Papers - MIHARA Hiroshi

消化器における神経内分泌癌の治療法及び治療成績の現状

塚田 健一郎, 安藤 孝将, 細川 歩, 吉田 啓紀, 植田 亮, 三原 弘, 梶浦 新也, 藤浪 斗, 西川 潤, 小川 浩平, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  111 ( 臨増大会 ) A972 - A972  2014.09

切除不能進行・再発胃癌に対する化学療法中に発症した消化管合併症の検討

元尾 伊織, 細川 歩, 安藤 孝将, 吉田 啓紀, 南條 宗八, 植田 亮, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  111 ( 臨増大会 ) A866 - A866  2014.09

Role of transient receptor potential vanilloid 4 activation in indomethacin-induced intestinal damage

Hidemoto Yamawaki, Hiroshi Mihara, Nobuhiro Suzuki, Hirofumi Nishizono, Kunitoshi Uchida, Shiro Watanabe, Makoto Tominaga, Toshiro Sugiyama

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY ( AMER PHYSIOLOGICAL SOC )  307 ( 1 ) G33 - G40  2014.07  [Refereed]

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Gastrointestinal ulcers and bleeding are serious complications of nonsteroidal anti-inflammatory drug (NSAID) use. Although administration of antibiotics and Toll-like receptor 4 knockdown mitigate NSAID-induced enteropathy, the molecular mechanism of these effects is poorly understood. Intestinal hyperpermeability is speculated to trigger the initial damage due to NSAID use. Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel expressed throughout the gastrointestinal tract epithelium that is activated by temperature, extension, and chemicals such as 5,6-epoxyeicosatrienoic acid (5,6-EET). The aim of this study was to investigate the possible role of TRPV4 in NSAID-induced intestinal damage. TRPV4 mRNA and protein expression was confirmed by RT-PCR and immunochemistry, respectively, in mouse and human tissues while TRPV4 channel activity of the intestinal cell line IEC-6 was assessed by Ca2+ -imaging analysis. TRPV4 activators or the NSAID indomethacin significantly decreased transepithelial resistance (TER) in IEC-6 cells, and indomethacin-induced TER decreases were inhibited by specific TRPV4 inhibitors or small-interfering RNA TRPV4 knockdown, as well as by the epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, which decreased 5,6-EET levels. In TRPV4 knockout mice, indomethacin-induced intestinal damage was significantly reduced compared with WT mice. Taken together, these results show that TRPV4 activation in the intestinal epithelium caused epithelial hyperpermeability in response to NSAID-induced arachidonic acid metabolites and contributed to NSAID-induced intestinal damage. Thus, TRPV4 could be a promising new therapeutic target for the prevention of NSAID-induced intestinal damage.

DOI PubMed

切除不能大腸がんに対する原発巣術後の転移巣増大と関連する背景因子の探索

安藤 孝将, 細川 歩, 明石 桃子, 吉田 啓紀, 植田 亮, 南條 宗八, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 北条 荘三, 吉田 徹, 塚田 一博, 杉山 敏郎

日本癌治療学会誌 ( (一社)日本癌治療学会 )  49 ( 3 ) 976 - 976  2014.06

進行胃癌に対するS-1+Cisplatin療法中に下痢を発症し、カプセル内視鏡で多発性の小腸潰瘍を認めた1例

元尾 伊織, 細川 歩, 安藤 孝将, 吉田 啓紀, 南條 宗八, 植田 亮, 金 辰彦, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  30 ( 1 ) 92 - 92  2014.05

DCF療法が奏効し根治的化学放射線療法で完全奏効が得られた進行食道がんの1症例

吉田 啓紀, 細川 歩, 中田 直克, 鈴木 庸弘, 南條 宗八, 植田 亮, 金 辰彦, 三原 弘, 安藤 孝将, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 杉山 敏郎

腫瘍内科 ( (有)科学評論社 )  13 ( 5 ) 669 - 673  2014.05

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症例は64歳男性で、嚥下時のつかえ感、体重減少を主訴に、近医の上部消化管内視鏡検査にて食道の腫瘍性病変を指摘され、当科紹介となった。上部消化管内視鏡・生検・胸腹部造影CT検査の結果、cStage IIIの胸部上部食道癌と診断し、術前化学療法としてDCF療法を開始した。1コース施行中にgrade 4の白血球減少、好中球減少、発熱性好中球減少を認めたが、セフタジジムとG-CSF製剤を用いていずれも改善した。2コース目は予防的にシプロフロキサシンを投与し発熱なく経過した。2コース終了時に腫瘍の著明な縮小、狭窄の改善を認めたため、手術を予定したが患者は希望しなかったため、根治的化学放射線療法を2コース行ったところ、CRが得られた。治療開始後3年10ヵ月経過した現在、無再発生存中である。

[Report from the 40th Hokuriku Chapter Educational Seminar: overview and evaluation results of the second abdominal emergency medical training course (AbdEMeT)].

Mihara H, Okazawa S, Wada A, Matsui S, Kajinami K

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   103 ( 4 ) 983 - 986  2014.04  [Refereed]

PubMed

【オンコロジーエマージェンシー】消化管の閉塞、穿孔、出血

細川 歩, 吉田 啓紀, 中田 直克, 南條 宗八, 鈴木 庸弘, 植田 亮, 金 辰彦, 三原 弘, 安藤 孝将, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 杉山 敏郎

癌の臨床 ( (株)篠原出版新社 )  60 ( 1 ) 41 - 46  2014.02

Pulmonary involvement: A rare extraintestinal manifestation of ulcerative colitis

Jun Nishikawa, Ayumu Hosokawa, Hiroshi Mihara, Ryuji Hayashi, Shigeharu Miwa, Tatsuhiko Kane, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Masami Minemura, Toshiro Sugiyama

Clinical Journal of Gastroenterology ( Springer-Verlag Tokyo )  7 ( 2 ) 155 - 158  2014  [Refereed]

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Ulcerative colitis (UC) is associated with a number of extraintestinal manifestations (EIMs) that may affect most organ systems. Among the EIMs, those involving the lung are rare. We report a case of pulmonary involvement and pyoderma gangrenosum in a patient with refractory UC. A chest computed tomography showed multiple nodular infiltrates in bilateral lungs. The patient had no respiratory symptoms. No infectious agents were detected. A transbronchial biopsy specimen showed nonspecific features. Prednisolone was initiated with significant improvement in the patient's abdominal symptoms and pyoderma gangrenosum. Subsequent imaging after steroid therapy showed improvement of the pulmonary infiltrates. The patient's abdominal symptoms relapsed when prednisolone was tapered. The patient subsequently received a proctocolectomy. Chest radiographs have shown resolution of pulmonary infiltrates. Because pulmonary involvement follows an independent course and a proctocolectomy may not be protective against a recurrence of pulmonary involvement, a careful follow-up should be continued. © 2014 Springer.

DOI PubMed

Immune-mediated Protein-losing Enteropathy with Down Syndrome

Sohachi Nanjo, Jun Nishikawa, Shigeharu Miwa, Hiroshi Mihara, Haruka Fujinami, Hiroki Yoshita, Akira Ueda, Shinya Kajiura, Yushi Hasumoto, Takayuki Ando, Ayumu Hosokawa, Toshiro Sugiyama

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  53 ( 20 ) 2301 - 2305  2014  [Refereed]

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A 28-year-old woman previously diagnosed to have Down syndrome presented with a one-month history of severe hypoalbuminemia, lower extremity edema, and diarrhea. Her urine was negative for protein. She was diagnosed with immune-mediated protein-losing enteropathy (PLE) based on clinical findings, protein loss evident on (99m)Technetium-labeled human serum albumin scintigraphy, and IgM and complement C3 deposition in the duodenum. She did not exhibit any manifestations of collagen diseases. A dramatic remission was achieved and maintained with corticosteroid administration. This is the first report of immune-mediated PLE in a patient with Down syndrome.

DOI PubMed

Non-randomized Comparison Between Irinotecan plus Mitomycin C and Irinotecan Alone in Patients with Advanced Gastric Cancer Refractory to Fluoropyrimidine and Platinum

Akira Ueda, Ayumu Hosokawa, Kohei Ogawa, Hiroki Yoshita, Hiroshi Mihara, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Jun Nishikawa, Masami Minemura, Mitsuhiro Terada, Takashi Kobayashi, Naoki Horikawa, Kazuhisa Yabushita, Masayuki Note, Toshiro Sugiyama

ANTICANCER RESEARCH ( INT INST ANTICANCER RESEARCH )  33 ( 11 ) 5107 - 5111  2013.11  [Refereed]

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Background: Irinotecan alone and plus mitomycin C have been proven to be effective as second-line chemotherapy for advanced gastric cancer. The objective of the present study was to compare the efficacy and safety of irinotecan alone (CA) and with mitomycin C (CM) in clinical practice. Patients and Methods: Between November 2006 and December 2011, 46 patients with advanced gastric cancer refractory to fluoropyrimidine and platinum were treated with CM (n=22) or CA (n=24). Results: Baseline characteristics of the patients were similar in the two treatment groups, with the exception of the sex ratio. The median progression-free survival was 3.9 months in the CM arm and 3.7 months in the CA arm (p=0.25), and the median overall survival was 9.6 and 8.7 months (p=0.36), respectively. The overall response rate was 18% in the CA arm and 9% in the CM arm (p=0.38). Grade 314 neutropenia (45% vs. 25%), anemia (36% vs. 4%), febrile neutropenia (14% vs. 8%), anorexia (14% vs. 8%) tended to be higher in the CM arm than in the CA arm. Conclusion: Although the efficacy of CM and CA for advanced gastric cancer refractory to fluoropyrimidine and platinum was not significantly different, CM tended to lead to greater incidence of adverse events in clinical practice.

PubMed

大腸内視鏡挿入困難例に対するダブルバルーン小腸内視鏡の有用性

明石 桃子, 三原 弘, 西川 潤, 藤浪 斗, 蓮本 祐史, 植田 亮, 南條 宗八, 油尾 英未, 植田 優子, 安藤 孝将, 梶浦 新也, 細川 歩, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  29 ( 2 ) 157 - 157  2013.10

クローン病に対する小腸用カプセル内視鏡の有用性と安全性の検討

三原 弘, 藤浪 斗, 西川 潤, 吉田 啓紀, 山脇 秀元, 安藤 孝将, 梶浦 新也, 細川 歩, 魚谷 英之, 伊藤 博行, 七澤 洋, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  29 ( 2 ) 158 - 158  2013.10

大腸癌肝転移の初回化学療法における形態学的変化の有用性

吉田 啓紀, 細川 歩, 植田 亮, 三原 弘, 安藤 孝将, 梶浦 新也, 藤浪 斗, 西川 潤, 加藤 洋, 川部 秀人, 富澤 岳人, 堀川 直樹, 藪下 和久, 野手 雅幸, 杉山 敏郎

日本癌治療学会誌 ( (一社)日本癌治療学会 )  48 ( 3 ) 1605 - 1605  2013.09

オンコロジーエマージェンシー 消化管の閉塞、穿孔、出血

細川 歩, 吉田 啓紀, 植田 亮, 金 辰彦, 三原 弘, 安藤 孝将, 藤浪 斗, 梶浦 新也, 西川 潤, 小川 浩平, 杉山 敏郎

日本癌治療学会誌 ( (一社)日本癌治療学会 )  48 ( 3 ) 775 - 775  2013.09

消化器疾患DIC症例に対するリコンビナントトロンボモジュリンの使用経験

藤浪 斗, 細川 歩, 西川 潤, 田尻 和人, 梶浦 新也, 河合 健吾, 安藤 孝将, 三原 弘, 植田 亮, 吉田 啓紀, 峯村 正実, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  110 ( 臨増大会 ) A961 - A961  2013.09

腹膜播種による腹水または水腎症を有する胃癌に対するS-1/Docetaxel療法の検討

塚田 健一郎, 植田 亮, 細川 歩, 吉田 啓紀, 三原 弘, 安藤 孝将, 藤浪 斗, 梶浦 新也, 西川 潤, 西水 俊准, 岩本 真也, 菓子井 良郎, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  110 ( 臨増大会 ) A904 - A904  2013.09

経口摂取困難なHER2陽性切除不能進行胃癌・食道胃接合部癌に対する5-FU+CDDP+Trastuzumab療法の検討

小川 浩平, 植田 亮, 細川 歩, 本藤 有智, 澤崎 拓郎, 國谷 等, 西田 泰之, 平井 信行, 吉田 啓紀, 南條 宗八, 三原 弘, 安藤 孝将, 梶浦 新也, 藤浪 斗, 西川 潤, 寺田 光宏, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  110 ( 臨増大会 ) A904 - A904  2013.09

Systemic Sclerosis in Small Bowel

Jun Nishikawa, Hiroshi Mihara, Toshiro Sugiyama

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY ( ELSEVIER SCIENCE INC )  11 ( 4 ) A21 - A21  2013.04  [Refereed]

DOI PubMed

TRPV2 ion channels expressed in inhibitory motor neurons of gastric myenteric plexus contribute to gastric adaptive relaxation and gastric emptying in mice

Hiroshi Mihara, Nobuhiro Suzuki, Hidemoto Yamawaki, Makoto Tominaga, Toshiro Sugiyama

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY ( AMER PHYSIOLOGICAL SOC )  304 ( 3 ) G235 - G240  2013.02  [Refereed]

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Mihara H, Suzuki N, Yamawaki H, Tominaga M, Sugiyama T. TRPV2 ion channels expressed in inhibitory motor neurons of gastric myenteric plexus contribute to gastric adaptive relaxation and gastric emptying in mice. Am J Physiol Gastrointest Liver Physiol 304: G235-G240, 2013. First published November 29, 2012; doi:10.1152/ajpgi.00256.2012.-Gastric adaptive relaxation (GAR) is impaired in similar to 40% of functional dyspepsia (FD) patients, and nitric oxide (NO) released from inhibitory motor neurons plays an important role in this relaxation. Although the underlying molecular mechanism of GAR is poorly understood, transient receptor potential channel vanilloid 2 (TRPV2) mechano- and chemoreceptors are expressed in mouse intestinal inhibitory motor neurons and are involved in intestinal relaxation. The aim of this study was to evaluate the distribution of TRPV2 in inhibitory motor neurons throughout the mouse gastrointestinal tract and the contribution of TRPV2 to GAR. RT-PCR and immunohistochemical analyses were used to detect TRPV2 mRNA and protein, respectively. Intragastric pressure was determined with an isolated mouse stomach. Gastric emptying (GE) in vivo was determined using a test meal. TRPV2 mRNA was detected throughout the mouse gastrointestinal tract, and TRPV2 immunoreactivity was detected in 84.3% of neuronal nitric oxide synthase-expressing myenteric neurons in the stomach. GAR, which was expressed as the rate of decline of intragastric pressure in response to volume stimuli, was significantly enhanced by the TRPV2 activator probenecid, and the enhancement was inhibited by the TRPV2 inhibitor tranilast. GE was significantly accelerated by TRPV2 agonist applications, and the probenecid-induced enhancement was significantly inhibited by tranilast coapplication. Mechanosensitive TRPV2 was expressed in inhibitory motor neurons in the mouse stomach and contributed to GAR and GE. TRPV2 may be a promising target for FD patients with impaired GAR.

DOI PubMed