Biochemical and Functional Biomarkers of Cachexia in Cancer Patients

Patients: Patients with upper and lower gastrointestinal cancer for planned resectional surgery will be recruited. Patients will be identified by the clinical team at the relevant multidisciplinary team meeting and then approached for study information and consent in the surgical clinic. Age-matched, healthy controls undergoing elective surgery for benign conditions (e.g. hernias) will also be recruited.

Patient Phenotyping: CT scans performed as a routine part of diagnosis and staging will be used for analysis of body composition. All patients recruited will have their CT scans analysed where present. Control patients (e.g. hernias) may not have CT scans, but where available, will be analysed. A transverse CT image from the third lumbar vertebrae will be assessed and tissue volumes estimated by a single trained observer. Cross-sectional area for muscle and adipose tissue will be normalized for stature (cm2/m2). Estimates of whole body stores will be generated from raw data (cm2) using regression equations. Cutoffs for low muscularity are based on CT-based sarcopenia plus obesity studies of cancer patients. In a previous study, the median time to muscle biopsy after CT scan was 18 days. Phenotyping will also involve measuring basic physical attributes (e. g. weight, height etc) and self-reported physical abilities (through questionnaires).

Muscle function/Physical activity assessment: An objective assessment of physical ability will be undertaken in the clinic for all patients. This will involve a "timed up and go" test and a "6 minute walk" test. These tests have been well-validated in the literature and have good inter-rater reliability. Whilst they do add a slight burden of inconvenience to the patient clinic visit this is minimal. Additionally, a physical activity meter will be applied to the patients' thigh under a waterproof dressing. The Investigators have validated these meters in cancer patients, and they are small (35x53x7mm) and light (20g). When used in previous studies as above the patients have found them unobtrusive and they have been well-tolerated. Where possible, the Investigators will ask the patients to repeat the "timed up and go" and "6 minute walk test" in postoperative clinic up to 12 months after surgery.

Patient self-reported assessment: At routine clinic, all patients will be asked to complete validated questionnaires regarding their physical health, and their perceptions of this. These will be used to assess severity of co-morbidity, and also to assess frailty. Example questionnaires include the Scottish Co-Morbidity Severity Score, the Charlson Co-morbidity Index, and the Edmonton Frail Scale. Other questionnaires relating to self-reported appetite and function will be considered but the overall aim will be to ask select questions to reduce the burden of questioning and prevent questionnaire fatigue. The Investigators will ask participants to repeat these questionnaires in routine clinic up to 12 months post surgery.

Blood and urine sampling: At routine National Health Service (NHS) clinic, all patients will be asked to provide a blood and a urine sample. Where this is not possible, the research team will ask for permission to take these samples under general anaesthetic at planned surgery via urinary and vascular catheters inserted as part of routine care. In the postoperative phase the Investigators will ask participants to provide blood and urine samples, where possible, in routine clinic up to 12 months following surgery.