Substrate balances across colonic carcinomas in humans.

To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo.

Protein metabolism in human colon carcinomas: in vivo investigations using a modified tracer technique with L-[1-13C]leucine.

To quantify the protein anabolism of tumors it is not sufficient simply to determine the level of protein synthesis. The decisive factor is the net balance. This is the first attempt to establish this parameter in human tumors in vivo. Intraoperative tumor leucine/protein metabolism was studied in 15 patients with resectable malignant colon tumors using a balance model and L[1-13C]leucine as the tracer substance. Comparative measurements were also carried out simultaneously for peripheral tissue (forearm); in addition, protein kinetics parameters were established for the whole body using a proven two-pool model (with the same tracer as above). In view of the frequently conflicting data on amino acid metabolism in tumors, the tumoral and peripheral exchange rates of 20 amino acids were also determined. In tumors, essential and branched-chain amino acid uptakes were found to be 1.68 +/- 0.59 (SE) and 1.52 +/- 0.23 mumol/100 g tissue/min, respectively; in peripheral tissue there was overall an amino acid release [-0.11 +/- 0.06 and -0.05 +/- 0.04 mumol/100 g/min; in either case P < 0.01 (tumor versus periphery)]. Tracer analyses yielded a net retention for the tumors but a protein loss for peripheral tissue (8.941 +/- 3.113 versus -0.557 +/- 0.53 g/kg/24 h; P < 0.01) and for the whole body (-0.363 +/- 0.04 g/kg/24 h). The tumors were divided into two prognostic groups on the basis of their histology. Significant differences were found between the two groups in terms of the net retention rate for 10 amino acids, including leucine; retention was elevated in tumors with an unfavorable prognosis, possibly due to a higher amino acid requirement because of more rapid growth or for export processes (mucus production). The protein balance model used here has proved satisfactory for our purposes and could also be used to directly evaluate dietary measures (e.g., adjuvant parenteral nutrition in connection with chemotherapy).