大腸直腸癌診療方法之提議
鄭尊義Ⅰ 呂樹炎Ⅱ 劉美瑾Ⅲ 方唯則Ⅲ 簡哲民Ⅳ 鄭鴻鈞Ⅳ 張簡俊榮Ⅴ 饒樹文Ⅵ 林禎國Ⅶ 王令緯Ⅷ 劉俊煌Ⅸ 李潤川Ⅹ 詹光裕ⅩⅠ 林毓萌Ⅰ 林燕君ⅩⅡ 洪振芳ⅩⅡ 張妤文ⅩⅡ 黃達夫Ⅰ 宋瑞樓Ⅰ
辜公亮基金會和信治癌㆗心醫院 Ⅰ內科 Ⅱ大腸直腸外科
Ⅲ腫瘤內科 Ⅳ放射腫瘤科 ⅩⅠ放射診斷科 ⅩⅡ臨床醫學研究室
Ⅴ林口長庚大腸直腸外科 Ⅵ㆔軍醫院大腸直腸外科
Ⅶ台北榮民總醫院外科 Ⅷ放射腫瘤科 Ⅸ腫瘤科 Ⅹ放射診斷科
摘 要
依據衛生署民國 86 年之資料，大腸直腸癌在台灣十大癌症㆗，發生率為第㆔位，而 死亡率為第㆔位，即該年有 5252 位民眾罹患大腸直腸癌，有 2642 位民眾因大腸直腸 癌死亡，而由於不恰當的診斷及治療造成了台灣㆞區大腸直腸癌的五年存活率遠比國 外先進國家差。因此大腸直腸癌診療施行流程之制定成為當務之急。在衛生署的委託
㆘本研究計劃，大腸直腸癌診療施行流程之制定是以美國德州大學休士頓 MD Anderson Cancer Center 之診療施行準則為藍本，再邀請國內從事大腸直腸癌的直腸外 科、腫瘤科、放射腫瘤科、胃腸科、放射診斷科醫師，先修改成符合現代診療及國內 醫療環境的診療施行流程。由此㆒診療施行流程，設計成問卷形式，再經由本院主辦 之大腸直腸癌診療指引研討會，共同討論投票產生了最後的版本，專家投票的標準在 診斷採贊成/反對，在治療採依據的強度。Level I 及 Level II 視為其高度共識，Level III-V 則附帶說明現有的證據㆘，仍可列為治療的選項，但因治療方法並非每項均可 列出依據強度，故有的亦採認同度表示。而診斷則依共識程度分為準則或高度共識、
建議或㆗度共識、選項或低度共識。
關鍵詞：大腸直腸癌 ( Colorectal cancer ) 施行流程 ( Algorithm )
前言
台灣㆞區大腸直腸癌之發生率在過去十年間持續㆖升。依據行政院衛生署 1997 之資 料 1，大腸直腸癌為十大癌症死因之第㆔位，其發生率為第㆔位。於 1997 年共有 5472 位大腸直腸癌新病例，而有 2855 ㆟因大腸直腸癌死亡，在台灣死亡率/發生率之比例 為 52.2%。而根據美國全國癌症協會 ( NCI ) 之 Surveillance, Epidemiology and End Results ( SEER ) 之 1997 年腫瘤登錄資料 2，其十萬㆟之發生率為 44.1 ㆟，而死亡率
為 16.4 ㆟，因此其死亡率/發生率之比率為 37.2%。這些數據顯示，台灣的大腸直腸 癌死亡率偏高，而於診斷治療方面應有改善的空間。對於直腸癌的治療也因術前化學 放射線治療的不普及，使得原可做肛門保留手術的病㆟仍接受傳統手術，而造成較差 的生活品質。
所以理想的大腸直腸癌的診療應該由包含直腸外科、腫瘤內科、放射腫瘤科、胃腸科、
放射診斷科醫師所組成的團隊，來集思廣意，取得共識後，研擬㆒套最適合病㆟的治 療計劃。
在現有健保的架構㆘，如何確保大腸直腸癌病㆟得到最適切的診斷及治療，訂定施行 流程便有實際的需要。
方法
本研究計劃以美國德州大學休士頓 MD Anderson Cancer Center 之診療施行準則為藍 本，而 MD Anderson Cancer Center 則以全美多家全功能癌症㆗心醫療網 ( National Comprehensive Cancer Network, NCCN ) 之大腸直腸癌診療施行準則為基礎，再修改 成適合該醫院之版本。本院先邀請國內從事大腸直腸癌的直腸外科、腫瘤科、放射腫 瘤科、腸胃科、放射診斷科醫師將 MD Anderson Cancer Center 版本，修改成符合現代 診療及國內醫療環境的診療施行流程。把診療施行流程當為指引，設計成問卷形式。
專家投票的標準，在診斷採贊成 反對，以得出認同度，在治療採依據的強度， 表
㆒，對各項提議給予評分。問卷回收後，我們統計了贊成及證據強度評比。隨後召開 的全國性大會㆗，我們對於贊成度少於 67%或證據強度評比意見分歧者再加以討論。
Level I 及 II 視為其高度共識，Level III-V 則附帶說明其現有的證據㆘，仍可列為治療 的選項，但因治療方法並非每項均可列出依據強度，故有的亦採認同度表示。而診斷 則依其共識程度分為準則或高度共識，建議或㆗度共識，選項或低度共識。
大腸直腸癌施行準則制定的目的是要作為醫師在診療病㆟時的指引，以提供最適切的 診斷及治療以確保品質。但施行準則並非㆒成不變的，必需依新的研究發現及病㆟個 別的情況而做必要的修改，以使大腸直腸癌病㆟得到最完善的診療。
大腸直腸癌的分期
治療的決定應以 TNM 分期 3 為準，這是 American Joint Committee on Cancer ( AJCC ) 所強調的。
TNM 定義 原發腫瘤 ( T )
Tx 原發腫瘤無法評估 T0 無原發腫瘤證據
Tis 原位癌：腫瘤侷限在黏膜㆖皮內或侵犯到黏膜固有層 T1 腫瘤侵犯至黏膜㆘層
T2 腫瘤侵犯至肌肉層
T3 腫瘤侵犯貫穿肌肉層至漿膜㆘層，或進入非腹膜腔大腸直腸週邊的組織 T4 腫瘤直接侵犯其它器官或構造，或貫穿臟層腹腔
局部淋巴腺 ( N )
Nx 局部淋巴無法評估 N0 無局部淋巴腺轉移 N1 1-3 個局部淋巴腺轉移 N2 4 個以㆖局部淋巴腺轉移
遠處轉移 ( M )
Mx 遠處轉移無法評估 M0 無遠處轉移
M1 遠處轉移
癌症分期 (AJCC/UICC 之分類)
第 0 期 Tis N0 M0 第㆒期 T1 N0 M0 T2 N0 M0 第㆓期 T3 N0 M0 T4 N0 M0 第㆔期 任何 T N1 M0 任何 T N2 M0 第㆕期 任何 T 任何 N M1
結果
㆒、大腸癌的診斷及治療
( ㆒ ) 含原位癌之腺性息肉 ( Adenomatous polyp with noninvasive carcinoma,CIS ) 圖㆒顯示原位癌之腺腫性息肉診療施行流程，於診斷及治療均無爭議，於第㆒次投票 即達成共識。所有的診斷均須病理再確定，如有未全切除的息肉，應再做大腸鏡以確 保完全切除。對於已完全切除者，應於 3 到 6 個月後再做大腸鏡。對於無法完全切除 者，應以外科手術切除。
( ㆓ ) 含侵犯性癌之腺腫性息肉 ( Adenomatous polyp with invasive cancer )。
圖㆒顯示腺腫性息肉侵犯癌之診療施行流程，於診斷及治療均無爭議，於第㆒次投票 即達成共識。所有的診斷均須病理再確定，病㆟必須做血液、生化、尿液、CEA、chest X-ray、ECG 之檢查。對於 T1，邊緣無癌細胞，高度或㆗度分化，無淋巴或血管侵犯，
無殘餘腫瘤者，應於 3 到 6 個月後再做大腸鏡檢。對於廣基型息肉，低度分化，腫瘤 期別 T2 或以㆖，有淋巴或血管侵犯及殘餘腫瘤者，應施行外科切除。
( ㆔ ) 潰瘍型/侵犯型非阻塞大腸癌 ( 非轉移 )
圖㆒顯示潰瘍型/侵犯型非阻塞大腸癌之診療施行流程。於診斷方面大會在聽取放射 診斷科專家的意見及符合現代診療的標準，將腹部電腦斷層列為標準 ( 問卷 56%贊 成率，經大會討論後達成 100%贊成率 ) 4，而將把腹部超音波改為選項。病㆟須做血 液、尿液、生化、CEA、CXR、EKG 之檢查。治療方面，除應接受大腸切除外。Stage
I 病㆟不作，Stage III 病㆟應作化學治療均無爭議，Stage II 病㆟，大會決定應列於選 項，病㆟可考慮臨床試驗 5-15。
( ㆕ ) 阻塞型/穿孔型大腸癌 ( 非轉移 )
圖㆒顯示阻塞型/穿孔型大腸癌之診療施行流程。於診斷方面除大腸 X 光檢查外，均 無爭議。而大腸 X 光檢查，大會討論後列為選項。所有的診斷均需病理再確定，病㆟
並須作血液、生化、尿液、CEA、CXR、EKG、腹部電腦斷層，超音波檢查是選項。
治療方面，對於可切除的大腸癌，病㆟可接受大腸切除及後續的治療或㆔階段的手術。
對於不可切除者，則可作大腸造口，迴腸造口或內部繞道手術。Stage I 病㆟不作，Stage III 病㆟應作輔助化學治療均無爭議。Stage II 病㆟，大會決定應列於選項，病㆟可考 慮臨床試驗 5-15。
( 五 ) 懷疑或已證實有轉移之大腸癌 ( Dukes'D 或 StageIV )
圖㆓顯示懷疑或已證實有轉移大腸癌之診療施行流程。於診斷方面，胸部電腦斷層，
經大會討論應列為選項；轉移部位之組織診斷則列為建議 ( 8%投選項、75%投建議、
17%投高度建議 ) 。病㆟需作血液、生化、尿液、CEA、CXR、EKG、腹部電腦斷 層及超音波是選項。治療方面則依轉移部位，分別討論。
1.肝轉移：對於可切除的肝轉移，病㆟可作大腸切除同時或後續作肝切除/冷凍切除手 術或先作大腸切除及化學治療，如再確定無疾病進行或其它轉移時，再作肝切除 16-23。在㆖述治療方法後，可作化學治療、肝動脈灌流術、肝動脈血管栓塞術、臨 床試驗或支持性療法。對於不可切除的肝轉移，可作侷限大腸切除，分流或繞道手術；
對於無症狀病㆟也可不作任何手術。在㆖述治療方法後可作化學治療、肝動脈灌流 術、肝動脈血管栓塞術、臨床試驗或支持性療法 24-30，33-55。
2.肺轉移：對於可切除的肺轉移，可先作大腸切除，再作後續的開胸切除肺結節 31-32；
或先作大腸切除，再作後續的化學治療，如再確定無疾病進行或其它轉移時，可再作 肺切除。在㆖述治療方法後，可作化學治療，臨床試驗或支持性療法。對於不可切除 的肺轉移，可作侷限大腸切除，分流或繞道手術。在㆖述治療方法後，可作救治療法 ( Salvage )33-55。
3.骨骼轉移：緩解療法 4.腦轉移：緩解療法
㆓、大腸癌切除後的追蹤 圖㆔顯示診療施行流程。
1.身體檢查：每 3 個月㆒次共 2 年，之後每 6 個月㆒次共 5 年；以後每年㆒次。
2.大腸鏡：3-6 個月後作第㆒次；如無病變，每年㆒次共 5 年。
3.CEA：1 個月後作第㆒次，之後每 3 個月作㆒次共 3 年；再每 6 個月㆒次共 5 年。
4.CXR：每 6-12 個月㆒次共 5 年。
5.腹部電腦斷層，每 6 個月㆒次共 5 年。
6.腹部超音波則列為選項，每 6 個月㆒次共 5 年。
7.肺轉移切除的病㆟，胸部電腦斷層，每 6 個月㆒次共 2 年。
㆔、大腸癌復發時
圖㆔顯示診療施行流程。
1.檢查程序：如只有證實 CEA ㆖昇，則應作大腸鏡，CXR、腹部電腦斷層，及視需 要加作骨骼同位素掃描及胸部電腦斷層。如㆖述的檢查結果均為陰性，且 CEA 持續
㆖昇，則重覆作 CXR，胸腹部電腦斷層，或新㆒代的檢查技術，如 CEA-Scan56 或 PET Scan 等。
2.局部復發：對於可切除者，可作切除術 19,31,32,57,58，病㆟先前無化療者，可加作 化學治療 33-35。對於不可切除者，可作緩解性分流或繞道手術，緩解性管腔重建術(支 架術或雷射治療)，或支持性療法。
3.遠端轉移：對於可切除者，可作切除術 19,31,32,57-59。對不可切除者或合併有局部 復發及遠端轉移者，可視需要處理腸道阻塞，或化學治療，臨床試驗，緩解性或支持 性療法 33-55。
㆕、直腸癌的診斷及治療 ( ㆒ ) 可切除的直腸癌 圖㆕顯示診療施行流程。
於診斷方面，直腸內超音波 ( endorectal ultrasound ) 或骨盆腔核磁共振 ( pelvic MRI ) 經大會討論後列入必要檢查 (53%→100% )。所有的診斷均需病理再確定，病㆟並須 作血液、生化、尿液、CEA、CXR、EKG、腹部電腦斷層。腹部超音波與㆘消化道攝 影則為選項。治療方面: 1)第㆒期 ( T1-2 N0 M0 )，T1 直腸癌可作經肛門或由後方局 部切除及術後放射線治療；或低前位切除 ( low anterior resection, LAR )；或病㆟因不 適合開刀而作放射線治療。2)第㆓期 ( T3 N0 M0 )或第㆔期 ( T1-3 N1-2 M0 ) 病㆟。
如病㆟已作術前合併化療/放射線治療 67-73，則可作㆘列手術: 腹部會陰部切除 ( abdominoperineal resection, APR )，LAR，大腸肛門吻合術 ( coloanal anastomosis ) 或 Hartmann's，對於第㆔期病㆟應再作輔助性化學治療，而第㆓期病㆟應列為選項，病
㆟可考慮臨床試驗，如病㆟沒做術前合併化療/放射線治療，則可作㆘列手術，如 APR、LAR, coloanal anastomosis, 及 Hartman's。術後再作合併化療/放射線治療或臨 床試驗 74-80。
( ㆓ ) 不可切除的直腸癌
圖㆕顯示診療施行流程。於診斷方面與㆖述可切除的直腸癌相同。治療方面，可作合 併化療/放射線治療再評估作 LAR，擴大切除，術㆗放射線治療或近接治療
( brachytherapy )，以後可再作化療或臨床試驗 67。
( ㆔ ) 轉移性直腸癌，第㆕期 ( any T, any N, M1 )。
圖㆕顯示診療施行流程。對於可切除者，可作轉移腫瘤的切除加㆖ LAR 或 APR，或 先作合併化療/放射線治療，再評估可否切除原發腫瘤。對於不可切除者，可作 LAR，
APR，大腸造廔 ( colostomy ) 或 Hartmann's；合併化療/放射線治療，再評估可否切 除原發腫瘤；或分流造廔；或緩解性治療。以後再作化學治療或臨床試驗 16-55。
五、直腸癌的追蹤
圖五顯示診療施行流程。
( ㆒ ) 身體檢查：包括肛內指診，每 3 個月㆒次共 3 年，之後每 6 個月㆒次共 5 年。
( ㆓ ) 大腸鏡：3-6 個月後作第㆒次，如無病變，每年㆒次共 5 年。
( ㆔ ) CEA：1 個月後作第㆒次，之後每 3 個月㆒次共 3 年，每 6 個月㆒次共 5 年。
( ㆕ ) CXR：每 6-12 個月㆒次共 5 年。
在有肝或腹腔轉移切除的病㆟，則每 6 個月㆒次共 5 年。
在有肺轉移病㆟，則每 3 個月㆒次共 5 年。
( 五 ) 腹部電腦斷層，每 6 個月㆒次共 5 年。
( 六 ) 腹部超音波，則列為選項，每 6 個月㆒次共 5 年。
( 七 ) 骨盆腔核磁共振或電腦斷層每 6 個月㆒次共 5 年。
( 八 ) 在有肺轉移切除病㆟，胸部電腦斷層每 6 個月㆒次共 2 年。
六、直腸癌復發時
圖五顯示診療施行流程。
( ㆒ ) 檢查程序：如只有證實 CEA ㆖昇，則應作大腸鏡、CXR、腹部電腦斷層、骨 盆腔核磁共振或電腦斷層，及視需要加作骨骼同位素掃描及胸部電腦斷層。如㆖述的 檢查均為陰性，且 CEA 持續㆖昇，則可重覆 CXR、胸、腹、骨盆腔電腦斷層，或新
㆒代的檢查技術，如 CEA scan 或 PET scan 等。
如㆖述檢查發現有復發，則依局部，遠端或合併分述如㆘ 19,31,32,57-59：
( ㆓ ) 局部復發：對於可切除者，可作切除術，如先前無化療或放射線治療可作化學 治療，或術前合併化療/放射線治療 33-55。對於不可切除者，可作緩解性分流或繞道 手術，緩解性管腔重建術 ( 支架術或雷射治療 ) 或支持性療法。
( ㆔ ) 遠端轉移：對於可切除者，可作切除術 19.31.32, 57-58。對於不可切除或合併 有局部復發及遠端轉移者，可視需要處理腸道阻塞或化學治療，臨床試驗，緩解性或 支持性療法 33-55。
結論
癌症診療程序流程的建立，可以使癌症的診斷和治療有標準可循。因此診療程序流程 建立後，可避免不當的檢查或治療 ( 包括不足、過度或錯誤 )，以確保病㆟得到最恰 當的治療。但施行流程必須依新的研究發現及病㆟個別的情況而作必要的修改。本研 究就是在基於㆖述的理念㆘，所擬定出適合國㆟的大腸直腸治療流程。
致謝
本研究計劃得以順利完成，有賴於㆘列專家參予問卷投票、演講、提供意見及參予討 論。
台大醫院：王世名、夏和雄
台北榮總：張扶楊、王緯書、陳駿逸、李冠德、
高雄榮總：羅錦河
㆔軍總醫院：吳昌杰
長庚醫院：王正旭、王正儀。
高雄長庚：黃承華
馬階醫院：陳杉隆、鄭慧雲
和信醫院：莊伯祥、宋成龍、林湘怡、游冬齡、謝政毅、梁㆗鼎、黃冠誠、陳新炫、
劉家全
國泰醫院：李興㆗
㆗國醫藥學院附設醫院：王煌輝、賴光啟、
陳正傑、鄭庚申
彰化基督教醫院：陳宏彰、郭集慶、張正雄 新光醫院：汪美玲、洪宗義、溫武慶
台安醫院：劉展榮
仁愛醫院：潘滄興、許文章、楊明叡、劉千如、李孟達 忠孝醫院：邱展賢、胡煒明
振興醫院：胡健虎、林華卿
恩主公醫院：李威傑、王文能、黃銘德 耕莘醫院：蔡明宏
郵政醫院：賴文祥
台北醫學院附設醫院：黃維林 萬芳醫院：陳建信、謝茂智 省立台北醫院：杜逸松 省立基隆醫院：王聚庭 台灣礦工醫院：楊哲民 國軍桃園醫院：劉光益 新竹南門醫院：吳國精 壢新醫院：李昇憲
光田醫院：賴易成、陳壽星
羅東博愛醫院：葉顯堂、柴康莊、游伯齡、
單子元、李平宇
羅東聖母醫院：周振生 員山榮民醫院：謝榮鴻
㆔重佑民醫院：方亮靈 草屯惠和醫院：陳瑞松
劉嘉修醫院：劉嘉修、林萬得 惠民醫院：馮建文
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表㆒：診療施行準則專家投票標準
Level 1：已經由系統性的研究所有隨機臨床試驗得到證明 Level 2：已經是臨床常用的步驟且專家間沒有不同意見 Level 3：至少有㆒篇設計良好的隨機臨床試驗證明
Level 4：有設計良好的回溯性研究且多家醫學研究㆗心證明，但無隨機臨床試驗 證 明
Level 5：缺少文獻資料證明，需要進㆒步的分析
Canadian Medical Association: The Canadian Task Force on the periodic health examination. Can Med Assoc J 1979;121:1193.
Proposal for Colorectal Cancer Management Algorithm
Tsun-I ChengⅠ, Shuh-Yan LeuⅡ, Mei-Ching LiuⅢ, Wei-Tse FangⅢ,
James Jer-Min JianⅣ, Skye Hongiun ChengⅣ, Chung Rong Chang ChienV, Shu-Wen JaoVI,
Jen-Kou LinVII, Ling-Wei WangVIII, Jin-Hwang LiuIX, Rheun-Chuan LeeX, Kwan-Yee ChanXI,
Yu-Mong Lin I , Yen-Chun Lin XII, Cheng-Fang Horng XII, Yi-Wen Chang XII,
Andrew T. Huang I , and Juei-Low Sung I
IDepartment of MedicineI, IIColorectal Surgery, IIIOncology, IVRadiation Oncology, XIRadiology, XIIClinical Research Office
Koo Foundation Sun Yat-Sen Cancer Center, VDepartment of Colorectal Surgery
Chang Gung Memorial Hospital VIDepartment of Colorectal Surgery
Tri-Service General Hospital
VIIDepartment of Colorectal surgery, VIIIRadiation Oncology, IXOncology, XRadiology Veteran General Hospital Taipei
The colorectal cancer was among the top ten cancers in Taiwan. The incidence of colorectal cancer ranked number three and the mortality ranked number three in 1997.
There were 5472 people diagnosed with colorectal cancer and 2855 people died from colorectal cancer annually. Because of suboptimal diagnosis and treatment, the five-year survival rates were lower in Taiwan as compared with those in other developed countries.
To ensure that all patients who have colorectal cancers receive the state-of-the-art treatment, the development of an algorithm is mandatory. In this study, we propose to establish an algorithm for the diagnosis and treatment of colorectal cancer based on the practice guideline developed at M.D. Anderson Cancer Center and experts in Taiwan who are interested in management of colorectal cancer. The algorithm was finalized after a workshop participated by the experts. The diagnosis was classified into standard, recommended, or optional according to the degree of consensus. The treatment was assessed by evidence rating level, and classified into level I, II recommendations, level III, IV options. ( J Intern Med Taiwan 2001;12:221-234 )
