Table 1 Effects of surgery on cancer recurrence

Action

Consequences

Direct effect on tumor cell survival

Surgical tumor manipulation

Release of cancer cells into the bloodstream ➔ metastatic spread to distant organs

Surgical tumor manipulation

Intraperitoneal seeding➔ Transcoelomic spread

Surgical tumor manipulation and incision

Endothelial disruption ➔ increase hydrostatic and oncotic pressure➔dissemination of tumor cells through lymphatic routes

Minimal residual disease in surgical margins

Local or lymphatic spread

Action

Consequences

Indirect effect on tumor cell survival

Physiological response to perioperative stress factors

Activating the systemic inflammatory response➔ migration of macrophages, neutrophils, fibroblasts on the site of the surgery ➔ Release of cytokines, growth factors and prostaglandin➔ promoting cancer growth, lymphangiogenesis, angiogenesis, and consequent dissemination

Physiological response to perioperative stress factors

Activating the systemic inflammatory response➔ state of relative immunosuppression➔ immune escaping of cancer cells➔appropriate microenvironment for tumor growth

Physiological response to perioperative stress factors

Trigger the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system➔ release of hormonal mediators➔ enhance tumor growth

Physiological response to perioperative stress factors

Expression of specific genes and/or molecular pathways➔ promotion of angiogenesis, cell proliferation, and metastasis

Physiological response to perioperative stress factors

Activation of pro-angiogenic signaling pathways➔ increasing the metastatic invasiveness