Details of a Researcher - MIHARA Hiroshi

Papers - MIHARA Hiroshi

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若年者の切除不能進行・再発胃癌に対する化学療法の治療成績

高木宏明, 安藤孝将, 細川歩, 元尾伊織, 中田直克, 吉田啓紀, 南條宗八, 三原弘, 梶浦新也, 藤浪斗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 113 ( 臨増大会 ) A667 - A667 2016.09

多発肝転移による高度黄疸を伴う進行胃癌に対しCapecitabine/Oxaliplatin療法が奏効した1例

高木宏明, 安藤孝将, 細川歩, 西野貴晶, 三原弘, 吉田啓紀, 中田直克, 南條宗八, 三浦慶昭, 梶浦新也, 藤浪斗, 杉山敏郎

癌と化学療法 ( (株)癌と化学療法社 ) 43 ( 9 ) 1117 - 1119 2016.09

症例は74歳,男性。進行胃癌のため当院を紹介された。多発肝転移による肝障害(total bilirubin 1.6mg/dL)を伴っており,S-1/cisplatin療法を開始したところ6日後に高度の下痢(CTCAE Grade 3)を認め,S-1を中止した。これにより下痢は改善したが肝転移は増大し,黄疸も進行した(total bilirubin 10.3mg/dL)。この状況下でcapecitabine/oxaliplatin療法(capecitabine 3,600mg/day on day 1～14,oxaliplatin 130mg/m2 on day 1,q3 weeks)を開始したところ黄疸は速やかに改善し,効果判定ではpartial response(RECIST v1.1)が得られた。その後,同治療を15ヵ月間継続している。高度黄疸を伴う切除不能進行胃癌に対して,capecitabine/oxaliplatin療法は有効な治療の選択肢の一つとなる可能性が示唆された。(著者抄録)

Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

Hiroshi Mihara, Nobuhiro Suzuki, Ammar Abdullkader Boudaka, Jibran Sualeh Muhammad, Makoto Tominaga, Yoshiaki Tabuchi, Toshiro Sugiyama

WORLD JOURNAL OF GASTROENTEROLOGY ( BAISHIDENG PUBLISHING GROUP INC ) 22 ( 24 ) 5512 - 5519 2016.06 [Refereed]

AIM: To explore the expression of transient receptor potential vanilloid 4 (TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 mRNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line (RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 mRNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist (GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells and RGE1-01 cells, but not TRPV4KO cells. GSK1016790A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.

DOI PubMed

Crohn病との鑑別を要したエルシニア腸炎の一例

長田巧平, 吉田啓紀, 藤浪斗, 南條宗八, 三原弘, 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 ) 32 ( 1 ) 74 - 74 2016.05

Phase I Study of Docetaxel Plus Nedaplatin in Patients With Metastatic or Recurrent Esophageal Squamous Cell Carcinoma After Cisplatin Plus 5-Fluorouracil Treatment

Shinya Kajiura, Ayumu Hosokawa, Hiroki Yoshita, Yuko Ueda, Akira Ueda, Hiroshi Mihara, Takayuki Ando, Haruka Fujinami, Jun Nishikawa, Kohei Ogawa, Masami Minemura, Toshiro Sugiyama

AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS ( LIPPINCOTT WILLIAMS & WILKINS ) 39 ( 1 ) 13 - 17 2016.02 [Refereed]

Objectives:To date, no second-line chemotherapy regimen for esophageal squamous cell carcinoma (SCC) has been established. This clinical trial aimed to assess the optimum dose of docetaxel plus nedaplatin (cis-diammine-glycolate platinum) as second-line chemotherapy.Methods:Patients with metastatic or recurrent esophageal SCC after treatment with cisplatin plus 5-fluorouracil received docetaxel (50 or 60 mg/m(2)) plus nedaplatin (70 mg/m(2)) on day 1 every 4 weeks. The recommended dose was based on dose-limiting toxicities defined during the first cycle.Results:From February 2009 to November 2011, 9 patients were enrolled in the study. Their median age was 62 years (range, 58 to 72 y). Six patients had undergone radiotherapy and 4 had undergone surgical resection of primary lesions. Dose-limiting toxicities were observed in 2 patients at dose level 1 (60 mg/m(2) docetaxel, 70 mg/m(2) nedaplatin) but not at dose level 0 (50 mg/m(2) docetaxel, 70 mg/m(2) nedaplatin). Thus, the maximum tolerated dose was established at dose level 1. No severe nonhematological toxicity was observed. No patient achieved complete response, but 2 (22%; 95% confidence interval, 0%-49%) achieved partial response and 3 had stable disease. Median progression-free and overall survival times were 2.1 and 9.5 months, respectively.Conclusions:Docetaxel plus nedaplatin chemotherapy seems to be a safe and feasible second-line regimen for the treatment of esophageal SCC. We recommend the administration of 50 mg/m(2) docetaxel (day 1) plus 70 mg/m(2) nedaplatin (day 1) every 4 weeks in a phase II study.

DOI PubMed

The Practice Guidelines for Primary Care of Acute Abdomen 2015

Toshihiko Mayumi, Masahiro Yoshida, Susumu Tazuma, Akira Furukawa, Osamu Nishii, Kunihiro Shigematsu, Takeo Azuhata, Atsuo Itakura, Seiji Kamei, Hiroshi Kondo, Shigenobu Maeda, Hiroshi Mihara, Masafumi Mizooka, Toshihiko Nishidate, Hideaki Obara, Norio Sato, Yuichi Takayama, Tomoyuki Tsujikawa, Tomoyuki Fujii, Tetsuro Miyata, Izumi Maruyama, Hiroshi Honda, Koichi Hirata

JAPANESE JOURNAL OF RADIOLOGY ( SPRINGER ) 34 ( 1 ) 80 - 115 2016.01 [Refereed]

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines [all clinical questions (CQs) and recommendations are shown in supplementary information]. A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

DOI PubMed

Practice Guidelines for Primary Care of Acute Abdomen 2015

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES ( SPRINGER JAPAN KK ) 23 ( 1 ) 3 - 36 2016.01 [Refereed]

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine, in collaboration with four other medical societies, launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all clinical questions and recommendations were shown in supplementary information). A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on nine subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

DOI PubMed

Protease-Activated Receptor-2 Up-Regulates Transient Receptor Potential Vanilloid 4 Function in Mouse Esophageal Keratinocyte

Nobuhiro Suzuki, Hiroshi Mihara, Hirofumi Nishizono, Makoto Tominaga, Toshiro Sugiyama

DIGESTIVE DISEASES AND SCIENCES ( SPRINGER ) 60 ( 12 ) 3570 - 3578 2015.12 [Refereed]

Background The reflux of pancreatic-duodenal fluids is implicated in the pathophysiology of proton-pump inhibitor-resistant gastroesophageal reflux disease (GERD). Protease-activated receptor-2 (PAR-2) is activated by proteases, the pancreatic enzyme, trypsin, and the activated PAR-2 enhances transient receptor potential vanilloid 4 (TRPV4) function in neurons. TRPV4 stimulates ATP exocytosis in conjunction with the vesicular nucleotide transporter, which mediates mechano-transduction and vagal stimulation. The aim of the present study was to verify whether the activated PAR-2 up-regulates TRPV4 function in mouse esophageal keratinocytes, which may link to the pathophysiology in PPI-resistant GERD. MethodsTRPV4 and PAR-2 expressions were detected by RT-PCR, immunostaining, and western blotting in mouse esophageal keratinocytes. The functional response of TRPV4 to esophageal keratinocytes was analyzed using a Ca2+ imaging system. Cellular ATP release was examined by luciferase-luciferin reaction. TRPV4 phosphorylation was studied by immunoprecipitation and western blotting. Results PAR-2 and TRPV4 mRNAs and proteins were expressed in esophageal keratinocytes. Pre-treatment with trypsin significantly increased the responses to TRPV4 activator in esophageal keratinocytes, probably via the phosphorylation of serine residue of TRPV4 by protein kinase C and resulted in cellular ATP release from the cells. ConclusionsActivated PAR-2 with trypsin exposure up-regulated TRPV4 function and increased ATP release in mouse esophageal keratinocytes. This mechanism might be related to the pathophysiology of GERD, especially non-erosive GERD.

DOI PubMed

IgA vasculitis associated with anti-TNF-α inhibitors in a patient with Crohn's disease

Jun Nishikawa, Ayumu Hosokawa, Momoko Akashi, Hiroshi Mihara, Sohachi Nanjo, Hiroki Yoshita, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Toshiro Sugiyama

Journal of Japanese Society of Gastroenterology ( Japanese Society of Gastroenterology ) 112 ( 10 ) 1852 - 1857 2015.10 [Refereed]

Anti-TNF-α inhibitors have been widely used in the treatment of inflammatory bowel disease. Although they have good clinical efficacy and tolerance, they remain a matter of concern because they cause drug-induced autoimmune disorders as side effects. Here, we report a case of a patient with Crohn's disease who developed IgA vasculitis after infliximab and adalimumab treatment. A 17-year-old male with Crohn's disease who had received scheduled infliximab treatment for the preceding 19 months complained of purpura on his lower limbs. He was diagnosed with infliximab-induced IgA vasculitis. Switching infliximab to adalimumab resulted in rapid improvement of the condition. However, 21 months after switching to adalimumab, his purpura recurred. Drug-induced IgA vasculitis is a rare complication caused by infliximab and adalimumab however, diagnosis in the early phase and appropriate management of patients receiving anti-TNF-α inhibitors is critical to a successful patient outcome.

DOI PubMed

抗TNF-α製剤投与によりIgA血管炎を発症したクローン病の1例

西川潤, 細川歩, 明石桃子, 三原弘, 南條宗八, 吉田啓紀, 安藤孝将, 梶浦新也, 藤浪斗, 杉山敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 112 ( 10 ) 1852 - 1857 2015.10

胃高齢者胃がんの治療ストラテジー進行再発胃がんに対する化学療法誘発性下痢症の発症経緯及びカプセル内視鏡所見の検討

安藤孝将, 細川歩, 三原弘, 高木宏明, 吉田啓紀, 植田亮, 南條宗八, 高取俊介, 藤浪斗, 梶浦新也, 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 ) 50 ( 3 ) 1367 - 1367 2015.09

進行・再発大腸粘液癌に対するFOLFOX及びFOLFIRI療法の検討

西野貴晶, 安藤孝将, 細川歩, 高取俊介, 中田直克, 吉田啓紀, 植田亮, 南條宗八, 三原弘, 藤浪斗, 梶浦新也, 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 ) 50 ( 3 ) 1740 - 1740 2015.09

腹膜播種を有する大腸癌に対する化学療法の治療成績

高取俊介, 細川歩, 安藤孝将, 吉田啓紀, 南條宗八, 三原弘, 藤浪斗, 梶浦新也, 三浦慶昭, 杉山敏郎

日本癌治療学会誌 ( (一社)日本癌治療学会 ) 50 ( 3 ) 2412 - 2412 2015.09

Effective healing of endoscopic submucosal dissection-induced ulcers by a single week of proton pump inhibitor treatment: A retrospective study

Shinya Kajiura, Ayumu Hosokawa, Akira Ueda, Hiroshi Mihara, Takayuki Ando, Haruka Fujinami, Jun Nishikawa, Kohei Ogawa, Masami Minemura, Toshiro Sugiyama

BMC Research Notes ( BioMed Central Ltd. ) 8 ( 1 ) 150 2015.04 [Refereed]

Background: Although artificial ulcers generally heal faster than Helicobacter pylori-related or nonsteroidal anti-inflammatory drug-related peptic ulcers, endoscopic submucosal dissection (ESD)-induced gastric ulcers are usually treated with a proton pump inhibitor (PPI) for 4-8 weeks. The effect of oral administration of a PPI for 1 week on ESD-induced gastric ulcers has not yet been evaluated. In the present study, we evaluated the efficacy of oral PPI for 1 week in patients with ESD-induced ulcers. Methods: We selected 45 patients who underwent ESD for gastric mucosal tumors between June 2005 and July 2006 at Toyama University Hospital, and who met our inclusion criteria. All patients received omeprazole intravenously for 2 days after ESD and then orally for 1 week to prevent bleeding. Twenty two patients received no further omeprazole therapy (1-week group) and the rest received omeprazole orally for 7 more weeks (8-week group). Follow-up endoscopy was performed at 1 day, 4 weeks, and 8 weeks after ESD. We compared the ulcer healing rates between both groups. Results: There were no significant differences between the groups in the ulcer-healing rate, because ulcers healed in 22 (96%) and 20 (91%) patients from the 8-week and 1-week groups, respectively. Conclusions: In our study, oral administration of omeprazole for 1 week was sufficient to achieve healing of ESD-induced artificial gastric ulcers. A larger prospective trial will be required to confirm these findings.

DOI PubMed

The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia

Reona Aijima, Bing Wang, Tomoka Takao, Hiroshi Mihara, Makiko Kashio, Yasuyoshi Ohsaki, Jing-Qi Zhang, Atsuko Mizuno, Makoto Suzuki, Yoshio Yamashita, Sadahiko Masuko, Masaaki Goto, Makoto Tominaga, Mizuho A. Kido

FASEB JOURNAL ( FEDERATION AMER SOC EXP BIOL ) 29 ( 1 ) 182 - 192 2015.01 [Refereed]

The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca2+-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33 degrees C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa.

DOI PubMed

Amrubicin Monotherapy for Patients with Platinum-Refractory Gastroenteropancreatic Neuroendocrine Carcinoma

Takayuki Ando, Ayumu Hosokawa, Hiroki Yoshita, Akira Ueda, Shinya Kajiura, Hiroshi Mihara, Sohachi Nanjo, Haruka Fujinami, Jun Nishikawa, Kohei Ogawa, Takahiko Nakajima, Johji Imura, Toshiro Sugiyama

GASTROENTEROLOGY RESEARCH AND PRACTICE ( HINDAWI PUBLISHING CORPORATION ) 2015 425876 2015 [Refereed]

Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results. Eight males and two females (median age, 67 years (range, 52-78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively. Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.

DOI PubMed

Multiple Colon Ulcers with Typical Small Intestinal Lesions Induced by Non-Steroidal Anti-Inflammatory Drugs

Momoko Akashi, Takayuki Ando, Takeru Hamashima, Hiroki Yoshita, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Shinya Kajiura, Jun Nishikawa, Yoshiaki Miura, Ayumu Hosokawa, Toshiro Sugiyama

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 54 ( 16 ) 1995 - 1999 2015 [Refereed]

The diagnosis of NSAID-induced colon ulcers is difficult when the distribution or endoscopic findings are not typical. An 83-year-old woman was transferred to our hospital for hemorrhagic diarrhea. Colonoscopy showed multiple ulcers in the entire colon, particularly longitudinal ulcers in the transverse colon. These were unusual for NSAID-induced colopathy, although she had been on meloxicam. However, capsule endoscopy revealed multiple scars and erosions, characteristic of NSAIDs users. The final diagnosis was NSAID-induced enteropathy, and all lesions were in remission after meloxicam discontinuation. We herein emphasize the value of an endoscopic assessment of the entire digestive tract in the diagnosis of NSAID-induced mucosal lesions.

DOI PubMed

Direct Spraying of Shakuyakukanzoto onto the Duodenal Papilla: A Novel Method for Preventing Pancreatitis following Endoscopic Retrograde Cholangiopancreatography

Haruka Fujinami, Shinya Kajiura, Takayuki Ando, Hiroshi Mihara, Ayumu Hosokawa, Toshiro Sugiyama

DIGESTION ( KARGER ) 91 ( 1 ) 42 - 45 2015 [Refereed]

Background/Aims: Topical epinephrine application to the duodenal papilla reduces spasm of the sphincter of Oddi and prevents acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Shakuyakukanzoto (TJ-68) has an inhibitory effect on muscle contraction. Therefore, TJ-68 potentially allows the relaxation of the sphincter of Oddi, which can aid in the prevention of post-ERCP pancreatitis. Methods: Thirty-six patients planned for ERCP were divided into TJ-68 (n = 17) and control groups (n = 19). In the TJ-68 group, the TJ-68 solution was endoscopically sprayed directly onto the duodenal papilla of patients. To assess the effects of TJ-68, serum amylase levels were measured at 1 h and 1 day after ERCP and symptoms were evaluated. Results: The serum amylase levels at 1 h after ERCP were 273.6 +/- 212.0 IU/l in the TJ-68 group and 428.7 +/- 281.6 IU/l in the control group, showing a statistically significant difference (p = 0.036). The serum amylase levels at 24 h after ERCP were 230.0 +/- 182.7 IU/l in the TJ-68 group and 497.4 +/- 514.0 IU/l in the control group (p = 0.011). Post-ERCP pancreatitis was observed in 0 and 4 patients (21.1%) in the TJ-68 and control groups, respectively, which was not statistically significant (p = 0.11). Conclusion: Direct TJ-68 solution application to the duodenal papilla significantly inhibited the elevation of serum amylase levels. However, the preventive effect regarding post-ERCP pancreatitis was not confirmed in this study. (C) 2015 S. Karger AG, Basel

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

明石桃子, 安藤孝将, 細川歩, 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, 北条荘三, 吉田徹, 塚田一博

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 ) A906 - A906 2014.09

胃食道逆流症に対するPPIの功罪

藤浪斗, 三原弘, 吉田啓紀, 安藤孝将, 梶浦新也, 西川潤, 細川歩, 杉山敏郎

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 56 ( Suppl.2 ) 3062 - 3062 2014.09

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