Faculty Profiles - NAKAMURA, Masanao

内視鏡的小腸カプセル内視鏡 (CE) 留置術の安全性・有効性に関する全国多施設共同研究

大宮直木, 岡志郎, 中山佳子, 岩間達, 中村正直, 田中信治

日本小腸学会学術集会プログラム・抄録集 Vol. 5 ( 0 ) page： 48 - 48 2021

Language：Japanese Publisher：日本小腸学会

【目的】今回、小児・成人例におけるCE挿入補助器具の使用実態について調査し、その有効性および安全性を遡及的に多施設共同で検討した。【方法】REDCap®を用いて、１．CE検査数、２．CE内服不可または不可と予測された件数、３．内服不可（予測含む）および挿入補助具使用の内訳：性別、年齢、身長、体重、検査契機、病名、既往歴、CE嚥下可能・不可・不可（予測）、嚥下不可（予測含む）であった理由、補助具種類、カプセル留置部位、有害事象、全小腸観察の有無をオンライン登録した。【結果】全国20施設（消化器内科11施設、小児科9施設）で施行されたCE 10,156件のうち、内視鏡的留置術を行ったCEは546件(5.4%)。有害事象は治療不要な出血、粘膜損傷等の軽微なもののみで163件（29.9％）。十二指腸または空腸へのCE留置成功率は16歳未満で92.0% (335/364)、16歳以上で92.3% (168/182) と有意差なかったが、全小腸観察率は16歳未満で91.7%、16歳以上で76.2%と有意差あり（P<0.0001）。16歳以上でCE嚥下不可能の全小腸観察率は87.3%、胃内停滞例の全小腸観察率は64.2%と有意に低下していた（P=0.0010）。CEの食道停滞例は28例（5.1％）で、28.6％が心疾患、胃停滞例は69例（12.6％）で、糖尿病（15.7％）、腹部術後（15.7％) 等の基礎疾患。16歳未満のCE嚥下不可能（予測も含む）を推測するカットオフ値は身長132cm、体重24.8kg、年齢9歳2ヶ月。【結語】小児・成人に対する内視鏡的経口ＣＥ留置術は安全かつ有用な手技であるが、食道・胃停滞例では蠕動を促す他の処置も必要である。

DOI： 10.32264/shocho.5.0_48

炎症性腸疾患に対するインフラマソーム標的治療法の開発

池上脩二, 前田啓子, 中村正直

日本小腸学会学術集会プログラム・抄録集 Vol. 5 ( 0 ) page： 51 - 51 2021

Language：Japanese Publisher：日本小腸学会

【背景と目的】近年, 炎症性腸疾患（IBD）患者の急増とともに, 治療抵抗性の難治例が増加し, 病態に応じた新規治療薬開発が課題となっている．その病態には粘膜免疫の破綻，腸内細菌の関与とともに，両者を制御するインフラマソーム経路の重要性が認識されている．私達は, 治療抵抗性のIBD患者の血液, 腸管組織においてインフラマソーム関連サイトカインであるインターロイキン18（IL-18）の発現の上昇を見出した．本研究の目的は, 難治性IBDへの治療応用を見据え, 抗ヒト活性型IL-18モノクローナル抗体を作成し, IBDモデルマウスを用いて腸炎抑制効果, 作用機序の解明を行うことである．【方法】ヒトIL-18プロ体をカスパーゼで切断し活性型IL-18を作製し，ヒト活性型IL-18に対するモノクローナル抗体を樹立した．構造解析，機能阻害アッセイを行い, 阻害効果を持つ抗体を選別した．DSS誘導性腸炎モデルマウスを作成し, 抗IL-18抗体の腹腔内投与を行い, 腸炎スコア, 体重減少率を評価した．病理学的評価, 炎症性サイトカインの発現, FITC-Dextranの透過量の測定, NGSによる腸内細菌叢の解析を行った．【結果】高い親和性でIL-18と結合し, IL-18が誘導するIFN-γ産生を強力に抑制する抗ヒト活性型IL-18抗体の作成に成功した．抗体投与により腸炎の改善を認め, IFN-γ, TNF-αの発現抑制, FITC-Dextranの透過量の低下, 腸炎により増加したEnterococcus属, Staphylococcus属の低下を認めた. 更に抗TNF-α抗体との併用ではより強力に腸炎を抑制した．【結論】抗IL-18抗体は, 炎症性サイトカインの分泌抑制に加え, 腸内細菌叢の制御，腸管上皮透過性亢進の改善を介して腸炎を改善させた. 既存治療薬との併用により腸炎抑制効果の増強が認められ，難治例への治療応用が期待される．

DOI： 10.32264/shocho.5.0_51

A novel Lugol's iodine staining technique to visualize the upper margin of the surgical anal canal intraoperatively for Hirschsprung disease: a case series

Yokota Kazuki, Amano Hizuru, Kudo Toyoki, Yamamura Takeshi, Tanaka Yujiro, Tainaka Takahisa, Shirota Chiyoe, Sumida Wataru, Makita Satoshi, Takimoto Aitaro, Nakamura Masanao, Fujishiro Mitsuhiro, Hinoki Akinari, Uchida Hiroo

BMC SURGERY Vol. 20 ( 1 ) page： 317 2020.12

Language：English Publisher：BMC Surgery

Background: In cases of Hirschsprung disease, complete and reproducible resection of the aganglionic bowel is ideal to achieve good postoperative bowel function. Reliable identification of the upper margin of the surgical anal canal, which is the squamous-columnar junction, is necessary during transanal pull-through. Here, we describe a novel staining technique using Lugol’s iodine stain to visualize the upper margin of the surgical anal canal. Methods: Lugol’s iodine staining was performed in five patients with Hirschsprung disease treated using a single-stage laparoscopic transanal pull-through modified Swenson procedure. In two of these patients, endocytoscopic observation with ultra-high magnification was performed using methylene blue and crystal violet to mark the border of the squamous epithelium at 1 week before surgery. The alignment between the incisional line, which was revealed using Lugol’s iodine staining and endocytoscopic marking, was evaluated. Complications, including postoperative bowel dysfunction, were evaluated. Results: In all cases, Lugol’s iodine staining produced a well-demarcated line. The endocytoscopic marking of the upper margin of the surgical anal canal was aligned with the line revealed by Lugol’s iodine staining. There were no complications associated with the transanal pull-through procedure, including postoperative bowel dysfunction. Conclusions: Lugol’s iodine staining could be a safe and practical method to visualize the upper margin of the surgical anal canal intraoperatively. This finding may be useful for surgeons to make a consistent removal of the aganglionic bowel during surgery for Hirschsprung disease.

DOI： 10.1186/s12893-020-00986-3

Glycoproteomic analysis identifies cryptdin-related sequence 1 as O-glycosylated protein modified with α1,2-fucose in the small intestine

Hashiguchi Hiroki, Tsukamoto Yohei, Ogawa Mitsutaka, Tashima Yuko, Takeuchi Hideyuki, Nakamura Masanao, Kawashima Hiroki, Fujishiro Mitsuhiro, Okajima Tetsuya

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 695 page： 108653 2020.11

Language：English Publisher：Archives of Biochemistry and Biophysics

The modification of galactose with α1,2-fucose is involved in symbiosis with intestinal bacteria and elimination of pathogenic bacteria. It is postulated that α1,2-fucosylated mucin secreted from goblet cells is involved in defending an organism against infections, but the detailed molecular mechanisms are yet to be elucidated. It was previously reported that Paneth cells of the small intestine were positive for UEA-1 lectin staining. However, glycoproteins in Paneth cells carrying α1,2-fucose have not yet been identified. Glycoproteomic analysis of ileal lysates identified 3212 O-linked and 2962 N-linked glycopeptides. In particular, cryptdin-related sequence 1 (CRS1) expressed in Paneth cells was found to be α1,2-fucosylated. Unlike other antimicrobial α-defensin proteins, CRS1 contains unique Thr residues, which are modified with O-glycans, with 3HexNAc2Hex1Fuc1NeuAc being the main glycoform. Identification of α1,2-fucose on the O-glycans of CRS1 expressed in Paneth cells will pave the way for a mechanistic understanding of α1,2-fucose-dependent symbiosis with intestinal bacteria and elimination of pathogenic bacteria in the intestine.

DOI： 10.1016/j.abb.2020.108653

Accuracy of carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography using double-balloon endoscopy. International journal

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

World journal of gastroenterology Vol. 26 ( 42 ) page： 6669 - 6678 2020.11

Language：English Publishing type：Research paper (scientific journal) Publisher：World Journal of Gastroenterology

BACKGROUND Retrograde cholangiopancreatography using double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable technique to treat biliary stone and jejunobiliary anastomotic stenosis in patients with altered gastrointestinal anatomy. The accurate selection of the route at the anastomosis branch is one of the most important factors in reaching the target in a timely manner. AIM To determine the accuracy of carbon dioxide insufflation enterography (CDE) at the branch for selecting the correct route during DBERC. METHODS We enrolled 52 consecutive patients scheduled for DBERC at our institution from June 2015 to November 2017. Route selection via two methods (visual observation and CDE) was performed in each patient. We determined the correct rate of route selection using CDE. RESULTS Thirty-three patients had a jejunojejunal anastomosis and 19 patients had a gastrojejunal anastomosis. The therapeutic target region was reached in 50 patients. The mean procedure times from the teeth to the target (total insertion time), from the teeth to the branch, and from the branch to the target, and the mean total examination time were 15.2, 5.0, 8.2, and 60.3 min, respectively. The rate of correct route selection using visual observation and CDE were 36/52 (69.2%) and 48/52 (92.3%), respectively (P = 0.002). The rate of correct route selection using CDE in patients with a jejunojejunal anastomosis was 29/33 (87.8%), and the rate in patients with a gastrojejunal anastomosis was 19/19 (100%). CONCLUSION CDE is helpful in selecting the route at the branch in the anastomosis for more timely access to the target in patients with altered gastrointestinal anatomy undergoing DBERC.

DOI： 10.3748/wjg.v26.i42.6669

特集ガイドラインには書いていない-胃癌治療のCQ -ESD後の追加胃切除の真の適応-消化器内科医はどのような場合に心から追加胃切除を勧めるか?

特集除菌後時代を迎えた胃癌診療　-残された課題を巡って 1 .除菌後胃癌を巡る課題(3)除菌後胃癌の診断を巡って　e.除菌後胃癌-診断困難例を巡って　② 除菌による側方進展への影響

伊藤信仁, 舩坂好平, 古川和宏, 角嶋直美, 中村正直, 藤城光弘

臨床消化器内科 Vol. 35 ( 12 ) page： 1459 - 1464 2020.10

伊藤信仁, 古川和宏, 角嶋直美, 柴田寛幸, 平井恵子, 飛田恵美子, 鈴木孝弘, 鈴木智彦, 室井航一, 廣瀨崇, 和田啓孝, 古根聡, 中村正直, 藤城光弘

臨床外科 Vol. 75 ( 10 ) page： 1147 - 1151 2020.10

特集食道胃接合部癌update III. 治療 1.食道胃接合部癌の内視鏡治療適応と根治基準

鈴木孝弘, 古川和宏, 角嶋直美, 古根聡, 伊藤信仁, 和田啓孝, 廣瀬崇, 室井航一, 鈴木智彦, 飛田恵美子, 平井恵子, 柴田寛幸, 中村正直, 藤城光弘

外科 Vol. 82 ( 11 ) page： 1120 - 1123 2020.10

特集 ESDアフターケアが一番大事! [胃　中長期のマネージメント]治癒切除後のサーベイランス

廣瀬崇, 古川和宏, 角嶋直美, 中村正直, 藤城光弘

消化器内視鏡 Vol. 32 ( 9 ) page： 1320 - 1324 2020.9

Monitoring for Disease Activity Using Fecal Markers in Quiescent Patients with Inflammatory Bowel Disease

平岡佐規子, 安富絵里子, 岡昌平, 井口俊博, 高原政宏, 岡田裕之

臨床消化器内科 Vol. 35 ( 10 ) page： 1275 - 1279 2020.8

特集クローン病小腸狭窄病変に対する内視鏡的バルーン拡張術─基本からピットフォールまで Ⅱ.クローン病小腸狭窄病変に対するバルーン拡張術(4)クローン病におけるバルーン拡張術のコツ　a.ダブルバルーン内視鏡の立場から

中村正直, 山村健史, 前田啓子, 澤田つな騎, 水谷泰之, 石川恵里, 古川和宏, 角嶋　直美, 藤城光弘

INTESTINE Vol. 24 ( 3 ) page： 197 - 202 2020.8

Monitoring for Disease Activity Using Fecal Markers in Quiescent Patients with Inflammatory Bowel Disease

平岡佐規子, 安富絵里子, 岡昌平, 井口俊博, 高原政宏, 岡田裕之

臨床消化器内科 Vol. 35 ( 10 ) page： 1267 - 1273 2020.8

特集薬剤性消化器疾患の診療 4 .その他の薬剤性消化器疾患(4)免疫チェックポイント阻害薬による消化器障害

伊藤隆徳, 澤田つな騎, 中村正直, 本多隆, 石上雅敏, 藤城光弘

臨床消化器内科 Vol. 35 ( 7 ) page： 759 - 765 2020.6

TOPICS 文献紹介〈炎症関連＊〉クローン病診断に有用なカプセル内視鏡所見に関する検討─本邦多施設症例対照研究〔Review from ─ J Gastroenterol　2019;54:249-260〕

江﨑幹宏, 松本主之, 大宮直木, 鷲尾恵万, 森下寿文, 坂本圭, 安倍弘生, 山本章二朗, 金城徹, 冨樫一智, 渡辺憲治, 平井郁仁, 中村正直, 能田貞治, 芦塚伸也, 大森鉄平, 河内修司, 梁井俊一, 冬野雄太, 平野敦士, 梅野淳嗣, 北園孝成, 金城福則, 渡辺守, 松井敏幸, 鈴木康夫

INTESTINE Vol. 24 ( 2 ) page： 157 - 159 2020.6

連載手技の解説 Sit‒stand endoscopic workstation-人間工学から考える内視鏡

松崎一平, 服部昌志, 山本孔次郎, 榎原毅, 中村正直, 藤城光弘

臨床消化器内科 Vol. 35 ( 6 ) page： 661 - 666 2020.5

Nonexposed wall-inversion surgery as a novel local resection method for neoplasms in the gastrointestinal tract

Fujishiro Mitsuhiro, Furukawa Kazuhiro, Yamamura Takeshi, Nakamura Masanao, Honda Takashi, Maeda Osamu, Ishigami Masatoshi, Kawashima Hiroki

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 82 ( 2 ) page： 175 - 182 2020.5

Language：English Publisher：Nagoya Journal of Medical Science

Nonexposed wall-inversion surgery was invented for the treatment of node-negative gastrointestinal tumors that are difficult to be resected using the endoluminal approach alone. The advantages of this surgery include 1. full-thickness resection procedure of gastrointestinal wall with minimum necessary tumor-negative margins and 2. less risk of bacterial contamination and tumor seeding into the abdominal cavity. We conducted a PubMed search to select relevant articles published until the end of October 2019 for pooled case analyses using the keyword "nonexposed wall-inversion surgery, " Based on our search, we enrolled the data of 88 gastric lesions and 1 duodenal lesion retrieved from 7 case report articles and 4 original articles of clinical cases. The gastric lesions consisted of 59 gastrointestinal stromal tumors, 7 ectopic pancreases, 5 leiomyomas, 3 early gastric cancers, and 14 others, with a mean maximal tumor diameter of 25.0 mm. In 5 lesions (5.7%), intraoperative perforation was performed, and 2 lesions (2.3%) were retrieved by the transabdominal route. All 4 major postoperative complications (4.5%) were managed without resurgical interventions. The duodenal case, neuroendocrine tumor, measuring 13 mm in size, was curatively resected without complications. Nonexposed wall-inversion surgery appears to be an acceptable treatment for node-negative gastric and duodenal tumors; however, further accumulation of cases is necessary to confirm the feasibility.

DOI： 10.18999/nagjms.82.2.175

An International Study on the Diagnostic Accuracy of the Japan Narrow-Band Imaging Expert Team Classification for Colorectal Polyps Observed with Blue Laser Imaging

Suzuki Hiroto, Yamamura Takeshi, Nakamura Masanao, Hsu Chen-Ming, Su Ming-Yao, Chen Tsung-Hsing, Chiu Cheng-Tang, Hirooka Yoshiki, Goto Hidemi

DIGESTION Vol. 101 ( 3 ) page： 339 - 346 2020.5

Language：English Publisher：Digestion

Background: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. Methods: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. Results: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). Conclusions: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.

DOI： 10.1159/000499856

特集ここまで明らかになった小腸疾患小腸の各疾患　血管性病変

澤田つな騎, 中村正直, 藤城光弘

診断と治療 Vol. 108 ( 1 ) page： 67 - 72 2020.1

COMPARISON OF 8- AND 10-MM DIAMETER FULLY COVERED SELFEXPANDABLE METAL STENTS: A MULTICENTER PROSPECTIVE STUDY IN PATIENTS WITH DISTAL MALIGNANT BILIARY OBSTRUCTION

KAWASHIMA Hiroki, HASHIMOTO Senju, OHNO Eizaburo, ISHIKAWA Takuya, MORISHIMA Tomomasa, MATSUBARA Hiroshi, SUGIMOTO Hiroyuki, NONOGAKI Koji, KANAMORI Akira, HARA Kazuo, KUWAHARA Takamichi, NAKAMURA Masanao, MIYAHARA Ryoji, ISHIGAMI Masatoshi, ANDO Masahiko, HIROOKA Yoshiki, The Nagoya Biliary Stent Study(NABIS) -01 Group.

GASTROENTEROLOGICAL ENDOSCOPY Vol. 62 ( 5 ) page： 593 - 603 2020

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

Objectives: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self-expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8- and 10- mm diameter FCSEMS.Methods: Eighteen tertiary-care centers participated in the study. Patients were allocated to the 8- and 10-mm diameter groups. TRBO, non-inferiority of the 8-mm FCSEMS, overall survival time, frequency and type of adverse events, and nonrecurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups.Results: Median TRBO did not differ significantly between the 8-mm (n=102) and 10-mm (n=100) groups (275 vs 293 days, P=0.971). The hazard ratio of the 8- to 10-mm groups was 0.90 (80% confidence interval, 0.77-1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8-mm diameter stent was determined to be non-inferior to the 10-mm diameter stent. Survival time, incidence of adverse events and non-RBO rate at the time of death did not differ significantly between the two groups.Conclusions: Time to RBO with an 8-mm diameter FCSEMS was non-inferior to that with a 10-mm diameter FCSEMS. This finding is important for development of future SEMS.

DOI： 10.11280/gee.62.593