Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.

Objectives: This systematic review set out to identify, evaluate and synthesise the evidence examining the effect of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery.Methods: Five electronic databases (MEDLINE 1946-2020, EMBASE 1947-2020, CINAHL 1937-2020, PEDro 1999-2020, and Cochrane Central Registry of Controlled Trials 1991-2020) were systematically searched (until August 2020) for randomised controlled trials (RCTs) that investigated the effects of prehabilitation interventions in patients undergoing abdominal cancer surgery. This review included any form of prehabilitation either unimodal or multimodal that included whole body and/or respiratory exercises as a stand-alone intervention or in addition to other prehabilitation interventions (such as nutrition and psychology) compared to standard care.Results: Twenty-two studies were included in the systematic review and 21 studies in the meta-analysis. There was moderate quality of evidence that multimodal prehabilitation improves pre-operative functional capacity as measured by 6 min walk distance (Mean difference [MD] 33.09 metres, 95% CI 17.69–48.50; p = <0.01) but improvement in cardiorespiratory fitness such as preoperative oxygen consumption at peak exercise (VO2 peak; MD 1.74 mL/kg/min, 95% CI −0.03–3.50; p = 0.05) and anaerobic threshold (AT; MD 1.21 mL/kg/min, 95% CI −0.34–2.76; p = 0.13) were not significant. A reduction in hospital length of stay (MD 3.68 days, 95% CI 0.92–6.44; p = 0.009) was observed but no effect was observed for postoperative complications (Odds Ratio [OR] 0.81, 95% CI 0.55–1.18; p = 0.27), pulmonary complications (OR 0.53, 95% CI 0.28–1.01; p = 0.05), hospital re-admission (OR 1.07, 95% CI 0.61–1.90; p = 0.81) or postoperative mortality (OR 0.95, 95% CI 0.43–2.09, p = 0.90).Conclusion: Multimodal prehabilitation improves preoperative functional capacity with reduction in hospital length of stay. This supports the need for ongoing research on innovative cost-effective prehabilitation approaches, research within large multicentre studies to verify this effect and to explore implementation strategies within clinical practise.

Total hip or knee arthroplasty is associated with significant blood loss. Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic haemodilution have been used to reduce the need for allogeneic blood transfusion. Tranexamic acid has been used to reduce blood loss and transfusion requirement for total hip and knee arthroplasty, with variable results. This meta-analysis aims to evaluate whether intravenous tranexamic acid, when compared with placebo, reduces blood loss and transfusion requirement in total hip and knee joint replacement surgery and whether it might increase the risk of thromboembolic complications. The literature search was based on MEDLINE, EMBASE, Cochrane Controlled Trials Register, and information from the pharmaceutical company that produces tranexamic acid (Pharmacia-Upjohn). We identified 15 clinical trials and 12 were considered suitable for detailed data extraction. Tranexamic acid reduces the proportion of patients requiring allogeneic blood transfusion (OR 0.16, 95% CI: 0.09-0.26), total amount of blood loss (WMD 460 ml, 95% CI: 274-626 ml), and the total number of units of allogeneic blood transfused (WMD 0.85 unit, 95% CI: 0.36-1.33). Tranexamic acid does not increase the risk of thromboemobolic complications such as deep vein thrombosis, pulmonary embolism, thrombotic cerebral vascular accident, or myocardial infarction (OR 0.98, 95% CI: 0.45-2.12). Intravenous tranexamic acid appears effective and safe in reducing allogeneic blood transfusion and blood loss in total hip and knee arthroplasty.