摘要：本計劃是一個承襲先前此一主題的國科會計畫（NSC 97-2314-B-002 -025 -MY3），過去的三年研究，我們針對晚期直腸癌病患以隨機前瞻性研究的方式比較腹腔鏡與傳統剖腹手術之手術侵襲性、併發症、術後功能恢復與病患存活的利弊得失，做一個全面性的分析。目前直腸癌外科治療的重點在於針對病患個人情況的「個人化醫療」，而其執行的重點在「腫瘤根治切除」的前提下，盡量使病患術後的侵襲性降到最低，免疫受到壓制的程度降至最低，且得到術後較佳的生活品質。根據這些理念，術前放射線合併化療(CCRT)，然後再以微創手術切除腫瘤可能是目前對晚期直腸癌病患值得發展的術式。隨著科技的進步，低侵襲性腹腔鏡大腸直腸切除手術（minimally invasive surgery）已在世界醫學中心如火如荼地進行。然而，CCRT後的骨盆組織纖維化，一直使我們不敢以腹腔鏡手術實施直腸癌切除。根據之前計畫的經驗，我們以為在腹腔鏡下進行直腸癌切除合併自律神經保留手術時，優點是解剖構造如下腹神經、薦骨筋膜、外側韌帶、儲精囊、甚至中痔動脈在視野上比傳統手術看得更清楚，使得病患得到術後較佳的性功能與膀胱功能保留。另外，在腹腔鏡下，由於對骨盆底的視野較佳，因此不論進行雙重釘合技巧（Double-stapling technique）或Pull-through術式CCRT並不會太增加手術難度（Liang et al. Dis Colon Rectum Sep,2005），而且腫瘤切除的遠端安全距離或周邊安全距離也不會比傳統剖腹手術遜色。之前的研究計畫，我們已驗證腹腔鏡手術可得到比傳統手術較佳的術後功能恢復，而且分析CD4+/CD8+、ESR、CRP、IL-6在腹腔鏡內局部傷口及血清中濃度的定量比較，也證實腹腔鏡手術對病患手術中或手術後的免疫抑制情況較輕微，這對直腸癌的治療效果是正面的。由於本計劃是一個隨機前瞻性研究，病例收集相當不易，根據統計學的估算，必須至少收集約558位病例（兩組各約為279位），方有統計意義（假設兩組治療成果差異在10%以內，並達到80%統計學效度）。過去三年來，雖然我們已經收集兩組各約126名病患。然而，目前的文獻顯示病患至少需追蹤三年方能代表整個存活情形。因此，本計畫必須再進行長達三年才能使病患存活的追蹤時間達到中位數三年以上，並達到足夠的統計學效度。過去三年執行先前計畫的過程中，我們初步對126病例的結果分析顯示，腹腔鏡手術較傳統手術對病患而言侵襲性較低、較快恢復、腫瘤切除範圍及淋巴腺摘取數目與傳統手術相同，且亦不會增加腫瘤手術中擴散的機會，此一正面成果鼓勵我們繼續完成此一3年期研究，本計劃的重點將放在病患腫瘤復發情況的長期追蹤，由於直腸癌的腹腔鏡手術成果目前世界上尚無第一級的證據，我們深信此計劃的進行將會提高台灣大腸直腸外科學術地位及提高病患照料品質。
Abstract: This is a three-year research project following our previous study （NSC 97-2314-B-002-025-MY3）. During the last3 years, we have made a comprehensive comparison between laparoscopic total mesorectal excision and traditionalopen method regarding the parameters of functional recovery and oncologic results of patients with advanced rectalcancer. The current trend for the surgical treatment of rectal cancer is tailored, individualized therapy, of which theclinical practice is focused on radical tunor excision, mild intra-operative and post-operative invasiveness, and lessoperative stress. Based on such visionary points, pre-operative concurrent chemoradition therapy followed by a minimalinvasive laparoscopic total mesorectal excision maybe a new treatment paradigm for patients with low rectal cancer.With the progress of medical technology, the minimally invasive laparoscopic colorectal surgery is currentlyenthusiastically performed in the medical center all over the world. Because preoperative CCRT can induce fibrosis ofpelvic tissues, most colorectal surgeons have been hesistant to apply the laparoscopic approach to the resection ofirradiated rectal cancer. However, based on our preliminary experience(Liang et al. Dis Colon Rectum Sep,2005), wefound that if rectal cancers were resected by laparoscopic approach, the advantages include better visualization ofanatomical structures such as paired hypogastric nerves, presacral fascia, lateral ligament, seminal vesicles and middlehemorrhoidal artery, as compared to traditional open method. Moreover, the conduction of laparoscopic double-staplingtechnique or pull-through procedure was not jeopardized by CCRT even when the pelvis is narrow in male patient.Based on the experience from previous study, we feel that laparoscopic procedure is feasible and safe for inrradiatedrectal cancers, and can even achieve adequate circumferential resection margin and distal safety margin. Our previousstudy has indicated that laparosopic approach for total mesorectal excision induced less operative stress than traditionalopen laparotomy, as evaulated by objective surgical stress-related factors including CD4+/CD8+, ESR, CRP, and IL-6(both in serum and intra-peritoneal surgical wounds). Such favorable outcomes may be beneficial for our patients fromthe viewpoint of surgical oncology.Because this is a randomized prospective clinical trial, it is uneasy to accrue enough patients. According to thestatistical estimation, at least 558 patients should be recruited and randomized to either traditional open group andlaparoscopic group to reach a statistical significance. Moreover, it has been reported that in order to represent theoverall survival, the patients have to be followed up for at least 3 years after treatment. Therefore, it is necessary thatthis project should be further conducted for at least 3 years, with a view to achieveing median time of patient follow-upup to 3 years. Based on our preliminary results in the previous 3-year conduction of this research, we found thatlaparoscopic technique facilitated patients with rectal cancer after CCRT less surgical invasiveness, faster postoperativerecovery, similar extent of dissection and the number of harvested lymph nodes, and did not increase of tumordissemination during surgical manipulation, as compared with traditional open surgery. Seeing that the level-oneevidence of the laparoscopic TME for the treatment of low retcal cancer is still lack of, the previous encouraging resultsshould inspire us to further conduct this 3-year project, with a view to enhancing the academic reputation of TaiwanColorectal Surgery and the quality of clinical management for patients with rectal cancer in Taiwan.