Liquid Biopsyによる肝内胆管癌molecular subtype分類

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K09217
• Research Institution: Okayama University
• Principal Investigator: 楳田 祐三 岡山大学, 医歯薬学域, 准教授 (10573735)
• Co-Investigator(Kenkyū-buntansha): 藤原 俊義 岡山大学, 医歯薬学域, 教授 (00304303) ; 八木 孝仁 岡山大学, 大学病院, 教授 (00304353) ; 永坂 岳司 川崎医科大学, 医学部, 准教授 (30452569) ; 吉田 一博 岡山大学, 大学病院, 助教 (60824761) ; 重安 邦俊 岡山大学, 大学病院, 助教 (70544071)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝内胆管癌

Outline of Annual Research Achievements

1. これまでの肝内胆管癌切除症例の組織サンプルより、腫瘍局所における腫瘍関連免疫反応を評価し、全身免疫栄養指標との関連性を検討することで、末梢血液における免疫指標の意義を検討している。腫瘍内外における腫瘍浸潤T細胞(TIL: Tumor Infiltrating Lymphocyte)を免疫組織染色にて把握し、CD8/Foxp3を用いた機能評価・スコア化を行い、主予後規定因子であるリンパ節転移状況と切除予後との層別化を試みた。
2. 腫瘍・宿主免疫応答評価として、各種免疫栄養指標の評価(CONUT score, prognostic nutritional index (PNI), Glasgow Prognostic Score)を算出し、再 発予後・生存予後との比較を行った。
3. これまでの解析より、術前の免疫栄養指標は鋭敏に肝内胆管癌の切除予後を反映することを明らかにした（World journal of surgery 2021, BMC cancer 2021）。更にTILについてCD8/Foxp3からなる腫瘍On-siteでの免疫栄養疲弊の評価が切除予後規定因子とな ることを認めており、今後免疫栄養指標との関連性について解析し論文投稿予定である。

4. これまでに集積してきた肝内胆管癌患者の術前・術後血液サンプルに対して、既に確立されている血中メチル化DNA/miRNA測定を継続しており、これまでの実験結果・研究成果と合わせ評価することでLiquid biopsyとしての精度の検証を継続していく予定である。

Research Products

• [Journal Article] Impact of lymph node dissection on clinical outcomes of intrahepatic cholangiocarcinoma: Inverse probability of treatment weighting with survival analysis. (2022)
  • Author(s): Umeda Y, Mitsuhashi T, Kojima T, Satoh D, Sui K, Endo Y, Inagaki M, Oishi M, Yagi T, Fujiwara T.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 29 (2) Pages: 217-229
  • DOI: 10.1002/jhbp.1038
  • Peer Reviewed / Open Access
• [Journal Article] Technique of vessel-skeletonized parenchyma-sparing hepatectomy for the oncological treatment of bilobar colorectal liver metastases. (2022)
  • Author(s): Umeda Y, Nagasaka T, Takagi K, Yoshida R, Yoshida K, Fuji T, Matsuda T, Yasui K, Kumano K, Sato H, Yagi T, Fujiwara T.
  • Journal Title: Langenbecks Arch Surg. Volume: 407 (2) Pages: 685-697
  • DOI: 10.1007/s00423-021-02373-9
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms. (2022)
  • Author(s): Matsumoto K, Ohara T, Fujisawa M, Takaki A, Takahara M, Kato H, Yoshida R, Umeda Y, Yagi T, Matsukawa A, Okada H.
  • Journal Title: J Gastrointest Surg. Volume: - Pages: -
  • DOI: 10.1007/s11605-021-05197-6
  • Peer Reviewed / Open Access
• [Journal Article] A Systematic Review of Minimally Invasive Versus Open Radical Antegrade Modular Pancreatosplenectomy for Pancreatic Cancer. (2022)
  • Author(s): Takagi K, Umeda Y, Yoshida R, Yagi T, Fujiwara T.
  • Journal Title: Anticancer Res. Volume: 42 (2) Pages: 653-660
  • DOI: 10.21873/anticanres.15523
  • Peer Reviewed / Open Access
• [Journal Article] Surgical technique of suprapancreatic D2 lymphadenectomy focusing on the posterior hepatic plexus for advanced gastric cancer. (2022)
  • Author(s): Kanaya N, Kuroda S, Kakiuchi Y, Takeda S, Kikuchi S, Noma K, Yoshida R, Umeda Y, Teraishi F, Nishizaki M, Kagawa S, Fujiwara T.
  • Journal Title: Langenbecks Arch Surg. Volume: 407 (2) Pages: 871-877
  • DOI: 10.1007/s00423-022-02437-4
  • Peer Reviewed
• [Journal Article] Prognostic Value of the Regional Lymph Node Station in Pancreatoduodenectomy for Ampullary Carcinoma. (2022)
  • Author(s): Takagi K, Nagai Y, Umeda Y, Yoshida R, Yoshida K, Fuji T, Kumano K, Yasui K, Yagi T, Fujiwara T.
  • Journal Title: In Vivo. Volume: 36 (2) Pages: 973-978
  • DOI: 10.21873/invivo.12789
  • Peer Reviewed
• [Journal Article] Prognostic Value of the Regional Lymph Node Station in Pancreatic Neuroendocrine Tumor. (2022)
  • Author(s): Takagi K, Umeda Y, Yoshida R, Yoshida K, Fuji T, Kumano K, Yasui K, Yagi T, Fujiwara T.
  • Journal Title: Anticancer Res. Volume: 42 (5) Pages: 2797-2801
  • DOI: 10.21873/anticanres.15760
  • Peer Reviewed
• [Journal Article] The Gastrohepatic Ligament Approach in Robotic Spleen-Preserving Distal Pancreatectomy with Resection of the Splenic Vessels: The Superior Window Approach in the Warshaw Technique. (2022)
  • Author(s): Takagi K, Umeda Y, Yoshida R, Yagi T, Fujiwara T.
  • Journal Title: J Gastrointest Surg. Volume: - Pages: -
  • DOI: 10.1007/s11605-022-05286-0
  • Peer Reviewed
• [Journal Article] Robotic spleen-preserving distal pancreatectomy using indocyanine green fluorescence imaging (with video). (2022)
  • Author(s): Takagi K, Umeda Y, Yoshida R, Yagi T.
  • Journal Title: Asian J Surg. Volume: 45 (1) Pages: 596-597
  • DOI: 10.1016/j.asjsur.2021.10.005
  • Peer Reviewed
• [Journal Article] Preoperative prognostic nutritional index predicts postoperative infectious complications and oncological outcomes after hepatectomy in intrahepatic cholangiocarcinoma. (2021)
  • Author(s): Matsuda T, Umeda Y, Matsuda T, Endo Y, Sato D, Kojima T, Sui K, Inagaki M, Ota T, Hioki M, Oishi M, Kimura M, Murata T, Ishido N, Yagi T, Fujiwara T.
  • Journal Title: BMC Cancer. Volume: 21 (1) Pages: 708
  • DOI: 10.1186/s12885-021-08424-0
  • Peer Reviewed / Open Access
• [Journal Article] Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer. (2021)
  • Author(s): Ako S, Kato H, Nouso K, Kinugasa H, Terasawa H, Matushita H, Takada S, Saragai Y, Mizukawa S, Muro S, Uchida D, Tomoda T, Matsumoto K, Horiguchi S, Nobuoka D, Yoshida R, Umeda Y, Yagi T, Okada H.
  • Journal Title: Cancer Biol Ther. Volume: 22 (10-12) Pages: 564-570
  • DOI: 10.1080/15384047.2021.1980312
  • Peer Reviewed / Open Access
• [Journal Article] Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer. (2021)
  • Author(s): Taniguchi F, Nyuya A, Toshima T, Yasui K, Mori Y, Okawaki M, Kishimoto H, Umeda Y, Fujiwara T, Tanioka H, Yamaguchi Y, Goel A, Nagasaka T.
  • Journal Title: Future Sci OA. Volume: 7 (10) Pages: -
  • DOI: 10.2144/fsoa-2021-0059
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prediction of Early Recurrence After Surgery for Liver Tumor (ERASL): An International Validation of the ERASL Risk Models. (2021)
  • Author(s): Beumer BR, Takagi K, Vervoort B, Buettner S, Umeda Y, Yagi T, Fujiwara T, Steyerberg EW, IJzermans JNM.
  • Journal Title: Ann Surg Oncol. 2021 Volume: 28 (13) Pages: 8211-8220
  • DOI: 10.1245/s10434-021-10235-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations. (2021)
  • Author(s): Kawai T, Nyuya A, Mori Y, Tanaka T, Tanioka H, Yasui K, Toshima T, Taniguchi F, Shigeyasu K, Umeda Y, Fujiwara T, Okawaki M, Yamaguchi Y, Goel A, Nagasaka T.
  • Journal Title: Clin Epigenetics. Volume: 13 (1) Pages: -
  • DOI: 10.1186/s13148-021-01104-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robotic Radical Antegrade Modular Pancreatosplenectomy Using the Supracolic Anterior Superior Mesenteric Artery Approach. (2021)
  • Author(s): Takagi K, Umeda Y, Yoshida R, Yagi T, Fujiwara T.
  • Journal Title: J Gastrointest Surg. Volume: 25 (11) Pages: 3015-3018
  • DOI: 10.1007/s11605-021-05112-z
  • Peer Reviewed
• [Journal Article] Laparoscopic Hepatectomy for the Patient with Hemophilia A with High Titer Factor VIII Inhibitor. (2021)
  • Author(s): Matsuda T, Umeda Y, Yoshida K, Matsuda T, Uno M, Abe M, Asada N, Maeda Y, Yagi T, Fujiwara T.
  • Journal Title: Acta Med Okayama. Volume: 75 (2) Pages: 199-204
  • DOI: 10.18926/AMO/61901
  • Peer Reviewed / Open Access
• [Journal Article] Accreditation as a qualified surgeon improves surgical outcomes in laparoscopic distal gastrectomy. (2021)
  • Author(s): Kikuchi S, Kagawa T, Kuroda S, Nishizaki M, Takata N, Kuwada K, Shoji R, Kakiuchi Y, Mitsuhashi T, Umeda Y, Noma K, Kagawa S, Fujiwara T.
  • Journal Title: Surg Today. Volume: 51 (12) Pages: 1978-1984
  • DOI: 10.1007/s00595-021-02309-2
  • Peer Reviewed
• [Presentation] 消化器外科における多施設共同研究の意義-地方からのevidence発信を目指して- (2021)
  • Author(s): 楳田祐三、黒田新士、香川俊輔、吉田龍一、菊地覚次、杭瀬崇、吉田一博、安井和也、西﨑正彦、八木孝仁、藤原俊義
  • Organizer: 第121回日本外科学会定期学術集会
• [Presentation] Enhanced one-stage removal of multiple scattered colorectal liver metastasis by parenchymal sparing & skeletonized hepatectomy (2021)
  • Author(s): Umeda Y,Yoshida R,Kuise T,Yoshida K,Takagi K,Yasui K,Sato H,Okabayashi H,Fujiwara T,Yagi T
  • Organizer: 第33回日本肝胆膵外科学会学術集会
• [Presentation] 肝移植における免疫抑制 - 臨床課題とエベロリムスへの期待- (2021)
  • Author(s): 楳田祐三
  • Organizer: 第39回日本肝移植学会学術集会
  • Invited
• [Presentation] 肝癌肝移植の長期予後に向けて肝移植適応の選別と再発時治療 (2021)
  • Author(s): 楳田祐三、吉田龍一、吉田一博、高木弘誠、安井和也、黒田新士、野間和広、香川俊輔、八木孝仁、藤原俊義
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] Designed Hepatectomy to Increase Resectability and Safety (2021)
  • Author(s): Umeda Y
  • Organizer: Annual congress of the Korean Surgical Society, Korea
  • Int'l Joint Research / Invited
• [Presentation] 肝移植における免疫抑制のニューノーマル-これからの時代を見据えた免疫抑制の最適化- (2021)
  • Author(s): 楳田祐三
  • Organizer: 第47回日本臓器保存生物医学会学術集会
  • Invited
• [Presentation] Prediction of early recurrence of hepatocellular carcinoma afterresection: an international validation of the ERASL risk models (2021)
  • Author(s): Takagi K,Umeda Y,Berend R Beumer,Bastiaan Vervoort,Stefan Buettner,Ewout W Steyerberg,Jan NM IJzermans,Yagi T,Fujiwara T
  • Organizer: JDDW2021
• [Presentation] Clinical Significance of KRAS Mutations in Circulating Tumor DNA for Appropriate Surgical Indication and Timing in Patients with Borderline Resectable or Unresectable Pancreatic Cancer (2021)
  • Author(s): Yoshida R,Yasui K,Umeda Y,Kuise T,Yoshida K,Takagi K,Sato H,Miyamoto K,Yagi T,Fujiwara T
  • Organizer: 第33回日本肝胆膵外科学会学術集会
• [Presentation] De novo Malignancies after Liver Transplantation (2021)
  • Author(s): Yoshida K,Umeda Y,Yoshida R,Kuise T,Yasui K,Takagi K,Okabayashi H,Sato H,Nagai Y,Fujiwara T,Yagi T
  • Organizer: 第33回日本肝胆膵外科学会学術集会
• [Presentation] Surgical training model and safe implementation of robotic pancreatoduodenectomy in Japan:learning from the Dutch training system (2021)
  • Author(s): Takagi K,Umeda Y,Yoshida R,Kuise T, Yoshida K,Yasui K,Yagi T,Fujiwara T,Bas Groot Koerkamp
  • Organizer: 第33回日本肝胆膵外科学会学術集会
• [Presentation] Analysis of Resection Margin Status in Pancreatectomy for Pancreatic Ductal Adenocarcinoma (2021)
  • Author(s): Yasui K,Yoshida R,Sato H,Umeda Y,Kuise T,Yoshida K,Takagi K,Okabayashi H,Nagai Y,Yagi T,Fujiwara T
  • Organizer: 第33回日本肝胆膵外科学会学術集会
• [Presentation] Retrospective study of induction chemotherapy and surgery for esophagogastric junction cancer (2021)
  • Author(s): Tanabe S,Noma K,Maeda N,Kikuchi S,KurodaS,Sakurama K,Umeda Y,Teraishi F,Shirakawa Y,Fujiwara T
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] Standardization of robotic-assisted thoracoscopic esophagectomy (2021)
  • Author(s): Noma K,Maeda N,Kikuchi S,Tanabe S,Kuroda S,Sakurama K,Teraishi F,Umeda Y,Shirakawa Y,Fujiwara T
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 大腸癌肝転移における術前化学療法の適応選別-RAS・RAF変異による肝外進展リスク- (2021)
  • Author(s): 岡林弘樹、楳田祐三、吉田龍一、吉田一博、高木弘誠、安井和也、黒田新士、八木孝仁、藤原俊義
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 進行膵癌集学的治療における術前血中KRAS遺伝子変異の新規バイオマーカーとしての有用性に関する検討 (2021)
  • Author(s): 吉田龍一、安井和也、楳田祐三、吉田一博、高木弘誠、佐藤博紀、黒田新士、野間和広、八木孝仁、藤原俊義
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 肝内胆管癌におけるNeutrophil Extracellular Traps産生のための血小板の役割 (2021)
  • Author(s): 吉本匡志、香川俊輔、梶原義典、藤智和、菊地覚次、黒田新士、吉田龍一、楳田祐三、田澤大、藤原俊義
  • Organizer: 第59回日本癌治療学会学術集会