1. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.194
Figure 2 Putative mechanisms of postoperative cancer recurrence and metastasis
Figure 2 | Putative mechanisms of postoperative cancer recurrence and metastasis. a | A fraction of cancer cells might remain following tumour resection owing to incomplete resection margins, exfoliation into the surgical field, and distribution across major body cavities during surgery. b | Some of these cells disseminate via haematogenous and lymphatic routes, leading to spikes in circulating tumour cell (CTC) numbers in the days following surgery. Lymphatic trafficking accompanies the routine clearance of wound debris and is increased by elevated hydrostatic pressure following wound oedema and innervation of lymphangions by the sympathetic nervous system. c | The inflammatory response to surgical tissue trauma initiates the recruitment of bone-marrow-derived immune cells and endothelial cells and promotes the activation of fibroblasts, neovascularization, and the release of growth factors and cytokines. These conditions, which occur following wound hypoxia and the upregulation of hypoxia-inducible factor-1α (HIF1α), provide an ideal environment for the re-establishment of residual cancer cells. d | The surgical stress response induces inflammation, thrombocytosis, hypercoagulation, and impaired immunity. Perioperatively, CTCs have the potential to form aggregates and complexes with activated platelets, enabling them to withstand intravascular stresses and evade both circulating and specialized marginalized leukocytes. Platelets also release TGFβ and stromal-cell-derived factor 1 (SDF1), thus promoting CTC chemotaxis, and might initiate the transition of CTCs to a more-invasive, mesenchymal phenotype. e | The systemic inflammatory response to surgery aids the margination of CTCs in distant organ capillaries through endothelial activation, platelet interactions, formation of microthrombi, and the activation of neutrophil extracellular traps (NETs), which form a pre-metastatic niche. Surgical stress and exposure to general anaesthesia give rise to postoperative immunosuppression, providing CTCs with a privileged period with opportunities to colonize distant organs. COX, cyclooxygenase; MMP, matrix metalloproteinase; NK, natural killer; PG, prostaglandin.
Hiller, J. G. et al. (2017) Perioperative events influence cancer recurrence risk after surgery
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