大酒家における食道表在癌内視鏡切除後の2次癌―癌のない大酒家の長期経過との比較

Risk of Cancer in the Upper Aerodigestive Tract in Japanese Alcoholic Men with Superficial Esophageal Cancer, Esophageal Dysplasia, or Inactive Aldehyde Dehydrogenase-2: An Endoscopic Follow-up Study

要旨　アルコール依存症者（ア症）の食道癌の内視鏡的粘膜切除（EMR）後の異時性発癌と，癌のなかったア症の発癌とを内視鏡経過観察で比較した．食道癌と口腔咽喉癌の6年発生率はそれぞれEMR後（n＝84）で56％と35％，食道異形成患者（n＝112）で31％と20％と高頻度だが，食道ヨード不染帯のなかった患者（n＝616）では4％と4％であった．ハザード比は不染帯のない患者を基準として，EMR後で23.8倍と14.2倍，食道異形成患者で11.2倍と6.55倍であった．アルデヒド脱水素酵素2（ALDH2）ヘテロ欠損者では，それぞれの6年発生率は，EMR後（n＝44）で70％と46％，癌がない患者（n＝72）で34％と30％といずれも高く，ALDH2正常者では，EMR後（n＝40）で30％と8％，癌がない患者（n＝484）で5％と5％であった．ハザード比はALDH2正常で癌がない患者を基準として，ALDH2欠損でEMR後の患者で32.6倍と21.8倍，ALDH2欠損で癌のない患者で11.7倍と11.6倍，ALDH2正常でEMR後の患者で8.12倍と7.36倍であった．ア症ではEMR後の異時性癌の頻度がALDH2欠損者で特に高いが，癌がない患者でも食道異形成やALDH2欠損があると非常に高い発癌リスクがみられ，これらの患者では厳重な長期間の内視鏡観察が必要である．

　Japanese studies have consistently demonstrated a strong relationship between multiple development of squamous cell carcinoma (SCC) of the upper aerodigestive tract and alcohol consumption combined with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2^＊1/^＊2). Japanese alcoholic men diagnosed as cancer-free by an initial endoscopic screening examination and those with esophageal SCC, which was treated by endoscopic mucosal resection (EMR), received follow-up examinations. The 6-year cumulative rates of new primary SCC in the esophagus/oropharyngolarynx were 56％/35％ in EMR cases (n＝84), 31％/20％ in cancer-free cases with esophageal dysplasia≧5 mm (n＝112), and 4％/4％ in cancer-free cases without distinct iodine-unstained lesion≧5 mm (DIUL; n＝616), respectively. Cox proportional hazards analysis showed that in comparison with cases without DIUL, the adjusted relative hazards for SCC in the esophagus/oropharygolarynx were 23.8(95％ CI; 11.4～49.5)/14.2(8.03～25.0) in EMR cases and 11.2(5.26～24.0)/6.55(3.62～11.8) in cases with esophageal dysplasia. The 6-year cumulative rates of new primary SCC in the esophagus/oropharyngolarynx were 70％/46％ in ALDH2^＊1/^＊2 EMR cases (n＝44), 34％/30％ in ALDH2^＊1/^＊2 cancer-free cases (n＝72), 30％/8％ in ALDH2^＊1/^＊1 EMR cases (n＝40), and 5％/5％ in ALDH2^＊1/^＊1 cancer-free cases (n＝484). In comparison with ALDH2^＊1/^＊1 cancer-free cases, the adjusted relative hazards for SCC in the esophagus/oropharygolarynx were 32.6(14.3～74.2)/21.8(11.1～42.9) in ALDH2^＊1/^＊2 EMR cases, 11.7(4.77～28.9)/11.6(5.70～23.4) in ALDH2^＊1/^＊2 cancer-free cases, and 8.12(2.45～26.9)/7.36(2.80～19.3)in ALDH2^＊1/^＊1 EMR cases. Japanese alcoholics after EMR for esophageal SCC have an extremely high risk of metachronous SCC in the upper aerodigestive tract, especially in ALDH2^＊1/^＊2 heterozygotes. Cancer-free patients with esophageal dysplasia or inactive ALDH2^＊1/^＊2 also have very high risk of the SCC. All these patients need careful long-term follow-up examinations.