In a study reported in JAMA Network Open, Fleming et al found that low skeletal muscle area and high visceral-to-total fat ratio were associated with increased expression of proinflammatory cytokines and VEGF as well as worse 5-year outcomes in patients with nonmetastatic colon cancer.
Study Details
In the Irish multicenter study, 28 patients undergoing surgical resection with curative intent were evaluated for preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), VEGF, and cell surface receptor expression levels (CD11b and CD14). Patients could not have underlying chronic inflammatory disorders or be receiving anti-inflammatory drugs.
All patients were followed for at least 5 years for disease recurrence and disease-specific mortality. Low skeletal muscle area was defined as < 10th percentile of age- and sex-specific levels in the general population; high adiposity measure levels were defined as those ≥ the 60th percentile.
These findings suggest that low skeletal muscle area and high visceral-to-total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.— Fleming et al
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Key Findings
Patients with low skeletal muscle area (hazard ratio [HR] = 2.30, 95% confidence interval [CI] = 1.41–2.89, P = .04) and those with high visceral-to-total fat ratio (HR = 5.78, 95% CI = 3.66–7.95, P = .02) had a significantly increased risk of disease recurrence at 5 years. Patients with high visceral-to-total fat ratio had significantly greater 5-year disease-specific mortality (HR = 5.92, 95% CI = 4.04–8.00, P = .02). Low skeletal muscle area was not significantly associated with increased risk (HR = 3.22, 95% CI = 0.13–8.37, P = .48).
Among patients with low skeletal muscle area, those who developed recurrence vs those who did not had higher levels of C-reactive protein (mean = 31.24 vs 8.11 mg/dL, P = .003), IL-6 (mean = 1.93 vs 0.88 ng/mL, P = .004), VEGF (mean = 310.03 vs 176.12 ng/mL, P = .007), and CD14 (mean = 521.23 vs 322.07 ng/mL, P = .03) and lower levels of albumin (mean = 3.8 vs 43.50 g/dL, P = .01), IL-2 (mean = 0.45 vs 0.94 ng/mL, P < .001), IL-10 (mean = 8.15 vs 16.32 ng/mL, P = .004), and interferon γ (mean = 2.61 vs 14.87 ng/mL, P = .02).
Among patients with high visceral-to-total fat ratio, those who developed recurrence vs those who did not had higher levels of IL-6 (mean = 5.26 vs 2.76 ng/mL, P = .03) and tumor necrosis factor α (mean = 5.74 vs 4.50 ng/mL, P = .03).
The investigators concluded, “These findings suggest that low skeletal muscle area and high visceral-to-total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.”
Christina A. Fleming, MD, of the Department of Academic Surgery, Cork University Hospital, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
