The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 µg g-1; ip injection) with or without 4 µg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1ß (IL1ß), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

Correction to: Can routine perioperative haemodynamic parameters predict postoperative morbidity after major surgery?

[This corrects the article DOI: 10.1186/s13741-020-0139-6.].

Can routine perioperative haemodynamic parameters predict postoperative morbidity after major surgery?

BACKGROUND: Postoperative morbidity occurs in 10-15% of patients undergoing major noncardiac surgery. Predicting patients at higher risk of morbidity may help to optimize perioperative prevention. Preoperative haemodynamic parameters, systolic arterial pressure (SAP) < 100 mmHg, pulse pressure (PP) > 62 mmHg or < 53 mmHg, and heart rate (HR) > 87 min-1 are associated with increased postoperative morbidity. We evaluated the correlation between these and other routine haemodynamic parameters, measured intraoperatively, with postoperative morbidity. Postoperative morbidity was measured using the Comprehensive Complication Index (CCI) and length of stay (LOS). Additionally we correlated CCI with the cardiac risk biomarker, preoperative NT-ProBNP. METHODS: This is a retrospective analysis of patients in MET-REPAIR, a European observational study correlating self-reported physical activity with postoperative morbidity. Patients' electronic anaesthetic records (EARs) including perioperative haemodynamic data were correlated with 30-day postoperative morbidity, CCI and LOS parameters. Statistical analysis to assess for correlation was by Kendall's Correlation Coefficient for tied ranks (Tau-B) or Spearman's Correlation Coefficient. Blood for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurement was collected < 31 days before surgery. RESULTS: Data from n = 50 patients were analysed. When stratified according to age > 70 years and ASA > 3, the duration of MAP < 100 mmHg, < 75 mmHg or < 55 mmHg were associated with a higher CCI (tau = 0.57, p = 0.001) and duration < 75 mmHg was associated with prolonged LOS (tau = 0.39, p = 0.02). The intraoperative duration of PP > 62 mmHg was associated with LOS (tau = 0.317, p = 0.007). There was no correlation between preoperative NT-proBNP and either CCI or LOS. CONCLUSIONS: In older and higher risk patients, duration of intraoperative hypotension by a variety of definitions, or PP > 62 mmHg, are associated with increased postoperative CCI and LOS. These findings warrant confirmation in larger databases with evaluation of whether real-time intraoperative intervention could reduce postoperative morbidity.

Effects of Lidocaine and Src Inhibition on Metastasis in a Murine Model of Breast Cancer Surgery.

Breast cancer recurs in 20% of patients following intended curative resection. In vitro data indicates that amide local anaesthetics, including lidocaine, inhibit cancer cell metastasis by inhibiting the tyrosine kinase enzyme Src. In a murine breast cancer surgery model, systemic lidocaine reduces postoperative pulmonary metastases. We investigated whether the additional administration of bosutinib (a known Src inhibitor) influences lidocaine's observed beneficial effect in this in vivo model. Female BALB/c mice (n = 95) were inoculated with 25,000 4T1 cells into the mammary fad pad and after 7 days the resulting tumours were excised under sevoflurane anaesthesia. Experimental animals were randomized to one of four treatments administered intravenously prior to excision: lidocaine, bosutinib, both lidocaine and bosutinib in combination, or saline. Animals were euthanized 14 days post-surgery and lung and liver metastatic colonies were evaluated. Post-mortem serum was analysed for MMP-2 and MMP-9, pro-metastatic enzymes whose expression is influenced by the Src pathway. Lidocaine reduced lung, but not liver metastatic colonies versus sevoflurane alone (p = 0.041), but bosutinib alone had no metastasis-inhibiting effect. When combined with lidocaine, bosutinib reversed the anti-metastatic effect observed with lidocaine on sevoflurane anaesthesia. Only lidocaine alone reduced MMP-2 versus sevoflurane (p = 0.044). Both bosutinib (p = 0.001) and bosutinib/lidocaine combined (p = 0.001) reduced MMP-9 versus sevoflurane, whereas lidocaine alone did not. In a murine surgical breast cancer model, the anti-metastatic effects of lidocaine under sevoflurane anaesthesia are abolished by the Src inhibitor bosutinib, and lidocaine reduces serum MMP-2. These results suggest that lidocaine may act, at least partly, via an inhibitory effect on MMP-2 expression to reduce pulmonary metastasis, but whether this is due to an effect on Src or via another pathway remains unclear.

Adjuvant analgesics in spinal surgery.

Peri- and postoperative pain control can present a challenge to any doctor, particularly in the setting of spinal surgery. The use of adjuvant pain agents and multimodal analgesia is changing the face of modern anaesthesia and offering clinicians more avenues to control perioperative pain. This article discusses the use of adjuvant medications and some of the evidence surrounding their use in spinal surgery.