Laparoscopic Surgery and the Nuances of Systemic Immunity

The trauma of surgery evokes a variety of physiologic and immunologic alterations in the host.1,2 The magnitude of this stress response is generally believed to be proportional to the degree of insult. Tissue trauma, as a result of incisions, tissue dissection, organ manipulation, and vascular compromise, stimulates an initial inflammatory response that is presumably directed toward host defense.3 However, an exaggerated response to injury may result in transient immunosuppression, resulting in significant postoperative morbidity, organ failure, sepsis, and death. 3 And, of course, everything occurs amidst the overall acute and chronic comorbidities of a given patient. Since the introduction of laparoscopic cholecystectomy in the 1980s, minimally invasive surgery has emerged as a historic breakthrough in 20th century surgery. Small access incisions, decreased postoperative pain, shortened hospital stays, improved cosmesis, and speedy functional recovery rapidly guaranteed today's worldwide popularity of minimally invasive techniques. Laparoscopy is now the preferred surgical approach to adrenalectomy, antireflux fundoplication, splenectomy, and nephrectomy. Laparoscopic colectomy, prostatectomy, and hepatectomy are being increasingly offered in specialty centers. Although laparoscopy is “minimally invasive,” systemic immune responses are undeniably still activated. 1 Because the degree of surgical trauma is significantly reduced with laparoscopy in comparison with conventional laparotomy, most assume that the reduced inflammatory response and minimal immunosuppression equate with an overall beneficial host defense response. The rapid recovery of patients supports this argument. Laboratory evidence has shown that laparoscopy compares favorably to open surgery in decreased perioperative cytokine (tumor necrosis factor [alpha], interleukin 1 [IL-1], IL-6, IL-8) levels.4–9 Acute phase reactants and mediators, such as C-reactive protein and reactive oxygen species, are significantly lower in laparoscopy.9–12 However, many questions remain, especially in humans. Why are some, but not all, systemic immune responses affected? Which ones matter, and which do not? What are the implications for surgical injury overall? As part of the cell-mediated host defense system, neutrophils exert powerful local and systemic effects. Derailment of neutrophil activation and function increases the risk of postoperative infection.5,13 In this issue of the Journal, Altamura et al.14 report experimental findings that human neutrophil and monocyte-mediated cytotoxicities are better preserved after laparoscopic cholecystectomy than after open procedure. The authors were unable to confirm several earlier reports of preserved T-cell-mediated immunity after laparoscopy.8,15,16 Discrepancies such as these are common in the literature of laparoscopic surgery and systemic immunity. To some extent, they reflect variabilities in experimental design, but perhaps more accurately, they also reflect the tender balance of an immune response that may be only partially measured. The gut usually prevents bacterial translocation from the gastrointestinal lumen into our systemic milieu.17,18 But this barrier can be compromised by surgical stress alone.19 Intestinal manipulation may result in transient enterocyte structural changes and the initiation of a systemic inflammatory response.18 Enterocyte production of immune cytokines is increased proportionally to the extent of abdominal surgery.17 Minimal bowel manipulation and retraction during laparoscopic surgery may avoid excessive enterocyte stimulation and trauma. This, in turn, may result in diminished proinflammatory stimuli, reduced bacterial translocation across the gut barrier, and fewer postoperative infectious complications. To date, very few studies in humans have considered this. Additionally, the local environment of the peritoneal cavity is protected during laparoscopy. Peritoneal macrophages-responsible for the clearance of pathogens from the abdomen-remain phagocytic and cytotoxic after laparoscopy.1,20 The exclusion of air from the peritoneal cavity during laparoscopy significantly abrogates the immunosuppressive effects of laparotomy.11,21,22 Some investigators implicate visceral desiccation; others, certain insufflation gases and pressures.23,24 In all, it is a multifactorial local and systemic response that is far from being fully understood. In humans, diminished neutrophil and monocyte functions predict death in severely injured patients.25–27 Animal models of peritonitis revealed reduced systemic and intraperitoneal infections because of preserved immune function after laparoscopy.20,28 Pharmacologic immunosuppression, as in transplant patients, results in lower levels of serum leukocyte markers that clearly correlate with clinical outcome and risk of infection.25 The future development and perioperative use of immunomodulating agents requires our dedication to understanding the nuances of postoperative immune status. Laparoscopy provides us a refined surgical stress by which to study it. Beyond question, the clinical efficacy of minimally invasive surgery has been proven. It is apparent, though, that the systemic immune and metabolic responses of surgery in general may not always apply to laparoscopy. Clinical implications mandate ongoing studies, such as that which is presented in this issue of the Journal.14 Most investigators now attack hypotheses from cellular and molecular levels, with utmost attention to controls. As these efforts progress, the systemic immune response to laparoscopic surgery will be better understood and, hopefully, patients will be the beneficiaries.