In this retrospective cohort of high-risk patients presenting for major abdominal cancer surgery we found that postoperative morbidity was significantly associated with twelve variables: age, BMI, WHO status, cancer stage (TNM classified), CPET-generated data (AT, VO2 Max and AT VE/VCO2), pre-existing co-morbidities (chronic renal impairment, COPD, diabetes mellitus and a previous history of TIA or stroke) and whether a minimally invasive or an open approach was undertaken. These variables were shown to have good strength in discriminating postoperative morbidity in a prospective group of major abdominal cancer surgical patients. Using a scoring system based on the significance of each of these variables on post-operative morbidity, a simple risk scoring system called the “Marsden Morbidity Index” was devised. This index can be used in our institution to predict morbidity in patients scheduled for major abdominal surgery as a means of aiding decision making, consent and resource allocation.
The CPET variables we found to be associated with morbidity were in keeping with findings from previous studies where CPET was evaluated as a risk prediction tool in major abdominal surgery.25-27 Our study demonstrated that AT and VO2 Max were significant (p<0.001) variables at the multivariate analysis level and predictive of poor surgical outcomes. In the perioperative context both have been shown to be strong ergometric predictors of postoperative complications and mortality in a number of cohorts analysing outcomes post major abdominal and thoracic surgery.28-30 West et al.31 conducted a prospective blinded observational study to investigate for any association between CPET findings and postoperative morbidity after major colonic surgery. Patients who suffered postoperative complications had significantly lower oxygen uptake at lactate threshold, lower VO2 at peak, and higher AT VE/VCO2. These variables were found to be independently predictive of morbidity post rectal cancer surgery and major colonic surgery. Lee et al.32 demonstrated a significant association between pre-operative oxygen consumption on a 6-minute walk test and postoperative medical complications (P<0.01) but not surgical and all complications post elective colorectal resection.
In our analysis, VE/VCO2 at anaerobic threshold had the strongest weighting in the model for postoperative morbidity in major abdominal surgery. This is a measure of ventilatory efficiency and is elevated in conditions such as heart failure, pulmonary embolism and chronic lung disease.33 It is thus unsurprising that this variable is so strongly associated with morbidity. According to Junejo et al.,34 CPET findings for preoperative risk assessment before pancreatoduodenectomy showed VE/VCO2 at AT to be the only CPET variable independently associated with postoperative morbidity, with an AUC of 0.65 (95% CI 0.53–0.77). Similar to our study, CPET was applied in patients deemed high risk and POMS scores were used to assess postoperative morbidity. An AT VE/VCO2 of ≥ 34.5 ml/kg/min was found to have a specificity of 84% and a sensitivity of 47%, with a PPV of 76% and an NPV of 60%, for POMS-defined morbidity.
Anaerobic threshold (VO2 at AT) was a significant CPET variable associated with postoperative morbidity in this analysis of high-risk patients undergoing major abdominal cancer surgery. This is consistent with one of our previous studies that demonstrated VO2 at AT <10.2 ml/kg/min as a significant predictor of POMS-defined morbidity on POD 3 in patients undergoing major hepatic resection.35 Peak VO2 or AT is a measure of aerobic capacity and classified as an important predictor of perioperative morbidity in multiple studies.36-37
Objective risk identification and stratification is pivotal in linking preoperative co-morbidities to risk-adapted intraoperative approaches and targeted postoperative care pathways. There are multiple grading and risk stratification tools currently in use for surgical patients. Perhaps the most commonly used grading system by anaesthetists is the American Society of Anaesthesiologists (ASA), a system dating back to 1963.38 However, this system is largely subjective and does not take into account any surgery-related factors. The methodology for risk evaluation has evolved significantly over the years to models that can generate pre-calculated quantitative estimations of morbidity and mortality risks.39 These developments also reflect the necessity for objective validated risk assessment tools with advancing perioperative care in order to reduce subjective bias.
The “Marsden Morbidity Index” was developed on the strong advocacy for CPET as an objective risk prediction tool based on current evidence and literature.40 However, CPET alone was deemed not enough due to its limitations.41 Our aim was to combine CPET variables with premorbid variables to increase acuity in risk prediction. Our study thence demonstrated that the incorporation of CPET variables into a risk prediction tool that also takes other significant clinical variables into account, yields data that can improve the precision of perioperative risks evaluation. The comorbidities we identified are strongly validated in other risk scoring systems42-45 currently in use, reflecting the precision of this new model. For this model the AUC to discriminate morbidity was 0.81 and 0.79 in the fitted model binary classification and the temporal validation model respectively.
Premorbid variables deemed significant in the generation of the “Marsden Morbidity Index” risk prediction tool can be further sub-grouped into baseline parameters (age, BMI, WHO category and TNM-classified cancer stage) and chronic conditions (COPD, diabetes mellitus, chronic renal impairment and a previous history of TIA or stroke). The majority of these variables have been strongly validated in multiple risk prediction scores, like CHA2DS2-VASc,42 p-POSSUM,43 Lee’s Revised Cardiac Risk Index44 and SORT45 where one or more of these premorbid variables are incorporated in a multifactorial risk-score calculation tool.
An interesting finding of our analysis showed that a low BMI scored higher than a high BMI. The effect of BMI on postoperative complications have been long studied with weight taken as a reflection of general health status from a broader perspective. From a preoperative evaluation, it reflects preoperative nutritional status, functional status, presence of co-morbidities, anticipation of intraoperative challenges and a tailored multi-disciplinary team input required for preoptimization and rehabilitation. While obesity is generally assumed to be a risk factor for postoperative adverse events, there is no convincing data to support this assumption.46 A study published by Tjeertes et al.46 to seek more understanding of the obesity paradox revealed that while obesity alone is a significant risk factor for wound infection, more surgical blood loss and a longer operation time, being obese is also associated with improved long-term survival. Complication and mortality rates were found to be significantly worse for underweight patients, who were most at risk of major postoperative complications, including long-term mortality. We also know from current literature that many of the CPET variables, like peak or VO2 Max, are highly correlated with muscle mass.47-48 While there is no available data on the direct comparison between CPET outcomes for high versus low BMI in cancer patients, the findings are a cause of concern that patients with low BMI are likely to perform equivocally if not worse than obese patients, which needs confirmation by a more comprehensive investigation.
In addition, our study featured patients who underwent an open laparotomy were more likely to suffer from postoperative complications (P<0.001) when compared to minimally invasive surgery, i.e. robotic-assisted or laparoscopy. These findings are in keeping with the literature where the unique benefits and superiority of minimally invasive procedures over open procedures in selected patients have been shown.49 A systematic review and meta-analysis by Wang et al. comparing the two approaches for pancreatico-duodenectomy showed significant reductions in estimated blood loss, postoperative haemorrhage, transfusion rate, wound infection and length of hospital stay.50 Similar findings from comparison between laparoscopy and laparotomy for rectal cancer include reductions in postoperative pain, length of stay, incisional hernia, adhesive bowel obstruction, wound complications, and mortality.51 The use of robotic-assisted surgery in the management of cancer continues to increase with numerous evidence in the literature of a shorter convalescence period postoperatively.52
In conclusion, we found the CPET variables of AT, VO2 Max and AT VE/VCO2, and a number of pre-operative baseline demographics and co-morbidities commonly associated with increased risk of postoperative morbidity, were shown to be associated with postoperative surgical morbidity following major abdominal oncological surgery. Our study shows that the incorporation of CPET variables into a risk prediction tool produces a model with a strong ability to discriminate postoperative complications when morbidity was assessed using a combination of the Clavien–Dindo classification scoring system and the Postoperative Morbidity Survey. Such acuity has the potential to systematically optimize outcomes for surgical intervention.
While this model has helped us create a useful institutional tool for perioperative risks, it needs further validation in other centres performing oncological surgery. To our knowledge, the Marsden Morbidity Index is unique in that is one of only a few validated risk scoring tools that directly incorporates CPET variables as part of their algorithms to predict perioperative outcomes.