Wang Li Dong, Zhou Qi, Feng Chang Wei, Liu Bin, Qi Yi Jun, Zhang Yan Run, Gao Shan Shan, Fan Zong Min, Zhou Yun, Yang Chang S, Wei Jun Ping, Zheng Shu
Laboratory for Cancer Research, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
Gan To Kagaku Ryoho. 2002 Feb;29 Suppl 1:159-72.
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.
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.
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).
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.
食管癌（EC）仍是中国北方河南省林州（原林县）和辉县癌症相关死亡的主要原因，这两个地区已被公认为是食管癌发病率最高的地区。缺乏有效的化学预防剂和早期检测方法是这些地区食管癌发病率稳定的关键因素。人类食管癌的发生被认为是一个多步骤的渐进过程。然而，食管癌的自然史尚不清楚。
对来自林州和辉县的778名受试者进行了线性重复活检和组织病理学检查的随访研究。在这些受试者中，578名受试者随访了11年（1989 - 2000年），400名患有不同严重程度食管癌前病变的受试者被随机分为两组，分别用钙和脱咖啡因绿茶（DGT）进行干预研究。每组包括200名受试者（100名治疗组，100名安慰剂组）。在钙组中，每位受试者每天口服补充1200毫克钙，持续11个月。在DGT组中，每位受试者每天服用5毫克DGT，持续12个月。在安慰剂组中，每位受试者服用安慰剂丸11个月（钙组）和12个月（DGT组）。在试验开始和结束时，从每位受试者食管中、下三分之一处以及仅从肉眼可见病变处取食管活检标本。
DGT试验在缓解食管癌前病变和异常细胞增殖方面，治疗组与安慰剂组之间未显示出明显差异。对于钙干预研究，经过11年的随访，钙组中有10名受试者发展为癌症（10%，8例食管癌和2例贲门癌），安慰剂组中有8名受试者发展为食管癌（8%）。所有这些患者均在癌症极早期被诊断（无症状）。在578名受试者中，在11年的随访期间，有25名（18名男性和7名女性）发展为食管癌（n = 23，4.3%）和贲门癌（GCA，n = 2，0.3%）。癌症发展的平均时间（从随访研究开始到癌症检测）为男性5.0±2.9年，女性4.7±3.2年。在25例食管癌和贲门癌患者中，11例来自随访研究开始时活检组织形态学“正常”的387名随访受试者（3%，11/387），2例来自I级基底细胞增生（BCH I）受试者（2%，2/94），7例来自II级BCH（BCH II）受试者（10%，7/72），5例来自BCH III和发育异常受试者（20%，5/25）。
DGT试验未显示出在缓解食管癌前病变和异常细胞增殖模式方面有有益作用。补充钙对食管癌未产生明显的长期影响。BCH II可被视为食管癌的癌前病变。根据增殖基底细胞层数进行的定量组织病理学分析对于确定食管癌的高危受试者和评估干预结果具有重要意义。通过重复内镜活检进行随访研究是在高发地区早期检测和控制食管癌及贲门癌死亡率的有力策略。
