Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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ESDにおける新型デバイス(ISSEN)の使用経験

吉井新二, 瀧澤歩, 大和田紗恵, 山川司, 風間友江, 平山大輔, 能正勝彦, 山野泰穂, 仲瀬裕志

日本大腸肛門病学会雑誌 ( (一社)日本大腸肛門病学会 ) 74 ( 3 ) 197 - 197 2021.03

メサラジン製剤の効果が示唆された放射線性直腸炎の1例

平山大輔, 瀧澤歩, 大和田紗恵, 山川司, 風間友江, 吉井新二, 山野泰穂, 仲瀬裕志

日本大腸肛門病学会雑誌 ( (一社)日本大腸肛門病学会 ) 74 ( 3 ) 190 - 191 2021.03

胆膵癌でのMSI検査におけるEUS-FNA検体の検討

川上裕次郎, 本谷雅代, 平野雄大, 我妻康平, 沼田泰尚, 石上敬介, 柾木喜晴, 室田文子, 阿久津典之, 佐々木茂, 杉田真太朗, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 128回・122回 72 - 72 2021.03

異所性再燃で診断されたIgG4関連胆嚢炎の2例

高田夢実, 川上裕次郎, 平野雄大, 我妻康平, 沼田泰尚, 石上敬介, 柾木喜晴, 室田文子, 阿久津典之, 本谷雅代, 佐々木茂, 木村康利, 高橋裕樹, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 128回・122回 55 - 55 2021.03

Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.

Toshihiro Kita, Sinya Ashizuka, Naoki Ohmiya, Takayuki Yamamoto, Takanori Kanai, Satoshi Motoya, Fumihito Hirai, Hiroshi Nakase, Tomohiko Moriyama, Masanao Nakamura, Yasuo Suzuki, Shuji Kanmura, Taku Kobayashi, Hidehisa Ohi, Ryoichi Nozaki, Keiichi Mitsuyama, Shojiro Yamamoto, Haruhiko Inatsu, Koji Watanabe, Toshifumi Hibi, Kazuo Kitamura

Journal of gastroenterology 56 ( 2 ) 147 - 157 2021.02 [Domestic journal]

BACKGROUND: Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC. METHODS: This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0. RESULTS: No differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (- 9.3 ± 1.2 vs. - 3.0 ± 2.8, P = 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%, P = 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM. CONCLUSIONS: In this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM. CLINICAL TRIAL REGISTRY: JAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp .

DOI PubMed

Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis.

Kazuya Ishiguro, Hiroshi Kitajima, Takeshi Niinuma, Reo Maruyama, Naotaka Nishiyama, Hitoshi Ohtani, Gota Sudo, Mutsumi Toyota, Hajime Sasaki, Eiichiro Yamamoto, Masahiro Kai, Hiroshi Nakase, Hiromu Suzuki

Cell death discovery 7 ( 1 ) 7 - 7 2021.01 [International journal]

Epigenetic mechanisms such as histone modification play key roles in the pathogenesis of multiple myeloma (MM). We previously showed that EZH2, a histone H3 lysine 27 (H3K27) methyltransferase, and G9, a H3K9 methyltransferase, are potential therapeutic targets in MM. Moreover, recent studies suggest EZH2 and G9a cooperate to regulate gene expression. We therefore evaluated the antitumor effect of dual EZH2 and G9a inhibition in MM. A combination of an EZH2 inhibitor and a G9a inhibitor strongly suppressed MM cell proliferation in vitro by inducing cell cycle arrest and apoptosis. Dual EZH2/G9a inhibition also suppressed xenograft formation by MM cells in vivo. In datasets from the Gene Expression Omnibus, higher EZH2 and EHMT2 (encoding G9a) expression was significantly associated with poorer prognoses in MM patients. Microarray analysis revealed that EZH2/G9a inhibition significantly upregulated interferon (IFN)-stimulated genes and suppressed IRF4-MYC axis genes in MM cells. Notably, dual EZH2/G9a inhibition reduced H3K27/H3K9 methylation levels in MM cells and increased expression of endogenous retrovirus (ERV) genes, which suggests that activation of ERV genes may induce the IFN response. These results suggest that dual targeting of EZH2 and G9a may be an effective therapeutic strategy for MM.

DOI PubMed

COVID-19パンデミック状況下における適切なIBD診療の実践を目指して JAPAN IBD COVID-19 TASKFORCEからの提言と取り組み

松浦稔, 仲瀬裕志, 松本主之, 飯島英樹, 松岡克善, 大宮直木, 石原俊治, 平井郁仁, 久松理一

日本消化管学会雑誌 ( (一社)日本消化管学会 ) 5 ( Suppl. ) 124 - 124 2021.01

Idiopathic retroperitoneal fibrosis diagnosed by endoscopic ultrasonography-guided fine-needle biopsy.

Yujiro Kawakami, Yumemi Takada, Keisuke Ishigami, Takehiro Hirano, Kohei Wagatsuma, Yoshiharu Masaki, Ayako Murota, Masayo Motoya, Mitsuhiro Tsujiwaki, Hiroki Takahashi, Hiroshi Nakase

JGH open : an open access journal of gastroenterology and hepatology 5 ( 1 ) 151 - 152 2021.01 [International journal]

DOI PubMed

Expert Opinions on the Current Therapeutic Management of Inflammatory Bowel Disease during the COVID-19 Pandemic: Japan IBD COVID-19 Taskforce, Intractable Diseases, the Health and Labor Sciences Research.

Hiroshi Nakase, Takayuki Matsumoto, Minoru Matsuura, Hideki Iijima, Katsuyoshi Matsuoka, Naoki Ohmiya, Shunji Ishihara, Fumihito Hirai, Kouhei Wagatsuma, Yoshihiro Yokoyama, Tadakazu Hisamatsu

Digestion 102 ( 5 ) 814 - 822 2021 [International journal]

BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a dramatic challenge for all healthcare systems worldwide. This outbreak immediately affected gastroenterologists as well as global physicians worldwide because COVID-19 can be associated with not only triggering respiratory inflammation but also gastrointestinal (GI) inflammation based on the mechanism by which SARS-CoV-2 enters cells via its receptor the angiotensin-converting enzyme 2, which is expressed on GI cells. However, the comorbidity spectrum of digestive system in patients with COVID-19 remains unknown. Because the inflammatory bowel disease (IBD) management involves treating uncontrolled inflammation with immune-based therapies, physicians, and patients have great concern about whether IBD patients are more susceptible to SARS-CoV-2 infection and have worsened disease courses. SUMMARY: It is necessary to precisely ascertain the risk of SARS-CoV-2 infection and the COVID-19 severity in IBD patients and to acknowledge the IBD management during the COVID-19 pandemic with clinically reliable information from COVID-19 cohorts and IBD experts' opinions. In this review, we highlight clinical questions regarding IBD management during the COVID-19 pandemic and make comments corresponding to each question based on recent publications. Key Messages: We propose that there is (1) no evidence that IBD itself increases the risk of SARS-CoV-2 infection, (2) to basically prioritize the control of disease activity of IBD, (3) no need for physicians to suddenly discontinue immunomodulatory or biologic therapy in patients with quiescent IBD, and (4) a need for careful observation of elderly (>60 years old) and IBD patients receiving corticosteroid treatment during the COVID-19 pandemic.

DOI PubMed

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

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 (Australia) 36 ( 7 ) 1744 - 1753 2021

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 PubMed

[A case of mediastinal pancreatic pseudocyst diagnosed and treated successfully by endoscopic procedure].

Tomoya Nakamura, Yoshiharu Masaki, Yujiro Kawakami, Keisuke Ishigami, Ayako Murota, Masayo Motoya, Hiroshi Nakase

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 118 ( 6 ) 578 - 585 2021 [Domestic journal]

A 60-year-old man was admitted for investigation of a mediastinal cystic lesion. During endoscopic retrograde pancreatography, the contrast medium leaked from the head of the main pancreatic duct, and the cystic fluid collected with endoscopic ultrasonography (EUS) -guided aspiration showed high levels of pancreatic enzymes. Therefore, we diagnosed mediastinal pancreatic pseudocyst. The pseudocyst shrank as a result of EUS-guided drainage, and an endoscopic nasopancreatic drainage tube was then placed to close the fistula of the pancreatic duct. This case suggests that endoscopic procedures could be useful for the diagnosis and treatment of mediastinal pancreatic pseudocyst. We review 48 case reports of mediastinal pancreatic pseudocyst and discuss the usefulness of endoscopic procedures for diagnosis and treatment.

DOI PubMed

A case of hepatitis b virus and hepatitis c virus co-infection that achieved sustained virological response 12 following treatment with glecaprevir hydrate/pibrentasvir for 3 days

Yasunao Numata, Shigeru Sasaki, Noriyuki Akutsu, Takehiro Hirano, Kohei Wagatsuma, Yujiro Kawakami, Keisuke Ishigami, Hiroshi Nakase

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 62 ( 9 ) 578 - 584 2021

An 82-year-old female patient who was co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) was regularly followed at our institution. The patient was taking clarithromycin because of comorbid nontuberculous mycobacteriosis (NTM) lung disease. Since chronic liver damage has possibly progressed, the patient was treated with direct-acting antiviral (DAA). Soon after taking DAA, severe pruritus appeared, and the patient stopped it in 3 days. However, HCV RNA level decreased to an undetectable level 2 weeks after the start of the treatment and achieved sustained virological response (SVR) 12. Two factors were considered for the success of DAA treatment in a short period in this case. One factor was that the immune response for HCV elimination was easily generated due to the patient’s high immunological activity caused by the effects of co-existing NTM lung disease and co-infection with HBV. The other reason is that the blood level of DAA was high because of the concomitant drug.

DOI

【大腸鋸歯状病変の新展開】分類不能鋸歯状病変を由来としたTraditional serrated adenomaの癌化症例

山川司, 吉井新二, 市原真, 大和田紗恵, 柴田泰洋, 風間友江, 平山大輔, 久保俊之, 能正勝彦, 須藤豪太, 山本英一郎, 鈴木拓, 山野泰穂, 仲瀬裕志

胃と腸 ( (株)医学書院 ) 55 ( 13 ) 1631 - 1638 2020.12

＜文献概要＞患者は40歳代,女性.血便を主訴に近医を受診し,下部消化管内視鏡検査にて上部直腸(Ra)に径約35mmのLST-GMを認めた.本病変は辺縁に平坦部分を伴い複数の分葉構造を呈し,拡大所見では平坦部分は鋸歯状構造を伴ったII型様pitで構成されていたが,既存の分類には合致しない鋸歯状病変と考えられた.病変の大部分を占める中心の隆起部ではIV型pitを主体としcytological dysplasiaを疑った.病理組織像では平坦部の表層部分にわずかに鋸歯状構造は認めるが,深部はうねった管状腺管で腺腫様であり,免疫染色Ki-67では陽性細胞が散在し腺腫や既存の鋸歯状病変にも当てはまらない組織像であった.一方,隆起部では鋸歯状変化を呈するTSA様の領域と,絨毛状の形態をとりtubulovillous adenomaと考えられる領域が混在していた.また,隆起部の粘膜深部に細胞異型,構造異型が強く,腺管が密に増殖した領域があり,同部位でp53,Ki-67がびまん性の陽性を示しtub1相当の腺癌(Tis)と診断した.遺伝子解析では平坦部,隆起部いずれもKRAS変異陽性(G13D)で一連の病変と考えられた.本症例は内視鏡所見や免疫染色,遺伝子解析結果から既存の分類に当てはまらない鋸歯状病変を基盤として発育進展した病変と考え,ここに報告する.

Successful treatment with endoscopic transpapillary drainage for gallbladder perforation associated with steroid treatment for interstitial pneumonia (with video).

Yujiro Kawakami, Kazuya Suzuki, Masakazu Akahonai, Takakazu Miyake, Masahiro Taniguchi, Hiroshi Nakase

JGH open : an open access journal of gastroenterology and hepatology 4 ( 6 ) 1233 - 1235 2020.12 [International journal]

This case report highlights the clinical efficacy of endoscopic transpapillary drainage for gallbladder perforation in a high-risk surgical patient with a history of steroid treatment for interstitial pneumonia. The usefulness of endoscopic transpapillary gallbladder drainage in high-risk surgical patients with acute cholecystitis has not been established. In difficult cases of emergent surgery, such as described here, endoscopic transpapillary drainage is a promising method to manage gallbladder perforation and acute cholecystitis recurrence.

DOI PubMed

Autophagy and Autophagy-Related Diseases: A Review.

Tadashi Ichimiya, Tsukasa Yamakawa, Takehiro Hirano, Yoshihiro Yokoyama, Yuki Hayashi, Daisuke Hirayama, Kohei Wagatsuma, Takao Itoi, Hiroshi Nakase

International journal of molecular sciences 21 ( 23 ) 2020.11 [International journal]

Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.

DOI PubMed

Haemorrhagic exfoliative oesophagitis associated with nasogastric tube placement.

Gota Sudo, Akira Goto, Takashi Fujisawa, Hiroshi Nakase

BMJ case reports 13 ( 11 ) 2020.11 [International journal]

A 92-year-old man hospitalised for cerebral infarction developed haematemesis. The patient was taking low-dose aspirin and apixaban for his cerebral infarction and non-valvular atrial fibrillation. His enteral nutrition was administrated through nasogastric tube. Upper endoscopy revealed active bleeding from a protruded lesion in the upper oesophagus. The lesion was removed by washing with a water jet, followed by successful endoscopic haemostasis. Histopathological examination revealed degenerated squamous epithelium without specific findings; the diagnosis was exfoliative oesophagitis. In our case, mechanical mucosal injury caused by nasogastric tube placement may result in exfoliative oesophagitis. In addition, the use of low-dose aspirin with apixaban may have contributed to the bleeding. We then performed a wire-guided nasogastric tube placement under fluoroscopy. No further bleeding was observed, but the patient died of sepsis 1 month later. This case highlights the importance of a risk assessment and management of oesophageal complications associated with nasogastric tube placement.

DOI PubMed

【拡大内視鏡を極める】拡大・超拡大内視鏡診断を極める Pit pattern診断を極める

山野泰穂, 吉井新二, 久保俊之, 柴田泰洋, 齋藤潤信, 松下弘雄, 吉川健二郎, 仲瀬裕志

Intestine ( (株)日本メディカルセンター ) 24 ( 4 ) 337 - 346 2020.11

＜文献概要＞拡大内視鏡,pit pattern診断は近年における内視鏡診断学を大きく発展させた.pit pattern診断は一般的になりつつあるが,単純な分類型に当てはめる診断法では通用しない.その理由はpit pattern分類は大腸上皮性腫瘍性病変(腺腫,癌)において成立しており,それ以外の病変まで網羅していないこと,腺腫・癌においてもpit patternには亜型が存在すること,病理学の概念が変わることで対応しきれないことなどが挙げられる.しかし拡大内視鏡における観察の仕方,pit patternの理論や病態が拡大所見へ及ぼす影響などを理解することで極めることができると考える.

Long-term clinical effectiveness of ustekinumab in patients with Crohn’s disease: A retrospective cohort study

Takahiro Ito, Atsuo Maemoto, Takehiko Katsurada, Hiroki Tanaka, Satoshi Motoya, Nobuhiro Ueno, Mikihiro Fujiya, Toshifumi Ashida, Daisuke Hirayama, Hiroshi Nakase

Crohn's and Colitis 360 2 ( 4 ) 1 - 9 2020.10

Background: This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn’s disease (CD) patients. Methods: A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents. Results: The clinical remission rate at week 52 was 32.4% in moderate to severely active CD patients. The achievement of clinical remission for 8 weeks after ustekinumab therapy induction was associated with clinical remission at week 52. Ustekinumab persistence rate at week 104 was 81.4%. Conclusion: Ustekinumab is effective and persistent in CD patients with the previous treatment history of several biologics.

DOI

Exploratory study of the effectiveness of granulocyte and monocyte adsorptive apheresis before initiation of steroids in patients with active ulcerative colitis (EXPECT study): A multicenter prospective clinical trial

Kazuki Kakimoto, Minoru Matsuura, Takumi Fukuchi, Hitoshi Hongo, Tsuguhiro Kimura, Nobuo Aoyama, Yorihide Okuda, Kazuki Aomatsu, Noriko Kamata, Yoko Yokoyama, Chiemi Mizuno, Takuya Inoue, Takako Miyazaki, Shiro Nakamura, Kazuhide Higuchi, Hiroshi Nakase

Crohn's and Colitis 360 ( Oxford University Press ) 2 ( 4 ) 2020.10

Background: Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods: We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results: The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions: GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

DOI

術後再発し、進展が早かった肝内胆管粘液癌における遺伝子異常

柾木喜晴, 足立靖, 石上敬介, 室田文子, 阿久津典之, 久保俊之, 岩田徳和, 本谷雅代, 佐々木茂, 遠藤高夫, 石井良文, 佐々木泰史, 仲瀬裕志

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 58回 O23 - 3 2020.10

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Papers - NAKASE Hiroshi