Physical activity in the aetiology and preoperative management of oesophageal adenocarcinoma

• Main Author: Lam, Stephen
• Published: University of East Anglia 2018
• Subjects: 610
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753894

Oesophageal adenocarcinoma has the fastest growing incidence of any solid tumour in the western world. Physical activity affects gastric emptying, intra-gastric pressure, systemic inflammation, and the regulation of body weight and may play an important role in the aetiology of the metaplasia-dysplasia-carcinoma sequence of oesophageal adenocarcinoma. Furthermore, exercise causes physiological adaptations resulting in improved cardiac output and lung ventilation volumes, as well as increased capillary and mitochondrial density in skeletal muscle, all of which improves efficiency in cellular aerobic respiration. As major surgery places large physiological stresses on the human body through; blood loss, catabolic muscle breakdown, systemic inflammatory vasodilation, and disruption of normal lung mechanics, the adaptive changes, achieved through preoperative exercise, may maximise cardiopulmonary and skeletal muscle reserves and reduce the risk of postoperative complications after cancer resection surgery (oesophagectomy). This research aimed to investigate: 1) associations between both occupational and recreational levels of physical activity and the development of Barrett’s oesophagus, the precursor lesion of oesophageal adenocarcinoma; 2) the feasibility of delivering a shortterm preoperative exercise programme (prehabilitation) in a feasibility randomised controlled trial; and (3) associations between preoperative aerobic fitness, as measured objectively by cardiopulmonary exercise testing, and postoperative outcomes after oesophagectomy. Results from a population-based prospective cohort study of 30 445 participants suggested a U-shaped association between occupational levels of physical activity and the risk of Barrett’s oesophagus, where moderate levels of activity in standing occupations had an inverse association with disease risk (when compared to sedentary occupations), HR=0.50, 95% CI 0.31-0.82, p=0.006, but heavy manual occupations were associated with an increased risk, HR=1.66, 95% CI 0.91-3.00, p=0.09. No associations were found between recreational activity and the risk of Barrett’s oesophagus (HR 1.34, 95% CI 0.72-2.50, p=0.35, highest vs. lowest levels of activity). A single blinded, parallel group, randomised controlled feasibility trial of prehabilitation in 11 patients with oesophageal adenocarcinoma showed that a hospital-based exercise programme in the time period between completion of neoadjuvant chemotherapy and surgery was safe and acceptable to patients awaiting curative surgery. A hospital-based cohort study of 254 patients found that there was no association between aerobic fitness (VO2peak) and postoperative complications after oesophagectomy (OR 1.00, 95% CI 0.94-1.07, p=0.86). This suggests that the impact of fitness on postoperative outcome, in the context of oesophagectomy, is likely to be insubstantial. Overall, this thesis suggests that occupational levels of physical activity may play a role in the aetiology of oesophageal adenocarcinoma, but preoperative fitness, even if feasibly modifiable with prehabilitation, may not significantly affect the risk of short-term postoperative morbidity after oesophagectomy.