The Effect of Adding Intraoperative Regional Anesthesia on Cancer Recurrence in Patients Undergoing Lung Cancer Resection

Surgery is the primary treatment of lung cancer, but surgery releases tumor cells into the
systemic circulation. Whether this minimal residual disease results in clinical metastases
is a function of host defense. At least three perioperative factors shift the balance toward
initiation and progression of minimal residual disease. (1) Surgery per se depresses
cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors
(e.g., angiostatin and endostatin), and increases concentrations of pro-angiogenic factors
such as VEGF. (2) Anesthesia impairs numerous immune functions, including neutrophil,
macrophages, dendritic cells, T lymphocytes (T-cell), and Natural killer cell (NK-cell)
functions. (3) Opioid analgesics inhibit both cellular and humoral immune function in
humans, and promote tumor growth in rodents. Regional analgesia attenuates each of these
adverse effects. For example, regional anesthesia largely prevents the neuroendocrine stress
response to surgery by blocking afferent neural transmission. With combined regional and
general anesthesia/analgesia, the amount of general anesthetic required is much reduced — as
is, presumably, immune suppression. And finally, regional analgesia provides superb pain
relief, essentially obliterating the need for postoperative opioids. Animal studies show
that regional anesthesia improves natural kill cell function and reduces the metastatic
burden in animals inoculated with carcinoma cells. Preliminary retrospective data in cancer
patients showed, that paravertebral analgesia for breast cancer surgery reduced risk of
recurrence or metastasis by 40% during a 2.5 to 4-year follow-up period.

The investigators thus propose to evaluate the effect of combined epidural-general
anesthesia compared to general anesthesia on cancer recurrence semi-annually over a period
of 5 years.