43 ONCOLOGIC EMERGENCIES
Harrison’s Manual of Medicine
Structural/Obstructive Oncologic Emergencies
Emergent Paraneoplastic Syndromes
Emergencies in the cancer pt may be classified into three categories: effects from tumor expansion, metabolic or hormonal effects mediated by tumor products, and treatment complications.
STRUCTURAL/OBSTRUCTIVE ONCOLOGIC EMERGENCIES
The most common problems are: superior vena cava syndrome; pericardial effusion/tamponade, spinal cord compression; seizures (Chap. 182) and/or increased intracranial pressure; and intestinal, urinary, or biliary obstruction. The last three conditions are discussed in Chap. 102 in HPIM-15.
SUPERIOR VENA CAVA SYNDROME Obstruction of the superior vena cava reduces venous return from the head, neck, and upper extremities. About 85% of cases are due to lung cancer; lymphoma and thrombosis of central venous catheters are also causes. Pts often present with facial swelling, dyspnea, and cough. In severe cases, the mediastinal mass lesion may cause tracheal obstruction. Dilated neck veins and increased collateral veins on anterior chest wall are noted on physical exam. CXR documents widening of the superior mediastinum; 25% of pts have a right-sided pleural effusion.
Radiation therapy is the treatment of choice for non-small cell lung cancer; addition of chemotherapy to radiation therapy is effective in small cell lung cancer and lymphoma. Clotted central catheters producing this syndrome should be withdrawn, and anticoagulation therapy initiated.
PERICARDIAL EFFUSION/TAMPONADE Accumulation of fluid in the pericardium impairs filling of the heart and decreases cardiac output. Most commonly seen in pts with lung or breast cancers, leukemias, or lymphomas, pericardial tamponade may also develop as a late complication of mediastinal radiation therapy. Common symptoms are dyspnea, cough, chest pain, orthopnea, and weakness. Pleural effusion, sinus tachycardia, jugular venous distention, hepatomegaly, and cyanosis are frequent physical findings. Paradoxical pulse, decreased heart sounds, pulsus alternans, and friction rub are less common with malignant than nonmalignant pericardial disease. Echocardiography is diagnostic; pericardiocentesis may show serous or bloody exudate, and cytology usually shows malignant cells.
Drainage of fluid from the pericardial sac may be lifesaving until a definitive surgical procedure can be performed.
SPINAL CORD COMPRESSION Primary spinal cord tumors occur rarely, and cord compression is most commonly due to epidural metastases from vertebral bodies involved with tumor, especially from prostate, lung, breast, lymphoma, and myeloma primaries. Pts present with back pain, worse when recumbent, with local tenderness. Loss of bowel and bladder control may occur. On physical exam, pts have a loss of sensation below a horizontal line on the trunk, called a sensory level, that usually corresponds to one or two vertebrae below the site of compression. Weakness and spasticity of the legs and hyperactive reflexes with upgoing toes on Babinski testing are often noted. Spine radiographs may reveal erosion of the pedicles (winking owl sign), lytic or sclerotic vertebral body lesions, and vertebral collapse. Collapse alone is not a reliable indicator of tumor; it is a common manifestation of a more common disease, osteoporosis. MRI can visualize the cord throughout its length and define the extent of tumor involvement.
Radiation therapy plus dexamethasone, 4 mg IV or PO q4h, is successful in arresting and reversing symptoms in about 75% of pts who are diagnosed while still ambulatory. Only 10% of pts made paraplegic by the tumor recover the ability to ambulate.
EMERGENT PARANEOPLASTIC SYNDROMES
Most paraneoplastic syndromes have an insidious onset (Chap. 75). Hypercalcemia, syndrome of inappropriate antidiuretic hormone (SIADH), and adrenal insufficiency may present as emergencies.
HYPERCALCEMIA The most common paraneoplastic syndrome, it occurs in about 10% of cancer pts, particularly those with lung, breast, head and neck, and kidney cancer and myeloma. Bone resorption mediated by parathormone-related protein is the most common mechanism; IL-1, IL-6, tumor necrosis factor, and transforming growth factor-b may act locally in tumor-involved bone. Pts usually present with nonspecific symptoms: fatigue, anorexia, constipation, weakness. Hypoalbuminemia associated with malignancy may make symptoms worse for any given serum calcium level because less calcium will be protein bound and more will be free.
Saline hydration, antiresorptive agents (such as pamidronate, 60–90 mg IV over 4 h), and glucocorticoids usually lower calcium levels significantly within 1–3 days. Treatment of the underlying malignancy is also important.
SIADH Induced by the action of arginine vasopressin produced by certain tumors (especially small cell cancer of the lung), SIADH is characterized by hyponatremia, inappropriately concentrated urine, and high urine sodium excretion in the absence of volume depletion. Most pts with SIADH are asymptomatic. When serum sodium falls to <115 meq/L, pts may experience anorexia, depression, lethargy, irritability, confusion, weakness, and personality changes.
Water restriction controls mild forms. Demeclocycline (900–1200 mg PO bid) inhibits the effects of vasopressin on the renal tubule. Treatment of the underlying malignancy is also important.
ADRENAL INSUFFICIENCY The infiltration of the adrenals by tumor and their destruction by hemorrhage are the two most common causes. Symptoms such as nausea, vomiting, anorexia, and orthostatic hypotension may be attributed to progressive cancer or to treatment side effects. Certain treatments (e.g., ketoconazole, aminoglutethimide) may directly interfere with steroid synthesis in the adrenal.
In emergencies, a bolus of 100 mg IV hydrocortisone is followed by a continuous infusion of 10 mg/h. In nonemergent but stressful circumstances, 100–200 mg/d oral hydrocortisone is the beginning dose, tapered to maintenance of 15–37.5 mg/d. Fludrocortisone (0.1 mg/d) may be required in the presence of hyperkalemia.
Complications from treatment may occur acutely or emerge only many years after treatment. Toxicity may be related either to the agents used to treat the cancer or from the response of the cancer to the treatment (e.g., leaving a perforation in a hollow viscus or causing metabolic complications such as the tumor lysis syndrome). Several treatment complications present as emergencies. Fever and neutropenia and tumor lysis syndrome will be discussed here; others are discussed in Chap. 102 in HPIM-15.
FEVER AND NEUTROPENIA Many cancer pts are treated with myelotoxic agents. When peripheral blood granulocyte counts are <1000/µL, the risk of infection is substantially increased (48 infections/100 pts). A neutropenic pt who develops a fever (>38°C) should undergo physical exam with special attention to skin lesions, mucous membranes, IV catheter sites, and perirectal area. Two sets of blood cultures from different sites should be drawn, and a CXR performed, and any additional tests should be guided by findings from the history and physical exam. Any fluid collections should be tapped, and urine and/or fluids should be examined under the microscope for evidence of infection.
After cultures are obtained, all pts should receive IV broad-spectrum antibiotics (e.g., ceftazidime 1 g q8h). If an obvious infectious site is found, the antibiotic regimen is designed to cover organisms that may cause the infection. Usually therapy should be started with an agent or agents that cover both gram-positive and -negative organisms. If the fever resolves, treatment should continue until neutropenia resolves. If the pt remains febrile and neutropenic after 7 days, amphotericin B should be added to the antibiotic regimen.
TUMOR LYSIS SYNDROME When rapidly growing tumors are treated with effective chemotherapy regimens, the rapid destruction of tumor cells can lead to the release of large amounts of nucleic acid breakdown products (chiefly uric acid), potassium, phosphate, and lactic acid. The phosphate elevations can lead to hypocalcemia. The increased uric acid, especially in the setting of acidosis, can precipitate in the renal tubules and lead to renal failure. The renal failure can exacerbate the hyperkalemia.
Prevention is the best approach. Maintain hydration with 3 L/d of saline, keep urine pH > 7.0 with bicarbonate administration, and start allopurinol 300 mg/m2 per day 24 h before starting chemotherapy. Once chemotherapy is given, monitor serum electrolytes every 6 h. If serum potassium is > 6.0 meq/L and renal failure ensues, hemodialysis may be required. Maintain normal calcium levels.
For a more detailed discussion, see Finberg R: Infections in Patients with Cancer, Chap. 85, p. 547; and Gucalp R, Dutcher J: Oncologic Emergencies, Chap. 102, p. 642 in HPIM-15.