Background: Esophageal cancer (EC) remains a leading cause of cancer-related deaths in Linzhou (formerly Linxian) and Huixian of Henan province, northern China, which has been well recognized as the highest incidence area for EC. The lack of useful chemoprevention agents and early detection methods is the key factors for stable EC incidence in these areas. Human esophageal carcinogensis has been considered as a multistep progressive process. The natural history for EC, however is not very clear.
Methods: Follow-up studies with linear repeated biopsies and histopathological examination were performed on 778 subjects from Linzhou and Huixian. Of these subjects, 578 subjects were followed for 11 years (1989-2000), 400 subjects with different severity of esophageal precancerous lesions were randomly divided into 2 groups for intervention studies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 subjects for treatment, and 100 subjects for placebo). In calcium group, each subject received an oral supplementation of 1,200 mg of calcium daily for 11 months. In DGT group, each subject received 5 mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calcium group) and 12 month (DGT group). At the entry and the end of the trial, esophageal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic lesions, if only, of each subject.
Results: DGT trail did not show apparent difference between the treatment and placebo group in alleviating the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years' follow-up, 10 subjects had developed into cancers in the calcium group (10%, 8 EC and 2 GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n = 23, 4.3%) and gastric cardia cancer (GCA, n = 2, 0.3%), during the 11 years' follow-up. The mean time of cancer development (from entry of the follow-up study to the cancer detection) was 5.0 +/- 2.9 years (males) and 4.7 +/- 3.2 years (females). Of the 25 patients with EC and GCA, 11 were from the 387 followed subjects with "normal" histomorphology of biopsy at the entry of the follow-up study (3%, 11/387), 2 were from the subjects with basal cell hyperplasia, grade I (BCH I, 2%, 2/94), 7 from the subjects with BCH grade II (BCH II, 10%, 7/72), and 5 from BCH III and dysplasia (20%, 5/25).
Conclusions: DGT trail was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns. Calcium supplementation did not produce apparent long-term effects on EC. BCH II could be considered as precancerous lesions of EC. The quantitative histopathological analysis in terms of number of proliferating basal cell layers is of importance in determining the high-risk subjects for EC and evaluating the intervention results. Follow-up studies with repeated endoscopic biopsies are the powerful strategy for early detection and mortality control of EC and GAC in the high incidence area.