INTRODUCTION
True oncologic emergencies are relatively infrequent. However, physicians who treat cancer patients are often called on to rule out an oncologic emergency. To diagnose and appropriately treat an oncologic emergency, physicians must have a working knowledge of the distinct presentation, appropriate diagnostic testing, and management of a wide array of complications that are often unique to cancer patients. These complications primarily result from pressure or obstruction by space-occupying lesions, metabolic abnormalities, or cytopenias.
MALIGNANT PERICARDIAL EFFUSION AND TAMPONADE
GENERAL PRINCIPLES
Malignancy is a frequent cause of pericardial disease including pericardial effusion, cardiac tamponade, and constrictive pericarditis. An autopsy series of 3314 patients found that cardiac metastases occur in 10% of patients dying of cancer.1 However, many of these cases were not clinically significant. Malignant pericardial disease is generally a manifestation of an advanced malignancy.
The most common malignancies associated with pericardial involvement are lung cancer, breast cancer, and lymphoma.
Pathophysiology
Breast and lung tumors generally spread locally to cause pericardial disease. Lymphomas involving the mediastinum can involve the pericardium, whereas leukemias can infiltrate the myocardium, resulting in a pericardial effusion. Tumors in the pericardial space can cause bleeding and create a more rapidly accumulating effusion than in an exudative or transudative process. Patients with acute promyelocytic leukemia treated with all-trans retinoic acid can develop a treatment-related pericardial effusion.
DIAGNOSIS
Clinical Presentation
Patients with small, slowly expanding effusions may present with subtle nonspecific complaints such as weakness, fatigue, and dyspnea. If a large effusion accumulates rapidly, patients can develop cardiac tamponade and hemodynamic collapse.
On evaluation, patients with tamponade exhibit signs of hypotension, tachycardia, jugular venous distention, and dulled heart tones. Another sign indicative of tamponade is pulsus paradoxus. The difference in systolic pressures at which the Korotkoff sounds are heard between inspiration and expiration quantifies the pulsus paradoxus, which is normally no more than 10 mm Hg. Classically, Ewart’s sign (dullness at the left infrascapular area due to bronchial compression by a large effusion) may be seen, but it is rarely observed in practice.2
Differential Diagnosis
The differential diagnosis of pericardial disease in a patient with malignancy also includes nonmalignant causes, such as radiation-induced effusion, hypothyroidism, autoimmune disorders, infection, drug induced, uremia, and idiopathic pericardial disease.
Other pathologic entities may present with similar symptoms in the cancer patient.
Cardiotoxicity leading to congestive heart failure can result from chemo-therapy (such as anthracyclines, mitoxantrone, ifosfamide, and cyclophosphamide) or biologics (such as the monoclonal antibody trastuzumab). 5-Fluorouracil (5-FU), a commonly used antimetabolite, is associated with acute cardiotoxicity that can lead to cardiac arrhythmia, myocardial ischemia, and, rarely, cardiogenic shock. Radiation therapy can also cause cardiomyopathy in the absence of pericardial disease (especially in the setting of mediastinal radiation for non-Hodgkin or Hodgkin lymphoma and left breast radiation for breast cancer). One must always consider other causes of cardiovascular emergencies in the cancer patient, such as coronary artery disease, heart failure, and infectious endocarditis.
Diagnostic Testing
Patients with suspected pericardial disease should have an immediate chest radiograph and electrocardiogram (ECG).
On chest x-ray, in the presence of a large effusion, the cardiac silhouette is enlarged in a globular, symmetric fashion. Chest x-ray may also reveal signs of pulmonary congestion and/or pleural effusions.
ECG commonly shows sinus tachycardia and may reveal reduced voltage or, with very large effusions, electrical alternans.
Transthoracic echocardiography is the diagnostic test of choice and should be ordered emergently whenever the diagnosis of tamponade is suspected. It will diagnose the effusion and indicate the degree of hemodynamic compromise. Early signs of tamponade on echo include right atrial and ventricular collapse.
CT scan is also sensitive for diagnosing an effusion. It can detect as little as 50 mL of pericardial fluid and, similar to an echocardiogram, can give an idea of intracardiac masses.
MRI also can provide direct imaging of the pericardium. Both of these tests can give some clues as to the nature of the fluid (bloody, serous, chylous), but they rarely provide clinically useful information.
TREATMENT
With severe hemodynamic compromise, emergent pericardiocentesis by a percutaneous, subxiphoid approach should be performed. Giving a rapid IV fluid bolus and inotropics can be temporizing measures to support the patient until echocardiographic guidance is available.
Complications with “blind” approach include ventricular perforation, arrhythmias, and pneumothoraxes, and range from 5% to 20%. Complications are less likely (about 2%) when echocardiography is used to delineate the size and location of the fluid with respect to normal cardiac structures.3
A pericardial drain or a pericardial window may be necessary. To prevent recurrence, sclerosing agents such as thiotepa are available but are often less effective and have more risks than placing a surgical pericardial window. A surgical pericardial window is generally the definitive treatment for a clinically significant pericardial effusion.
Radiation therapy can be used to manage pericardial effusions secondary to radiosensitive tumors, such as leukemia and lymphoma. Small asymptomatic effusions may be observed without therapy.
SUPERIOR VENA CAVA SYNDROME
GENERAL PRINCIPLES
Definition
Superior vena cava syndrome (SVCS) is the result of obstruction of the SVC, by either external compression or internal thrombosis.
Etiology
Lung cancer (non-small-cell lung cancer followed by small-cell lung cancer) and lymphoma are the most common causes (~85%), although SVCS has been reported in breast cancer and other malignancies of the chest as well. 4 These less common malignancies of the chest include germ cell tumors, thymoma, and mesothelioma.
Thrombosis of the SVC in patients with central venous catheters is an increasingly common cause of SVCS. Other nonmalignant causes of SVCS include granulomatous infections, goiter, aortic aneurysms, and fibrosing mediastinitis.
DIAGNOSIS
Clinical Presentation
Patients typically present with swelling of the neck, face, and upper extremities. Jugular venous distention, cyanosis, and facial plethora may also be present.
Shortness of breath, dizziness, and rarely obtundation from cerebral edema are possible if the onset is rapid. Very rarely, the process causes laryngeal edema and compromise of the upper airway.
Vocal cord paralysis and Horner syndrome are also possible if neural structures are invaded. With slowly progressive obstruction, collateral flow has time to develop, and symptoms related to vascular obstruction may be subtle.
Diagnostic Testing
Chest radiography may show a widened superior mediastinum and pleural effusions.
CT scan of the chest with IV contrast is the diagnostic test of choice. CT findings are notable for reduced or absent opacification of central venous structures with prominent collateral venous circulation. There is no advantage of MRI over CT.
A diagnosis of the mass should be attempted before treatment is begun if the tissue type of tumor is unknown. Sputum cytology, biopsy of lymph nodes, bronchoscopy, thoracentesis (if a pleural effusion is present), mediastinoscopy, or thoracotomy can be diagnostic. The workup generally progresses first through less invasive diagnostic testing (e.g., sputum cytology) before more invasive tests are performed (e.g., mediastinoscopy).
TREATMENT
Supportive measures including a low-salt diet, head elevation, and oxygen can be temporizing.
Diuretics and corticosteroids (e.g., dexamethasone, 4 mg IV every 6 hours) have traditionally been used for treatment at presentation. Although corticosteroids are likely only helpful in SVCS caused by lymphoma, diuretics have not been shown to be helpful at all. If compression is not life-threatening, then a tissue diagnosis should be made before beginning treatment.
Radiation therapy is useful for non-small-cell lung carcinoma and other metastatic solid tumors. 5
Chemotherapy is more useful in small-cell lung cancer and lymphoma owing to their exquisite chemosensitivity, but small trials suggest that chemotherapy may be as effective as radiation therapy in treating SVCS secondary to non-small-cell lung cancer, which is relatively chemoinsensitive.
SVCS resulting from catheter-related thrombus is treated by anticoagulation and, in limited cases, fibrinolysis. For emergent cases in which a prompt response is needed, experienced centers can perform angioplasty and stent placement. These approaches have largely replaced open surgical intervention, which is now generally done only when the surgical resection of the tumor is of benefit.
PROGNOSIS
Multiple studies suggest that patients with SVCS do not have shortened survival compared to similarly staged patients with the same underlying malignancy and no history of SVCS.
ACUTE TUMOR LYSIS SYNDROME
GENERAL PRINCIPLES
Acute tumor lysis syndrome (ATLS) represents a myriad of metabolic and electrolyte abnormalities that results from the release of intracellular products by rapidly dividing tumor cells prior to therapy or from the lysis of sensitive tumor cells during therapy. ATLS usually occurs in the setting of therapy of rapidly growing, hematologic malignancies, classically acute lymphoblastic leukemia and high-grade non-Hodgkin lymphoma (e.g., Burkitt lymphoma). Rarely, ATLS has been described after the treatment of solid tumors such as breast cancer. The size of the tumor, rate of tumor growth, and sensitivity of the tumor cells to chemotherapy determine the risk of development of ATLS (Table 35-1).
DIAGNOSIS
Clinical Presentation
ATLS is characterized by the following electrolyte derangements: hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte abnormalities place patients at risk for cardiac arrhythmias and seizures. Acute renal failure and uremia can develop from precipitation of uric acid and calcium phosphate crystals in the renal tubules(Table 35-2).
TREATMENT
The best management of ATLS includes identifying patients at risk for ATLS and taking preventive measures.
IV hydration should occur 24 to 48 hours before initiation of chemotherapy (3 L/m 2/d) and during therapy. Consider using IV furosemide (Lasix) to improve urine flow rate if it is <100mL/m2/d. Electrolytes including phosphorus, calcium, and magnesium; uric acid; blood urea nitrogen; and creatinine should be measured three times a day in patients at risk for ATLS.
Hyperkalemia should be treated with standard therapy: glucose and insulin (acutely), sodium–potassium exchange resins (Kayexalate), and IV calcium if ECG changes are noted.
Hyperuricemia can be controlled with allopurinol (maximum 800 mg/d PO or 600 mg/d IV in adults) and/or rasburicase. Uric acid is relatively insoluble and can precipitate in renal tubules, causing acute renal failure. Allopurinol decreases the production of uric acid by inhibiting the enzyme, xanthine oxidase, which converts xanthine and hypoxanthine to uric acid. Allopurinol must be dose-reduced in patients with renal failure. Also, allopurinol inhibits the degradation of 6-mercaptopurine and azathioprine so these drugs must be dose-reduced if the patient is taking allopurinol. Allopurinol does not decrease the amount of uric acid already present. Thus, one must initiate allopurinol before chemotherapy in patients with preexisting hyperuricemia or in those at high risk for ATLS.
Rasburicase is a recombinant form of the enzyme, urate oxidase, which is derived from yeast and not found in humans. Urate oxidase breaks down uric acid to form allantoin. Allantoin is much more soluble in the urine than uric acid and can thus be renally excreted. Rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency, as it can cause hemolysis. Other side effects of rasburicase include methemoglobinemia, bronchospasm, and anaphylaxis. The dosing of rasburicase is still not defined, but many institutions use 0.15 to 0.2 mg/kg for one dose and repeat doses only if hyperuricemia is still present. 6 Rasburicase has not yet been rigorously tested in randomized, controlled trials in adults; however, case reports and pediatric data have demonstrated its efficacy. Rasburicase is now generally the standard of care for pediatric and adult patients with ATLS, while allopurinol remains the standard prophylactic therapy.
Alkalinization of the urine to increase uric acid excretion can also be considered in the treatment of hyperuricemia. However, there is no clear evidence that it improves outcomes.
IV calcium should not be administered for hypocalcemia unless the patient is symptomatic or hyperphosphatemia is corrected. Symptoms of hypocalcemia include muscular (cramps, spasms, and tetany), cardiac (arrhythmias and hypotension), and neurologic (confusion or seizures) abnormalities. A positive Chvostek or Trousseau sign is indicative of symptomatic hypokalemia. With a high serum phosphate level, IV calcium repletion may result in metastatic calcification and renal failure.
In the setting of hyperphosphatemia, mild cases may be managed with PO antacids (phosphate binders), but dialysis may be necessary in patients with poor renal function or metabolic abnormalities not corrected by conservative measures.
HYPERCALCEMIA OF MALIGNANCY
GENERAL PRINCIPLES
Hypercalcemia is the most common paraneoplastic syndrome, seen in 10% to 20% of patients with cancer. Malignancies of the lung, breast, head/neck, and kidney, as well as multiple myeloma, are most often associated with hypercalcemia. 7
Etiology
Most commonly, a tumor causes hypercalcemia by producing ectopic parathormone-related protein (PTHrP), which stimulates osteoclasts to cause bone resorption as well as causing renal tubular calcium retention. Less commonly, tumor in bone can have a direct osteolytic activity through local cytokines. Rarely, lymphomas can produce ectopic activated vitamin D to cause hypercalcemia.
DIAGNOSIS
Clinical Presentation
Presentation is often nonspecific. Common symptoms include fatigue, anorexia, constipation, polydipsia, polyuria, nausea, vomiting, lethargy, and apathy. Nephrolithiasis is possible. In severe cases, mental status alterations, seizures, and coma can be seen. Hypercalcemia can cause renal parenchymal damage and nephrogenic diabetes insipidus. Hypercalcemia produces a brisk diuresis, and patients are often severely volume depleted. Most clinicians will remember the symptoms of hypercalcemia from the mnemonic: “stones, bones, abdominal groans, and psychic moans.”
Diagnostic Testing
Management includes obtaining an ionized calcium level (or an albumin level to correct for the hypoalbuminemia that is frequently seen in cancer patients). Serum intact parathormone (PTH) levels should be checked to rule out primary hyperparathyroidism. Intact PTH levels are suppressed in the hypercalcemia of malignancy. There is generally no need to check a PTHrP, as the diagnosis of malignant hypercalcemia is often made by history alone. Other causes of hypercalcemia such as thiazide diuretics, granulomatous disease, and vitamin D intoxication can also be ruled out by history alone. A serum phosphate level must be checked, as hypercalcemia often leads to clinically significant hypophosphatemia.
TREATMENT
The acute treatment of hypercalcemia begins with IV fluids (4 to 8 L). Normal saline is started at 200 to 500 mL/h and decreased after the volume deficit is corrected. At least 3 to 4 L should be given in the first 24 hours, and a positive fluid balance of at least 2 L should be achieved. Further saline diuresis (100 to 200 mL/h) will aid in calcium excretion. Serum electrolytes, including potassium, phosphate and magnesium, should be measured every 6 to 12 hours and corrected accordingly. Oral phosphate repletion is standard if the serum phosphate level is low and the patient has normal renal function. With IV phosphate repletion, there is the risk of calcium phosphate precipitation and renal failure. Its use should be reserved for serious cases of hypophosphatemia managed by experienced physicians. Furosemide can lead to greater calcium loss through the urine; however, its use is contraindicated until the patient is euvolemic, and it is generally not necessary.
Other than IV fluids, the mainstay of the treatment of hypercalcemia is a bisphosphonate. Two bisphosphonates are FDA approved for the treatment of hypercalcemia of malignancy: pamidronate (Aredia; 60 to 90 mg IV over 2 hours) and zoledronic acid (Zometa; 4 mg IV over 15 minutes).
Bisphosphonates work by inhibiting bone resorption by osteoclasts.
Side effects include flulike symptoms and fever, as well as renal failure (rarely). These drugs must be used with extreme caution in patients with underlying renal insufficiency and generally avoided in patients with significant renal impairment (creatinine clearance, < 30 mL/min). Also, the dose of bisphosphonates will often need to be reduced in patients with renal insufficiency. Rarely, patients treated with bisphosphonates develop osteonecrosis of the jaw. The onset of action of the bisphosphonates is at between 2 and 4 days, with the peak effect generally between day 4 and day 7.
Salmon calcitonin (4 international units/kg) is usually administered intramuscularly or subcutaneously every 12 hours; doses can be increased up to 6 to 8 IU/kg every 6 hours. Nasal application of calcitonin is not efficacious for treatment of hypercalcemia. Calcitonin is safe and relatively nontoxic. It lowers the serum calcium concentration by a maximum of 1 to 2 mg/dL beginning within 4 to 6 hours. Thus, it is useful in combination with hydration for the initial management of severe hypercalcemia. The efficacy of calcitonin is limited to the first 48 hours, even with repeated doses, indicating the development of tachyphylaxis, perhaps due to receptor downregulation . Because of its limited duration of effect, calcitonin is most beneficial in symptomatic patients with calcium >14 mg/L, when combined with hydration and bisphosphonates. Calcitonin and hydration provide a rapid reduction in serum calcium concentration, while a bisphosphonate provides a more sustained effect.
Glucocorticoids (e.g., prednisone at an initial dose of 0.5 to 1 mg/kg/d) may be effective in hypercalcemia due to some hematologic malignancies and myeloma. Results may take up to 10 days and side effects from steroid treatment are common. In addition, dialysis is effective if other treatments fail. Other drugs that are rarely used (now mostly in hypercalcemia refractory to bisphosphonates) include calcitonin, gallium nitrate, and plicamycin (mithramycin). Of course, the definitive treatment of hypercalcemia is successful treatment of the underlying malignancy.
SYNDROME OF INAPPROPRIATE ANTIDIURESIS AND HYPONATREMIA
GENERAL PRINCIPLES
The syndrome of inappropriate antidiuresis (SIAD) was formerly known as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is now recognized that antidiuretic hormone (ADH)/vasopressin levels are commonly suppressed in patients with the syndrome, but affected patients have their homeostatic set-point for sodium set at a lower level than normal. SIAD is seen most commonly in small-cell lung cancer but can also be seen in many other malignancies including tumors of the upper gastrointestinal and genitourinary tract.
Etiology
In addition to SIAD directly related to the malignancy, drugs can also cause the inappropriate release of vasopressin or attenuate its action. Common drugs that can cause SIAD include morphine, vincristine sulfate, and cyclophosphamide. Pulmonary and central nervous system disease can also cause SIAD that is not related to an underlying malignancy.
DIAGNOSIS
Clinical Presentation
Patients with SIAD and hyponatremia may present with complaints of anorexia and nausea. With rapid and severe decline in serum sodium concentrations, they may also present with confusion, coma, and seizures. Look for decreased serum osmolality (< 270 mOsm/L) and urine that is not maximally dilute (>100 mOsm/L). In addition to the previously mentioned findings, the diagnosis of SIAD requires the absence of a hypervolemic state(manifest by ascites, edema) and absence of volume contraction, along with normal thyroid, renal, and adrenal function.
TREATMENT
Acute management includes IV normal saline or, in more severe cases, 3% sodium chloride (which should typically only be given with the assistance of someone skilled in its use, such as a nephrologist). Allow only 1 to 2 mEq/L/h of correction for the first 3 to 4 hours and ≤0.5 mEq/L/h thereafter to avoid demyelination syndromes (use even lower rates of correction for patients with chronic hyponatremia or hyponatremia of unknown duration—generally 0.5 to 1 mEq/L/h). To avoid potentially catastrophic demyelination, the overall rate of correction is limited to 8 to 10 mEq/L at 24 hours and less than 18 mEq at 48 hours. 8Furosemide may add to free water loss when given with saline. Demeclocycline is an antibiotic that lowers urine osmolality and can be useful in long-term therapy, but renal toxicity limits its use.
Vasopressin-receptor antagonists are a new option for the treatment of SIAD. The vasopressin receptor antagonists produce a selective water diuresis without affecting sodium and potassium excretion. Intravenous conivaptan(which is used in hospitalized patients) and oral tolvaptan are available and approved for use in patients with hyponatremia due to SIADH. The utility of tolvaptan therapy is limited by excessive thirst, prohibitive cost (at least in the United States), and the potential for overly rapid correction of the hyponatremia which has led to the necessity for hospitalization for the initiation of therapy. 9
NEUTROPENIC FEVER
GENERAL PRINCIPLES
Neutropenic fever is one of the most common complications of chemotherapy. Risk of infection is slightly increased with granulocyte counts <1000/μL, markedly increased with granulocytes <500/μL, and highest with granulocyte counts <100/μL. Eighty percent of infections in the neutropenic patient originate from the patient’s own flora. As many neutropenic patients also have long-term vascular access in place, these are common sources as well. Likely microbes include both grampositive (Staphylococcus, Streptococcus) and gram-negative aerobes (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa).
Definition
Neutropenic fever is defined as a single temperature >38.3°C (or a temperature >38.0°C for >1 hour) in patients with an absolute neutrophil count <500/ μL (or <1000/μL that is expected to decrease to <500/μL).
DIAGNOSIS
Clinical Presentation
Signs of infection, such as exudate, erythema, and warmth, may not be evident because of the reduced numbers of neutrophils. Pneumonias may only be evident by rales, as an infiltrate on chest x-ray may be lacking. Physical examination should focus on the skin, ocular fundus, sinuses, CNS, pelvis, and perirectal area.
Diagnostic Testing
Management includes searching for a source of infection by obtaining two sets of blood cultures, with one set from any indwelling intravascular catheter. Sputum and urine cultures are indicated, and chest x-ray should also be obtained. If diarrhea is present, a workup for infectious etiologies is indicated including stool culture and Clostridium difficile antigen testing. Lumbar puncture is not indicated unless clinical signs of meningitis are present,as neutropenia does not predispose to meningitis. In addition, lumbar puncture in the setting of thrombocytopenia can be dangerous.
TREATMENT
Medications
Antimicrobial therapy. Antimicrobial therapy SHOULD NOT wait the results of diagnostic tests, as patients can die of gram-negative sepsis in a matter of hours after their first fever, despite appearing well at initial presentation.10
Empiric antimicrobial therapy in neutropenic fever
Initial therapy is antipseudomonal beta-lactam ± aminoglycoside. A single agent such as cefepime (2 g IV every 8 hours in patients with normal renal function) may be used, depending on local sensitivities.
If the patient is still febrile after 3 days of treatment: add vancomycin (1 g IV every 12 hours in normal renal function or adjusted based on trough levels).
If the patient is still febrile after 5 to 7 days, antifungal coverage should be added. Caspofungin, Micafiungin, voriconazole, and posaconazole are reasonable choices, depending on the clinical circumstances. Treatment with amphotericin B is usually limited to refractory infections or critically ill patients who have not responded to the above agents.
The above are only general guidelines. If the patient is penicillin allergic, consider substituting a fourth-generation fluoroquinolone or aztreonam. If contra-indications to aminoglycosides are present, substitute a fluoroquinolone or aztreonam. One should consider using vancomycin or linezolid as initial therapy in addition to the previously mentioned antibiotics if the patient is hypotensive, has severe mucositis, is colonized with methicillin-resistant Staphylococcus aureus, recent quinolone prophylaxis or has signs of obvious catheter infection.
Antibacterial choice may vary depending on organisms and resistance patterns at particular hospitals or communities. Always consider other causes of fever in the febrile neutropenic, such as thrombosis.
Antimicrobials should be continued until the neutrophil count rises above 500/mm3 for 2 days and the patient has been afebrile without evidence of infection for the same duration.
The role of colony-stimulating factors in neutropenic fever is controversial, but administration should be considered in critically ill patients.
Other Non-Pharmacologic Therapies
Other precautions, such as visitor screening, hand washing, and proper isolation measures, should be maintained during this period.
EPIDURAL SPINAL CORD COMPRESSION
GENERAL PRINCIPLES
Epidural spinal cord compression (ESCC), occurring in 5% of cancer patients, is one of the most common oncologic emergencies. The dural sac is compressed by tumor in the epidural space at the level of the spinal cord or cauda equine; neurologic deficits may result. If ESCC is caught early, when pain is the only symptom, the patient can be spared significant disability.
Etiology
Any malignancy can produce epidural compression, with lung, breast, and prostate cancers being the most common, followed by lymphoma, myeloma, and sarcoma. The thoracic spine is the most common location, followed by the lumbosacral and then the cervical spine. Osteolytic lesions of the vertebral column cause most cases. Compression occurs either by direct extension from metastases in the vertebral bone or by tumor growth through the intervertebral foramina. On occasion, tumor can metastasize directly to the epidural space.
DIAGNOSIS
Clinical Presentation
Back pain is the first symptom in 90% of patients. The pain localizes in the back, near the midline, and is frequently accompanied by referred or radicular pain. The pain, unlike the pain of a herniated disc, may be exacerbated by recumbency and improved by the upright position. Many patients are unaware that back pain is related to their underlying malignancy and do not seek treatment.
Weakness and sensory impairment may follow from hours to months after the onset of pain. Regardless of the spinal compression site, weakness tends to begin in the proximal legs. The weakness can progress to paraplegia and occasionally develops abruptly without prior clinical signs. At presentation, about 80% of patients complain of weakness, usually affecting gait. About 50% of patients have sensory complaints at presentation. These complaints range from paresthesias to loss of sensation.
Autonomic dysfunction, including impotence and bowel/bladder dysfunction, occurs late and is generally not the sole presenting symptom.
Diagnostic Testing
Whole-spine MRI is the diagnostic test of choice for ESCC. The entire spine should be imaged because of the high incidence of asymptomatic multilevel disease.
CT myelography is necessary for patients with contraindications for MRI. In published studies, CT myelography is as accurate as MRI, but MRI is noninvasive, safer, and better tolerated. One must also consider other causes of spinal cord dysfunction, such as myelopathy, intramedullary metastases, hematoma, and abscess.
Lumbar puncture to search for additional causes should not be performed until spinal cord compression is excluded.
TREATMENT
Dexamethasone is the indicated medical treatment of nearly all patients with ESCC. Treatment should begin immediately after the diagnosis is suspected and not be delayed until the results of imaging studies are available. The dose is controversial, but a common regimen is a 10-mg IV bolus followed by 4 mg IV every 6 hours (although this regimen is not supported by published evidence).
Next, all patients should have an immediate neurosurgical consultation. Patchell and colleagues (2005) published a pivotal randomized study showing that initial operative treatment benefits a subgroup of patients with ESCC. 11 The general indications for surgery include spinal instability with bony compression, neurologic progression during or after radiation therapy, unknown primary site with surgical decompression and biopsy, and a single site of cord compression. The exclusion criteria of the published study were patients with paraplegia for >48 hours prior to study entry, multiple compressive lesions, preexisting neurologic conditions including brain metastases, and radiosensitive tumors (lymphoma, leukemia, multiple myeloma, and germ cell tumors).
Radiation therapy is also indicated in nearly all patients with ESCC, either in lieu of surgery or after surgery. The most common regimen is 10 uninterrupted fractions of 3 Gy each.
OTHER NEUROLOGIC EMERGENCIES
Increased intracerebral pressure and cerebral herniation (from brain metastases, hemorrhage, venous sinus thrombosis, meningitis, head trauma, infarction, or abscess). Again, immediate consultation with neurosurgery is often essential. The patient should be stabilized, and maneuvers to lower intracranial pressures such as hyperventilation and IV mannitol and/or dexamethasone should be attempted. A head CT scan can aid in determining whether surgery is indicated.
Status epilepticus (from brain metastases, metabolic derangement, or neurotoxicity of cancer therapy). Ensuring an airway should be the first and foremost concern. Laboratory studies such as glucose, electrolytes, Ca, Mg, serum and urine toxicology screens, serum alcohol level, CBC, urinalysis, and any pertinent medication levels must be obtained. IV benzodiazepines, phenytoin, and barbiturates are used in the treatment of status epilepticus. If the patient does not have IV access, benzodiazepines are also available in rectal, IM, or intranasal formulations.
Intracerebral hemorrhage (from metastatic tumor, thrombocytopenia, or leukostasis). Headache, vomiting, and mental status changes are symptoms of significantly increased intracranial pressure and hemorrhage. Workup should include imaging with a STAT noncontrast head CT scan and possibly a lumbar puncture (if CT is nondiagnostic). Therapy largely focuses on maintenance of adequate blood pressure, supportive care, correction of coagulopathy and thrombocytopenia, and surgical consultation when appropriate.
PATHOLOGIC FRACTURES
GENERAL PRINCIPLES
Pathologic fractures are defined as fractures occurring in diseased bone.
Breast, prostate, kidney, and lung are the most common carcinomas to metastasize to bone and potentially cause fracture. The majority of patients have multiple metastatic lesions.
DIAGNOSIS
Clinical Presentation
Symptoms include new-onset bone pain in patients with a history of a primary carcinoma.
TREATMENT
In the management of the pathologic fracture, consider life expectancy, as most fractures are best treated surgically with internal fixation. IV narcotics and fracture immobilization are used to control pain and bleeding. Consultation with orthopedics is necessary. Hip and femur fractures will require traction, whereas casts or splints may be used for distal fractures. Radiographs of the region in at least two planes are needed. A bone scan may be obtained to locate occult lesions. Radiographs of involved bones may identify other areas of impending fracture. Both the pathologic fracture and impending fractures could thus be repaired during one surgery.
Bisphosphonates have an expanding role in the prevention of further pathologic fracture, and treatment with pamidronate or zoledronic acid should be considered in patients with pathologic fracture.
Consultation with radiation oncology is indicated to determine whether the patient could benefit from radiation therapy as well.
REFERENCES
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