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[食管癌的化学预防]

[Chemoprevention in adenocarcinoma of the esophagus].

作者信息

Lanas Angel, Alcedo González Javier

机构信息

Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, España.

出版信息

Acta Gastroenterol Latinoam. 2007 Mar;37(1):37-48.

Abstract

The incidence of the adenocarcinoma of the esophagus (ACE) has dramatically for the last decades in western countries, which has been associated with a parallel increase in the incidence and prevalence of symptoms associated with gastroesophageal reflux diseases (GERD) and Barrett's esophagus (BE). Both conditions are now considered risk factors for ACE. Different pathways, including overexpression of cyclooxygenase (COX) isoenzymes, has been proposed to explain the carcinogenic process leading from normal esophagus to esophagitis, BE and ACE. The survival rate in patients with ACE is very low because of the poor outcomes of surgery and the limited benefits obtained with concomitant chemo-radiotherapy Several strategies based on early detection and surveillance of preneoplastic lessions have failed to have a global and significant impact on the prognosis of the ACE. Recent epidemiological and experimental studies suggest that chemoprevention could be useful in the management of patients with GERD and especially in those with BE. The current therapy with protom pump inhibitors (PPI) is effective to reduce the esophageal acid exposure, to improve reflux symptoms, and to heal inflammatory injuries, but probably is not enough to avoid the dysplastic progression of the metaplastic epithelium. Regular use of COX inhibitors (aspirin and other non steroid antiinflamatory drugs) has been associated with reduction of the risk of ACE and to decrease the incidence of ACE in animal models. In humans, the association of PPI with COX inhibitors could be a cost-effectiveness strategy but direct evidence is lacking. Other potential agents that have shown some chemoprevention potential include troglitazone, free radical scavengers, tamoxifen or prostaglandin receptor blockers, but the available scientific evidence is still poor and not ready to be tested in humans.

摘要

在西方国家,过去几十年来食管腺癌(ACE)的发病率急剧上升,这与胃食管反流病(GERD)和巴雷特食管(BE)相关症状的发病率和患病率的平行上升有关。现在这两种情况都被认为是ACE的危险因素。已经提出了不同的途径,包括环氧化酶(COX)同工酶的过表达,来解释从正常食管到食管炎、BE和ACE的致癌过程。由于手术效果不佳以及同步放化疗的获益有限,ACE患者的生存率非常低。基于对癌前病变的早期检测和监测的几种策略未能对ACE的预后产生全面而显著的影响。最近的流行病学和实验研究表明,化学预防可能对GERD患者的管理有用,尤其是对BE患者。目前使用质子泵抑制剂(PPI)的治疗有效地减少了食管酸暴露,改善了反流症状,并治愈了炎症损伤,但可能不足以避免化生上皮的发育异常进展。经常使用COX抑制剂(阿司匹林和其他非甾体抗炎药)与降低ACE风险以及在动物模型中降低ACE发病率有关。在人类中,PPI与COX抑制剂的联合使用可能是一种具有成本效益的策略,但缺乏直接证据。其他已显示出一定化学预防潜力的潜在药物包括曲格列酮、自由基清除剂、他莫昔芬或前列腺素受体阻滞剂,但现有的科学证据仍然不足,尚未准备好在人体中进行试验。

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