Table 1.
Perioperative factors affecting long-term oncological outcomes
| Surgical aspect | Suggested mediating mechanisms | Potential perioperative interventions | Evidence supporting intervention* (for references see text) |
|---|---|---|---|
| Anaesthesia and analgesia | Excess release of catecholamines, prostaglandins and glucocorticoids Direct effects on MRD Suppression of antimetastatic immunity: for example, NK-cell activity Pro-metastatic immune responses: for example TREG-cell activity Increased angiogenesis and tumour proliferation |
Replacing GA by RA or adding RA to GA Minimizing opiate use without compromising pain alleviation Substituting morphine/opiates with the pseudo-opiate tramadol Using β-adrenergic blockers and COX2 inhibitors |
Animal: multiple consistent evidence Human: moderate evidence regarding cancer outcomes RCT: RA decreased VEGF levels (n = 22) |
| Blood transfusion | Excess release of prostaglandins Suppression of antimetastatic immunity: for example, NK-cell activity and immune tolerance Excess aberrant erythrocytes that apprehend immunocytes |
Minimizing amount of blood transfused (‘bloodless surgery’) Use packed red cells and blood with short storage time Using COX2 inhibitors |
Animal: few studies but with solid outcomes Human: good evidence regarding cancer outcomes RCT: advantage for packed cells over whole blood (n = 197); other aspects, such as age of transfused blood during surgery, were not studied |
| Intraoperative hypothermia | Excess release of catecholamines and glucocorticoids Suppression of antimetastatic immunity: for example, NK-cell activity, IL-1β, IL-2 and lymphocyte proliferation |
Maintaining normothermia Using β-adrenergic blockers |
Animal: multiple consistent evidence Human: none RCT: no effect in a single trial (n = 51) |
| Tissue damage extent: minimally invasive versus open surgery | Open surgery results in more profound suppression of antimetastatic immunity for some, but not other indices (for example, NK-cell number) Pro-metastatic immune responses: for example, IL-6 Proinflammatory responses |
Using β-adrenergic blockers and COX2 inhibitors in both minimally invasive and open surgery | Animal: multiple studies showed only short-term benefits for minimally invasive surgery Human: only short-term benefits for laparoscopy RCT: inconsistent evidence regarding recurrence |
| Margins | Local residual disease | Achieving negative CRMs even if doing so necessitates extended tissue damage | Animal: multiple consistent evidence Human: good evidence regarding disease-free survival; inconsistent evidence regarding remote metastases RCT: none |
| Menstrual cycle: unopposed oestrogen (breast cancer) | Heightened expression levels of β-adrenergic receptors in cancer cells and lymphocytes Greater suppression of antimetastatic immunity: such as NK-cell activity Potentiated cancer-cell growth Facilitated shedding of tumour cells into the circulation |
Administering hydroxyprogesterone to patients preoperatively, preferably to lymph-node-positive patients Operating during the hormonally validated luteal phase Using β-adrenergic blockers and COX2 inhibitors |
Animal: few studies but with solid outcomes Human: inconsistent evidence regarding cancer outcomes, possibly due to inaccurate hormonal phase determination RCT: positive effect for hydroxyprogesterone injection (n = 1,000) in patients with lymph-node-positive breast cancer |
| Psychological stress | Excess release of catecholamines, glucocorticoids, and other stress factors Suppression of antimetastatic immunity: for example, NK-cell activity and IL-12 production Elevated proinflammatory gene expression in circulating leukocytes |
Using psychopharmacological or pharmacological stress-inhibiting interventions (for example, benzodiazepine or β-blockers) Initiating psychological intervention before surgery, as early as possible |
Animal: multiple consistent evidence regarding immunity and cancer outcomes Human: influence on immune and endocrine factors RCT: inconsistent regarding cancer outcomes. Significant effects when interventions initiated before surgery |
*
Animal refers to studies in animal models of cancer; human refers to retrospective, and prospective non-randomized studies; and RCT refers to randomized clinical trials. Abbreviations: COX2, cyclooxygenase-2; CRM, circumferential resection margin; GA, general anaesthesia; MRD, minimal residual disease; NK, natural killer; TREG, T regulatory; RA, regional anaesthesia; RCT, randomized clinical trial; VEGF, vascular endothelial growth factor.