With the progress of medical technology, the minimally invasive laparoscopic colorectal surgery is currently enthusiastically performed in the medical center all over the world. Because preoperative CCRT can induce fibrosis of pelvic tissues, most colorectal surgeons have been hesistant to apply the laparoscopic approach to the resection of irradiated rectal cancer. However, based on our preliminary experience(Liang et al. Dis Colon Rectum Sep,2005), we found that if rectal cancers were resected by laparoscopic approach, the advantages include better visualization of anatomical structures such as paired hypogastric nerves, presacral fascia, lateral ligament, seminal vesicles and middle hemorrhoidal artery, as compared to traditional open method. Moreover, the conduction of laparoscopic double-stapling technique or pull-through procedure was not jeopardized by CCRT even when the pelvis is narrow in male patient. That is, with the current surgical technique, we feel that laparoscopic procedure is feasible and safe for inrradiated rectal cancers. Because the application of this technique in the resection of rectal cancer after CCRT is not reported before and has academic importance, it is mandatory for us to conduct this randomized prospective study. Remarkably, some objective surgical stress-related factors including CD4+/CD8+, ESR, CRP, and IL-6 (both in serum and intra-peritoneal surgical wounds), and the presence of cancer cells in either laparoscopic and open group of patients were analyzed and compared. Moreover, the translational research regarding the expression of genes and their prognostic significance before and after chemoradiation therapy have been scarce. In this project, we plan to explore the influence of chemo radiation therapy on the gene expression by microarray analysis according to the reproducible experiences developed by our colleagues in the research of gastric cancer (JCO 2005;23:7286-95). Initially, we will focus on the expression difference of the commonly mentioned genes related to the chemosensitivity of colorectal cancer, including mismatch repair genes, thymidylate synthetase, Dipyrimidine dehydrogenase (DPD), and epidermal growth factor receptor (EGFR), and then extend to the screening of the whole genome. Moreover, some recent reports indicated that the cell population harboring CD-133 were ther potential colorectal cancer stem cells. In this project, we will also explore the changes of histopathology and CD-133 cellular population in advanced rectal cancer after CCRT.

Because this is a randomized prospective clinical trial, it is uneasy to accrue enough patients. According to the statistical estimation, at least 558 patients should be recruited and randomized to either traditional open group and laparoscopic group to reach a statistical significance. Moreover, it has been reported that in order to represent the overall survival, the patients have to be followed up for at least 3 years after treatment. Therefore, it is necessary that this project should be further conducted for at least 3 years. Based on our preliminary results in the previous 2-year conduction of this project, we found that laparoscopic technique facilitated patients with rectal cancer after CCRT less surgical invasiveness, faster postoperative recovery, similar extent of dissection and the number of harvested lymph nodes, and did not increase of tumor dissemination during surgical manipulation, as compared with traditional open surgery. This encouraging results inspired us to complete this 3-year project, with a view to enhancing the academic reputation of Taiwan Colorectal Surgery and the quality of clinical management for patients with rectal cancer.