Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits? Calvin S. H. Ng, M.B.B.S.(Hons), 1 Richard L. Whelan, M.D., 2 Antonio M. Lacy, M.D., 3 Anthony P.C. Yim, M.D. 1 1 Division of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong 2 Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York, USA 3 Department of Gastrointestinal Surgery, Hospital Clinic, Corporacio Sanitaria Clinic, University of Barcelona, Barcelona, Spain Published Online: June 30, 2005 Abstract. Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better pre- served following laparoscopic procedures when compared with their respective open approaches, CO 2 pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Im- paired cellular immunity after CO 2 pneumoperitoneum may have sig- nificant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO 2 insuf- flation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO 2 pneu- moperitoneum. Better preservation of early postoperative cellular im- mune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparo- scopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions. The development of minimal access surgery in the past two decades has changed the way many conditions are being treated. In particular, laparoscopic procedures and video-assisted thoracic surgery (VATS) have gained popularity among patients and cli- nicians because of the faster recovery after surgery, less postop- erative pain, and better cosmesis. It is well known that surgical trauma can induce a systemic inflammatory response and that it can affect the postoperative systemic immune response [1]. Minimal access surgery is associated with a reduced postoperative systemic inflammatory response, and recent evidence suggests that it can result in a lesser degree of postoperative immuno- suppression than that associated with conventional surgery. Maintenance of immune function after minimally invasive pro- cedures may favorably influence the following parameters: the rate of postoperative infection [2], the length of hospital stay [3], and the long-term prognosis (recurrence and survival) after can- cer surgery [4, 5]. Obviously, each of these factors must be care- fully studied and validated before any definitive statements or conclusions can be made. In this review, the current literature on postoperative systemic and regional inflammatory response after laparoscopic and VATS are appraised, with particular focus on postoperative cellular immunity and its potential influence on tumor immunosurveillance. Surgical Trauma and the Inflammatory Response It is well documented that surgical trauma can induce the release of major acute-phase response mediators including C-reactive protein (CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor- a (TNF-a) [1]. Most studies that have compared laparoscopic and open cholecystectomy have confirmed reduced CRP levels [1, 6, 7] following the minimally invasive operation; it is assumed that this finding reflects the lesser degree of surgical trauma associated with the laparoscopic approach. Serum IL-6 concentration, an early marker of surgical or other trauma, can rise as early as 1 hour after the start of surgery [8]; it usually peaks between 2 and 4 hours postoperatively, and serum levels may remain elevated above baseline for several days after surgery. [8–12] After laparoscopic cholecystectomy the vast majority of studies have reported lower postoperative IL-6 levels when compared to the open results [6, 13, 14]. The CRP and IL-6 results suggest a close relationship between these acute inflammatory mediators and the degree of surgical trauma [15]. Not all open procedures are equivalent; the length of the abdominal wall incision directly correlates with the extent of surgical trauma incurred. For example, when open cholecystectomy done via a ‘‘mini’’ incision, which incurs less abdominal wall trauma than a standard incision, was compared to laparoscopic cholecystectomy, no differences in IL-6 and CRP levels were noted between groups [16]. Also of note, when oper- ations that require only a limited incision are assessed, such as appendectomy and hernia repair, significant differences in IL-6 Correspondence to: Anthony P.C. Yim, M.D., e-mail: yimap@cuhk. edu.hk World J. Surg. 29, 975–981 (2005) DOI: 10.1007/s00268-005-0029-6 Editorial Update