Nutrition Nutrition

Cancer cachexia is very common even in patients maintaining normal food intake, indeed weight loss may be the first sign of the presence of a malignancy. In humans patients with cancer cachexia have reduced quality of life, are less responsive to treatment and have reduced survival times compared with similar patients maintaining body weight. The weight loss that occurs in cancer patients is due to a net energy deficiency resulting from inadequate intake, excessive energy expenditure or both. Possible factors include:

(1) Reduced food intake:
  • altered taste or smell sensation

  • intermediary metabolites acting on the satiety centre (e.g. serotonin)

  • hepatic disease

  • paraneoplastic syndrome - hypercalcaemia

  • mechanical disorders - pain, tumour presence, post-treatment.

(2) Hypermetabolism. Increased metabolic rate resulting in increased rate of energy utilization.

(3) Energy competition. The neoplasm competes with the body for energy. It has been demonstrated that tumour cells preferentially metabolise glucose using anaerobic glycolysis, which is an energy wasting metabolic pathway, resulting in lactate production. The glu used by the cancer is lost to the patient and the lactate produced is converted by the Con cycle back to glucose, which further utilises energy. It has been estimated that the rate of turnover of glucose in cancer patients is 80% greater than in normal patients.

Dogs with lymphoma (before the development of cachexia) have increased lactate and insulin serum concentrations compared with control dogs and therefore they have significant alterations in carbometabolism (Vail et al. 1989). For this reason rehydration with glucose containing or lactated Ringer's solution should be avoided.

(4) Impaired gastrointestinal function. This may result in reduced digestion or absorption due to the physical presence of the tumour, a side-effect of treatment or paraneoplastic syndrome.

(5) Impaired metabolic function. Impaired metabolic function (e.g. haematopoietic, hepatic, renal or other) may result in impaired transportation, and metabolism of nutrients.

(6) Paraneoplastic syndrome. Many tumours induce metabolic changes which contribute to cachexia.

(7) Excessive nutrient losses. Losses may be caused by, e.g. gastrointestinal lymphosarcoma, haemorrhage, nephrotic syndrome.

(8) Side-effects of cancer treatment. These occur particularly with chemotherapy, radiotherapy and major surgery.

One consequence of cancer cachexia is negative nitrogen balance caused by protein degradation because the tumour uses amino acids for protein synthesis and for energy, at a rate which exceeds the patient's rate of protein synthesis. The resulting loss of lean body mass and protein

depletion results in impaired immune function, reduced gastrointestinal function, hypoalbuminaemi~ and poor wound healing.

Several changes in lipid metabolism including a net depletion of lipid stores and hyperlipidaemia occur in cancer patients. The latter has been associated with immunosuppression and is possibly related to the poor survival times of some patients. Insulin resistance and sometimes insulin deficiency both develop in some cancer patients and this encourages fat mobilisation and leads to hyperglycaemia and poor glucose utilisation by the body cells, forcing them to use fat and protein for energy.

The mechanisms causing these metabolic changes have still to be fully elucidated, but it is known that they can occur before weight loss. Various factors including interferons and interleukons are probably involved as is the polypeptide tumour necrosis factor (also called cachectin) which causes lipid mobilisation, as does toxohormone, another tumour derived hormone.

So far therapeutic treatments alone have not proved successful at reversing cancer cachexia, and so whatever the underlying cause adequate and sometimes aggressive nutritional support should be provided for patients showing significant weight loss. Animals in a catabolic state are vulnerable to the side-effects of many of the treatment modalities that are recommended in the management of cancer, so stabilisation is recombefore commencing such treatment.

Feeding methods should be designed to:

(1) increase nutrient intake
(2) inhibit gluconeogensis and glycolysis
(3) prevent glucose utilisation by the cancer cells
(4) maintain nitrogen balance with amino acids
(5) provide branched-chain amino acids to decrease brain uptake of tryptophan and excess serotonin synthesis.

Diets containing 30-50% of calories as fat (which cannot be used as an energy source by cancer cells) have been shown to decrease glucose intolerance, fat loss and tumour growth and at the same time increase host weight, nitrogen and energy balance.

Whenever possible patients should be fed a high energy ration orally, but if voluntary food intake is inadequate nasogastric, pharyngostomy, oesophageal or gastric feeding should be employed. For debilitated cases a percutaneous endoscopically placed gastrostomy (PEG) tube is an easy procedure which is now routinely practised in many referral centres. Jejunostomy is another enteral route that can be utilised and, as a last resort, partial or total parenteral nutrition can be performed, but these

techniques need to be carried out under the guidance of a trained clinical nutritionist.

There is some evidence that zinc supplementation might improve appetite and immune function in cancer patients and some authors recommend supplements.

Patients receiving nutritional support should be monitored regularly to assess progress. Body weight change and alterations in other parameters such as serum albumin, blood urea, red blood cell count and white blood cell count should be evaluated every 2 weeks.