潰瘍性大腸炎に伴う大腸癌発生―日本人潰瘍性大腸炎患者の実態と細胞動態からみた癌化機構に関する研究

Development of Colorectal Cancer in Ulcerative Colitis, Clinicopathological Study of 347 Patients and New Concepts of Cancer Development from Analysis of Mucosal Cell Proliferation Activity

要旨　都内3病院において21年間に確認・経過観察された潰瘍性大腸炎347症例（男女比1：1）を臨床病理学的に観察し，大腸癌の累積発生頻度：10年罹患で1.1％，15年3.2％，20年11.1％を算出して諸外国と比較した．潰瘍性大腸炎患者大腸切除32例，大腸切除後の残存直腸23例の観察から高率にdysplasia（それぞれ12.5％，8.7％）の出現を認め，日本人潰瘍性大腸炎患者も罹病期間の長期化に伴いdysplasia，carcinomaが明らかに出現してくることを示した．またsporadicな大腸癌と比較して有意に若齢者（平均46.8歳）に発生すること，大腸炎重症例，腫瘍性病変は女性に多いことを明らかにした．粘膜上皮のmitosis index，核内AgNORs顆粒，PCNA陽性細胞を観察した結果，大腸炎の反復に伴い壊死と再生によって粘膜上皮の細胞分裂・増殖が亢進していることが，突然変異による癌化を生じやすい大きな原因の1つとして挙げられた．

　By clinicopathological analysis of 347 patients (male 178, female 169) of ulcerative colitis (UC) on which follow-up study has been performed at three hospital in Tokyo metropolitan area, cumulative probabilities of developing colorectal cancer were estimated as follows: 10 year period, 1.1%; 15 year period, 3.2%; 20 year period, 11.1%. Histopathological study of 32 surgically resected specimens of the colon and 23 remaining recturns after colectomy showed a high incidence of dysplasia (12.5%, 8.7% respectively). These results suggest that carcinoma and dysplasia may arise in Japanese UC patients with long suffering periods. UC patients with neoplasms were significantly younger (46.8 years of age) and more female dominant than those with sporadic colorectal cancers.

　Histopathological findings of mitosis index, AgNORs granules and PCNA positive cells revealed that mitosis and cellular proliferation of mucosal epithelium obtained from active UC patients were more prominent than those from UC in remission phase or non-UC patients. In conclusion, the repetition of necrosis and regeneration may cause the pre-malignant change and the increase in incidence of colorectal cancer.