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Understanding the effects of exercise on the body’s responses to complex abdominal cancer surgery

ABSTRACT: Interventions: Patients included in this substudy will be recruited from the PRIORITY trial (Preoperative exercise for patients undergoing major abdominal cancer surgery). PRIORITY is an NHMRC-funded multicentre randomised controlled trial, investigating primarily the effects of a structured preoperative exercise program on in-hospital complications following major abdominal cancer surgery. For complete details regarding the PRIORITY trial, please see registration ACTRN12621000617864. This substudy will collect plasma biomarkers from a sample of the PRIORITY cohort, intending to recruit 144 patients for the purposes of this study. The first 144 patients recruited to PRIORITY will be invited to participate in this substudy. Biomarkers will be collected at the following timepoints: (i) within the week preceding planned surgery, and (ii) postoperatively on each day for the first 4 days following surgery. We will also screen for delirium before and after surgery and assess cognition at baseline and at 1 year following surgery. Primary outcome(s): Postoperative inflammation between intervention and control groups determined by CRP assessed using blood samples collected preoperatively and postoperatively. [ Baseline (preoperative) and for 4 postoperative days. ]

DISEASE(S): Major Abdominal Cancer Surgery,Cancer-biliary Tree (gall Bladder And Bile Duct),Surgery-other Surgery,Cancer-bowel-back Passage (rectum) Or Large Bowel (colon),Cancer-ovarian And Primary Peritoneal,Cancer-oesophageal (gullet),Cancer-liver

PROVIDER: 2473378 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Rationale Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality. Objectives To describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia. Methods and Measurements From a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing. Main Results Compared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naÃƒÂ¯ve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection. Conclusions Major-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.

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Understanding the effects of exercise on the body’s responses to complex abdominal cancer surgery

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