Improving the perioperative management of resectable colorectal liver metastases

Background Colorectal liver metastases (CRLM) are more prevalent with advancing age. Worldwide trends towards longer life expectancy result in a more prevalent disease in an increasingly aged co-morbid population. Utilising enhanced recovery after surgery (ERAS) and better preoperative assessment of patients using cardiopulmonary exercise testing (CPET) may in part mitigate the challenges of dealing with a more elderly co-morbid population. However significant challenges remain. Prehabilitation seeks to prevent injury, or minimise its impact before it occurs. This thesis describes the development and validation of a prehabilitation program in patients prior to hepatectomy for colorectal liver metastases. Methodology An exercise program was developed within a laboratory and validated in 12 health volunteers. This program was then tested in a randomized clinical trial of patients prior to hepatectomy for colorectal liver metastases. The measurement of liver function and prediction of post hepatectomy liver failure (PHLF) is a challenge. Further work measuring liver function is needed, and a component of this thesis demonstrated the application of liver slicing as a model of human hepatic functioning. Results The part of this thesis demonstrates that a 4 week exercise program can deliver meaningful (1.5 ml.kg-1.min-1) improvements in the Oxygen uptake (Vo2 uptake ml.kg-1.min-1) at the anaerobic threshold (AT). Within the main component of this thesis (the randomized trial) 38 patients were randomized (20 prehabilitation, 18 standard care). 35 (25 male, 10 female) completed both preoperative assessments and were analysed. There were no differences in baseline characteristics. Prehabilitation led to improvements in the preoperative Vo2 uptake (Oxygen uptake ml.kg-1.min-1) at both anaerobic threshold (AT) (+1.5 ml.kg-1.min-1, 95% Confidence Interval (CI) 0.2 - 2.9 ml.kg-1.min-1) and peak exercise (+2.0 ml.kg-1.min-1, 95% CI 0 – 4.0 ml.kg-1.min-1). The O2 pulse (Oxygen uptake per heart beat) at the anaerobic threshold improved (+0.8 ml.beat-1, 95% CI 0 - 1.9 ml.beat-1) and a higher peak work rate (+13 watts, 95% CI 4 – 22 Watts) was achieved. This was associated with improved preoperative QoL, with overall SF-36 increasing by 11 (95% CI 1:21) (p<0.05) and overall SF-36 mental health by 11 (95% CI 1:21)(p