Visceral adipose tissue fuels a state of chronic inflammation( Reference Kershaw and Flier 1 ) and has been identified as a risk factor for post-op complications( Reference Doyle, Lysaght and Reynolds 2 ). In this study we first aimed to retrospectively investigate the association between visceral obesity and post-op inflammation using the markers CRP and CRP:albumin ratio. Secondly, we aimed to identify additional inflammatory mediators that are differentially regulated in viscerally obese patients post-op using prospectively recruited patients.
Retrospectively, visceral fat area (VFA) was calculated from diagnostic CT scans of gastrointestinal cancer patients undergoing resection (n=324). Visceral obesity was classified as a VFA>130 cm2 ( Reference Despres and Lamarche 3 ). CRP and albumin levels pre-op and at days 1, 3, 7 and 14 post-op were obtained from the laboratory database. As part of ongoing prospective studies, peripheral blood mononuclear cells (PBMC), serum and plasma samples are collected on oesophageal adenocarcinoma patients pre-op and on days 1, 3, 7 and 14 post-op. In a test cohort of 3 non-obese and 3 obese patients, PBMC collected pre-op and on days 1 and 7 post-op were analysed for expression of 370 genes involved in acute inflammatory response using a PCR based array. Circulating levels of TNF-α, IL-6, IL-8 and IFN-γ were measured by ELISA in 12 non-obese and 16 obese patients at all time points. In all cases p<0.05 was considered statistically significant.
Following resection, visceral obesity was significantly associated with higher CRP on days 1, 3, 7 and 14 post-op and higher CRP:albumin ratio on day 3 post-op (p<0.05). Higher circulating levels of TNF-α, IL-6, IL-8 and IFN-γ were observed in obese compared to non-obese patients on day 1 post-op but these differences were not significant. The inflammatory array revealed an upregulation on post-op day 1 in IL-6 expression (>7-fold) in PBMC from obese compared to non-obese patients. In addition, members of the TNF super family, TNFSF14 and lymphotoxin-γ, which induce inflammatory cytokine production and NFkB activation, were upregulated in obese (>5-fold and>2-fold respectively) compared to non-obese patients.
Excess visceral adiposity significantly alters the acute inflammatory response post-op. Inflammatory mediators such as IL-6, TNFSF14 and lymphotoxin-β may prove important targets for pharmacotherapy and immunonutrition to improve post-op outcomes in obese patients.
