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Cachexia is pervasive among patients suffering from chronic diseases, including cancer, liver cirrhosis and chronic renal failure. The development of cachexia dramatically impacts on the clinical course of the underlying disease, by increasing morbidity and mortality, and impinging on patients’ quality of life. Also, weight loss influences outcome by increasing drug-induced toxicity and impeding completion of the therapeutic schedule. Particularly in cancer patients, weight loss is a reliable predictor for toxicity from treatment and shorter survival [ 1 ].

Experienced oncologists acknowledge that the cancer anorexia/weight loss syndrome predicts a shorter survival for patients with advanced, incurable disease. Several powerful, well-conducted studies have borne out this clinical impression. DeWys et al. focused on weight loss in a multiinstitutional, retrospective review of 3047 cancer patients and observed that loss of more than 5% of premorbid weight predicted an early demise [ 1 ]. This prognostic effect occurred independently of tumour stage, tumour histology and patient performance status. Weight loss was also associated with a trend towards lower chemotherapy response rates.

For a long time the use of testosterone-derivative drugs (nandrolone decanoate and others) has been indicated for patients with cancer anorexiacachexia syndrome (CACS) on the basis of a truly protein anabolic effect [ 1 ], but the above drugs have a limited use because of some severe sideeffects (liver damage, endocrine effects).

Over the past few years, many authors have approached the problem of the treatment of cancer cachexia focusing on either the knowledge of the main pathogenetic events, or the outcomes of the treatment in terms of symptoms or improvement in quality of life [ 1 ] [ 8 ]. The relevance of clinical investigations of cancer anorexia-cachexia has epidemiological and clinical roots, considering that it is very frequent in advanced and terminal disease (up to 40% of patients with advanced disease, and more than 80% of terminal patients), and that its clinical manifestations often represent a source of great concern for both patients and relatives [ 1 ] [ 5 ]. The clinical approach to cancer anorexia-cachexia has been directed towards different targets, and it can be aetiological, pathogenetic or symptomatic according to the attention paid to tumour growth, the main pathogenetic events, or the clinical behaviour of the syndrome. However, it is mandatory to define both the biological and clinical rationale of the different therapeutic options, and the outcomes of every therapeutic approach, using an evidence-based model.

Cyclo-oxygenase-2 (COX-2) is an enzyme catalysing the synthesis of prostaglandins (PGs) from arachidonic acid. Cells contain genes coding for two isoforms of COX (COX-1 and COX-2). COX-1 is expressed constitutively in most tissues and appears to be responsible for the production of PGs that mediate normal physiological functions, such as maintenance of the integrity of the gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is undetectable in most normal tissues: it is induced by cytokines, growth factors, oncogenes and tumour promoters, and it contributes to the synthesis of PGs in inflamed and neoplastic tissues [ 1 ]. COX-2 is induced in many human tumours and is associated with aberrant angiogenesis in a number of pathological settings, especially those involving inflammation. It has been well demonstrated that dysregulation of COX-2 expression correlates with development of gastrointestinal cancers.

Cachexia is characterised by accelerated loss of adipose tissue and skeletal muscle in the context of a chronic inflammatory response [ 1 ] [ 3 ]. It is a common complication of advanced cancer [ 4 ]. About half of all cancer patients suffer from this syndrome, which is among the most debilitating and life-threatening complications [ 5 ]. The key feature of this syndrome is weight loss, but other symptoms, such as anorexia, fatigue, vomiting and anaemia, and accelerated malnutrition with depletion of whole-body lipid and protein stores are frequently observed. Cancer cachexia contributes to immobility, a propensity to infection, shortened duration of survival, and overall decreased quality of life [ 6 ].

Cancer-related anorexia-cachexia syndrome (CACS) is a complex syndrome characterised by progressive weight loss with depletion of host reserves of skeletal muscle and, to a lesser extent, adipose tissue, anorexia, reduced food intake, poor performance status and quality of life that often precedes death [ 1 ]. At the time of diagnosis, 80% of patients with upper gastrointestinal cancers and 60% with lung cancer have already experienced substantial weight loss [ 2 ]. The prevalence of cachexia increases from 50 to > 80% before death and in > 20% cachexia is the main cause of death [ 2 ]. CACS results from the interaction of the host and the tumour. However, its nature is incompletely understood [ 3 ] [ 6 ], including the dynamics of host response (activation of systemic inflammatory response, metabolic, immune and neuroendocrine changes) and those tumour characteristics or tumour-derived products that influence expression of the syndrome (e.g. proteolysis-inducing factor, PIF).

Numerous studies have shown that weight loss is associated with an increase in mortality [ 1 ] [ 4 ]. Treating weight loss in the elderly can ameliorate many medical conditions. For example, rehabilitation time following post-hip fractures has been shown to decrease with nutritional supplementation [ 5 ]. In hospitalised geriatric patients, nutritional supplementation resulted in improvement in serum protein, nutritional status, and decreased mortality [ 6 ]. In a subset of geriatric inpatients, low serum albumin with weight loss predicts those patients at highest risk for dying during the subsequent 2 years [ 7 ]. Riquelme and Torres et al. [ 8 ] carried out a multivariate analysis of risk and prognostic factors in community-acquired pneumonia in the elderly and found that age by itself was not a significant factor related to prognosis. Among the significant risk factors, only nutritional status is amenable to medical intervention. In the cachectic elderly, medical, cognitive, and psychiatric disorders may diminish self-sufficiency in activities of daily living (ADL), thus reducing the quality of life and increasing the frequency of secondary procedures, hospitalisations, and need for skilled care [ 2 , 9 ].

Cachexia is defined as physical wasting with loss of muscle mass and weight that is caused by disease [ 1 ]. It is common for elderly individuals who have disease to exhibit cachexia.Additionally,muscle mass loss is characteristic of the conditions of frailty and sarcopenia. Sarcopenia is the age-related loss of muscle mass [ 2 ]. Physical frailty has been characterised by Fried et al. [ 3 ] as a condition that results from reduced strength, reduced gait velocity, reduced physical activity, weight loss, and exhaustion. Clearly, sarcopenia and frailty could be classified as cachectic conditions because they are associated with muscle mass loss. This chapter will describe the causes of sarcopenia, treatment of sarcopenia, causes of cachexia in elderly individuals, and treatment of cachexia in elderly individuals.

The causes of significant weight loss in older persons are: (1) anorexia/starvation, (2) sarcopenia, (3) cachexia, and (4) dehydration. Thus, the first step in management of weight loss is to make the diagnosis. Depression, which is the most common cause of weight loss in older persons [ 1 , 2 ], can be treated with antidepressants, which can also reverse weight loss, but monoamine oxidase inhibitors and mirtazapine (Remeron) appear to have specific orexigenic effects. The management of cachexia in older persons is extraordinarily complex, and involves both treatment of the underlying disease and specific nutritional therapy. Similarly, severe anorexia, often due to cytokine excess,must be treated.