Management of Oncologic Emergencies

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[edit] Management of Oncologic Emergencies

Ana Maria Lopez

Although patients with cancer often have chronic medical problems, oncologic emergencies arise as predictable complications of malignant primaries, metastases, or their treatments. The generalist is responsible for pursuing the signs and symptoms of these emergent problems, which if unrecognized, could result in patient morbidity and mortality.

[edit] METABOLIC EMERGENCIES

[edit] Hypercalcemia

[edit] Etiology.

Malignant hypercalcemia is the leading cause of hypercalcemia in hospital practice. The most common cause of hypercalcemia in the outpatient setting is hyperparathyroidism. Malignant hypercalcemia may be associated with solid tumors or hematologic diseases. The solid tumors most often associated with hypercalcemia are of squamous cell origin. Elevation in the calcium level is the most common life-threatening metabolic disorder associated with cancer, affecting 10% to 20% of all patients. Approximately 150 new cases per million people are diagnosed each year (Box 120-1).

[edit] Pathophysiology.

Malignant hypercalcemia may result from bone resorption secondary to skeletal invasion or from production of humoral factors, specifically parathyroid-like hormone. Elevated calcium levels impair the kidneys' ability to concentrate urine, resulting in further volume depletion.

[edit] Signs and Symptoms.

Clinical suspicion in recognizing the symptom complex is the first step in making the diagnosis of malignant hypercalcemia. The clinical findings in hypercalcemia have been well documented and range from constipation to obtundation and death. Rapid recognition of this symptom complex may be lifesaving (Box 120-2). Symptoms may occur at calcium levels lower than those noted with benign hypercalcemia, perhaps because of the more rapid rate of calcium elevation in malignant hypercalcemia.

[edit] Diagnosis.

Hypercalcemia is an elevation in unbound, ionized serum calcium concentration. Serum calcium levels measure total calcium values. Calcium is normally bound to albumin in the serum. Since many patients with underlying malignancies have low albumin levels because of poor nutrition and depletion of protein stores, a normal calcium level may actually represent hypercalcemia. The unbound calcium level may be calculated based on the albumin concentration as follows:

Corrected calcium (mg/dl) = Measured calcium (mg/dl)+0.8 mg/dl for each gram of measured albumin less than 4.5 gm/dl.

[edit] Treatment.

The goal of treatment is to improve the patient's quality of life. Hypercalcemia may be reversed by reducing or eliminating tumor burden, increasing renal clearance of calcium, and inhibiting osteoclastic bone resorption (Fig.120-1). Since most cases of malignant hypercalcemia occur late in the course of the disease, curative options are usually limited. The cornerstone of therapy is volume replacement with isotonic fluid. Rehydration alone is effective in 30% of cases. Furosemide may be added to promote calciuria but may increase dehydration. The response to fluids is usually not long lasting, since the underlying process has not been affected. Drug therapy is usually required to provide longer control.

Figure 120-1 Therapy for hypercalcemia.

Bisphosphonates inhibit osteoclastic function directly. Pamidronate is used in malignant hypercalcemia: 60 mg over 2 to 3 hours for calcium levels less than 13.5 mg/dl and 90 mg over 2 to 3 hours for calcium levels greater than 13.5 mg/dl. Patients may experience a febrile reaction. Phlebitis at the intravenous site is not uncommon. New agents in this class are being investigated and appear promising.

Other drugs that have been effective in hypercalcemia are calcitonin and mithramycin. Calcitonin is a potent inhibitor of bone resorption that acts within 12 to 24 hours. Although drug effects last approximately 72 hours, patients may quickly become refractory to the drug. Mithramycin is an antineoplastic antibiotic that possesses direct osteoclast inhibitory effects. The standard dose of mithramycin (25 μg/kg IV) usually leads to a decline in serum calcium levels in 6 to 48 hours. If no response is evident in 48 hours, the dose maybe repeated. Mithramycin has renal, hepatic, and bone marrow toxicities.

[edit] Syndrome of Inappropriate Antidiuretic Hormone

[edit] Etiology.

Syndrome of inappropriate antidiuretic hormone (SIADH) is a common cause of hyponatremia and is associated with a plethora of benign causes that must be considered before deciding that cancer is responsible. Pulmonary infections such as pneumonia, tuberculosis, and lung abscesses may produce SIADH. Abnormalities in the central nervous system may also result in SIADH. Medications such as opiates, thiazides, chlorpropamide, and the chemotherapeutic agents cyclophosphamide and vincristine may also contribute to SIADH.

[edit] Pathophysiology.

Malignancy-related SIADH is thought to result from tumor secretion of humoral factors with ADH-like activity. Vasopressin acts on the renal tubule to conserve water, resulting in dilutional hyponatremia. In a typical patient, water retention results in a weight gain of approximately 3 kg or roughly 10% of body water. Increased volume status promotes water and sodium losses despite a low serum sodium level. Natriuresis produces the characteristically elevated urinary sodium concentration coupled with serum hyponatremia.

[edit] Signs and Symptoms.

Clinical findings in SIADH are related to water intoxication. Initial drops in the serum sodium level cause the patient to complain of nausea, anorexia, fatigue, headache, and myalgia. When the serum sodium level drops below 120 mEq/L, increases in the total body water level result in brain swelling. At this level of hyponatremia an extensive range of neurologic symptoms are evident. Hyponatremia is a medical emergency that, if progressive and untreated, is uniformly fatal (Box 120-3).

[edit] Diagnosis.

Diagnostic evaluation of hyponatremia may be prompted by a sudden change in mental status or by the incidental finding of a low serum sodium level (less than 130 mEq/L). A careful physical examination and history, laboratory evaluation of renal function, and measurement of urinary and serum osmolality and sodium concentration allow the physician to determine the physiologic appropriateness of the patient's hyponatremia. An elevated urine osmolality (>120 mOsm/kg) associated with a decreased serum osmolality (<280 mOsm/kg) is consistent with a diagnosis of SIADH (Table 120-1).

Table 120-1 Diagnostic Criteria of SIADH

[edit] Treatment.

The goal of therapy is to restore serum osmolality to normal. If efforts to control the tumor with chemotherapy are instituted, care must be taken not to promote hyponatremia with the pretreatment hydration required by some chemotherapeutic regimens. In mild cases of hyponatremia, fluid restriction to 1000 ml per day may be sufficient to produce volume contraction with an approximate 2-to 3-kg weight loss, reverse sodium wasting, and correction of serum sodium.

If the patient is unable to comply with fluid restriction, demeclocycline may be used. Demeclocycline restores sodium homeostasis by interfering with the renal tubular effects of vasopressin. Demeclocycline's main side effect is azotemia. Hypersensitivity to the sun and decreased gastrointestinal absorption with antacids, milk, and vitamins may also occur. Demeclocycline at a daily dose of 600 mg may be used in two or four divided doses. Dosages should be reduced for patients with renal insufficiency. To correct severe hyponatremia (less than 120 mEq/L), serum sodium levels may be corrected slowly with normal or hypertonic saline. The latter may be necessary in life-threatening hyponatremia. Sodium replacement needs may be calculated as follows:

Sodium deficit (mEq/L)=125 mEq/L−(Measured serum sodium [mEq/L]×0.6 × body weight in kg)

The goal is to correct the serum sodium level to 125 mEq/L at a rate of 0.5 mEq/L per hour or 14 mEq per day to minimize the risk of central nervous system damage in the form of central pontine myelinolysis (CPM). CPM is characterized clinically by dysphagia, facial weakness, flaccid quadriplegia or paraplegia, and eventually coma resulting from demyelination in the pons (Fig. 120-2).

Figure 120-2 Treatment for SIADH associated with malignancy.

[edit] Tumor Lysis Syndrome

[edit] Etiology.

Tumor lysis syndrome occurs due to the effects of chemotherapy or rapid tumor growth, either of which may result in the rapid release of the products of cytolysis into the systemic circulation. This syndrome may lead to irreversible renal compromise and death.

[edit] Pathophysiology.

Patients with both solid tumors and hematopoietic malignancies are at risk for tumor lysis syndrome, particularly if the tumor burden is high or the tumor is in a stage of rapid cell division, in which sensitivity to chemotherapy is increased. The rapid release of the products of cytolysis into the systemic circulation leads to elevations in the levels of uric acid, potassium, and phosphate, all of which may contribute to renal failure.Hyperphosphatemia promotes hypocalcemia. The release of these intracellular metabolites occurs at a rate that exceeds the excretory capacity of the kidneys. Uric acid and phosphorus may precipitate in the renal tubules, impairing renal excretory function and causing further elevations in these metabolites. At particular risk is the patient who is dehydrated or who has baseline renal insufficiency.

[edit] Signs and Symptoms.

One of the earliest clinical signs of nephropathy related to uric acid elevation is oliguria. Signs and symptoms of uremia (nausea, vomiting, mental status depression, fluid overload), edema, and congestive heart failure may follow. High phosphate levels contribute to the nephropathy, and acidosis and anuria may develop.

Hyperkalemia and hypocalcemia primarily affect cardiac function. Dysrhythmias may be asymptomatic and seen only on the electrocardiogram (ECG). Hypocalcemia may result in complaints of muscle cramps, tetany, and seizures (Box 120-4).

[edit] Diagnosis.

In the oliguric cancer patient, tumor lysis syndrome should be considered when ultrasound evaluation of the kidneys rules out obstruction. Elevated uric acid levels and electrolyte abnormalities may be noted. Microscopic examination of the urine may reveal the precipitated uric acid crystals confirming the diagnosis of tumor lysis syndrome; however, their absence does not exclude the diagnosis.

[edit] Treatment.

Since tumor lysis syndrome is a common and predictable complication of certain malignancies, therapeutic intervention is primarily focused on prevention with hydration and the prophylactic use of allopurinol to impair the production of uric acid (Fig. 120-3). Normal saline rates, 100 to 150 ml per hour, are usually sufficient to produce a dilute urine. Allopurinol at oral dosages of 300 mg per day should be initiated 48 hours before the onset of chemotherapy, and continuation is advised until tumor lysis risk has passed. The dose of allopurinol should be adjusted for renal function. Electrolytes, renal function, and uric acid levels should be monitored daily to detect metabolic aberrations early. Furosemide may be used cautiously to aid with diuresis.

Figure 120-3 Treatment of tumor lysis syndrome.

Hemodialysis is considered when potassium levels are greater than 6 mEq/L, uric acid levels are greater than 10 mg/dl, or phosphate levels are greater than 10 mg/dl. These interventions have resulted in a significant decline in mortality resulting from tumor lysis.

[edit] CARDIAC EMERGENCIES

[edit] Superior Vena Cava Syndrome

[edit] Etiology.

The etiology of superior vena cava syndrome (SVCS) has changed since Ehrlich's review in 1934 (Table 120-2). At that time, 46% of the cases were associated with malignancies, 36% were due to aortic aneurysms, and 18% were due to infectious or other benign etiologies. Recent reviews have demonstrated that malignant causes account for 97% of the cases of SVCS, with most attributed to lung cancer or lymphoma.

Table 120-2 Etiology of SVCS

[edit] Pathophysiology.

The mass effect of a tumor or other space-occupying lesion may be a partial or complete obstruction of blood flow through the SVC to the right atrium, producing SVCS. The SVC is sensitive to mass effect because of its thin walls and low pressure.

[edit] Signs and Symptoms.

The most dramatic presentation of SVCS is a rapid progressive development of facial and upper body edema. Alternatively, clinical symptoms may develop slowly over the course of several weeks. The patient may complain of headache, nausea, dizziness, vision changes, hoarseness, cough, dysphagia, and syncope. Stridor and dyspnea, especially when the patient is supine, are associated with airway obstruction. Increased intracranial pressure and consequent cerebral edema result in nightmares, stupor, and seizures, but death is rarely attributed to SVCS.

Physical examination is often remarkable for neck vein distention, facial edema, and trunk and upper extremity swelling. Enlarged, dilated, cutaneous vessels in the anterior chest and upper abdomen provide evidence for collateral blood flow. Plethora and tachypnea may also be noted. In later stages, papilledema, lethargy, mental status changes, seizures, and coma may develop (Box 120-5).

[edit] Diagnosis.

The diagnosis of SVCS is based primarily on the patient's symptoms and the physical examination findings. Chest radiographs may reveal a superior mediastinal mass or hilar adenopathy. Computed tomography (CT) scan allows for visualization of the obstruction and evaluation of the extent of the disease.

SVCS usually arises as a subacute oncologic problem and not as a true emergency, since unrelieved obstruction is not life threatening except when tracheal obstruction is also present. In most previously undiagnosed cases, measures to determine the etiology of the mass lesion may be performed and serve as essential guides to therapy. Radiation therapy induces necrosis; therefore, when initiated before the diagnosis, it may impair diagnostic efforts.

[edit] Treatment.

Interim therapeutic measures such as elevation of the head, diuretics, and supplemental oxygen may be instituted for symptomatic relief. Dexamethasone may be used in patients with evidence of intracerebral edema. In patients with highly chemosensitive tumors, lymphoma, germ cell carcinoma, and small cell carcinoma of the lung, chemotherapy plays a significant role in treatment; however, in most patients, radiotherapy is the cornerstone of therapy. Balloon angioplasty and stent placement have been used to relieve the obstruction, but experience is limited (Fig. 120-4).

Figure 120-4 Treatment of superior vena cava syndrome.

[edit] Cardiac Tamponade

[edit] Etiology.

Cardiac tamponade is a life-threatening condition that, when recognized early, is treatable and often reversible. Tamponade occurs when fluid accumulates in the pericardial space and impairs adequate filling of the atria and ventricles. When caused by a malignant condition, this fluid contains malignant cells.

[edit] Pathophysiology.

The pericardial space normally contains approximately 20 ml of fluid maintained at a very low pressure. Malignant cells bring about changes in oncotic pressures that cause fluid to accumulate. Increased pericardial fluid increases the intrapericardial pressure, which may lead to hemodynamic compromise and collapse. The amount of pericardial fluid does not directly correlate with theintrapericardial pressure. Fluid that accumulates quickly may reach a hemodynamically significant pressure earlier than fluid that accumulates slowly and provides time for the heart to adapt to the hemodynamic changes.

[edit] Signs and Symptoms.

The patient's symptom complex is variable and may range from mild nausea and hiccups to cough, hoarseness, chest pressure, and dyspnea. Physical examination is often notable for tachycardia and high jugular venous pressures. Pulsus paradoxus is pathognomonic for tamponade. With frank tamponade bradycardia, low-output failure, shock, and death may occur (Box 120-6).

[edit] Diagnosis.

Once the diagnosis of cardiac tamponade is suspected clinically, a definitive evaluation must be pursued. The chest radiograph is often remarkable for a large, globular heart shadow. ECG may reveal sinus tachycardia, low voltage, and electrical alternans. Echocardiogram allows for the visualization of the pericardial fluid and the collapse of the atrial and ventricular walls caused by high intrapericardial pressure. Swan-Ganz pressure measurements characteristically reveal equalization of the right atrial, right ventricular, pulmonary artery, and pulmonary capillary wedge pressures (Box 120-7).

[edit] Treatment.

The goal of intervention is to decompress the heart with pericardiocentesis. The pericardial fluid may be serous, serosanguineous, or hemorrhagic. It may be distinguished from cardiac chamber blood because of its absence of clot formation and because its hematocrit is lower than that of venous blood. Once it is identified as pericardial fluid, a sample should be sent for culture, sensitivity, and cytologic testing. Potential complications of pericardiocentesis are laceration of the myocardium or coronary artery, hemorrhage, arrhythmia, and cardiac arrest.

If due to a malignant etiology, the fluid will reaccumulate without a more definitive intervention. An intrapericardial catheter may be placed in the pericardial space and left to drain. Sclerosis of the pericardial space may be successful. The significant chest discomfort often requires narcotic analgesia. Creation of a pericardial window is reserved for cases that are difficult to control. Whenever possible, treatment options should address the underlying malignancy (Fig. 120-5).

Figure 120-5 Management of malignant pericardial effusion producing cardiac tamponade.

[edit] HEMATOLOGIC EMERGENCIES

[edit] Disseminated Intravascular Coagulopathy

[edit] Etiology.

After infection and trauma, cancer is the third most common cause of disseminated intravascular coagulopathy (DIC). DIC is the principal coagulopathy encountered in cancer patients (Box 120-8). The most common malignant associations are melanoma; acute myelogenous leukemia (AML), especially the M3 promyelocytic subtype (APL); and mucin-producing adenocarcinomas such as those from the gastrointestinal tract, prostate, lung, and breast.

[edit] Pathophysiology.

DIC results from general activation of the coagulation system. The formation of small thrombi throughout the microvasculature results in the consumption of platelets and coagulation factors associated with thehemorrhagic phase of DIC. Procoagulants induce the thrombotic phase of DIC. Thrombotic events may produce ischemia and subsequent tissue damage.

[edit] Signs and Symptoms.

Patients may have hemorrhagic or thrombotic events. Any site of trauma such as a venipuncture site or surgical incision may demonstrate poor hemostasis associated with the depletion of coagulation factors and thrombocytopenia. Thrombotic complications are less common than hemorrhagic ones but may be seen if significant blood flow obstruction takes place. Cancer patients may be asymptomatic.

[edit] Diagnosis.

DIC is characterized by specific laboratory findings, including a prolonged prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) accompanied by evidence of clotting factor consumption with low fibrinogen levels, elevated fibrin split products, and thrombocytopenia. Examination of the peripheral smear may reveal schistocytes. In chronic DIC, laboratory abnormalities may be only minimally out of range (Box 120-9).

[edit] Treatment.

Once it is recognized, DIC should be urgently addressed to prevent potentially fatal complications (Fig. 120-6). When feasible, control of the underlying malignancy is essential; however, symptom control and subsequent prevention of recurrence often constitute the sole therapeutic option. Blood product support with platelets, packed red cells, cryoprecipitate, and fresh frozen plasma is frequently necessary. The use of heparin is controversial but is generally favored in conditions in which the thrombotic component predominates.

Figure 120-6 Therapeutic approach to DIC.

[edit] Migratory Thrombophlebitis: Trousseau's Syndrome

[edit] Etiology.

Various malignant conditions are thought to be associated with hypercoagulability and thrombosis and are clinically characterized primarily as a migratory superficial thrombophlebitis, although larger vessels also may be affected. Clinical thromboembolic disease has been estimated to occur in 10% of patients, although postmortem studies often reveal a higher incidence. On occasion a thrombotic event may be the harbinger of an underlying malignancy. The most common malignancies associated with increased thrombotic events are melanoma, lymphoma, leukemia, and carcinoma of the lung or gastrointestinal tract, etiologies similar to those that result in DIC. As in all patients, hypercoagulability is heightened in the postoperative period and with bed rest.

[edit] Pathophysiology.

The mechanism of migratory thrombophlebitis is not clearly understood and may precede detection of the underlying malignancy by several months. Normal hemostasis may be disrupted mechanically or biochemically by the presence of the tumor. Disseminated clotting may be triggered by the release of procoagulant substances from mucin-producing carcinomas. The role of other hypercoagulability risk factors such as advanced age and sedentary lifestyle also needs to be considered.

[edit] Signs and Symptoms.

The patient typically comes to the primary care physician with complaints of a swollen, erythematous, and tender extremity consistent with deep venous thrombosis or with evidence of superficial thrombophlebitis. Less commonly, symptoms of pulmonary embolus with dyspnea and acute-onset pleuritic chest pain occur and require urgent attention. The hallmark of this syndrome is its recurrent nature.

[edit] Diagnosis.

The usual diagnostic approach to superficial thrombophlebitis, deep venous thrombosis, and pulmonaryembolus should be pursued and is not reviewed here. Although the presence of a malignancy may predispose to hypercoagulability, a single thrombotic event does not mandate an extensive search for a malignancy. Recent investigation, however, reveals a higher incidence of subsequent carcinoma in patients who have idiopathic deep venous thrombosis or pulmonary embolism.

[edit] Treatment.

The therapeutic approach is not particular to cancer patients. The use of heparin quickly followed by oral anticoagulants is standard. Hypercoagulable cancer patients require anticoagulation for as long as the malignancy is active, which for many patients is the remainder of their life. For patients who are refractory to anticoagulation or in whom anticoagulation is contraindicated, a Greenfield filter may be surgically placed in the inferior vena cava (see Chapter 4 ).

[edit] NEUROLOGIC EMERGENCIES

[edit] Cord Compression

[edit] Etiology.

Since new onset back pain in a patient with a known malignancy may be secondary to cord compressions, prompt diagnosis and urgent intervention may prevent serious and permanent neurologic impairments and result in a marked improvement in the patient's quality of life. Nearly 20% of patients develop neurologic complications related to their underlying cancer. Spinal cord or cauda equina compression occurs in 5% to 10% of patients with cancer, affecting approximately 20,000 persons annually. An increased incidence of this oncologic complication appears to be related to the increased survival of patients with cancer (Box 120-10).

[edit] Pathophysiology.

The most common scenario for cord compression is the direct extension of a metastatic lesion from the vertebrae into the epidural space. Although metastatic lesions are more common, cord compression may be the initial presentation of the tumor. Half of the metastatic lesions are due to lung, breast, or prostate cancer. The most common site of compression is the thoracic spine (70%). The lumbar spine is affected 20% of the time, with the cervical spine affected in 10% of cases.

[edit] Signs and Symptoms.

About 95% of patients have new onset back pain, which is worse with movement and is accompanied by motor and sensory deficits that progressively move upward. In time, autonomic dysfunction may take place, with bladder and bowel incontinence. In contrast, back pain caused by degenerative joint disease is often improved with recumbency. It is not associated with progressive neurologic impairment and is most frequent in the cervical or lumbar spine.

Physical examination is remarkable for tenderness to percussion of the involved vertebrae, brisk deep tendon reflexes, and motor and sensory deficits. Sequential neurologic examinations may be used to clinically document the progression of the cord compression.

[edit] Diagnosis.

Clinical suspicion of cord compression is based on a thorough history and physical examination. In over half of cases the malignant lesion may be visualized on plain radiographs of the spine. Although better visualized on either a spinal myelogram or magnetic resonance imaging (MRI), MRI is noninvasive, has no radiation exposure, and carries no risk of allergic reaction to dye. Intramedullary disease may be visually enhanced with the use of gadolinium.

[edit] Treatment.

Untreated sensory loss produces progressive anesthesia; motor deficits result in paralysis and loss of sphincter control. The best prognostic markers regarding the potential effectiveness of treatment are the patient's physical findings and functional status at the time that therapy is instituted. The majority of patients who are ambulatory at the time of diagnosis are ambulatory at the completion of treatment. Approximately 20% of patients who are paraplegic at the onset of treatment are able to ambulate after treatment, but fewer than 10% of patients who begin treatment with paralysis are ambulatory at the end of treatment.

The goal of therapy is to decompress the spinal cord (Fig. 120-7). Traditionally, a bolus of 10 to 20 mg of dexamethasone given intravenously is followed by oral doses of 2 to 10 mg four times daily. Decompression with radiotherapy can then be pursued. Surgical decompression is considered if the lesion is not radiosensitive, progresses despite appropriate radiation doses, occurs in an area of prior radiation, or is the only site of disease and a tissue diagnosis has not been made. Definitive decompression efforts should be instituted as soon as possible after the diagnosis is made.

Figure 120-7 Management of spinal cord compression.

[edit] Intracerebral Metastases

[edit] Etiology.

Metastases to the brain are a frequent complication of bronchogenic carcinoma, lymphoma, melanoma, as well as other adenocarcinomas.

[edit] Pathophysiology.

As with any other mass lesion within the skull, the mass may produce edema and elevated intracranial pressure. Metastatic lesions are often multiple and less amenable to resection.

[edit] Signs and Symptoms.

Patients frequently visit the physician at the urging of family members who express concern regarding changes in mental status or personality. Focal neurologic deficits and new-onset seizures may also be noted. The clinical spectrum of increased intracranial pressure can range from headache and papilledema to loss of consciousness associated with frank herniation.

[edit] Diagnosis.

The neurologic symptoms described should lead the physician to obtain a thorough history and to perform a complete physical examination. The diagnosis of intracerebral metastases relies on a thorough evaluation of the symptoms, a thoughtful consideration of the differential diagnoses, and an imaging study to visualize the lesion. The greatest risk of a mass-producing lesion is increased intracranial pressure with potential uncal herniation, which carries a grave prognosis.

[edit] Treatment.

The initial treatment goal is to decrease the edema caused by the mass. This is accomplished with steroids as described in the management of spinal cord compression. Radiotherapy is the key therapeutic intervention for radiosensitive metastases. Because of their multiple nature, surgical resection of intracerebral metastases is usually not a therapeutic option.

End of life care and resources for supporting patients in the terminal phase of illness are presented in Chapters 9 and 164 .

[edit] ADDITIONAL READINGS

• TN Bryne: Spinal cord compression from epidural mets. N Engl J Med 1992; 327:614.
• SR Helms, MD Carlson: Cardiovascular emergencies. Semin Oncol 1989; 6:463.
• R Kamholtz, G Sze: Current imaging in spinal metastatic disease. Semin Oncol 1991; 18:158.
• AHG Paterson,et al.: Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 1993; 11:59.
• P Prandoni,et al.: Deep venous thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med 1992; 327:1128.
• OD Ratnoff: Hemostatic emergencies in malignancy. Semin Oncol 1989; 16:561.
• P Silverman, CW Distelhorst: Metabolic emergencies in clinical oncology. Semin Oncol 1989; 16:504.
• FR Singer: Treatment of hypercalcemia of malignancy with intravenous etidronate. Arch Intern Med 1991; 151:471.
• N Sundersan,et al.: Treatment of neoplastic spinal cord compression: results of a prospective study. Neurosurgery 1991; 29:645.
• RL Theriault: Hypercalcemia of malignancy: pathophysiology and implications for treatment. Oncology 1993; 7:47.
• HT Walpole,et al.: Superior vena cava syndrome treated by percutaneous transluminal balloon angioplasty. Am Heart J 1988; 115:1303.
• JKV Willson, TJ Masaryk: Neurologic emergencies in the cancer patient. Semin Oncol 1989; 16:490.