Faculty Profiles - HIRAOKA Sakiko

Papers - HIRAOKA Sakiko

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【潰瘍性大腸炎内科診療の即戦力を身につける!-急増する患者の日常診療に求められる必須アップデート-】基準治療 5-ASA製剤と局所製剤の最適化熟知し使いこなす!

安富絵里子, 井口俊博, 平岡佐規子

消化器内科 4 ( 6 ) 40 - 47 2022.6

Language：Japanese Publisher：(株)医学出版

5-aminosalicylic acid(5-ASA)製剤は軽症から中等症までの潰瘍性大腸炎(UC)の寛解導入・寛解維持の両方に用いることのできる基本薬である。日本ではサラゾスルファピリジンと3種類のメサラジン製剤およびそれらのジェネリック製剤、局所製剤(坐剤・注腸製剤)を使用することができる。5-ASA製剤の最大用量の投与により7割前後の症例で有効性が見込まれる。5-ASA製剤による治療中に再燃をきたした場合はアドヒアランスや用量の確認、局所製剤の追加や5-ASA製剤のローテーションも考慮される。また、5-ASA製剤は安全性の高い薬であるが、気を付けるべき副作用もある。特に、治療開始1〜2週間後に発熱、下痢、腹痛の悪化を呈した場合は5-ASA製剤によるアレルギーを疑う。UCの増悪と鑑別が難しい場合もあるが、疑わしい症例に遭遇した場合は5-ASAアレルギーの可能性を念頭におき、製剤を中止することが必要である。(著者抄録)

The diagnostic ability to classify neoplasias occurring in inflammatory bowel disease by artificial intelligence and endoscopists: A pilot study. International journal

Shumpei Yamamoto, Hideaki Kinugasa, Kenta Hamada, Masahiro Tomiya, Takayoshi Tanimoto, Akimitsu Ohto, Akira Toda, Daisuke Takei, Minoru Matsubara, Seiyu Suzuki, Kosuke Inoue, Takehiro Tanaka, Sakiko Hiraoka, Hiroyuki Okada, Yoshiro Kawahara

Journal of gastroenterology and hepatology 37 ( 8 ) 1610 - 1616 2022.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: Although endoscopic resection with careful surveillance instead of total proctocolectomy become to be permitted for visible low-grade dysplasia, it is unclear how accurately endoscopists can differentiate these lesions, as classifying neoplasias occurring in inflammatory bowel disease (IBDN) is exceedingly challenging due to background chronic inflammation. We evaluated a pilot model of an artificial intelligence (AI) system for classifying IBDN and compared it with the endoscopist's ability. METHODS: This study used a deep convolutional neural network, the EfficientNet-B3. Among patients who underwent treatment for IBDN at two hospitals between 2003 and 2021, we selected 862 non-magnified endoscopic images from 99 IBDN lesions and utilized 6 375 352 images that were increased by data augmentation for the development of AI. We evaluated the diagnostic ability of AI using two classifications: the "adenocarcinoma/high-grade dysplasia" and "low-grade dysplasia/sporadic adenoma/normal mucosa" groups. We compared the diagnostic accuracy between AI and endoscopists (three non-experts and four experts) using 186 test set images. RESULTS: The diagnostic ability of the experts/non-experts/AI for the two classifications in the test set images had a sensitivity of 60.5% (95% confidence interval [CI]: 54.5-66.3)/70.5% (95% CI: 63.8-76.6)/72.5% (95% CI: 60.4-82.5), specificity of 88.0% (95% CI: 84.7-90.8)/78.8% (95% CI: 74.3-83.1)/82.9% (95% CI: 74.8-89.2), and accuracy of 77.8% (95% CI: 74.7-80.8)/75.8% (95% CI: 72-79.3)/79.0% (95% CI: 72.5-84.6), respectively. CONCLUSIONS: The diagnostic accuracy of the two classifications of IBDN was higher than that of the experts. Our AI system is valuable enough to contribute to the next generation of clinical practice.

DOI： 10.1111/jgh.15904

Fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection for patients with immunosuppressants and steroids. International journal

Shumpei Yamamoto, Hideaki Kinugasa, Yasushi Yamasaki, Mami Hirai, Soichiro Ako, Kensuke Takei, Shoko Igawa, Eriko Yasutomi, Shohei Oka, Masayasu Ohmori, Toshihiro Inokuchi, Keita Harada, Sakiko Hiraoka, Kazuhiro Nouso, Takehiro Tanaka, Hiroyuki Okada

DEN open 2 ( 1 ) e83 2022.4

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post-ESD fever and post-ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). METHODS: This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post-ESD fever and PECS were investigated. RESULTS: Post-ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post-ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post-ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. CONCLUSIONS: The use of IM was a risk factor for both post-ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.

DOI： 10.1002/deo2.83

UnderwaterとUnder-gelでの大腸腫瘍性病変に対する境界診断能の検討

豊澤惇希, 山崎泰史, 岡田裕之, 竹井健介, 青山祐樹, 井川翔子, 安富絵里子, 山本峻平, 竹内桂子, 高原政宏, 衣笠秀明, 原田馨太, 平岡佐規子

Gastroenterological Endoscopy 64 ( Suppl.1 ) 761 - 761 2022.4

消化管の炎症性疾患における超音波の役割クローン病の活動性評価における経腹超音波検査の有用性

高原政宏, 平岡佐規子, 大森正泰, 竹内佳子, 井口俊博, 大西秀樹, 岡田裕之

超音波医学 49 ( Suppl. ) S243 - S243 2022.4

Metformin ameliorates chronic colitis in a mouse model by regulating interferon-γ-producing lamina propria CD4+ T cells through AMPK activation. International journal

Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Heiichiro Udono, Hiroyuki Okada

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 ( 2 ) e22139 2022.2

Language：English Publishing type：Research paper (scientific journal)

Metformin, a commonly prescribed drug for type 2 diabetes mellitus, has been shown to activate AMP-activated protein kinase (AMPK). Notably, AMPK activation has recently been observed to be associated with anti-inflammatory responses. Metformin is also reported to elicit anti-inflammatory responses in CD4+ T cells, resulting in improvement in experimental chronic inflammatory diseases, such as systemic lupus erythematosus. To investigate the effect of metformin on inflammatory bowel disease (IBD), we developed a T cell-transfer model of chronic colitis in which SCID mice were injected with CD4+ CD45RBhigh T cells to induce colitis. We examined the effects of metformin via in vitro and in vivo experiments on lamina propria (LP) CD4+ T cells. We observed that metformin suppresses the frequency of interferon (IFN) -γ-producing LP CD4+ T cells in vitro, which were regulated by AMPK activation, a process possibly induced by the inhibition of oxidative phosphorylation. Furthermore, we examined the effects of metformin on an in vivo IBD model. Metformin-treated mice showed AMPK activation in LP CD4+ T cells and ameliorated colitis. Our study demonstrates that metformin-induced AMPK activation in mucosal CD4+ T cells contributes to the improvement of IBD by suppressing IFN-γ production. Moreover, our results indicate that AMPK may be a target molecule for the regulation of mucosal immunity and inflammation. Thus, AMPK-activating drugs such as metformin may be potential therapeutic agents for the treatment of IBD.

DOI： 10.1096/fj.202100831RR

A consensus statement on health-care transition for childhood-onset inflammatory bowel disease patients. International journal

Hideki Kumagai, Toshiaki Shimizu, Itaru Iwama, Shin-Ichiro Hagiwara, Takahiro Kudo, Michiko Takahashi, Takeshi Saito, Reiko Kunisaki, Motoi Uchino, Sakiko Hiraoka, Makoto Naganuma, Ken Sugimoto, Jun Miyoshi, Tomoyoshi Shibuya, Tadakazu Hisamatsu

Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e15241 2022.1

Language：English Publishing type：Research paper (scientific journal)

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the intestine. The incidence of IBD is increasing worldwide, including Japan, and in approximately 25% of all affected patients it is diagnosed before 18 years of age. For the health maintenance of such patients, planned transition to adult care systems is essential. Previous Japanese surveys have revealed gaps between adult and pediatric gastroenterologists with regard to their knowledge and perception of health-care transition for patients with childhood-onset IBD. In 2021-2022, several Web workshops to discuss issues related to the transitional care of IBD patients were held by the Ministry of Health, Labour and Welfare of Japan as part of their program for research on intractable diseases. Clinicians experienced in IBD treatment for pediatric and adult patients participated. As a result, this panel of adult and pediatric gastroenterologists developed five consensus statements on the issue of "transfer from pediatric to adult care" and nine statements on the issue of "addressing transitional care (transition program)." To address current gaps in health-care transition for childhood-onset IBD patients, a programmed approach to transition, and better partnerships between pediatric and adult gastroenterologists are indicated. It is hoped that this consensus statement will provide a basis for the development of appropriate guidelines for clinical practice.

DOI： 10.1111/ped.15241

潰瘍性大腸炎患者における直腸粘膜内のリンパ球分画構成の検討

岩室雅也, 高橋孝英, 田中健大, 平岡佐規子, 岡田裕之

日本消化管学会雑誌 6 ( Suppl. ) 208 - 208 2022.1

[The medical treatment of elderly patients with ulcerative colitis and its limitation].

Toshihiro Inokuchi, Masahiro Takahara, Sakiko Hiraoka

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 119 ( 11 ) 992 - 1003 2022

Enriched CD45RA-CD62L+ central memory T and decreased CD3+CD56+ natural killer T lymphocyte subsets in the rectum of ulcerative colitis patients. International journal

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

International journal of immunopathology and pharmacology 36 20587384211051982 - 20587384211051982 2022

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis. METHODS: We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients (n = 13) and control patients (n = 5). RESULTS: CD62L+/CD3+CD4+ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L+/CD3+CD4- cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA-CD62L+/CD3+CD4+, that is, central memory T cell fraction in CD4+ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56+/CD3+ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56+/CD3+ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%). CONCLUSION: We demonstrated that CD62L+ T lymphocytes, particularly the CD45RA-CD62L+ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56+/CD3+ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.

DOI： 10.1177/20587384211051982

Clinical utility of a serum glycome analysis in patients with colorectal cancer Reviewed International journal

Takei D, Harada K, Nouso K, MiyaharaK, Dohi C, Matsushita H, Kinugasa H, Hiraoka S, Nishimura S-I, Okada H

J. Gastroen. Hepatol. 37 ( 4 ) 727 - 733 2022

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: Serum glycans are known to be good markers for the early diagnosis and prognostic prediction in many cancers. The aims of this study were to reveal the serum glycan changes comprehensively during the process of carcinogenesis from colorectal adenoma (CRA) to colorectal cancer (CRC) and to evaluate the usefulness of the glycan profiles as clinical markers for CRC. METHODS: Serum samples were obtained from 80 histologically proven CRC and 36 CRA cases. The levels of glycans in the serum were examined with a comprehensive, quantitative, high-throughput unique glycome analysis, and their diagnostic and prognostic abilities were evaluated. RESULTS: Among 34 stably detected glycans, nine were differentially expressed between CRC and CRA. Serum levels of hybrid type glycans were increased in patients with CRC compared with those with CRA (P < 0.001), and both hybrid-type and multi-antennary glycans were significantly increased in advanced cancer cases. The glycan, m/z 1914, showed the highest diagnostic value among the decreased glycans, whereas m/z 1708 showed the highest among the increased glycans. The glycan ratio m/z 1708/1914 showed a higher area under the receiver operating characteristic curve (0.889) than any other single glycan or conventional tumor marker, such as carcinoembryonic antigen (0.766, P = 0.040) and carbohydrate antigen 19-9 (0.615, P < 0.001). High m/z 1708/1914 was also correlated with an advanced cancer stage and short overall survival. CONCLUSION: Serum glycans, especially the m/z 1708/1914 ratio, were useful for the diagnosis, staging, and prognosis prediction of CRC.

DOI： 10.1111/jgh.15781

A nationwide survey concerning the mortality and risk of progressing severity due to arterial and venous thromboembolism in inflammatory bowel disease in Japan.

Katsuyoshi Ando, Mikihiro Fujiya, Kenji Watanabe, Sakiko Hiraoka, Hisashi Shiga, Shinji Tanaka, Hideki Iijima, Tsunekazu Mizushima, Taku Kobayashi, Masakazu Nagahori, Hiroki Ikeuchi, Shingo Kato, Takehiro Torisu, Kiyonori Kobayashi, Masaaki Higashiyama, Toshiro Fukui, Takashi Kagaya, Motohiro Esaki, Shunichi Yanai, Daiki Abukawa, Makoto Naganuma, Satoshi Motoya, Masayuki Saruta, Shigeki Bamba, Makoto Sasaki, Kazuhiko Uchiyama, Katsuyuki Fukuda, Hideo Suzuki, Hiroshi Nakase, Toshiaki Shimizu, Masahiro Iizuka, Mamoru Watanabe, Yasuo Suzuki, Tadakazu Hisamatsu

Journal of gastroenterology 56 ( 12 ) 1062 - 1079 2021.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

DOI： 10.1007/s00535-021-01829-5

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan. International journal

Atsushi Nishikawa, Keiko Tanaka, Yoshihiro Miyake, Chisato Nagata, Shinya Furukawa, Akira Andoh, Tetsuji Yokoyama, Naoki Yoshimura, Kenichiro Mori, Tomoyuki Ninomiya, Yasunori Yamamoto, Eiji Takeshita, Yoshio Ikeda, Mitsuru Saito, Katsuhisa Ohashi, Hirotsugu Imaeda, Kazuki Kakimoto, Kazuhide Higuchi, Hiroaki Nunoi, Yuji Mizukami, Seiyuu Suzuki, Sakiko Hiraoka, Hiroyuki Okada, Keitarou Kawasaki, Masaaki Higashiyama, Ryota Hokari, Hiromasa Miura, Teruki Miyake, Teru Kumagi, Hiromasa Kato, Naohito Hato, Koji Sayama, Yoichi Hiasa

Journal of gastroenterology and hepatology 37 ( 4 ) 653 - 659 2021.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

DOI： 10.1111/jgh.15745

Evaluation of complete cold forceps polypectomy resection rate for 3- to 5-mm colorectal polyps. International journal

Yasushi Yamasaki, Keita Harada, Shumpei Yamamoto, Eriko Yasutomi, Mami Hirai, Masayasu Ohmori, Shohei Oka, Toshihiro Inokuchi, Hideaki Kinugasa, Yuusaku Sugihara, Masahiro Takahara, Sakiko Hiraoka, Takehiro Tanaka, Toshiharu Mitsuhashi, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 6 ) 948 - 954 2021.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND STUDY AIMS: The propriety of cold forceps polypectomy (CFP) using jumbo biopsy forceps for diminutive polyps remains controversial. We conducted a prospective study to evaluate the complete CFP resection rate of 3-5-mm polyps using additional endoscopic mucosal resection (EMR) specimens following CFP. PATIENTS AND METHODS: Patients with 3-5-mm protruded or flat elevated colorectal polyps diagnosed endoscopically as adenomas or serrated lesions were prospectively enrolled. CFP using jumbo biopsy forceps was used to remove the eligible polyps and repeated until the absence of residuals were confirmed via image-enhanced endoscopy or chromoendoscopy. After CFP, saline was injected at the defect, and the marginal specimen of the defect was resected using EMR to histologically evaluate the residue. The primary outcome was the complete CFP resection rate, which was defined as no residue at the EMR site. Other outcomes were the number of CFP bites and the complete resection rate by lesion size. RESULTS: Eighty patients with 120 polyps were enrolled. The mean polyp size was 4.1 ± 0.7 mm. The overall complete resection rate was 96.7% (95% confidence interval [CI], 91.7-98.7), and the rates for 3-, 4- and 5-mm polyps were 100% (95% CI, 86.7-100), 96.0% (95% CI, 86.5-98.9) and 95.5% (95% CI, 85.1-98.8), respectively. The one-bite CFP rates were 92%, 60% and 31% for the 3-, 4- and 5-mm polyps, respectively. CONCLUSIONS: The complete CFP resection rate for 3-5-mm polyps was acceptable, although the one-bite clearance rate decreased as the polyp size increased (UMIN000028841).

DOI： 10.1111/den.13895

A novel clip closure method using precutting and a reopenable clip after colorectal endoscopic submucosal dissection. International journal

Masayasu Ohmori, Yasushi Yamasaki, Shumpei Yamamoto, Hideaki Kinugasa, Keita Harada, Sakiko Hiraoka, Hiroyuki Okada

Endoscopy 54 ( 8 ) E401-E402 2021.8

Anti-proteinase 3 antineutrophil cytoplasmic antibody reflects disease activity and predicts the response to steroid therapy in ulcerative colitis. International journal

Yuki Aoyama, Tomoki Inaba, Sakuma Takahashi, Hisae Yasuhara, Sakiko Hiraoka, Takeshi Morimoto, Hugh Shunsuke Colvin, Masaki Wato, Midori Ando, Satoko Nakamura, Koichi Mizobuchi, Hiroyuki Okada

BMC gastroenterology 21 ( 1 ) 325 - 325 2021.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin. METHODS: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission. RESULTS: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023). CONCLUSIONS: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC. TRIAL REGISTRATION: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020.

DOI： 10.1186/s12876-021-01903-5

Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta-analysis. International journal

Takeo Yoshihara, Shinichiro Shinzaki, Takahiro Amano, Hideki Iijima, Tetsuo Takehara, Nagamu Inoue, Motoi Uchino, Motohiro Esaki, Taku Kobayashi, Masayuki Saruta, Ken Sugimoto, Shiro Nakamura, Keisuke Hata, Fumihito Hirai, Sakiko Hiraoka, Toshimitsu Fujii, Minoru Matsuura, Katsuyoshi Matsuoka, Kenji Watanabe, Hiroshi Nakase, Mamoru Watanabe

Journal of gastroenterology and hepatology 36 ( 7 ) 1744 - 1753 2021.7

Language：English Publishing type：Research paper (scientific journal)

Background and aim: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. Methods: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6–12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios. Results: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06–1.71], P = 0.015). The heterogeneity among studies was low (I2 = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. Conclusion: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.

DOI： 10.1111/jgh.15401

Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer. International journal

Shumpei Yamamoto, Hideaki Kinugasa, Mami Hirai, Hiroyuki Terasawa, Eriko Yasutomi, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Keita Harada, Sakiko Hiraoka, Kazuhiro Nouso, Takehiro Tanaka, Fuminori Teraishi, Toshiyoshi Fujiwara, Hiroyuki Okada

Journal of gastroenterology and hepatology 36 ( 7 ) 1869 - 1876 2021.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: Fusobacterium nucleatum (Fn) is involved in colorectal cancer (CRC) growth and is a biomarker for patient prognosis and management. However, the ecology of Fn in CRC and the distribution of intratumoral Fn are unknown. METHODS: We evaluated Fn and the status of KRAS and BRAF in 200 colorectal neoplasms (118 adenomas and 82 cancers) and 149 matched adjacent normal mucosas. The differentiation status between "surface" and "deep" areas of cancer tissue and matched normal mucosa were analyzed in 46 surgical samples; the Ki-67 index was also evaluated in these samples. RESULTS: Fusobacterium nucleatum presence in the tumor increased according to pathological stage (5.9% [adenoma] to 81.8% [stage III/IV]), while Fn presence in normal mucosa also increased (7.6% [adenoma] to 40.9% [stage III/IV]). The detection rates of Fn on the tumor surface and in deep areas were 45.7% and 32.6%, while that of normal mucosa were 26.1% and 23.9%, respectively. Stage III/IV tumors showed high Fn surface area expression (66.7%). Fn intratumoral heterogeneity (34.8%) was higher than that of KRAS (4.3%; P < 0.001) and BRAF (2.2%; P < 0.001). The Ki-67 index in Fn-positive cases was higher than that in negative cases (93.9% vs 89.0%; P = 0.01). CONCLUSIONS: Fusobacterium nucleatum was strongly present in CRC superficial areas at stage III/IV. The presence of Fn in the deep areas of adjacent normal mucosa also increased. The intratumoral heterogeneity of Fn is important in the use of Fn as a biomarker, as Fn is associated with CRC proliferative capacity.

DOI： 10.1111/jgh.15361

Two Cases of Endometriosis in the Cecum Detected by Contrast-enhanced Computed Tomography with Air/Carbon Dioxide Insufflation.

Masaya Iwamuro, Takehiro Tanaka, Yuusaku Sugihara, Keita Harada, Sakiko Hiraoka, Yoshitaka Kondo, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 60 ( 11 ) 1697 - 1701 2021.6

Language：English Publishing type：Research paper (scientific journal)

We herein report two patients with endometriosis in the cecum. Both patients presented with a protruding, subepithelial tumor on colonoscopy and were diagnosed with cecal endometriosis after surgical resection. It is notable that the cecal lesions were not initially identified on computed tomography (CT), while CT colonography with air/carbon dioxide insufflation resulted in the detection of the cecal tumor. These cases highlight the possibility of false-negative results on conventional CT in patients with cecal endometriosis. We consider CT colonography with air/carbon dioxide insufflation useful for detecting cecal tumors in such cases.

DOI： 10.2169/internalmedicine.6418-20

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study.

Shinichiro Shinzaki, Katsuyoshi Matsuoka, Hiroki Tanaka, Fuminao Takeshima, Shingo Kato, Takehiro Torisu, Yuki Ohta, Kenji Watanabe, Shiro Nakamura, Naoki Yoshimura, Taku Kobayashi, Akiko Shiotani, Fumihito Hirai, Sakiko Hiraoka, Mamoru Watanabe, Minoru Matsuura, Shohei Nishimoto, Shinta Mizuno, Hideki Iijima, Tetsuo Takehara, Tetsuji Naka, Takanori Kanai, Takayuki Matsumoto

Journal of gastroenterology 56 ( 6 ) 560 - 569 2021.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). METHODS: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn's disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. RESULTS: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). CONCLUSIONS: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

DOI： 10.1007/s00535-021-01793-0

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