The level of the acute-phase response is a major predictor of survival in patients with advanced pancreatic cancer. This study examines the association between the acute-phase protein response, as determined by serum C-reactive protein, and serum levels of interleukin-6, soluble interleukin-6 receptor and the soluble tumour necrosis factor receptors in patients with pancreatic cancer. Thirty-four blood samples were collected from 13 patients with advanced pancreatic cancer. Samples were also collected from six healthy subjects. Levels of C-reactive protein, interleukin-6, soluble interleukin-6 receptor and soluble tumour necrosis factor receptors 55 and 75 were measured by indirect ELISA. Serum levels of C-reactive protein, interleukin-6 and soluble tumour necrosis factor receptors 55 and 75 were significantly higher in cancer patients than in controls. Levels of serum soluble interleukin-6 receptor were not significantly different between the two groups. In cancer patients, a significant positive association was found between the level of the acute-phase protein response and serum levels of interleukin-6, soluble tumour necrosis factor receptor 55 and soluble tumour necrosis factor receptor 75. No association was found between levels of soluble interleukin-6 receptor and any other factor. There is no significant relationship between the level of soluble interleukin-6 receptor and the acute-phase protein response in vivo and the biological role of soluble interleukin-6 receptor in the chronic inflammatory component of cachexia remains unclear.
Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); P<0.05]. Over the 4 h feeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); P<0.01]. After 3 weeks of the EPA-enriched supplement, the body weight of the cancer patients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g. kg(-1).min(-1) (0.8-1.18), again no longer significantly different from baseline healthy control values. While weight-losing patients with advanced pancreatic cancer have an increased resting energy expenditure and increased fat oxidation, the energy cost of feeding is, in fact, reduced. Provision of a fish-oil-enriched nutritional supplement results in some normalization of the metabolic response in both the fasted and fed states, in association with an improvement in nutritional status.
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