Patients' and carers' views on research priorities in prehabilitation for cancer surgery.

INTRODUCTION: The views of patients and carers are important for the development of research priorities. This study aimed to determine and compare the top research priorities of cancer patients and carers with those of multidisciplinary clinicians with expertise in prehabilitation. MATERIALS AND METHODS: This cross-sectional study surveyed patients recovering from cancer surgery at a major tertiary hospital in Sydney, Australia, and/or their carers between March and July 2023. Consenting patients and carers were provided a list of research priorities according to clinicians with expertise in prehabilitation, as determined in a recent International Delphi study. Participants were asked to rate the importance of each research priority using a 5-item Likert scale (ranging from 1 = very high research priority to 5 = very low research priority). RESULTS: A total of 101 patients and 50 carers participated in this study. Four areas were identified as research priorities, achieving consensus of highest importance (> 70% rated as "high" or "very high" priority) by patients, carers, and clinical experts. These were "optimal composition of prehabilitation programs" (77% vs. 82% vs. 88%), "effect of prehabilitation on surgical outcomes" (85% vs. 90% vs. 95%), "effect of prehabilitation on functional outcomes" (83% vs. 86% vs. 79%), and "effect of prehabilitation on patient reported outcomes" (78% vs. 84% vs. 79%). Priorities that did not reach consensus of high importance by patients despite reaching consensus of highest importance by experts included "identifying populations most likely to benefit from prehabilitation" (70% vs. 76% vs. 90%) and "defining prehabilitation core outcome measures" (66% vs. 74% vs. 87%). "Prehabilitation during neoadjuvant therapies" reached consensus of high importance by patients but not by experts or carers (81% vs. 68% vs. 69%). CONCLUSION: This study delineated the primary prehabilitation research priorities as determined by patients and carers, against those previously identified by clinicians with expertise in prehabilitation. It is recommended that subsequent high-quality research and resource allocation be directed towards these highlighted areas of importance.

Hemodynamic, ventilatory and gas exchange responses to exercise using a cycle ergometer and the incremental shuttle walk test in pregnant women.

BACKGROUND: Cardiovascular disease, including hypertension, in pregnant women is a leading cause of morbidity and mortality globally. The development of reference intervals for cardiovascular responses using exercising testing to measure oxygen utilisation (V̇O2) with cardiopulmonary exercise testing (CPET), and distances walked using the incremental shuttle walk test (ISWT), may be promising methods to assess and stratify pregnant women regarding their risk of adverse pregnancy outcomes, to encourage exercise during pregnancy, and to improve exercise prescriptions during pregnancy. We aimed to determine the reference intervals for V̇O2 at rest, anaerobic threshold (AT), and submaximal exercise using CPET, and the reference interval for the ISWT, to develop a correlation equitation that predicts submaximal V̇O2 from the distance walked in the ISWT, and to explore the relationship between hemoglobin (Hb) and ferritin concentration and V̇O2 at AT in women in second trimester. METHODS: After prospective IRB approval (HREC 15/23) and clinical trials registration (ANZCTR ACTRN12615000964516), and informed written consent, we conducted CPET and the ISWT according to international guidelines in a university associated tertiary referral obstetric and adult medicine hospital, in healthy pregnant women in second trimester (14 to 27 gestational weeks). Hemoglobin and ferritin concentrations were recorded from pathology results in the participants' medical records at the time of exercise testing. Adverse events were recorded. RESULTS: About 90 participants undertook CPET, 28 of which also completed the ISWT. The mean ± SD age and body mass index (BMI) were 32 ± 3.2 years, and 25 ± 2.7 kg/m2. Median (IQR) gestation was 23 (22-24) weeks. One in 4 women were 24 weeks or greater gestation. The reference intervals for V̇O2 at rest, AT, and submaximal exercise were 2.9 to 5.3, 8.1 to 20.7, and 14.1 to 30.5 mL/kg/min respectively. The reference interval for the ISWT was 218 to 1058 meters. The correlation equation to predict submaximal V̇O2 from the distance walked in the ISWT was submaximal V̇O2 (mL/kg/min) = 0.012*distance walked in ISWT (m) + 14.7 (95%CI slope 0.005-0.070, Pearson r = 0.5426 95%CI 0.2126-0.7615, P = .0029). Hemoglobin concentration was positively correlated with V̇O2 at AT (AT V̇O2 (mL/kg/min) = 0.08*Hb (g/L) + 4.9 (95%CI slope 0.0791-0.143, Pearson r = 0.2538 95%CI 0.049-0.438, P = .016). There was no linear association between ferritin and submaximal V̇O2 (Pearson r = 0.431 P = .697). There were no maternal or fetal complications. CONCLUSIONS: CPET and ISWT are safe and feasible in women in second trimester including those at or beyond 24 weeks gestation. We have established the reference interval for V̇O2 at rest, AT, and submaximal exercise by CPET, the reference interval for the distance walked for the ISWT, and a correlation equation to predict submaximal V̇O2 for use in clinical practice and research. Hemoglobin rather than ferritin is likely correlated with exercise capacity in pregnancy suggesting vigilance to correct lower hemoglobin levels may positively impact maternal health. CLINICAL TRIALS REGISTRY: The study was prospectively registered with the Australian and New Zealand Clinical Date of registration - 15/9/2015; Date of initial participant enrolment - 4/11/2015; Clinical trial identification number; ACTRN12615000964516; URL of the registration site - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369216.

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.

Sex-related differences in functional capacity and its implications in risk stratification before major non-cardiac surgery: a post hoc analysis of the international METS study.

Background: Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. Methods: We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14 mL kg-1 min-1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Findings: Female patients (n = 480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg-1 min-1 versus 21.2 (6.5) mL kg-1 min-1, p < 0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p = 0.018) than males (n = 786). The optimal peak VO2 threshold for predicting postoperative complications was 12.4 mL kg-1 min-1 for females and 22.3 mL kg-1 min-1 for males, respectively. In the multivariable regression model, low non-sex-specific peak VO2 did not independently predict postoperative complications. In contrast, low sex-specific peak VO2 was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p < 0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p = 0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI = 0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI = 0.09; 95% CI: -0.04, 0.22). Interpretation: Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO2 thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options. Funding: There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Postoperative analgesia for upper gastrointestinal surgery: a retrospective cohort analysis.

BACKGROUND: Thoracic epidural analgesia is commonly used for upper gastrointestinal surgery. Intrathecal morphine is an appealing opioid-sparing non-epidural analgesic option, especially for laparoscopic gastrointestinal surgery. METHODS: Following ethics committee approval, we extracted data from the electronic medical records of patients at Royal North Shore Hospital (Sydney, Australia) that had upper gastrointestinal surgery between November 2015 and October 2020. Postoperative morphine consumption and pain scores were modelled with a Bayesian mixed effect model. RESULTS: A total of 427 patients were identified who underwent open (n = 300), laparoscopic (n = 120) or laparoscopic converted to open (n = 7) upper gastrointestinal surgery. The majority of patients undergoing open surgery received a neuraxial technique (thoracic epidural [58%, n = 174]; intrathecal morphine [21%, n = 63]) compared to a minority in laparoscopic approaches (thoracic epidural [3%, n = 4]; intrathecal morphine [12%, n = 14]). Intrathecal morphine was superior over non-neuraxial analgesia in terms of lower median oral morphine equivalent consumption and higher probability of adequate pain control; however, this effect was not sustained beyond postoperative day 2. Thoracic epidural analgesia was superior to both intrathecal and non-neuraxial analgesia options for both primary outcomes, but at the expense of higher rates of postoperative hypotension (60%, n = 113) and substantial technique failure rates (32%). CONCLUSIONS: We found that thoracic epidural analgesia was superior to intrathecal morphine, and intrathecal morphine was superior to non-neuraxial analgesia, in terms of reduced postoperative morphine requirements and the probability of adequate pain control in patients who underwent upper gastrointestinal surgery. However, the benefits of thoracic epidural analgesia and intrathecal morphine were not sustained across all time periods regarding control of pain. The study is limited by its retrospective design, heterogenous group of upper gastrointestinal surgeries and confounding by indication.

The Impact of Peri-operative Enteral Immunonutrition on Post-operative Complications in Gastrointestinal Cancer Surgery: A Meta-Analysis.

BACKGROUND: Immunonutrition (IMN) in gastrointestinal (GI) cancer surgery remains under-utilised and contentious. Despite previous meta-analysis reporting benefit, most recent randomised control trials (RCTs) have failed to demonstrate this and have recommended against its routine use. A contemporary meta-analysis may contribute to the recommendations for immunonutrition use and help select which patients may benefit. The objective of this study was to review IMN and its impact on post-operative outcomes in GI cancer surgery, exploring its role in both malnourished and non-malnourished populations, the optimal dose to use, cancer type of patients using IMN and the timing of IMN relative to the peri-operative period. PATIENTS AND METHODS: The EMBASE and Medline databases were searched from 2000 to 2022 for RCTs evaluating IMN in adults undergoing GI cancer surgery. RESULTS: Thirty-seven studies were included (22 pre-operative IMN studies, 11 peri-operative IMN trials and 9 post-operative IMN trials; 4 trials had multiple IMN protocols) that reported on 3793 patients. The main outcome of post-operative infectious complications was reduced with IMN [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.47-0.72]. This association was significant in subgroup analysis only with pre-operative and peri-operative administration and in trials including upper GI cancers, colorectal cancer and 'mixed GI' cancer populations, and significance was independent of nutritional status. IMN in pooled analysis reduced surgical site infection (SSI) (OR 0.65, 95% CI 0.52-0.81), anastomotic leak (OR 0.67, 95% CI 0.47-0.93) and length of stay (LOS) by 1.94 days (95% CI - 3 to - 0.87). CONCLUSION: Immunonutrition was associated with reduced post-operative complications. Peri-operative administration may be the preferred strategy in reducing infectious complications, anastomotic leak, SSI and LOS.

End-tidal carbon dioxide in the early phase of cardiopulmonary exercise testing prior to major colorectal cancer surgery associates with postoperative outcome.

BACKGROUND: Cardiopulmonary exercise testing (CPET) objectively informs preoperative risk stratification prior to major surgery. CPET facilities are resource intensive and therefore more cost-effective triage methods are desirable for scalability. We tested two dynamic CPET parameters (end-tidal CO2 (PetCO2) and heart rate (HR)) to early phase exercise and resting diffusion capacity (DLCO) as potential point of care assessments that could be used outside of formal CPET testing facilities. METHODS: We conducted a retrospective cohort study including 84 patients who underwent CPET prior to elective major abdominal cancer surgery. Data were analyzed for PetCO2 and HR in response to early phase (2 minutes) exercise as well as resting DLCO against postoperative complications and two-year survival. Complications were classified according to Clavien-Dindo classification into less severe and severe (CD>IIIb) grades. Optimal cut points for predicting outcomes were determined using the Youden Index of receiver operating characteristic (ROC) curves. Multivariate regression modeling including both logistic and Cox proportional-hazards model adjusted to age and comorbidity burden was used to analyse the association between the selected parameters and postoperative outcomes. RESULTS: PetCO2, in response to two minutes of loaded exercise was higher in survivors than in non-survivors (median (IQR) 40.0 (4.2) mmHg vs. 34.5 (5.2) mmHg, P<0.001). There was no association between chronotropic response and postoperative outcome. The optimal cut point for predicting postoperative complications and survival was 38 mmHg and 37.1 mmHg for PetCO2, respectively. Low PetCO2 was associated with considerably lower odds of survival (OR 0.12; 95% CI 0.03, 0.47; P=0.003) and additionally increased odds of severe postoperative complications (OR 6.77; 95% CI 1.45, 38.4; P=0.019). Reduced age-predicted DLCO% <80% was associated with increased mortality (HR 5.27; 95% CI 1.09, 25.5; P=0.039). CONCLUSIONS: Assessment of DLCO at rest and dynamic assessment of PetCO2 during the early phase of exercise may potentially be developed as inexpensive point-of-care triage tools to scale objective preoperative risk assessment.

Trajectory of plasma syndecan-1 and heparan sulphate during major surgery: A retrospective observational study.

BACKGROUND: Surgical trauma-induced inflammation during major surgery may disrupt endothelial integrity and affect plasma concentrations of glycocalyx constituents, such as syndecan-1 and heparan sulphate. To date, no studies have focused on their perioperative temporal changes. METHODS: As part of a trial, we obtained plasma and urine specimens sampled during the perioperative period in 72 patients undergoing major abdominal surgery. The plasma concentration of syndecan-1 and heparan sulphate was measured on five occasions, from baseline to the second postoperative day. Plasma and urinary creatinine and urinary syndecan-1 concentrations were measured before surgery and on the first postoperative morning. RESULTS: We observed three different temporal patterns of plasma syndecan-1 concentration. Group 1 'low' (64% of patients) showed only minor changes from baseline despite a median heparan sulphate increase of 67% (p < .005). Group 2 'increase' (21% of patients) showed a marked increase in median plasma syndecan-1 from 27 µg/L to 118 µg/L during the first postoperative day (p < .001) with a substantial (+670%; p < .005) increase in median plasma heparan sulphate from 279 to 2196 µg/L. Group 3 'high' (14% of patients) showed a constant elevation of plasma syndecan-1 to >100 µg/L, but low heparan sulphate levels. The plasma C-reactive protein concentration did not differ across the three groups and 90% of colon surgeries occurred in Group 1. Treatment with dexamethasone was similar across the three groups. Surgical blood loss, duration of surgery and liver resection were greatest in Group 2. CONCLUSION: Changes in syndecan-1 and heparan sulphate after surgery appear to show three different patterns, with the greatest increases in those patients with greater blood loss, more liver surgery and longer operations. These observations suggest that increases in syndecan-1 and heparan sulphate reflect the degree of surgical injury.

Preoperative exercise induces endothelial progenitor cell mobilisation in patients undergoing major surgery - A prospective randomised controlled clinical proof-of-concept trial.

Introduction: Prehabilitation is increasingly recognised as a therapeutic option to reduce postoperative complications. Investigating the beneficial effects of exercise on cellular mechanisms, we have previously shown that a single episode of exhaustive exercise effectively stimulates endothelial progenitor cells (a cell population associated with vascular maintenance, repair, angiogenesis, and neovascularization) in correlation with fewer postoperative complications, despite the ongoing debate about the appropriate cell surface marker profiles of these cells (common phenotypical definitions include CD45dim, CD133+, CD34+ and/or CD31+). In order to translate these findings into clinical application, a feasible prehabilitation programme achieving both functional and cellular benefits in a suitable timeframe to expedite surgery is necessary. Objective: The objective of this study was to test the hypothesis that a four-week prehabilitation programme of vigorous-intensity interval exercise training is feasible, increases physical capacity (primary outcome) and the circulatory number of endothelial progenitor cells within peripheral blood. Methods: In this unblinded, parallel-group, randomised controlled proof-of-concept clinical trial (German Clinical Trial Register number: DRKS00000527) conducted between 01st December 2014 and 30th November 2016, fifteen female adult patients scheduled for incontinence surgery with abdominal laparotomy at the University Hospital Cologne were allocated to either an exercise (n = 8, exclusion of 1 patient, analysed n = 7) or non-exercise group (n = 7, exclusion of 1 patient, analysed n = 6). The exercise group's intervention consisted of a vigorous-intensity interval training for four weeks preoperatively. Cardiopulmonary Exercise Testing accompanied by peripheral blood collection was performed before and after the (non-)training phase. Cellular investigations were conducted by flow cytometry and cluster-based analyses. Results: Vigorous-intensity interval training over four weeks was feasible in the exercise group (successful completion by 8 out of 8 patients without any harms), with significant improvements in patients' functional capacity (increased oxygen uptake at anaerobic threshold [intervention group mean + 1.71 ± 3.20 mL/min/kg vs. control group mean -1.83 ± 2.14 mL/min/kg; p = 0.042] and peak exercise [intervention group mean + 1.71 ± 1.60 mL/min/kg vs. control group mean -1.67 ± 1.37 mL/min/kg; p = 0.002]) and a significant increase in the circulatory number of endothelial progenitor cells (proportionate CD45dim/CD14dim/CD133+/CD309+/CD34+/CD31 + subpopulation within the circulating CD45-pool [p = 0.016]). Conclusions: We introduce a novel prehabilitation concept that shows effective stimulation of an endothelial progenitor cell subpopulation within four weeks of preoperative exercise, serving as a clinical cell-mediated intervention with the aim to reduce surgical complications. Funding: Institutional funding. DFG (German Research Foundation, 491454339) support for the Article Processing Charge.

Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study.

BACKGROUND: Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery. METHODS: Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications. RESULTS: Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63-77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low-with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions. CONCLUSION: Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000073909 ) retrospectively registered.

Current approaches to acute postoperative pain management after major abdominal surgery: a narrative review and future directions.

Poorly controlled postoperative pain is associated with increased morbidity, negatively affects quality of life and functional recovery, and is a risk factor for persistent pain and longer-term opioid use. Up to 10% of opioid-naïve patients have persistent opioid use after many types of surgeries. Opioid-related side-effects and the opioid abuse epidemic emphasise the need for alternative, opioid-minimising, multimodal analgesic strategies, including neuraxial (epidural/intrathecal) techniques, truncal nerve blocks, and lidocaine infusions. The preference for minimally invasive surgical techniques has changed anaesthetic and analgesic requirements in abdominal surgery compared with open laparotomy, leading to a decline in popularity of epidural anaesthesia and an increasing interest in intrathecal morphine and truncal nerve blocks. Limited research exists on patient quality of recovery using specific analgesic techniques after intra-abdominal surgery. Poorly controlled postoperative pain after major abdominal surgery should be a research priority as it affects patient-centred short-term and long-term outcomes (including quality of life scores, return to function measurements, disability-free survival) and has broad community health and economic implications.

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.

Clinical covariates that improve surgical risk prediction and guide targeted prehabilitation: an exploratory, retrospective cohort study of major colorectal cancer surgery patients evaluated with preoperative cardiopulmonary exercise testing.

BACKGROUND: Preoperative risk stratification is used to derive an optimal treatment plan for patients requiring cancer surgery. Patients with reversible risk factors are candidates for prehabilitation programmes. This pilot study explores the impact of preoperative covariates of comorbid disease (Charlson Co-morbidity Index), preoperative serum biomarkers, and traditional cardiopulmonary exercise testing (CPET)-derived parameters of functional capacity on postoperative outcomes after major colorectal cancer surgery. METHODS: Consecutive patients who underwent CPET prior to colorectal cancer surgery over a 2-year period were identified and a minimum of 2-year postoperative follow-up was performed. Postoperative assessment included: Clavien-Dindo complication score, Comprehensive Complication Index, Days at Home within 90 days (DAH-90) after surgery, and overall survival. RESULTS: The Charlson Co-morbidity Index did not discriminate postoperative complications, or overall survival. In contrast, low preoperative haemoglobin, low albumin, or high neutrophil count were associated with postoperative complications and reduced overall survival. CPET-derived parameters predictive of postoperative complications, DAH-90, and reduced overall survival included measures of VCO2 kinetics at anaerobic threshold (AT), peakVO2 (corrected to body surface area), and VO2 kinetics during the post-exercise recovery phase. Inflammatory parameters and CO2 kinetics added significant predictive value to peakVO2 within bi-variable models for postoperative complications and overall survival (P < 0.0001). CONCLUSION: Consideration of modifiable 'triple low' preoperative risk (anaemia, malnutrition, deconditioning) factors and inflammation will improve surgical risk prediction and guide prehabilitation. Gas exchange parameters that focus on VCO2 kinetics at AT and correcting peakVO2 to body surface area (rather than absolute weight) may improve CPET-derived preoperative risk assessment.

PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL).

BACKGROUND: Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients' fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. METHODS: This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. DISCUSSION: The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery. TRIAL REGISTRATION: This trial was registered prospectively with the Australian New Zealand Clinical Trials Registry ( ACTRN12621000617864 ) on 24th May 2021.