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大腸癌における腫瘍の増大速度と悪性度に関する検討

三宅, 弘章 東京大学 DOI:10.15083/0002007081

2023.03.24

概要

[課程-2]
審査の結果の要旨
氏名 三宅 弘章
本研究は、癌の増殖速度の指標として腫瘍の体積が 2 倍になるまでの時間である doubling time
(DT) に着目し、大腸癌の悪性度や再発時期との相関について検証した。第 1 章では大腸癌術後
腹膜播種再発切除症例において、播種再発巣の DT ならびに代表的な腫瘍マーカーである CEA
(carcinoembryonic antigen) における CEA-DT と予後に関する検証を行い、第 2 章では切除を行
っていない患者も含め、大腸癌術後肝・肺・腹膜播種再発患者において、DT の予後因子としての
検討と、DT の短い (short DT) 群・長い (long DT) 群それぞれにおける再発巣の切除の有用性
を検証し、第 3 章では DT を元に現行の日本の大腸癌術後サーベイランスの妥当性を検証し、下
記の結果を得ている。
1. 第 1 章では大腸癌術後腹膜播種再発切除症例 33 例において、播種巣の short DT, short
CEA-DT は OS (overall survival)、RFS (relapse-free survival) において有意な予後不良因子であ
ることが示され、DT は腹膜播種再発患者の手術適応を決定する上で考慮すべき一つの指標とな
ると考えられた。
2. 第 2 章では stage I-IV 大腸癌に対し根治切除を行った 1941 例のうち、肝、肺、腹膜播種再発
をきたした患者の再発後予後を解析した。その結果、大腸癌術後肝、腹膜播種再発症例におい
て、short DT は独立した予後不良因子であることが示された。さらに、大腸癌術後肝、肺、腹膜播
種再発症例のいずれでも、DT の長さによらず切除群は非切除群と比較し有意に予後良好であっ
た。特に interaction test による解析から、肝、腹膜播種再発患者の long DT 群は short DT 群と比
較し、切除の有用性が高いことが示され、より良い手術適応と考えられた。
3. 第 3 章では stage I-III 大腸癌に対し R0 根治切除を行った 1774 例を対象にし、再発巣の DT
が長いものは大腸癌術後サーベイランスを減らしても、大きさの変化が少なく切除率への影響が少
ないという仮説のもと、DT の概念を組み込むことで、より効率的な新しい less intensive なサーベイ
ランスを作成した。その結果、理論上 32.5%のサーベイランスに伴う費用削減の可能性が示唆さ
れ、新しく予測される再発腫瘍径の増大率も、DT の長い時期のサーベイランス間隔を伸ばすこと
で、最大で 31%にとどまることが示された。
以上、本論文は、DT が大腸癌術後再発症例の手術適応や大腸癌術後サーベイランススケジュー
ルを決定する上で考慮すべき有用な一つの指標になることを示した。

本研究は、大腸癌術後再発患者の予後予測や、より効率的な大腸癌術後サーベイランスを作成
する研究に新たな知見を与えるものであると考えられる。
よって本論文は博士( 医学 )の学位請求論文として合格と認められる。

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