Surgery, wound healing, and metastasis: recent insights and clinical implications.

BACKGROUND Surgery-induced acceleration of tumour growth has been observed since several centuries. METHODS We reviewed recent insights from in vitro data, animal experimentation, and clinical studies on how surgery-induced wound healing or resection of a primary cancer influences the tumour-host ecosystem in patients harbouring minimal residual or metastatic disease. RESULTS Most of the growth factors, chemokines, and cytokines orchestrating surgical wound healing promote tumour growth, invasion, or angiogenesis. In addition, resection of a primary tumour may accelerate synchronous metastatic growth. In the clinical setting, indirect evidence supports the relevance of the above findings. Randomized clinical trials are underway comparing resection versus observation in metastatic breast and colon cancer with asymptomatic primary tumours. CONCLUSIONS In depth knowledge of how surgical intervention alters the tumour-host-metastasis communicating ecosystems could have important implications for clinical decision making in patients with synchronous metastatic disease and for the design and timing of multimodality treatment strategies.