研究者詳細 - 髙原　政宏

論文 - 髙原　政宏

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【潰瘍性大腸炎内科診療の新時代】日常診療に有用な潰瘍性大腸炎のバイオマーカー

青山祐樹, 平岡佐規子, 井口俊博, 竹井健介, 井川翔子, 竹内桂子, 高原政宏

医学と薬学 79 ( 11 ) 1461 - 1468 2022年10月

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

生検検体を用いた胆道癌におけるPD-L1発現の検討

松本和幸, 高木章乃夫, 大原利章, 藤澤真義, 高原政宏, 加藤博也, 吉田龍一, 楳田祐三, 八木孝仁, 松川昭博

日本消化器病学会雑誌 119 ( 臨増大会 ) A730 - A730 2022年10月

生検検体を用いた胆道癌におけるPD-L1発現の検討

松本和幸, 高木章乃夫, 大原利章, 藤澤真義, 高原政宏, 加藤博也, 吉田龍一, 楳田祐三, 八木孝仁, 松川昭博

日本消化器病学会雑誌 119 ( 臨増大会 ) A730 - A730 2022年10月

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

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

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

担当区分：筆頭著者記述言語：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

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消化管疾患と性差女性IBD患者における月経周期と腹部症状との関わりを探る

井口俊博, 平岡佐規子, 青山祐樹, 竹井健介, 井川翔子, 竹内桂子, 高原政宏, 近藤喜太

日本高齢消化器病学会誌 25 ( 1 ) 144 - 144 2022年7月

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

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 2022年6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

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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

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年4月

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年4月

Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms. 査読国際誌

Kazuyuki Matsumoto, Toshiaki Ohara, Masayoshi Fujisawa, Akinobu Takaki, Masahiro Takahara, Hironari Kato, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Akihiro Matsukawa, Hiroyuki Okada

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 26 ( 6 ) 1213 - 1223 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. METHODS: Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. RESULTS: The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). CONCLUSIONS: Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates.

DOI： 10.1007/s11605-021-05197-6

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

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

担当区分：筆頭著者記述言語：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

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[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年

胆嚢良性リンパ性ポリープと胆管lymphoid hyperplasiaが併存した一例

松原弘樹, 宮本和也, 松本和幸, 神尾智宏, 原田圭, 木村彰吾, 平田翔一郎, 石田正也, 岡本雄貴, 熊原加奈, 榮浩行, 高原政宏, 竹中龍太, 藤木茂篤

日本消化器病学会中国支部例会・日本消化器内視鏡学会中国支部例会プログラム・抄録集 116回・127回 110 - 110 2021年11月

診断講座症例から学ぶIBD鑑別診断のコツ(第50回) 5-ASAアレルギー

安富絵里子, 平岡佐規子, 竹井健介, 井川翔子, 岡昌平, 井口俊博, 高原政宏, 岡田裕之

IBD Research 15 ( 2 ) 109 - 114 2021年6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)製剤は軽症から中等症の潰瘍性大腸炎(UC)に対する第一選択薬で基本的には安全な薬剤である。しかしながら、5-ASA製剤の投与に伴いUCの増悪と鑑別がむずかしい下痢・血便の増悪を伴う『5-ASAアレルギー』が起こり得、さらに最近、その頻度も増加傾向にあるとされ注目されている。まず5-ASAアレルギーという病態があることを認識し、経過から5-ASAアレルギーの可能性を疑う場合、5-ASA製剤を中止する『勇気』をもつことが大事である。また、その後の経過が難治になる症例もありうるため、早めに専門医への紹介を考慮すべきである。(著者抄録)

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

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

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IBD診療における超音波の有用性クローン病小腸狭窄病変に対する経腹壁超音波検査の病変検出率の検討

竹内桂子, 井口俊博, 高原政宏, 大森正泰, 竹井健介, 安富絵里子, 岡昌平, 大西秀樹, 平岡佐規子, 岡田裕之

超音波医学 48 ( Suppl. ) S309 - S309 2021年4月

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

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

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

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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