Chikatoshi Katada1, Tetsuji Yokoyama2, Tomonori Yano3, Kazuhiro Kaneko3, Ichiro Oda4, Yuichi Shimizu5, Hisashi Doyama6, Tomoyuki Koike7, Kohei Takizawa8, Motohiro Hirao9, Hiroyuki Okada10, Takako Yoshii11, Kazuo Konishi12, Takenori Yamanouchi13, Takashi Tsuda14, Tai Omori15, Nozomu Kobayashi16, Tadakazu Shimoda17, Atsushi Ochiai18, Yusuke Amanuma19, Shinya Ohashi19, Tomonari Matsuda20, Hideki Ishikawa21, Akira Yokoyama22, Manabu Muto23. 1. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan. 2. Department of Health Promotion, National Institute of Public Health, Wako, Japan. 3. Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan. 4. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan. 5. Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 6. Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan. 7. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. 8. Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan. 9. Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan. 10. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 11. Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. 12. Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. 13. Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan. 14. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. 15. Department of Endoscopy Center, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan. 16. Department of Diagnostic Imaging, Tochigi Cancer Center, Utsunomiya, Japan. 17. Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan. 18. Division of Pathology, National Cancer Center Hospital and Hospital East, Tokyo, Japan. 19. Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 20. Research Center for Environmental Quality Management, Kyoto University, Otsu, Japan. 21. Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan. 22. Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan. 23. Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: mmuto@kuhp.kyoto-u.ac.jp.
Abstract
BACKGROUND & AIMS: Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. METHODS: We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1-9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. RESULTS: Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C (P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C (P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C (P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25-0.91; P = .025), whereas smoking abstinence did not. CONCLUSIONS: Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
BACKGROUND & AIMS: Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. METHODS: We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1-9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. RESULTS: Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C (P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C (P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C (P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25-0.91; P = .025), whereas smoking abstinence did not. CONCLUSIONS:Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.