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A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn’s disease

  • Original Article—Alimentary Tract
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Abstract

Background

Small bowel stricture is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.

Methods

Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.

Results

A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.

Conclusions

In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.

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Acknowledgements

This study has not received any direct financial support. Although recruitment of investigators to this study was conducted in part at a conference called the AIM Jr meeting, funded by Eisai Co., Ltd. and EA Pharma Co., Ltd., the study design, including development of the protocol, statistical analysis and drafting of the manuscript were performed only by the investigators. Therefore, this study does not have any relationship with Eisai Co., Ltd. and EA Pharma Co., Ltd.

Author information

Author notes

  1. Shigeki Bamba, Ryosuke Sakemi and Toshimitsu Fujii contributed equally to this study.

Authors and Affiliations

  1. Division of Clinical Nutrition, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan

    Shigeki Bamba

  2. Department of Gastroenterology, Tobata Kyoritsu Hospital, Kitakyusyu, Japan

    Ryosuke Sakemi

  3. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan

    Toshimitsu Fujii & Kento Takenaka

  4. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan

    Teruyuki Takeda

  5. Department of Medicine and Clinical Science, Kyushu University Graduate Schools of Medical Science, Fukuoka, Japan

    Shin Fujioka

  6. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Hiroki Kitamoto

  7. Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital, Kamakura, Japan

    Shotaro Umezawa

  8. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Hirotake Sakuraba

  9. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Okayama, Japan

    Toshihiro Inokuchi

  10. Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan

    Norimasa Fukata

  11. Division of Gastroenterology and Hepatology, Keio University School of Medicine, Tokyo, Japan

    Shinta Mizuno

  12. Division of Gastroenterology and Hepatology, Saint Marianna University School of Medicine, Kawasaki, Japan

    Masaki Yamashita

  13. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan

    Shinichiro Shinzaki

  14. IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan

    Hiroki Tanaka

  15. Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan

    Hidetoshi Takedatsu

  16. Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan

    Ryo Ozaki, Taku Kobayashi & Toshifumi Hibi

  17. Department of Gastroenterology and Hepatology, Nara Medical University School of Medicine, Kashihara, Japan

    Kei Moriya

  18. Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan

    Manabu Ishii

  19. Department of Endoscopy, University of Ryukyus Hospital, Nishihara, Japan

    Tetsu Kinjo

  20. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Keiji Ozeki

  21. Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Makoto Ooi

  22. Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan

    Ryohei Hayashi

  23. 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan

    Kazuki Kakimoto

  24. Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Japan

    Yuichi Shimodate

  25. Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan

    Kazuya Kitamura

  26. Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan

    Akihiro Yamada

  27. Department of Gastroenterology, Oita University, Yufu, Japan

    Akira Sonoda

  28. Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yu Nishida

  29. Department of Gastroenterology, Kure Kyosai Hospital, Kure, Japan

    Kyouko Yoshioka

  30. Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Shinya Ashizuka

  31. Department of Internal Medicine, Japanese Red Cross Ashikaga Hospital, Ashikaga, Japan

    Fumiaki Takahashi

  32. Department of Medical Data Science, Graduate School of Medicine, Wakayama Medical University, Wakayama, Japan

    Toshio Shimokawa

  33. Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan

    Akira Andoh

Authors
  1. Shigeki Bamba
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  2. Ryosuke Sakemi
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  3. Toshimitsu Fujii
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  4. Teruyuki Takeda
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  5. Shin Fujioka
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  6. Kento Takenaka
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  7. Hiroki Kitamoto
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  8. Shotaro Umezawa
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  9. Hirotake Sakuraba
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  10. Toshihiro Inokuchi
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  11. Norimasa Fukata
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  12. Shinta Mizuno
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  36. Toshifumi Hibi
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Contributions

Conceptualization: SB and RS. Methodology: SB, RS, TF, SS, and TK. Formal analysis: SB and RS. Investigations: all authors. Writing—original draft: SB. Writing—review and editing: SB and RS. Supervision: TF, SS, KM, TS, TK, AA, and TH. Approval of final manuscript: all authors.

Corresponding author

Correspondence to Shigeki Bamba.

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Conflict of interest

SB received lecture fees from AbbVie GK, Mitsubishi Tanabe Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Janssen, Mochida Pharmaceutical, Nippon Kayaku, Zeria Pharmaceutical Co., Ltd., and EA Pharma Co., Ltd., and research support from AbbVie GK, and MSD Inc. RS received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd., Janssen, AbbVie GK, EA Pharma Co., Ltd., and Nippon Kayaku. TF received research support from Eisai Co., Ltd., and Alfresa Co., Ltd., and lecture fees from AbbVie, Ajinomoto Pharma, Boehringer Ingelheim, Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Janssen, Kissei Pharmaceutical, Kyorin Pharmaceutical Co., Ltd., Kyowa Hakko Kirin, Mitsubishi Tanabe Pharma Co., Ltd., Mochida Pharmaceutical, Nippon Kayaku, and Zeria Pharmaceutical Co., Ltd. HS received research support from Bristol-Myers Squibb, AbbVie GK, MSD Inc., Daiichi Sankyo Co., Ltd., and Zeria Pharmaceutical Co., Ltd. SS received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd., AbbVie GK, EA Pharma Co., Ltd., and Nippon Kayaku. HTan received lecture fees from JIMRO Co., Ltd., AbbVie GK, EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Mitsubishi Tanabe Pharma Co., Ltd. RO received lecture fees from AbbVie GK. KKa received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd. and AbbVie GK. YS received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd. and EA Pharma Co., Ltd. KKi received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd., AbbVie GK, EA Pharma Co., Ltd., Janssen, Nippon Kayaku, and Olympus, and research support from AbbVie GK and Zeria Pharmaceutical. SA received lecture fees from Janssen, Mitsubishi Tanabe Pharma Co., Ltd., and JIMRO Co., Ltd. TKo received lecture fees from AbbVie GK, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, EA Pharma Co., Ltd., Eisai Co., Ltd., Gilead Sciences, Janssen, JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku, Mochida Pharmaceutical, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Co., Ltd., and ZERIA Pharmaceutical Co., Ltd., and consulting fees from Alfresa Pharma, Covidien, Eli Lilly, Ferring Pharmaceuticals, Janssen, Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, and Thermo Scientific, and research support from EA Pharma Co., Ltd., Thermo Fisher Scientific, Alfresa Pharma, Nippon Kayaku, and Asahi Kasei Medical. AA received lecture fees from AbbVie GK, Mitsubishi Tanabe Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Janssen, Astellas, Zeria Pharmaceutical, Miyarisan Pharmaceutical, Takeda Pharmaceutical, Bristol-Myers Squibb, Gilead Sciences, MSD Inc., and EA Pharma Co., Ltd., and research support from EA Pharma Co., Ltd., AbbVie GK, MSD Inc., and Mochida Pharmaceutical, and consulting fees from Mochida Pharmaceutical Co., Ltd., and Takeda Pharmaceutical. TH received lecture fees from Mitsubishi Tanabe Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., AbbVie GK, Janssen, JIMRO Co., Ltd., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical, Gilead Sciences, Celltrion, Nippon Kayaku, Kissei Pharmaceutical, Miyarisan Pharmaceutical, Zeria Pharmaceutical Co., Ltd., and Ferring Pharmaceutical, and advisory/consultancy fees from AbbVie GK, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Co., Ltd., JIMRO Co., Ltd., EA Pharma Co., Ltd., Eli Lilly, Pfizer Japan Inc, Nichi-Iko Pharmaceutical, and Nippon Kayaku, and research support from EA Pharma, AbbVie GK, JIMRO Co., Ltd., Zeria Pharmaceutical Co. Ltd., and Otsuka Pharmaceutical Co., Ltd. However, none of the above is relevant to this article.

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Supplementary file1 (DOCX 15 kb)

535_2020_1670_MOESM2_ESM.tif

Supplementary file2 Supplementary Figure 1. Cumulative surgery-free survival for all patients. Kaplan-Meier curves depicting cumulative surgery-free survival for all patients stratified by sex (a), disease location (b), disease behavior (c), perianal lesion (d), smoking (e), location of stricture (f), number of strictures (g). P values on each curve were calculated using the log-rank test. L1: ileal; L3: ileocolonic; B1: non-stricturing, non-penetrating; B2: stricturing (TIF 1090 kb)

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Bamba, S., Sakemi, R., Fujii, T. et al. A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn’s disease. J Gastroenterol 55, 615–626 (2020). https://doi.org/10.1007/s00535-020-01670-2

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  • DOI: https://doi.org/10.1007/s00535-020-01670-2

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