Trial Information

A Randomized Controlled Clinical Trial Comparing Oncological Results and Functional Recovery Between Laparoscopic and Open Method for the Treatment of Advanced Rectal Cancer After Concurrent Chemoradiation Therapy (CCRT)

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.