On the horns of a dilemma: choosing total intravenous anaesthesia or volatile anaesthesia for cancer surgery, an enduring controversy.

Two methods for administering general anaesthesia are widely used: propofol-based total intravenous anaesthesia (propofol-TIVA) and inhalation volatile agent-based anaesthesia. Both modalities, which have been standards of care for several decades, boast a robust safety profile. Nevertheless, the potential differential effects of these anaesthetic techniques on immediate, intermediate, and extended postoperative outcomes remain a subject of inquiry. We discuss a recently published longitudinal analysis stemming from a multicentre randomised controlled trial comparing sevoflurane-based inhalation anaesthesia with propofol-TIVA in older patients with cancer, which showed a reduced incidence of emergence and postoperative delirium, comparable postoperative complication rates within 30 days after surgery, and comparable long-term survival rates. We undertake an assessment of the trial's methodological strengths and limitations, contextualise its results within the broader scientific evidence, and explore avenues for resolving the extant controversies in anaesthetic choice for cancer surgery. We aim to pave the way for the incorporation of precision medicine paradigms into the evolving landscape of perioperative care for patients with cancer.

Type of anesthesia for cancer resection surgery: No differential impact on cancer recurrence in mouse models of breast cancer.

BACKGROUND: Surgery is essential for curative treatment of solid tumors. Evidence from recent retrospective clinical analyses suggests that use of propofol-based total intravenous anesthesia during cancer resection surgery is associated with improved overall survival compared to inhaled volatile anesthesia. Evaluating these findings in prospective clinical studies is required to inform definitive clinical guidelines but will take many years and requires biomarkers to monitor treatment effect. Therefore, we examined the effect of different anesthetic agents on cancer recurrence in mouse models of breast cancer with the overarching goal of evaluating plausible mechanisms that could be used as biomarkers of treatment response. METHODS: To test the hypothesis that volatile anesthesia accelerates breast cancer recurrence after surgical resection of the primary tumor, we used three mouse models of breast cancer. We compared volatile sevoflurane anesthesia with intravenous propofol anesthesia and used serial non-invasive bioluminescent imaging to track primary tumor recurrence and metastatic recurrence. To determine short-term perioperative effects, we evaluated the effect of anesthesia on vascular integrity and immune cell changes after surgery in animal models. RESULTS: Survival analyses found that the kinetics of cancer recurrence and impact on survival were similar regardless of the anesthetic agent used during cancer surgery. Vascular permeability, immune cell infiltration and cytokine profiles showed no statistical difference after resection with inhaled sevoflurane or intravenous propofol anesthesia. CONCLUSIONS: These preclinical studies found no evidence that choice of anesthetic agent used during cancer resection surgery affected either short-term perioperative events or long-term cancer outcomes in mouse models of breast cancer. These findings raise the possibility that mouse models do not recapitulate perioperative events in cancer patients. Nonetheless, the findings suggest that future evaluation of effects of anesthesia on cancer outcomes should focus on cancer types other than breast cancer.

On the horns of a dilemma: choosing total intravenous anaesthesia or volatile anaesthesia.

There are two established techniques of delivering general anaesthesia: propofol-based total intravenous anaesthesia (TIVA) and volatile agent-based inhaled anaesthesia. Both techniques are offered as standard of care and have an established safety track record lasting more than 30 years. However, it is not currently known whether the choice of anaesthetic technique results in a fundamentally different patient experience or affects early, intermediate-term, and longer-term postoperative outcomes. This editorial comments on a recently published study that suggests that inhaled volatile anaesthesia might be associated with fewer postoperative surgical complications than propofol-based TIVA for patients undergoing colorectal cancer surgery. We consider the strengths and limitations of the study, place these findings in the context of the broader evidence, and discuss how the current controversies regarding anaesthetic technique can be resolved, thereby helping to bring precision medicine into the modern practice of perioperative care.

An In Vivo Mouse Model of Total Intravenous Anesthesia during Cancer Resection Surgery.

Anesthesia is a routine component of cancer care that is used for diagnostic and therapeutic procedures. The anesthetic technique has recently been implicated in impacting long-term cancer outcomes, possibly through modulation of adrenergic-inflammatory responses that impact cancer cell behavior and immune cell function. Emerging evidence suggests that propofol-based total intravenous anesthesia (TIVA) may be beneficial for long-term cancer outcomes when compared to inhaled volatile anesthesia. However, the available clinical findings are inconsistent. Preclinical studies that identify the underlying mechanisms involved are critically needed to guide the design of clinical studies that will expedite insight. Most preclinical models of anesthesia have been extrapolated from the use of anesthesia in in vivo research and are not optimally designed to study the impact of anesthesia itself as the primary endpoint. This paper describes a method for delivering propofol-TIVA anesthesia in a mouse model of breast cancer resection that replicates key aspects of clinical delivery in cancer patients. The model can be used to study mechanisms of action of anesthesia on cancer outcomes in diverse cancer types and can be extrapolated to other non-cancer areas of preclinical anesthesia research.

Anesthetic technique and cancer surgery outcomes.

PURPOSE OF REVIEW: Surgery remains integral to treating solid cancers. However, the surgical stress response, characterized by physiologic perturbation of the adrenergic, inflammatory, and immune systems, may promote procancerous pathways. Anesthetic technique per se may attenuate/enhance these pathways and thereby could be implicated in long-term cancer outcomes. RECENT FINDINGS: To date, clinical studies have predominantly been retrospective and underpowered and, thus limit meaningful conclusions. More recently, prospective studies of regional anesthesia for breast and colorectal cancer surgery have failed to demonstrate long-term cancer outcome benefit. However, based on the consistent observation of protumorigenic effects of surgical stress and that of volatile anesthesia in preclinical studies, supported by in vivo models of tumor progression and metastasis, we await robust prospective clinical studies exploring the role of propofol-based total intravenous anesthesia (cf. inhalational volatiles). Additionally, anti-adrenergic/anti-inflammatory adjuncts, such as lidocaine, nonsteroidal anti-inflammatory drugs and the anti-adrenergic propranolol warrant ongoing research. SUMMARY: The biologic perturbation of the perioperative period, compounded by the effects of anesthetic agents, renders patients with cancer particularly vulnerable to enhanced viability of minimal residual disease, with long-term outcome consequences. However, low level and often conflicting clinical evidence equipoise currently exists with regards to optimal oncoanesthesia techniques. Large, prospective, randomized control trials are urgently needed to inform evidence-based clinical practice guidelines.

Correction to: Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia.

There was an isolated error relating to the Oh et al. study (1) within our recurrence-free survival analysis. When the reported estimates for Oh et al. are corrected, the pooled hazard ratio (HR) is now 0.87; 95% confidence interval (CI), 0.66 to 1.15; P=0.32.

Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia.

PURPOSE: Cancer-related mortality, a leading cause of death worldwide, is often the result of metastatic disease recurrence. Anesthetic techniques have varying effects on innate and cellular immunity, activation of adrenergic-inflammatory pathways, and activation of cancer-promoting cellular signaling pathways; these effects may translate into an influence of anesthetic technique on long-term cancer outcomes. To further analyze the effects of propofol (intravenous) and volatile (inhalational gas) anesthesia on cancer recurrence and survival, we undertook a systematic review with meta-analysis. SOURCE: Databases were searched up to 14 November 2018. Comparative studies examining the effect of inhalational volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on cancer outcomes were included. The Newcastle Ottawa Scale (NOS) was used to assess methodological quality and bias. Reported hazard ratios (HRs) were pooled and 95% confidence intervals (CIs) calculated. PRINCIPAL FINDINGS: Ten studies were included; six studies examined the effect of anesthetic agent type on recurrence-free survival following breast, esophageal, and non-small cell lung cancer (n = 7,866). The use of TIVA was associated with improved recurrence-free survival in all cancer types (pooled HR, 0.78; 95% CI, 0.65 to 0.94; P < 0.01). Eight studies (n = 18,778) explored the effect of anesthetic agent type on overall survival, with TIVA use associated with improved overall survival (pooled HR, 0.76; 95% CI, 0.63 to 0.92; P < 0.01). CONCLUSION: This meta-analysis suggests that propofol-TIVA use may be associated with improved recurrence-free survival and overall survival in patients having cancer surgery. This is especially evident where major cancer surgery was undertaken. Nevertheless, given the inherent limitations of studies included in this meta-analysis these findings necessitate prospective randomized trials to guide clinical practice. TRIAL REGISTRATION: PROSPERO (CRD42018081478); registered 8 October, 2018.

RéSUMé: OBJECTIF: La mortalité liée au cancer, une cause majeure de décès dans le monde entier, est bien souvent le résultat de la récurrence de la maladie métastatique. Les techniques anesthésiques ont des effets variés sur l'immunité naturelle et cellulaire, l'activation des voies adrénergiques inflammatoires, et l'activation des voies de signalisation cellulaire promouvant le cancer; ces effets pourraient se traduire dans une influence de la technique anesthésique sur les pronostics de cancer à long terme. Afin d'approfondir l'analyse des effets de l'anesthésie au propofol (voie intraveineuse) et par inhalation (gaz) sur la récurrence du cancer et la survie, nous avons entrepris une revue systématique avec méta-analyse. SOURCE: Nous avons réalisé des recherches dans les bases de données jusqu'au 14 novembre 2018. Les études comparatives examinant l'effet d'une anesthésie par inhalation et d'une anesthésie intraveineuse totale (TIVA) avec propofol sur les pronostics de cancer ont été incluses dans notre revue. L'échelle de Newcastle-Ottawa (NOS) a été utilisée pour évaluer la qualité méthodologique et le biais. Les rapports de risque (RR) rapportés ont été pondérés et les intervalles de confiance (IC) à 95 % calculés. CONSTATATIONS PRINCIPALES: Dix études ont été incluses; six études ont examiné l'effet du type d'agent anesthésique sur la survie sans récurrence après un cancer du sein, de l'œsophage et du cancer pulmonaire non à petites cellules (n = 7866). L'utilisation d'une TIVA était associée à une amélioration de la survie sans récurrence, tous types de cancer confondus (RR pondéré, 0,78; IC 95 %, 0,65 à 0,94; P < 0,01). Huit études (n = 18 778) ont exploré l'effet du type d'agent anesthésique sur la survie globale, l'utilisation d'une TIVA étant alors associée à une amélioration de la survie globale (RR pondéré, 0,76; IC 95 %, 0,63 à 0,92; P < 0,01). CONCLUSION: Cette méta-analyse suggère que l'administration d'une TIVA à base de propofol pourrait être associée à une amélioration de la survie sans récurrence et de la survie globale chez les patients subissant une chirurgie oncologique. Cette observation est particulièrement frappante dans les cas de chirurgie oncologique majeure. Toutefois, étant donné les lacunes inhérentes des études incluses dans cette méta-analyse, ces résultats nécessitent la réalisation d'études randomisées prospectives afin d'éclairer la pratique clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42018081478); enregistrée le 8 octobre 2018.

Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis.

Cancer, currently the leading cause of death in the population aged less than 85 years, poses a significant global disease burden and is anticipated to continue to increase in incidence in both developed and developing nations. A substantial proportion of cancers are amenable to surgery, with more than 60% of patients undergoing tumour resection. Up to 80% of patients will receive anaesthesia for diagnostic, therapeutic or palliative intervention. Alarmingly, retrospective studies have implicated surgical stress in disease progression that is predominantly characterised by metastatic disease-the primary cause of cancer-associated mortality. Our understanding of the mechanisms of surgical stress and impact of perioperative interventions is, however, far from complete. Accumulating evidence from preclinical studies suggests that adrenergic-inflammatory pathways may contribute to cancer progression. Importantly, these pathways are amenable to modulation by adapting surgical (e.g. minimally invasive surgery) and anaesthetic technique (e.g. general vs. neuraxial anaesthesia). Disturbingly, drugs used for general anaesthesia (e.g. inhalational vs. intravenous anaesthesia and potentially opioid analgesia) may also affect behaviour of tumour cells and immune cells, suggesting that choice of anaesthetic agent may also be linked to adverse long-term cancer outcomes. Critically, current clinical practice guidelines on the use of anaesthetic techniques, anaesthetic agents and perioperative adjuvants (e.g. anti-inflammatory drugs) during cancer surgery do not take into account their potential effect on cancer outcomes due to a lack of robust prospective data. To help address this gap, we provide an up-to-date review of current clinical evidence supporting or refuting the role of perioperative stress, anaesthetic techniques and anaesthetic agents in cancer progression and review pre-clinical studies that provide insights into biological mechanisms.

Are cognitive and behavioural factors associated with knee pain? A systematic review.

OBJECTIVES: Although studies that have examined the relationship between cognitive and behavioural factors and knee pain report conflicting results, no systematic review has been performed to summarise the evidence. The aim of this systematic review was to examine the relationship between cognitive and behavioural factors and pain at the knee. METHODS: Electronic searches of MEDLINE, EMBASE and PsycINFO were performed to identify relevant studies published up to April 2014 using MeSH terms and keywords. Studies that met a set of predefined criteria were included. Coping, self-efficacy, somatising, pain catastrophising and helplessness were grouped together as "cognitive factors," while kinesiophobia and pain-related fear-avoidance were considered "behavioural factors." Two independent reviewers extracted the data and assessed the methodological quality of the selected studies. Due to the heterogeneity of the studies, a best-evidence synthesis was performed. RESULTS: A total of 14 studies were included in the review, of which nine examined cognitive factors, one investigated behavioural factors and four studied both cognitive and behavioural factors. Eight of 14 studies were of high quality. The best-evidence synthesis showed moderate evidence for a relationship between cognitive factors and knee pain and limited evidence for no association between the behavioural factors and knee pain. CONCLUSION: This review found evidence for a relationship between cognitive factors, but not behavioural factors, and knee pain. These findings will need to be confirmed with high-quality longitudinal studies, but the data suggest that cognitive factors may be important to target in the management of knee pain.

Are depression, anxiety and poor mental health risk factors for knee pain? A systematic review.

BACKGROUND: While it is recognized that psychosocial factors are important in the development and progression of musculoskeletal pain and disability, no systematic review has specifically focused on examining the relationship between psychosocial factors and knee pain. We aimed to systematically review the evidence to determine whether psychosocial factors, specifically depression, anxiety and poor mental health, are risk factors for knee pain. METHODS: Electronic searches of MEDLINE, EMBASE and PsycINFO were performed to identify relevant studies published up to August 2012 using MESH terms and keywords. We included studies that met a set of predefined criteria and two independent reviewers assessed the methodological quality of the selected studies. Due to the heterogeneity of the studies, a best evidence synthesis was performed. RESULTS: Sixteen studies were included in the review, of which 9 were considered high quality. The study populations were heterogeneous in terms of diagnosis of knee pain. We found a strong level of evidence for a relationship between depression and knee pain, limited evidence for no relationship between anxiety and knee pain, and minimal evidence for no relationship between poor mental health and knee pain. CONCLUSIONS: Despite the heterogeneity of the included studies, these data show that depression plays a significant role in knee pain, and that a biopsychosocial approach to the management of this condition is integral to optimising outcomes for knee pain.