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From the Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
Correspondence: Address correspondence and reprint requests to: Shamgar Ben-Eliyahu, PhD, Department of Psychology, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel; Fax: 972-3-640-9547; E-mail: shamgar{at}post.tau.ac.il
Background: Removing the primary tumor is indispensable for eliminating the major pool of metastasizing cells, but the surgical procedure itself is suspected of promoting metastases. This adverse effect is attributed to several mechanisms acting in synergy, including mechanical release of tumor cells, enhanced angiogenesis, secretion of growth factors, and immunosuppression. Here we provide new insights into mechanisms of postoperative immunosuppression and assess the assumptions underlying the hypothesis that, by suppressing cell-mediated immunity (CMI), surgery may render the patient vulnerable to metastases that otherwise could have been controlled.
Methods: An extensive review of relevant articles in English identified by using the MEDLINE database and cross-referencing.
Results: Current literature suggests that (1) CMI can control minimal residual disease, especially if surgery is performed early; (2) major surgery transiently but markedly suppresses CMI through multiple mechanisms now better understood; (3) surgical stress promotes experimental metastasis through immunosuppression, but the clinical evidence remains indirect because of ethical limitations.
Conclusions: Minimizing postoperative immunosuppression seems feasible, may limit recurrence, and should be introduced into the broader array of considerations when planning oncological surgeries. In the short run, physicians could try to avoid immunosuppressive anesthetic approaches, inadvertent hypothermia, excessive blood transfusions, and untended postoperative pain. When feasible, minimally invasive surgery should be considered. In the long run, clinical trials should evaluate prophylactic measures, including perioperative immunostimulation and several antagonists to cytokines and hormones specified herein.
Key Words: Immunosuppression • Neuroimmunomodulation • Postoperative complications • Surgical stress • Tumor immunology • Tumor metastasis
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