Faculty Profiles - NAKAMURA, Masanao

Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial. International journal

Toshihiro Kita, Shinya Ashizuka, Teruyuki Takeda, Takayuki Matsumoto, Naoki Ohmiya, Hiroshi Nakase, Satoshi Motoya, Hidehisa Ohi, Keiichi Mitsuyama, Tadakazu Hisamatsu, Shuji Kanmura, Naoya Kato, Shunji Ishihara, Masanao Nakamura, Tomohiko Moriyama, Masayuki Saruta, Ryoichi Nozaki, Shojiro Yamamoto, Haruhiko Inatsu, Koji Watanabe, Kazuo Kitamura

Journal of gastroenterology and hepatology Vol. 37 ( 11 ) page： 2051 - 2059 2022.11

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

BACKGROUND AND AIM: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD). METHODS: This was a multicenter, double-blind, placebo-controlled phase 2a trial that evaluated 24 patients with biologic-resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24. RESULTS: No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin-treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin. CONCLUSION: In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.

DOI： 10.1111/jgh.15945

当院におけるPeutz-Jeghers症候群症例に併存する膵疾患,悪性疾患の頻度に関する検討

クローン病深部小腸狭窄に対する内視鏡的バルーン拡張術の成績

大宮直木, 中村正直

Gastroenterological Endoscopy Vol. 64 ( Suppl.2 ) page： 1850 - 1850 2022.10

クローン病深部小腸狭窄に対する内視鏡的バルーン拡張術の成績

大宮直木, 中村正直

Gastroenterological Endoscopy Vol. 64 ( Suppl.2 ) page： 1850 - 1850 2022.10

大野栄三郎, 石川卓哉, 水谷泰之, 飯田忠, 植月康太, 八鹿潤, 宜保憲明, 青木聡典, 片岡邦夫, 森裕, 高田善久, 高橋秀和, 青井広典, 石川恵里, 澤田つな騎, 前田啓子, 山村健史, 古川和宏, 中村正直, 川嶋啓揮

日本消化器病学会雑誌 Vol. 119 ( 臨増大会 ) page： A793 - A793 2022.10

Modified N score is helpful for identifying patients who need endoscopic intervention among those with black stools without hematemesis. International journal

Nobuhito Ito, Kohei Funasaka, Toshihisa Fujiyoshi, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takuya Ishikawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Ryoji Miyahara, Yoshiki Hirooka, Jun-Ichi Haruta, Mitsuhiro Fujishiro

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Vol. 34 ( 6 ) page： 1157 - 1165 2022.9

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

OBJECTIVES: Although black stools are one of the signs of upper gastrointestinal bleeding, not all patients without hematemesis need endoscopic intervention. There is no apparent indicator to select who needs treatment thus far. The aim of this study was to establish a novel score that predicts the need for endoscopic intervention in patients with black stools without hematemesis. METHODS: We retrospectively enrolled 721 consecutive patients with black stools without hematemesis who underwent emergency endoscopy from two facilities. In the development stage (from January 2016 to December 2018), risk factors that predict the need for endoscopic intervention were determined from the data of 422 patients by multivariate logistic regression analysis, and a novel scoring system, named the modified Nagoya University score (modified N score), was developed. In the validation stage (from January 2019 to September 2020), we evaluated the diagnostic value of the modified N score for 299 patients. RESULTS: Multivariate logistic regression analysis revealed four predictive factors for endoscopic intervention: syncope, the blood urea nitrogen (BUN) level, and the BUN/creatinine ratio as positive indicators and anticoagulant drug use as a negative indicator. In the validation stage, the area under the curve of the modified N score was 0.731, and the modified N score showed a sensitivity of 82.0% and a specificity of 58.8%. CONCLUSIONS: Our modified N score, which consists of only four factors, can identify patients who need endoscopic intervention among those with black stools without hematemesis.

DOI： 10.1111/den.14323

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. International journal

Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, Mitsuhiro Fujishiro

BMC gastroenterology Vol. 22 ( 1 ) page： 342 - 342 2022.7

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

BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene. RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

DOI： 10.1186/s12876-022-02408-5

【小腸疾患-診断・治療の最新動向-】血行障害・血管性病変血管性病変動静脈奇形

(I章)消化管(上・下) 小腸腫瘍に対する診療の進歩

中村正直, 大宮直木

消化器内科学レビュー Vol. 2022-'23 page： 48 - 53 2022.7

Language：Japanese Publisher：(株)総合医学社

＜最近の動向とガイドライン＞●2000年以降に導入されたカプセル内視鏡とバルーン内視鏡による小腸内視鏡診断の進歩に伴って、小腸腫瘍の内視鏡所見から病態までが明らかにされてきた。2015年には「小腸内視鏡診療ガイドライン」が発表されたことで、一般臨床への導入が進んだ。●小腸内視鏡の導入から20年が経った現在において、インパクトの高い臨床研究は少ないが、ガイドラインに追加、補完できる臨床研究、症例報告を多数認めた。小腸腫瘍の存在について画像診断が単独のモダリティでは困難であることも検討し、小腸腫瘍が疑われた場合は、複数の画像診断によって正確な診断が得られる。●gastrointestinal stromal tumor(GIST)の診断について、内視鏡分類が提案された。GISTは悪性ポテンシャル、消化管出血といったリスクを有するため、今後は治療前に分類化され診療ストラテジーが確立されることを期待する。●内視鏡治療についても新たなアイディアが発表された。Peutz-Jeghers syndrome(PJS)における小腸ポリポーシスに対する内視鏡治療の意義は大きいが、治療時間の長いことや腸穿孔、後出血のリスクを有するためさらに有効な治療法が望まれる。大きなポリープについては基部にクリップを留置するもしくは留置スネアを用いて基部を絞扼する治療が報告された。PJSは術後例が多いので、腹腔鏡によって小腸内視鏡の進行をアシストする報告もあった。(著者抄録)

山村健史, 澤田つな騎, 石川恵里, 前田啓子, 中村正直

日本臨床 Vol. 80 ( 増刊7 小腸疾患 ) page： 305 - 311 2022.7

【転移性消化管腫瘍】転移性小腸腫瘍の画像診断・形態学的特徴

山田健太朗, 山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 飯田忠, 水谷泰之, 山雄健太郎, 石川卓哉, 古川和宏, 大野栄三郎, 川嶋啓揮

胃と腸 Vol. 57 ( 8 ) page： 1018 - 1026 2022.7

Language：Japanese Publisher：(株)医学書院

＜文献概要＞転移性小腸腫瘍は小腸腫瘍の中でもまれな疾患であるが,カプセル内視鏡検査やバルーン内視鏡検査といった小腸内視鏡検査が普及してきたことにより遭遇する機会が増加している.本稿では転移性小腸腫瘍を診断するのに有用な臨床的特徴を病態,検査,転移様式別(脈管性転移,直接浸潤,播種性転移)に,既報と自験例に基づいて概説した.転移性小腸腫瘍はさまざまな形態を呈するため,小腸腫瘍の鑑別疾患として念頭に置き,患者背景と検査所見から総合的に診断していく必要がある.

膵胆道領域のピットフォールと対策膵嚢胞性腫瘍に対するEUS診断 EUS形態診断にて鑑別が困難な病変の特徴

大野栄三郎, 石川卓哉, 植月康太, 山田健太, 八鹿潤, 宜保憲明, 片岡邦夫, 中村正直, 本多隆, 川嶋啓揮

超音波医学 Vol. 49 ( Suppl. ) page： S207 - S207 2022.4

胆膵:超音波像の成り立ちと解釈:病理との対応 IPMNにおける粘液塊の性状と病理像との関連性に関する検討

八鹿潤, 大野栄三郎, 石川卓哉, 植月康太, 山田健太, 宜保憲明, 片岡邦夫, 中村正直, 本多隆, 川嶋啓揮

超音波医学 Vol. 49 ( Suppl. ) page： S218 - S218 2022.4

膵癌診療における超音波の役割～存在・鑑別・進行度・予後診断～膵癌肝転移診断における造影MRIと比較した造影EUS後経腹壁超音波検査の有用性

石川卓哉, 大野栄三郎, 植月康太, 山田健太, 宜保憲明, 本多隆, 中村正直, 石津洋二, 山本健太, 川嶋啓揮

超音波医学 Vol. 49 ( Suppl. ) page： S201 - S201 2022.4

Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis. Reviewed International journal

Maeda Keiko

Biomedicines Vol. 10 ( 4 ) 2022.4

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

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

DOI： 10.3390/biomedicines10040872

Diagnostic performance of endoscopic classifications for neoplastic lesions in patients with ulcerative colitis: A retrospective case-control study. International journal

Yuichi Kida, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yasuyuki Mizutani, Naomi Kakushima, Kazuhiro Furukawa, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Masatoshi Ishigami, Mitsuhiro Fujishiro

World journal of gastroenterology Vol. 28 ( 10 ) page： 1055 - 1066 2022.3

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

BACKGROUND: It is unclear whether the Japan Narrow-Band Imaging Expert Team (JNET) classification and pit pattern classification are applicable for diagnosing neoplastic lesions in patients with ulcerative colitis (UC). AIM: To clarify the diagnostic performance of these classifications for neoplastic lesions in patients with UC. METHODS: This study was conducted as a single-center, retrospective case-control study. Twenty-one lesions in 19 patients with UC-associated neoplasms (UCAN) and 23 lesions in 22 UC patients with sporadic neoplasms (SN), evaluated by magnifying image-enhanced endoscopy, were retrospectively and separately assessed by six endoscopists (three experts, three non-experts), using the JNET and pit pattern classifications. The results were compared with the pathological diagnoses to evaluate the diagnostic performance. Inter- and intra-observer agreements were calculated. RESULTS: In this study, JNET type 2A and pit pattern type III/IV were used as indicators of low-grade dysplasia, JNET type 2B and pit pattern type VI low irregularity were used as indicators of high-grade dysplasia to shallow submucosal invasive carcinoma, JNET type 3 and pit pattern type VI high irregularity/VN were used as indicators of deep submucosal invasive carcinoma. In the UCAN group, JNET type 2A and pit pattern type III/IV had a low positive predictive value (PPV; 50.0% and 40.0%, respectively); however, they had a high negative predictive value (NPV; 94.7% and 100%, respectively). Conversely, in the SN group, JNET type 2A and pit pattern type III/IV had a high PPV (100% for both) but a low NPV (63.6% and 77.8%, respectively). In both groups, JNET type 3 and pit pattern type VI-high irregularity/VN showed high specificity. The inter-observer agreement of JNET classification and pit pattern classification for UCAN among experts were 0.401 and 0.364, in the same manner for SN, 0.666 and 0.597, respectively. The intra-observer agreements of JNET classification and pit pattern classification for UCAN among experts were 0.387, 0.454, for SN, 0.803 and 0.567, respectively. CONCLUSION: The accuracy of endoscopic diagnosis using both classifications was lower for UCAN than for SN. Endoscopic diagnosis of UCAN tended to be underestimated compared with the pathological results.

DOI： 10.3748/wjg.v28.i10.1055

A novel scoring system to predict therapeutic intervention for non-variceal upper gastrointestinal bleeding. International journal

Nobuhito Ito, Kohei Funasaka, Kazuhiro Furukawa, Naomi Kakushima, Takashi Hirose, Koichi Muroi, Tomohiko Suzuki, Takahiro Suzuki, Emiko Hida, Takuya Ishikawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Ryoji Miyahara, Mitsuhiro Fujishiro

Internal and emergency medicine Vol. 17 ( 2 ) page： 423 - 430 2022.3

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

Various scoring systems have been developed to predict the need for endoscopic treatment in patients with non-variceal upper gastrointestinal bleeding (NVUGIB). However, they have rarely been applied in clinical practice because the processes are complicated. The aim of this study was to establish a simple scoring system that predicts the need for endoscopic intervention in patients with NVUGIB. We retrospectively enrolled 509 consecutive patients with suspected NVUGIB who underwent emergency endoscopy. In the development cohort (from January 2016 to December 2018), risk factors that predict the need for endoscopic intervention were determined from 349 patients' data by multivariate logistic regression analysis. This led to the development of a novel scoring system named the Nagoya University score (N score). In the validation cohort (from January 2019 to September 2020), we evaluated the diagnostic value of the N score, the Hirosaki score, and the Glasgow-Blatchford scores (GBS) by receiver operating characteristic (ROC) curves using another 160 patients' data. Multivariate logistic regression analysis revealed syncope, hematemesis, blood urea nitrogen (BUN), and BUN/Cr as significant predictive factors for endoscopic intervention. In the validation study, the N score was superior to the GBS and equal to the Hirosaki score in predicting the endoscopic intervention (AUC, N score 0.776 [95% CI 0.702-0.851] vs. GBS 0.615 [0.523-0.708], Hirosaki 0.719 [0.636-0.803]). The N score revealed a sensitivity of 84.5% and a specificity of 61.8%. Our N score, which is consisted of only four factors, would select patients who require endoscopic intervention with high probability.

DOI： 10.1007/s11739-021-02822-9

炎症性腸疾患の病態からみた診療を考えるクローン病深部小腸狭窄に対する内視鏡的バルーン拡張術における抗体製剤の意義

大宮直木, 中村正直

日本消化器病学会雑誌 Vol. 119 ( 臨増総会 ) page： A111 - A111 2022.3

消化器疾患診療に必要なバイオマーカー開発のための研究潰瘍性大腸炎の内視鏡的活動性と粘膜治癒を反映するバイオマーカーの同定

前田啓子, 中村正直, 石上雅敏

日本消化器病学会雑誌 Vol. 119 ( 臨増総会 ) page： A170 - A170 2022.3

炎症性消化管疾患の最前線 IBD治療と外科・内科のコラボレーションクローン病深部小腸狭窄に対する内視鏡的バルーン拡張術の成績

大宮直木, 中村正直

日本消化管学会雑誌 Vol. 6 ( Suppl. ) page： 106 - 106 2022.1

Comparison of Endoscopic Ultrasonography and Conventional Endoscopy for Prediction of Tumor Depth in Superficial Nonampullary Duodenal Epithelial Tumors. International journal

Noritaka Matsuda, Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

Digestion Vol. 103 ( 4 ) page： 319 - 328 2022

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

BACKGROUND: The utility of endoscopic ultrasonography (EUS) in predicting tumor depth among superficial nonampullary duodenal epithelial tumors (SNADETs) is unclear. The aim was to compare EUS with conventional endoscopy (CE) for the evaluation of tumor invasion of SNADETs. METHODS: A retrospective analysis was performed on consecutive 174 lesions/169 patients with duodenal dysplasia or adenocarcinoma with invasion up to submucosa who underwent both CE and EUS before endoscopic (n = 133) or surgical (n = 41) treatment. Endoscopic staging by CE was performed based on the characteristic endoscopic criteria of submucosal invasion (irregular surface, submucosal tumor [SMT]-like marginal elevation, and fusion of converging folds). The diagnostic performance of each test was compared with the final histology. RESULTS: The sensitivity and accuracy of estimating the depth were higher for CE compared to that of EUS (99.4% vs. 89.4%, p < 0.01 and 97.7% vs. 87.9%, p < 0.01, respectively). Univariate analysis of endoscopic factors revealed that tumor diameter, red color, SMT-like appearance, and hypoechogenicity were factors related to advanced histology. Multivariate analysis revealed that the presence of SMT-like appearance based on CE was an independent factor to predict submucosal invasion (p = 0.025). Gross morphology of the combined type was associated to incorrect diagnosis of EUS (p = 0.007). Among 3 cases in which EUS overestimated the tumor depth, carcinoma extension in submucosal Brunner's gland or nontumorous submucosal cystic dilation was observed. CONCLUSION: EUS may not be necessary, and CE may be sufficient for determining the optimal therapeutic strategy for SNADETs.

DOI： 10.1159/000524841