Drinking alcohol, smoking, multiple dysplastic lesions and the risk of field cancerization of squamous cell carcinoma in the esophagus and head and...

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Oesophageal Cancer
Presenter Chikatoshi Katada
Citation Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247
Authors C. Katada1, T. Yokoyama2, T. Yano3, I. Oda4, Y. Shimizu5, H. Doyama6, T. Koike7, K. Takizawa8, M. Hirao9, H. Okada10, H. Ishikawa11, A. Yokoyama12, M. Muto13
  • 1Department Of Gastroenterology, Kitasato University School of Medicine, 252-0329 - Sagamihara/JP
  • 2Department Of Health Promotion, National Institute of Public Health, Wako/JP
  • 3Department Of Gastroenterology And Endoscopy, National Cancer Center Hospital East, Kashiwa/JP
  • 4Endoscopy Division, National Cancer Center Hospital, Tokyo/JP
  • 5Department Of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo/JP
  • 6Department Of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa/JP
  • 7Division Of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai/JP
  • 8Division Of Endoscopy, Shizuoka Cancer Center, Shizuoka/JP
  • 9Department Of Surgery, National Hospital Organization Osaka National Hospital, Osaka/JP
  • 10Department Of Gastroenterology And Hepatology, Okayama University Graduate School of Medicine, Okayama/JP
  • 11Department Of Molecular-targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto/JP
  • 12Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka/JP
  • 13Department Of Clinical Oncology, Kyoto University Hospital, 606-8507 - Kyoto/JP



Multiple development of squamous cell carcinoma (SCC) in the upper aero-digestive tract is known as the field cancerization phenomenon. We examined the association of this phenomenon with dysplastic squamous epithelium in the background mucosa, drinking alcohol, and smoking.


331 patients with early esophageal SCC were enrolled. Using Lugol chromoendoscopy, we evaluated the dysplastic squamous epithelium in the esophagus. Lugol voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The endpoint of this cohort study was the cumulative incidence of metachronous multiple SCC in the esophagus or head and neck after endoscopic resection of esophageal SCC according to the grade of LVL. At study entry, all patients were instructed to abstain from drinking alcohol and smoking. Data collected from a different cross-sectional cohort (n = 1042) were used as an historical control. ALDH2 status was determined by questionnaire facial flushing after drinking alcohol (present and past flushing=inactive ALDH2, never flushing=active ALDH2).


In the median follow-up period of 69.6 months, LVL grade (A to B to C) was associated with progressive increases in the 5-year cumulative incidence of metachronous multiple SCC (esophagus = 6.0%, 17.8% and 47.1%, respectively, p = 0.022 for A vs. B and p < 0.0001 for A vs. C; head and neck = 0.0%, 4.3% and 13.3%, respectively, p = 0.12 for A vs. B and p = 0.0007 for A vs. C; esophagus or head and neck = 6.0%, 19.8% and 52.6%, respectively, p = 0.012 for A vs. B and p < 0.0001 for A vs. C). Alcohol and smoking abstinence decreased the risk of multiple SCC of the esophagus (adjusted hazard ratio=0.47 and 0.49, respectively) (p = 0.013 for alcohol and p = 0.024 for smoking). Adjusted odds ratio (OR) of LVL grade B and C associated with heavy drinking was significantly stronger in inactive ALDH2 (OR = 47.5 and 358, respectively) than active ALDH2 (OR = 12.8 and 138, respectively) (p < 0.05 for B and p < 0.05 for C).


Multiple dysplastic lesions in the esophagus are a useful predictor of the risk of multiple SCC associated with field cancerization. Alcohol and smoking abstinence is required to prevent a second primary SCC.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

JEC study group.


National Cancer Center Research and Development Fund 36 by the Ministry of Health, Labour and Welfare of Japan.


All authors have declared no conflicts of interest.