胃癌的化學預防

雖然胃癌的發生率有逐漸下降的趨勢，但是它仍是常見的惡性腫瘤，且是全世界腫瘤死因的第二位，故胃癌還是重要的公共衛生議題。胃癌的預後取決於早期診斷並且加以適當的手術切術。近十年來，內視鏡合併切片檢查已廣泛使用於胃癌的早期診斷，然而除了日本因為有做大規模的篩檢外，其餘國家報告的早期胃癌與進行型胃癌的比例，仍未見明顯增加。此外，儘管手術切除和化學治療已有顯著進步，但是對於進行型胃癌的治癒率仍然偏低而且罹病率也居高不下。由於胃癌在早期的診斷和進行型胃癌的治療上仍有許多的限制，因此化學預防就成為胃癌另類治療和預防的不錯選擇。這一方面已有許多實驗室和流行病學的研究提供有關利用幽門桿菌治療，非固醇類抗發炎藥物和微營養物補充等方式可以降低胃癌風險的証據。用萎縮性胃炎和腸性化生做臨床試驗的中間生物標記的研究則顯示以幽門桿菌根除和微營養成分補充的方式的確可調整胃癌的危險性。而以胃癌發生率是否減少的關鍵研究也証實若早一點給予幽門桿菌治療，可以有效預防胃癌的發生。這些成果顯示化學預防觀念不僅可行而且值得研究。最近一些體外試驗和流行病學觀察也發現非固醇類抗發炎藥物似乎具胃癌化學預防的潛力，但是其真正效果仍有待臨床試驗証實，而且其長期使用的安全性，特別是胃腸和心臟的副作用，也值得注意。利用新發展的技術和基因體研究的進展，可以對胃癌的相關分子機轉做更深入的了解，這些研究將有助於發現胃癌的新生物標記和擬定更好的化學預防策略。

關鍵字

預防性抗生素；藥物使用評估；醫療品質

並列摘要

Despite its decline in incidence, gastric adenocarcinoma (GAC) still poses a formidable public health problem. It remains one of the most commonly diagnosed solid malignancies and the second leading cause of cancer-related deaths in the world. The prognosis of GAC depends mainly on early detection and adequate surgical resection. In recent decades, endoscopy with biopsy has been widely used for early diagnosis. However, the proportion of early to advanced GAC being found through this method has not appreciably increased except in countries like Japan, where a nationwide screening campaign was conducted. Moreover, the cure rate for advanced GAC remains low and the morbidity remains high despite the fact remarkable improvement in surgical techniques and chemotherapy has been made. Given the limitations associated with early diagnosis and treatment of advanced GAC, chemoprevention has emerged as an attractive option for therapeutic interventions. Encouraging laboratory and epidemiologic studies have provided a strong scientific rational for applications of H. pylori treatment, non-steroidal anti-inflammatory drugs (NSAIDs) and micronutrient supplementation to reduce GAC risks. The clinical trials using atrophic gastritis and intestinal metaplasia as intermediate surrogate biomarkers have demonstrated that modulation of GAC risk through eradication of H. pylori and micronutrients is possible. The seminal study with GAC occurrence as the final outcome indicated that anti-H. pylori therapy is effective to prevent GAC if such therapy was given due in early course of infection. These success showed the concept is valid and worth pursuing. Recent in vitro studies and epidemiologic observations have suggested NSAIDs appear a promising chemopreventive agent for GAC but their efficacy remains to be determined in clinical trials and their safety has been questioned in view of unwanted gastrointestinal and cardiovascular toxicities. A greater understanding of molecular events associated with gastrocarcinogeneis with the use of emerging technologies and advances in genetic research will further enhance the development of surrogate biomarkers and better strategies for the chemoprevention of GAC.

並列關鍵字

gastric cancer ； chemoprevention ； H. pylori ； cyclooxygenase ； nutrition

國際替代計量

胃癌的化學預防

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