Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence

Ryungsa Kim, Ryungsa Kim

Abstract

Background: The relationship between surgery and anesthetic-induced immunosuppression and cancer recurrence remains unresolved. Surgery and anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) to cause immunosuppression through several tumor-derived soluble factors. The potential impact of surgery and anesthesia on cancer recurrence was reviewed to provide guidance for cancer surgical treatment.

Methods: PubMed was searched up to December 31, 2016 using search terms such as, "anesthetic technique and cancer recurrence," "regional anesthesia and cancer recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and immunosuppression," and "anesthetic technique and oncologic surgery."

Results: Surgery-induced stress responses and surgical manipulation enhance tumor metastasis via release of angiogenic factors and suppression of natural killer (NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes. Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis, and enhance angiogenesis through hypoxia inducible factor-1α (HIF-1α) activity. Opioids suppress NK cell activity and increase regulatory T cells.

Conclusion: Local anesthetics such as lidocaine increase NK cell activity. Anesthetics such as propofol and locoregional anesthesia, which decrease surgery-induced neuroendocrine responses through HPA-axis and SNS suppression, may cause less immunosuppression and recurrence of certain types of cancer compared to volatile anesthetics and opioids.

Keywords: Anesthetic agent; Anesthetic technique; Cancer recurrence; Cancer surgery; Immunosuppression.

Figures

Fig. 1
Fig. 1
Perioperative period and immune balance. a The perioperative period includes the preoperative period, intraoperative period, and postoperative period. During these periods, several anesthetics agents and techniques may affect immune response and cancer recurrence after surgery. b Immune balance during the perioperative period is achieved through control of positive effects from regional anesthesia, propofol, and local anesthetics, with negative effects from volatile anesthetics, thiopental, and opioids. The immune balance needs to be shifted toward positive effects to reduce immunosuppression, which promotes cancer metastasis
Fig. 2
Fig. 2
Hypothesis to explain cancer metastasis and recurrence caused by surgery- and anesthetic-induced immunosuppression in the perioperative period. Surgery, anesthesia, and analgesia stimulate the HPA-axis and SNS during the perioperative period. Activated neuroendocrine mediators lead to increases in several immunosuppressive soluble factors that promote tumor progression and metastasis, resulting in increase of cancer recurrence. Combined regional anesthesia with propofol decreases anesthesia-induced immunosuppression and avoids volatile anesthetics and opioids, which may increase the risk of cancer recurrence

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Source: PubMed

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