Fig. 1. Hypotheses of surgery-triggered cancer metastasis.

During tumor resection, tumor cells can be released due to mechanical pressure and vascular injury. Due to surgical stress, the hypothalamic–pituitary–adrenal axis is activated, finally leading to the release of glucocorticoids and catecholamine hormones. These hormones negatively regulate the antitumor activities of innate and adaptive immune cells. Tumor-derived angiogenic inhibitors disappear after removing the primary tumor, which allows metastases to regrow with active neoangiogenesis.