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INTRODUCTION

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The effects of perioperative regional anesthesia (RA) on cancer recurrence and overall survival after surgery have been a subject of much interest and controversy. This chapter discusses the available evidence and possible mechanisms by which RA could have beneficial effects in these patients.

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Surgical treatment of cancer is well established. An important consideration with oncological surgery is that the procedure may disseminate tumor cells in patients with micrometastases.1,2 Metastatic recurrence, rather than the primary cancer, accounts for approximately 90% of cancer-related deaths.3 Cancer cell development in local and metastatic recurrence is dependent on the interplay between the host defenses and the tumor's ability to seed, proliferate, and attract new blood vessels.4,5 However, these in turn may be influenced by surgery, general anesthesia, and opioid administration, which are three of several perioperative factors that may contribute to metastatic spread.

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There are several mechanisms through which these perioperative factors potentially affect cancer cell evolution. Surgery itself is a major physiological stress that may depress cell-mediated immunity, particularly the activity of natural killer (NK) cells and macrophages that would otherwise destroy various tumor cells.6 This immunosuppression may be induced by factors such as neuroendocrine stress responses,7 blood transfusion,8 and hypothermia.9 Surgery may also reduce antiangiogenic factors while increasing proangiogenic10 and growth factors that cause malignant cells to proliferate.11,12 In addition, general anesthesia with halogenated volatile agents or intravenous drugs such as thiopental may contribute to postoperative immune suppression by inhibiting the function of NK cells, neutrophils, dendritic cells, and macrophages.12,13 Intraoperative and postoperative opioid use has been shown to interfere with immune function, specifically by altering the levels of NK cells, B cells, and T lymphocytes, as well as stimulate angiogenesis via alterations in cytokine levels.13 Thus, these perioperative factors may complicate surgical treatment of cancer by increasing growth factors and modulating host immunity (Figure 18–1).

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Figure 18–1.

Perioperative factors affecting cancer cell evolution.

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Regional anesthesia and analgesia are commonly used for perioperative pain management and may have implications in both short- and long-term outcomes following oncological surgery. Regional anesthesia could potentially attenuate the stress response related to surgery, preserve immune function, and slow the surgical promotion of metastases.6,14 Furthermore, it decreases the intraoperative use of volatile anesthetics and perioperative opioids.15 In combination, these effects may lead to better preservation of perioperative immune function and a reduced incidence of cancer recurrence.

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A recently published systematic review and meta-analysis evaluated these effects.16 The meta-analysis included studies that compared the effects of RA on cancer recurrence and mortality with those of general anesthesia.

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A total of 20 studies published between 2006 and 2014 met inclusion criteria and yielded 54,541 patients; 16,618 ...

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