膵癌リンパ管侵襲の病態解明とそれを抑制する新規治療法の開発

• Project/Area Number: 20K08364
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Jichi Medical University
• Principal Investigator: 大城 久 自治医科大学, 医学部, 教授 (60381513)
• Co-Investigator(Kenkyū-buntansha): 池田 啓子 独立行政法人国立病院機構村山医療センター(臨床研究部), 病態生理学研究室, 室長 (10265241) ; 福嶋 敬宜 自治医科大学, 医学部, 教授 (40384937) ; 仲矢 丈雄 自治医科大学, 医学部, 准教授 (80512277)
• Project Period (FY): 2020-04-01 – 2025-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2023: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膵体尾部癌 / 浸潤性膵管癌 / D2-40 / podoplanin / prox1 / CD31 / リンパ管侵襲 / 術前化学療法 / 膵体尾部切除術 / 膵頭部癌 / ポドプラニン / Podoplanin / Prox1 / Allred score / 感度 / 特異度 / リンパ管 / 胸管 / 膵癌

Outline of Research at the Start

膵癌は予後不良な疾患である。癌のリンパ管侵襲の程度が膵癌術後の予後を正確に予測し，リンパ管侵襲の抑制が予後の改善に繋がる可能性が報告されているが、膵癌がリンパ管内に侵入する機序は解明されていない。本研究では膵癌リンパ管侵襲の病態を解明し、リンパ管侵襲を抑制する新規治療法の開発に繋げることを目指す。

Outline of Annual Research Achievements

膵体尾部癌における術前化学療法が癌のリンパ管侵襲に与える影響については良く分かっていない．本年度はpilot studyとして膵体尾部原発の浸潤性膵管癌の手術症例（n=26）を後方視的，臨床病理学的に解析し，術前化学療法が癌のリンパ管侵襲本数に与える影響を検討した．リンパ管侵襲本数の測定には病理組織標本を作製し，hematoxylin and eosin染色とともに，Elastica-van Gieson染色，D2-40（podoplanin）染色，prox1染色，CD31染色を用いた．
症例は男12例，女14例，年齢の中央値は75（最小値57，最大値83），術前化学療法施行例が19例，Stage Iが9例，Stage IIが17例（Stage IIAが9例，IIBが8例，），リンパ節転移陽性例が8例，リンパ管侵襲陽性例が7例であった．術前化学療法の有無にかかわらず， Stage IおよびStage IIAではリンパ管侵襲は認められなかった．癌の最大割面におけるリンパ管侵襲の本数の中央値は0（最小値0，最大値16）であった．リンパ管侵襲本数の中央値は術前化学療法未施行例では0（最小値0，最大値16），術前化学療法施行例では0（最小値0，最大値16）であった．
膵体尾部癌において術前化学療法施行群では未施行群よりもリンパ管侵襲本数が少ない傾向が示唆された．しかしながら，本年度の解析症例数は統計学的検定を行うための十分なサンプル数に達していなかったため，術前化学療法の有無がリンパ管侵襲本数に与える影響については明らかにできなかった．

Current Status of Research Progress

4: Progress in research has been delayed.

Reason

膵体尾部癌の解析症例数が統計学的検定を行うための十分なサンプル数に達していなかったため，術前化学療法の有無がリンパ管侵襲本数に与える影響を明らかにできなかった．

Strategy for Future Research Activity

体尾部原発の浸潤性膵管癌の解析症例数をさらに増やし，術前化学療法が癌のリンパ管侵襲本数に与える影響やその病態，予後との関連性等を明らかにしていく予定である．

Research Products

• [Journal Article] Primary Bile Duct Diffuse Large B-cell Lymphoma Diagnosed by Repeated Endoscopic Ultrasound-guided Fine-needle Aspiration and Endoscopic Retrograde Cholangiopancreatography (2024)
  • Author(s): Imai Y, Sekine M, Aoyama K, Kojima S, Sasaki G, Sato A, Matsumoto K, Morino M, Kashima H, Koito Y, Miura T, Takahashi Y, Ishii T, Tsuboi R, Otake H, Yoshikawa S, Uehara T, Asano T, Matsumoto S, Miyatani H, Oshiro H, Mashima H.
  • Journal Title: Internal Medicine Volume: 63 Issue: 4 Pages: 493-501
  • DOI: 10.2169/internalmedicine.1776-23
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2024-02-15
  • Peer Reviewed
• [Journal Article] Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report. (2024)
  • Author(s): Watanabe Y, Hirai K, Hirata M, Kitano T, Ito K, Ookawara S, Oshiro H, Morishita Y.
  • Journal Title: BMC Nephrol Volume: 25 Issue: 1 Pages: 53-53
  • DOI: 10.1186/s12882-024-03485-2
  • Peer Reviewed
• [Journal Article] Mycobacterium abscessus subspecies massiliense infection with anti-interferon-gamma autoantibodies (2024)
  • Author(s): Marino Hirata, Takahiko Fukuchi, Hitoshi Sugawara, Ibuki Kurihara, Keishiro Sueda, Akira Ishi a, Maya Takazawa, Yasuhiro Yamaguchi, Hisashi Oshiro, Takuro Sakagami
  • Journal Title: Clinical Infection in Practice Volume: 21 Pages: 100333-100333
  • DOI: 10.1016/j.clinpr.2023.100333
  • Peer Reviewed
• [Journal Article] Secondary Budd-Chiari syndrome caused by adult T-cell leukemia/lymphoma. (2023)
  • Author(s): Tominaga R, Yoshimura K, Kawamura M, Kako S, Kanda Y, Morikawa H, Ando S, Okabe N, Hiruta M, Tanaka A, Oshiro H.
  • Journal Title: Pathol Int Volume: 73 Issue: 10 Pages: 520-522
  • DOI: 10.1111/pin.13358
  • Peer Reviewed
• [Journal Article] 18F-FDG PET/CT findings in autopsy confirmed a case of ischemic cardiac disease at an early stage (2023)
  • Author(s): Osamu Manabe, Takunori Tsukui, Kazuki Yoshimura, Hisashi Oshiro, Noriko Oyama-Manabe, Tadao Aikawa, Keiko Takahashi, Kenichi Sakakura, Hideo Fujita
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 50 Issue: 7 Pages: 2224-2225
  • DOI: 10.1007/s00259-023-06116-4
  • Peer Reviewed
• [Journal Article] 膵神経内分泌腫瘍の1例 (2023)
  • Author(s): 織田聖月，河野哲也，中村啓子，小島朋子，細田健太，猪山和美，守川春花，岡部直太，蛭田昌宏，田中 亨，大城 久
  • Journal Title: 埼玉県臨床細胞学会雑誌 Volume: 41
  • Peer Reviewed
• [Journal Article] A case of asymmetric insulin-derived localised amyloid deposition associated with long-acting insulin analog administration (2022)
  • Author(s): Hirai Keiji、Imamura Shigeki、Hirai Aizan、Umemoto Naoka、Oshiro Hisashi、Kametani Fuyuki、Katoh Nagaaki、Yazaki Masahide、Ookawara Susumu、Morishita Yoshiyuki
  • Journal Title: Amyloid Volume: - Issue: 3 Pages: 1-3
  • DOI: 10.1080/13506129.2022.2047019
  • Peer Reviewed
• [Journal Article] Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation Study (2021)
  • Author(s): Sugimoto Katsutoshi、Lee Dong Ho、Lee Jae Young、Yu Su Jong、Moriyasu Fuminori、Sakamaki Kentaro、Oshiro Hisashi、Takahashi Hiroshi、Kakegawa Tatsuya、Tomita Yusuke、Abe Masakazu、Yoshimasu Yu、Takeuchi Hirohito、Choi Byung Ihn、Itoi Takao
  • Journal Title: Radiology Volume: 301 Issue: 3 Pages: 625-634
  • DOI: 10.1148/radiol.2021210046
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A case of prominent immunoglobulin IgG4‐positive lymphadenopathy in response to microscopic lung cancer (2021)
  • Author(s): Yuzawa Motoi、Ohta Hiromitsu、Nomura Motoko、Minegishi Kentaro、Oshiro Hisashi、Yamaguchi Yasuhiro
  • Journal Title: Respirology Case Reports Volume: 9 Issue: 11
  • DOI: 10.1002/rcr2.854
  • Peer Reviewed
• [Journal Article] Cytological detection of metastatic chordoma cells in pleural effusions: A case report (2021)
  • Author(s): Tamba‐Sakaguchi Mio、Oshiro Hisashi、Mato Naoko、Kikkawa Ichiro、Endo Teruaki、Yanagita Miki、Suzuki Tomoko、Akimoto Maho、Okabe Naota、Hiruta Masahiro、Ikeda Eriko、Fukushima Noriyoshi
  • Journal Title: Diagnostic Cytopathology Volume: 49 Issue: 11
  • DOI: 10.1002/dc.24832
  • Peer Reviewed
• [Journal Article] The most appropriate region-of-interest position for attenuation coefficient measurement in the evaluation of liver steatosis (2021)
  • Author(s): Sugimoto Katsutoshi、Abe Masakazu、Oshiro Hisashi、Takahashi Hiroshi、Kakegawa Tatsuya、Tomita Yusuke、Yoshimasu Yu、Takeuchi Hirohito、Itoi Takao
  • Journal Title: Journal of Medical Ultrasonics Volume: 48 Issue: 4 Pages: 615-621
  • DOI: 10.1007/s10396-021-01124-z
  • Peer Reviewed
• [Journal Article] Elucidation of spleen elasticity and viscosity in a carbon tetrachloride rat model of liver cirrhosis using a new ultrasound elastography (2021)
  • Author(s): Furuichi Yoshihiro、Sugimoto Katsutoshi、Oshiro Hisashi、Abe Masakazu、Takeuchi Hirohito、Yoshimasu Yuu、Itoi Takao
  • Journal Title: Journal of Medical Ultrasonics Volume: 48 Issue: 4 Pages: 431-437
  • DOI: 10.1007/s10396-021-01110-5
  • Peer Reviewed
• [Journal Article] Clinical case of lung spindle cell carcinoma markedly responsive to pembrolizumab. (2021)
  • Author(s): Mizushina, Y., Ohyanagi, F., Shiihara, J., Nomura, M., Ohta, H., Oshiro, H., Tsubochi, H., Kusaka, G. and Yamaguchi, Y.
  • Journal Title: Thorac Cancer Volume: 12 Issue: 16 Pages: 2279-2282
  • DOI: 10.1111/1759-7714.14068
  • Peer Reviewed / Open Access
• [Journal Article] A method to obtain reproducible Ki-67 indices in lung adenocarcinoma (2021)
  • Author(s): Koji Okudela, Tetsukan Woo, Yusuke Saigusa, Hiromasa Arai, Mai Matsumura, Hideaki Mitsui, Misaki Sugiyama, Motoki Sekiya, Yoshihiro Ishikawa, Hisashi Oshiro, Yoichi Kameda, Kenichi Ohashi
  • Journal Title: Histopathology Volume: 78(3) Issue: 3 Pages: 414-423
  • DOI: 10.1111/his.14234
  • Peer Reviewed / Open Access
• [Journal Article] Adenomyoepithelioma with a human epidermal growth factor receptor 2-fluorescence in situ hybridization-confirmed ductal carcinoma in situ component (2020)
  • Author(s): Amano Yusuke、Sakaguchi-Tamba Mio、Sasaki Yumiko、Oshiro Hisashi、Fukushima Noriyoshi、Fujita Takashi、Masuda Shinobu、Niki Toshiro
  • Journal Title: Medicine Volume: 99 Issue: 42 Pages: e22665-e22665
  • DOI: 10.1097/md.0000000000022665
  • Peer Reviewed / Open Access
• [Journal Article] Pancreaticoduodenectomy for a primary duodenal capicua transcriptional repressor (CIC) -rearranged sarcoma with severe bleeding: a case report (2020)
  • Author(s): Aoki Yuichi、Oshiro Hisashi、Yoshida Akihiko、Morishima Kazue、Miki Atsushi、Sasanuma Hideki、Sakuma Yasunaru、Lefor Alan Kawarai、Sata Naohiro
  • Journal Title: BMC Gastroenterology Volume: 20 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s12876-020-01266-3
  • Peer Reviewed
• [Journal Article] Clinical utilization of shear wave dispersion imaging in diffuse liver disease. (2020)
  • Author(s): Sugimoto K, Moriyasu F, Oshiro H, Takeuchi H, Yoshimasu Y, Kasai Y, Itoi T.
  • Journal Title: Ultrasonography. Volume: 39 Issue: 1 Pages: 3-10
  • DOI: 10.14366/usg.19031
  • Peer Reviewed
• [Journal Article] The Role of Multiparametric US of the Liver for the Evaluation of Nonalcoholic Steatohepatitis (2020)
  • Author(s): Sugimoto Katsutoshi、Moriyasu Fuminori、Oshiro Hisashi、Takeuchi Hirohito、Abe Masakazu、Yoshimasu Yu、Kasai Yoshitaka、Sakamaki Kentaro、Hara Takeshi、Itoi Takao
  • Journal Title: Radiology Volume: 296 Issue: 3 Pages: 532-540
  • DOI: 10.1148/radiol.2020192665
  • Peer Reviewed
• [Presentation] 膵癌に対する術前化学療法症例の早期再発危険因子 (2022)
  • Author(s): 高橋 礼, 渡部 文昭, 相澤 栄俊, 前田 晋平, 加藤 高晴, 野田 弘志, 大城 久, 力山 敏樹
  • Organizer: 第122回日本外科学会定期学術集会
• [Presentation] 独自の重層コンパウンド法によるセルブロック作製方法の運用 (2021)
  • Author(s): 河野 哲也, 中村 啓子, 細田 健太, 猪山 和美, 織田 聖月, 須田 さおり, 小島 朋子, 大城 久, 田中 亨
  • Organizer: 第62回日本臨床細胞学会春期大会