The Washington Manual of Oncology, 3 Ed.

Oncologic Emergencies

Manik Amin

 I. METABOLIC EMERGENCIES

1. Hypercalcemia
2. Pathophysiology. Most common cancers associated with hypercalcemia are breast cancer, lung cancer, and multiple myeloma. Patients with hypercalcemia of malignancy often have poor prognosis. Hypercalcemia of malignancy results from three main mechanisms: (1) secretion of a PTHrP, (2) local osteolytic activity, and (3) abnormal production of 1,25-dihydroxyvitamin D (Calcitrol). Humoral secretion of PTHrP accounts for more than 70% of patients with hypercalcemia of malignancy and is seen in a variety of cancers such as squamous cell cancer (e.g., of head and neck, esophagus, cervix, or lung), renal cancer, ovarian cancer, endometrial cancer, non-Hodgkin’s lymphoma, and breast cancer. Malignant hypercalcemia due to osteolytic activity is seen in approximately 20% of patients with hypercalcemia of malignancy and is mediated by osteoclasts and is a complex interplay between RANKL/RANK interaction/activation and cytokine production. It usually develops in patients with extensive skeletal metastases (e.g., breast cancer, lung cancer, prostate cancer, or multiple myeloma). In Hodgkin’s lymphoma and few non-Hodgkin’s lymphoma, malignant lymphocytes secrete the active form of vitamin D, 1, 25-dihydroxyvitamin D, resulting in increased osteoclastic bone resorption and intestinal absorption of calcium resulting in hypercalcemia.
3. Signs and symptoms. Patients with mild hypercalcemia, with calcium levels less than 12 mg/dL, are usually asymptomatic or may have nonspecific symptoms such as constipation and fatigue. Symptoms generally develop at serum calcium levels greater than 12 mg/dL and depend upon the acute rise in serum calcium concentration. Serum calcium levels between 12 and 14 mg/dL developing over few months may be well tolerated by patients, whereas a sudden increase in the serum calcium levels may manifest with altered mental status. Patients with severe hypercalcemia of more than 14 mg/dL usually present with nausea, vomiting, anorexia, abdominal pain, constipation, muscle weakness altered mental status, coma, and seizures. Patients usually develop renal dysfunction with dehydration, elevated creatinine, polyuria (from decreased concentrating ability in distal tubules), and polydipsia. Chronic hypercalcemia (from nonmalignant cause) may present as nephrogenic diabetes insipidus and nephrolithiasis. Long-standing hypercalcemia can also result in demineralization and frequent fractures of the long bones. Acute hypercalcemia, on the other hand, can cause myocardial damage leading to conduction abnormalities such as ventricular or supraventricular arrhythmias. Physical examination may reveal altered mental status, distended abdomen from ileus, and signs of dehydration. In the absence of prompt recognition and treatment, hypercalcemia can progress to renal failure, coma, and death.
4. Workup. The normal range for total serum calcium is 8.6 to 10.3 mg/dL (2.15 to 2.57 mM). About half the amount of the circulating calcium is bound by albumin, and the remaining unbound ionized calcium (normal range, 4.5 to 5.1 mg/dL) is responsible for the biologic functions. Since a low or high albumin level may result in an inaccurate ionized calcium level, the effective total calcium should be calculated with following formula: corrected Ca (mg/dL) = measured Ca (mg/dL) − albumin (g/dL) + 4.

 In patients with hypercalcemia without malignancy, other causes of hypercalcemia should be considered such as primary hyperparathyroidism, thyrotoxicosis, adrenal insufficiency, 1, 25(OH)² vitamin D toxicity (through ingestion or granulomatous conversion), and inherited disorders of calcium metabolism. Patients with elevated PTH rather than PTHrpP are more likely to have primary hyperparathyroidism than malignant hypercalcemia. But if both Parathyroid hormone (PTH) and Parathyroid hormone-related protein (PTHrP) concentrations are high, then coexisting primary hyperparathyroidism along with hypercalcemia of malignancy are likely.

4. Treatment. The treatment of hypercalcemia depends on the serum calcium level and the symptoms. Asymptomatic or mildly symptomatic patients (calcium <12 mg/dL) may not require immediate treatment, whereas symptomatic patients or calcium >14 mg/dL irrespective of symptoms require aggressive treatment. The main goals of treatment are lowering the serum calcium and treatment of underlying disease. The treatment of severe hypercalcemia involves simultaneous administration of isotonic saline, calcitonin, and bisphosphonate (Table 38-1).
5. Volume expansion. Patients should be rehydrated with isotonic saline at an initial rate of 200 to 300 mL/hour up to 2 to 3 L and then adjusted to maintain the urine output at 100 to 150 mL/hour. Saline infusion should be stopped in patients who develop fluid overload due to impaired renal function or heart failure and loop diuretics should be used. Loop diuretics not only reduce the volume load but also decrease calcium reabsorption in the loop of Henle. Potassium and magnesium should be carefully monitored and replaced as needed. Hypophosphatemia is common in hypercalcemia but should not be replete unless symptomatic, because an increase in the calcium × phosphorus product to 70 or more can cause precipitation of calcium salts in the kidney and other soft tissues.
6. Calcitonin. Calcitonin decreases the serum calcium concentration by increasing renal calcium excretion and by decreasing bone resorption by osteoclasts. Salmon calcitonin (4 to 8 IU/kg) is usually administered intramuscularly or subcutaneously every 12 hours, with a dose increase to 6 to 8 IU/kg every 6 hours if needed. Nasal calcitonin is not efficacious in the treatment of hypercalcemia. Calcitonin works rapidly and usually decreases the serum calcium concentration by 1 to 2 mg/dL within 4 to 6 hours of administration. It is safe, nontoxic, and rapidly acting, but efficacy is limited to the first 48 hours, owing to the development of tachyphylaxis by receptor downregulation and hence may be used to manage severe hypercalcemia (serum calcium >14 mg/dL) before bisphosphonates reach full effect.
7. Intravenous bisphosphonates. The bisphosphonates are nonhydrolyzable analogs of inorganic pyrophosphate, which adsorb to the surface of bone hydroxyapatite and inhibit calcium reabsorption by reducing the activity of the osteoclasts. These drugs have become the agents of choice for malignancy-associated hypercalcemia, and can successfully control serum calcium in 80% to 90% of patients. They are more potent, but their maximum effects occur in 2 to 4 days and hence are given with isotonic saline and calcitonin. Current bisphosphonates of choice are intravenous pamidronate and zolendronic acid (ZA). ZA is a third-generation bisphosphonate and is administered at a dose of 4 mg i.v. over 15 minutes, whereas pamidronate can be used as either 60 or 90 mg over 24 hours. Other bisphosphonate as effective as pamidronate is Ibandronate given at the dose of 2 mg IV over 2 hours. The side effects of bisphosphonates are flulike symptoms (fever, arthralgia, fatigue, and bone pain), hypocalcaemia, hypophosphatemia, nephrotic syndrome, uveitis, and osteonecrosis of jaw. Clodronate and etidronate are first-generation bisphosphonates and are weak inhibitors of bone resorption and not very commonly used. Oral bisphosphonates have not been shown to be as effective and are not recommended.

1. Other agents. Corticosteroids may be effective in controlling hypercalcemia due to sarcoidosis or other granulomatous diseases. A dose of 20 to 40 mg/day prednisone orally or its equivalent can be given to control hypercalcemia from excess ingestion of vitamin D or endogenous production of calcitrol. In patients with malignancies producing 1,25dihydroxyvitamin D such as myeloma or lymphomas, IV steroids can be used alone or in combination with bisphosphonates before definitive therapy of the underlying malignancy. Steroids are not effective in the treatment of hypercalcemia in patients with solid tumors. Hemodialysis is usually reserved for severe cases of hypercalcemia not responding to recommended treatments. Several new inhibitors of bone resorption such as osteoprotegerin (an antagonist of RANKL receptor), monoclonal antibodies directed against RANKL, monoclonal antibodies neutralizing PTHrP, and 22-oxacalcitriol are being studied currently.
2. Tumor lysis syndrome
3. Pathophysiology. The tumor lysis syndrome (TLS) results from excessive tumor breakdown either spontaneously or during therapy, leading to sudden and large amount of potassium, phosphates, and nucleic acids into systemic circulation. Catabolism of nucleic acid to uric acid causes hyperuricemia and other variety of metabolic abnormalities such as hyperkalemia, hyperphosphatemia, secondary hypocalcaemia, and acute kidney injury. The TLS occurs most frequently in patients with tumors having high growth rate and substantial systemic tumor burden that are very sensitive to chemotherapy and radiotherapy such as leukemia’s (ALL) and high-grade lymphomas (Burkitts). TLS is rarely encountered in patients with epithelial malignancies.
4. Signs and symptoms. The onset of TLS can be before the initiation of cytotoxic therapy, but is often within 12 to 72 hours after administration of cytotoxic therapy and/or radiation therapy (RT). A high level of suspicion is required because TLS symptoms can be very nonspecific and symptoms are often a result of associated electrolyte imbalances. The patients may present with nausea, vomiting, diarrhea, anorexia, congestive heart failure, cardiac arrhythmias, seizures, tetany, syncope, and possibly sudden death, often due to cardiac arrest.

 The most worrisome metabolic consequences of TLS are hyperkalemia, hypercalcemia, and renal failure. Acute renal failure results from precipitation of phosphate and uric acid in the renal tubules causing renal vasoconstriction decreased renal blood flow and acute kidney injury, which creates a vicious cycle, thereby resulting in further deterioration of renal function. Patients with baseline elevated levels of uric acid, phosphorus, and lactate dehydrogenase (LDH) before treatment may be at risk for TLS.

3. Classification of TLS. Laboratory TLS (LTLS) is defined as the presence of two or more of the following laboratory parameters within three days before or seven days after cytotoxic chemotherapy: (a) uric acid ≥8 mg/dL or 25% increase from baseline; (b) potassium ≥6.0 mEq/L or 25% increase from baseline; (c) phosphate level ≥4.5 mg/dL or 25% increase from baseline; and (d) calcium ≤7 mg/dL or 25% decrease from baseline. Clinical TLS (CTLS) is defined as the presence of laboratory TLS plus at least one clinical complication such as renal failure and/or cardiac arrhythmias and/or seizures and/or sudden death (Br J Haematol2004;127:3).
4. Management. Management of TLS involves treatment of the underlying electrolyte abnormalities along with coexisting renal failure or cardiac arrhythmias. The best approach to managing TLS is prevention. Tumor- and patient-related factors are used to calculate the risk of TLS in individual patients. High-risk patients are pretreated with isotonic saline to maintain high urine output (80 to 100 mL per hour) and are recommended to give at least single dose of Rasburicase and should also be pretreated for at least 2 days with allopurinol (600 mg/day). Uric acid levels are closely monitored and dose of Rasburicase may be repeated for persistent hyperuricemia. The dose of allopurinol should be decreased for preexisting renal insufficiency.
5. Intermediate-risk patient are also pretreated with isotonic saline to maintain high urine output and pretreatment allopurinol if the baseline uric acid levels are <8 mg/dL. If the uric acid levels are ≥8 mg/dL, Rasburicase should also be given.
6. For low-risk patients, a wait-and-watch approach is used with hydration and close monitoring.
7. Furosemide may be given to maintain urine output and also to decrease the hyperkalemia. Urine alkalinization with either one ampoule of NaHCO³ in 0.5 N saline or two to three ampoules in D5W may be needed to maintain the urine solutes (calcium, uric acid, and oxalates) in ionic form and thereby prevent crystallization and also to help correct metabolic acidosis accompanying TLS. Blood chemistries (electrolytes, creatinine, phosphorus, calcium, and LDH) need to be checked in patients at risk every 8 to 12 hours during the first 2 to 3 days of treatment.
8. Hyperkalemia may develop rapidly, and patients at risk should have serum electrolytes checked at least every 12 hours, and more frequently if TLS develops. Mild hyperkalemia (5.5 to 6.0 mEq/L) may be treated with sodium polystyrene sulfonate (Kayexalate resin) and hydration. More severe hyperkalemia (greater than 6 mEq/L or with electrocardiogram [EKG] changes) may be treated immediately with 50 mL of 50% glucose solution with 15 U of regular insulin, i.v. piggyback over an hour. Indications for hemodialysis include volume overload, serum uric acid greater than 10 mg/dL, or rapidly increasing phosphorus levels and uncontrolled hyperkalemia. Renal failure caused by TLS is usually reversible, and even patients requiring hemodialysis often regain normal kidney function as the TLS subsides.
9. Syndrome of inappropriate antidiuretic hormone (SIADH)
10. Pathophysiology. SIADH is a syndrome of excessive inappropriate secretion of ADH resulting in water retention and hyponatremia. Excessive secretion of ADH causes increased urine osmolality and increased sodium loss, resulting in concentrated urine. Small-cell lung cancer (SCLC) is the most common cancer causing SIADH, with over 15% patients with SCLC developing SIADH at some point during the course of the illness. Head and neck cancers, olfactory neuroblastomas, and extrapulmonary small-cell carcinomas are some less common causes of SIADH.
11. Signs and symptoms. Patients initially present with headache and fatigue and if left uncorrected may rapidly progress to confusion, seizure, coma, and death. A low plasma osmolality with elevated urine osmolality (more than 100 mosmol/kg), urine sodium more than 40 mEq/L, low blood urea nitrogen (BUN) 10 mg/dL, serum uric acid level <4 mg/dL, FE_Na >1%, and normal acid–base and serum potassium levels are all suggestive of SIADH.
12. Management. The treatment of SIADH varies with the severity of hyponatremia and presence of symptoms. Fluid restriction is the initial step of management for patients with mild-to-moderate SIADH. In patients with acute (less than 48 hours) and severe symptomatic hyponatremia, an urgent intervention with 100 mL of hypertonic saline is given as bolus and can be repeated 1 to 2 times at 10 min interval depending upon the persistent of neurological symptoms. This treatment should raise the serum Na concentration by approximately 1.5 to 2.0 mEq/L. For patients with serum sodium <120 mEq/L and less severe symptoms (more than 48 hours), the goal of correction is to increase serum sodium 1 mEq/L per hour for 3 to 4 hours. When the serum Na levels reach 120 mEq/L, then the 3% saline should be stopped and fluid restriction instituted. For patients with no symptoms or mild symptoms, initial treatment with fluid restriction with oral salt tablets is recommended (Table 38-2).
13. Maintenance therapy in previously symptomatic patients is to maintain fluid restriction to less than 800 mL/day with monitoring of serum sodium levels to >130 mEq/L (Table 38-3).
14. For chronic SIADH, treatment options include demeclocycline (300 to 600 mg daily) and vasopressin receptor antagonists such as tolvaptan (15 to 60 mg oral daily) or conivaptan (20 to 40 mg intravenously daily) (J Endocrinol Metab 2013;98:1321).

1. NEUROLOGIC EMERGENCIES
2. Epidural spinal cord compression
3. Pathophysiology. Spinal cord compression is a common complication of cancers most commonly due to metastasis to the spinal column, causing pain and possibly irreversible loss of neurologic function involving the thoracic spine (65%), the lumbosacral spine (25%), and the cervical spine (10%). Intramedullary, intradural, or leptomeningeal metastases are rarely encountered. Patients with neurologic impairment secondary to cord compression have a markedly reduced quality of life and a significantly shortened overall survival. Spinal cord compression is seen most commonly in patients with following underlying cancers: lung, breast cancer, multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma, and prostate cancer. The main mechanism involved is the tumor invading the epidural space causing compression of thecal sac. The direct extension of the soft tissue epidural disease can compromise epidural venous plexus causing vasogenic edema, inflammation with release of serotonin and prostaglandins, and eventually infarction of the spinal cord. Other less common causes of cord compression include metastases to the posterior vertebral elements, benign and malignant tumors primary to the spine, vascular malformations, and infections. It is critical to begin therapy as soon as possible.
4. Signs and symptoms. The symptoms of cord compression may begin abruptly or progress gradually. Back pain is the most common symptom in almost all patients with spinal cord compression. New onset of back pain in a patient at risk mandates a careful neurologic examination. The pain may be localized to the back or may radiate either unilaterally or bilaterally in the distribution of spinal roots. Back pain may be exacerbated by flexion of the back, Valsalva maneuver, and coughing. Unlike back pain resulting from degenerative disc disease, the back pain due to spinal cord compression is not relieved by recumbent position but may be exacerbated. Majority of patients may present with motor weakness symmetric in both lower extremities and depending upon the level of the lesion may present with either typical pyramidal symptoms (lesion at or above conus medularis) or weakness of extensors of upper extremities (lesion above thoracic spine). Sensory findings are overall less common, but ascending numbness and paresthesias along the dermatome of the corresponding spinal roots may be seen.

 Other symptoms such as bowel and bladder dysfunction (sphincter disturbances, urinary/fecal incontinence, or retention) and gait ataxia occur late in the course of cord compression but are serious symptoms and need urgent attention since associated with poor prognosis. Acute, severe cord compression can cause spinal shock, with hyporeflexia and flaccid paralysis of all regions below the lesion.

3. Workup. The workup involves detailed clinical neurologic examination and preferably a magnetic resonance imaging (MRI) for all patients with suspected cord compression. MRI is the modality of choice when available since it can provide a detailed evaluation of spinal cord and extent of disease with involvement of bone and soft tissue. Myelography combined with contrast computed tomography (CT) is recommended if MRI cannot be performed. It is important to image the entire spine, as some patients may have more than one region of compression. Plain films and bone scans have a limited role since they do not provide anatomical information regarding epidural space and thecal sac. If the nature of the compressing mass is uncertain, surgical or image-guided biopsy for tissue diagnosis may be required. When cord compression is the initial presentation of cancer, further staging evaluation may reveal more accessible lesions such as a lymph node for biopsy and subsequent diagnosis.
4. Management. Spinal cord compression requires prompt recognition because delay in treatment may result in permanent neurologic damage and poor outcome. Pretreatment neurological status is the most important prognostic indicator of posttreatment outcome. Immediate treatment of cord compression includes corticosteroids administration, surgery, and RT with external beam radiation therapy (EBRT).

 Corticosteroids decrease the edema associated with cord compression and improve neurologic symptoms transiently. We recommend a 10-mg loading dose of Dexamethasone IV or PO followed by 4 mg every 6 hours. Dexamethasone should be tapered off over a few weeks. Spinal cord stability should be assessed. Traditional indications for surgical intervention include the need for a tissue diagnosis, resection of “radioresistant” tumors and tumors primarily treated by surgery (such as sarcomas), and cord compression in a previously irradiated spine. A very rapid onset of symptoms suggests the possibility of vertebral burst fracture causing bony impingement on the cord and hence is an indication for urgent surgical intervention. Patients with extensive bony destruction by tumor and vertebral instability may be at risk for further compression fracture and symptom recurrence after completing X-ray therapy (XRT); these patients should be considered for vertebral stabilization with vertebroplasty and kyphoplasty.

 EBRT is the treatment of choice and should begin as soon as the diagnosis is confirmed. Standard radiation doses range from 2,500 to 4,000 cGy delivered in 10 to 20 fractions. Surgical patients usually require 7 to 10 days for wound healing before beginning radiation. In select groups of patients, the addition of decompressive surgery to RT improved neurologic outcomes as compared with radiotherapy alone (Lancet2005;366(9486):643). Systemic therapy using hormonal and/or chemotherapeutic agents should be considered when appropriate (e.g., in patients with lymphoma).

 Symptomatic treatment is considered with pain medications, appropriate ambulatory restrictions, anticoagulation if no other contraindications (no anticoagulation if surgery planned), and symptom management from sphincter dysfunction (urinary/bowel retention vs. incontinence).

 III. HEMATOLOGIC EMERGENCIES

1. Leukostasis
2. Pathophysiology. Leukastasis is a syndrome commonly seen in acute leukemia’s and comprises of hyperleukocytosis (WBC >50,000 to 100,000/µL) with respiratory distress, abnormal chest radiograph (CXR), confusion, and CNS bleeding. If not treated, leukostasis has very poor prognosis with a high mortality rate. High and rapidly increasing blast counts are characteristic of leukostasis with classic pathologic finding of occlusive intravascular aggregates of blasts blocking the circulation in multiple organs, especially the lungs and brain.
3. Signs and symptoms. Leukostasis is a clinical diagnosis. Patients may present with respiratory symptoms of dyspnea, hypoxia, fever, etc. Pulse oximetry assesses the O₂ saturation more accurately than arterial blood gas (ABG) analysis since WBC in the blood sample consume oxygen and spuriously lower the PO₂ of the specimen if not processed in a timely manner. Chest X-ray may show diffuse alveolar or interstitial infiltrate. Fever may be from inflammation or concomitant infection and broad-spectrum antibiotics are recommended. CNS involvement may present with headaches, dizziness, vision changes, confusion, gait abnormality, and even coma. These patients have a high risk of intracranial hemorrhage after starting chemotherapy even in the absence of disseminated intravascular coagulation (DIC) or thrombocytopenia. Less commonly, impairment of other end organs with leukastasis may present as heart failure, myocardial infarction, renal failure, bowel infarction, priapism, etc. Symptoms may be fulminant, leading to death in a matter of days or even hours.
4. Management. Leukastasis is treated with prompt cytoreduction treatment in conjunction with leukapheresis with the goal of rapidly decreasing WBC count. Cytoreduction with induction chemotherapy should be initiated whenever possible, especially in acute leukemia, but if induction chemotherapy is delayed, cytoreduction with hydroxyurea is attempted. Hydroxyurea given at 50 to 100 mg/kg/day usually reduces the WBC by 50% in 24 to 48 hours and is continued until WBC is <50,000/µL. Patients who receive leukapheresis have a lower incidence of intracerebral bleeds after starting chemotherapy and also decrease the incidence of TLS. Leukapheresis should be considered in all patients with a leukemic blasts count greater than 100,000/dL. Leukapheresis is not recommended if acute promyelocytic leukemia (APL) is suspected since it may worsen the coagulopathy associated with leukemia. Red blood cell transfusion should be avoided since it can worsen the symptoms associated with leukastasis. Thrombocytopenia and coagulation factors need to be corrected to minimize the risk of CNS bleeding. Patients with signs of sepsis need to have blood drawn for culture and treated empirically with broad-spectrum antibiotics. The underlying malignancy needs to be treated appropriately. Low-dose cranial irradiation may be considered in patients with very severe CNS symptoms.

 IV. CARDIAC EMERGENCIES

1. Cardiac tamponade
2. Pathophysiology. Cardiac tamponade is an accumulation of pericardial fluid under pressure causing abnormal compression of all cardiac chambers and impaired cardiac filling and subsequently hemodynamic compromise. This can be acute, subacute, or chronic. Some of the causes of moderate-to-large pericardial effusions leading to tamponade are idiopathic, malignancy, uremia, iatrogenic, acute myocardial infarction, collagen vascular diseases, hypothyroidism, etc. Overall 10% of patients dying of cancer are found to have pericardial involvement at autopsy. Thoracic malignancies are the most common cause of malignant pericardial effusion and tamponade.
3. Signs and symptoms. Presenting symptoms may vary depending upon the acuteness of tamponade. Patients with acute tamponade present with chest pain and dyspnea, whereas patients with subacute or chronic tamponade may present with fatigue, cough, chest pain, and edema. Hypotension is a common feature due to the decline in cardiac output. Severe hypotension and pulseless electrical activity are the final consequences of untreated tamponade. More often cardiac tamponade manifests in a less dramatic way with increased filling pressures and decreased cardiac output. Features of right-heart failure, such as peripheral edema, hypotension, and elevated jugular venous pressure (JVP), may be seen. Pulsus paradoxus (a decrease in systolic blood pressure of 10 mmHg or more on inspiration) is classically associated with pericardial effusion. Often a pericardial rub may be heard due to associated inflammatory pericarditis. Acute cardiac tamponade presenting with signs of right heart failure must be differentiated from a right-sided acute myocardial infarction and an aortic dissection.
4. Workup. The clinical diagnosis of cardiac tamponade is usually confirmed by the physical findings supplemented by electrocardiography (EKG), CXR, and echocardiography (ECHO). The EKG shows sinus tachycardia with low voltage. The characteristic findings on EKG in patients with pericardial effusion include electrical alternans (beat-to-beat alteration in QRS complex) as the heart swings within the pericardial fluid. Electrical alternans has a low sensitivity but high specificity. CXR may reveal an enlarged cardiac silhouette (water-bottle heart) with clear lung fields. At least 200 mL of fluid must accumulate before the cardiac silhouette is enlarged on chest X-ray, and hence this is often absent in acute tamponade. ECHO shows moderate-to-large effusion and swinging of the heart within the effusion and diastolic collapse of the right atrium and right ventricle. Collapse of the right atrium occurs when the extrinsic compression by the effusion overcomes venous pressure and prevents right heart filling. Right atrial collapse for more than one-third of the cardiac cycle is highly sensitive and specific for cardiac tamponade. Examination of pericardial fluid is often required in cancer patients to ascertain the diagnosis of malignant effusion and to rule out other causes. In malignant pericardial effusion, cytology will be positive in only 65% to 85% of cases. A positive cytology may be predictive of a poorer outcome in patients with neoplastic pericardial disease. Pericardial biopsy is the gold standard for establishing definitive diagnosis.
5. Management. Asymptomatic patients with mild effusion do not require treatment unless the etiology is unclear. Symptomatic patients, however, require intervention. Definitive treatment of tamponade involves removal or drainage of pericardial fluid and relieving intrapericardial pressure. Pericardial fluid can be drained percutaneously by pericardiocentesis with echocardiographic guidance or surgical pericardiectomy. Pericardiocentesis is usually safely done in most of the patients; however, it is relatively contraindicated in severe pulmonary hypertension and severe coagulopathy. Pericardiocentesis is done after local anesthesia; the needle is inserted to the right of the xiphoid and advanced toward the tip of the left scapula, with constant aspiration during the procedure. A large syringe or a catheter with a stopcock should be available to allow removal of 50 to 60 mL of fluid. This results in rapid improvement in symptoms. Despite marked improvement in the symptoms, reaccumulation of fluid occurs in as many as 60% of patients. In this situation, a surgical pericardial window will usually prevent repeat accumulation. Balloon pericardiotomy is an alternative to surgical creation of a pericardial window. In this procedure an uninflated balloon catheter is placed in the pericardial space using a subxiphoid approach under guidance. The balloon is then inflated and pulled out of pericardium to create a “window,” thereby allowing drainage of fluid into the pleural or peritoneal space. This technique has shown a decrease in the reaccumulation in 80% to 100% of cases. This approach may be a reasonable alternative to surgery in patients with malignant tamponade, especially in those who are poor surgical candidates.
6. Superior vena cava syndrome
7. Pathophysiology and mechanism. Superior vena cava (SVC) syndrome results from the obstruction of blood flow in the SVC caused by invasion or external compression of the SVC by a pathologic process involving right lung, lymph nodes, and mediastinal structures. When the blood flow in SVC is obstructed, venous collaterals are formed as alternate pathways to venous return. Thoracic malignancies such as lung cancer (SCLC more often than non-SCLC), non-Hodgkin’s lymphoma- DLBCL, lymphoblastic lymphoma, and primary mediastinal B cell lymphoma are common cause of SVC syndrome. Other nonmalignant causes of SVC syndrome are compression of the SVC from indwelling central venous devices that result in SVC thrombosis, aortic aneurysms, and fibrosing mediastinitis.
8. Signs and symptoms. Dyspnea is common. Patients with SVC syndrome commonly complain of dyspnea, swelling of the face, neck, upper extremities, and pain (chest pain or headaches). Symptoms may develop rapidly or gradually and may vary in severity by position. Bending forward or lying flat may worsen symptoms as a result of increased venous pressure proximal to the obstruction. Even in the presence of severe symptoms, patients are rarely critically ill as a result of SVC syndrome alone. Dilated neck veins are usually present along with collateral veins that develop as a result of long-standing occlusion.
9. Workup. The CXR may show mediastinal widening and pleural effusion. Contrast-enhanced CT is extremely helpful in detecting the location and extent of venous blockage and presence of collateral venous drainage. It also provides very useful information regarding the adjacent structures, including the presence or absence of compressive mass lesions, and is useful in planning subsequent biopsy or therapeutic intervention. MRI may be useful for patients who are unable to undergo a contrast CT. A histologic diagnosis is essential in the management of SVC syndrome, as specific treatment may be influenced by the tumor type. Patients without a tissue diagnosis or in whom the diagnosis is uncertain should undergo surgical or percutaneous biopsy of an accessible site. Sputum cytology, pleural fluid cytology, and biopsy of enlarged thoracic lymph nodes may be diagnostic in most cases. Bronchoscopy, mediastinoscopy, or thoracotomy may be required if the diagnosis is in doubt. Bone marrow biopsy may provide a diagnosis in suspected NHL or SCLC.
10. Treatment. Relief of symptoms and treatment of the underlying disease is the mainstay in the treatment of SVC syndrome. Accurate histologic diagnosis of the underlying etiology is essential prior to initiation of therapy. Malignancy-associated SVC syndrome has poor prognosis.

 Malignant SVC was considered an emergency in the past, requiring emergent RT to relieve obstructive symptoms, but nowadays emergent RT is no longer considered necessary treatment unless patients present with severe symptoms including respiratory stridor due to airway obstruction and laryngeal edema or comatose patients presenting with cerebral edema in whom RT and intraluminal stent placement is considered an emergent treatment option.

 Prebiopsy empirical treatment may obscure the histologic diagnosis and make further management of the underlying disease complicated. For patients with SCLC, NHL, and germ cell tumors, initial chemotherapy is the treatment of choice for symptomatic patients. In limited SCLC and some NHLs, the addition of RT to chemotherapy decreases the local recurrence rate. Endovascular therapy (i.e., intraluminal stenting) may be considered in some patients with severe symptoms and in patients with underlying malignancy not responsive to chemotherapy or radiation.

 The role of steroids in managing SVC syndrome is not proven and hence not recommended except in steroid responsive malignancies such as lymphomas. If SVC thrombus is present, systemic anticoagulation should be considered.

 SVC obstruction resulting from indwelling central venous catheters and pacemakers can be managed effectively by thrombolytic therapy (unless contraindicated). Anticoagulation is recommended as long as the central catheter is in place and can be discontinued in 3 months if the catheter is removed.

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