Papers - MIHARA Hiroshi

急性腹症診療ガイドライン改訂 教育章

井上 祐真, 井上 明星, 刑部 恵介, 貝田 佐知子, 亀井 誠二, 亀田 徹, 近藤 浩史, 関根 慎一, 渡口 真史, 畠 二郎, 丸山 憲一, 矢吹 拓, 山岸 俊介, 山田 岳史, 和田 慎司, 三原 弘

日本病院総合診療医学会雑誌 ( (一社)日本病院総合診療医学会 )  20 ( 臨増2 ) 110 - 110  2024.09

ボーリング生検により診断し得た局所進行食道verrucous carcinomaの1例

田畑 和久, 元尾 伊織, 安藤 孝将, 中嶋 隆彦, 芳尾 幸松, 作村 美穂, 三原 弘, 梶浦 新也, 中谷 敦子, 安田 一朗

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  66 ( 8 ) 1581 - 1587  2024.08

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症例は63歳男性.嚥下困難を主訴に受診し,上部消化管内視鏡検査で胸部下部食道に全周性の疣状,角化の目立つ白色隆起性病変を認めた.また,切歯28cmに深い陥凹を認め,左気管支と瘻孔を形成していた.3回の内視鏡検査により生検を繰り返したが,癌の診断には至らず,特徴的な内視鏡像から食道verrucous carcinoma(VC)を疑った.瘻孔に沿ってボーリング生検を施行した結果,VCに矛盾しない太い釘脚の下方への進展像が確認でき,食道VCと診断し得た.本症例のように切除不能な食道VCの診断においてボーリング生検は考慮すべき手技であると考えられた.(著者抄録)

Feasibility and reliability of the pandemic-adapted online-onsite hybrid graduation OSCE in Japan.

Satoshi Hara, Kunio Ohta, Daisuke Aono, Toshikatsu Tamai, Makoto Kurachi, Kimikazu Sugimori, Hiroshi Mihara, Hiroshi Ichimura, Yasuhiko Yamamoto, Hideki Nomura

Advances in health sciences education : theory and practice   29 ( 3 ) 949 - 965  2024.07  [International journal]

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Objective structured clinical examination (OSCE) is widely used to assess medical students' clinical skills. Virtual OSCEs were used in place of in-person OSCEs during the COVID-19 pandemic; however, their reliability is yet to be robustly analyzed. By applying generalizability (G) theory, this study aimed to evaluate the reliability of a hybrid OSCE, which admixed in-person and online methods, and gain insights into improving OSCEs' reliability. During the 2020-2021 hybrid OSCEs, one examinee, one rater, and a vinyl mannequin for physical examination participated onsite, and a standardized simulated patient (SP) for medical interviewing and another rater joined online in one virtual breakout room on an audiovisual conferencing system. G-coefficients and 95% confidence intervals of the borderline score, namely border zone (BZ), under the standard 6-station, 2-rater, and 6-item setting were calculated. G-coefficients of in-person (2017-2019) and hybrid OSCEs (2020-2021) under the standard setting were estimated to be 0.624, 0.770, 0.782, 0.759, and 0.823, respectively. The BZ scores were estimated to be 2.43-3.57, 2.55-3.45, 2.59-3.41, 2.59-3.41, and 2.51-3.49, respectively, in the score range from 1 to 6. Although hybrid OSCEs showed reliability comparable to in-person OSCEs, they need further improvement as a very high-stakes examination. In addition to increasing clinical vignettes, having more proficient online/on-demand raters and/or online SPs for medical interviews could improve the reliability of OSCEs. Reliability can also be ensured through supplementary examination and by increasing the number of online raters for a small number of students within the BZs.

DOI PubMed

Artificial intelligence model for analyzing colonic endoscopy images to detect changes associated with irritable bowel syndrome.

Kazuhisa Tabata, Hiroshi Mihara, Sohachi Nanjo, Iori Motoo, Takayuki Ando, Akira Teramoto, Haruka Fujinami, Ichiro Yasuda

PLOS digital health   2 ( 2 ) e0000058  2023.02  [International journal]

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IBS is not considered to be an organic disease and usually shows no abnormality on lower gastrointestinal endoscopy, although biofilm formation, dysbiosis, and histological microinflammation have recently been reported in patients with IBS. In this study, we investigated whether an artificial intelligence (AI) colorectal image model can identify minute endoscopic changes, which cannot typically be detected by human investigators, that are associated with IBS. Study subjects were identified based on electronic medical records and categorized as IBS (Group I; n = 11), IBS with predominant constipation (IBS-C; Group C; n = 12), and IBS with predominant diarrhea (IBS-D; Group D; n = 12). The study subjects had no other diseases. Colonoscopy images from IBS patients and from asymptomatic healthy subjects (Group N; n = 88) were obtained. Google Cloud Platform AutoML Vision (single-label classification) was used to construct AI image models to calculate sensitivity, specificity, predictive value, and AUC. A total of 2479, 382, 538, and 484 images were randomly selected for Groups N, I, C and D, respectively. The AUC of the model discriminating between Group N and I was 0.95. Sensitivity, specificity, positive predictive value, and negative predictive value of Group I detection were 30.8%, 97.6%, 66.7%, and 90.2%, respectively. The overall AUC of the model discriminating between Groups N, C, and D was 0.83; sensitivity, specificity, and positive predictive value of Group N were 87.5%, 46.2%, and 79.9%, respectively. Using the image AI model, colonoscopy images of IBS could be discriminated from healthy subjects at AUC 0.95. Prospective studies are needed to further validate whether this externally validated model has similar diagnostic capabilities at other facilities and whether it can be used to determine treatment efficacy.

DOI PubMed

Colonic TRPV4 overexpression is related to constipation severity.

Hiroshi Mihara, Kunitoshi Uchida, Yoshiyuki Watanabe, Sohachi Nanjo, Miho Sakumura, Iori Motoo, Takayuki Ando, Masami Minemura, Jibran Sualeh Muhammad, Hiroyuki Yamamoto, Fumio Itoh, Ichiro Yasuda

BMC gastroenterology   23 ( 1 ) 13 - 13  2023.01  [International journal]

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BACKGROUND: Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. METHODS: Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids. TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. RESULTS: Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyrate or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 h were associated with increased E. faecalis frequency. CONCLUSIONS: Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.

DOI PubMed

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer

Takayuki Ando, Ayumu Hosokawa, Miho Sakumura, Iori Motoo, Shinya Kajiura, Katsuhisa Hirano, Takeshi Miwa, Tomotaka Yokota, Naokatsu Nakada, Yuko Ueda, Akira Ueda, Kenichiro Tsukada, Kohei Ogawa, Atsuko Nakaya, Akira Teramoto, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Tsutomu Fujii, Ichiro Yasuda

Oncology (Switzerland)   101 ( 1 ) 59 - 68  2023.01

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Introduction: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. Methods: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. Results: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. Conclusions: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

DOI PubMed

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

Takayuki Ando, Ayumu Hosokawa, Miho Sakumura, Iori Motoo, Shinya Kajiura, Katsuhisa Hirano, Takeshi Miwa, Tomotaka Yokota, Naokatsu Nakada, Yuko Ueda, Akira Ueda, Kenichiro Tsukada, Kohei Ogawa, Atsuko Nakaya, Akira Teramoto, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Tsutomu Fujii, Ichiro Yasuda

Oncology   101 ( 1 ) 59 - 68  2023  [International journal]

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INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

DOI PubMed

EUS下胆道ドレナージルートから胆道鏡下結石破砕術を行った総胆管結石の一例

北村 和紀, 井上 祐真, 圓谷 俊貴, 広島 康久, 松野 潤, 中村 佳史, 林 伸彦, 元尾 伊織, 植田 亮, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  38 ( 2 ) 177 - 177  2022.12

【診療ガイドラインに基づいた胆膵疾患の診断】胆嚢結石・総胆管結石の診断

井上 祐真, 安田 一朗, 圓谷 俊貴, 松野 潤, 広島 康久, 中村 佳史, 林 伸彦, 元尾 伊織, 植田 亮, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

消化器クリニカルアップデート ( 医学図書出版(株) )  4 ( 1 ) 18 - 22  2022.10

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臨床の場で遭遇することの多い疾患である胆嚢結石,総胆管結石の診断について診療ガイドラインに基づいて概説した。胆嚢結石は診断そのものに迷うことは少ないが,急性胆嚢炎や総胆管結石の合併を見逃さないように検査を進める。総胆管結石については非石灰化結石や微小結石などで見落としやすい症例がある。臨床症状・所見や血液検査などから存在が疑われる場合には,USやCTのみでなく適宜MRIやEUSも組み合わせて診断を行う。(著者抄録)

胆道狭窄鑑別診断におけるPOCS下生検の現時点での位置づけ

松野 潤, 林 伸彦, 安田 一朗, 中村 佳史, 井上 祐真, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

胆道 ( (一社)日本胆道学会 )  36 ( 3 ) 382 - 382  2022.09

Protein-losing Enteropathy Complicated with Primary Intestinal Follicular Lymphoma.

Tomoki Minemura, Shohei Kikuchi, Hiroshi Mihara, Yusuke Kamihara, Akinori Wada, Mayo Fuchino, Sohachi Nanjo, Akira Noguchi, Takashi Minamisaka, Jun Murakami, Ichiro Yasuda, Tsutomu Sato

Internal medicine (Tokyo, Japan)   61 ( 13 ) 2051 - 2055  2022.07  [Domestic journal]

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Protein-losing enteropathy (PLE) is a rare syndrome characterized by hypoproteinemia due to gastrointestinal (GI) protein loss. Primary intestinal follicular lymphoma (PIFL), a specific variant of follicular lymphoma with essential only GI involvement, has not been reported as an etiology of PLE. We herein report a case of PLE complicated with PIFL that was successfully treated with rituximab, resulting in rapid improvement of PLE and a complete response of PIFL. Macroscopic findings of ulcerative lesions with diffuse involvement, which were precisely described by capsule and double-balloon enteroscopy at the diagnosis, also improved following the treatment. This case provides a clue suggesting factors that promote PLE in PIFL.

DOI PubMed

自作過敏性腸症候群検出用大腸内視鏡画像AIモデルにおける有症状者検出精度の検討

田畑 和久, 三原 弘, 安藤 孝将, 元尾 伊織, 高橋 冴子, 寺本 彰, 作村 美穂, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  38 ( 1 ) 96 - 96  2022.07

上部消化管内視鏡撮影部位のAI判定とスクリーニング内視鏡への応用

藤浪 斗, 三原 弘, 高橋 冴子, 植田 優子, 作村 美穂, 元尾 伊織, 寺本 彰, 南條 宗八, 安藤 孝将, 梶浦 新也, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  38 ( 1 ) 99 - 99  2022.07

ERCP胆管挿管困難例に対する当院のストラテジーとEUS-rendezvous法の有用性

北村 和紀, 林 伸彦, 松野 潤, 中村 佳史, 井上 祐真, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  38 ( 1 ) 98 - 98  2022.07

膵神経内分泌腫瘍の術後再発病変に対して術前EUS-guided fine needle tattooing(EUS-FNT)が有効であった1例

中尾 萌音, 林 伸彦, 松野 潤, 中村 佳史, 井上 祐真, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 平野 勝久, 渋谷 和人, 藤井 努, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  133回   37 - 37  2022.06

Borderline resectable膵癌における胆道ドレナージの化学療法と手術に対する影響について

中村 佳史, 林 伸彦, 安田 一朗, 松野 潤, 井上 祐真, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  64 ( Suppl.1 ) 865 - 865  2022.04

【エキスパートが教える最新胆膵内視鏡診断・治療】ERCP関連手技 急性胆嚢炎に対する経乳頭的ドレナージの基本と応用【動画付】

井上 祐真, 安田 一朗, 松野 潤, 中村 佳史, 林 伸彦, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

胆と膵 ( 医学図書出版(株) )  43 ( 4 ) 313 - 318  2022.04

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中等症以上の急性胆嚢炎症例で、緊急あるいは早期の手術が難しく、さらに抗血栓薬内服中などで経皮経肝胆嚢ドレナージ(percutaneous transhepatic gallbladder drainage:PTGBD)が不適の症例に対しては、胆膵内視鏡のエキスパートのいる施設では、内視鏡的経乳頭的胆嚢ドレナージを選択することができる。その手技成功率は、PTGBDに比べるとやや劣るものの、臨床的奏効率は同等とされている。しかし、膵炎以外にもガイドワイヤによる胆嚢管穿孔や胆汁瘻といった偶発症が起こりうるため、手技を安全かつ確実に行うためには、準備をしっかり整えて、処置具や手技のコツを十分に理解したうえで手技に臨む必要がある。(著者抄録)

胆管空腸吻合術後肝内結石に対する内視鏡治療

井上 祐真, 林 伸彦, 安田 一朗, 松野 潤, 中村 佳史, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  119 ( 臨増総会 ) A370 - A370  2022.03

【診療ガイドライン改訂後の膵炎診療】胆道狭窄に対する治療 プラスチックステントor FCSEMS

中村 佳史, 安田 一朗, 松野 潤, 井上 祐真, 林 伸彦, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

肝胆膵 ( (株)アークメディア )  84 ( 3 ) 361 - 367  2022.03

Evidence-based clinical practice guidelines for functional dyspepsia 2021.

Hiroto Miwa, Akihito Nagahara, Akihiro Asakawa, Makoto Arai, Tadayuki Oshima, Kunio Kasugai, Kazuhiro Kamada, Hidekazu Suzuki, Fumio Tanaka, Kazunari Tominaga, Seiji Futagami, Mariko Hojo, Hiroshi Mihara, Kazuhide Higuchi, Motoyasu Kusano, Tomiyasu Arisawa, Mototsugu Kato, Takashi Joh, Satoshi Mochida, Nobuyuki Enomoto, Tooru Shimosegawa, Kazuhiko Koike

Journal of gastroenterology   57 ( 2 ) 47 - 61  2022.02  [Domestic journal]

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BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

DOI PubMed

A Review of Potential Role of Capsule Endoscopy in the Work-Up for Chemotherapy-Induced Diarrhea.

Takayuki Ando, Miho Sakumura, Hiroshi Mihara, Haruka Fujinami, Ichiro Yasuda

Healthcare (Basel, Switzerland)   10 ( 2 )  2022.01  [International journal]

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Chemotherapy-induced diarrhea (CID) is a common, severe side effect of chemotherapy, immunotherapy, and targeted therapy. Because patients are more prone to continuing chemotherapy if they do not suffer from CID, appropriate diagnosis and monitoring of this disease are essential. However, suitable monitoring methods are yet to be developed. To date, several studies have shown that small-bowel capsule endoscopy (SBCE) is useful in visualizing the entire small intestinal mucosa and detecting small intestinal abnormalities, including bleeding, malignant tumors, and mucosal injury, associated with the use of nonsteroidal anti-inflammatory drugs and low-dose aspirin. Currently, limited studies have evaluated the small intestinal mucosa using SBCE in patients receiving fluoropyrimidine-based chemotherapy or immune checkpoint inhibitors. These studies have reported that small intestinal mucosal injury is common in patients with severe fluoropyrimidine-induced diarrhea. SBCE might be a useful screening method for the early detection of enterocolitis induced by immune checkpoint inhibitors. SBCE may be a powerful tool for the diagnosis and monitoring of CID, and understanding its indication, contraindication, and capsule-retention risk for each patient is important for clinicians.

DOI PubMed

Intensive surveillance endoscopy for multiple gastrointestinal tumors in a patient with constitutional mismatch repair deficiency: case report

Takayuki Ando, Takahiko Nakajima, Rei Fukuda, Keiko Nomura, Yo Niida, Miho Sakumura, Iori Motoo, Hiroshi Mihara, Sohachi Nanjo, Shinya Kajiura, Haruka Fujinami, Shojo Hojo, Tsutomu Fujii, Ichiro Yasuda

BMC Gastroenterology ( Springer Science and Business Media LLC )  21 ( 1 ) 326 - 326  2021.12  [International journal]

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Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient’s condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD. A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1). Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient’s condition.

DOI PubMed

瘻孔近傍のボーリング生検で診断し得た疣状食道癌(verrucous carcinoma)の一例

田畑 和久, 元尾 伊織, 作村 美穂, 三原 弘, 安藤 孝将, 荻野 万里, 寺本 彰, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  37 ( 2 ) 154 - 154  2021.12

「ESD手技の工夫・こだわり」 けん引クリップを用いた胃ESDの工夫

高橋 冴子, 藤浪 斗, 作村 美穂, 寺本 彰, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  37 ( 2 ) 161 - 161  2021.12

当院で施行した内視鏡的異物除去術の臨床的検討

荻野 万里, 藤浪 斗, 寺本 彰, 高橋 冴子, 南條 宗八, 田畑 和久, 作村 美穂, 元尾 伊織, 三原 弘, 安藤 孝将, 梶浦 新也, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  37 ( 2 ) 153 - 153  2021.12

【胆道狭窄の診断と治療】各論(治療) 術後良性胆管空腸吻合部狭窄に対する内視鏡治療

井上 祐真, 安田 一朗, 松野 潤, 花岡 辰行, 中村 佳史, 林 伸彦, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

肝胆膵 ( (株)アークメディア )  83 ( 5 ) 797 - 805  2021.11

Bilateral Serous Retinal Detachment Associated with a Mitogen-activated Protein KinaseKinase Inhibitor in a Patient with BRAF-mutant Colorectal Cancer.

Miho Sakumura, Takayuki Ando, Tomoko Ueda-Consolvo, Iori Motoo, Hiroshi Mihara, Shinya Kajiura, Akira Teramoto, Sohachi Nanjo, Haruka Fujinami, Ichiro Yasuda

Internal medicine (Tokyo, Japan)   61 ( 11 ) 1707 - 1712  2021.10  [Domestic journal]

　View Summary

We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.

DOI PubMed

Google Cloud Platform機械学習で構築したAIモデルでの食道炎分類精度の検討

三原 弘, 倉石 俊, 小川 健二, 清水 沙也香, 平木 将矢, 南條 宗八, 安藤 孝将, 梶浦 新也, 藤浪 斗, 安田 一朗

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  63 ( Suppl.2 ) 2014 - 2014  2021.10

MEK阻害薬により両側性漿液性網膜剥離を生じたBRAF V600E変異陽性進行大腸癌の一例

伊藤 顕太郎, 作村 美穂, 安藤 孝将, 元尾 伊織, 寺本 彰, 三原 弘, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  132回   41 - 41  2021.10

ニボルマブ療法を受けた進行食道癌患者における免疫関連有害事象の特徴と治療成績に及ぼす影響

作村 美穂, 安藤 孝将, 中田 直克, 元尾 伊織, 梶浦 新也, 渕野 真代, 南條 宗八, 三原 弘, 藤浪 斗, 小川 浩平, 塚田 健一郎, 中島 孝治, 細川 歩, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A738 - A738  2021.10

DICを合併する進行胃癌に対する一次治療としてのFOLFOX療法の有効性と安全性

高橋 直希, 安藤 孝将, 元尾 伊織, 作村 美穂, 梶浦 新也, 中島 孝治, 細川 歩, 植田 亮, 鈴木 庸弘, 渕野 真代, 三原 弘, 南條 宗八, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A719 - A719  2021.10

潰瘍性大腸炎における血清ロイシンリッチα2グリコプロテイン測定の有用性の検討

南條 宗八, 渕野 真代, 高橋 冴子, 三原 弘, 渡辺 かすみ, 高橋 直希, 花岡 辰行, 植田 優子, 作村 美穂, 高橋 孝輔, 荒木 康宏, 元尾 伊織, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A762 - A762  2021.10

高度な食道狭窄を呈したバレット食道の一例

渡邊 かすみ, 南條 宗八, 渕野 真代, 藤浪 斗, 高橋 直希, 高橋 冴子, 植田 優子, 作村 美穂, 元尾 伊織, 三原 弘, 梶浦 新也, 安藤 孝将, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  37 ( 1 ) 49 - 49  2021.07

HIV感染に合併したHPV関連肛門管癌の一例

鍵谷 聡一郎, 元尾 伊織, 安藤 孝将, 三原 弘, 作村 美穂, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  131回   39 - 39  2021.06

【緊急内視鏡の今】胆膵領域の緊急内視鏡 急性胆嚢炎

安田 一朗, 花岡 辰行, 高橋 孝輔, 荒木 康宏, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 土井 晋平

消化器内視鏡 ( (株)東京医学社 )  33 ( 4 ) 762 - 768  2021.04

【緊急内視鏡の今】胆膵領域の緊急内視鏡 急性胆嚢炎

安田 一朗, 花岡 辰行, 高橋 孝輔, 荒木 康宏, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 土井 晋平

消化器内視鏡 ( (株)東京医学社 )  33 ( 4 ) 762 - 768  2021.04

Endoscopic Ultrasound-guided Fine Needle Aspiration for the Diagnosis of Duodenal Stenosis Due to Urothelial Carcinoma.

Iori Motoo, Takayuki Ando, Hiroshi Mihara, Shinichi Tanaka, Sohachi Nanjo, Shinya Kajiura, Haruka Fujinami, Kosuke Takahashi, Ichiro Yasuda

Internal medicine (Tokyo, Japan)   60 ( 5 ) 719 - 724  2021.03  [Domestic journal]

　View Summary

Upper tract urothelial carcinoma (UTUC) initially presents with hematuria and hydronephrosis. We report a case of UTUC presenting with initial findings of duodenal stenosis before the appearance of hydronephrosis. A 59-year-old man presented with upper abdominal symptoms on his initial visit. Esophagogastroduodenoscopy (EGD) revealed circumferential stenosis at the descending part of the duodenum. However, the underlying cause of duodenal stenosis was unknown as repeated histopathological examinations of endoscopic biopsy specimens showed no specific findings. We then performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the thickened duodenal wall, and successfully diagnosed duodenal metastasis of UTUC. EUS-FNA is an effective diagnostic method in cases in which the cause of duodenal stenosis is unknown.

DOI PubMed

【胆道ドレナージを極める】経乳頭的アプローチ 悪性遠位胆管狭窄に対する経乳頭的ドレナージ

安田 一朗, 花岡 辰行, 高橋 孝輔, 荒木 康宏, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

消化器内視鏡 ( (株)東京医学社 )  33 ( 3 ) 488 - 495  2021.03

合併するアレルギー性疾患に対して抗IgE抗体オマリズマブを併用した好酸球性胃腸炎4例の検討

渡辺 かすみ, 渕野 真代, 三原 弘, 作村 美穂, 元尾 伊織, 南條 宗八, 安藤 孝将, 梶浦 新也, 藤浪 斗, 安田 一朗

日本消化管学会雑誌 ( (一社)日本消化管学会 )  5 ( Suppl. ) 309 - 309  2021.01

機能性消化管疾患の病態と治療 機能性消化管疾患のUp-to-date-病態から治療法まで- 肥満細胞トリプターゼは十二指腸(小腸)上皮のTRPV4機能を増強させることで上皮の透過性亢進を誘発しうる

三原 弘, 渕野 真代, 南條 宗八, 藤浪 斗, 安藤 孝将, 梶浦 新也, 安田 一朗

日本消化管学会雑誌 ( (一社)日本消化管学会 )  5 ( Suppl. ) 154 - 154  2021.01

Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese National Database

Hiroshi Mihara, Aiko Murayama, Sohachi Nanjo, Takayuki Ando, Kazuto Tajiri, Haruka Fujinami, Masaaki Yamada, Ichiro Yasuda

BMC Gastroenterology ( Springer Science and Business Media LLC )  20 ( 1 ) 284 - 284  2020.12  [International journal]

　View Summary

The prevalence of chronic constipation is increased in females and with age or environmental (low temperature), racial, socioeconomic, and habitual risk factors. The impact of low outside temperature on constipation drug use remains unclear. Here, we investigated risk factors for constipation drug use by evaluating data from the Japanese National Database. This ecological study used the 2016 open Japanese National Database of health insurance claims (prescriptions) to acquire the number of health insurance prescription claims in all 47 prefectures for drugs to relieve constipation, antihypertensives, vasodilators, as well as medical check-ups and questionnaire responses. Internet survey on room temperatures in 2010 were also used. Pearson correlation coefficients (r) between the number of population-based prescriptions for each item were calculated and multiple linear regression analysis (MLR) was performed. Prescriptions for magnesium laxatives significantly correlated with aging (r = 0.58), vasodilators (r = 0.53), being female (r = 0.43), antihypertensives (r = 0.39), and inversely with eating ≤2 h before bedtime (r = − 0.37), total crime rate (r = − 0.33), insomnia (r = − 0.33), and population density (r = − 0.31). Stimulant laxatives (sennoside and picosulfate) were significantly correlated with antihypertensives (r = 0.79), aging (r = 0.69), vasodilators (r = 0.67), and being female (r = 0.56), and were inversely associated with average outside temperature (r = − 0.62), total crime rate (r = − 0.52), average income (r = − 0.51), and 30-min of vigorous exercise (r = − 0.44). Fecal interventions were significantly correlated with aging (r = 0.55) and female (r = 0.59), and inversely correlated with population density (r = − 0.41) and total crime rate (r = − 0.38). MLR analysis identified aging as the only significant risk factor for magnesium laxative use (partial slope [β] = 1241.0). Female sex and antihypertensives were independent risk factors for stimulant laxative prescriptions (β = 44,547.0 and 0.2) and average outside temperature and 30-min of vigorous exercise were independent preventive factors (β = − 616.8 and − 219.1). We identified associations of magnesium laxatives with aging, stimulant laxatives with female sex, antihypertensives, low outside temperature and less 30 min of vigorous exercise.

DOI PubMed

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea

Miho Sakumura, Takayuki Ando, Ayumu Hosokawa, Takahiko Nakajima, Iori Motoo, Hiroshi Mihara, Akira Ueda, Shinya Kajiura, Sohachi Nanjo, Haruka Fujinami, Kohei Ogawa, Ichiro Yasuda

BMC Gastroenterology ( Springer Science and Business Media LLC )  20 ( 1 ) 355 - 355  2020.12  [International journal]

　View Summary

Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID. In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID. Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06–8.19). Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

DOI PubMed

特集 進化するEUS 治療的EUS WONに対する治療戦略

高橋 孝輔, 花岡 辰行, 荒木 康宏, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 安田 一朗

消化器内視鏡 ( (株)東京医学社 )  32 ( 11 ) 1708 - 1713  2020.11

DOI

【進化するEUS】治療的EUS WONに対する治療戦略

高橋 孝輔, 花岡 辰行, 荒木 康宏, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 安田 一朗

消化器内視鏡 ( (株)東京医学社 )  32 ( 11 ) 1708 - 1713  2020.11

BRAF変異大腸癌に対してDabrafenib+Trametinib+Panitumumabを導入した一例

後藤 柚乃, 元尾 伊織, 安藤 孝将, 三原 弘, 作村 美穂, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  130回   43 - 43  2020.11

小腸難治性疾患の診断と治療の新知見 好酸球性胃腸炎における好酸球浸潤の部位・程度と臨床的病態・治療反応性との関連についての検討

渕野 真代, 三原 弘, 作村 美穂, 元尾 伊織, 南條 宗八, 安藤 孝将, 梶浦 新也, 藤浪 斗, 安田 一朗

日本小腸学会学術集会プログラム・抄録集 ( 日本小腸学会 )  58回   54 - 54  2020.10

進行胃癌に対するNivolumab療法における転移臓器別の治療効果に関する検討

村山 愛子, 安藤 孝将, 植田 亮, 元尾 伊織, 渕野 真代, 作村 美穂, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  117 ( 臨増大会 ) A775 - A775  2020.10

白血球数、リンパ球数減少が潰瘍性大腸炎患者におけるトファシチニブ減量後の非再燃を予測する

渕野 真代, 南條 宗八, 高嶋 祐介, 元尾 伊織, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  117 ( 臨増大会 ) A760 - A760  2020.10

消化器癌に対するMSI検査の実際と今後の課題

圓谷 俊貴, 安藤 孝将, 大屋 柚乃, 渕野 真代, 小林 才人, 元尾 伊織, 高橋 孝輔, 南條 宗八, 三原 弘, 藤浪 斗, 梶浦 新也, 田尻 和人, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  117 ( 臨増大会 ) A757 - A757  2020.10

【肝胆膵における結石診療のベストプラクティス】肝外/肝内胆管結石症 ERCPによる総胆管結石治療のベストプラクティス

安田 一朗, 花岡 辰行, 高橋 孝輔, 荒木 康宏, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人

肝胆膵 ( (株)アークメディア )  81 ( 2 ) 221 - 227  2020.08

【消化器疾患とステント治療】良性胆道狭窄に対するステント治療

高橋 孝輔, 安田 一朗, 圓谷 俊貴, 二日市 有花, 小林 才人, 高嶋 祐介, 元尾 伊織, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 藤浪 斗, 田尻 和人, 小松 直広, 小澤 栄介, 中尾 一彦

消化器・肝臓内科 ( (有)科学評論社 )  8 ( 1 ) 42 - 49  2020.07

クローン病におけるインフリキシマブ・バイオシミラーの有効性と安全性の検討

高嶋 祐介, 三原 弘, 元尾 伊織, 南條 宗八, 梶浦 新也, 安藤 孝将, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  117 ( 臨増総会 ) A282 - A282  2020.07

特集 胆膵内視鏡治療におけるトラブルシューティング ERCP関連治療における偶発症予防とトラブルシューティング ERCP関連治療における留意点と偶発症

安田 一朗, 小林 才人, 高橋 孝輔, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

消化器内視鏡 ( (株)東京医学社 )  32 ( 3 ) 314 - 322  2020.03

DOI

下痢と便秘の診断:問題点と対策 ナルデメジンの使用は経口オキシコドンの最高用量を増加させるか

梶浦 新也, 近岡 伸悟, 横田 朋学, 高嶋 祐介, 南條 宗八, 三原 弘, 安藤 孝将, 藤浪 斗, 安田 一朗, 林 龍二, 富山大学附属病院緩和ケアチーム

日本消化管学会雑誌 ( (一社)日本消化管学会 )  4 ( Suppl. ) 184 - 184  2020.01

[Approaching Upper Gastrointestinal Diseases-A New Approach from Morphology and Function].

Ikuji Nigami, Tomohiro Tada, Yoshiyuki Watanabe, Hiroshi Mihara, Yamawaki

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   117 ( 10 ) 876 - 887  2020  [Domestic journal]

DOI PubMed

好酸球性胃腸炎における好酸球浸潤の部位・程度と臨床的病態・治療反応性との関連についての検討

渕野 真代, 三原 弘, 作村 美穂, 元尾 伊織, 南條 宗八, 安藤 孝将, 梶浦 新也, 藤浪 斗, 安田 一朗

日本小腸学会学術集会プログラム・抄録集 ( 日本小腸学会 )  4   54 - 54  2020

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【目的】好酸球性胃腸炎症例における、病理組織学的所見と臨床的病態・治療反応性との関連性について検討した。 【方法】2006年11月から2020年6月に富山大学附属病院で好酸球性胃腸炎と診断された患者33例を対象とし、臨床的・病理組織学的所見を後方視的に検討した。検討項目は患者背景（性別、年齢）、臨床症状（腹痛、嘔気、下痢、食欲不振、腹部不快感）、血液検査所見（好酸球数、CRP、IgE）、病理所見（好酸球浸潤部位・程度）及び、治療経過（治療内容、臨床的寛解の有無）であり、電子カルテから情報を抽出した。臨床的寛解の定義は症状消失とした。 【結果】男性17例、女性16例、年齢中央値35歳（10-69歳）であり、治療内容は抗アレルギー薬28例、ステロイド15例、臨床的寛解に至った症例は25例（75.7%）、自然寛解は4例（12.1％）であった。各臨床症状と好酸球浸潤部位・程度には有意な相関はみられなかった。小腸・大腸に好酸球浸潤を認める場合は有意にCRPが高かった（P=0.032、0.019）。胃好酸球浸潤数20未満/HPF群は40以上/HPF群に比べ臨床的寛解率が高く（P=0.025）、また男性で臨床的寛解率が高かった（P=0.006）。 【結論】今回の検討より男性・胃好酸球浸潤の程度は臨床的寛解予測因子になり得ること、CRP高値は小腸大腸病変を示唆する可能性があることが示唆された。

DOI CiNii

Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.

Mihara H, Boudaka A, Tominaga M, Sugiyama T

Digestion   101 ( 1 ) 6 - 11  2020  [Refereed]  [International journal]

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BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation. SUMMARY: TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.

DOI PubMed

Management of Remnant or Recurrent Lesions after Endoscopic Papillectomy.

Yasuda I, Kobayashi S, Takahashi K, Nanjo S, Mihara H, Kajiura S, Ando T, Tajiri K, Fujinami H

Clinical endoscopy   53 ( 6 ) 659 - 662  2019.12  [Refereed]  [International journal]

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Endoscopic papillectomy (EP) for ampullary adenomas achieves cure rates ranging from 76% to 90%, and recurrence rates are as high as 33%. If remnant or recurrent lesions after prior EP are endoscopically visible and are not suspected of intraductal extension into the biliary or pancreatic duct, repeated snaring and cutting can be performed until all visible lesions are completely resected. However, endoscopic ablative therapies, particularly argon plasma coagulation, can be attempted for tiny or uncertain remnant and recurrent lesions. In addition, intraductal radiofrequency ablation has recently been attempted for residual intraductal lesions after EP at several institutions. Although still under investigation, it has shown some promise. It might be offered as an alternative to surgery, particularly in patients who are unfit for surgery or those who refuse to undergo surgery.

DOI PubMed

特集 結石除去を極める 総胆管結石の画像診断と標準的治療戦略

安田 一朗, 小林 才人, 高橋 孝輔, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

消化器内視鏡 ( (株)東京医学社 )  31 ( 11 ) 1601 - 1607  2019.11

DOI

Serum soluble interleukin-2 receptor levels for screening for malignant lymphomas and differential diagnosis from other conditions.

Murakami J, Arita K, Wada A, Mihara H, Origasa H, Kigawa M, Yasuda I, Sato T

Molecular and clinical oncology   11 ( 5 ) 474 - 482  2019.11  [Refereed]  [International journal]

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The serum soluble interleukin 2 receptor (sIL2R) level is elevated in patients with most types of lymphoid neoplasms, and is also elevated in patients with solid tumors or reactive conditions, such as severe inflammation. To evaluate the diagnostic significance of sIL2R levels for the screening and differential diagnosis of lymphomas, data from 248 consecutive adult patients with suspected lymphoma were retrospectively analyzed in order to determine its diagnostic characteristics and the clinical parameters that affect diagnosis. In 133 patients with aggressive or indolent lymphomas or related neoplasms, the sIL2R level was higher (median: 920 U/ml, standard deviation: 7,312 U/ml) compared with that of 115 patients with other diagnoses (median: 520 U/ml, standard deviation: 727 U/ml), including solid tumors, infection, inflammation, and others. When the cutoff value of sIL2R was 1,104 U/ml, the specificity was 80%, at which point lymphoma was suspected. When the threshold levels were increased from 1,500 to 2,000 U/ml, the specificity increased from 87 to 93%, with the positive likelihood ratio increasing from 2.99 to 4.97, strongly suggesting the diagnosis of lymphoma. The receiver operating characteristic curve for prediction of lymphoma by sIL2R revealed that the area under the curve was 0.695. The curve was nearest to the left corner of the plot when the threshold was 1,946 U/ml; at this point, the sensitivity, specificity and positive likelihood ratio were 35%, 93% and 5.06, respectively. Multivariate analysis demonstrated that an age >46 years and lactate dehydrogenase level >173 U/l appeared to increase the risk of malignant lymphoma diagnosis. Although sIL2R appears to be a less specific marker for the screening of lymphomas, its detection at higher levels strongly suggests the diagnosis of lymphomas. Therefore, sIL2R may be more useful compared with any other parameter for lymphoma diagnosis, provided other false-positive conditions are taken into consideration.

DOI PubMed

EUS-FNAで診断し得た尿管癌の浸潤による十二指腸狭窄の一例

笹川 都, 元尾 伊織, 植田 優子, 三原 弘, 安藤 孝将, 高嶋 祐介, 南條 宗八, 藤浪 斗, 梶浦 新也, 高橋 孝輔, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  129回   37 - 37  2019.11

クローン病に対するウステキヌマブの有効性、安全性の検討

中山 優吏佳, 南條 宗八, 高嶋 祐介, 三原 弘, 徳永 麻美, 村石 望, 横田 朋学, 植田 優子, 吉田 啓紀, 安藤 孝将, 梶浦 新也, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  116 ( 臨増大会 ) A812 - A812  2019.11

特徴的な病歴と身体所見を伴う腺腫性ポリポーシスからCMMRDの診断に至った症例の家系調査

圓谷 俊貴, 安藤 孝将, 横田 朋学, 野村 恵子, 作村 美穂, 三原 弘, 梶浦 新也, 吉田 啓紀, 南条 宗八, 藤浪 斗, 新井田 要, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  116 ( 臨増大会 ) A841 - A841  2019.11

DICを伴う切除非適応膵癌に対する薬物療法の治療成績

長田 巧平, 安藤 孝将, 二日市 有花, 高嶋 祐介, 小林 才人, 在田 幸太郎, 吉田 啓紀, 和田 暁法, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 田尻 和人, 峯村 正実, 安村 敏, 高原 照美, 佐藤 勉, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  116 ( 臨増大会 ) A829 - A829  2019.11

実診療におけるナルテメジンの処方状況と効果について

横田 朋学, 植田 優子, 梶浦 新也, 村石 望, 徳永 麻美, 高嶋 祐介, 元尾 伊織, 吉田 啓紀, 南條 宗八, 三原 弘, 安藤 孝将, 藤浪 斗, 近岡 伸悟, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  116 ( 臨増大会 ) A858 - A858  2019.11

【膵癌における内視鏡診断・治療の最前線】切除不能膵癌に対する内視鏡的胆道ステンティング

安田 一朗, 小林 才人, 高橋 孝輔, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

胆と膵 ( 医学図書出版(株) )  40 ( 9 ) 785 - 790  2019.09

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切除不能膵癌による胆道閉塞に対する治療法としては、現在、内視鏡的胆道ステンティングが第一選択として行われている。ステントの種類については、化学療法の進歩に伴い、より長期の開存が期待されるようになったことから、self-expandable metallic stent(SEMS)を使用する施設が増えており、とくに我が国においてはcovered SEMS(CSEMS)の評価が高い。しかし、海外では異論もあり、今後のさらなる比較検討が必要である。また、さらに長期の開存をめざして、新たなステントの開発も進められており、今後の展開が期待される。(著者抄録)

Gemcitabine療法が奏効し播種性血管内凝固症候群を離脱し得た進行膵癌の一例

中山 優吏佳, 吉田 啓紀, 高嶋 祐介, 元尾 伊織, 南條 宗八, 三原 弘, 安藤 孝将, 梶浦 新也, 藤浪 斗, 高原 照美, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  128回   35 - 35  2019.06

腸閉塞を来した腎細胞癌大腸転移の一例

村石 望, 安藤 孝将, 作村 美穂, 高嶋 祐介, 吉田 啓紀, 三原 弘, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  35 ( 1 ) 75 - 75  2019.06

胆管空腸吻合術後に胆管内に形成された過形成性ポリープを内視鏡的に切除しえた一例

横田 朋学, 三原 弘, 作村 美穂, 安藤 孝将, 梶浦 新也, 田尻 和人, 藤浪 斗, 峯村 正実, 安田 一朗

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  35 ( 1 ) 76 - 76  2019.06

【膵癌・胆道癌最新動向-変わる!膵癌周術期化学療法と免疫チェックポイント阻害剤-】膵癌・胆道癌の診断留意事項up to date 胆道鏡下生検の診断的意義

安田 一朗, 長田 巧平, 小林 才人, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗, 高原 照美

肝胆膵 ( (株)アークメディア )  78 ( 5 ) 803 - 808  2019.05

北陸地方初の大腸カプセル内視鏡導入の結果報告

横田 朋学, 三原 弘, 藤浪 斗, 吉田 啓紀, 南條 宗八, 梶浦 新也, 安藤 孝将, 安田 一朗

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  61 ( Suppl.1 ) 977 - 977  2019.05

当院における好酸球性胃腸炎の特徴

村石 望, 三原 弘, 長田 巧平, 作村 美穂, 吉田 啓紀, 南條 宗八, 梶浦 新也, 安藤 孝将, 藤浪 斗, 安田 一朗

日本内科学会雑誌 ( (一社)日本内科学会 )  108 ( 臨増 ) 260 - 260  2019.02

切除不能進行胃癌に対するニボルマブ療法1コース後に重症間質性肺炎を発症した1例

島田 清太郎, 安藤 孝将, 横田 朋学, 作村 美穂, 吉田 啓紀, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 安田 一朗

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  116 ( 2 ) 153 - 160  2019.02

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症例は66歳男性。進行胃癌に対してニボルマブ療法を開始後14日目に発熱と呼吸困難を自覚し、胸部CT検査で浸潤影主体の多発病変と周囲のすりガラス影を認めた。各種検査および経過から、ニボルマブによる器質化類似パターンの間質性肺炎と診断した。ステロイドパルス療法で軽快したが、ステロイド減量中に2度肺炎が増悪した。胃癌ニボルマブ投与後早期から発症した重篤な間質性肺炎はまれであり、報告した。(著者抄録)

[Severe interstitial lung disease after one cycle of nivolumab treatment in a patient with advanced gastric cancer].

Shimada S, Ando T, Yokota T, Sakumura M, Yoshita H, Nanjo S, Mihara H, Kajiura S, Fujinami H, Yasuda I

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   116 ( 2 ) 153 - 160  2019  [Refereed]  [Domestic journal]

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Although nivolumab was previously reported to cause immune-related interstitial lung diseases (ILD), the detailed characteristics of ILD in gastric cancer are not fully understood. We herein present a rare case of a 66-year-old male with advanced gastric cancer who experienced acute-onset high-grade fever and dyspnea and diagnosed with early-onset ILD during the first cycle of nivolumab. Computed tomography revealed patchy infiltrative shadows and ground-glass opacities. No pathological bacteria were detected in the sputum or the bronchoalveolar lavage, and serous antigens for virus and beta-D-glucan were below the detection limit. These findings were consistent with nivolumab-induced organizing pneumonia. The steroid pulse therapy was effective for ILD, and the patient had complete radiological response, although he relapsed twice during the steroid tapering period.

DOI PubMed

【選択的胆管挿管100%をめざして-We're gonna do it!-】カテーテル挿管法

安田 一朗, 長田 巧平, 小林 才人, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

胆と膵 ( 医学図書出版(株) )  39 ( 12 ) 1319 - 1323  2018.12

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近年欧米においては、ガイドワイヤーを用いた胆管挿管法が主流となっているが、日本においては造影カテーテルを用いた胆管挿管が今なお多くの施設で行われている。カテーテル挿管法においては、まず乳頭の形態から胆管の走行軸を想定し、これにカテーテルが進む軸を合わせるようにスコープのポジショニングを調整する。次いで内視鏡のアップアングルを上手く使って胆管挿管を試みる。Narrow distal segment(NDS)が長かったり、屈曲していたりする症例は、ときに選択的胆管挿管が難しいが、NDSの走行に合わせたスコープ、カテーテル操作を丁寧に行っていくことによって胆管挿管を成功させる。また、胆管挿管困難例に対しては、膵管ガイドワイヤー法がサルベージ手技として広く行われている。(著者抄録)

【胆膵ドレナージupdate】[胆道ドレナージ 総論]胆道ドレナージの動向と病態に応じた選択

安田 一朗, 長田 巧平, 小林 才人, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

消化器内視鏡 ( (株)東京医学社 )  30 ( 11 ) 1502 - 1509  2018.11

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現在、胆道ドレナージは非手術的な手技が第一選択とされ、さまざまな非手術的胆道ドレナージが病態に応じて行われている。胆嚢においては、従来の経皮経肝的アプローチに加えて内視鏡的経乳頭的ドレナージや超音波内視鏡下のドレナージも行われるようになっており、胆管については、閉塞部位、閉塞原因、患者の状態によってドレナージの方法が選択されている。胆管へのアプローチの基本は、内視鏡的経乳頭的アプローチであるが、使用するステントは従来のプラスチックステントに加えて、自己拡張型金属ステント(SEMS)やcovered SEMS、あるいは経鼻胆管ドレナージが病態に応じて選択されている。また、内視鏡的アプローチが困難な症例に対しては、EUS下の各種アプローチが近年盛んに行われている。本稿では病態に応じた胆道ドレナージの最近の動向について解説する。(著者抄録)

【Biliary access大辞典】経乳頭的biliary access カニュレーションテクニック ERCP後膵炎を最小にするテクニック・マネージメント

安田 一朗, 長田 巧平, 小林 才人, 南條 宗八, 三原 弘, 梶浦 新也, 安藤 孝将, 田尻 和人, 藤浪 斗

胆と膵 ( 医学図書出版(株) )  39 ( 臨増特大 ) 993 - 996  2018.11

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ERCP後膵炎はERCP関連手技におけるもっとも頻度の高い偶発症であるが、その発生機序についてはいまだ十分に明らかにされておらず、有効な対策も確立されていない。繰り返しの胆管カニュレーションによる乳頭浮腫やこれに伴う膵液のうっ滞・膵管内圧の上昇、膵管造影などが発症因子となっている可能性があることから、術者は乳頭へのアプローチをできる限り愛護的に行い、できるだけ少ないアプローチで胆管挿管を成功させるべく手技を工夫し、助手もまた造影剤注入のタイミングや注入量、ガイドワイヤー操作に細心の注意を払うよう心がける。また、胆管挿管困難例に対するサルベージ手技についても手技の選択や切り替えのタイミングを適切に判断する必要がある。(著者抄録)

骨髄癌腫症を伴うPS不良の若年性胃癌に対してFOL-FOX療法を施行した一例

長森 正和, 安藤 孝将, 作村 美穂, 三原 弘, 横田 朋学, 高島 祐介, 吉田 啓紀, 南條 宗八, 藤浪 斗, 梶浦 新也, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  127回   40 - 40  2018.11

進行大腸癌に対する化学療法中に意識障害を認めた2症例

桑野 博之, 高嶋 祐介, 梶浦 新也, 徳永 麻実, 横田 朋学, 村石 望, 重田 浩平, 二日市 有花, 小林 才人, 元尾 伊織, 長田 巧平, 作村 美穂, 吉田 啓紀, 南條 宗八, 三原 弘, 安藤 孝将, 藤浪 斗, 安田 一朗

日本消化器病学会北陸支部例会プログラム・抄録集 ( 日本消化器病学会-北陸支部 )  127回   42 - 42  2018.11

消化器癌に対する化学療法誘発性下痢症における小腸粘膜障害の検討

作村 美穂, 安藤 孝将, 吉田 啓紀, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 細川 歩, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  115 ( 臨増大会 ) A759 - A759  2018.10

高齢者の転移性・再発大腸癌患者におけるBevacizumab併用化学療法の有効性と安全性の検討

西野 貴晶, 梶浦 新也, 作村 美穂, 高木 宏明, 吉田 啓紀, 南條 宗八, 三原 弘, 安藤 孝将, 藤浪 斗, 杉山 敏郎

日本老年医学会雑誌 ( (一社)日本老年医学会 )  55 ( 4 ) 707 - 707  2018.10

実診療におけるナルデメジンの処方状況と効果について

二日市 有花, 梶浦 新也, 橋本 伊佐也, 猪又 峰彦, 島 友子, 堀川 英世, 藤浪 斗, 安藤 孝将, 三原 弘, 南條 宗八, 吉田 啓紀, 高木 宏明, 高嶋 祐介, 西野 貴明, 島田 清太郎, 作村 美穂, 高木 昭佳, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  115 ( 臨増大会 ) A790 - A790  2018.10

クローン病におけるインフリキシマブ・バイオシミラーの有効性、安全性の検討

高嶋 祐介, 南條 宗八, 三原 弘, 二日市 有花, 島田 清太郎, 作村 美穂, 西野 貴晶, 小林 才人, 明石 桃子, 高木 宏明, 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 )  115 ( 臨増大会 ) A767 - A767  2018.10

BBP不応切除不能大腸癌におけるFOLFIRI plus ramucirumab or afribercept療法の有効性

吉田 啓紀, 安藤 孝将, 島田 清太郎, 作村 美穂, 高嶋 祐介, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 小林 由夏, 安田 一朗, 杉山 敏郎

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  56回   P19 - 1  2018.10

Multiple Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum.

Mami Tokunaga, Sohachi Nanjo, Hiroki Yoshita, Haruka Fujinami, Tohru Watanabe, Yoko Ishii, Saito Kobayashi, Momoko Akashi, Hiroaki Takagi, Hiroshi Mihara, Shinya Kajiura, Takayuki Ando, Isaya Hashimoto, Shozo Hojo, Tomoyuki Okumura, Toshiro Sugiyama

Internal medicine (Tokyo, Japan)   57 ( 12 ) 1719 - 1723  2018.06  [Refereed]  [Domestic journal]

　View Summary

A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.

DOI PubMed

当科におけるクローン病に対するブデソニドの使用経験

長田 巧平, 三原 弘, 高木 宏明, 吉田 啓紀, 南條 宗八, 梶浦 新也, 安藤 孝将, 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 )  115 ( 臨増総会 ) A333 - A333  2018.03

Involvement of VNUT-exocytosis in transient receptor potential vanilloid 4-dependent ATP release from gastrointestinal epithelium.

Mihara H, Uchida K, Koizumi S, Moriyama Y

PloS one   13 ( 10 ) e0206276  2018  [Refereed]  [International journal]

　View Summary

Adenosine triphosphate (ATP) modulates mechanosensitive vagal afferent nerves in the gastrointestinal tract. ATP is stored in secretory vesicles via the ATP transporter VNUT. Recently, the bisphosphate clodronate was reported to inhibit VNUT and was suggested to be a safe potent therapeutic option for chronic pain. Transient receptor potential vanilloid 4 (TRPV4) is activated by mechanical stimuli and some epoxyeicosatrienoic acids and becomes sensitized under inflammatory conditions. We have previously reported that TRPV4 and VNUT are expressed in mouse esophageal keratinocytes and that TRPV4 activation induces ATP release in gastric epithelial cells. Here we show the expression of TRPV4 and VNUT in normal human gastrointestinal cell derived cell lines (GES-1 and CCD 841) and in tissues from normal and VNUT-KO mice. TRPV4 agonists (GSK101 or 8,9-EET) induced an increase in cytosolic Ca2+ and/or current responses in mouse primary colonic epithelial cells and CCD 841 cells, but not in cells isolated from TRPV4-KO mice. TRPV4 agonists (GSK101 or 5.6-EET) also induced ATP release in GES-1 and CCD 841 cells, which could be blocked by the VNUT inhibitor, clodronate. Thus, VNUT inhibition with clodronate could represent a novel therapeutic option for visceral pain.

DOI PubMed

Neuroendocrine carcinoma of the stomach: A response to combination chemotherapy consisting of ramucirumab plus paclitaxel

Yuki Matsubara, Takayuki Ando, Ayumu Hosokawa, Hiroshi Mihara, Hiroaki Takagi, Naokatsu Nakata, Hiroki Yoshita, Sohachi Nanjo, Shinya Kajiura, Haruka Fujinami, Toshiro Sugiyama

Internal Medicine ( Japanese Society of Internal Medicine )  57 ( 5 ) 671 - 675  2018  [Refereed]  [Domestic journal]

　View Summary

Extrapulmonary neuroendocrine carcinoma (NEC) is a rare disease, and there is no standard chemotherapy. A 73-year-old man was diagnosed with advanced gastric NEC. He received chemotherapy of irinotecan plus cisplatin, and amrubicin monotherapy. After failure of second-line chemotherapy, he received ramucirumab plus paclitaxel this treatment was chosen because vascular endothelial growth factor 2 was strongly expressed in the tumor endothelial cells. After two cycles, his NEC had markedly reduced in size, and he continued with this treatment for over eight months. In this case, the combination of an anti-angiogenic inhibitor and a cytotoxic agent was highly effective for gastric NEC.

DOI PubMed

EUS-FNAによる診断後、集学的治療により良好な経過を得ている悪性腹膜中皮腫の一例

横田 朋学, 安藤 孝将, 細川 歩, 三原 弘, 橋本 伊佐也, 北条 荘三, 吉田 啓紀, 南條 宗八, 梶浦 新也, 藤浪 斗, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  33 ( 2 ) 147 - 147  2017.11

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, 吉田 啓紀, 南條 宗八, 三原 弘, 梶浦 新也, 藤浪 斗, 杉山 敏郎

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  55回   P85 - 6  2017.10

Phase I/II Study of S-1 Plus Cisplatin Alternating With S-1 Plus Docetaxel in Patients With Advanced Gastric Cancer.

Hosokawa A, Ando T, Ogawa K, Ueda A, Yoshita H, Mihara H, Fujinami H, Kajiura S, Yabushita K, Horikawa N, Kobayashi Y, Yoshioka A, Origasa H, Sugiyama T

American journal of clinical oncology ( Ovid Technologies (Wolters Kluwer Health) )  41 ( 10 ) 977 - 981  2017.09  [Refereed]

DOI PubMed

当科におけるクローン病消化管癌合併例の検討

渕野 真代, 三原 弘, 南條 宗八, 藤浪 斗, 明石 桃子, 高木 宏明, 吉田 啓紀, 梶浦 新也, 安藤 孝将, 細川 歩, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  114 ( 臨増大会 ) A791 - A791  2017.09

Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium

Hiroshi Mihara, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa, Toshiro Sugiyama

HELICOBACTER ( WILEY )  22 ( 2 )  2017.04  [Refereed]

　View Summary

BackgroundHelicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. Materials and MethodsHuman gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca2+ imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay. ResultsTRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner. ConclusionHP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia.

DOI PubMed

膵内分泌細胞腫瘍に対する超音波内視鏡下穿刺吸引法の安全性と有用性の検討

高木 宏明, 梶浦 新也, 細川 歩, 中田 直克, 吉田 啓紀, 南條 宗八, 河合 健吾, 三原 弘, 安藤 孝将, 田尻 和人, 藤浪 斗, 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 )  114 ( 臨増総会 ) A347 - A347  2017.03

クローン病における免疫調節薬中止後の再燃リスク因子の検討

明石 桃子, 南條 宗八, 三原 弘, 松原 裕樹, 渕野 真代, 北林 誠, 高木 宏明, 中田 直克, 吉田 啓紀, 安藤 孝将, 藤浪 斗, 梶浦 新也, 細川 歩, 杉山 敏郎

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  114 ( 臨増総会 ) A335 - A335  2017.03

超音波内視鏡下穿刺吸引法で診断された膵神経内分泌腫瘍の5例

高木 宏明, 梶浦 新也, 細川 歩, 中田 直克, 吉田 啓紀, 南條 宗八, 河合 健吾, 三原 弘, 安藤 孝将, 田尻 和人, 藤浪 斗, 峯村 正実, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  32 ( 2 ) 157 - 157  2016.11

胃 腹膜播種 腹水を有する進行胃癌に対するサルベージ治療としてのIrinotecan療法の有効性

安藤 孝将, 細川 歩, 植田 亮, 北林 誠, 高木 宏明, 吉田 啓紀, 中田 直克, 南條 宗八, 三原 弘, 藤浪 斗, 梶浦 新也, 小川 浩平, 杉山 敏郎

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  54回   WS56 - 3  2016.10

Cisplatin投与困難な進行胃癌症例に対するS-1+Oxaliplatin療法の治療成績

島田 清太郎, 安藤 孝将, 細川 歩, 高木 宏明, 高取 俊介, 中田 直克, 吉田 啓紀, 三原 弘, 梶浦 新也, 三浦 慶昭, 藤浪 斗, 杉山 敏郎

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  54回   P32 - 6  2016.10

TAS102療法中に発症した血球貪食症候群の1例

二日市 有花, 梶浦 新也, 細川 歩, 元尾 伊織, 中田 直克, 吉田 啓紀, 在田 幸太郎, 和田 暁法, 南條 宗八, 三原 弘, 安藤 孝将, 藤浪 斗, 村上 純, 杉山 敏郎

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  54回   P74 - 3  2016.10

A case of advanced gastric cancer with severe jaundice from multiple liver metastases that was significantly improved after capecitabine plus oxaliplatin treatment

Hiroaki Takagi, Takayuki Ando, Ayumu Hosokawa, Takaaki Nishino, Hiroshi Mihara, Hiroki Yoshita, Naokatsu Nakada, Sohachi Nanjo, Yoshiaki Miura, Shinya Kajiura, Haruka Fujinami, Toshiro Sugiyama

Japanese Journal of Cancer and Chemotherapy ( Japanese Journal of Cancer and Chemotherapy Publishers Inc. )  43 ( 9 ) 1117 - 1119  2016.09  [Refereed]

　View Summary

A 74-year-old man with advanced gastric cancer was admitted to our hospital. His liver function was impaired (total bilirubin 1.6 mg/dL) with multiple liver metastases. He was treated with chemotherapy of S-1 plus cisplatin but it was discontinued due to severe diarrhea (CTCAE Grade 3) on day 6 and his liver dysfunction progressed (total bilirubin 10.3 mg/dL). After his diarrhea improved, he was treated with capecitabine plus oxaliplatin (capecitabine 3,600 mg/day on day 1-14, oxaliplatin 130 mg/m2 on day 1, q3 weeks). His severe jaundice and general condition improved without severe non-hematological toxicity, and he was ultimately discharged. He achieved a partial response (RECIST vl.1) after capecitabine plus oxaliplatin treatment, and this therapy has been continued for 15 months. This case suggests that capecitabine plus oxaliplatin may be beneficial even in advanced gastric cancer patients with impaired liver function from multiple liver metastases.

PubMed

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

　View Summary

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]

　View Summary

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]

　View Summary

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]

　View Summary

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

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

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

　View Summary

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]

　View Summary

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]

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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

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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例を経験した。Infliximab投与開始19ヵ月後に紫斑が出現し、皮膚生検で白血球破砕性血管炎を認めIgA血管炎と診断した。Adalimumabへの変更当初は紫斑消失を認めていたが、Adalimumabに変更した21ヵ月後に紫斑の再発を認めた。(著者抄録)

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]

　View Summary

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]

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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]

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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]

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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]

　View Summary

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

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]

　View Summary

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

　View Summary

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]

　View Summary

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]

　View Summary

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]

　View Summary

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]

　View Summary

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

潰瘍性大腸炎における発がんリスクマーカーとしてのmiR-124aのDNAメチル化異常

板谷 優子, 安藤 孝将, 南條 宗八, 吉田 啓紀, 植田 亮, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 細川 歩, 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 ( 臨増総会 ) A224 - A224  2013.02

HER2陽性進行胃癌に対するTrastuzumabの使用経験

植田 亮, 細川 歩, 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, 小川 浩平, 杉山 敏郎

日本胃癌学会総会記事 ( (一社)日本胃癌学会 )  85回   335 - 335  2013.02

腹水を有する進行・再発胃癌の化学療法における血清CA125早期低下の意義

安藤 孝将, 細川 歩, 板谷 優子, 吉田 啓紀, 植田 亮, 三原 弘, 藤浪 斗, 梶浦 新也, 西川 潤, 小林 隆司, 堀川 直樹, 薮下 和久, 野手 雅幸, 杉山 敏郎

日本胃癌学会総会記事 ( (一社)日本胃癌学会 )  85回   273 - 273  2013.02

HER2陽性進行胃癌に対するTrastuzumabの使用経験

植田 亮, 細川 歩, 禿 晃仁, 高木 宏明, 吉田 啓紀, 齋藤 聖子, 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 )  47 ( 3 ) 2209 - 2209  2012.10

Fragmented CagA Protein is Highly Immunoreactive in Japanese Patients

Kazuki Yamada, Toshiro Sugiyama, Hiroshi Mihara, Shinya Kajiura, Seiko Saito, Yuko Itaya, Hidemoto Yamawaki, Takayuki Ando, Takahiko Kudo, Ayumu Hosokawa, Masumi Okuda, Kenichi Fukunaga, Junko K. Akada, Teruko Nakazawa

HELICOBACTER ( WILEY-BLACKWELL )  17 ( 3 ) 187 - 192  2012.06  [Refereed]

　View Summary

Background: High-molecular-weight cell-associated proteins (HM-CAP) assay is the most popular serological immunoassay worldwide and has been developed from US isolates as the antigens. The accuracy is reduced when the sera are from adults and children in East Asia including Japan. To overcome the reduced accuracy, an enzyme immunoassay using Japanese strainderived HM-CAP (JHM-CAP) was developed, in which the antigens were prepared by exactly the same procedure as HM-CAP. The performance of JHM-CAP was better than that of HM-CAP in Japanese adults as well as in children. The higher sensitivity was because of the presence of 100-kDa protein that was absent in the preparation of HM-CAP antigen. Materials and Methods: Immunoblot analysis and peptide mass fingerprinting methods were used to identify the distinctive 100-kDa protein present in JHM-CAP antigens. The peptide sequence and identification were analyzed by Mascot Search on the database of Helicobacter pylori. The identified protein was confirmed by immunoblot with a specific antibody and inhibition assay by the sera. Results: The distinctive 100-kDa protein was a fragment of CagA derived from Japanese clinical isolates, and the sera of Japanese patients had strongly reacted to the protein, probably to the exposed epitope on the fragmented CagA. The fragmentation of CagA had occurred in the process of antigen preparation in Japanese isolates, not in US isolates even under the same preparation. Conclusion: The distinctive 100-kDa protein was a fragment of CagA protein of H. pylori derived from Japanese clinical isolates, and Japanese patients including children are likely to react strongly to the exposed epitopes on fragmented CagA.

DOI PubMed

最近10年間における出血性胃・十二指腸潰瘍の経年的変化

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

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  28 ( 1 ) 78 - 78  2012.05

Endoscopic hemostasis attempt during intra-aortic balloon occlusion for massively bleeding duodenal ulcer. A case report

Masaaki Yamada, Keizo Kato, Rei Kashima, Makoto Fujimoto, Hiroshi Mihara, Shinya Kajiura, Haruka Fujinami, Michio Tanaka

Endoscopic Forum for Digestive Disease   28 ( 1 ) 35 - 41  2012.05

　View Summary

A 71-year-old man was admitted in an unconscious state with bloody stools. By endoscopy we detected a large amount of blood in the duodenal bulb and a portion of an ulcer lesion on the posterior wall. We were unable to locate the bleeding vessel because of duodenal deformity and massive hemorrhage. Despite blood transfusion, the patient's state continued to deteriorate. His blood pressure was below 80 mm Hg. To treat the shock, we inserted the intra-aortic balloon occlusion (IABO) catheter, which maintained the blood pressure of the upper half of the body and lessened gastrointestinal bleeding. We then attempted endoscopic hemostasis without success. We were able to transfer the patient to the operation room with while maintaining the blood pressure. The operative findings indicated penetration of the duodenal ulcer into the pancreas and stiff adhesion with the peritoneum. Oozing was observed at several locations of the ulcer floor (pancreas itself) and the gastro-duodenal artery had ruptured at 2 sites. The JSGE guideline for the management of peptic ulcer recommends interventional radiology and surgery in cases where endoscopic hemostasis is difficult. However, in patients exhibiting hemodynamic instability with critically uncontrollable hemorrhagic shock, IABO can be effective in maintaining blood pressure and transferring patients safely.

出血性十二指腸潰瘍によるショック離脱困難例に対する、内視鏡的止血術と大動脈閉塞バルーン(IABO)挿入法併用の1例

山田 正明, 加藤 慶三, 鹿島 励, 藤本 誠, 三原 弘, 梶浦 新也, 藤浪 斗, 田中 三千雄

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  28 ( 1 ) 35 - 41  2012.05

　View Summary

外傷や産科関連の疾患による出血などの腹部救急領域において、出血性ショック時の治療の一環として大動脈閉塞バルーン(intra-aortic balloon occlusion、IABO)が頻用されている。今回、出血性十二指腸潰瘍によってショックから離脱できなかった症例に対し、IABO挿入法を併用した内視鏡的止血術を施行した。内視鏡止血術では止血に至らなかったが、IABOによる下行大動脈遮断によって、上半身の血圧維持が可能となり、緊急外科手術のための手術室への移送が可能となった。従来、消化管出血に対する内視鏡的止血術が困難な例には外科手術、IVRが適応とされてきた。しかし、その様な治療を行う場所への移送も困難な程に高度なショック状態にある症例に対しては、IABO挿入法の併用は移送を可能にし、有用な手段であると考えられた。(著者抄録)

[The 38th Hokuriku Branch Seminar Report: overview and evaluation results of the first abdominal emergency medical training course (AbdEMeT)].

Mihara H, Okazawa S, Wada A, Murakami J, Sugiyama T, Nomura H, Kajinami K

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   101 ( 4 ) 1112 - 1116  2012.04  [Refereed]  [Domestic journal]

PubMed

Two cases of thiopurine-induced acute pancreatitis in inflammatory bowel disease

Jun Nishikawa, Takahiko Kudo, Takako Miyazaki, Hiroshi Mihara, Akira Ueda, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Kohei Ogawa, Ayumu Hosokawa, Toshiro Sugiyama

Journal of Japanese Society of Gastroenterology   109 ( 2 ) 224 - 230  2012.02  [Refereed]

　View Summary

Thiopurine drugs have been widely used in the treatment of inflammatory bowel disease. However, their use is limited by adverse effect that can lead to cessation of therapy. We report 2 cases of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease. Both patients complained of abdominal pain, showed elevated pancreatic enzymes, and swollen pancreases on computed tomography. The patients' signs and symptoms resolved uneventfully after withdrawal of the thiopurine drugs. Although the mechanism of thiopurine-induced pancreatitis remains unclear, close monitoring and early recognition of acute pancreatitis is important in the management of new thiopurine users.

DOI PubMed

悪性リンパ腫診断における血清可溶性インターロイキン-2受容体値の再検討

村上 純, 三原 弘, 在田 幸太郎, 和田 暁法, 宮園 卓宜, 杉山 敏郎

日本内科学会雑誌 ( (一社)日本内科学会 )  101 ( Suppl. ) 257 - 257  2012.02

Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Kohei Ogawa, Ayumu Hosokawa, Akira Ueda, Seiko Saito, Hiroshi Mihara, Takayuki Ando, Shinya Kajiura, Mitsuhiro Terada, Yuji Tsukioka, Naoki Horikawa, Takashi Kobayashi, Masayuki Note, Kunihiro Sawasaki, Junya Fukuoka, Toshiro Sugiyama

GASTROENTEROLOGY RESEARCH AND PRACTICE ( HINDAWI PUBLISHING CORPORATION )  2012   640401  2012  [Refereed]

　View Summary

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.

DOI PubMed

集学的内視鏡検査が、止血に役立った小腸血管異形成の一例

三原 弘, 菅谷 彰, 植田 亮, 安藤 孝将, 西川 潤, 藤浪 斗, 梶浦 新也, 小川 浩平, 細川 歩, 魚谷 英之, 杉山 敏郎

ENDOSCOPIC FORUM for digestive disease ( (株)癌と化学療法社 )  27 ( 2 ) 174 - 174  2011.11

Infliximab-induced lupus erythematosus in a case of ulcerative colitis

Jun Nishikawa, Takako Miyazaki, Nobuhiro Suzuki, Yuko Itaya, Hidemoto Yamawaki, Hiroshi Mihara, Yushi Hasumoto, Haruka Fujinami, Kohei Ogawa, Ayumu Hosokawa, Takahiko Kudo, Toshiro Sugiyama

Journal of Japanese Society of Gastroenterology   108 ( 9 ) 1535 - 1539  2011.09  [Refereed]

　View Summary

Infliximab is widely used in the treatment of inflammatory bowel disease, but despite its good clinical efficacy and tolerance, drug-induced autoimmune disorders have been reported as adverse reactions and are a matter of concern. Here we report a patient with ulcerative colitis who developed drug-induced lupus erythematosus after infliximab treatment While this is a rare complication of infliximab, early diagnosis and successful management are essential.

DOI PubMed

進行・再発胃癌の化学療法における血清CA125の有用性

板谷 優子, 安藤 孝将, 細川 歩, 中田 直克, 鈴木 庸弘, 植田 亮, 山脇 秀元, 齋藤 聖子, 三原 弘, 蓮本 祐史, 藤浪 斗, 梶浦 新也, 西川 潤, 宮嵜 孝子, 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 )  108 ( 臨増大会 ) A808 - A808  2011.09

抗血小板薬・抗凝固薬服用例の出血性胃十二指腸潰瘍に対する最適な止血術の検討

藤浪 斗, 細川 歩, 小川 浩平, 宮嵜 孝子, 西川 潤, 梶浦 新也, 蓮本 祐史, 安藤 孝将, 三原 弘, 板谷 優子, 植田 亮, 山脇 秀元, 鈴木 庸弘, 中田 直克, 杉山 敏郎

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  53 ( Suppl.2 ) 2793 - 2793  2011.09

Transient receptor potential vanilloid 4 (TRPV4)-dependent calcium influx and ATP release in mouse oesophageal keratinocytes

Hiroshi Mihara, Ammar Boudaka, Toshiro Sugiyama, Yoshinori Moriyama, Makoto Tominaga

JOURNAL OF PHYSIOLOGY-LONDON ( WILEY-BLACKWELL )  589 ( 14 ) 3471 - 3482  2011.07  [Refereed]

　View Summary

Gastro-oesophageal reflux disease (GERD) is amulti-factorial disease that may involve oesophageal hypersensitivity to mechanical or heat stimulus as well as acids. Intraganglionic laminar endings (IGLEs) are the most prominent terminal structures of oesophageal vagal mechanosensitive afferents and may modulate mechanotransduction via purinergic receptors. Transient receptor potential channel vanilloid 4 (TRPV4) can detect various stimuli such as warm temperature, stretch and some chemicals, including 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) and GSK1016790A. TRPV4 is expressed in many tissues, including renal epithelium, skin keratinocytes and urinary bladder epithelium, but its expression and function in the oesophagus is poorly understood. Here, we show anatomical and functional TRPV4 expression in mouse oesophagus and its involvement in ATP release. TRPV4 mRNA and protein were detected in oesophageal keratinocytes. Several known TRPV4 activators (chemicals, heat and stretch stimulus) increased cytosolic Ca(2+) concentrations in cultured WT keratinocytes but not in TRPV4 knockout (KO) cells. Moreover, the TRPV4 agonist GSK1016790A and heat stimulus evoked TRPV4-like current responses in isolated WT keratinocytes, but not in TRPV4KO cells. GSK1016790A and heat stimulus also significantly increased ATP release from WT oesophageal keratinocytes compared to TRPV4KO cells. The vesicle-trafficking inhibitor brefeldin A (BFA) inhibited the ATP release. This ATP release could be mediated by the newly identified vesicle ATP transporter, VNUT, which is expressed by oesophageal keratinocytes at the mRNA and protein levels. In conclusion, in response to heat, chemical and possibly mechanical stimuli, TRPV4 contributes to ATP release in the oesophagus. Thus, TRPV4 could be involved in oesophageal mechano -and heat hypersensitivity.

DOI PubMed

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

Hiroshi Mihara, Ammar Boudaka, Koji Shibasaki, Akihiro Yamanaka, Toshiro Sugiyama, Makoto Tominaga

JOURNAL OF NEUROSCIENCE ( SOC NEUROSCIENCE )  30 ( 49 ) 16536 - 16544  2010.12  [Refereed]

　View Summary

Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52 degrees C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca(2+) concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.

DOI PubMed

The modified glucose clearance test: a novel non-invasive method for differentiating non-erosive reflux disease and erosive oesophagitis

H. FUJINAMI, T. KUDO, T. MIYAZAKI, A. HOSOKAWA, H. MIHARA, T. ANDO, T. SUGIYAMA

Alimentary Pharmacology & Therapeutics ( Wiley )  28 ( 10 ) 1259 - 1264  2008.11  [Refereed]

DOI

IgM-M蛋白を伴う慢性炎症性脱髄性多発神経炎の経過中に発症した小腸MALTリンパ腫

嶋 香菜子, 村上 純, 在田 幸太郎, 米澤 和美, 宮園 卓宜, 三原 弘, 折原 正周, 杉山 敏郎, 田口 芳治, 道具 伸浩, 高嶋 修太郎, 野本 一博, 石澤 伸, 高野 康雄

臨床血液 ( (一社)日本血液学会-東京事務局 )  49 ( 9 ) 1116 - 1116  2008.09

十二指腸転移をきたした大腸癌の1例

植田 亮, 細川 歩, 三原 弘, 安藤 孝将, 梶浦 新也, 小川 浩平, 岸 遂忠, 藤浪 斗, 西川 潤, 宮嵜 孝子, 工藤 俊彦, 折原 正周, 杉山 敏郎

腫瘍内科 ( (有)科学評論社 )  2 ( 3 ) 268 - 272  2008.06

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61歳男。3年3ヵ月前にS状結腸癌、右肺転移で手術を施行し、その7ヵ月後と2年後に肺転移で手術を施行した。10ヵ月後に縦隔および腹部リンパ節転移を認めてFOLFIRI療法で腫瘍は縮小したが、3ヵ月後より悪心・嘔吐、食欲不振が持続し、精査加療目的入院となった。肝胆道系酵素、アミラーゼ値の上昇、血清アルブミン値、コリンエステラーゼ値の低下を認め、癌胎児性抗原値の上昇を認めた。上部消化管内視鏡で十二指腸下行脚に結節性の隆起性病変、肛門側に全周性の壁肥厚像、内腔の狭窄像を認め、ガストログラフィンによる十二指腸造影では十二指腸下行脚から水平脚にかけて全周性に壁不整像、狭窄像、可動性の低下を認めた。病理所見では、中分化腺癌の増殖を認めるも、腫瘍は十二指腸粘膜固有の腺管との連続を示さず、周囲の十二指腸の腺管に異常は認めず、CK7陰性、CK20陽性であった。また、リンパ管侵襲を認めた。以上の所見から、リンパ行性の大腸癌の転移と診断した。FOLFIRI療法に抵抗性のため、第3病日よりmodified FOLFOX6療法を施行し、食欲不振の自覚症状は改善し退院した。画像所見の改善を認め、胆道系酵素、血清アミラーゼ値も低下した。

Idiopathic portal thrombosis, improved by conservative management: A case report

Hiroshi Mihara, Seiko Yoshida, Mitsuru Yagi, Hiroyuki Ito, Hiroshi Nanasawa

Japanese Journal of Gastroenterology   104 ( 7 ) 1057 - 1062  2007.07  [Refereed]

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A 40-year-old man complaining of epigastralgia for one week was admitted. Subacute chronic idiopathic portal thrombosis was diagnosed and he improved by anti-coagulation and fibrinolytic therapy. No predisposing factor was identified. As there are many idiopathic portal thrombosis cases in Japan, and there is a possibility that some inherent thrombus predisposing factors are hidden, further study of this condition is necessary.

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Cholangiocarcinoma at the cystic duct discovered by lymph node metastases with clear cell transformation

Kazuto Tajiri, Yukihiro Shimizu, Hiroshi Mihara, Yoshihiro Kawanishi, Tadahiro Orihara, Hiroyuki Takahashi, Shin Ishizawa, Satoshi Kawai, Toshiro Sugiyama

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  45 ( 18 ) 1045 - 1048  2006  [Refereed]

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We encountered a case with cholangiocarcinoma of the cystic duct, which was first manifested by multiple lymph node metastases with clear cell changes resembling clear cell adenocarcinoma (CCC). Because the clear cell changes were not prominent at the primary site, clear cell transformation might have occurred preferentially at the metastatic lesion in this case. Alternatively, tumor cells with clear cell transformation, found at the primary site, might have high metastatic potential. The patient showed thromboembolism and hypercalcemia as paraneoplastic syndromes at the terminal stage as reported in patients with CCC of the ovary. Those complications might be common biological features of CCC.

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