Abstract
BackgroundCancer surgery can promote tumour metastases and worsen prognosis, however, the effect of perioperative complications on metastatic disease remains unclear. In this study we sought to evaluate the effect of common perioperative complications including perioperative blood loss, hypothermia, and sepsis on tumour metastases in a murine model.MethodsPrior to surgery, pulmonary metastases were established by intravenous challenge of CT26LacZ colon cancer cells in BALB/c mice. Surgical stress was generated through partial hepatectomy (PH) or left nephrectomy (LN). Sepsis was induced by puncturing the cecum to express stool into the abdomen. Hemorrhagic shock was induced by removal of 30% of total blood volume (i.e. stage 3 hemorrhage) via the saphenous vein. Hypothermia was induced by removing the heating apparatus during surgery and lowering core body temperatures to 30 °C. Lung tumour burden was quantified 3 days following surgery.ResultsSurgically stressed mice subjected to stage 3 hemorrhage or hypothermia did not show an additional increase in lung tumour burden. In contrast, surgically stressed mice subjected to intraoperative sepsis demonstrated an additional 2-fold increase in the number of tumour metastases. Furthermore, natural killer (NK) cell function, as assessed by YAC-1 tumour cell lysis, was significantly attenuated in surgically stressed mice subjected to intraoperative sepsis. Both NK cell-mediated cytotoxic function and lung tumour burden were improved with perioperative administration of polyI:C, which is a toll-like receptor (TLR)-3 ligand.ConclusionsPerioperative sepsis alone, but not hemorrhage or hypothermia, enhances the prometastatic effect of surgery in murine models of cancer. Understanding the cellular mechanisms underlying perioperative immune suppression will facilitate the development of immunomodulation strategies that can attenuate metastatic disease.
Highlights
Cancer surgery can promote tumour metastases and worsen prognosis, the effect of perioperative complications on metastatic disease remains unclear
Severe hypovolemia increases pulmonary metastases, but is not additive when combined with surgical stress To discern the effect of hypovolemic shock on perioperative metastases, mice were first exsanguinated through the saphenous vein while systolic blood pressure was measured using a tail cuff sphygmomanometer (Fig. 1a)
In the absence of surgical stress, hypovolemic changes due to 30% blood loss significantly increased the number of pulmonary metastases when compared to mice that did not undergo any blood loss (438.3 ± 56.89 vs. 205.0 ± 24.88, p = 0.0212) (Fig. 1c)
Summary
Cancer surgery can promote tumour metastases and worsen prognosis, the effect of perioperative complications on metastatic disease remains unclear. In this study we sought to evaluate the effect of common perioperative complications including perioperative blood loss, hypothermia, and sepsis on tumour metastases in a murine model. Tai et al BMC Cancer (2018) 18:277 between coagulation and NK cell function in the development of metastases following cancer surgery [8]; while, more recently, we employed validated murine models of surgical stress and spontaneous metastases [11] to provide in vivo evidence of global NK cell dysfunction in postoperative metastatic disease. Modern surgical techniques minimize the adverse consequences of perioperative events, such as intraoperative blood loss, sepsis, and hypothermia. 8.5% of all cancer-related deaths are due to the concurrent onset of severe sepsis [34], and hypothermia, which is defined as a core body temperature of < 36 °C, occurs in 70% of postoperative patients [35]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
