Taking all these data as justification and as a basis, the objectives set out in this review address anesthetic agents and techniques used during oncological surgery to promote metastatic development and investigate whether “antitumor” techniques increase the survival of the oncological patient. These possible pathways implicated could be modulated by adapting surgical and anesthetic technique ( 13– 17). In recent years, accumulating evidence from preclinical studies suggests that adrenergic-inflammatory pathways may contribute to cancer progression. The hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system (SNS) regulate immune responses, and surgery-induced or anesthesia-induced activation of these two systems may facilitate metastasis through several tumor-derived soluble factors ( 12). During surgery, the tissue microenvironment is disrupted, and the perioperative period could create an environment that promotes survival, proliferation, and progression of residual cancer cells ( 11). It is known that during the perioperative period, surgery-induced stress responses and anesthetic-induced immunosuppression may play a critical role in the establishment and growth of metastatic lesions ( 7– 10).
Surgery (with or without chemotherapy and/or associated radiotherapy) is an increasingly common strategy used in the therapeutic management of cancer. Even so, tumor recurrence and the development of metastases are very frequent even after surgical treatment, and are responsible for up to 90% of cancer-related mortality ( 5, 6). The population estimates point to as many as 29.5 million cancer cases worldwide in 2040 ( 1, 2).Ĭurrently, surgical resection is considered the most effective method of removing the primary tumor ( 3) and to increase long-term survival in the vast majority of solid tumors ( 4). The number of patients diagnosed with tumor pathology grows exponentially year by year, has increased in incidence from 4 million cases worldwide in 2012 to 19.3 million in 2020. The current data generate hypotheses about the influence of anesthesia on metastatic development, although prospective trials that determinate causality are necessary to make changes in clinical practice.Ĭancer is one of the main causes of morbidity and mortality in the world. Epidural anesthesia and propofol have been shown to maintain immune activity and reduce catecholaminergic and inflammatory responses, considering the protective techniques against tumor spread. Through understanding of pharmacological mechanisms of anesthetics and their effects on tumor cells, new perioperative approaches emerge with the aim of halting and controlling metastatic development.
The possibility of using “immunoprotective” or “antitumor” anesthetic techniques would represent a turning point in clinical practice. The likely benefit of reducing their use, or even replacing them as much as possible with anesthetic techniques that protect patients from the metastatic process, is still being investigated. Scientific evidence indicates that inhaled anesthetics and opioids benefit immunosuppression, cell proliferation, and angiogenesis, providing the ideal microenvironment for tumor progression. Anesthetic agents and techniques, in relation to metastatic development, are investigated for their impact on long-term survival. The stress response triggered by the surgical aggression and the transient immunosuppression produced by anesthetic agents stimulate the inadvertent dispersion of neoplastic cells and, paradoxically, tumor progression during the perioperative period.
3General and Digestive Surgery, Hospital of Mérida, Mérida, Spain.2Anesthesiology and Resuscitation, Clinic Hospital of Zaragoza, Zaragoza, Spain.1Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.Sonia Santander Ballestín 1 *, Andrea Lanuza Bardaji 2, Cristina Marco Continente 3 and María José Luesma Bartolomé 4
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