CANCER CACHEXIA

31 May

It is important to remember, in considering neoplasia as defined in this book, that two entities are involved, the host and the neoplasm. Each is independent yet in many ways dependent on the other. The neoplasm is dependent on the host for its blood supply and other supporting tissues, and the host responds to the viability and the nutritional requirements  of the neoplasm in the maintenance of the internal milieu of the organism. Weiss (1976) pointed out that the host-tumor relation is quite analogous to the host-parasite relation, which is usually considered in infectious diseases. The tumor-bearing host is confronted with a population of living cells sufficiently inde- pendent of the host (relative autonomy) and sufficiently different at the molecular level to war- rant designation as parasitic. Yet the analogy of the neoplastic cell to an exogenous parasite is not altogether correct, because in this case the relation to the host is much more subtle, in that the parasitic element is derived from the host’s own tissues.

This relation between host and tumor is perhaps the major factor in the clinical symptom- atology seen in patients with cancer. According to the late Jesse Greenstein (1958), “The host- tumor relationship is the key to the cancer problem.” With the rapid advances in our knowledge of mechanisms in pathobiology, however, the problem of the host-tumor relation has been some- what deemphasized; yet it is as significant today as it has ever been.

CANCER  CACHEXIA

It is not unusual for humans and lower animals with advanced cancer to lose weight and to be- come emaciated even to the point that the host appears to die of starvation rather than as a result of any localized effects of the neoplasm.  In the initial growth phase, the neoplasm  may give evidence of host restraints. However, after the neoplasm reaches a substantial  size within the host, it often continues to grow, regardless of the nutritional and hormonal needs of the host. A neoplasm transplanted to mice that were fasted for 48 or 60 hours with interval 24-hour access to food showed a significant  decrease in growth (Pavelic′,  1982). In some experimental  animals, body growth ceases when the neoplasm  becomes  grossly demonstrable;  thereafter,  the body weight may remain essentially constant or decrease somewhat, while the neoplasm continues to increase in size and cell number. In animals this latter phase may be correlated with the involu- tion of the thymus (Ertl, 1972).

The sum of the changes noted above has been termed cachexia, which may also be seen as a similar symptomatology  in a number of disease states other than cancer, such as the acquired immunodeficiency  syndrome  (AIDS),  major trauma,  extensive  surgery,  malabsorption  syn- dromes, and severe sepsis (Tisdale, 1997). Cachexia differs from starvation, either self-induced (anorexia nervosa) or as the result of circumstances,  in that in the latter situations, especially during continued starvation, there is a much greater loss of adipose tissue than other compo- nents, while in cancer cachexia there is equal loss of both fat and muscle (Moley et al., 1987). Furthermore, in contrast to simple starvation, the changes in body composition seen in patients with cancer cachexia cannot be reversed by the provision of extra calories.

Cachexia has been defined by Costa (1963) as “the sum of those effects produced by neo- plasms in the host, which are not the immediate result of mechanical interference with recogniz- able structures.”  About 50% of all cancer patients exhibit the syndrome  of cancer cachexia, characterized  by loss of adipose tissue and skeletal muscle mass, weakness, anorexia (loss of appetite), depletion of host components such as lipid and protein, electrolyte and water abnor- malities, and a progressive fading of vital functions (cf. Tisdale, 1997, Table 17.1). Accompany- ing asthenia is a prevalence of fatigue, which may, in turn, be related to anemia, pain, nutritional deficiency, infection with fever, or depression (Groopman,  1998). In cancer patients receiving chemotherapy (Chapter 20), the prevalence of fatigue has been reported to range from 75 to 96% (cf. Stone et al., 1998). The degree of cachexia, however, is not correlated in any simple manner with caloric intake, tumor burden, tumor cell type, or anatomical site of involvement. Some indi- viduals with widespread neoplasms exhibit no clinically recognizable cachexia, whereas others with extremely  small neoplasms  may show characteristics  of this syndrome  (cf. Costa and Donaldson, 1980). For example, cachexia is relatively uncommon in patients with adenocarci- noma of the breast, while it is very common in other forms of adenocarcinoma, as of the lung or pancreas (MacDonald et al., 1995).

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