Medical complications of malignant disease.docx

Medical complications of malignant disease Robert Coleman Cancer can cause a huge variety of medical and metabolic problems. These can be due to the physical presence of the tumour causing obstruction of, for example, the bile duct or a ureter, secretion of fluid into a body cavity such as the pleur...

Medical complications of malignant disease Robert Coleman Cancer can cause a huge variety of medical and metabolic problems. These can be due to the physical presence of the tumour causing obstruction of, for example, the bile duct or a ureter, secretion of fluid into a body cavity such as the pleura (an effusion) or local invasion of adjacent structures. In addition, can- cers frequently predispose the patient to infection and may cause constitutional disturbances which are not due to the local effect of the tumour but are collective- ly known as paraneoplastic syndromes. The problems of invasion into neighbouring structures are discussed in Chapter 17. In this chapter we discuss the problems caused by effusions, infection and paraneoplastic syndromes (Table 38.1) in malignancy. EFFUSIONS SECONDARY TO MALIGNANT DISEASE Normally, the pleural, pericardial and peritoneal spaces contain only a few millilitres of fluid to lubri- cate the inner and outer surfaces. However, in cancer the normal capillary and lymphatic vessels can become damaged and the hydrostatic pressures which regulate the transfer of fluid from one compartment of the body to another are disturbed. A build-up of fluid at any of these three sites can cause unpleasant symp- toms which require treatment. Although effusions are usually a sign of advanced malignancy and treatment is only palliative, intervention is worthwhile and can provide useful benefit and improvement in quality of life. Pleural effusions The commonest malignancy to cause a pleural effusion is carcinoma of the bronchus. In addition, metastasis from carcinoma of the breast, other adenocarcinomas and lymphoma may also quite frequently cause pleural 648 MEDICAL COMPLICATIONS OF MALIGNANT DISEASE 649 Table 38.1 Endocrine and paraneoplastic manifestations of malignancy a System Endocrine Neurological Haematological/vascular Musculoskeletal Dermatological Renal Manifestation Hypercalcaemia due to parathyroid hormone related peptide Water retention due to inappropriate ADH secretion Cushing's syndrome due to ACTH Hypoglycaemia due to insulin-like proteins/somatomedins Gynaecomastia due to human chorionic gonadotrophin Thyrotoxicosis due to human chorionic gonadotrophin Peripheral neuropathy Cerebellar ataxia Dementia Transverse myelitis Myasthenia gravis Eaton---Lambert syndrome Anaemia Polycythaemia Thrombophlebitis Red cell aplasia Thromboembolism Disseminated intravascular coagulation Non-bacterial endocarditis Polymyalgia rheumatica Arthralgia Clubbing Hypertrophic pulmonary osteoarthropathy Pruritus Various skin rashes Nephrotic syndrome effusions. Clinical detection is not possible until at least 500 ml has accumulated, and typically the effusion comprises 1000-4000 ml of fluid. This is usually straw coloured but may be blood-stained and will cause increasing shortness of breath, a dry cough and some- times pain as it increases in size. Drainage of the fluid is required for relief of symp- toms. This can be performed through a needle insert- ed into the pleural space, which provides good emergency management, but, to prevent recurrence of the effusion, either effective treatment of the underly- ing cancer is required or the effusion must be drained to dryness. To achieve this, a flexible drainage tube needs to be inserted into the pleural space and the fluid allowed to drain via a sealed drainage system which prevents air from replacing the fluid. Drainage should be relatively slow as sudden removal of large volumes of fluid causes distress to the patient due to shift of the mediastinal structures, and this may also precipitate pulmonary oedema. After 2448 hours, when the effusion has drained to dryness, it is usual to inject a drug or chemical into the pleural space to effect a pleurodesis. This will inflame the pleural surfaces to encourage sticking together of the two layers and the development of fibrosis. Tetracycline and bleomycin are the most commonly used agents and will prevent recurrence of the effusion in 50-75% of patients. If recurrent effusions remain a problem after this approach, referral to to a thoracic surgeon may be worthwhile drain the fluid under general anaesthetic and insufflate talcum powder, a more effective method of achieving a pleurodesis. Pericardial effusions Pericardial effusions are much less common than pleu- ral effusions. Again the same tumour types are usual- ly responsible but probably less than 1% of cancer patients will develop a symptomatic collection of peri- cardial fluid. When this does occur the build-up of fluid restricts normal cardiac function and produces symptoms and signs of cardiac failure, first affecting the right ventricle, which as it worsens subsequently impairs left ventricular function, a condition known as cardiac tamponade. Patients with tamponade are unable to lie flat, have chest discomfort, oedema and breathlessness. When cardiac tamponade develops, urgent drainage of the the pericardial fluid can be life-saving and is indicated if patient is otherwise in reasonable health. 650 RADIOTHERAPY AND ONCOLOGY Pericardial drainage is technically more difficult than pleural drainage and is best performed by a cardiolo- gist with ultrasound control to ensure safe placement of the drainage catheter. Treatment of the underlying malignancy will usually prevent recurrence but, if this is not possible, injection of sclerosants into the pericar- dial space is occasionally advised. However, to pre- vent recurrent pericardial effusions, the formation of a pericardial window by a thoracic surgeon is preferred if the general condition of the patient makes this a real- istic option. Peritoneal effusions (ascites) In cancer, ascites is usually caused by widespread peri- toneal seedling metastases which exude protein-rich fluid. Liver metastases may contribute to the problem through hypoalbuminaemia or portal hypertension. Ascites is most commonly caused by advanced carcin- omas of the ovary, gastrointestinal tract, breast and pancreas. Patients present with abdominal distension which becomes progressively uncomfortable, limits food intake and splints the diaphragm, making breath- ing difficult. Diagnosis is by clinical examination and is confirmed by ultrasound and aspiration cytology. Treatment is by tube drainage (paracentesis) and should be performed relatively slowly, generally not exceeding a rate of 500 ml/hour. Drainage to dryness is not realistic and therefore sclerosants are less effec- tive for ascites than for pleural effusions. Diuretics are commonly prescribed to prevent reaccumulation but are rarely effective in relieving established ascites. Intraperitoneal radioactive colloids or chemotherapy are sometimes of benefit and agents such as thiotepa, mitoxantrone (mitozantrone) and carboplatin have been used with some success. For recurrent ascites, surgical procedures should be considered if medical treatments have failed to control the underlying dis- ease. A peritoneovenous shunt can be inserted, which drains the fluid through a one-way valve into the venous system. Interestingly, despite drainage of large numbers of malignant cells into the circulation, metastatic disease in the lungs and other sites do not appear to be more common. METABOLIC AND ENDOCRINE MANIFESTATIONS OF MALIGNANCY i ypercalcaemia F spercalcaemia is a complication in around 5% of p tients with advanced malignancy, and is particular- ly common in patients with carcinomas of the breast, lung and multiple myeloma. Three mechanisms are involved. Firstly, metastatic cancer cells in bone stimu- late osteoclasts, the normal bone cells which break down bone, to destroy bone faster than the osteoblasts, the normal bone cells which build bone, can repair the damage. Secondly, the tumour may secrete proteins into the circulation which have similar destructive effects on bone but also promote the kidney to reab- sorb more calcium from the urine than is appropriate. Finally, dehydration or damage to the kidney, as com- monly occurs in multiple myeloma, can be important. Hypercalcaemia causes many symptoms including lethargy, nausea, thirst, constipation and drowsiness. Because the symptoms are non-specific and common- ly encountered in many patients with advanced can- cer, the diagnosis can be easily missed. Treatment, however, will rapidly improve the patient's condition and relieve the unpleasant symptoms. This can be reli- ably achieved without side-effects by rehydration of the patient and inhibition of bone breakdown by one of the class of drugs called bisphosphonates. A single short infusion of one of the potent bisphosphonates that are now available will restore the serum calcium to normal in around 90% of patients. Inappropriate secretion of antidiuretic hormone (ADH) This syndrome results in retention of fluid by the kidney and is characterised by a low serum sodium. This causes weakness and confusion, occurring most commonly in patients with small cell lung cancer. Treatment is by fluid restriction, drugs such as deme- clocycline which inhibit the action of ADH, and chemotherapy for the underlying malignancy. Other endocrine manifestations of malignancy Many cancers produce hormones and peptides with biological activity. These include ACTH, which may result in the features of Cushing's syndrome, hypogly- caemia from production of insulin-like substances and gynaecomastia from tumour production of human chorionic gonadotrophin (HCG). Hyperuricaemia and tumour lysis syndrome An acute metabolic disturbance may result from the rapid destruction of a tumour following chemother- apy. This is particularly likely to occur in childhood MEDICAL COMPLICATIONS OF MALIGNANT DISEASE 651 leukaemia and rapidly growing lymphomas. As chemotherapy kills the cancer, the cells release prod- ucts of nitrogen metabolism, especially urea and urate, plus large amounts of potassium and phosphate into the circulation. The high urate concentration may result in urate crystal formation in the kidneys and lead to acute renal failure. High potassium levels can cause cardiac dysrhythmias, and increased phosphate may cause tetany. The syndrome can be prevented by prescribing allopurinol to prevent the production of large amounts of urate and intravenous fluids to encourage the kidneys to excrete the products of cell breakdown. INFECTION Infections are a major cause of death in cancer. Not only do they occur frequently but they are often more severe than in other patients, less responsive to ther- apy and sometimes are produced by organisms which in normal health would not cause any problem. The susceptibility of cancer patients to infection results from suppression of host defence mechanisms pro- duced by the disease and its treatment. Infections are particularly frequent when the neutrophil count is suppressed by chemotherapy. Advanced cancer and the treatments prescribed are associated with impaired neutrophil and lymphocyte function, depressed cell-mediated and humoral immu- nity, and damage to skin and mucous membranes which allows organisms to enter the bloodstream more easily. Escherischia coli, pseudomonas, staphylo- cocci and streptococci are the most frequent bacterial pathogens. Viruses such as herpes simplex and zoster (shingles), fungi, particularly candida, and protozoal infection of the lungs with pneumocystis are impor- tant non-bacterial causes of infection requiring specif- ic treatment. Most of the infecting organisms come from within the patient, for example gut bacteria, and, providing sensible precautions are taken, infections transmitted from family or health care staff are of rela- tively minor importance. If patients are infected while neutropenic, urgent admission to hospital and treatment with broad-spec- trum intravenous antibiotics are required, as untreated septicaemia can be rapidly fatal. Occasionally, even in specialist cancer centres and despite efficient and aggres- sive treatment of infection, patients still die from over- whelming infection following chemotherapy. PARANEOPLASTIC SYNDROMES Neurological Cancers, particularly of the bronchus, are associated with a number of neurological syndromes which are unrelated to direct compression or infiltration of neural tissue. The mechanisms which give rise to these problems are poorly understood. They are uncommon and usually are possible to diagnose only by excluding the presence of malignant disease in the central nerv- ous system or around nerve roots. The syndromes include numbness and weakness due to sensory and motor peripheral neuropathies respectively, paralysis from spinal cord damage, unsteadiness from cerebel- lar degeneration, dementia from cerebral damage and a form of muscle weakness which resembles myasthe- nia gravis. These neurological conditions may be the first manifestation of cancer. Sadly, treatment for the underlying cancer frequently fails to produce much neurological improvement. Hypertrophic pulmonary osteoarthropathy Lung cancer is the principal cause of this condition in which the bones of the forearms and shins become inflamed and painful. Plain radiographs show charac- teristic appearances and usually the patient has a deformity of the nails known as clubbing. Anti-inflam- matory drugs relieve many of the symptoms and the condition may improve if the underlying tumour can be removed or destroyed. Other paraneoplastic syndromes A variety of general effects of cancer are sometimes described as paraneoplastic phenomena, and almost every organ in the body can be affected by one of these syndromes. Fever, cachexia and anaemia are relatively common and may be the presenting symptoms of malig- nancy. In addition, thrombophlebitis and \_ clotting disorders, arthritis, skin rashes, itching, muscle inflam- mation and renal impairment are uncommon but well- recognised complications of malignant disease.