ABSTRACT
PURPOSE OF REVIEW: Neutrophil extracellular trap (NET) formation is a newly discovered, reactive oxygen species-dependent regulated process, whereby neutrophils degranulate and extrude genetic material, after engulfing various infectious or neoplastic antigens, culminating in a measurable serologic footprint. Recent research has highlighted the involvement of NETs in cancer and cancer-related pathologies. We review the role of NET formation in cancer biology, prognosis and potential therapeutic modulators. RECENT FINDINGS: Elevated NET levels are associated with cancer metastasis and may be modified by some anaesthetic-analgesic techniques during tumour resection surgery. It promotes tumour cell migration, angiogenesis and hypercoagulability. Although there are potential anti-NET formation therapeutics available, their role has not been formally assessed in cancer patients. Limited available evidence suggests an association between elevated NET expression and cancer metastasis, but its validity as a prognostic indicator for cancer-related outcomes is inconclusive. Further observational and interventional studies are warranted to comprehend the potential prognostic and therapeutic role of NETs in cancer.
Subject(s)
Extracellular Traps/metabolism , Neoplasms/pathology , Neutrophils/metabolism , Thrombosis/pathology , Analgesia , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Extracellular Traps/drug effects , Extracellular Traps/immunology , Humans , Neoplasm Metastasis , Neoplasms/immunology , Neoplasms/therapy , Neovascularization, Pathologic , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/pathology , Perioperative Care , Thrombosis/immunology , Thrombosis/therapyABSTRACT
BACKGROUND: Some experimental and retrospective clinical studies signal an association between certain anaesthetic techniques and tumour metastasis following breast cancer surgery. Neutrophil Extracellular Trapping (NETosis) is an immunological process, whereby neutrophils engulf tumour antigen then degranulate, leaving a serologic marker. NETosis expression among breast cancer patients is associated with an increased risk of metastasis. We investigated the effect of two distinct anaesthetic techniques on the expression of NETosis in women who underwent potentially curative breast cancer surgery. METHODS: In a parallel-group, randomised controlled trial, a subset of women (n = 40) undergoing breast cancer resection surgery, who were partaking in a larger trial (NCT00418457), were randomly assigned to receive volatile general anaesthesia (GA) or propofol GA combined with paravertebral regional anaesthesia (PPA) for their surgery. Serum was taken and stored before and 24 hours post-operatively. NETosis was measured by ELISA using Neutrophil Myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) biomarkers, which were the co-primary end points. RESULTS: Patient and breast cancer characteristics did not differ significantly between groups. Recurrence occurred in 7.5% patients. GA patients received more opioids and reported higher post-operative pain than PPA. There was no difference in post-operative MPO in GA vs PPA (10.5 ± 6.6 vs 11.5 ± 4.7 ng mL-1 , P = .60). Regarding CitH3, there was no difference post-operatively in GA vs PPA (3.6 ± 2.3 vs 4.0 ± 5.9, P = .80). NET expression did not differ before or after anaesthesia and surgery in either group, for either biomarker. CONCLUSION: Anaesthetic technique did not affect NETosis expression in breast cancer patients, indicating that it is not a viable marker of the effect of anaesthetic technique on breast cancer recurrence.
