Protein-Energy Malnutrition and Cancer Cachexia
Protein-energy malnutrition is the result of inadequate intake of both protein and calories. This syndrome is well described in hospitalized humans, and has been linked to an increased incidence of complications, prolonged hospital stays, and poor response to therapy for the underlying disease. The protein-energy malnutrition specifically associated with neoplastic disease is often called “cancer cachexia.” Weight loss in human cancer patients is more common in individuals with advanced disease and poor performance scores, and is an important prognostic indicator: patients with weight loss have shorter survival times than those without weight loss, regardless of their specific diagnosis. The incidence of weight loss varies with tumor type, occurring in approximately one-third of people with treatment-responsive lymphomas, breast cancer or sarcomas, one-half to two-thirds of people with colon cancer, prostate cancer, lung cancer or treatment-nonresponsive lymphomas, and 80 to 90% of people with pancreatic or gastric cancers.
Weight loss can occur in both human and veterinary cancer patients due to either reduced nutrient intake secondary to the physical location of the tumor, or to complications caused by anticancer therapy. In addition, weight loss appears to occur in some individuals secondary to unique, tumor-related biochemical alterations that lead to inefficient metabolism of consumed calories. Affected patients suffer progressive depletion of both lean body mass and adipose stores, caused by abnormalities involving the intermediary metabolism of carbohydrates, proteins and lipids. Similar changes have been documented in rodents bearing implanted tumors and dogs with naturally occurring tumors. It is likely that direct physical effects of the tumor, as well as the host endocrine and cytokine response to the presence of neoplastic disease, play roles in the pathogenesis of cancer cachexia, although the syndrome is not completely understood.
The rapid growth typical of neoplastic tissue leads to increased tumor cell requirements for amino acid nitrogen, as well as energy. Energy must be supplied in the form of glucose, because tumor cells are unable to use fat-derived fuels effectively. The patient is forced to serve as the source of both amino acids and glucose: amino acids are produced through catabolism of host lean body mass, and glucose is generated primarily through gluconeogenesis from host amino acids or lactate (the Cori Cycle). The host’s neuroendocrine response to physiologic stress and malignant disease is likely to further increase catabolism of body protein and energy stores. Ultimately, these metabolic demands lead to futile cycling and increased flux through numerous biochemical pathways, theoretically wasting energy and causing many of the changes considered “typical” of the tumor-bearing state. Alterations specifically documented in tumor-bearing people and animals include increased serum lactate concentrations, increased rates of whole body glucose turnover and disposal, increased rates of gluconeogensis, increased whole body protein turnover, and accelerated lipolysis.
Frequent attempts have been made to quantify the precise amount of energy lost by the tumor-bearing host through these mechanisms, using indirect calorimetry. However, the results obtained from these studies are widely variable. Tumor type and stage of disease both influence energy expenditure; it may be increased, unchanged or even decreased under various circumstances in the same patient. In addition, study design may significantly impact the conclusions that can be drawn from indirect calorimetry studies: some authors describe measurement of energy expenditure in tumor-bearing subjects prior to any weight loss at all, while others compare the energy expenditure of cachectic patients with cancer to that of healthy, weight stable controls. Arguably, the most appropriate comparison is between weight-losing cancer patients, and weight-losing patients with nonmalignant disease.
While biochemical abnormalities analogous to those present in human patients with cancer cachexia have been demonstrated in dogs with a variety of tumors, many of the dogs described to date have not had documented concurrent weight loss. The incidence of true “cancer cachexia” among animals with cancer is not known, but preliminary data suggests that regardless of the biochemical changes present, the proportion of cats or dogs with cancer-related weight loss is less than that observed in people. One study reported less than one-third of cats and dogs with malignant disease had documented weight loss at the time of diagnosis, while approximately half of dogs with malignant disease were in obese body condition. Furthermore, there was no significant difference in the proportion of cats or dogs with documented weight loss when animals with malignant and nonmalignant disease were compared. A potential explanation for these observations is that cats and dogs are more commonly diagnosed with and treated for tumors less likely to cause weight loss in human patients, such as lymphoma, breast cancer, and sarcomas. Tumors more commonly associated with weight loss in humans, such as gastric, colon, prostate, and lung cancers, are rare in cats and dogs.
Diagnosis of Cancer Cachexia
Cats and dogs with cancer cachexia are best identified through nutritional assessment. Nutritional assessment systematically evaluates patient protein and energy status by integrating data obtained from a diet history, thorough physical examination including body condition scoring, and routine hematologic and biochemical testing. In addition to confirming a diagnosis of existing protein-energy malnutrition, nutritional assessment can be used to predict which animals are at increased risk for protein-energy malnutrition; it also provides an accurate and dynamic measurement of patient response to nutritional support.
A thorough diet history is the first step in nutritional assessment, and should include a detailed description of the patient’s current and normal diet including product brand name, form (i.e., canned, dry or semi-moist), flavor, amount and frequency of feeding, and current medications or nutritional supplements. After the history has been obtained, a complete physical examination is performed. With the exception of the tumor itself, the physical examination abnormalities associated with cancer cachexia are the same as those present in protein-energy malnutrition of any etiology. The difficulty is that associated clinical signs are nonspecific and often subtle, and an increased index of suspicion must be preserved in order to identify affected individuals. One or more abnormalities may be present, including muscle wasting, pallor, weakness, poor hair coat, hepatomegaly, splenomegaly, evidence of chronic infections, lymphadenopathy, and peripheral edema.
Body condition scoring is a useful technique that is easily incorporated into the physical examination of cats and dogs. It yields valuable information about lean body mass and body adipose stores, especially when serial scores are followed over time. A five or nine point scale in which each point corresponds to a particular body condition as defined by specific, standardized criteria is generally employed. For instance: “cachectic” (no detectable body fat); “optimal” (good muscle mass and tone, some body fat present but ribs still easily palpable); or, “obese” (large quantities of subcutaneous and abdominal fat completely obscure underlying anatomic structures). Published studies confirm that there is good correlation between body condition score, and the proportion of lean body mass to adipose tissue (i.e., body composition) in cats and dogs.
Routine clinical pathology testing is usually the final step in nutritional assessment for canine and feline patients. Abnormalities in several parameters may be used as supporting evidence of the presence of cancer cachexia, although none is particularly sensitive or specific. Normochromic, normocytic, nonregenerative anemia (anemia of chronic disease) and lymphopenia are often present. Biochemical abnormalities may include decreased blood urea nitrogen concentrations, secondary to decreased protein intake; decreased serum creatinine concentrations, due to attrition of lean body mass; and, hypoalbuminemia caused by increased protein catabolism with decreased protein synthesis. The unusually high protein requirement of the cat likely predisposes this species to protein-energy malnutrition, and may lead to additional serum biochemical abnormalities. Increased serum concentrations of creatine kinase may be observed as skeletal muscle is rapidly catabolized to meet requirements for amino acids. Protein deficiency may also be a factor in the pathogenesis of idiopathic feline hepatic lipidosis, with affected cats typically having increased serum concentrations of hepatocellular leakage enzymes and alkaline phosphatase.
Feeding Cats and Dogs with Cancer
Highly palatable, highly digestible, nutrient dense rations are often recommended as a way to maintain optimal nutritional status in cats and dogs with cancer. Rations may also be designed to take advantage of the metabolic differences between host tissues and tumor cells: high fat, low carbohydrate diets should theoretically supply energy to the host at the expense of the tumor. Objective benefits have been documented in human and canine cancer patients fed such diets, including more effective preservation of lean body mass and adipose stores, decreased glucose intolerance, and prolonged survival times. Quality of life and the ability to tolerate antineoplastic therapy may also be improved. The commercial rations most likely to fit the desired profile are prescription products designed for use during performance or stress, “premium” cat and dog foods, and kitten or puppy foods. A prescription product specifically designed for use in dogs with neoplastic disease is also available. Complete and balanced products made by a reputable manufacturer and tested using established AAFCO feeding protocols are preferred over home-cooked diets. Either dry or canned rations are acceptable, although dry foods are often more energy dense than canned products and may be advantageous in animals with ongoing weight loss.
It is essential to recognize, however, that all cats and dogs with neoplastic disease will not benefit equally from nutrient dense or high fat rations. The best diet for an individual patient is determined by careful assessment of body condition, concurrent diseases, and previous dietary history. For instance, many cats and dogs with cancer are already obese, and careless use of high fat diets in these patients may promote further weight gain. High fat diets should also be avoided in animals that are likely to tolerate fat poorly (i.e., dogs with a history of pancreatitis or hyperlipidemia). Specific therapeutic diets may be important adjuncts in the management of concurrent conditions including gastrointestinal, renal or hepatic disease. Finally, individual flavor and formulation (dry vs. canned vs. semi-moist) preferences, as well as historical episodes of food intolerance must be considered. Clearly, no single ration will provide optimal nutrition for every small animal with cancer.
There are three primary methods available for feeding cats and dogs with cancer: voluntary intake, assisted enteral feeding, and assisted parenteral feeding. The preferred route is dictated primarily by the animal’s underlying disease process, although cost must often be considered as well. Voluntary intake is favored as long as it meets the patient’s needs: it is simple, convenient and cost effective. Initially, the chosen ration is offered in quantities that will meet the animal’s estimated daily caloric requirement; intake is then adjusted as necessary to maintain optimal body condition. Actual intake must be monitored carefully and compared to the estimated requirement. If a deficit is present, voluntary intake may be improved by hand feeding of frequent small meals, the use of highly palatable foods, or the use of nutrient dense products that maximize calorie intake. If these measures are unsuccessful, some form of assisted feeding should be instituted without delay.
Assisted enteral feeding is the optimal method of nutritional support for the majority of feline and canine cancer patients that are unable to meet their requirements through voluntary intake. Delivery of nutrients directly into the intestinal tract takes advantage of existing pathways and physiologic adaptations, and promotes normal organ function. The presence of food within the intestine supports enterocyte health and decreases villous atrophy; it also maintains gut immune function and prevents bacterial translocation, which may otherwise lead to systemic bacterial infection and sepsis. Assisted enteral feeding is usually easier to administer than parenteral feeding, has fewer potential complications, and is less expensive. There are few disadvantages associated with enteral feeding, although it is obviously contraindicated if the gastrointestinal tract is nonfunctional. Long periods of transition may also be required to reach full intake in patients with long preceding periods of anorexia.
Assisted parenteral feeding is the only option for nutritional support in a selected group of feline and canine cancer patients with nonfunctional gastrointestinal tracts due to decreased digestive or absorptive capacity, or anatomic or physiologic obstruction. Parenteral feeding may benefit patients with inflammatory gastrointestinal conditions such as inflammatory bowel disease or pancreatitis, because it allows complete bowel rest. In addition, the lack of ingesta within the upper gastrointestinal tract during parenteral feeding may be advantageous in comatose patients at high risk for aspiration. Assisted parenteral feeding may also be considered for animals not sufficiently stable to withstand the general anesthesia that may be required for feeding tube placement, or patients with severe coagulopathies. However, parenteral feeding has several potential disadvantages that must be recognized. Mechanical, infectious and biochemical complications (i.e. hyperglycemia, hyperlipidemia or refeeding syndrome) are all possible, and patients must be carefully monitored to avoid them. The lack of ingesta within the intestinal tract during parenteral nutrition also promotes clinically significant villous atrophy, predisposing critically ill patients to bacterial translocation from the gut. An increased level of nursing care, as well as specialized equipment and products, are required. Finally, assisted parenteral feeding is often considerably more costly than assisted enteral feeding. The use of parenteral nutrition should be restricted to those patients in whom it is clearly indicated.
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