Surgical trauma, minimal residual disease and locoregional cancer recurrence

The persistence of residual tumour is associated with the histology and stage of the primary cancer, the completeness and quality of surgery, and postoperative events such as anastomotic leakage or entrapment of cells in exudating wound surfaces. At present, there is no clinical evidence that the use of laparoscopic techniques adversely influences the risk of residual disease. The inflammatory process associated with surgery shares a number of central mediators and pathways with tumour growth and invasiveness. Both cellular components (mainly macrophages and fibroblasts) and humoral factors associated with inflammation have been shown to enhance tumour growth in numerous preclinical studies. Tumour foci at a distance from the main cancer are kept in a dormant state by a range of anti-angiogenic mediators produced by the main cancer. Preclinical studies have shown that removal of the primary cancer reactivates proliferative and metastatic pathways in the residual tumour. Clinically, this phenomenon has been proposed as underlying the observed rapid systemic relapse after surgery in young node positive breast cancer patients. Strategies proposed to prevent residual disease encompass avoidance of tumour spill and minimization of surgical trauma and related inflammation. Efforts to remove or kill free intraperitoneal cells by local antiseptic or cytotoxic regimens have met only limited clinical success. Specific targeted therapy aimed at inhibiting the inflammatory response, tumour cell adhesion, or the metastatic phenotype of dormant cells appears promising in preclinical models and needs to be addressed in future clinical trials.