Home parenteral nutrition in advanced cancer: where are we?

Patients with advanced and incurable cancer are a compelling group. Questions and comments that these individuals and their families have may include: "My daughter is expecting our first grandchild in 3 months--can I hope to see our new family member?"; "I can't keep any food down--is there anything I can do?"; "I am worried about losing so much weight, and feeling tired and weak--is there anything that may help?"; "Will I suffer a lot?". Indeed, the most pressing concerns of the patient relate to predictions about survival and control of symptoms. The clinician taking care of the patient may wonder what is the utility or futility of home parenteral nutrition (HPN) in both the individual with advanced cancer and in this population of patients at large, whether there is potential for harm such as increasing the burden of care or prolonging suffering, and how to optimize care and communication with the patient and their families. The nutrition scientist may want to know what the implications of advanced cancer are on nutrient requirements and utilization, whether there are markers that would differentiate between cachexia and simple starvation, and whether it is possible to use specific nutrients to modify the disease process. This review will provide insights into the understanding of the role of HPN in advanced cancer and opportunities for further investigation.

Investigations of branched-chain amino acids and their metabolites in animal models of cancer.

Many of the features of BCAA metabolism in the tumor-bearing state are similar to the other disease states that feature involuntary weight loss and skeletal muscle atrophy. These states are generally characterized by altered BCAA availability (low BCAA intakes, elevated rates of BCAA oxidation, and gluconeogenesis), which are concurrent with activation of proteolysis and suppression of protein synthesis in skeletal muscle and ultimately lead to erosion of lean tissue mass. These features in turn imply BCAA deficiency compared with whole-body requirements and are the basis of suggestions for dietary supplementation with BCAA or their metabolites. Recent studies on BCAA supplementation in cancer focus on leucine and its derivative, beta-methyl beta-hydroxybutyrate, as regulators of skeletal muscle metabolism, although their relative efficacy is unknown. However, what would otherwise be a relatively straightforward consideration of amino acid supply and demand is confounded by the presence of the tumor and its potential utilization of BCAA for its proliferative and invasive activities. Positron emission tomography with (11)C-leucine, used for in vivo tumor imaging, points to the high avidity of tumor amino acid uptake. These features have incited research in opposing directions, probing BCAA deprivation, with a view to limiting tumor growth, as well as BCAA supplementation, with a view to supporting maintenance of host lean tissue. No clear conclusion is presently available from the sum of these efforts. Animal models with relevant clinical features are essential to determine if amino acid therapy can alter the balance between the host and the tumor in a manner that favors the host overall.

A proinflammatory tumor that activates protein degradation sensitizes rats to catabolic effects of endotoxin.

Chronic or acute inflammation may participate in the etiology of cancer cachexia. To investigate the interaction between tumor and a secondary inflammatory stimulus on muscle wasting, rats with and without tumors (Yoshida ascites hepatoma) received low doses of endotoxin (LPS, 400 microg/kg sc) or saline. Nitrogen balance was measured 24 h before and after LPS/saline. Epitrochlearis muscle was used to measure in vitro protein metabolism, and gastrocnemius muscle was used for quantification of the mRNA for components of the ubiquitin proteolytic pathway. The YAH reduced muscle mass (P = 0.002), increased muscle protein degradation (P = 0.042), and elevated mRNA expression of components of the ubiquitin proteolytic pathway (P < 0.01) including ubiquitin, ubiquitin-conjugating enzyme E2(14k), and ubiquitin ligases muscle RING Finger 1 and atrogin-1. Although the selected low dose of LPS had no impact on protein metabolism in control rats, LPS in rats bearing YAH caused weight loss (P = 0.0007), lowered nitrogen balance (P = <0.0001), and increased muscle protein degradation (P = 0.0336). In conclusion, the presence of a tumor can potentiate whole body and muscle-specific catabolic losses of protein in response to a stimulus that is not catabolic in healthy animals. This effect might be dependent on the inflammatory nature of the tumor.