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

Abstract

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 6 SEM age: 66 6 3 y; BMI (in kg/m 2 ): 27.6 6 1.1] and matched healthy controls (n = 8; age: 71 6 2 y; BMI: 26.2 6 1). Control subjects underwent a single study, whereas CRC patients were studied twice before and w6 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 6 456 compared with 7839 6 617 g; P , 0.05) and had an additional decline after surgery (5840 6 456 g; P , 0.001). Although postabsorptive MPS was unaffected, catabolic changes with tumor burden included the complete blunting of postprandial MPS (0.038 6 0.004%/h in the CRC group compared with 0.065 6 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 (27.2%), 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.

Incidence and risk factor analysis for sarcopenia in patients with cancer

“…As the preferred method of treatment, surgery can achieve resection of the tumor to avoid skeletal muscle consumption originating from the tumor burden (24). However, a significant association between surgical cancer treatment and the development of sarcopenia was not observed in the present study.…”

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

“…Two previous short term studies (<6 hours) using a primed constant infusion of isotope tracer have shown that skeletal muscle protein FSR may be reduced in the fed state in patients with lung cancer (9) or may be unchanged (colorectal cancer) but with a blunted response to intravenous infusion of amino acids (2). Any potential reduction in muscle protein FSR would be expected to be more apparent during the present protocol than during a short-term infusion protocol as the oral tracer design incorporates the potentially cumulative anabolic effect of many meals over the one week protocol.…”

“…Loss of skeletal muscle mass in cancer is well described (1)(2)(3) and is a defining characteristic of the cachexia syndrome (4). Low muscle mass is associated with a variety of clinical consequences including prolonged hospitalization, reduced mobility, and increased chemotherapy toxicity (5).…”

Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function

“…Blood samples were precipitated with perchloric acid and the supernatant was neutralized before purification by cation exchange chromatography. The subsequent eluent was dried under nitrogen before derivatizing the amino acids to their tert-butyldimethylsilyl derivatives using standard techniques (21). Concentrations and enrichments were determined by gas chromatographymass spectrometry (Trace DSQ; Thermo Scientific, U.K.), with norleucine and d 2 -phenylalanine used as internal standards.…”

“…These benchmarks were based on reports that serum CRP concentrations .1.35 mg $ mL 21 are associated with increased levels of IL-6 and TNF-a in obese individuals (16). All individuals not meeting these criteria were excluded from participating.…”