Hypothesis: the provision of parenteral nutrition to malnourished patients with gastrointestinal malignancies before major surgical resection leads to decreased complications and improved postoperative outcome. We postulate the mechanism to be enhanced whole body protein synthesis because proteins play crucial roles in virtually all biological processes ranging from enzyme activity to muscle function. Enhanced protein synthesis in response to nutrient support results in increased muscle protein and hepatic albumin synthesis, because there are no inert storage pools for amino acids and nitrogen. Furthermore, differential effects on whole body protein dynamics by qualitatively different nutrient solutions may result in different outcome. In a randomized controlled trial, using (leucine-enriched) and conventional amino acid solutions, biochemical and metabolic interrelationships will be correlated to repletion and outcome by studying: (1) Protein dynamics after infusion of (1-13C)leucine and (15N)glycine to determine a) muscle protein synthesis rate from 13C-enrichment of intracellular muscle leucine, b) whole body leucine kinetics from 13C-enrichment of plasma leucine and expired 13CO2, c) serum albumin synthesis from 15N-enrichment of plasma glycine and guanidino-15N arginine derived from albumin. Stable isotope enrichment will be measured by chemical ionization and isotope ratio-gas chromatography-mass spectrometry. (2) Quality of weight change as determined by skinfold thickness (lean body mass) and total body water using 18 O water, (3) Muscle function, by adductor nerve function test, (4) Nitrogen retention and muscle breakdown by 24 hr urine N and urinary 3-methylhistidine:creatinine. (5) Plasma amino acid levels, by amino acid analysis. The proposed studies will be significant in three aspects. In design they will utilize only those patients able to show a postoperative effect from preoperative TPN, they will utilize a standard common biologic end point indicator of repletion and will employ a different TPN formulation not previously evaluated in detail in cancer bearing patients. Results of these studies should provide an objective evaluation of the significance of nutritional support in patients with localized solid tumor, and should lead to a rational nutrition program in surgical oncology.
