DrHew Torrance

Improving Outcomes After Major Abdominal Cancer Surgery

Major abdominal cancer surgery offers curative potential, yet postoperative infection and cancer recurrence remain major causes of morbidity and mortality. Up to 20% of older surgical patients develop serious infections, and postoperative pneumonia dramatically increases short-term mortality. At the same time, recurrence remains the predominant driver of long-term cancer death. Despite these risks, we lack tools to identify vulnerable patients and have no targeted perioperative immunomodulatory strategies.

Surgical trauma triggers a systemic inflammatory response through damage-associated molecular patterns (DAMPs). Insights from the UK GAinS Collaborative demonstrate substantial inter-individual variability in responses to pathogen-associated molecular patterns (PAMPs), suggesting that susceptibility to postoperative complications may reflect patient-specific immune biology rather than operative factors alone.

I hypothesise that perioperative inflammation disrupts neutrophil function and induces longer-term reprogramming of myeloid progenitors, creating a transient but clinically significant state of innate immune dysfunction. This state links two critical outcomes:

1. Increased infection susceptibility, due to impaired neutrophil antimicrobial activity.

2. Reduced tumour immunosurveillance, enabling survival and outgrowth of circulating tumour cells released during surgery.

Postoperative infections, occurring in up to 40% of cancer operations, further amplify immunosuppression and are independently associated with higher recurrence rates. Neutrophils, which can both fail in pathogen control and actively promote tumour cell adhesion, proliferation and metastasis, sit at the centre of this shared pathway. Epigenetic “trained immunity” changes may prolong these vulnerabilities beyond the immediate postoperative window.

This programme will use multi-omic profiling to define inter-individual immune responses, identify biomarkers predicting infection and recurrence, and reveal targets for perioperative immune reprogramming. Ultimately, we aim to convert the perioperative period from a risk window into an opportunity to enhance immune competence and improve long-term cancer outcomes.