The immunologic consequences of laparoscopy in oncology.
The last decade has seen the publication of many studies regarding the impact of both traditional open methods and minimally invasive techniques on a variety of immune function parameters. Clearly, major surgery results in period of cell-mediated immunosuppression that can have an impact on the patient's recovery that would best be avoided. Although there are conflicting data among studies regarding some immune parameters there is general agreement in regards to other variables. The DTH and LPA studies uniformly have shown that open methods result in significantly more immunosuppression than laparoscopic techniques. It seems that the choice of surgical approach does not impact on the absolute number of lymphocytes or lymphocyte subpopulations. There is evidence of a short-lived (less than 1 day) greater shift towards Th2 function, mainly through suppression of the Th1 lymphocyte population, after open surgery than after closed procedures. Regarding circulating monocytes, laparotomy seems to result in greater decreases in HLA-DR expression and monocyte-mediated cytotoxicity while at the same time activating monocytes to elaborate more TNF-alpha and superoxide anion than laparoscopic methods. The data regarding peritoneal macrophages is most confusing; however, most studies do agree that laparotomy results in increased release of cytokines and respiratory burst mediators. The degree to which CO2 pneumoperitoneum suppresses macrophage function is uncertain because, although some studies have shown that CO2 pneumoperitoneum suppresses macrophage function in regards to control animal results, other studies found that the CO2 and control group results are similar. It also is impossible to draw a firm conclusion in regards to the bacterial clearance studies presently. Similarly, the data regarding NK cell counts and function conflict also to the point that a definite conclusion cannot be made. Serum cortisol levels are similar after both types of surgery. The clear majority of the data suggests that open surgery is associated with significantly higher levels of IL-6 and CRP. Minimally invasive methods are less stressful, as judged by these parameters. It seems that one way to avoid or minimize immunosuppression after surgery is to use minimally invasive methods. In theory, based on the animal evidence reviewed in the previous text, laparoscopic cancer resection methods may be associated with improved long-term oncologic outcome. There is no human evidence to support this hypothesis. Middle range results from nonrandomized human cancer colectomy studies, thus far, have yielded outcomes similar to those following open surgery. The incidence of incisional tumor recurrences is similar after both open and closed approaches. The results of the randomized prospective colectomy trials are anxiously awaited. If, as is the case with closed methods, merely preserving the majority of an animal's immune function after surgery lowers the chances of tumor cells establishing metastases, then purposefully stimulating the immune system perioperatively may be a way to avoid the detrimental effects of laparotomy. Such up-regulation of immune function also might improve further the oncologic results after minimally invasive cancer surgery. The early postoperative period may be an ideal window for immune-based anticancer therapies because the tumor burden is at its absolute lowest immediately following resection of the primary. There is strong evidence in the animal setting that a whole host of agents that broadly stimulate the immune system are effective in reducing significantly the incidence of tumor metastases and the growth of tumors after surgery. There also is preliminary evidence that suggests that preoperative tumor vaccines may be an effective means of establishing specific immune responses against the tumor before resection. In theory, the combination of nonspecific perioperative immune up-regulation and preoperative tumor vaccines would provide the patient with the ability to kill tumor cells immediately following surgery period through specific and innate (i.e., nonspecific) immune responses. The arrival of advanced laparoscopic methods for the resection of cancers has led to research that has made it clear that surgery has important detrimental immune consequences. This work also has suggested novel means to avoid postoperative immunosuppression. Minimally invasive methods may be associated with oncologic advantages that go well beyond less pain, a quicker recovery, and a shorter length of stay. More basic science and human studies are needed to shed more light on this intriguing area.
Carter
J J
JJ
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Whelan
R L
RL
D000818:Animals; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D010535:Laparoscopy; D007813:Laparotomy; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery*