Nutrition and metabolic disorders are very frequent and are of great concern for the patient's family. Seeing a patient eating nothing is, for the family, a great source of suffering, synonymous to imminent death.
Cancer cachexia
Treatment of cachexia
Hypercalcaemia
Hyponatremia
Cachexia or general state alteration including major weight loss is the consequence of both anorexia and evolution of the cancer process. Various factors have been incriminated:Cancer cachexia:
The easiest way to measure cachexia is to weigh the patient although the weight loss may be masked by oedema or effusion (like ascites). A loss of 10% to 20% of normal weight can be observed in cancers of the stomach or the oesophagus. There is a clear correlation between the weight loss observed before treatment and poor cancer prognosis.
- diversion of the normal metabolism by the growing tumour,
- mass effect of the tumour itself as well as secretion of cytokines with a necrotic effect (see above),
- direct effect on the digestive tract (sub-occlusions, absorption disorders),
- previous poor alimentation or under nourishment due to alcoholism and smoking,
- liver metastases (poor metabolism of normal nutriments).
Severe under nourishment may be observed during complicated treatment (such as radiotherapy for head and neck cancers or poorly tolerated chemotherapy). These therapies may have to be temporarily stopped in order to take corrective measures (such as hyperalimentation by nutritive components or IV feeding).
Severe cachexia is frequently observed at the end of life. Major emaciation is due to the disappearance of all muscular and fat masses. The skin becomes very fragile like parchment, dentures become too big for the mouth, the patient becomes skeletal. In such a state of under nourishment, complications arise very quickly: a dry mouth further reduces feeding, the body support zones are the target of necrosis process (decubitus bedsore).
Biologically, such cachexia induces an increased metabolism of lipids and proteins, anaemia (without any clear aetiology), hypo-albuminemia (further inducing oedema), hyponatremia.
Treatment of anorexia :
The main goal of palliative care is to improve the patient's comfort.
Anorexia is an almost constant symptom during the terminal phase of cancer: it is a concern for family members who generally wish to see their patient eating correctly.
Many metabolic factors may promote anorexia during the terminal phase: among which, TNF secretion (Tumour Necrosis Factor) and various Interleukin factors. Moreover, anorexia is a sign of the chronic depression which is observed in most patients at the end of life. Finally, local organic causes will increase this anorexia: chronic constipation, mouth dryness, intracranial hypertension, chronic nausea (in relation to morphine treatment, metabolic abnormalities, analgesic radiotherapy, etc..).
Whereas the patient should be encouraged to eat some food, he/she should not be force-fed against his/her personal will and comfort. Certain carers are tempted to use parenteral nutrition very early on in disease progression: if such nutrition may be useful during acute treatment phases (during radiotherapy or intense chemotherapy, to prepare surgery), it has no place in the terminal phase, since it totally disregards the patient's liberty for only minimal benefit. Randomised studies have shown that parenteral nutrition does not increase patient survival and this aspect should be explained to families in order to calm their anxiety.
A few drugs may be useful. Progesterone derivatives such as megestrol at relatively high dosages (800 to 1,600 mg per day) may have a stimulatory effect on appetite.
Corticosteroids are to be largely employed for their numerous beneficial effects during terminal phase (particularly on appetite).
Practically, very simple therapeutic means may often be sufficient: fractionation of feeding into smaller, more frequent meals, taking care to respect patient taste (meat is not necessary!), treatment of permanent nausea, mouth care.
Anorexia is one symptom of terminal cancer: it should therefore be respected and explained to the patient's family. Giving precise information to family members on the futility of parenteral infusions may reassure them: a French by-word says that 'when appetite is OK everything is OK'. For families, a patient who does not eat, is never going to be cured. Unfortunately, this is the precise truth and one should learn to respect patient anorexia if it is well supported by the patient him/herself (the absence of ravenous hunger crises due to hypoglycaemia). Such respect will facilitate dialogue between the dying person and his/her family.
Hypercalcemia :
Hypercalcaemia is a common manifestation among cancer sufferers: 20 – 40 % of multiple myeloma, 35% of lung cancers, 24% of kidney cancers, 8-10% of breast cancer. Hypercalcaemia generally underlines the poor prognosis of cancer, although new therapies may offer longer patient survival.
Physiopathological mechanisms
There are two different circumstances, whether osteolytic lesions are present or not.If osteolytic lesions are present, then hypercalcaemia is generally a late phenomenon underlining poor prognosis. Hypercalcaemia induces symptoms that should be corrected with efficient palliative care.
Many hypercalcaemia appear without any osteolytic lesions and are therefore true paraneoplastic syndromes possibly due to several mechanisms:
There is no clear relationship between the presence of bone metastases and the elevation of serum calcium: some diffuse metastases, with major mechanical complications, never produce hypercalcaemia, whereas some very evolutive hypercalcaemia, difficult to reduce, have normal imaging even with gammagraphy and RMI.
- Production of proteins which bind to the parathormone receptor (PTH-like): in the tumour DNA, a gene expresses a polypeptide (PTH-RP or parathormone related protein) with 70% homology with normal parathormone. This gene is normally expressed in mammary tissue during lactation.
- Myeloma tumour cells produce a factor that stimulates osteoclasts (or OAF: Osteoclast Activating factor) which can be produced by in vitro stimulated normal leukocytes. OAF is one member of a larger family of factors called lymphokines, with lymphotoxine (produced by activated lymphocytes) and TNF (tumor necrosis factor or cachectine) produced by normal monocytes. Both factors stimulate osteoclasts.
- Several lymphoma, bone tumours or sarcoma can induce hypercalcaemia by transforming normal 25-hydroxy-vitamine D into 1,25 – dydroxy- vitamine D (the final active metabolite of vitamine D).
Symptoms
The main symptoms of hypercalcaemia are:Diagnosis is made by calcaemic dosage which should systematically be requested in the case of doubt.
- Anorexia, thirst, constipation or even occlusion,
- Consciousness disorders: fatigue, somnolence, lethargy, coma
- More or less intense dehydration, initially extra-cellular then intra-cellular.
Untreated hypercalcaemia leads to severe dehydration and possibly to patient death by cardiac rhythm disorders.
Biological diagnosis
Malignant hypercalcaemia is easy to distinguish from other forms of hypercalcaemia: generally blood phosphorus is normal or elevated (as opposed to hyperparathyroidism).Treatment
Several treatment modalities have been proposed depending on the clinical severity of hypercalcaemia.However, diphosphonates (in particular intravenous forms) have totally modified such modalities allowing ambulatory treatment over several weeks, with prolonged survival and good quality of life.
The only major point to ensure is correct patient rehydration, if necessary intravenously. Corticosteroids are still useful if hypercalcaemia is very high.
Hyponatremia:
Cancer patients frequently suffer from hyponatraemia, the physiopathology of which is not always clearly understood. Generally, it is fortuitously discovered on a systematic ionogram. However, hyponatraemia increases patient fatigue and can possibly be complicated by somnolence or seizures.
Hyponatraemia is often observed in preterminal stages of severe disease. Patients excrete the sodium excesses administered in order to correct hyponatraemia and liquid restriction leads to more severe dehydration than that already observed. Surprisingly, if patients are able to resume normal eating, a spontaneous correction of hyponatraemia is observed.
Thus, this preterminal hyponatraemia should be distinguished from an inappropriate secretion of ADH which is a genuine paraneoplastic syndrome (occurring in lung cancer for instance). Hyponatraemia leads to severe neurological disorders and to an exaggerated water excretion by the kidney (excessive urinary osmolality). In such cases, fluid restriction is useful, but more particularly the treatment of cancer, where possible, will improve the clinical situation.
Another frequent cause of hyponatraemia in cancer patients is the presence of oedema leading to a dilution syndrome. Such a clinical situation can be observed when ascitis or major pleural effusion occur. Whereas symptomatic treatment (ascitic puncture, diuretics) may be useful, only aetiological treatment will actually correct hyponatraemia for a reasonably long time.
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