Propofol doses differ in total intravenous anaesthesia (TIVA) for cancer and no cancer surgery - observational cohort study.

OBJECTIVE: Propofol (2,6-diisopropylphenol) is a broadly used anaesthetic in total intravenous anaesthesia (TIVA) that might alter course of disease in patients who underwent oncology surgery. High inter-individual variability of the propofol dose needed for the same level of consciousness during surgical tumour removal is influenced by many factors. PATIENTS AND METHODS: This is a retrospective observational cohort study of prospectively collected patients data over 20 month's period. The main endpoint of the study was to compare propofol consumption needed for cancer and no cancer surgical interventions. The secondary endpoints were to find out whether there is a difference in recovery time between the two groups of patients and to reveal potential correlations between propofol consumption and age, duration of anaesthesia, body weight and Charlson co-morbidity index (CCI) in cancer and no cancer surgery. RESULTS: There were 103 patients with cancer (mean age 59.3 yr ± 10.7) and 109 patients operated due to other reasons (mean age 47.6 yr ± 17.52). Female sex predominated in both groups (70.9% in cancer and 67.9% in no cancer patients). They differed regarding CCI, 4.48 (±2.1) in cancer in contrast to 1.49 (±1.83) in no cancer patients, and anaesthesia time, 92.67 minutes ± 46.15 vs. 75.24 ± 37.28, respectively (p = 0.0012). Propofol induction dose did not differ significantly between the two groups (p = 0.193), while total propofol consumption was 85.86 mcg/kgBW/min (± 25.98) in cancer and 95.77 (± 31.48) in no cancer patients (p = 0.01). Propofol consumption negatively correlated with duration of anaesthesia and body weight in cancer group. However, in no cancer patients there was very strong negative association with age, duration of anaesthesia and CCI, and significant but weaker negative association with body weight. The time to awakening did not differ significantly between the groups (p = 0.219). CONCLUSIONS: Propofol dose differed in cancer comparing to no cancer patients under general anaesthesia. There was no need for dose adjustment regarding the age and sex in patients with cancer in contrast to no cancer surgery.

'Warburg effect' controls tumor growth, bacterial, viral infections and immunity - Genetic deconstruction and therapeutic perspectives.

The evolutionary pressure for life transitioning from extended periods of hypoxia to an increasingly oxygenated atmosphere initiated drastic selections for a variety of biochemical pathways supporting the robust life currently present on the planet. First, we discuss how fermentative glycolysis, a primitive metabolic pathway present at the emergence of life, is instrumental for the rapid growth of cancer, regenerating tissues, immune cells but also bacteria and viruses during infections. The 'Warburg effect', activated via Myc and HIF-1 in response to growth factors and hypoxia, is an essential metabolic and energetic pathway which satisfies nutritional and energetic demands required for rapid genome replication. Second, we present the key role of lactic acid, the end-product of fermentative glycolysis able to move across cell membranes in both directions via monocarboxylate transporting proteins (i.e., MCT1/4) contributing to cell-pH homeostasis but also to the complex immune response via acidosis of the tumor microenvironment. Importantly lactate is recycled in multiple organs as a major metabolic precursor of gluconeogenesis and energy source protecting cells and animals from harsh nutritional or oxygen restrictions. Third, we revisit the Warburg effect via CRISPR-Cas9 disruption of glucose-6-phosphate isomerase (GPI-KO) or lactate dehydrogenases (LDHA/B-DKO) in two aggressive tumors (melanoma B16-F10, human adenocarcinoma LS174T). Full suppression of lactic acid production reduces but does not suppress tumor growth due to reactivation of OXPHOS. In contrast, disruption of the lactic acid transporters MCT1/4 suppressed glycolysis, mTORC1, and tumor growth as a result of intracellular acidosis. Finally, we briefly discuss the current clinical developments of an MCT1 specific drug AZ3965, and the recent progress for a specific in vivo MCT4 inhibitor, two drugs of very high potential for future cancer clinical applications.