Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity

Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Along with peoples' transition of life styles and food habits, the incidence rate of colorectal cancer gets rising for the past few years. Nowadays, surgery is still to remain as a principal method to treat colorectal cancer. Since the first laparoscopic cholecystectomy performed in France by Phillippe Mouriat of Lyons in 1987[1], the development of minimally invasive surgery has allowed major changes in the surgical treatment of various benign and malignant diseases, especially because it limits surgical trauma[2]. During recent years, the laparoscopic approach has developed as an interesting therapeutic alternative for the resection of various colorectal diseases[3–6]. In China, The first series of laparoscopic colorectal resection was reported by Shanghai Ruijin Hospital in 1993. Since 2000, there has been a remarkable increase in this field. Laparoscopic colorectal surgery has been routinely performed in most of the general teaching hospitals[7]. This procedure has been shown to be feasible in most patients with malignant disease and can be performed with faster recovery and shorter hospitalization than the open approach[8–11].

Despite the promising clinical results, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This prospective clinical study was of major clinical interest because the reduced surgical trauma should result in reduced postoperative immune, especially cellular immune dysfunction in patients undergoing laparoscopic surgery, thus contributing to clinical and oncologic advantages for these patients.

Until now, it has been reported that the degree of postoperative inflammatory is reduced after laparoscopic surgery[12, 13]. Other groups also observed significantly better preservation of cell-mediated immunity after laparoscopic vs open colorectal surgery[14, 15]. Furthermore, it has been observed that cell-mediated immunity, as assessed by delayed-type hypersensitivity testing in humans, is better preserved after laparoscopic vs open colorectal resection[16].

Our study was performed to evalute perioperative immune parameters in 68 patients with colorectal cancer. We herein analyzed the effects of laparoscopic and open surgery on proinflammatory C-reative protein(CRP) levels. Furthermore, we measured lymphocyte subpopulations, leukocyte and neutrophils counts, and circulating natural killer(NK) cells before surgery and on days1, 4, and 7 after surgery. This study, therefore, allowed assessment of the effects of laparoscopic and conventional open colorectal surgery on cellular immune responses after major abdominal surgery.

Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality all over the world. Nowadays, surgery is still to remain as a principal method to treat colorectal cancer. On the other hand, tumor immunity, mainly defined as the immune responses in the body against tumor, acts an important role during the process when patients fight against tomors. When tumor antigens were recognised by antigen presenting cells(APC), they were processed as peptides, and these peptides presented by APC acted as first and second signals to activate naive CD4⁺T cells and CD8⁺T cells. As naive CD4⁺T cells and CD8⁺T cells received these signals, they differentiated into Th0 cells and pCTL. When Th0 cells received different allostimulatory signals, they were activated as Th1 and Th2 cells. IL-4 secreted by Th2 cells acted as allostimulatory signal to activate B cells. Activated B cells could secrete generous tumor specific antibodies and killed tumor cells through complement dependent cytotoxicity(CDC) and antibody dependent cell-mediated cytotoxicity(ADCC). IFN-γ secreted by Th1 cells acted as allostimulatory signal to activate pCTL. Activated CTL could kill tumor cells directly. Besides, IFN-γ secreted by Th1 cells could enhance the activity of NK cells and Mφ, which could fight against tumors through ADCC. After antitumor immune responses, part of activated T cells could differentiate into memory T cells(CD45RO⁺T cells), which had quick reaction against tumor cells in twice antitumor immune responses[17, 18]. It can be seen that cellular immunity acts an predominant role in tumor immunity. Although surgery is regarded as the most important way in tumor therapy, many reports have confirmed that surgery stress has great depressant effect on cellular immunity in the body, which would bring negative influence to prognosis of patients[16, 19, 20]. So to think of a way to decrease surgery stress as well as the influence of cellular immunity becomes quite important.

The development of minimally invasive surgery has allowed major changes in the surgical treatment of various benign and malignant diseases, especially because it limits surgical trauma. Since Jacobs[21] reported the first case of laparoscopic sigmoidectomy, during recent years, the laparoscopic approach has developed as an interesting therapeutic alternative for the resection of colorectal cancer. Because the surgical trauma is limited, the laparoscopic approach usually allows for a rapid return to preoperative activity levels with significantly shorter hospitalization.

This study found that the operating time of LCR group and OCR group were 137.29 ± 34.58 min and 130.61 ± 36.72 min, prospectively. There was no difference between the two groups. Conventional versus laparoscopic assisted surgery in colorectal cancer (CLASSICC)[22], Colon cancer laparoscopic or open resection study group (COLOR)[6] and Lezoche[8] also observed similar results. Our findings shew that the intraoperative blood loss in LCR group and OCR group were 117.27 ± 65.21 ml and 159.39 ± 83.40 ml, prospectively. We found the intraoperative blood loss was much less in LCR group. Barcelona[5] and COLOR[6] also observed similar outcomes as we did. Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay. This observation confirmed findings reported by Breukink[23]. Our findings suggested that short-term quality-of-life benefits could be observed with LCR when compared with OCR.

Besides the promising clinical results, we focused on the perioperative cellular immunological effects of LCR when compared with OCR.

Many researches have confirmed that prognosis of cancers depends on invasion of tumors and immunoreaction of bodies. Paholyuk[24] found that NK cells played an important role in suppressing growth of colorectal cancers of stage II. Milašienė[25] reported that counts of CD4⁺T cells, CD8⁺T cells and NK cells directly correlated with long-term overall survivals of patients with colorectal cancers and gastric cancers of stage III.

Hiki[12] reported that in laparoscopy there was generally less manipulation and exposure of the intestine than in open surgery, with a further reduction in host inflammatory responses. Our findings shew that minimally invasive surgery resulted in a less pronounced proinflammatory response to surgical trauma. Jung[13] also got similar results in the research, who found laparoscopic surgery got less influence on CRP than open surgery.

Many researches have observed that there is a distinct immunologic advantage to laparoscopic surgery[26–29]. Our findings confirmed better preserved cellular immune responses in patients undergoing laparoscopic colorectal resections. The counts of CD4⁺T cells, CD8⁺T cells, CD45RO⁺T cells and NK cells were more in LCR group than OCR group, especially on POD 4. This observation was in agreement with the findings of Whelan[16], who also observed better preserved cellular immune responses in patients undergoing laparoscopic surgeries. Although our findings were not completely comparable with the researches from Wichmann[14], we found similar change tendency of NK cells. Han[15] also reported that laparoscopic resections got less influence on cellular immune functions of the patients with colorectal cancers of stage III. Peng[30] found the perioperative immune response was less obvious after a laparoscopic procedure compared with a conventional approach in patients with renal cell carcinoma.

Compared with the previous research articles, our study more comprehensively reflected the progress of laparoscopic colorectal cancer radical resections and the improvement of cellular immune protection nowadays in Mainland of China.

There is a suggestion that cancers demonstrate a more aggressive phenotype after open surgery, with the more profound immunosuppression contributing to more rapid cancer growth[31]. Milašienė[25] reported that better cellular immunity correlated with higher postoperative survival rates in patients. The long-term effects of better preserved cellular immune responses and its relationship with the prognosis of patients still remain obscure. However, we can assume that our observation of better preserved cellular immunity in patients after laparoscopic colorectal surgeries has beneficial effects on the prognosis of patients.

In conclusion, our study demonstrates that laparoscopic colorectal resection gets less surgery stress and short-term advantages compared with open resection. Also, cellular immune respond appears to be less affected by laparoscopic colorectal resection when compared with open resection.