Abstract
BACKGROUND: There is a gap in knowledge regarding the utility of preoperative exercise (PEx) among gastrointestinal (GI) cancer patients undergoing surgery and how PEx impacts surgical outcomes. This study seeks to evaluate the mechanism behind PEx among patients undergoing major abdominal surgery for GI cancer through a randomized controlled trial (RCT). METHODS: This was a single center RCT conducted at The Ohio State University Wexner Medical Center. Eligible patients diagnosed with GI cancers with planned abdominal surgery were randomized to receive PEx or a Sedentary (Non-PEx) arm between October 2020 and May 2022. To investigate if PEx could lead to systemic change in circulation, we employed secretomics and metabolomics analyses of patient serum samples before and after exercise to detect inflammatory and tumorigenic responses, with the primary endpoint of investigating the mechanisms through which PEx modulates the inflammatory response in patients undergoing GI cancer surgery. RESULTS: Between October 2020 and May 2022, 64 patients were enrolled in the study, with 28 randomized to the PEx group and 36 to the non-PEx group. The two cohorts were comparable in terms of age, gender, and comorbidity burden. The median length of stay was 6 days across the entire cohort, with no significant differences between the groups. Similarly, the overall 30-day readmission rate was 15.7%, and the median comprehensive complication index score was 20.9, both of which showed no differences between the PEx and non-PEx groups. Secretomics and metabolomics analyses of patient serum samples revealed a shift towards an anti-inflammatory and anti-tumorigenic phenotype, with significant changes in secretion and metabolic profiles observed in post-PEx serum compared to pre-PEx serum from the same patients. CONCLUSIONS: PEx has the potential to mitigate the pro-inflammatory and pro-tumorigenic state of GI cancer by modulating specific cellular pathways. This study provides evidence into the mechanisms underlying these effects, but additional research is required to explore their applicability in therapeutic development. These findings build upon existing research to support the advancement of exercise-inspired therapeutic strategies in the future. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (NCT04602026) on 20/10/2020.