研究者詳細 - 井口　俊博

論文 - 井口　俊博

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炎症性腸疾患の内視鏡的モニタリング(下部) 潰瘍性大腸炎においてLeucine-rich alpha 2 glycoprotein(LRG)は内視鏡的および組織学的活動性の変化の予測に有用である

青山祐樹, 井口俊博, 平岡佐規子

Gastroenterological Endoscopy 65 ( Suppl.1 ) 728 - 728 2023年4月

【あなたの知らないIBD診療の世界】新規治療法・検査法 IBDに対するバイオマーカーの使い方血中マーカーと便中マーカー

井口俊博, 平岡佐規子, 青山祐樹, 竹井健介, 井川翔子, 高原政宏

臨床消化器内科 38 ( 4 ) 422 - 428 2023年3月

記述言語：日本語出版者・発行元：(株)日本メディカルセンター

＜文献概要＞潰瘍性大腸炎およびクローン病を含む炎症性腸疾患(IBD)は,単なる症状の改善にとどまらず,内視鏡的な治癒を目指すことにより予後が改善することが証明されている.したがって内視鏡的活動性の把握が重要であり,内視鏡重症度の代替マーカーである,血中,便中マーカーをそれぞれ上手に使いこなすことが肝要である.一方で各マーカーの注意点があり,血中マーカーではCRPだけでなく,近年LRGが利用可能となり,実臨床での活用が期待される.また便中マーカーはとくに疾患活動性が落ちてきたステージでの利用がより有用であり,内視鏡的寛解の判断に強みをもつ.IBD診療においては,各マーカーの長所,注意点に習熟し,より良いモニタリングを行うことが求められる.

Usefulness of Intestinal Ultrasound to Detect Small Intestinal Stenosis in Patients With Crohn's Disease. 国際誌

Keiko Takeuchi, Toshihiro Inokuchi, Masahiro Takahara, Masayasu Ohmori, Eriko Yasutomi, Shohei Oka, Shoko Igawa, Kensuke Takei, Yuki Baba, Seiji Kawano, Yasushi Yamasaki, Hideaki Kinugasa, Keita Harada, Sakiko Hiraoka, Hiroyuki Okada

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 42 ( 2 ) 373 - 383 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Double balloon enteroscopy (DBE) with retrograde contrast is useful as a monitoring tool for small intestinal lesions in Crohn's disease (CD), but these are burdensome for patients. Intestinal ultrasound (IUS) can be used with ease in daily clinical practice, but there is less evidence regarding the accuracy of detection of small intestinal stenosis in CD. This study aimed to examine the diagnostic power of IUS for small intestinal stenosis in patients with CD. METHODS: The findings of DBE and IUS in 86 patients with CD with small intestinal lesions were evaluated. Using DBE as the reference standard, we examined the detection rate of IUS for small intestinal stenosis. We evaluated three parameters: luminal narrowing, prestenotic dilation, and to-and-fro movement for determining stenosis using IUS. In addition, we compared the characteristics between the stenosis-detectable and stenosis-undetectable groups by IUS. RESULTS: Of the 86 patients, 30 had small intestinal stenosis. In IUS findings, when lesions that met two or more of the three parameters were judged as stenosis, the detection rate was 70.0% for sensitivity, 98.2% for specificity, and 88.4% for accuracy. Moreover, there were patients with a younger age at diagnosis (P < 0.05) and more ileocolonic disease location (P < 0.05) in the stenosis-detectable group by IUS. The stenoses detected by IUS were significantly longer than those undetected by IUS (14.1 mm versus 5.2 mm, P < 0.05). CONCLUSIONS: IUS delivered reliable results for clinically important small intestinal stenosis of CD with high diagnostic accuracy.

DOI： 10.1002/jum.16038

RNA editing is a valuable biomarker for predicting carcinogenesis in ulcerative colitis. 国際誌

Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara

Journal of Crohn's & colitis 17 ( 5 ) 754 - 766 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

【IBDの既存治療を最新の知見から見直す!】IBDの5-ASA製剤による治療を見直す

高原政宏, 平岡佐規子, 井口俊博

IBD Research 16 ( 4 ) 219 - 224 2022年12月

記述言語：日本語出版者・発行元：(株)先端医学社

5-アミノサリチル酸(5-ASA)製剤は,安全性が高く,使用しやすい薬剤であり,炎症性腸疾患(IBD),とくに潰瘍性大腸炎においては,軽症～中等症の治療薬の第一選択薬として,寛解導入から寛解維持まで広く用いられている.わが国では,現在使用できる5-ASA製剤は4種類あり,各薬剤の特徴を理解したうえで,病勢や患者の状況に合わせて薬剤の選択をしていく.IBD患者の増加に伴い,5-ASA製剤の使用頻度は今後,さらに増していくであろう一方で,近年は5-ASA製剤の不耐症例も増加している.不耐の特徴や対処法に関する知識も必要とされ,適切な対応を取ることも求められている.(著者抄録)

【高齢者潰瘍性大腸炎の現状】高齢者潰瘍性大腸炎の内科的治療とその見極め

井口俊博, 高原政宏, 平岡佐規子

日本消化器病学会雑誌 119 ( 11 ) 992 - 1003 2022年11月

記述言語：日本語出版者・発行元：(一財)日本消化器病学会

近年,高齢潰瘍性大腸炎(UC)患者数が増加しており,特に若年発症して長期経過を追っている高齢UC症例と異なり,高齢になって新規に発症したUCは治療に難渋する症例が少なくない.また年齢だけで高齢者の全身状態を判断することはできず,症例によって脆弱性やリスクが異なるため,注意が必要である.現在使用できる治療薬はいずれも高齢者を対象とした試験を経ず保険収載されており,リアルワールドデータを基に有効性,安全性の判断をせざるを得ない.高齢者特有の併存疾患の管理,ポリファーマシーと相互作用,認知症,身体機能低下,易感染状態などのリスクを考慮し,重篤な状態になる前に常に早期介入を心掛ける必要がある.(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01118&link_issn=&doc_id=20221116250003&doc_link_id=%2Fck8syokb%2F2022%2F011911%2F003%2F0992-1003%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck8syokb%2F2022%2F011911%2F003%2F0992-1003%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

クローン病患者の内視鏡活動性と活動性の変化を予測するバイオマーカーは?

井口俊博, 平岡佐規子, 豊澤惇希, 竹井健介, 青山祐樹, 井川翔子, 竹内桂子, 山崎泰史, 衣笠秀明, 高原政宏, 原田馨太, 岡田裕之

日本消化器病学会雑誌 119 ( 臨増大会 ) A750 - A750 2022年10月

手技の解説クローン病におけるダブルバルーン内視鏡下逆行性造影の実際

井口俊博, 川野誠司, 平岡佐規子

Gastroenterological Endoscopy 64 ( 10 ) 2308 - 2316 2022年10月

記述言語：日本語出版者・発行元：(一社)日本消化器内視鏡学会

クローン病患者の7割以上が小腸病変を有するとされ,小腸病変のモニタリングとその制御は患者のQOLに直結する.従ってクローン病診療では,全小腸を高精度でかつ手軽に,そして低侵襲にモニタリングすることが求められるが,残念ながらすべてを兼ね備えた検査やマーカーは未だ存在しない.ダブルバルーン内視鏡検査は,クローン病小腸病変に対するモニタリング検査の1つとして,また時に内視鏡的拡張術目的に広く使用されている.当科ではダブルバルーン内視鏡検査の際に通常の観察に加えて先端バルーンを拡張させて逆行性造影を行い,それまでは難しかった深部小腸の評価をルーチンで行っている.本稿では,クローン病小腸病変に対するダブルバルーン内視鏡下逆行性造影の手順やコツを解説する.(著者抄録)

The Colon Wall Thickness Measured Using Transabdominal Ultrasonography Is Useful for Detecting Mucosal Inflammation in Ulcerative Colitis.

Masahiro Takahara, Sakiko Hiraoka, Masayasu Ohmori, Keiko Takeuchi, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Hideki Ohnishi, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 61 ( 18 ) 2703 - 2709 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Transabdominal ultrasonography (TUS) is a non-invasive procedure that is reportedly useful for managing ulcerative colitis (UC) and assessing bowel wall thickness (BWT), the most common measure of mucosal inflammation. However, the exact range of BWT that reflects disease activity remains undetermined. The present study clarified the BWT due to disease activity by comparing the use of TUS in each segment of the colon versus using colonoscopy (CS) and determined the usefulness of TUS in patients with UC. Methods We divided the colon into five segments and measured the BWT using TUS. The results were then compared to the Mayo endoscopic subscore (MES) classification to determine the accuracy of BWT measurement. Patients Eighty patients with UC who underwent TUS within 14 days of CS were retrospectively registered. Results We evaluated a total of 268 images depicting each segment among 80 patients with UC. The BWT was positively correlated with endoscopic activity (0.69, p<0.0001). In each segment, the relationship between a BWT>2 mm and an MES>0 had the highest sensitivity, specificity, and accuracy (0.85-1.00, 0.67-0.92, and 0.81-0.97, respectively). Conclusion This study concluded that TUS was a useful method of detecting an MES>0, which indicates the presence of inflammation and its location among UC patients. MES>0 was found to be highly accurate when a BWT>2 mm was considered positive. This non-invasive method may help control disease activity in patients with UC.

DOI： 10.2169/internalmedicine.8827-21

人工肛門造設状態で帝王切開による分娩が可能であった難治性クローン病の一例

安富有希, 井川翔子, 青山祐樹, 竹井健介, 安富絵里子, 井口俊博, 高原政宏, 平岡佐規子, 岡田裕之, 近藤喜太

日本消化器病学会中国支部例会プログラム・抄録集 117回 69 - 69 2022年6月

Fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection for patients with immunosuppressants and steroids. 国際誌

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

高齢者潰瘍性大腸炎の内科的治療とその見極め

井口俊博, 高原政宏, 平岡佐規子

日本消化器病学会雑誌(Web) 119 ( 11 ) 992 - 1003 2022年

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

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer. 国際誌

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年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. 国際誌

Eriko Yasutomi, Toshihiro Inokuchi, Sakiko Hiraoka, Kensuke Takei, Shoko Igawa, Shumpei Yamamoto, Masayasu Ohmori, Shohei Oka, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Keita Harada, Masaki Furukawa, Kouichi Itoshima, Ken Okada, Fumio Otsuka, Takehiro Tanaka, Toshiharu Mitsuhashi, Jun Kato, Hiroyuki Okada

Scientific reports 11 ( 1 ) 11086 - 11086 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

DOI： 10.1038/s41598-021-90441-x

潰瘍性大腸炎診療におけるバイオマーカーの位置づけを考える新規LRGも含め

安富絵里子, 平岡佐規子, 竹井健介, 井川翔子, 山本峻平, 大森正泰, 岡昌平, 山崎泰史, 井口俊博, 衣笠秀明, 原田馨太, 岡田裕之

日本消化器病学会雑誌 118 ( 臨増総会 ) A360 - A360 2021年3月

Multicenter survey on mesalamine intolerance in patients with ulcerative colitis. 国際誌

Sakiko Hiraoka, Akiko Fujiwara, Tatsuya Toyokawa, Reiji Higashi, Yuki Moritou, Shinjiro Takagi, Kazuhiro Matsueda, Seiyuu Suzuki, Jiro Miyaike, Toshihiro Inokuchi, Masahiro Takahara, Jun Kato, Hiroyuki Okada

Journal of gastroenterology and hepatology 36 ( 1 ) 137 - 143 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Although oral mesalamine is the first-choice drug for treating mild-to-moderate ulcerative colitis (UC), some patients show symptoms of intolerance, including exacerbation of diarrhea and abdominal pain. The present study clarified the current state and clinical courses of patients with mesalamine intolerance. METHODS: Patients who were diagnosed with UC and administered oral mesalamine at eight hospitals in Japan with a follow-up period exceeding 1 year were analyzed. RESULTS: Sixty-seven (11%) of 633 patients showed intolerance to at least one formulation of oral mesalamine. The frequency of mesalamine intolerance has increased in recent years, rising from 5.3% in 2007-2010 to 9.1% in 2011-2013 and 16.2% in 2014-2016. The most common complications were the exacerbation of diarrhea (n = 29), a fever (n = 25), and abdominal pain (n = 22). Readministration of mesalamine/sulfasalazine was attempted in 43 patients, mostly with other types of formulation of mesalamine, and more than half of these patients proved to be tolerant. The risk factors for mesalamine intolerance were female gender (odds ratio [OR] = 1.83; 95% confidence interval [CI], 1.08-3.12), age < 60 years old (OR = 2.82; CI, 1.19-8.33), and pancolitis (OR = 2.09; 95% CI, 1.23-3.60). There were no significant differences in the use of anti-tumor necrosis factor-α agents, colectomy, or steroid-free remission at the last visit between patients with and without mesalamine intolerance. CONCLUSIONS: Mesalamine intolerance is not rare, and its frequency has been increasing recently. The prognosis of patients with mesalamine intolerance did not differ significantly from that of those without intolerance.

DOI： 10.1111/jgh.15138

Liquid biopsy for patients with IBD-associated neoplasia. 国際誌

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

BMC cancer 20 ( 1 ) 1188 - 1188 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. METHODS: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. RESULTS: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. CONCLUSION: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

DOI： 10.1186/s12885-020-07699-z

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