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A viscerally driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole-body energy demands

¹ From the Departments of Oncology (MM and VEB) and Agriculture, Food and Nutritional Science (JRL, LJM, CMMP, and VEB), University of Alberta, Edmonton, Alberta, Canada, and the Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (KDH).

² Supported in part by the Intramural Research Program of the NIH, NIDDK; the Canadian Institutes for Heath Research Canada Graduate Scholarship Masters Award (to JRL); the Alberta Cancer Board Graduate Studentship from Alberta Cancer Board and Alberta Cancer Foundation, Edmonton, Canada (to JRL and CMMP); the Translational Research Training in Cancer fellowship from the Canadian Institute of Health Research (to MM and CMMP); and grants from the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Alberta Cancer Board, and Alberta Cancer Foundation.

³ Address reprint requests and correspondence to VE Baracos, Department of Oncology, Division of Palliative Care Medicine, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 Canada. E-mail: vickie.baracos{at}ualberta.ca.

Background: Cancer cachexia–associated weight loss is poorly understood; energetically demanding tissues (eg, organ and tumor mass) and resting energy expenditure (REE) are reported to increase with advanced cancer.

Objective: The objective was to quantify the potential contribution of increasing masses of energetically demanding tissues to REE with colorectal cancer cachexia progression.

Design: A longitudinal computed tomography (CT) image review was performed to quantify organ size (liver, including metastases, and spleen) and peripheral tissues (skeletal muscle and adipose tissue) during colorectal cancer cachexia progression (n = 34). Body composition was prospectively evaluated by CT and dual-energy X-ray absorptiometry, and REE was determined by indirect calorimetry in advanced colorectal cancer patients (n = 18).

Results: Eleven months from death, the liver (2.3 ± 0.7 kg) and spleen (0.32 ± 0.2 kg) were larger than reference values. One month from death, liver weight increased to 3.0 ± 1.5 kg (P = 0.010), spleen showed a trend to increase (P = 0.077), and concurrent losses of muscle (4.2 kg) and fat (3.5 kg) (P < 0.05) were observed. The estimated percentage of fat-free mass (FFM) occupied by the liver increased from 4.5% to 7.0% (P < 0.001). The most rapid loss of peripheral tissues and liver and metastases gain occurred within 3 mo of death. A positive linear relation existed between liver mass and measured whole-body REE (r² = 0.35, P = 0.010); because liver accounted for a larger percentage of FFM, measured REE · kg FFM^–1 · d^–1 increased (r² = 0.35, P = 0.010).

Conclusions: Increases in mass and in the proportion of high metabolic rate tissues, including liver and tumor, represented a cumulative incremental REE of 17,700 kcal during the last 3 mo of life and may contribute substantially to cachexia-associated weight loss.