臺灣博碩士論文加值系統

　　大腸直腸癌是十分重要且受到深入探討的癌症，尤其在台灣，更是發生率高居第一位，死亡人數第三位的新興癌症。台灣也從2004年開始有全國性的大腸直腸癌篩檢計劃。在篩檢過程中，除了發現癌症，也發現許多病人有大腸息肉，此為大腸直腸癌重要的癌前病變。在眾多的大腸息肉患者中，如何篩選未來追蹤時罹癌風險高或易復發的病人，密切監測，便成為十分重要的議題。本研究選出兩個具臨床意義的分子標記：在黏膜發炎癌化過程中扮演重要角色的第二型環氧合酶(COX-2)以及調控去氧核醣核酸甲基化的去氧核醣核酸甲基轉移酶3B(DNMT3B)，並研究其表現是否會影響高風險腺瘤與癌症的加速發生。首先，藉由病歷回顧方式，分析本校醫學院附設醫院追蹤性大腸鏡的執行情形。進而於病人接受大腸鏡追蹤時，收集息肉檢體，藉由免疫組織化學染色，分析COX-2及DNMT3B在不同病理組織型態息肉間的表現，並進一步研究息肉中COX-2及DNMT3B的表現強度，是否與高風險腺瘤或癌症之後續發生有所關聯。
　　於本研究期間接受追蹤性大腸鏡的病人，其大腸鏡追蹤間隔，多較美國多專科醫學會特別小組(USMSTF)之指引建議提早，但仍有20.2%的病人於追蹤時發現有高風險腺瘤，10.6%的病人發現有進階性腺瘤，0.7%則發現有大腸直腸癌。本研究亦發現病人較早發生高風險腺瘤或癌症之因子，包含年齡增加、前次大腸鏡發現有一公分以上的腺瘤、有三顆以上的腺瘤及右側腺瘤；而會使病人較早發生進階性腺瘤或癌症的風險因子，則包含前次大腸鏡發現有一公分以上的腺瘤、含絨毛樣病理變化之腺瘤、有三顆以上的腺瘤及右側腺瘤。
　　經由臨床切除之息肉及腺癌檢體染色分析，發現COX-2及DNMT3B的表現強度，從腸炎到增生性息肉、管狀腺瘤、絨毛樣腺瘤，以至於癌症，染色強度呈現漸次上升的趨勢。在單變項分析中，DNMT3B在前次大腸息肉高度表現，與高風險腺瘤的加速發生有明顯相關，而COX-2則無統計上意義。多變項分析中唯有年齡、前次大腸鏡發現有腺瘤、前次有高度變性腺瘤、大腸直腸癌經內視鏡切除術後等因子，與發生高風險腺瘤有明顯相關。
　　總結，於本院接受追蹤大腸鏡之患者，其追蹤間隔雖多較國際指引建議為短，卻仍有約20%及10%病人發現有高風險及進階性病灶。病人的年齡、前次大腸鏡所發現的腺瘤大小、位置、顆數、病理型態及組織變性為其發生之主要風險因子。息肉COX-2及DNMT3B的表現強度，也對追蹤時高風險病灶的發生有所影響，值得後續進一步研究探討。

The colorectal cancer is the third leading cause of cancer death and the first incidence cancer in Taiwan. Under nationwide colorectal cancer screening, in addition to colorectal cancer patients identified, many cases with colon polyps or adenomas were revealed. To optimize surveillance strategy after complete polypectomy, we used molecular markers cyclooxygenase (COX-2), as an important marker in inflammation and cancerization process, and DNA methyltransferase 3B (DNMT3B), as an important enzyme influencing DNA methylation, to see whether their expression would influence colon polyp recurrence or cancer development during surveillance. For most patients who received surveillance in our university hospital, the surveillance intervals were markedly shorter than USMSTF guideline suggestion. Still, 20.2% of patients were found to have high risk adenoma during surveillance, while 10.6% with advanced adenoma and 0.7% with colorectal cancer. The risk factors for occurrence of high risk adenoma or cancer during surveillance included: increased age, previous colonoscopy findings with one or more adenoma with size larger than one cm, more than three adenomas and with adenoma in right side colon. COX-2 and DNMT3B expression intensity in polyp tissue well correlates with polyp pathology progression. In univariate analysis, overexpression of DNMT3B in index colon polyp correlates to high risk adenoma occurrence during surveillance. However, the significance was not shown in multivariate analysis. Although the surveillance interval in our hospital were shorter than international guideline recommendation, some patients still developed high risk or advanced lesion. The number, size, location, pathology feature and tissue dysplasia of index colon polyp and patient age were major risk factors for these patients. The expression of COX-2 and DNMT3B in index polyp may also be involved in high risk lesion development during surveillance, warrant further investigation.

中文摘要 I
英文摘要(Extended Abstract) III
誌謝 VII
目 錄 IX
圖目錄 X
表目錄 XI
符號與縮寫對照表 XIII
儀器、藥品及試劑名稱 XV

第一章　　緒論 1
第二章　　材料與方法 17
第一節　　研究架構 17
第二節　　資料收集 17
第三節　　統計方法 23
第三章　　研究結果與討論 25
第一節　　研究結果 25
第二節　　討論 38
第三節　　總結 52

參考文獻 53
附 錄 63
自述 92

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