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3 "Hiroki Ikeuchi"
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Original Article
Colitis-associated colorectal neoplasia in ulcerative colitis with primary sclerosing cholangitis: a nationwide study
Koichi Komatsu, Takahide Shinagawa, Motoi Uchino, Hiroki Ikeuchi, Koji Okabayashi, Shiro Oka, Kitaro Futami, Michio Itabashi, Kazuhiro Watanabe, Masatsune Shibutani, Yoshiki Okita, Toshifumi Wakai, Yusuke Mizuuchi, Kinya Okamoto, Kazutaka Yamada, Yu Sato, Takayuki Ogino, Hideaki Kimura, Kenichi Takahashi, Koya Hida, Yusuke Kinugasa, Fumio Ishida, Junji Okuda, Koji Daito, Takayuki Yamamoto, Seiichiro Yamamoto, Fumikazu Koyama, Tsunekazu Hanai, Koji Komori, Dai Shida, Junya Arakaki, Yoshito Akagi, Shigeki Yamaguchi, Hideki Ueno, Keiji Matsuda, Atsuo Maemoto, Riichiro Nezu, Shin Sasaki, Eiji Sunami, Tatsuki Noguchi, Kenichi Sugihara, Yoichi Ajioka, Soichiro Ishihara, the Study Group for Inflammatory Bowel Disease Associated Intestinal Cancers by the Japanese Society for Cancer of the Colon and Rectum
Received July 14, 2025  Accepted September 21, 2025  Published online February 12, 2026  
DOI: https://doi.org/10.5217/ir.2025.00133    [Epub ahead of print]
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Background/Aims
Ulcerative colitis (UC)-associated colorectal neoplasia (UCAN) in patients with UC and primary sclerosing cholangitis (PSC) has not been studied well in Japan. This retrospective study examined the clinicopathological features and prognosis of UCAN in patients with PSC-UC.
Methods
A total of 808 patients with UCAN were enrolled from 1983 to 2020 and categorized into PSC (PSC-UCAN, n = 26) and no PSC (UCAN-alone, n = 782) groups. Clinicopathological features were compared between the 2 groups, and the 10-year overall survival (OS) and cancer-specific survival (CSS) were analyzed.
Results
The PSC-UCAN group had a shorter UC duration before UCAN diagnosis (12.8 years vs. 16.9 years, P= 0.044), were younger at UCAN diagnosis (47.8 years vs. 53.3 years, P= 0.046), and developed UCAN more frequently in the right-sided colon (34.6% vs. 15.9%, P= 0.028) than the UCAN-alone group. The PSC-UCAN group showed a trend toward a lower proportion of high-grade dysplasia (19.2% vs. 30.7%) and a higher proportion of early-stage cancers (53.9% vs. 31.2%). The 10-year OS (64.6% vs. 79.3%, P=0.080) and CSS (80.8% vs. 83.9%, P=0.60) were comparable.
Conclusions
Patients with PSC-UCAN showed earlier and younger development of UCAN than patients with only UCAN, with a high prevalence in the right-sided colon. Early-stage cancer was more frequently observed in the PSC-UCAN group, despite the shorter duration of UC. Patients with PSC-UC probably benefit from early initiation of surveillance colonoscopy.
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Statement
IBD
Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries
Taku Kobayashi, Tadakazu Hisamatsu, Yasuo Suzuki, Haruhiko Ogata, Akira Andoh, Toshimitsu Araki, Ryota Hokari, Hideki Iijima, Hiroki Ikeuchi, Yoh Ishiguro, Shingo Kato, Reiko Kunisaki, Takayuki Matsumoto, Satoshi Motoya, Masakazu Nagahori, Shiro Nakamura, Hiroshi Nakase, Tomoyuki Tsujikawa, Makoto Sasaki, Kaoru Yokoyama, Naoki Yoshimura, Kenji Watanabe, Miiko Katafuchi, Mamoru Watanabe, Toshifumi Hibi
Intest Res 2018;16(2):168-177.   Published online April 30, 2018
DOI: https://doi.org/10.5217/ir.2018.16.2.168
AbstractAbstract PDFPubReaderePub

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Citations

Citations to this article as recorded by  
  • Ear, Nose, and Throat Manifestations in Inflammatory Bowel Diseases: A Systematic Review of the Clinical Spectrum
    Eleni Litsou, Georgios Psychogios, Maria Saridi, Konstantinos H. Katsanos, Fotios Fousekis
    Medicina.2026; 62(5): 943.     CrossRef
  • Precision medicine in inflammatory bowel diseases
    Ashwin N. Ananthakrishnan
    Intestinal Research.2024; 22(1): 8.     CrossRef
  • Impact of Concomitant Prescriptions and Lifestyle Factors on the Initial Course of Newly Diagnosed Inflammatory Bowel Disease
    Hiromu Morikubo, Takayoshi Nagahama, Katsuhiko Nagai, Hajime Yamazaki, Taku Kobayashi
    Inflammatory Intestinal Diseases.2024; 9(1): 260.     CrossRef
  • A Retrospective Cohort Study of Clinical Features and Treatment Patterns With Ustekinumab in Patients With Crohn Disease Utilizing a Health Care Database in Japan
    Yanfang Liu, Choo Hua Goh, Hong Qiu, Kuan-Chih Huang, Hsingwen Chung, Carine Saadoun
    Annals of Pharmacotherapy.2023; 57(9): 1053.     CrossRef
  • Residual Short-Segment Distal Inflammation Has No Significant Impact on the Major Relapse of Extensive Ulcerative Colitis
    Kunio Asonuma, Taku Kobayashi, Masaru Nakano, Shintaro Sagami, Hiroki Kiyohara, Mao Matsubayashi, Hiromu Morikubo, Yusuke Miyatani, Shinji Okabayashi, Hajime Yamazaki, Yuichiro Kuroki, Toshifumi Hibi
    Inflammatory Bowel Diseases.2022; 28(2): 200.     CrossRef
  • Intestinal cancer in patients with Crohn's disease: A systematic review and meta‐analysis
    Motoi Uchino, Hiroki Ikeuchi, Keisuke Hata, Tomohiro Minagawa, Yuki Horio, Ryuichi Kuwahara, Shiro Nakamura, Kenji Watanabe, Masayuki Saruta, Toshimitsu Fujii, Taku Kobayashi, Ken Sugimoto, Fumihito Hirai, Motohiro Esaki, Sakiko Hiraoka, Katsuyoshi Matsuo
    Journal of Gastroenterology and Hepatology.2021; 36(2): 329.     CrossRef
  • MR-enterography in Crohn’s disease: what MRE mural parameters are associated to one-year therapeutic management outcome?
    Pier Paolo Mainenti, Fabiana Castiglione, Antonio Rispo, Ettore Laccetti, Salvatore Guarino, Valeria Romeo, Anna Testa, Leonardo Pace, Simone Maurea
    The British Journal of Radiology.2021;[Epub]     CrossRef
  • Incidence and Outcomes of Perianal Disease in an Asian Population with Crohn’s Disease: A Nationwide Population-Based Study
    Eun Mi Song, Ho-Su Lee, Ye-Jee Kim, Eun Hye Oh, Nam Seok Ham, Jeongseok Kim, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Jong Lyul Lee, Yong Sik Yoon, Chang Sik Yu, Suk-Kyun Yang
    Digestive Diseases and Sciences.2020; 65(4): 1189.     CrossRef
  • Passion fruit (Passiflora edulis) leaf aqueous extract ameliorates intestinal epithelial barrier dysfunction and reverts inflammatory parameters in Caco-2 cells monolayer
    Mônica Cristina Lopes do Carmo, Isabela Mateus Martins, Ana Elisa Ramos Magalhães, Mário Roberto Maróstica Júnior, Juliana Alves Macedo
    Food Research International.2020; 133: 109162.     CrossRef
  • Efficacy and safety of abrilumab, an α4β7 integrin inhibitor, in Japanese patients with moderate-to-severe ulcerative colitis: a phase II study
    Toshifumi Hibi, Satoshi Motoya, Toshifumi Ashida, Souken Sai, Yukinori Sameshima, Shiro Nakamura, Atsuo Maemoto, Masahiro Nii, Barbara A Sullivan, Robert A. Gasser Jr, Yasuo Suzuki
    Intestinal Research.2019; 17(3): 375.     CrossRef
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Original Article
NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
Intest Res 2017;15(3):328-337.   Published online June 12, 2017
DOI: https://doi.org/10.5217/ir.2017.15.3.328
AbstractAbstract PDFPubReaderePub
<b>Background/Aims</b><br/>

Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).

Methods

One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.

Results

None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.

Conclusions

Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.

Citations

Citations to this article as recorded by  
  • Genetic Determinants of Hematopoietic Toxicity Risk in Thai Pediatric Patients Undergoing 6‐Mercaptopurine Treatment
    Kanyarat Khaeso, Su‐on Chainansamit, Pitchayanan Kuwatjanakul, Patcharee Komvilaisak, Nontaya Nakkam, Kunanya Suwannaying, Suda Vannaprasaht, Areerat Dornsena, Wichittra Tassaneeyakul
    Clinical and Translational Science.2026;[Epub]     CrossRef
  • Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications
    Amirhossein Ghorbanpour, Pejman Rohani, Shabnam Shahrokh, Georges Dimitrov, Mehdi Totonchi, Stefan Dimitrov
    Molecular Medicine.2026;[Epub]     CrossRef
  • Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15
    Yitian Zhou, Lukas M. Lauschke, Volker M. Lauschke
    Human Genomics.2026;[Epub]     CrossRef
  • A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single‐center retrospective observational study
    Sho Katayama, Kentaro Izumi, Inkin Ujiie, Hideyuki Ujiie
    The Journal of Dermatology.2025; 52(2): 363.     CrossRef
  • Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis
    Qi-Hang Yang, Chuang-Nian Zhang
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • Establishment of a novel predictive model for thiopurine-induced leucopenia based on the polymorphisms in the DNA-thioguanine nucleotide metabolite pathway in Chinese patients with inflammatory bowel disease
    Xia Zhu, Xue-ding Wang, Qiao-lan Xuan, Shao-xing Guan, Yan-pin Guan, Xiang Gao, Kang Chao, Min Huang
    Drug Metabolism and Disposition.2025; 53(8): 100119.     CrossRef
  • Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study
    Motoki Makuuchi, Yoichi Kakuta, Junji Umeno, Toshimitsu Fujii, Tetsuya Takagawa, Takashi Ibuka, Miki Miura, Yu Sasaki, Sakuma Takahashi, Hiroshi Nakase, Hiroki Kiyohara, Keiichi Tominaga, Yosuke Shimodaira, Sakiko Hiraoka, Nobuhiro Ueno, Shunichi Yanai, T
    Journal of Gastroenterology.2024; 59(6): 468.     CrossRef
  • Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn’s disease: a Korean nationwide population-based study
    Yu Kyung Jun, Eunjeong Ji, Hye Ran Yang, Yonghoon Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee, Hyuk Yoon
    Therapeutic Advances in Gastroenterology.2024;[Epub]     CrossRef
  • A systematic review of aspects of NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression
    Rachel Palmer, Jaime Peters
    RPS Pharmacy and Pharmacology Reports.2024;[Epub]     CrossRef
  • m6A modification in inflammatory bowel disease provides new insights into clinical applications
    Jiamin Zhang, Bimei Song, Yue Zeng, Chao Xu, Liang Gao, Yan Guo, Jingbo Liu
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  • Targeting FTO by Dac51 contributes to attenuating DSS-induced colitis
    Chunyan Peng, Chang Zheng, Fan Zhou, Ying Xie, Lei Wang, Deyan Chen, Xiaoqi Zhang
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  • Single-Nucleotide Polymorphisms, c.415C > T (Arg139Cys) and c.416G > A (Arg139His), in the NUDT15 Gene Are Associated with Thiopurine-Induced Leukopenia
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  • NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
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  • Severe thiopurine‐induced leukocytopenia and hair loss in Japanese patients with defective NUDT15 variant: Retrospective case–control study
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  • Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis
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    Journal of Digestive Diseases.2018; 19(12): 753.     CrossRef
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