Analyses of the relevance between microscopic cancer spread of colorectal liver metastases and perioperative chemotherapy

• Project/Area Number: 26462038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Hasegawa Kiyoshi 東京大学, 医学部附属病院, 准教授 (20292906)
• Co-Investigator(Kenkyū-buntansha): 進藤 潤一 公益財団法人冲中記念成人病研究所, その他部局等, 研究員 (90701037) ; 大場 大 東京大学, 医学部附属病院, 助教 (10535529)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸癌肝転移 / 周術期化学療法 / 分子標的治療薬 / 微小転移 / 形態学的腫瘍変化 / 病理学的微小転移 / 遺伝学的微小転移 / 形態学的奏功 / 分子標的薬 / RAS変異 / APC / 遺伝子変異

Outline of Final Research Achievements

Micrometastases exists around 20% of colorectal liver metastases (CLM), and preoperative chemotherapy for CLM reduces its frequency. Biologic agents, both anti-VEGF and anti-EGFR antibody, are associated with a decrease in the incidence of microscopic cancer spread beyond a width of 1 mm from the main lesion. Furthermore, in predicting the frequency and distribution of micrometastases around CLM the morphologic change in preoperative computed tomography is more favorable than the traditional tumor size-based criteria.
In patients with suboptimal morphologic response to preoperative chemotherapy for CLM, taking surgical margin more than 1mm prolongs surgical outcome. However, patients with optimal morphologic response show very good prognosis regardless of whether surgical margin is over 1mm or not, and the current study suggested the hepatic surgery with histological positive surgical margin can be acceptable, where necessary, in those patients with marginally resectable disease.

Research Products

• [Journal Article] Clinical Impact of Preoperative Chemotherapy on Microscopic Cancer Spread Surrounding Colorectal Liver Metastases (2017)
  • Author(s): Nishioka Yujiro, Shindoh Junichi, Yoshioka Ryuji, Gonoi Wataru, Abe Hiroyuki, Okura Nnaoki, Yoshida Shuntaro, Sakamoto Yoshihiro, Hasegawa Kiyoshi, Fukayama Masashi, Kokudo Norihiro
  • Journal Title: Annals of Surgical Oncology Volume: 印刷中 Issue: 8 Pages: 2326-2333
  • DOI: 10.1245/s10434-017-5845-z
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Survival benefit of repeat resection of successive recurrences after the initial hepatic resection for colorectal liver metastases. (2016)
  • Author(s): Oba M, Hasegawa K, Shindoh J, Yamashita S, Sakamoto Y, Makuuchi M, Kokudo N.
  • Journal Title: Surgery Volume: 159 Issue: 2 Pages: 632-640
  • DOI: 10.1016/j.surg.2015.09.003
  • Peer Reviewed
• [Journal Article] Radiological Morphology of Colorectal Liver Metastases after Preoperative Chemotherapy Predicts Tumor Viability and Postoperative Outcomes. (2015)
  • Author(s): Nishioka Y, Shindoh J, Yoshioka R, Gonoi W, Abe H, Okura N, Yoshida S, Oba M, Hashimoto M, Watanabe G, Hasegawa K, Kokudo N.
  • Journal Title: J Gastrointest Surg. Volume: 19 Issue: 9 Pages: 1653-1661
  • DOI: 10.1007/s11605-015-2836-x
  • Peer Reviewed
• [Journal Article] 肝転移に対する外科治療の適応と術後補助化学療法； ここまできた専門的治療法―その進歩と最新の成績― (2015)
  • Author(s): 長谷川潔、國土典宏
  • Journal Title: Medical Practice Volume: 32 Pages: 1850-1856
• [Journal Article] Discrepancy Between Recurrence-Free Survival and Overall Survival in Patients with Resectable Colorectal Liver Metastases: A Potential Surrogate Endpoint for Time to Surgical Failure. (2014)
  • Author(s): Oba M, Hasegawa K, Matsuyama Y, Shindoh J, Mise Y, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, Kokudo N
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: 6 Pages: 1817-24
  • DOI: 10.1245/s10434-014-3504-1
  • Peer Reviewed
• [Presentation] エビデンスにもとづく大腸癌肝転移に対する治療戦略の構築 (2015)
  • Author(s): 長谷川潔、大場大、國土典宏
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15 – 2015-07-17
• [Presentation] Establishment of therapeutic strategy for coloectal liver metastasis based on evidences. (2015)
  • Author(s): 長谷川潔、大場大、國土典宏
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティ浜松，オークラアクトシティホテル浜松，ホテルクラウンパレス浜松（静岡県・浜松市）
  • Year and Date: 2015-07-15
• [Presentation] 腫瘍個数による大腸癌肝転移の手術適応の制限は適切か？ (2015)
  • Author(s): 長谷川潔、大場大、西岡裕次郎、吉岡龍二、進藤潤一、山本訓史、山下俊、赤松延久、有田淳一、金子順一、阪本良弘、國土典宏
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: ホテル グランパシフィック LE DAIBA （東京都・港区）
  • Year and Date: 2015-06-11
• [Presentation] Is it proper to restrict surgical indication for colorectal liver metastases by tumor number? (2015)
  • Author(s): Kiyoshi Hasegawa, Masaru Oba, Yujiro Nishioka, Ryuji Yoshioka, Junichi Shindoh, Satoshi Yamamoto, Suguru Yamashita, Nobuhisa Akamatsu, Junichi Arita, Junichi Kaneko, Yoshihiro Sakamoto, Norihiro Kokudo
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-11
• [Presentation] 大腸癌肝転移に対し、肝切除は何個まで挑戦すべきか？ (2014)
  • Author(s): 長谷川潔、大場大、山下俊、西岡裕次郎、山本訓史、吉岡龍二、進藤潤一、石沢武彰、赤松延久、金子順一、青木琢、阪本良弘、菅原寧彦、國土典宏
  • Organizer: 第69回日本大腸肛門病学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] 大腸癌肝転移再発に対する再切除を軸とした治療戦略 (2014)
  • Author(s): 長谷川潔、大場大、國土典宏
  • Organizer: JDDW 2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-24
• [Book] 肝転移の治療方針；第4章 治療図書『大腸腺腫・大腸癌 最新醫學別冊 診断と治療のABC 109 』 (2015)
  • Author(s): 長谷川潔、河口義邦、大道清彦、阪本良弘、國土典宏
  • Publisher: 最新医学社