Pathophysiology of Cancer Cachexia 262
Altered Caloric and Nutritional Intake 262
Metabolic Disorders 264
Treatment of Cancer Cachexia 266
Wound Healing 267
Effects of Radiation Therapy 268
Effects of Chemotherapy 268
Anthracycline Antitumor Antibiotics 269
Alkylating Agents 269
Vinca Alkaloids 269
Folic Acid Analogs 269
Growth Factors in Wound Healing 270
Nutrition Support in Cancer Patients 271
Nutritional Assessment of the Cancer Patient 271
Clinical Consequences of Malnutrition in the Postoperative Period 274
Perioperative Parenteral Nutrition 275
Perioperative Enteral Nutrition 278
Nutritional Support and Chemotherapy 281
Nutritional Support and Radiation Therapy 281
Recommendations for Nutritional Support in Cancer Patients 284
Nutrient Excess and Tumor Growth 286
Future Directions: Immunonutrition 288
Successful wound healing in the cancer patient can be a formidable task. The effects of malignancy on a patient's nutritional status are multifaceted and can make the achievement of wound healing a challenge. Cancer alters the body's ability to maintain sustenance by manipulating both gastrointestinal caloric intake and subsequent nutritional processing. Malnutrition with varying degrees of weight loss is a common sequela of many solid tumors. Depending on the inciting malignancy, some degree of malnutrition has been identified in 30 to 90% of studied groups.1 Up to one third of a large population in a multicenter survey demonstrated weight losses greater than 4%.2 At its greatest magnitude, malnutrition manifests as cachexia, which is characterized by progressive total body muscle and fat wasting. The most severe presentations are identified in the presence of head and neck as well as upper gastrointestinal cancers (i.e., esophagus, stomach, and pancreas). Weight loss in excess of 10% was demonstrated in 14% of patients with colon cancer and between 25 and 40% of those with gastric and pancreatic cancer.2 Conversely, such severe losses were seen in only 4 to 7% of patients with leukemias, sarcomas, or breast cancer.
Cachexia results from the inappropriate wasting of skeletal muscle and adipose tissue. This is in contrast to simple starvation, which preferentially depletes fat stores, thus sparing lean muscle mass. The mechanisms driving cancer cachexia are multiple and appear to be a complex interaction between the digestive and immune systems. As the mainstay of treatment for many malignancies remains complete surgical resection, the implications of cachexia on wound healing are significant. An understanding of the pathophysiology of cancer cachexia and the effects of malignancy on wound healing will allow treatment regimens to be devised to combat this difficult aspect of oncologic care.
pathophysiology of cancer cachexia
Cachexia in the setting of malignancy is a complex process with abnormalities identified in caloric intake, metabolism of nutrients, and humoral/inflammatory responses (Figure 12.1). Individual cancers uniquely affect each of those components, resulting in various degrees of the cachectic state.
altered caloric and nutritional intake
The ability to consume an adequate quantity of calories and nutrients is commonly decreased in the setting of malignancy. Dietary intake is often inappropriately decreased, even when the malignant condition has increased caloric needs.3 Anorexia is frequently present, manifesting as a loss of appetite with early satiety. This can be present in as many as one half of newly diagnosed cancer patients. Alterations in the taste and smell of food contribute to this phenomenon.2 Depression, which is not uncommon among the oncologic population, can greatly decrease a patient's appetite.1
A direct effect on the gastrointestinal tract can result in decreased nutritional intake. Cancer of the head and neck or upper gastrointestinal tract can result in dysphagia and odynophagia secondary to mechanical effects. Decreased gastric emptying and intestinal dysfunction lead to decreased bowel motility and subsequent early satiety, nausea, and vomiting. Tumor bulk can impinge upon the upper gastrointestinal tract, resulting in early satiety. Growth of tumor anywhere within the abdomen can compress or directly obstruct the intestinal lumen, resulting in partial or complete bowel obstructions. Also, postoperative changes after bowel surgery can
alter gastrointestinal physiology, resulting in abnormal function. Furthermore, intestinal mucosal atrophy or bacterial overgrowth within blind loops may contribute to nutrient malabsorption.4
The nonsurgical cancer treatments have also been associated with many conditions that negatively impact dietary intake. Chemotherapeutic agents can cause nausea, vomiting, cramping, and bloating. Mucositis, mucosal erosive lesions, and paralytic ileus have all been observed.1
The normal metabolic function is severely deranged in the cancer patient. The body responds inappropriately to metabolic demands on the host. Normal control systems malfunction, resulting in depletion of muscle and adipose stores. Despite experiencing decreased nutritional intake, the body is unable to downregulate energy expen-diture.5 Instead, the tumor causes an increase in energy expenditure thought to be secondary to an increased adrenergic state and an inflammatory response to the malignancy.1 Lung and pancreatic cancer have been particularly associated with a hypermetabolic state and, subsequently, demonstrate more severe weight loss.6
The metabolism of carbohydrates is altered by malignancy. Anaerobic glycolysis is favored by tumor cells, resulting in the production of lactate. Lactate is inefficiently recycled to glucose by gluconeogenesis in the Cori cycle. A substantial net loss of energy occurs through this wasteful process.7 Further altered carbohydrate metabolism includes reduced pancreatic insulin secretion as well as glucose intolerance, which is secondary to peripheral insulin resistance.8
Abnormal lipid metabolism demonstrates an increased oxidation of fatty acids with subsequent mobilization of peripheral fat. Malignancy stimulates an increased rate of lipolysis in adipose tissue. This is in contrast to normal subjects who are capable of regulating lipid oxidation during starvation.9 This is believed to be a result of stimulation by a lipid-mobilizing factor that acts directly on adipocytes in a cyclic adenosine monophosphate (cAMP)-dependent manner. Lipoprotein lipase activity is decreased, resulting in diminished uptake of fatty acids from circulating lipopro-teins.7 Ultimately, this results in depletion of total body lipid stores.
Additionally, the metabolism of proteins is abnormal, as demonstrated by increased protein turnover with a reduction in muscle protein synthesis.1 This protein catabolism escapes normal regulatory control, resulting in protein depletion and subsequent muscle atrophy. The escalation of hepatic acute phase reactants in the setting of malignancy also depletes protein stores.5 The breakdown of protein is mediated by a proteolytic inducing factor that utilizes an adenosine triphosphate (ATP)-ubiquitin-dependent pathway.10 This has been observed even in the presence of adequate protein consumption, again owing to the loss of homeostatic control in the oncologic patient.
The increased energy expenditure and metabolic abnormalities in cancer patients are of greater magnitude than would be explained by the tumor itself. This has been determined to be a result of an alteration in the release of multiple inflammatory mediators. Listed in Table 12.1 are the humoral mediators thought to be associated with cancer cachexia as well as their proposed effects.
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