Effect of tumor burden and subsequent surgical resection on skeletal muscle mass and protein turnover in colorectal cancer patients1234

• Published in: The American journal of clinical nutrition Vol. 96; no. 5; pp. 1064 - 1070
• Main Authors: Williams, John P, Phillips, Bethan E, Smith, Kenneth, Atherton, Philip J, Rankin, Debbie, Selby, Anna L, Liptrot, Sarah, Lund, Jonathan, Larvin, Mike, Rennie, Michael J
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2012
• Subjects: CRP; MPS; MAFBx; α-KIC; CRC; AKT; mRNA; P70S6K1; MuRF-1; MPB; 4EBP1
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.112.045708

Background: Cachexia is a consequence of tumor burden caused by ill-defined catabolic alterations in muscle protein turnover. Objective: We aimed to explore the effect of tumor burden and resection on muscle protein turnover in patients with nonmetastatic colorectal cancer (CRC), which is a surgically curable tumor that induces cachexia. Design: We recruited the following 2 groups: patients with CRC [n = 13; mean ± SEM age: 66 ± 3 y; BMI (in kg/m2): 27.6 ± 1.1] and matched healthy controls (n = 8; age: 71 ± 2 y; BMI: 26.2 ± 1). Control subjects underwent a single study, whereas CRC patients were studied twice before and ∼6 wk after surgical resection to assess muscle protein synthesis (MPS), muscle protein breakdown (MPB), and muscle mass by using dual-energy X-ray absorptiometry. Results: Leg muscle mass was lower in CRC patients than in control subjects (6290 ± 456 compared with 7839 ± 617 g; P < 0.05) and had an additional decline after surgery (5840 ± 456 g; P < 0.001). Although postabsorptive MPS was unaffected, catabolic changes with tumor burden included the complete blunting of postprandial MPS (0.038 ± 0.004%/h in the CRC group compared with 0.065 ± 0.006%/h in the control group; P < 0.01) and a trend toward increased MPB under postabsorptive conditions (P = 0.09). Although surgical resection exacerbated muscle atrophy (−7.2%), catabolic changes in protein metabolism had normalized 6 wk after surgery. The recovery in postprandial MPS after surgery was inversely related to the degree of muscle atrophy (r = 0.65, P < 0.01). Conclusions: CRC patients display reduced postprandial MPS and a trend toward increased MPB, and tumor resection reverses these derangements. With no effective treatment of cancer cachexia, future therapies directed at preserving muscle mass should concentrate on alleviating proteolysis and enhancing anabolic responses to nutrition before surgery while augmenting muscle anabolism after resection.