effectiveness of IFX. IFX was discontinued in only 18 cases (7.3%). Symptomatic high-level stricture
occurred in 33 patients (17.8%) in the maintenance group and the cumulative surgery-free rate
was significantly higher in the EBD combination vs. the non-EBD group (p<0.05). If EBD were
considered invasive intervention, the actual cumulative surgery rate in the maintenance group was
significantly lower vs. cumulative
invasive intervention rate (p<0.001).
Conclusion: Long-term treatment with IFX is highly effective. The surgery-free rate was
clearly higher in the maintenance group. Only concomitant EBD for intestinal stricture
helped in the avoidance of surgery.
101
P-40
Emerging trends in the incidence and prevalence of inflammatory
bowel disease: experience from a single center
Haruhiko Takahashi, Takashi Hisabe, Fuminito Hirai, Toshiyuki Matsui
Department of Gastroenterology, Fukuoka University Chikushi Hospital,
Chikushino, Fukuoka, Japan
Aims
In this study, we investigated trends in the incidence and prevalence of inflammatory bowel disease
(IBD) within a cohort of patients recruited from a single center to determine whether there were any
changes in the age-specific incidence rate for CD and UC.
Methods
In total 963(CD;499 UC;464) patients diagnosed with IBD who had been managed within the
Department of Gastroenterology, Fukuoka University Chikushi Hospital between 2006 and 2010
were recruited.
The patients were divided into 2 groups, according to when they were diagnosed with IBD, as either
pre-2000 (old group) or post-2001 group (new group). We then evaluated whether there were any
changes in the age-specific incidence rates for CD and UC between the two groups.
Results
The mean current age in CD and UC was 39.4 years and 43 years, respectively. Age at the time of
diagnosis differed significantly between the two groups for both the CD (p = 0.0076) and UC patients
(UC: p = 0.025). The proportion of UC patients where the onset of clinical symptoms occurred
over the age of 60 years was significantly greater in the new group (p = 0.0023). In contrast, for the
CD patients, there was no difference between the old or new group. The incidence of UC exhibited
a bimodal distribution with one peak at 15–25 years and a second peak occurring at 50–60 years.
However, the pattern for patients with CD was quite different. Although there was a only sharp peak
among patients at 15–25 years.
Conclusion
The findings of this study indicate that the age distribution of IBD is changing, particularly for
patients with UC. The proportion of UC patients with an onset age over 60 years was significantly
greater in patients diagnosed with UC post-2001 compared with patients with CD.
102
P-41
Clinical Significance of Fecal Leukocyte, Lactoferrin, and
Calprotectin in Moderate to Severe Acute Diarrhea
Hae Mi Lee1, Bo-In Lee1, Seungok Lee2, Joo-Yong Song1, Hye-Jung Choi1,
Bong Koo Kang1, Eun Joo Im1, Joon Sung Kim1,, Jong In Kim1,
Byung-Wook Kim1, Hwang Choi1
Department of 1Internal Medicine, 2Laboratory Medicine, College of Medicine,
The Catholic University of Korea, Seoul, Korea
Background/Aims: Presence of fecal leukocytes is known to suggest a more serious illness in
patients with acute diarrhea; however the accuracy of the test is not satisfactory. Fecal lactoferrin and
calprotectin can provide a useful marker for intestinal inflammation and infectious diarrhea. This
study was performed to compare the detection rate of bacterial pathogens between stool cultures and
multiplex PCR in patients with acute diarrhea and evaluate whether fecal leukocytes, lactoferrin, or
calprotectin can predict their clinical courses.
Methods: Patients hospitalized due to moderate to severe acute diarrhea were included. We conducted
a series of test; stool culture and mutiplex PCR, fecal leukocyte, lactoferrin, and calprotectin.
Sigmoidoscopy without bowel preparation was performed in selected patients with informed consent.
Results: 54 consecutive patients (23 males) were included (mean 43.8 years). Stool multiplex PCR
detected bacterial pathogens in 67.7% (21/31) of patients while culture was positive in 1.9% (1/54).
The concordance rate between fecal leukocytes and lactoferrin tests was 57%. Hospital stay was
shorter in patients with positive fecal leukocytes rather than patients with negative leukocytes (3.7
vs. 4.6 days, p=0.032). There was no significant difference in duration of diarrhea or hospital stay
according to the result of fecal lactoferrin although patients with positive lactoferrin test showed
more frequent dehydration and positive PCR than patients with negative lactoferrin test (21.4% vs.
2.5%, p=0.049; 100% vs. 56.5%, p=0.032). Higher fecal calprotectin level seemed to be correlated
with longer hospital stay although there was no statistical significance (R=0.280, p=0.065). Patients
with erosions or ulcers on sigmoidoscopy showed a tendency to be hospitalized for longer period but
there was no statistical significance (6.5 vs. 5.2 days, p=0.068).
Conclusions: Stool multiplex PCR can detect causative organisms in more patients with moderate to
severe acute diarrhea than stool culture. Fecal leukocyte, lactoferrin, or calprotectin cannot predict
clinical course or prognosis of patients with acute diarrhea although positive fecal lactoferrin is
related to bacterial enterocolitis and development of dehydration.
103
P-42
The Usefulness of C-reactive Protein as a Disease Activity Marker in
Crohn’s Disease According to the Location of Disease
Dong-Hoon Yang, Suk-Kyun Yang, Sang Hyoung Park, Sun-Jin Boo, Jae-Ho Park, Soo Young Na,
Kee Wook Jung, Kyung Jo Kim, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Jin-Ho Kim
Department of Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of Korea.
Background/aims: C-reactive protein (CRP) is commonly measured in Crohn’s disease (CD) patients. However, the usefulness of CRP
as a disease activity marker, especially in ileal CD, remains uncertain. We aimed to assess the usefulness of CRP in CD according to the
involved location.
Method: We investigated 435 patients with first treated at Asan Medical Center between June 1989 and January 2011. Factors associated
with CRP level and the correlation between CRP level and Crohn’s disease activity index (CDAI) at diagnosis were analyzed. The
association between the physician’s prediction on upcoming surgery and the sites of lesions related to surgery was analyzed.
Results: The median age at diagnosis was 24.7 years. Median duration of follow-up was 57 months. The location of disease at diagnosis
was ileum in 112 (25.7%), ileocolon in 293 (67.4%), and colon in 30 patients (6.9%). Multivariate analysis revealed that elevated ESR,
reduced serum albumin, moderate to severe (>220) CDAI, and ileocolonic or colonic location were associated with elevated CRP level (Table
1). At diagnosis, CRP level had significant correlation with CDAI in CD (r= 0.496), but the correlation coefficient was different according to
the locations (r= 0.394 in ileum, r= 0.507 in ileocolon, and r= 0.584 in colon). Among 74 bowel resections, 44 operations were related to ileal
lesions (ileum-main group) and 30 operations were related to ileocolonic or colonic lesions (ileocolon- or colon-main group). Physicians
predicted all operations of ileocolon- or colon-main group, but could not predict 11 (25%) operations of ileum-main group. The maximal
CRP level measured before surgery was lower in the ileum-main group than in the other groups (Table 2).
Conclusion: The association between CRP level and CDAI was relatively weak in ileal CD. The clinical usefulness of CRP as a disease
activity marker is limited in CD with isolated or mainly ileal lesions.
Table 1. Multivariate analysis for the predictive factors associated with elevated CRP level at diagnosis of Crohn’s disease
ESR*
Serum albumin
Location at diagnosis†
Disease Activity
Odds ratio (95% Confidence interval)
Reference
5.164 (2.842-9.386)
Reference
4.856 (2.052-11.492)
Reference
3.670 (1.938-6.948)
4.271 (1.029-17.721)
Reference
2.096 (0.988-4.444)
4.104 (1.927-8.739)
<20 mm/hr
≥20 mm/hr
≥3.3 g/dL
<3.3 g/dL
Ileum (L1)
Ileocolon (L2)
Colon (L3)
Inactive‡
Mild‡
Moderate to severe‡
p-value
<0.001
<0.001
<0.001
0.046
0.054
<0.001
*ESR, erythrocyte sedimentation rate
†Disease location was defined by Montreal classification.
‡Disease activity was categorized by Crohn’s disease activity index (CDAI) as follows; inactive for CDAI <150, mild for CDAI >150 and
≤220, and moderate to severe for CDAI >220.
Table 2. The association between the physician’s prediction on surgery and the sites of lesions related to surgery in the patients with Crohn’s
disease
Sites of lesions related to surgery
Ileum (n=44)
Acute abdomen/perforation (n, %)
Others (n, %)
Prediction of upcoming surgery at Predicted* (n, %)
Not predicted (n, %)
least 2 weeks before
Maximal CRP level before surgery† (mg/dL, mean±S.D.)
Indication of operation
12 (27.3)
32 (72.7)
33 (75.0)
11 (25.0)
3.88±4.15
Colon or both ileum and
colon (n=30)
3 (10.0)
27 (90.0)
30 (100)
0
7.28±6.58
* If the physician recommended surgery at least 2 weeks prior to operation, it was regarded as a ‘predicted’ surgery.
† Maximal CRP level measured from 6 months before surgery to 2 weeks before surgery
104
P-value
0.070
0.005
0.008
P-43
Long-term prognosis of jejunal involvement of
Crohn’s disease
Soo-Kyung Park, Suk-Kyun Yang, Byong Duk Ye, Dong-Hoon Yang,
Kee Wook Jung, Kyung Jo Kim, Jeong-Sik Byeon,
Seung-Jae Myung, and Jin-Ho Kim
Department of gastroenterology, University of Ulsan College of Medicine,
Asan Medical Center, Seoul, Republic of Korea
Backgrounds/Aims: Crohn’s disease (CD) in the jejunum is classified as upper gastrointestinal
tract disease, and is associated with poor prognosis in Caucasians. However, little is known about
the association in Asians. We investigated the prognosis of CD in Korean patients with jejunal
involvement.
Methods: We retrospectively reviewed the medical records of 1403 Korean patients with CD. A Cox
proportional hazards model was used to identify significant predictors of the cumulative probability
of medication use, first major surgery, and first hospitalization. A Poisson regression model was used
to identify significant predictors of the incidence rate of all major surgeries and all hospitalizations.
Results: Jejunal involvement was observed in 198 of 1403 (14.1%) patients at diagnosis. The
median age at diagnosis (24 years vs. 23 years, P= 0.158), proportion of male patients (72.7%
vs. 72.2%, P=0.932), and median duration of follow-up (61.0 months vs. 65.0 months, P=0.397)
were comparable between the jejunal and the non-jejunal groups. There were more ileal location
(28.3% vs. 20.6%, P<0.001) and stricturing behavior (16.7% vs. 9.4%, P=0.001) in the jejunal group
compared with the non-jejunal group. The cumulative probabilities of treatment with corticosteroids
(P=0.014) and thiopurines (P=0.008), first major surgery (P=0.021), and first hospitalization (P=0.015)
were significantly higher in the jejunal than in the non-jejunal group. Jejunal involvement was
independently associated with more common use of corticosteroids (hazard ratio [HR] 1.24; 95%
confidence interval [CI]: 1.02-1.50) and thiopurines (HR 1.26; 95% CI 1.06-1.49), higher incidence
rates of strictureplasties (relative risk [RR] 2.52; 95% CI 1.60-3.96) and hospitalizations (RR
1.29; 95% CI 1.14-1.47), and longer duration of hospitalizations (RR 1.30; 95% CI 1.25-1.34) after
adjustment for covariates.
Conclusion: Korean CD patients are more likely to have jejunal involvement than Western
patients. Jejunal involvement is one of the poor prognostic factors in Korean CD patients, as it is in
Westerners.
105
P-44
Increased risk of gallstone disease among people with inflammatory
bowel disease: a population-based retrospective cohort study
Chien-Chang Liao, PhD, MPH (Assistant Professor);
Ta-Liang Chen, MD, PhD (Professor)
Department of Anesthesiology, Taipei Medical University, Taipei 110, Taiwan
Background/Aim: The association between inflammatory bowel disease (IBD) and risk of gallstone
disease was still undetermined. Our purpose is to investigate whether patients with IBD at increased
risk of gallstone disease.
Methods: A nation-wide general population in Taiwan was obtained from National Health Insurance
Research Database between 2000 and 2008. In 2000-2003, we identified 7,000 patients with a
new diagnosis of IBD and 28,000 participants without diagnosis of IBD aged ≥ 40 years. Incident
gallstone disease was identified among participants with and without IBD during the follow-up
period. We used multivariate Cox proportional hazard models to calculate hazard ratios (HRs) and
95% confidence intervals (CIs) of gallstone disease associated with IBD.
Results: During more than 8-year follow-up period, the incidence of gallstone disease for people
with and without IBD were 10.9/1,000 person-years and 5.4/1,000 person-years, respectively. After
adjusted for sociodemographic factors and co-existing diseases, IBD cohort had higher risk to
develop gallstone disease compared with non-IBD cohort (HR=2.13, 95% CI=1.91-2.37). IBD patients
had experienced emergency care (HR=2.56, 95% CI=1.22-5.38) or inpatient care (HR=3.27, 95%
CI=1.46-7.30) was associated with significant risk of gallstone disease than non-IBD people. More
medical visits for treatment of IBD was significantly associated with increased risk of gallstone
disease (HR=5.83, 95% CI=5.13-6.63).
Conclusion: Our investigation is the first population-based cohort study to report the increased risk
of gallstone disease bleeding among people with IBD.
106
P-46
Growth disturbance in Japanese children with IBD
Toshiaki Shimizu , Tetsuo Shono, Yo Aoyagi, Tohru Fujii, Takahiro Kudo, Yoshikazu Ohtsuka.
Department of Pediatrics, Juntendo University Graduate School of Medicine
[Background/Aim] In Japan, there is as yet no report on growth retardation in children with IBD.
We therefore investigated the cause of growth retardation in Japanese children with IBD. [Methods]
The height, body weight, serum levels of albumin, IGF-I, CRP, and cytokines, and the amount of
corticosteroid administered in children with Crohn’s disease (CD, n=15) and ulcerative colitis (UC,
n=18) were investigated. [Results] Compared with the 1-year period before the start of treatment,
height SDS in children with CD at diagnosis was significantly lower (p<0.05). On the other hand, in
children with UC, there was no significant difference in height SDS when comparisons were made
between values obtained 1 year before the start of treatment and at diagnosis. Although we found that
the CRP level was significantly (p<0.05) elevated in subjects with CD compared with those with UC
at the initial assessment, there were no significant differences between any of the other parameters.
We found a significant negative correlation in both groups (CD group, p<0.01; UC group, p<0.05)
when we compared the correlation between the amount of PSL used and growth rate 1 year after the
start of treatment. We also found a negative correlation between the amount of PSL used and IGF-1
level in children with IBD. [Conclusion] Our results suggest that growth retardation is already present
before the initial visit in children with CD, and chronic inflammation may be responsible this growth
disturbance. Moreover, the amount of PSL used may contribute to growth retardation by decreasing
the serum levels of IGF-I in children with IBD.
107
P-47
Increased Risk of Hip Fracture in People With Inflammatory Bowel
Disease
Yi-Chun Chou, MD1; Ta-Liang Chen, MD2,3, PhD; Chien-Chang Liao, PhD, MPH2,3
1
Department of Physical Medicine and Rehabilitation,
China Medical University Hospital, Taichung 404, Taiwan
2
3
Department of Anesthesiology, Taipei Medical University Hospital, Taipei 110, Taiwan
Background/Aim: Risk of osteoporosis was related to inflammatory bowel disease (IBD). But there
was no information for the association between IBD and risk of hip fracture. This study used national
population-based representative sample to investigate risk of hip fracture after IBD an 8-year followup period.
Methods: Using Taiwan’s National Health Insurance Research Database, we conducted a
retrospective cohort study of 7,628 IBD patients and 30,512 non-IBD participants aged 40 years and
older. We identified new-onset hip fracture after IBD from reimbursement claims during the followup period. Hazard ratios and 95% confidence intervals for the risk of hip fracture associated with
IBD were analyzed with multivariate Cox proportional hazards regression models.
Results: Compared with non-IBD group, patients with IBD had higher proportion of low-income
status and living in low-urbanized area. The higher proportion of comorbidities was found in IBD
group than in non-IBD participants, such as Osteoporosis, mental disorders, herpes zoster, diabetes,
rheumatoid arthritis and hypothyroidism. The proportion of hip fracture for IBD cohort and nonIBD cohort were 2.4% and 1.6%, respectively. During follow-up, IBD patients had higher hazard
ratio (HR) to develop hip fracture compared with non-IBD participants (HR=1.53, 95% confidence
interval=1.29-1.83) after adjusted for age, sex urbanization, low-income status, and comorbidities.
Conclusion: IBD was associated with an increased risk of hip fracture.
108
P-48
The Seasonality in Flares of Korean Patients with Inflammatory
Bowel Disease: a Multicenter Study
Dong Il Park, M.D.,1 Chang Seok Song, M.D.,1 Jae Myung Cha, M.D.,2
Jae Hak Kim, M.D.,3 Suck Ho Lee, M.D.,4 Chang Soo Eun, M.D.,5
Dong Soo Han, M.D.,5 Eun Ran Kim, M.D.,6 Young Ho Kim, M.D.6
1
2
Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
3
Department of Internal Medicine, Dongguk University Ilsan Hospital, Seoul, Korea.
4
Department of Internal Medicine, Soonchunhyang University College of Medicine,
Cheonan, Korea
5
Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea
6
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Korea.
Backgrounds/Aim: Several studies have reported seasonality in flares of inflammatory bowel
disease (IBD). But little data are available in a Korean population. The purpose of this study was to
determine whether flares of patients with IBD follow a seasonal pattern.
Methods: Patients with a diagnosis of IBD established between January 2003 and December
2010 were investigated according to the onset of flares (month and season). A flare was identified
by; 1) receipt of a new prescription and increasing dose for either corticosteroids, 5-ASA,
immunosuppressant, cyclosporine, or infliximab in existing medications. 2) patient was to be
hospitalized and operated due to development and worsening of symptoms. The expected flares
were calculated according to the differences in the number of days in the month of 1 year. Statistical
analysis was performed using the chi-square test, and statistical significances were set at a P value of
0.05.
Results: A total of 448 patients with ulcerative colitis (UC) and 362 patients with Crohn’s disease
(CD) were enrolled in the study. A total of 700 flares of symptoms in UC patients and 602 flares of
symptoms in CD patients were determined. A flare peaks occurred in the winter and spring while
the nadir occurred in the autumn for patients with UC and CD, separately (UC; χ2(3 df) = 14.502, P
= 0.021, CD; χ2(3 df) = 14.318, P = 0.003). In contrast, there was lack of monthly seasonality in onset
of symptom for UC and CD. (UC; P = 0.473, CD; P = 0.146)
Conclusions: A seasonality of flares was observed both UC and CD. The finding may support that
environmental factors, such as seasonal changes in immune function, infection and smoking may be
associated with the symptoms flares of IBD.
Keyword: Seasonality; Crohn’s disease; Ulcerative colitis; Relapse
109
P-49
Comorbidity of depression and anxiety in inflammatory bowel
disease and its relationship with disease status in Korea
Chang Sup Lim1, Won Moon1, Seun Ja Park1, Moo In Park1,
Hyung Hun Kim1, Eun Soo Kim2,Seok Reyol Choi3
1
Crohn’s Disease and Ulcerative Colitis Clinic, Department of Internal Medicine,
2
3
Background/Aims: It is well known that psychological disorders are highly prevalent in patients
with inflammatory bowel disease (IBD). However, there was little data in Asian. In this study, we
aimed to assess the prevalence of depression and anxiety among IBD patients in Korea.
Methods: From May to November 2011, consecutive patients with IBD visited in Kosin University
were evaluated with cross-sectional survey up to three times for each patient at an interval of one
to two months. The patients were evaluated disease activity with Crohn’s disease activity index and
Mayo score and psychological status with the Hospital Anxiety and Depression Scale (HADS),
Becks Depression Inventory (BDI) scale and Brief Encounter Psychosocial Instrument (BEPSI)
scale.
Results: Ninety-two patients (31 women; mean age, 38.1 years) with Crohn’s disease (CD), n =47,
(43 in remission; 2 in mild; 2 in moderate) and ulcerative colitis (UC), n = 45 (32 in mild; 11 in
moderate; 2 in severe) were enrolled. The prevalence of depression and anxiety and both were 21.3%,
27.7%, and 10.6%, respectively in CD patients and those were 20.0%, 13.3% and 6.6% in UC without
difference between both diseases. The mean scores were 5.32 and 4.98 in HADS-D (p=0.552), 5.17
and 4.49 in HADS-A (p=0.227), 3.92 and 4.35 in BEPSI (p=0.020), respectively in CD and UC.
There was no relationship between severities of depression or anxiety or stress and disease activity
status of CD or UC. However, serum albumin levels in CD and hemoglobin level in UC were
adversely correlated with HADS-D and HADS-A. The corticosteroid doses were correlated with
HADS-D in CD and HADS-D and HADS-A in UC.
Conclusion: Comorbidity of depression and anxiety is in about one-fifth of IBD patients in Korea
without difference between CD and UC and associated with nutritional status including serum
albumin and hemoglobin.
Key words: Depression, Anxiety, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis
110
P-50
How are thiopurines dosed in Crohn’s disease? : A novel strategy,
maximum dose-titration based on the lower limit of leukocyte count
and tolerability
1
2
3
Background/Aims: Although general guidelines have been suggested for weight-based dosing of
azathioprine (2.5 mg/kg/day) for Crohn's disease (CD), substantial patients develop bone marrow
suppression. Therefore, maximum optimizing dosing of AZA/6-MP without serious side effects
may not only improve efficacy but also reduce the need to use additional therapy including biologic
agents. The aim of this study was to evaluate the maximum dose of AZA not based on weight but
titrated according to the lower limit of leukocyte count for maintaining remission in patients with
CD.
Methods: From 2010 to 2011, all the patients with CD treated with the maximum dose of
AZA meeting both drug-tolerability and leukocytes count more than 4000/mm 3 for steroid-free
maintaining remission were enrolled. We evaluated the titrated maximum AZA dose and its
relationship with weight.
Results: Forty-two (thirty-two, male; mean age, 31 years old) patients (remission, 34; mild, 4) were
enrolled. The maximum dose of AZA meeting both drug-tolerability and leukocytes count more
than 4000/mm3 for steroid-free maintaining remission was 49.1 mg/day (12.5-150 mg/day). The dose
per weight was 0.87 mg/kg/day (0.17-3.06 mg/kg/day) and negatively correlated with body weight (γ=
-0.51, p=0.01). Ten (23.8%) patients were in 0.1-0.5 mg/kg/day, twenty-three (54.8%) in 0.6-1.0 mg/
kg/day, six (14.3%) in 1.1-1.5 mg/kg/day, and three (7.2%) in 1.6-3.0 mg/kg/day. Between in patients
with 0.1-1.0 mg/kg/day and 1.1-3.0 mg/kg/day, significant differences of weight and height were noted
(61 kg vs. 52 kg, p=0.009 and 170 cm vs. 163 cm, p=0.029). The mean leukocyte count was 5269/
mm3.
Conclusions: Dose decision of AZA only based on weight could put the patients to inappropriately
low or high dose resulting in need of additional therapy or serious side effect, respectively. Therefore,
the maximum dose-titration based on the lower limit of leukocyte count and tolerability is a novel
valuable strategy in thiopurines dose-decision.
111
P-51
Importance of early inflammatory bowel disease: long diagnostic time
lag and prior frequent operation in tuberculosis-high risk country
1
2
3
Background/Aims: The symptoms of inflammatory bowel disease (IBD) are often generally
nonspecific. Therefore, the diagnoses of IBD are frequently delayed. However, there are little data of
time lag in diagnosis of IBD in Korea. This study was undertaken to determine the mean duration of
presenting symptoms, diagnostic time lag and operation frequency before diagnosis of IBD in Korea.
Methods: Medical records of patients diagnosed with IBD in Kosin University from 1990 to 2010
were reviewed.
Results: There were 65 patients (54 male) diagnosed with Crohn’s Disease (CD) and 93 (50 male)
with ulcerative colitis (UC). The mean ages of initial symptom were 24.6 years in CD and 44.5
in UC. The frequent initial symptoms were abdominal pain (54, 83.1%), diarrhea (37, 56.9%), anal
pain (17, 26.2%), anal discharge (14, 21.5%), and weight loss (13, 20%) in CD and hematochezia (77,
82.8%), diarrhea (67, 72.0%), and abdominal pain (47, 50.5%) in UC. The lag in diagnosis was 27.8
months (1-180 months) in CD and 19.5 months (2-240 months) in UC. Before diagnosis of CD, there
was history of anal operation in 21 (32.3%): hemorrhoidectomy in 6 (9.2%), fistulectomy in 13 (20%),
operation for perianal abscess in 5 (7.7%) and abdominal operation in 25 (38.5%): appendectomy in
11 (16.9%), small bowel resection in 17 (26.2%), colectomy 9 (13.8%). Before diagnosis of UC, there
was history of anal operation in 10 (10.8%): hemorrhoidectomy in 8 (8.6%), fistulectomy in 2 (2.2%),
operation for perianal abscess in 2 (2.2%) and abdominal operation in 11 (11.8%): appendectomy in 3
(3.2%), colectomy 4 (4.3%).
Conclusion: In Korea, the diagnoses of IBD are not readily established with long-time lag and prior
frequent operation. Therefore, physician awareness of the manifestations of IBD with a high index of
suspicion is important for the diagnosis of early IBD.
Key Words: Inflammatory bowel disease, Ulcerative colitis, Crohn’s disease, Diagnosis, Symptom
112
P-52
Questions about Crohn’s Disease by Patients: Survey of the Question
and Answer in the Homepage of Crohns’ Disease Fellow Asociation
Kyeong Ok Kim, Byung Ik Jang, Yu Kyung Park, Jae Hong Yang
Yeungnam University College of Medicine
Background/Aims Crohn’s disease is a chronic relapsing disorder of unknown etiology. Although
it is more common in western country, the incidence is rapidly increasing in Korean. However, well
systematized education program about the disease is not enough. And there are several specific
considerations in Korea. The aims of this study are to analyze the most common questions about CD
using the data of Question and Answer(Q and A) community in the homepage of Crohn’s disease
fellow association.
Methods We reviewed all 3000 questions about the Crohn’s disease in the homepage of Crohn’s
disease fellow association (http://crohn.or.kr/) and classified the questions into several categories.
And each catetories were subdivided again into several categories. Before analysis the Q and A, we
got the agreement from the manager of the homepage.
Results The questions were classified primarily into symptoms, diagnosis, treatment, medication,
complication, prognosis and others group. Questions about diagnosis (884 cases, 29.5%) was most
common and among them, questions about abdominal pain was in 208 cases(6.9%), about fistula was
in 174 cases (5.8%). Questions about treatment(873cases, 29.1%) were 2nd most common and medical
treatment (684 cases, 22.8%) were the most common in the treatment category. Questions about
immunomodulator and biologics were 222 cases(7.4%) and 193 cases (6.4%), respectively. Questions
about alternative medicine was in 10 cases (0.3%). Interestingly, questions about military service was
in 125 cases (4.2%) and the hospital expense including special calculation was in 203 cases (6.8%).
Conclusion Most Korean Crohn’s disease patients wanted more accurate information about their
symptoms and treatment. And there are several questions more specific to Korea such as military
service, alternative medicine and hospital expense. We need more systematized and practical
education programs for patients and these analysis can be used as a good basic data.
113
P-53
The Change of the Diagnosis in Crohn’s Disease and Intestinal
Tuberculosis According to the Endoscopic Scoring System and Short
Term anti-tuberculosis Medication Challenge.
Kyeong Ok Kim, Byung Ik Jang, Sung Ho Chun.
Division of Gastroenterology,
Department of Internal Medicine Yeungnam University College of Medicine
Background/Aims: It is difficult to differentiate Crohn’s disease(CD) and intestinl Tbc because
the prevalence of intestial Tbc is still high in Korea. The aims of this study is to review the clinical
outcomes of the patients with CD or intestinal Tbc according to the endoscopic scoring and short
term anti- Tbc medication.
Methods: We retrospectively reviewed the medical records of 51 patients whose clinical symptoms
and endoscopic findings were difficult to confirm CD or intestinal Tbc either. They were all treated
with short term anti-Tbc medication for differential diagnosis. The endoscopic scoring according
to Lee et al’s was done. Of the 51 patients, 26 patients who underwent follow up colonoscopy were
classified into suspected CD, suspected Tbc and equivocal groups, respectively according to the
endoscopic score. The change in treatment after follow up and final diagnosis were analyzed.
Results: At the diagnosis, the patient numbers of suspected tbc group was 12, 8 in suspected CD
and equivocal group was 6. Eleven patients stopped anti Tb medication after follow up colonoscopy.
Among them, 4 patients were in suspected Tb group initially, 5 patients were in CD group and the
other 2 patients were in equivocal group. The change of final diagnosis was noted in 2 patients.
Finally, 7 patients in the initially suspected Tb and 6 patients in the suspected CD groups were
confirmed the initial diagnosis. In 6 patients of equivocal group, 4 patients were diagnosed as
intestinal Tbc and the other 2 patients as CD.
Conclusion: Eleven patients changed from the initial diagnosis after follow up colonoscopy and 2
of them showed change in the final diagnosis. Endoscopic scoring in the differentiation of these two
diseases is useful and short term treatment with anti Tbc medication might have a role in the difficult
cases of differential diagnosis
114
P-54
Diagnostic role of CT enterography differentiating Crohn’s disease
from intestinal tuberculosis
Yoon Hea Park1, Joon Seok Lim2, Jae Hee Cheon1, Tae Il Kim1,
Won Ho Kim1, Sung Pil Hong1
1
2
Radiology Yonsei University College of Medicine, Seoul, Korea
Backgroud/Aims: Because intestinal tuberculosis (ITB) has similar clinical, pathological,
and endoscopic findings with Crohn’s disease (CD), it is challenge to differentiate from each
other. Recently CT enterography (CTE) is widely used to evaluate the small bowel involvement,
complication and disease activity in patients with CD. The aim of the present study was to evaluate
the diagnostic value of CTE in the distinguishing CD from ITB.
METHODS: From January 2006 to August 2011, 81 patients with suspected ITB or CD who
received CTE on initial work-up were included in the present study. The final diagnosis was
made after histology, microbiology, or follow-up by experimental treatment. The CTE findings
were reviewed by two radiologists who were blind to patient histories, endoscopic findings and
final diagnosis. In CTE, degree of bowel involvement, mural change, adjacent mesenteric change
and peritoneal change were assessed. Medical records and endoscopic findings were reviewed
retrospectively.
RESULTS: Among 81 patients, 64 patients (79%) had CD and 17 patients (21%) had ITB. Segmental
involvements (6-40 cm), comb sign, fibrofatty changes of adjacent mesentery, moderate wall
thickening, and asymmetric distribution were significantly more common in CD than in ITB (44.4%
vs. 0%, p= 0.005; 74.1% vs. 9.1%, p<0.001; 46.3% vs. 9.1%, p= 0.039; 55.6% vs. 18.2%, p= 0.011;
66.7% vs. 9.1%, p=0.001). Positive comb sign is the most suggestive finding of CD compared to ITB
(sensitivity 74.1%, specificity 90.9%, PPV 97.6%, NPV 41.7%, Accuracy 76.9%). Combination of
positive comb sign and another CTE finding was not more beneficial than positive comb sign only
differentiating CD from ITB.
CONCLUSION: CTE is a useful diagnostic modality differentiating CD from ITB. Especially,
positive comb sign of CTE is a most precise marker to diagnose CD.
115
P-55
Crohn’s Disease and Intestinal Behcet’s Disease: A Comparison of
the Long-term Clinical Outcomes
Yoon Suk Jung, Jae Hee Cheon, Soo Jung Park, Sung Pil Hong,
Tae Il Kim, and Won Ho Kim
Background: Both Crohn’s disease (CD) and intestinal Behcet’s disease (BD) are transmural
inflammatory diseases that have a fluctuating course characterized by repeated episodes of relapse
and remission and often require operation or reoperation. However, there has been no study that
directly compares the long term prognosis of these two diseases. The purpose of this study was thus
to compare the long-term clinical outcomes between two diseases.
Methods: We reviewed the medical records of 332 patients with CD and 276 patients with intestinal
BD who were regularly followed up at a single tertiary academic medical center between March
1986 and July 2010. The clinical outcomes after diagnosis (cumulative probabilities of operation,
admission, corticosteroid use, and immunosuppressant use) and operation (cumulative clinical
recurrence and reoperation rates) were analyzed using the Kaplan-Meier method and a log-rank test.
Results: There were no significant differences in cumulative probabilities of operation (at 5 and 10
years: 29.4% and 36.0% vs. 31.6% and 44.4%, p = 0.287) and admission (66.1% and 73.8% vs. 59.0%
and 69.2%, p = 0.259) between CD and intestinal BD. Furthermore, no differences were observed
between the two diseases in cumulative probabilities of postoperative clinical recurrence (p = 0.724)
and reoperation (p = 0.770). However, the cumulative probabilities of corticosteroid use (at 5 and 10
years: 63.8% and 76.6% vs. 42.6% and 59.4%, p<0.001), and immunosuppressant use (49.1% and
65.5% vs. 27.1% and 37.7%, p<0.001) were significantly higher in CD patients than in intestinal BD
patients.
Conclusions: There were no significant differences in the long-term clinical outcomes and
post-operative prognosis between CD and intestinal BD, although CD patients required more
corticosteroid or immunosuppressant therapy than intestinal BD patients.
116
P-56
Correlations between endoscopic severity and the clinical disease
activity index in intestinal Behcet’s disease
Hyun Jung Lee, M.D.,* Hui Won Jang, M.D.,* Han Ho Jeon, M.D., *
Eun Suk Jung, M.D.,* Soo Jung Park, M.D., Ph.D.,* Sung Pil Hong, M.D., Ph.D.,* Tae Il Kim, M.D.,
Ph.D.,* Won Ho Kim, M.D, Ph.D.,*,† Chung Mo Nam, Ph.D.,‡
Youn Nam Kim, MS.,‡‡ Jae Hee Cheon, M.D, Ph.D.*,†
*Department of Internal Medicine and Institute of Gastroenterology,
Yonsei University College of Medicine, Seoul, Republic of Korea;
†
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine,
Seoul, Republic of Korea;
‡
Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea;
‡‡
Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea.
Background/aims: To date there have been no studies investigating the correlations between
endoscopic and clinical activity of intestinal Behcet’s disease (BD). The aim of this study was to
develop an endoscopic severity model of intestinal BD and to evaluate the correlations between
disease activity index for intestinal BD and endoscopic severity.
Methods: We reviewed the medical records of 167 intestinal BD patients between March 1986
and April 2011. An endoscopic severity model was developed using their colonoscopic variables
identified by multivariate regression analysis and its correlation with disease activity index for
intestinal BD (DAIBD) was evaluated.
Results: Multivariate regression analysis identified more than two intestinal ulcers (P = 0.031)
and volcano-shaped ulcers (P = 0.001) were predictive factors for DAIBD. However, endoscopic
parameters used for multivariate analysis explained only 18.9% of the DAIBD variance. In patients
with severe DAIBD but moderately predicted disease with an endoscopic severity model had more
irritable bowel syndrome symptoms (21.4 vs. 4.9%, P = 0.026) and less use of corticosteroids (50.0
vs. 75.6%, P = 0.016) than endoscopically severe group.
Conclusions: Our study showed that more than two intestinal ulcers and volcano-shaped ulcers
were predictive factors for severe DAIBD. However, the correlation between endoscopic severity
and DAIBD (γ = 0.434) was weak. Clinicians should closely observe patients with these risk factors
which could help to make appropriate decisions regarding medical strategies.
Key words: intestinal Behcet’s disease, disease activity index, endoscopic severity
117
P-57
Ulcerative colitis patients should be instructed to conceive while in
remission.
Masaki Ujihara, Takafumi Ando, Kazuhiro Ishiguro, Osamu Watanabe,
Osamu Maeda, Satoshi Hibi, Toru Kamiya, Shunya Mimura, Yutaka Hirayama, Kazuhiro Morise,
Ryoji Miyahara, Naoki Omiya, Hidemi Goto
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
Background: Ulcerative colitis (UC) is relatively often occurred in women of reproductive age.
Despite the importance of a unified approach by specialists in the management of UC during
pregnancy, however, few reports concerning the progress and treatment of UC during pregnancy have
appeared from Asian countries, including Japan.
Patients and Methods: We retrospectively studied 90 pregnancies in 63 patients with UC experienced
at our hospital and related institutions in the past 20 years, focusing on the relation between the
progression of UC during pregnancy, the progress of the pregnancy itself, and the treatment of UC.
Results: Among the 90 pregnancies, UC severity at the time the patient became pregnant was
remission stage in 50 (55.6%), mild active stage in 19 (21.1%), and moderate active stage in 10 (11.1%).
UC had not yet been developed in 11 (12.2%). Exacerbation of UC occurred in 39.2% of pregnancies.
Being in moderate or severe active UC during pregnancy occurred in 14% of pregnancies in which
UC was in remission at onset, versus 48.3% of pregnancies in which UC was active at onset (p<0.01).
Ten percent of spontaneous abortions and terminations occurred in pregnancies with UC in remission
at onset and 29% in those with active UC (p<0.05). Exacerbation during pregnancy took place in
27.3% of the group who continued to receive pharmaceutical treatment versus 56.3% in those with a
dose decrease or discontinuation after onset (p<0.05).
Conclusion: Patients with UC who wish to conceive should wait until the condition is in remission.
Appropriate pharmaceutical management during pregnancy is crucial to avoiding relapse or any
worsening of UC.
118
P-58
Treatment Outcomes of Tacrolimus in Patients with Ulcerative Colitis
Miyuki Mukae, Kiyonori Kobayashi, Taishi Ogawa, Kaoru Yokoyama, Miwa Sada,
and Wasaburo Koizumi
Department of Gastroenterology, Kitasato University East Hospital
Objective: To clarify the short-term effectiveness and safety of tacrolimus in patients with refractory
ulcerative colitis(UC).
Methods: The study group comprised 11 patients (5 females) who received tacrolimus (13 courses).
The disease type was pancolitis in 10 patients and left-sided colitis in 1. The mean age at the time
of treatment was 38.5 years. The mean duration of disease was 8.9 years. Before starting treatment
with tacrolimus, all patients had received 5-aminosalicylic acid and 11 had received corticosteroids.
All were either steroid-resistant or steroid-dependent. The dose was adjusted to maintain a whole
blood trough concentration of 10 to 15 ng/mL 2 weeks after the start of treatment and 5 to 10 ng/
mL thereafter. Treatment response was evaluated according to the Seo index and C-reactive protein
(CRP) levels 2 weeks, 4 weeks, and 3 months after treatment began. The treatment response was also
evaluated according to Matts classification by colonoscopy.
Results: 1) The mean index and CRP level(mg/dL) were 191.7 ± 39.5 and 1.3 ± 1.3 before treatment
with tacrolimus, but significantly decreased to 122.2 ± 15.2 /0.2 ± 0.1,114.4 ± 18.6 /0.2 ± 0.2, 112.7 ±
27.4 / 0.2 ± 0.1 after 2 ,4 weeks and 3months (p<0.001/ p<0.01).When a Seo index of 120 or less was
defined as remission, remission induction rates after 2,4 weeks and 3 months were 33 ,78 and 71%.
2) In 3 of the 4 patients who underwent colonoscopy before and after treatment, the disease severity
had decreased from Matts grade 4 to 1. 3) Adverse events occurred 7 times (54%). Treatment was
discontinued in 3 who had fungal pneumonia, liver dysfunction, and general fatigue.
Conclusions: Tacrolimus is useful for the treatment of refractory UC and has good short-term
outcomes, however, is associated with a high incidence of adverse events, requiring close follow-up
of patients.
119
P-59
Efficacy of oral tacrolimus and infliximab in the treatment of active
ulcerative colitis.
Kouichi Asano1, Junji Umeno2, Tomohiko Moriyama2, Motohiro Esaki2,
Shotaro Nakamura2, and Takayuki Matsumoto2
1
Department of endoscopic diagnosis and diagnosis, Kyushu University Hospital, Fukuoka, Japan,
2
Department of Medicine and Clinical Science Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
Background: Recently, oral tacrolimus and infliximab were approved for the treatment of ulcerative
colitis (UC) in Japan.
Aims: To investigate the efficacy of oral tacrolimus and infliximab in the treatment of active UC
with active disease.
Methods: A total of 25 consecutive patients with steroid-refractory or moderate-to-severe UC were
recruited in the study from May 2007 to August 2011, in which 12 were treated with tacrolimus
and the others infliximab. Tacrolimus was administered orally with high trough levels of blood
concentration (10 – 15 ng/ml) in the first 2 weeks and with low trough levels after week 3 (5 – 10 ng/
ml). Infliximab was infused intravenously (5 mg/kg) at week 0, 2, 6, and then every 8 weeks. Disease
activity was calculated using Ulcerative Colitis Activity Index (UCAI) reported by Seo M, et al.
Clinical remission was defined as UCAI score of <150. We investigated the remission induction rates
of both drugs at week 8 and patients who had obtained clinical remission were followed up for 26
weeks.
Results: The mean total UCAI score at study entry was 210.4 ± 41.0 in the tacrolimus group and
218.8 ± 26.9 in the infliximab group. 83.3 percent of patients who received tacrolimus and 92.3
percent of those who received infliximab had a clinical response at week 8, with no difference in
remission induction rates between the two groups. At week 26, the clinical response rate was 75.0%
(9/12) in the tacrolimus group and 70.0% (7/10) in the infliximab group. A patient who received
infliximab developed uterus cancer 3 months after the first injection. On the other hands, a patient
who received tacrolimus occurred renal function impairment resulted in withdrawal of tacrolimus.
Conclusion: Both oral tacrolimus and infliximab were similarly efficacious in the treatment of
steroid-refractory or moderate-to-severe Ulcerative Colitis.
120
P-60
Nutritional Status Assessment of Newly-diagnosed Inflammatory
Bowel Disease patients
Min Ji Lee, Sung Hye Kim*, Mi Yong Rha*, Young Yun Cho*, Byung-Hoon Min,
Jun Haeng Lee, Dong Kyung Chang , Young-Ho Kim, Poong-Lyul Rhee,
Jae J. Kim, Jong Chul Rhee, Jin Yong Kim
Department of Medicine, *Department of Dietetics, Samsung Medical Center, Sungkyunkwan
University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
BACKGROUND/AIMS:
Nutritional derangements are important element in inflammatory bowel disease (IBD). We analyzed
the nutritional status of newly-diagnosed inflammatory bowel disease.
METHODS:
A total of 112 newly-diagnosed IBD patients (69 patients (age: 42.2 ± 14.7, male: 40.6%) with
ulcerative colitis (UC) and 43 patients (age: 29.3 ± 11.4, male: 74.4%) with Crohn’s disease (CD))
were assessed for their nutritional status.
RESULTS:
Large proportion of patients were taking less than calori in needs (<80%, 80-89%, and ≥90% for 62
patients (58.2%), 15 patients (13.6%) and 31 patients (28.2%), respectively). Weight reduction < 90%
(current body weight/usual body weight (%)) were noticed in 26 patients (23.2%) and 19 patients
(17.0%) were underweight (body mass index < 18.5 kg/m 2). Weight reduction < 90% (39.5% vs.
13.0%, p = 0.001) and underweight (25.6% vs. 11.6%, p = 0.055) were more prevalent in CD than UC.
Frequent disturbing symptoms for calori intake were hematochezia (86.1%), gas distension (59.7%),
and diarrhea (50.7%) in patients with UC, and were diarrhea (74.4%), gas distension (40.3%) and
hematochezia (13.9%) in patients with CD. Most prevalent food items that patients felt discomfort
while eating were fatty foods (42.9%) followed by milk (37.5%). Notably, more proportion of patients
with CD felt discomfort eating fruit or vegetable than UC (16.3% vs. 4.3%, p = 0.043). C-reactive
protein level correlated significantly with decreased calori intake (-0.239, p = 0.017), weight loss
(0.369, p < 0.001), and body mass index (-0.330, p = 0.001).
CONCLUSIONS:
Nutritional intake was inadequate in significant proportion of newly-diagnosed IBD patients. Patients
with CD have more severe nutritional problems than patients with UC, and nutritional status had
negative relationship with C-reactive protein. This data emphasize importance of early nutritional
support as an integral part of management in IBD patients, especially in patients with CD and
elevated C-reactive protein level.
121
P-61
The Cap Assisted Technique Enhances the Colonoscopy Training;
Prospective Randomised Study of Six Trainees.
Sang Man Park, M.D., Soon Hak Lee, M.D., Keun Young Shin, M.D., Jun Heo, M.D.,
Sang Hoon Sung, M.D., Soon Hong Park, M.D., So Young Choi, M.D.,
Dong Wook Lee, M.D., Hyun Gu Park, M.D., Hyun Seok Lee, M.D.,
Seong Woo Jeon M.D., Ph.D., Sung Kook Kim M.D., Ph.D.,
Min Kyu Jung, M.D., Ph.D.
Kyungpook National University School of Medicine, 50, Samduk-Dong 2 Ga,
Junggu, Daegu, 700-721, South Korea
Background: Colonoscopy and polypectomy procedures have effectively reduced the incidence of
colorectal cancer. Nowadays, competence in colonoscopies is one of the essential parts of the training
program of GI trainees. However, considerable training is required for the optimal performance of a
colonoscopy.
Aim: To compare the effectiveness of cap-assisted colonoscopy and non-cap-assisted colonoscopy
for improving trainee effectiveness.
Methods: This study involved 6 colonoscopy trainees. Three of them used cap and the others did
not. Each trainee performed 100 cases of screening colonoscopy from the beginning to end. The
success cecal intubation rate, cecal intubation time, polyp detection rate, adenoma detection rate,
advanced adenoma detection rate, adenocarcinoma detection rate was checked.
Result: The cecal intubation rate in the cap group was 80.7% (242/300) and in the non cap group
it was 63.3% (190/300). The average cecal intubation time was 13.7 min in the cap group and 18.7
min in the non cap group. Statistical analysis of these results suggested that the cap group had a
significantly higher success rate (p= 0.00) and shorter cecal intubation time (p= 0.00) than the noncap group. However, there were no significant differences between the two groups in the detection
rate of polyps (45.3% vs 43%, p= 0.311), adenomas (26.3% vs 25%, p= 0.390), advanced adenomas
(2.6% vs 0.6%, p= 0.053), and adenocarcinomas (5.3% vs 3%, p= 0.110).
Conclusion: Cap assisted colonoscopies might be helpful in increasing the successful cecal
intubation rate and shortening the cecal intubation time in GI trainees.
122
P-62
A Case of Soft Tissue Abscess Caused by Salmonella Serotype D
in a Patient Presenting As Acute Colitis
Eun Mi Song, Sung-Ae Jung, Seong-Eun Kim, Kyoung Joo Kwon,
Hye Won Kang, Ju Young Choi, Ki-Nam Shim, Hye-Kyung Jung,
Tae Hun Kim, Kwon Yoo, Il Hwan Moon
<Introduction>
Non-typhoidal salmonellosis, which is increasing nowdays in Korea, is manifested as gastroenteritis
in most cases, but many other disease can follow during or after bacteremia. Suppurative soft tissue
abscesses due to focal infection with salmonella are uncommon with an overall incidence of up to
1.7%. Here we report a case of soft tissue abscess caused by salmonella serotype D.
<Case>
A 70-year-old female visited our hospital because of a 5-day history of continous watery diarrhea.
She was taking medications for hypertension and cerebral infarction. Initial vital signs were stable
although she had watery diarrhea of 8~10 times a day and complained of severe general weakness
and dehydrartion. She didn’t have abdominal pain, vomiting nor fever. Laboratory findings revealed
white blood cell count of 12.3x103/uL with 78% neutrophils, and C-reactive protein 23.73 mg/dL. She
was treated for acute colitis with IV antibiotics and hydration. However, newly onset left thigh pain
and 38 ̊C fever suddenly developed on the hospital day 2. About 10 x 15 cm sized cystic mass was
palpable at the lateral side of the left thigh, accompanied with tenderness, redness and local heating.
A lower extremity CT scan revealed a 12 cm sized peripheral wall enhanced soft tissue lesion at the
subcutaneous layer adjacent to the tensor fascia lata. The patient underwent fine-needle aspiration
of the abscess under ultrasound guidance. Salmonella serotype D was isolated from the aspirated
fluid. The stool, urine and blood cultures were negative. In colonoscopy performed at hospital day
5, punched out shaped ulcerations with edema were noted in the ascending colon and cecum. The
patient was treated with IV ciprofloxacin after surgical open drainage of the abscess. Diarrhea
was stopped on hospital day 2, and fever subsided on 3rd day of drainage. She discharged with oral
antibiotics.
123
P-63
The outcome and interval between colonoscopy after a negative
colonoscopy
Won Kyung Yoon, Min Kyu Jung, Min Kim, Keun Young Shin,
Jun Heo, Seong Woo Jeon.
Internal Medicine Gastroenterology and Hepatology,
Kyungpook National University Hospital, Republic of Korea
Keywords: outcome, interval between colonoscopy
Background: To evaluate the outcome and interval between colonoscopy following performance of
a negative colonoscopy.
Methods: Subjects in this study comprised 486 patients with initial negative colonoscopic result in
Kyungpook National University Hospital, Republic of Korea between Jau. 2002 and Aug. 2009. The
clinical outcome and interval between 1st and 2nd colonoscopy were reviewed retrospectively.
Results: Among 486 patients, men were 234 (48.1%) and women were 253 (51.9%). The mean age of
patients was 53.6 ± 10.2. The outcomes of 2nd colonoscopy were normal (325, 66.9%), adenoma (80,
16.5%), advanced adenoma (10, 2.1%), adenocarcinoma (2, 0.4%), hyperplastic polyp (60, 12.3%) and
others (9, 1.9%). The intervals between colonoscopy were normal (1055.0 ± 541.3), adenoma (1265.1
± 562.7), advanced adenoma (1555.9 ± 665.1), adenocarcinoma (1470.0 ± 553.0), hyperplastic polyp
(1090.2 ± 550.3) and others (1198.0 ± 900.0).
Conclusion: There noted no statistical significance between outcome and interval between
colonoscopy. Further study is required to determine the optimal interval between colonoscopy
following performance of a negative colonoscopy.
124
P-64
Autophagy upregulates CXCL10 in primary intestinal epithelial cells
stimulated by Flagellin via TLR5 on basolateral membrane.
Xiu Zheng, Kiichiro Tsuchiya, Yoshihito Kano, Nobukatsu Horita,
Ryuichi Okamoto, Tetsuya Nakamura and Mamoru Watanabe
Background & Aims: The reaction to Flagellin via Toll like receptor 5 (TLR5) playing a central
role in mucosal barrier. TLR5 of IEC is expressed on the basolateral membrane, suggesting that IEC
react only to the invasive bacteria via TLR5 signaling. However, physiological reaction of IEC via
TLR5 on basolateral membrane has been impossible to be elucidated by using cell line or in vivo
study. Recently, Sato method (Nature 2009) enables to culture the primary IEC (pIEC). We therefore
aim to assess the reaction to flagellin of pIEC via TLR5 on basolateral membrane.
Methods: The localization of TLR5 in small intestine and pI ECs was analyzed by
immunofluorescence. Flagellin was added to the medium for either 3 hours or 7 days to stimulate
TLR5 on basal membrane at the outside of spheroid. Comprehensive genes induced by flagellin
were detected by microarray analysis. The response to flagellin in pIECs generated from MyD88
and ATG5 deficient mice were assessed for the effect of TLR signaling and the autophagy function,
respectively. Secreted CXCL10 protein was analyzed by ELISA.
Results: TLR5 of pIECs was specifically localized on the basal membrane at the outside of the
spheroid. Flagellin did not change the cell formation and the phenotypic gene expression of pIECs.
However, microarray analysis showed that various genes including cytokines, chemokines and
reactive oxygen species were induced by flagellin via MyD88 signaling. Especially, CXCL10 induced
by flagellin was secreted through the basal membrane of pIECs. Moreover, CXCL10 was overexpressed by flagellin stimulation to pIECs generated from ATG5 deficient mice.
Conclusion: IECs play various roles in the invasion of bacteria as a unit at the front line of mucosal
defense. Moreover, Malfunction of autophagy in IECs causes the overreaction to flagellin, suggesting
the one of the pathogenesis for Crohn’s disease.
125
P-65
Hes1 promotes IL-22-mediated epithelial regeneration through
enhancement of STAT3-dependent transcription in human intestinal
epithelial cells.
Tatsuro Murano, Ryuichi Okamoto, Hiromichi Shimizu,
Go Ito, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe
Background & Aims: We have previously shown that Notch-Hes1 signaling in intestinal epithelial
cells (IECs) plays an indispensable role in epithelial regeneration of IBD. IL-22 is up-regulated
in IBD, and has also been implicated in epithelial regeneration. Thus, we investigated whether
any interaction between Notch-Hes1 and IL-22/IL-22R pathway may exist in IECs, and thereby
contribute to regeneration of the intestinal epithelia in IBD.
Methods: Notch-Hes1 pathway was activated by forced expression of Notch intracellular domain
(NICD) or Hes1, in LS174T or DLD1 cells. IL-22/IL-22R pathway was activated in those cells
by addition of recombinant human IL-22. Under concomitant activation of these two pathways,
activity of RBP-J dependent- or STAT3-dependent transcription was measured by reporter assays.
Phosphorylation of STAT3 was examined by immunoblot analysis, and expressions of down stream
target genes were analyzed by quantitative RT-PCR.
Results: Upon concomitant activation of Notch-Hes1 and IL-22/IL-22R pathway, no significant
interaction was observed in RBP-J-dependent transcription. In sharp contrast, STAT3-dependent
transcription was significantly up-regulated by activation of both Notch-Hes1 and IL-22/IL-22R
pathway, compared to IL-22/IL-22R pathway alone. Such an additional effect on STAT3-dependent
transcription was mediated by Hes1, as forced expression of Hes1 in addition to IL-22 up-regulated
STAT3-dependent transcription up to 230 folds, whereas IL-22 alone up regulated its activity
up to 20 folds. Consistently, in response to IL-22, phosphorylation of STAT3 at Tyr705 could be
maintained at a high level for a significantly extended period of time by forced expression of Hes1.
Quantitative RT-PCR analysis showed that such a co-operation between Hes1 and IL-22/IL-22R
pathway not only enhanced STAT3 dependent transcriptional activity, but also further enhanced
expression of its target genes, such as REGI or REGIII, that are critically required for epithelial
regeneration.
Conclusion: Notch-Hes1 pathway enhances IL-22 mediated STAT3-dependent transcription and
subsequent regenerative response in IECs.
126
P-66
Notch-Hes1 pathway and TNF-α synergistically up-regulates OLFM4
expression in the inflamed mucosa of the human intestine
Ryuichi Okamoto, Junko Akiyama, Hiromichi Shimizu, Tatsuro Murano, Go Ito, Kiichiro Tsuchiya,
Tetsuya Nakamura, Mamoru Watanabe
Background & Aims: Studies have shown that OLFM4 is a robust marker for intestinal epithelial
stem cells. However, the precise distribution of OLFM4-expressing cells within the inflamed human
intestinal mucosa or the molecular mechanism regulating its expression remains largely unknown.
We have previously shown that Notch-Hes1 pathway is constitutively activated in intestinal epithelial
cells (IECs) of IBD, and function as a key pathway for lineage-specific gene expression. Thus we
planned to identify the distribution of OLFM4-expressing IECs, and the possible role of Notch-Hes1
pathway upon expression of OLFM4 in the inflamed mucosa of IBD.
Methods: Distribution of OLFM4-expressing cells was determined by immunostaining. Expression
level of OLFM4 was analyzed by RT-PCR. Notch-Hes1 pathway was activated by forced expression
of Notch intracellular domain (NICD) or Hes1, in LS174T or DLD1 cells. Series of promoter assay
was performed to analyze transcriptional regulation of the human OLFM4 gene.
Results: Immunostaining of normal human intestinal tissues showed OLFM4-positive IECs residing
at the lowest part of the crypt. However, in inflamed intestinal tissues of IBD, increased number of
OLFM4-expressing IECs was observed, expanding its distribution to the upper part of the crypt.
In LS174T cells, stimulation by TNF-α, but not by IL1-β and IFN-γ, significantly up-regulated the
mRNA expression of OLFM4. Also, forced expression of both NICD1 and Hes1 significantly upregulated mRNA expression of OLFM4. Combination of NICD1 or Hes1 over-expression with
TNF-α stimulation had synergistic effect upon up-regulation of OLFM-4 mRNA expression,
reaching up to 2500 fold increase in LS174T cells. Promoter assays revealed that such a synergistic
effect of TNF-α and Notch-Hes1 pathway is mediated through NF-κ-dependent transcription.
Consistently, TNF-α mediated NF-κB-dependent transcription was significantly enhanced by both
NICD1 and Hes1 over-expression in LS174T cells.
Conclusion: In the inflamed human intestinal mucosa, TNF-α and Notch-Hes1 pathway
synergistically up-regulate expression of OLFM4 in IECs.
127
P-67
Overexpression of Smad2/3, phosphorylated at specific linker
threonine residues, in the murine model of Dextran Sodium SulfateInduced Colitis
Masanobu Kishimoto , Toshiro Fukui , Yu Takahashi , Atsushi Nakajima ,
Yutaku Sakaguchi , Kazushige Uchida , Akiyoshi Nishio ,
Koichi Matsuzaki , Kazuichi Okazaki
Background Stem cells play roles in mucosal cell homeostasis and repair. They are supposed to
be located in the crypt base of the descending colon, and cellular migration occurs in an outward
direction. However, useful markers for stem cells in the colon have not been elucidated. We explored
whether Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), could serve
as a marker for stem cells. To clarify the behavior of pSmad2/3L-Thr expressing cells in the injury
or regeneration phase, we investigated these cells in the murine model of dextran sodium sulfate
(DSS)-induced colitis. Methods Normal colons from C57BL/6 mice and colons from the murine
model of DSS-induced colitis were examined. Double immunofluorescent staining of pSmad2/3LThr with Ki67, ChromograninA, cytokeratin8, or DCAMKL1 was performed, and pSmad2/3LThr immunostaining-positive cells were counted. After immunofluorescent staining, we stained the
same sections with hematoxylin-eosin and observed these cells under a light microscope. Results
In normal colons, pSmad2/3L-Thr positive cells were found in the crypt base and detected among
the Ki67 positive cells, but immunohistochemical co-localization of pSmad2/3L-Thr with Ki67 was
never observed. pSmad2/3L-Thr positive cells showed co-localization with cytokeratin8 and negative
staining for ChromograninA, and some of them showed similar localization with DCAMKL1
positive cells. Under a light microscope, pSmad2/3L-Thr positive cells indicated undifferentiated
morphological features and were confirmed in the crypt base. In the murine model of DSS-induced
colitis, pSmad2/3L-Thr positive cells were significantly increased in the regeneration phase and
decreased in the injury phase compared with those of normal C57BL/6 mice. The number of Ki67
positive cells in the regeneration phase was also much greater, and that in the injury phase was
also much smaller. Conclusions We have identified the significant expression of pSmad2/3L-Thr in
specific epithelial cells of the murine colon and have suggested these cells to be epithelial stem cells.
128
P-68
The novel host-probiotics interaction through activation of intestinal
epithelial autophagy
Yuhei Inaba1, Mikihiro Fujiya1, Nobuhiro Ueno1,
Eugene B Chang2 and Yutaka Kohgo1
1
Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan
2
Department of Medicine, University of Chicago, Chicago, Illinois, USA
Background
Probiotics are live microorganisms that promote gut health and regulate intestinal homeostasis.
How probiotics work is incompletely understood. Autophagy is believed to have an important role
in promoting cell survival under stressful conditions and in clearance of potentially disease-causing
intracellular microorganisms. Polymorphisms in autophagy genes have recently been linked to
increased risk of human IBD. The study aimed to clarify the role of autophagy on host-probiotic
interaction.
Methods
Intestinal epithelial cells (human colonic Caco2BBE or rat jejunal IEC18) were treated with
conditioned media from Bifidobacterium breve (BB-CM) or other bacteria. Initially time dependence
was determined using 1% CM and subsequently concentration dependence was determined at from
0.5 to 8 hours for rapid transduction events (MAP kinase, LC3 conjugation) versus long lived cellular
survival proteins (Hsps induction), next to figure out the characterization of autophagy-inducing
factor in BB-CM, we checked about the molecular weight, detection of protein or peptide, heat
stability and pH property. All were assessed by Western blot analysis.
Results
BB-CM induced autophagy in a time- and concentration-dependent manner. Western blot analysis
demonstrated LC3II activation by conjugation to phosphatidylethanolamine by 2 hours after BBCM. BB-CM also activated MAP kinase but within 0.5 hour. For BB-CM, inhibition of either p38
MAP kinase with SB203580 or JNK activation with SP60025 blocked LC3 activation. A wider panel
of gram positive and negative bacteria was tested on LC3 activation and while most gram positive
bacteria stimulated LC3 activation, most gram negative did not. Bioactive factor of BB-CM is
probably a peptide or protein of small molecular mass, heat stable and low-pH resistant.
Conclusions
These studies provide evidence that bioactive agents secreted by probiotic bacteria can induce
autophagy in gut epithelial cells. The induction of autophagy may underlie some of the beneficial
clinical effects attributed to a healthy enteric microbiota and probiotic agents.
129
P-69
A protective effect of vitamin C on DSS-induced colitis
Jong Pil Im1, Hyemin Kim2, Hang Rae Kim2, Young Il Hwang2,
Jae Seung Kang2, Wang Jae Lee2 and Joo Sung Kim1
Department of 1Internal Medicine and Liver Research Institute,
2
Anatomy and Tumor Immunity Medical Research Center,
Seoul National University College of Medicine,
28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea
Background/Aims: Intestinal mucosal damage in the inflammatory bowel diseases (IBD), Crohn’s
disease (CD) and ulcerative colitis (UC), involves the dysfunctional immunoregulation of the gut.
Among the immunoregulatory factors, reactive oxygen species (ROS) are produced in abnormally
high levels in IBD and, their destructive effects may contribute to the initiation or propagation of the
disease. Vitamin C not only scavenges free radicals as an antioxidant but also has anti-inflammatory
effects. Methods: We investigated the effect of vitamin C on DSS-induced colitis in gulo(-/-)
mice which cannot synthesize vitamin C. Results: Vitamin C-insufficient gulo(-/-) mice showed
decreased survival and lowering recovery efficacy. It accompanied with more severe colitis such as
epithelial erosion, infiltration of inflammatory cells and contraction of colon. The production of proinflammatory cytokine, IL-6 was remarkably higher in DSS-treated vitamin C-insufficient gulo(-/-)
mice than vitamin C-sufficient gulo(-/-) mice and wild type mice. In contrast, the production of antiinflammatory cytokine, IL-22 was significantly decreased in vitamin C-insufficient gulo(-/-) mice
in compared to vitamin C-sufficient gulo(-/-) mice and wild type mice after DSS administration.
Also, the phosphorylation of STAT3, a downstream signaling of IL-6 and IL-22, was increased in
both epithelial cells and lamina propria cells. Conclusion: It suggests that vitamin C represents a
protective effect on DSS-induced colitis by regulating the production of cytokine and the induction
of inflammation.
130
P-70
Immunoregulatory function of PIR-A/B+ DCs in the inflammatory
responses of dextran sodium sulfate induced colitis
Akiko Kurishima1, Muneo Inaba2, Yutaku Sakaguchi1, Toshiro Fukui1,
Kazushige Uchida1, Akiyoshi Nishio1, Shosaku Nomura2, Kazuichi Okazaki1
1
Kansai Medical University, Osaka, Japan.
2
First Department of Internal Medicine, Kansai Medical University, Osaka,Japan
Background/Aims: Dendritic cells (DCs) are antigen-pressenting cells, which may play an
important role in inflammatory bowel disease (IBD), including Crohn's disease and Ulcerative colitis.
DCs are generally recognized as initiators of acquired immunity by stimulating naïve T cells and
by inducing self-tolerance, and they are also involved in the regulation of innate immunity. We used
the animal model of colitis induced by dextran sodium sulfate (DSS), and examined whether DCs
prepared from the colon show immunoregulatory roles in the termination of DSS-induced colitis.
Methods: C57BL/6 mice exposed to DSS for 5 days developed acute colitis. DCs were isolated from
the large intestinal lamina propria and analysed by flow cytometry.We determined the expression of
paired immunogloburin-like receptor A/B (PIR-A/B) on colon-derived DCs in the kinetics of DSSinduced colitis. Results: Only PIR-A/Blow cDCs were detected in the steady state. However, after the
treatment of DSS, PIR-A/Bhigh cDCs appeared and gradually increased from day 5 to day 7, at which
time the DSS-induced colitis became to be terminated. Then allogenic mixed leukocyte reaction
(MLR) was performed. The stimulatory activity of PIR-A/Bhigh cDCs obtained on day 7 was lower
than those of PIR-A/Blow, and far lower than that of splenic DCs used as positive control DCs. We
compared the gene expression pattern between PIR-A/Bhigh cDCs and PIR-A/Blow cDCs using DNA
microarray analysis. To qualitatively determine the expression of candidate genes, we prepared
PIR-A/Bhigh cDCs and PIR-A/Blow cDCs and the message levels of TGF-βi and IFN-α were compared
between both DC subsets. The level of TGFβi was significantly higher in PIR-A/Bhigh cDCs while
that of IFN-γ was highly upregulated in PIR-A/Blow cDCs. Conclusion: PIR-A/Bhigh cDCs showed
the low stimulatory activity and rather had a suppressive function against activated T cell.
131
P-71
Intestinal CXCR4+IgG+ Immature Plasma Cells Contribute to the
Pathogenesis of Ulcerative Colitis through IgG-Immune
Complex-FcγR Signaling
Tadakazu Hisamatsu1, Michihide Uo1, Jun Miyoshi1, Kazuaki Yoneno1,
Katsuyoshi Matsuoka1, Takanori Kanai1, Haruhiko Ogata2, and Toshifumi Hibi1
1
Keio University School of Medicine, Tokyo, Japan.
2
Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University
Background and Aim: In health the vast majority of intestinal plasma cells (PCs) are IgA-producing
PCs, on the other hand, there is a massive influx of IgG-producing PCs into the inflamed mucosa
in UC. However, the precise mechanism of infiltration and their involvement in pathogenesis of UC
remain unclear. To clarify these unresolved questions, we analyzed the characteristic features of
intestinal PCs in patients with UC, and examined the possible involvement of IgG-immune complex
(IC)-FcγR signaling in intestinal inflammation. Methods: Human lamina propria mononuclear cells
(LPMCs) were isolated according to the protocol previously established. 1) Microarray analysis
was performed and the expression of surface and cytoplasmic antigens of intestinal PCs was
analyzed by flow cytometry. 2) LPMCs were stimulated by plate IgG-IC, and the amount of cytokine
produced was measured. Target cells which express FcγR were identified by flow cytometry.
More detailed analysis was performed using blocking antibodies against FcγR and FcγR signaling
inhibitor. Results: 1) The proportion of IgA+ PCs in LP PCs was negatively correlated with the
degree of local mucosal inflammation in UC, and coincidental increase of IgG+ PCs was observed.
Analysis of cell surface differentiation molecules revealed that PCs in inflamed mucosa of UC were
CD38highCD19+CD20-CD27low immature plasmablast-like phenotype. IgG+ PCs in patients
with UC specifically expressed chemokine receptor CXCR4, and lacked the expression of CCR10,
which is expressed in IgA+ PCs. 2) IgG-IC stimulation induced the production of inflammatory
cytokines such as TNF-α from LPMCs. We revealed that CD14+ unique intestinal macrophages
expressed FcγRs, and they produced a large amount of TNF-α by IgG-IC stimulation. Blocking
antibody against FcγR and FcγR signaling inhibitor selectively inhibited IgG-IC-induced TNF-α
production in dose-dependent manners. Conclusion: In UC, intestinal IgG+ PCs might infiltrate
into the inflamed mucosa via CXCL12-CXCR4 axis and be involved in the pathogenesis of UC by
exacerbating mucosal inflammation through IgG-IC-FcγR signaling.
132
P-72
Pleiotropic Action of Gut Tropic Factors Derived from Conditioned
Mesenchymal Stem Cells
Kanna Nagaishi1, Shuhei Watanabe2, Yasuyoshi Naishiro3, Kentaro Yamashita2,
Yoshiaki Arimura2, Mineko Fujimiya1, Yasuhisa Shinomura2, Kohzoh Imai4
1
3
4
2
Background/Aims: Although mounting evidence implicates mesenchymal stem cells (MSCs)
in intestinal tissue repair, the mechanism of action remains uncertain. Therefore, we focused on
humoral gut tropic factors derived from conditioned MSCs and their therapeutic effects through
paracrine interactions for achieving definitive repair.
Methods: Rat bone marrow MSCs were exposed to INFγ(designated as γCM), normoxia (norCM)
or hypoxia (hypoCM) to explore the optimal MSC-conditioned medium (MSC-CM). DSS colitis and
TNBS colitis was induced in Lewis rats and C57BL/6 mice, respectively. MSC-CM was systemically
administrated for five days after inducing colitis. The effects of MSC-CM on rat intestinal epithelial
cell (IEC-6) viability, mobility, apoptosis and cell cycle were assessed by MTT, scratch assay,
TUNEL reaction and FACS, respectively. Immunologic modulation of MSC-CM was evaluated on
cytokine production in both laminar propria lymphocytes (LPL) isolated from TNBS colitis-induced
mice and murine macrophage cell line (RAW264.7) stimulated with LPS. The contents of MSC-CM
were estimated using rat cytokines antibody array and MALDI-TOF/MS analysis.
Results: MSC-CM enhanced recovery from DSS colitis in rats and significantly alleviated TNBS
colitis in mice. Body weight restoration and disease activity index were significantly improved in the
group administrated MSC-CM. Strong driving force for the epithelial cell proliferation was revealed
by the Ki-67 labeling index. The effect to cell survival, migration and suppression of apoptosis in
IEC-6 were significantly superior in hypoCM to γCM and norCM treatment through the activation
of the PI3K-Akt pathway. IL-2, IFNγ and IL-17A secretions in LPL and TNFα and IL-6 secretions
in RAW cells were down-regulated with MSC-CM treatment while IL-10 secretion was up-regulated.
MSC-CM contains pleiotropic factors promoting anti-inflammatory, proliferative, and remodeling
phase in the wound healing machinery.
Conclusion: Optimization of pleiotropic gut tropic factors in MSC-CM is urgent as opening a new
avenue for drug discovery or basis for cell-based therapy for IBD.
133
P-73
Association between red cell distribution width and disease activity
in patients with inflammatory bowel disease
Chang Seok Song, M.D., Dong Il Park, M.D.
Background: Recent studies have suggested that a higher red blood cell distribution width (RDW)
is associated with disease activity in patients with inflammatory bowel disease (IBD). However, the
RDW in IBD patients without anemia has not been investigated. This study aimed to determine
whether or not RDW could be used for the assessment of disease activity in IBD patients with and
without anemia.
Methods: The serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR),
hemoglobin concentration, platelet (PLT) and white blood cell (WBC) counts, and RDW were
assessed in 221 IBD patients, comprised of 120 patients with ulcerative colitis (UC) and 101 patients
with Crohn’s disease (CD). Disease activity was determined for UC and CD with the Mayo score and
the Crohn’s disease activity index (CDAI), respectively.
Results: The CRP level, ESR, hemoglobin concentration, hematocrit, and RDW increased
according to disease activity in patients with and without anemia (all P < 0.05). Multivariate analysis
demonstrated that RDW was the best independent indicator for predicting disease activity in CD
patients without anemia [odd ratios (OR), 1.702; 95% confidence interval (CI), 1.185-2.445; P = 0.004]
and UC patients without anemia (OR, 4.921; 95% CI, 2.281-10.615; P < 0.001). Also, ROC curve
analysis showed the RDW to be the most significant indicator of non-anemic active IBD [area under
curve (AUC) in CD, 0.852, P < 0.001; AUC in UC, 0.827, P < 0.001].
Conclusion: The association between increased RDW and active IBD was evident in IBD patients
with and without anemia.
Keywords: inflammatory bowel disease; red cell distribution width; ulcerative colitis; Crohn’s
disease.
134
P-74
Novel Guggulsterone Derivative GG-52 Inhibits NF-κB Signaling in
Bone Marrow-Derived Dendritic Cells and Attenuates Colitis in
IL-10 Deficient Mice
Seung Joo Kang, Seong-Joon Koh, Joo Sung Kim
Seoul National University College of Medicine, Seoul, KOREA
Background/Aims: We previously demonstrated that a novel guggulsterone derivative, GG-52
inhibited NF-κB signals in intestinal epithelial cells and had preventive and therapeutic effect on
dextran sulfate sodium-induced colitis in mice. This study investigates the anti-inflammatory effects
of GG-52 on bone marrow-derived dendritic cells (BMDC) and colitis in IL-10 deficient mice.
Methods: BMDCs were generated from femur of C57BL/6 and IL-10 –/– mice with murine
recombinant GM-CSF and IL-4, which were confirmed by FACS staining of CD11c+ and CD11b+.
BMDCs were stimulated with lipopolysaccharide (LPS) with or without GG-52. The effect of GG52 on NF-κB signaling in BMDCs were examined by real-time RT-PCR for IL-12p40 and TNF-α,
Western blotting for IκBα phosphorylation/degradation, and electrophoretic mobility shift assay
(EMSA) for NF-κB DNA binding activity. For in vivo study, IL-10 –/– mice were fed piroxicam with
or without GG-52. Colitis was quantified by evaluation of histology, and double immunofluorescence
staining of CD11c and phospho-IKK-α was performed.
Results: GG-52 significantly inhibited LPS-induced IL-12p40 and TNF-α gene expression, IκBα
phosphorylation/degradation, and NF-κB DNA binding activity in BMDCs. In IL-10 –/– mice,
administration of GG-52 significantly reduced the severity of colitis as assessed by histology, and
suppressed IKK-α activation in dendritic cells in the intestinal lamina propria.
Conclusions: The novel guggulsterone derivative GG-52 may block NF-κB activation in BMDCs
and ameliorates colitis in IL-10 deficient mice, which suggesting that GG-52 is a potential therapeutic
agent for inflammatory bowel diseases.
135
P-75
Adipose Tissue-Derived Stem Cell Attenuate Colitis in Interleukin-10
Knockout Mice.
Byung Ik Jang1, In-Hwan Song2,, Kyeong Ok Kim1, Chang Hun Yang3
Division of Gastroenterology, Department of Internal Medicine1, Anatomy2 ,
Yeungnam University College of Medicine, Daegu, Division of Gastroenterology,
Department of Internal Medicine, Dongkuk Unversity College of Medicine, Kyeong Ju3, Korea
Background/Aims: Inflammatory bowel disease is characterized by chronic intestinal inflammation
with intermittent exacerbation or remission and unknown etiology. Interleukin-10 Knockout (IL-10
KO) Mice are known to develop a spontaneous intestinal inflammation that resemble Crohn's disease.
Mesenchymal stem cells have immunosuppressive properties and have beneficial influences in graft
versus host disease. We investigated if a human adipose-derived stem cells (h-ASCs) are capable to
attenuated colon inflammation in IL-10 KO mice.
Methods: h-ASCs were isolated from adipose tissues obtained from human donors. C57BL/6J
IL-10 KO mice and wild type strain(C57BL/6J) were bred under the specific pathogen free
condition. Colitis was induced in the mice by administration of piroxicam orally. Mice treated with
intraperitoneal h-ASCs injection(5x105 cells) or normal saline as control after induction of colitis.
All mice were euthanize 14 days after piroxicam administration. Histopathologic score and level of
inflammation related cytokines were evaluated in the affected organs or blood. Comparison were
made between h-ASCs treated or control non-treated IL-10 KO mice and wild type littermate.
Results: Clinical score was lower in h-ASCs treated IL-10 KO mice than in control. Histopathologic
assesment of large intestine showed lower inflammatory cells infiltration and less mucosal damage
in h-ASCs treated mice than in control littermates. The level of Monocyte chemoattractant protein-1
and Toll-like receptor 4 expression in the large intestine was lower and anti human IL-10 and anti
mouse IL-4 in the serum was higher in h-ASCs treated mice.
Conclusion: This findings suggested that administration of h-ASCs show beneficial effect on T-cell
induced spontaneous colitis model and emerge a therapeutic option in inflammatory bowel disease.
136
P-76
Intravital assessment of infliximab efficacy in murine ulcerative
colitis model using two photon laser scanning microscopy
Kohei Matsushita1, Koji Tanaka1, Yuhki Morimoto1, Masato Okigami1,
Mikio Kawamura1, Kiyosi Hashimoto1, Susumu Saigusa1, Yuji Toiyama1,
Yuuki Koike1, Yoshinaga Okugawa1, Yasuhiro Inoue1, Toshimitsu Araki1,
Keiichi Uchida1, Yasuhiko Mohri1, Akira Mizoguchi2, and Masato Kusunoki1
Departments of 1Gastrointestinal and Pediatric Surgery, and 2Neural Regeneration and Cell
Communication, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507
Background:
Anti-Tumor Necrosis Factor alpha antibody, infliximab (IFX), has been demonstrated to be beneficial
for the treatment of moderately to severely active ulcerative colitis (UC) patients. The molecular
mechanism of IFX efficacy on UC has not yet understood comprehensively.
In vivo real-time visualization of the colonic layers at the cellular level provides direct evidence of
what happens in crypts, lamina propria, muscular layers, and serosa just in time.
Aim:
We imaged the IFX efficacy in murine UC model using intravital multiphoton microscopy, and
examined its anti-inflammatory and mucosal healing effect in the same mouse by time-series
intravital imaging.
Methods:
Colitis was induced with dextran sulfate sodium (DSS) in green fluorescent protein (GFP) transgenic
mice. The DSS-induced colitis with or without IFX were imaged intravitally using two-photon
laser scanning microscopy (TPLSM). All layers of the cecum from serosa to luminal mucosa were
observed without opening the cecum (serasal-approaching method). The dynamic pathology was
obtained in the same mice on multiple time points by time-series intravital imaging.
Results:
Imaging on day 7 (2% DSS for 5 days), 14 (7 days after IFX administration), and 21 were obtained
in the same mice (approximately 70% in each group) using intravital TPLSM. The recovery from
body weight loss was faster in the IFX group. Time-series intravital TPLSM showed that leukocyte
infiltrations in sero-muscular layers and lamina propria on day 14 were fewer in the IFX group. The
crypt length on days 14 and 21 were longer in the IFX group than the control group.
Conclusion:
Time-series intravital TPLSM imaging of the colonic layers can provide us a dynamic pathology of
IFX efficacy such as anti-inflammatory action followed by crypt regeneration in murine UC model
of the same mice.
137
P-77
Glutamine induces intestinal epithelial heat shock response via
HSF-1 activation by polyamines
Toshio Sakiyama1, Yuji Iwashita1, Takuro Maeda1, Yuga Komaki1,
Hiroki Taguchi1, Masatsugu Numata1, Hiroshi Fujita1, Mark W. Musch2,
Eugene B. Chang2, Hirohito Tsubouchi1
1
Department of Digestive and Life-style related Diseases,
Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan and
2
Department of Medicine, University of Chicago, Chicago, Illinois.
Background and aims
Heat shock proteins (Hsps) are highly conserved proteins that play a role in cytoprotection and
maintaining intestinal homeostasis. The induction of Hsp70 and Hsp25 in intestinal epithelial
cells requires glutamine, a non-essential amino acid that is rapidly depleted from the body under
conditions of stress, e.g. inflammatory bowel disease. However, the mechanisms of glutaminedependent Hsp induction remain unclear. Glutamine is a substrate for polyamine synthesis and
stimulates the activity of ornithine decarboxylase (ODC), a key enzyme for polyamine synthesis,
in intestinal epithelial cells. Thus, we investigated whether polyamines (putrescine, spermidine
or spermine) and their precursor ornithine mediate the induction of Hsp expression in intestinal
epithelial cells.
Methods:
The normal rat small intestinal epithelial cells (IEC-18) were treated with glutamine, ornithine or
polyamines, alone or in combination with 5 mM α-difluoromethylornithine (DFMO), an irreversible
ODC inhibitor. Cells were heat stressed by incubating them at 42°C for 30 min. The expression of
Hsp70 and Hsp25 was assessed by Western blot analysis and real time RT-PCR. The heat shock
transcription factor 1 (HSF-1) localization and DNA binding were assessed by Western blot analysis
and electromobility shift assays respectively.
Results:
Under conditions of glutamine depletion, supplementation of ornithine or polyamines restored
the heat-induced expression of Hsp70 and Hsp25. DFMO significantly decreased the heat stress
induction of Hsp70 and Hsp25 even in the presence of glutamine. Ornithine, polyamines and DFMO
did not modify the nuclear localization of HSF-1. However, DFMO dramatically reduced glutaminedependent HSF-1 binding to an oligonucleotide with heat shock elements (HSE) which was increased
by glutamine. In addition, exogenous polyamines recovered the DNA binding activity.
Conclusions:
The intestinal epithelial heat shock response is dependent on glutamine which promotes polyamine
synthesis required for HSF-1 binding to the HSE. The studies provide insight into the essential role
of glutamine in cell stress.
138
P-78
Macrophages pre-exposed to heat-killed feces show
hyporesponsiveness to mRNA expression of inflammatory cytokines
induced by fatty acids exposure.
Chie Kurihara, Ryota Hokari, Toshihide Ueda, Shingo Sato,
Hideaki Hozumi, Hirokazu Sato, Kazuyuki Narimatsu, Yoshikiyo Okada,
Chikako Watanabe, Kengo Tomita, Shunsuke Komoto,
Astushi Kawaguchi, Shigeaki Nagao, Soichiro Miura
Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama Japan
Aims: Dietary fat is an important factor for triggering exacerbation of mucosal inflammation
in inflammatory bowel diseases. In addition, enterobacteria are implicated in intestinal immune
response. However, how fatty acid exposure affects function of intestinal macrophages (Mφs), and
whether endotoxin affects their response have not been reported. We investigated how exposure
to fatty acids affects cytokine expressions in Mφs from mesenteric lymph nodes (MLN-Mφs) and
compared with that of bone marrow (BM)-derived Mφs. Effect of pretreatment of Mφs by heatkilled feces (HKF) on the cytokine expressions were also investigated.
Methods: BM cells were isolated from C57BL/6 mice and CD11b+ cells were purified using a
magnetic cell sorting system. For induction of differentiation, BM derived CD11b+ cells were
cultured with recombinant M-CSF or GM-CSF; (M-Mφ, GM-Mφ). MLN-Mφs were also isolated
as CD11b+ cells from MLN. Mφs were treated with saturated (lauric acid, LA) or polyunsaturated
fatty acids (docosahexaenoic acid, DHA) and then cultured with or without prestimulation of HKF.
Expressions of inflammatory cytokines mRNA and their regulatory factors mRNA were determined
by quantitative RT-PCR.
Results: LA showed increased IL-6 mRNA expression in GM-Mφ and increased TNFα mRNA
expression in GM-Mφ and M-Mφ. DHA showed increased IL-10 mRNA expression in GM-Mφ, and
reduction in IL-6 mRNA expression in M-Mφ. In contrast to BM-derived Mφs, MLN-Mφ showed
hyporesponse on fatty acids, especially LA did not enhanced mRNA expression of inflammatory
cytokines. BM-derived Mφs pre-exposed to HKF also showed hyporesponsiveness to fatty acids
exposure, that is similar to MLN-Mφ. MLN-Mφ expressed significantly high amount of negative
regulator molecules of TLR signals compared to BM-derived Mφs.
Conclusion: MLN-Mφs were relatively hyporesponsiveness to fatty acid exposure compared with
BM-derived Mφs. Hyporesponsiveness was reproduced in BM-derived Mφs by fecal contents.
Luminal environment may cause hyporesponsiveness of intestinal Mφs to fatty acids through higher
expression of suppressor factor of TLR-mediated-signals.
139
P-79
Are PPIs Associated with Increased Intraepithelial Lymphocytes in
the Colon?
Yeon Hwa Yu, M.D., Dong Soo Han, M.D., Hyen Soo Kim. M.D.,
Eun Kyung Kim. M.D., Chang Soo Eun, M.D.,Ju Yeon Pyo, M.D. *
Department of Internal Medicine and Pathology*,
Hanyang University College of Medicine, Guri, Korea
Backgroud and Aims : Proton pump inhibitors (PPI) are some of the most widely prescribed
medications worldwide. They are thought to increase the incidence of microscopic colitis through
various ways, although the exact mechanism is not known. Both collagenous and lymphocytic
colitis are characterized by increased CD8+ T lymphocyte infiltration into the colonic epithelium.
In this study, we aimed to evaluate whether administration of PPI is related to the degree of colonic
intraepithelial lymphocyte infiltration and inflammation within lamina propria.
Methods : Forty patients taking PPI that underwent colonoscopic examination with biopsies between
January 2009 and December 2010 were enrolled retrospectively. The control group consisted of
randomly selected forty patients matched for gender and age during the same period. Intraepithelial
lymphocytes were assessed by H&E and immunohistochemical staining for CD3 and CD8,
performed on colonic tissue specimens of the PPI group and control group.
Results : The average age of the PPI group was 52.9 years (range 22-79 years) and 50% were male.
Intraepithelial lymphocytes in the PPI group averaged 14.5±5.2, significantly higher than the 6.2±3.5
of the control group (p<0.001). In addition, inflammation in the lamina propria was significantly
higher in the PPI group than in the control group. There were no correlations between the number of
intraepithelial lymphocytes and age, gender, or the type of PPI used.
Conclusions : Administration of PPI increases the number of intraepithelial lymphocytes and the
degree of inflammation in the lamina propria, and this may affect the development of microscopic
colitis.
Key words: Colitis, Microscopic · Proton pump inhibitors · Lymphocytes
140
P-80
Restraint Stress Induces and Exacerbates Intestinal Inflammation in
IL-10 Deficient Mice
Seong-Joon Koh1, Jong Pil Im1, Ji Won Kim2, Hyun Chae Jung1,
and Joo Sung Kim1
1
Seoul National University College of Medicine, Seoul, Korea
2
Department of Internal Medicine, Seoul National University Boramae Hospital,
Seoul National University College of Medicine, Seoul, Korea.
Background/Aims: Previous reports suggested that stressful condition might account for the
development and relapse of inflammatory bowel disease (IBD). However, few studies demonstrated
the impact of stress factors on chronic intestinal inflammation. Therefore, we investigated the effects
of restraint stress on intestinal inflammation in wild-type and IL-10 deficient (IL-10-/-) mice.
Methods: Seven-week-old SPF wild-type and IL-10 -/- mice on a C57BL/6 background were used
for this study. The first experiment was performed to evaluate the effect of restraint stress on the
induction of intestinal inflammation in wild-type and IL-10-/- mice. Both wild-type and IL-10-/- mice
were physically restrained in a well-ventilated, 50cc conical polypropylene tube for 2 h per day for 3
consecutive days. Mice were then euthanized 5 days after the final exposure to restraint stress. The
second experiment was performed to assess the effect of restraint stress on exacerbation of colitis
induced by piroxicam in IL-10-/- mice. IL-10-/- mice were exposed to restraint stress for 2h per day for
3 consecutive days. IL-10-/- mice were then treated with piroxicam for 5 days at a dose of 200 ppm
in the diet. The severity of colitis was assessed by body weight and histopathologic grade. IL-12p40
gene expression was determined by real-time RT-PCR.
Results: In the first experiment, none of the wild-type mice with or without restraint stress showed
clinical and histopathological abnormality in the gut. However, IL-10 -/- mice exposed to restraint
stress exhibited histologically significant intestinal inflammation as compared to those without
restraint stress. In the second experiment, restraint stress significantly reduced body weight and
increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10-/- mice.
Colonic IL12p40 mRNA expression was strongly increased in mice with restraint stress.
Conclusion: Restraint stress induced and exacerbated intestinal inflammation in IL-10 deficient
mice, which suggest that stress management could be a potential strategy for the treatment of IBD
141
P-81
Glutinous rice extract suppresses LPS-induced proinflammatory
mediator expression via blockage of NF-κB activation in intestinal
epithelial cells
Young-Eun Joo, Young-Lan Park, Seon-Young Park, Sung-Bum Cho,
Chang-Hwan Park, Hyun-Soo Kim, Sung-Kyu Choi, Jong-Sun Rew
Department of Internal Medicine, Chonnam National University Medical School,
8 Hak-Dong, Dong-ku, Gwangju 501-757, Korea
Background/Aims: Glutinous rice possesses some health beneficial properties including antiproliferative and anti-carcinogenic effects. The aim of current study was to determine the impact
of glutinous rice extract (GRE) on expression of proinflammatory mediators and activation of
lipopolysaccharide (LPS)-induced innate signaling in rat intestinal epithelial cells (RIE).
Methods: The effect of GRE on LPS-induced nuclear factor-kappa B (NF-κB) signaling
and expression of proinflammatory mediators was examined by RT-PCR, Western blotting,
immunofluorescence and electrophoretic mobility shift assay (EMSA). To examine the role of the
NF-κB signaling pathway in expression of proinflammatory mediators, we examined the effect of
Bay11-7082 (a NF-κB inhibitor) on LPS-induced proinflammatory mediator expression.
Results: LPS-induced IL12p40, IL23p19 and IL-1ß mRNA accumulations were inhibited by
GRE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65
were blocked by GRE. Also, GRE blocked NF-κB DNA-binding activity in EMSA. Bay 11-7082
suppressed the LPS-induced IL12p40, IL23p19 and IL-1ß mRNA accumulations.
Conclusions: These results indicate that GRE suppresses LPS-induced IL12p40, IL23p19 and IL-1ß
expressions through blockage of NF-κB activation in intestinal epithelial cells.
Key words: Glutinous rice; LPS; NF-κB; Intestinal epithelium
142
P-82
The role of SERPINB1 (monocyte neutrophil elastase inhibitor) in
the pathogenesis of ulcerative colitis
Kazuhiro Kamada, Yuji Naito, Kazuhiko Uchiyama, Tomohisa Takagi,
Katsura Mizusima, Yasuko Hirai, Kazuhiro Katada, Osamu Handa,
Nobuaki Yagi, Toshikazu Yoshikawa
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine
Background and Aims: SERPINB1, also known as monocyte neutrophil elastase inhibitor, is one
of the most efficient inhibitors of neutrophil elastase, cathepsin G, and proteinase-3. Recently, it
has been reported that SERPINB1 could provide protection in the airways by regulation protease
activity associated with inflammatory lung injury. Therefore, we postulated that SERPINB1 is
related to the pathogenesis of ulcerative colitis. In this study, we studied the role of SERPINB1
using clinical materials and the experimental animal model. Materials and Methods: DSSinduced colitis was used for a model of ulcerative colitis in mice. Protein expression in the DSSinduced inflamed colonic mucosa was examined by 2D-DIGE analysis, and several candidate
proteins were identified by MALDI-TOF MS analysis. Among them, we focused on SERPINB1. The
colonic expression of SERPINB1 mRNA and protein was measured by real time-PCR and western
blotting in normal and inflamed colonic mucosa from patients with ulcerative colitis. Localization
of SERPINB1 was identified by immunohistochemistry. Results: 2D DIGE followed by MALDITOF MS analysis of inflamed mucosa matched 1,438 spots compared to normal mucosa.SERPINB1
protein expression was increased compared to normal mice. Western blot analysis confirmed the upregulated expression of SERPINB1 in colonic mucosa obtained from mice experimental colitis as
well as patients with ulcerative colitis. Immunohistochemical examination showed that SERPINB1
expression was localized not only neutrophils and monocyte but in the epithelial cells. Conclusion:
SERPINB1 expression was increased in the colonic mucosa in human with ulcerative colitis and
murine ulcerative colitis model, indicating that SERPINB1 may be related to the pathogenesis of
ulcerative colitis.
143
P-83
Aberrant DNA methylation of FBN2 and TCERG1L genes in
Ulcerative Colitis Patients
TAE-OH KIM, JOO MI YI, HEUI SOO KIM
Department of Internal Medicine, Haeundae Paik Hospital, Inje University Colledgel of Medicine
Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS)
Division of Biological Sciences, College of Natural Sciences, Pusan National University
Backgrounds: Epigenetic regulation of genes has been known to be associated with gene silencing
in many types of cancer. Especially, promoter CpG island hypermethylation of tumor-suppressor
genes is a common hallmark of all human cancer. However, many researchers suggest that chronic
imflammation is also tightly associated with high levels of DNA methyaltion. Recently, genome-wide
profiling approach has been identified new molecular targets to detect not only early level of cancer
but also chronic imflammation diseases such as inflammatory bowel disease.
Methods: Two genes (FBN2 and TCERG1L) has been screened by DNA methylation analysis
(Methylation Specific PCR;MSP) using samples from 23 UC patients.
Results: Methylation of some of genes is a frequent and early event in IBD and IBD-associated
neoplasia. Recently, promoter DNA hypermethylation FBN2 and TCERG1L has been reported that
these are frequently methylated in adenoma which is early stage of colon cancer. In this our pilot
study, we found that FBN2 and TCERG1L genes are frequently methylated in 23 UC samples (40%
for FBN2, 100% for TCERG1L)..
Conclusion: Methylation of the FBN2 and TCERG1L genes is seen in patients with inflammation
disease such as UC. Our data suggest that DNA methylation could be a important biomarker to detect
IBD related diseases. Especially, DNA methylation frequency of TCERG1L gene in UC samples
suggest that it could be very sensitive biomarker candidate to detect from IBD to IBD associatedneoplasia. Moreover, these genes may serve as biomarkers for IBD-associated neoplasia.
144
P-84
Promoter polymorphism of the EED gene is associated with the
susceptibility to ulcerative colitis
Geom-Seog Seo,* Suck-Chei Choi,* Ki-Jung Yun,† Soo-Cheon Chae† *†Digestive Disease Research Institute, Department of Internal Medicine,* Pathology,† School of
Medicine, Wonkwang University, Iksan, Chonbuk 570-749, South Korea Backgrounds: Embryonic ectoderm development (EED) protein is involved in multiple cellular
protein complexes. EED mediates the repression of gene activity through histone deacetylation, and
it may act as a specific regulator of integrin’s function. This gene was identified as a candidate gene
for the susceptibility to IBD by our previous cDNA microarray analysis.
Aim: The present study aimed to validate the expression level of the EED gene in patients with
IBD by performing RT-PCR, and we investigated whether the polymorphisms in the EED gene are
associated with the susceptibility to UC, and whether a functional EED promoter polymorphism is
related to UC.
Methods: Genotype analysis of the EED SNPs was performed by single-base extension (SBE)
analysis. The haplotype frequencies of the EED gene for multiple loci were estimated using the
expectation maximization (EM) algorithm. The promoter region of the human EED gene, including
the g.-1850G>C allele, was isolated by PCR. The amplified PCR products were inserted into the
pGL3-basic vector and the luciferase activity was analyzed.
Results: The expression level of the EED gene was significantly decreased in both the UC and CD
patients and it was significantly higher in the liver and ileum than in the other tissues of the human
digestive system. The genotype and allele frequencies of the g.-1850G>C polymorphism of the EED
gene in the UC patients were significantly different from those of the healthy controls (P = 0.018 and
0.017, respectively). The luciferase activity assay showed that the promoter activity was decreased
about 2-fold in the construct containing the g.-1850G allele compared with that of the construct
containing the g.-1850C allele, which means that the allele G could produce less EED mRNA.
Conclusion: These results suggest that the g.-1850G>C polymorphism in the EED gene might be
associated with the susceptibility to UC by the change of the EED expression level.
Keywords: EED . WAIT-1 . promoter assay . Haplotype . IBD
145
P-85
Terminal restriction fragment length polymorphism analysis of the
diversity of fecal microbiota in patients with inflammatory bowel
disease and irritable bowel syndrome
Bong Ki Cha,1 Chang Hwan Choi,1 Se Kyung Chang,1 Kijeong Kim,2
Byung Chang Kim,3 Sung-Ae Jung4
Department of Internal Medicine1 and Microbiology,2 Chung-Ang University College of
Medicine,1,2 Department of Internal Medicine, National Cancer Center,3 Department of Internal
Medicine, Ewha Womans University School of Medicine,4 Seoul, Republic of Korea
Background & Aims: The aims of this study were to perform terminal restriction fragment length polymorphism (T-RFLP) analyses of fecal
microbiota in IBD and IBS patients and to investigate the potential alterations in fecal bacterial communities.
Methods: A total of 164 patients with ulcerative colitis (UC, n=56), Crohn’s disease (CD, n=33) and IBS (n=26) and healthy subjects (HS, n=49)
were enrolled. DNA was extracted from their stool samples, and the 16S rRNA genes were amplified by real time polymerase chain reaction (RTPCR). The PCR products were then digested with MspI and HinPlI restriction enzymes, and the length of the terminal restriction fragments (T-RFs)
was determined. The sizes of T-RFs were rounded to the nearest number between samples to produce operational taxonomic units (OTUs). We used
PRIMER v6 program for statistical analysis. A one-way analysis of similarity (ANOSIM) was used to compare the microbial communities between
each of the groups. Hierarchical clustering and non-metric multi-dimensional scaling (nMDS) were performed to visualize the degree of dissimilarity
among each of samples as dendrogram and multi-dimensional graphs. Analysis of similarity percentages (SIMPER) was done to determine the overall
average dissimilarity and the OTUs significantly contributing the dissimilarity in microbial community compositions among the groups. The bacterial
species of the significantly different OTUs were predicted from the database that we developed (http://microbiology.cau.ac.kr) based on the silico PCR
amplification and restriction of 16S rRNA sequences.
Results: The composition of the fecal bacterial communities in patients with UC, CD and IBS significantly differed from that of HS (P<0.05), and
were distinct from each other (P<0.001). Dendrogram and nMDS showed that the distribution of the fecal microbiota was clearly different among each
groups. Dissimilarities between the patient groups and the HS were as following: UC, 67.6%; CD, 78.6%; IBS, 78.6%. Several OTUs that significantly
contributed to the dissimilarities were found (Table). Bacteriodetes (Bacteroides, Prevotella, Porphyromonas) and Epsilon proteobacterium (Helicobacter,
Campylobacter) were significantly abundant in UC and IBS while Lactobacillus was significantly lack in CD compared to HS. Selenomonas and
Megasphaera elsdenii were significantly lack in all patient groups compared to HS.
Conclusions: The composition of fecal microbiota in patients with CD, UC and IBS significantly differs from that of HS, and also were distinct from
each other patient group. The lacking bacterial species in patients may be some therapeutic targets.
Table. Operational taxonomic units contributing significant differences in fecal bacterial communities between the patient groups and healthy subjects
UC
Abundant OTUs in Patient Groups
OTU Dis/HS Predicted bacteria
549
4.3
Uncultured bacterium
299
99
2.4
1.7
Prevotella, Bacteroides,
uncultured bacterium
539
97
1.7
1.7
547
1.5
Mycoplasma, uncultured bacterium
Bacteroidetes (Bacteroides,
Prevotella, Porphyromonas),
Epsilon proteobacterium
(Helicobacter, Campylobacter)
CD
IBS
99
97
2.5
2.1
216
90
2.1
1.6
Prevotella, Bacteroides, uncultured bacterium
Bacteroidetes (Bacteroides,
Prevotella, Porphyromonas),
Epsilon proteobacterium
(Helicobacter, Campylobacter)
Enterococcus, uncultured bacterium
Bacteroidetes, Aeromonas,
uncultured delta proteobacterium,
uncultured gamma proteobacterium
OTU
300
HS/Dis
3.0
301
3.3
29
522
31
191
222
300
3.2
3.1
2.4
1.8
1.8
1.6
Abundant OTUs in Healthy Subjects
Predicted bacteria
Selenomonas,Megasphaera
elsdenii, uncultured bacterium
Selenomonas, Megasphaera
elsdenii, uncultured bacterium
Lactobacillus
Selenomonas, Megasphaera elsdenii,
uncultured bacterium
OTU, operational taxonomic unit; HS, healthy subjects; Dis, disease; UC, ulcerative colitis; CD, Crohn’s disease; IBS, irritable bowel syndrome
146
P-86
The Study of Gene Expression Induced by Sleep Deprivation and
Melatonin Treatment on DSS Induced Colitis Mice.
Sang Soo Kim1, Sook Hee Jung2, Jae-Ho Shin3, Jin-Hyun Jun3,
Haeng Woon Baek4, Young-Sook Park1,5
1
Eulji Bio-medical Research Institute, Eulji University, Seongnam, Korea.
Dept. of Gastroenterology, Severance Hospital, Yonsei University, Seoul, Korea.
3
Dept. of Biomedical Laboratory Sciences College of Health Science,
Eulji University, Seongnam, Korea
4
Dept. of Biomedical Laboratory Sciences, School of Medicine, Eulji University, Daejon , Korea
5
Dept. of Internal Medicine, Eulji general hospital, Seoul, Korea
2
Introduction: There are complex and various causes in the pathogenesis of inflammatory bowel
disease. Environmental factor including stress, smoking and infection also may be important risk
factor. Stressful situations could aggravate or reactivate inflammatory bowel disease. We tried to
investigate the effect of the stress caused by sleep deprivation (SD) on 2% dextran sulfate sodium
(DSS) induced colitis model. And also, we designed to evaluate protective effect of melatonin on
such condition.
Materials and methods: We used the 5 groups of C57BL/6 mice. Group I: control, group II: 2% DSS
induced colitis, group III: 2% DSS induced colitis with sleep deprivation and group IV: 2% DSS
induced colitis and melatonin treatment. group V: 2% DSS induced colitis with SD and melatonin
treatment. We kept the experimental mice on our customized SD platform and monitored the status
of mice. We checked body weight daily. From H/E staining of the mice colon tissue, we compared
degree of inflammation among groups. RNA was isolated from the colon of mice in each group and
analyzed by microarray and ontology.
Results: Because of the stress from the platform, the body weight of the mice dramatically
decreased after sleep deprivation. H/E staining results of colon tissue appeared that SD aggravated
the inflammation and melatonin reduced it. 68 genes was significantly changed by 2% DSS, sleep
deprivation and melatonin in microarray. In real time PCR sleep deprivation increased E2f2, H2Ab1, and decreased that of Tnfsf10, adipoq. Melatonin increased mRNA of Aqp8, decreased that of
Cdk1, Mmp7.
Conclusion: Sleep deprivation acts as an aggravating factor, whereas melatonin acts as an improving
factor of inflammation. Sleep deprivation and melatonin affected genes which involved in
metabolism, gene expression, cell growth and apoptosis in process of inflammatory bowel disease.
147
Supporting members
ABBOT JAPAN CO., LTD.
AJINOMOTO PHARMACEUTICALS CO., LTD.
Asahi Kasei Kuraray Medical Co., Ltd.
Eisai Co., Ltd.
JIMRO Co., Ltd.
KYORIN Pharmaceutical Co., Ltd.
Kyowa Hakko Kirin Co., Ltd.
Mitsubishi Tanabe Pharma Corporation
MOCHIDA PHAMACEUTICAL CO., LTD.
Otsuka Pharmaceutical Co., Ltd.
UCB Japan Co., Ltd.
YAKULT HONSHA CO., LTD.
ZERIA Pharmaceutical Co., Ltd.
Sponsors
Astellas Pharma Inc.
AstraZeneca K.K.
Dainippon Sumitomo Pharma Co., Ltd.
GlaxoSmithKline K.K.
Janssen Pharmaceutical K.K.
Ono Pharmaceutical Co., Ltd.
Pfizer Japan Inc.
Toray Industries, Inc.
Yakult Honsha Co., Ltd.
(in an alphabetical order)

program (Abstract Book) - The 6th Korea

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