Superior vena cava syndrome (SVCS) is obstruction of blood flow through the superior vena cava (SVC).

It is a medical emergency and most often manifests in patients with a malignant disease process within the thorax. A patient withsuperior vena cava syndrome (SVCS) requires immediate diagnostic evaluation and therapy William Hunter first described the syndrome in 1757 in a patient with syphilitic aortic aneurysm. In 1954, Schechter reviewed 274 well-documented cases of superior vena cava syndrome (SVCS) reported in the literature; 40% of them were due to syphilitic aneurysms or [2] tuberculous mediastinitis. In more recent times, these infections have gradually decreased as the primary cause of superior vena cava (SVC) obstruction. Lung cancer, particularly adenocarcinoma, is now the underlying process in approximately 70% of the patients with superior vena cava syndrome [3, 4, 5] [6] (SVCS). However, up to 40% of the causes are due to nonmalignant causes. The superior vena cava (SVC) is the major drainage vessel for venous blood from the head, neck, upper extremities, and upper thorax. It is located in the middle mediastinum and is surrounded by relatively rigid structures such as the sternum, trachea, right bronchus, aorta, pulmonary artery, and the perihilar and paratracheal lymph nodes. It extends from the junction of the right and left innominate veins to the right atrium, a distance of 6-8 cm. It is a thin-walled, low-pressure, vascular structure. This wall is easily compressed as it traverses the right side of the mediastinum.[7] Obstruction of the superior vena cava (SVC) may be caused by neoplastic invasion of the venous wall associated with intravascular thrombosis or, more simply, by extrinsic pressure of a tumor mass against the relatively fixed thin-walled superior vena cava (SVC). Postmortem examinations reveal that complete superior vena cava (SVC) obstruction is the result of intravascular thrombosis in combination with extrinsic pressure. Incomplete superior vena cava (SVC) obstruction is more often secondary to extrinsic compression without thrombosis. Other causes include compression by intravascular arterial devices. The incidence is on the rise in line with the increased usage of endovascular devices.[4] An obstructed superior vena cava (SVC) initiates collateral venous return to the heart from the upper half of the body through 4 principal pathways. The first and most important pathway is the azygous venous system, which includes the azygous vein, the hemiazygous vein, and the connecting intercostal veins. The second pathway is the internal mammary venous system plus tributaries and secondary communications to the superior and inferior epigastric veins. The long thoracic venous system, with its connections to the femoral veins and vertebral veins, provides the third and fourth collateral routes, respectively. Despite these collateral pathways, venous pressure is almost always elevated in the upper compartment if obstruction of the superior vena cava (SVC) is present. Venous pressure as high as 200-500 cm H2 O has been recorded in patients with severe superior vena cava syndrome (SVCS).
[1]

Epidemiology
Frequency
United States Superior vena cava syndrome (SVCS) develops in 5-10% of patients with a right-sided malignant intrathoracic mass lesion. In 1969, Salsali and Cliffton observed superior vena cava syndrome (SVCS) in 4.2% of 4960 patients with lung cancer; 80% of the tumors inducing superior vena cava syndrome (SVCS) were of the right lung.[8] In 5 large series of small cell lung cancer, 9-19% of patients demonstrated superior vena cava syndrome (SVCS). In 1987, Armstrong and Perez found superior vena cava syndrome (SVCS) in 1.9% of 952 patients with lymphoma.[9]

Mortality/Morbidity
Survival in patients with superior vena cava syndrome (SVCS) depends mainly on the course of the underlying disease. No mortality, per se, results directly from mild venous congestion. In patients with benign superior vena cava syndrome (SVCS), life expectancy is unchanged. If superior vena cava syndrome (SVCS) is secondary to a malignant process, patient survival correlates with the histology of the tumor. Patients with signs and symptoms of laryngeal and cerebral edema have the most life-threatening manifestations of this syndrome and are in danger of sudden

death. Clinical observations show that approximately 10% of patients with a bronchogenic carcinoma and 45% of patients with lymphoma treated with irradiation live at least 30 months. In contrast, patients with untreated malignant superior vena cava syndrome (SVCS) survive only approximately 30 days.[5]

Race
The frequency of superior vena cava syndrome (SVCS) in different races depends largely on the frequency of lung cancer and lymphomas in these populations.

Sex
Malignant causes of superior vena cava syndrome (SVCS) are most commonly observed in males because of the high incidence of lung cancer in this population. In contrast, no sex difference is observed in cases related to benign causes.

Age
Malignant causes of superior vena cava syndrome (SVCS) are predominantly observed in individuals aged 40-60 years. Benign causes account for most of the cases diagnosed in individuals aged 30-40 years. Obstruction of the superior vena cava (SVC) in the pediatric age group is rare and has a different etiologic spectrum.

Clinical Presentation
Early in the clinical course, partial superior vena cava (SVC) obstruction may be asymptomatic, but more often, minor symptoms and signs are overlooked. As the syndrome advances toward total superior vena cava (SVC) obstruction, the classic symptoms and signs become more obvious. Dyspnea is the most common symptom and is observed in 63% of patients with superior vena cava syndrome (SVCS).[7, 10] Other symptoms include facial swelling, head fullness, cough, arm swelling,chest pain, dysphagia, orthopnea, distorted vision, hoarseness, stridor,headache, nasal stuffiness, nausea, pleural effusions, and light-headedness.[7, 10, 11]

Physical findings The characteristic physical findings of superior vena cava syndrome (SVCS) include venous distension of the neck and chest wall, facial edema, upper extremity edema, mental changes, plethora, cyanosis, papilledema, stupor, and even coma. Bending forward or lying down may aggravate the symptoms and signs. Etiology

More than 80% of cases of superior vena cava syndrome (SVCS) are caused by malignant mediastinal tumors.[12, 13, 14] Bronchogenic carcinomas account for 75-80% of all these cases, with most of these being small-cell carcinomas.[3] Non-Hodgkin lymphoma (especially the large cell type) represents 10-15% of cases. Causes of superior vena cava syndrome (SVCS) appear similar to the relative incidence of primary lung and mediastinal tumors. Rare malignant diagnoses include Hodgkin disease, metastatic cancers,[15]primary leiomyosarcomas of the mediastinal vessels, and plasmocytomas.[16, 17, 18] Nonmalignant conditions causing superior vena cava syndrome (SVCS) include mediastinal fibrosis; vascular diseases such as aortic aneurysm, vasculitis, andarteriovenous fistulas; infections such as histoplasmosis, tuberculosis, syphilis, and actinomycosis; benign mediastinal tumors such as teratoma, cystic hygroma, thymoma, and dermoid cyst; cardiac causes, such as pericarditis and atrial myxoma; and thrombosis related to the presence of central vein catheters. These account for approximately 22% of the causes of superior vena cava syndrome (SVCS).[16, 19, 20, 21]

Differential Diagnoses
Acute Respiratory Distress Syndrome Cardiac Tamponade Chronic Obstructive Pulmonary Disease Mediastinitis Pneumonia, Bacterial Pneumonia, Fungal Pneumonia, Viral Syphilis Tuberculosis

Workup Patients presenting with overt superior vena cava syndrome (SVCS) may be diagnosed by means of physical examination alone. However, subtle presentations require diagnostic imaging. Chest radiography may reveal a widened mediastinum or a mass in the right side of the chest. Only 16% of the patients studied by Parish and colleagues in 1981 had normal findings on chest radiography. [19] CT has the advantage of providing more accurate information on the location of the obstruction and may guide attempts at biopsy by mediastinoscopy, bronchoscopy, or percutaneous fine-needle aspiration.[7] It also provides information on other critical structures such as the bronchi and the vocal cords. A CT scan of the chest is the initial test of choice to determine whether an obstruction is due to external compression or due to thrombosis. The additional information is necessary because the involvement of these structures requires prompt action for relief of pressure. MRI has not been sufficiently investigated, but it appears promising. It has several potential advantages over CT scanning, including the fact that it provides images in several planes of view and allows direct visualization of blood flow. Furthermore, MRI does not require iodinated contrast material. This is especially important when stenting is anticipated. [20] MRI is an acceptable alternative for patients with renal failure or those with contrast allergies. Disadvantages may include increased scanning time with attendant problems in patient compliance and increased cost. Invasive contrast venography is the most conclusive diagnostic tool. It precisely defines the etiology of obstruction. It is especially important if surgical management is being considered for the obstructed vena cava. Radionuclide technetium-99m venography is an alternative minimally invasive method of imaging the venous system. Although images obtained by this method are not as well defined as those [22] achieved with contrast venography, they demonstrate potency and flow patterns. Most patients with superior vena cava syndrome (SVCS) present before the primary diagnosis is established. Controversy often arises in the treatment of a patient with superior vena cava syndrome (SVCS) in regard to the need for pathologic confirmation of malignancy before the start of therapy. Treatment without an established diagnosis should be initiated only in patients with rapidly progressive symptoms or those in whom multiple attempts to obtain a tissue diagnosis have been unsuccessful. Fortunately, relatively noninvasive measures establish the diagnosis in a high percentage of patients with superior vena cava syndrome (SVCS). Sputum cytologic results are diagnostic in 68% of the cases, whereas biopsy of a palpable supraclavicular node is positive in 87%.[23] Bronchoscopy has a 60% success rate, while thoracotomy is 100% successful.[23] Open biopsy is rarely needed for diagnosis. Dosios et al showed that cervical mediastinoscopy and anterior mediastinoscopy are effective in establishing a histiologic diagnosis. [24]

Medical care The goals of superior vena cava syndrome (SVCS) management are to relieve symptoms and to attempt cure of the primary malignant process. Only a small percentage of patients with a rapid-onset superior vena cava (SVC) obstruction are at risk for life-threatening complications.[17] Patients with clinical superior vena cava syndrome (SVCS) often gain significant symptomatic improvement from conservative treatment measures, including elevation of the head of the bed and supplemental oxygen.[23] Emergency treatment is indicated when brain edema, decreased cardiac output, or upper airway edema is present. Corticosteroids and diuretics are often used to relieve laryngeal or cerebral edema, although documentation of their efficacy is questionable. Radiotherapy has been advocated as a standard treatment for most patients with superior vena cava syndrome (SVCS). It is used as the initial treatment if a histologic diagnosis cannot be established and the clinical status of the patient is deteriorating; however, recent reviews suggest that superior vena cava syndrome (SVCS) obstruction alone rarely represents an absolute emergency that requires treatment without a specific diagnosis.[3, 25] The fractionation schedule of radiation usually includes 2-4 large initial fractions of 300-400 cGy, followed by conventional fractionation of 150-200 cGy daily, to a total dose of 3000-5000 cGy. The radiation dose depends on tumor size and radioresponsiveness. The radiation portal should include a 2-cm margin around the tumor. During irradiation, patients improve clinically before objective signs of tumor shrinkage are evident on chest radiography. Radiation therapy palliates superior vena cava (SVC) obstruction in 70% of patients with lung carcinoma and in more than 95% with lymphoma. In patients with superior vena cava syndrome (SVCS) secondary to non small-cell carcinoma of the lung, radiotherapy is the primary treatment. The likelihood of patients benefiting from such therapy is high, but the overall prognosis of these patients is poor.[26] Chemotherapy may be preferable to radiation for patients with chemosensitive tumors. [26] In 1983, Maddox and associates reported on 56 patients with small-cell lung cancer who presented with superior vena cava syndrome (SVCS). Correction of superior vena cava syndrome (SVCS) was obtained in 9 (56%) of 16 patients treated with radiation therapy alone, in 23 (100%) of 23 given chemotherapy, and in 5 (83%) of 6 who received combined therapy.[27] The most extensive experience in superior vena cava syndrome (SVCS) management secondary to non-Hodgkin lymphoma is reported from the M.D. Anderson cancer center. Patients were treated with chemotherapy alone, chemotherapy combined with radiation therapy, or radiation therapy alone. All patients achieved complete relief of superior vena cava syndrome (SVCS) symptoms within 2 weeks of the institution of any type of treatment. No treatment modality appeared to be superior in achieving clinical improvement.[28] When superior vena cava syndrome (SVCS) is due to thrombus around a central venous catheter, patients may be treated with thrombolytics (eg, streptokinase, urokinase, recombinant tissue-type plasminogen activator) or anticoagulants (eg, heparin, oral anticoagulants). Removal of the catheter, if possible, is another option, and it should be combined with anticoagulation to avoid embolization. [7, 21] . They are most effective when patients are treated within 5 days after the onset of symptoms. In a 1988 report, Adelstein et al discuss prophylaxis against embolic events in the presence of a superior vena cava (SVC) obstruction in the management of 25 patients with malignant superior vena cava syndrome (SVCS).[29] Ten patients were retrospectively reviewed after having been diagnosed clinically without venography and treated without anticoagulation. Five thromboembolic complications occurred, 2 of which proved fatal. Fifteen patients were prospectively evaluated by means of angiography and then treated with anticoagulants. Angiographic evidence of intraluminal subclavian vein or superior vena cava (SVC) thrombosis was found in 5 of these patients, and no thromboembolic complications occurred. Of the 20 patients who were ultimately given anticoagulation therapy, 2 had fatal intracranial hemorrhages. The authors suggested the need for randomized prospective trials if the role of venography and anticoagulation in this syndrome is to be determined.[29]

o o

Surgical care Surgical bypass of the superior vena cava (SVC) may be a useful way to palliate symptoms in carefully selected patients.

Indications to proceed with such procedures are much less clear. For the most part, these are patients with advanced intrathoracic disease amenable only to palliative therapy (ie, after failure of radiation therapy and chemotherapy). Patients with benign disease appear to be the best candidates for bypass. [30, 31] Superior vena cava (SVC) stenting can provide rapid symptomatic relief within few days in most patients with superior vena cava syndrome (SVCS) Superior vena cava (SVC) stenting may provide relief of severe symptoms for patients while the histological diagnosis of the malignancy causing the obstruction is being actively pursued. [20, 25, 31] Stenting may also be indicated in patients in whom chemotherapy or radiation has failed.[32, 33, 34] Some literature recommends stenting as a first-line treatment to be performed early in the management of superior vena cava syndrome (SVCS).[32, 33, 34] Cases of excimer laser removal of pacemaker leads followed by venoplasty and stenting have been reported.[35] Drug Therapy

Corticosteroids
Class Summary
These agents reduce swelling in patients with cerebral or laryngeal edema. Dexamethasone Important therapeutic agent in a number of malignant diseases. Exerts biologic action predominately by binding to glucocorticoid receptor. For symptomatic management in tumor-associated edema. Trombolytics

The potential benefits of thrombolytics for the treatment of pulmonary embolism include fast dissolution of physiologically compromising pulmonary emboli, quickened recovery, prevention of recurrent thrombus formation, and rapid restoration of hemodynamic disturbances. For deep vein thrombosis, lysis of the thrombus can prevent pulmonary embolism and permanent pathologic changes, such as venous valvular dysfunction and postphlebitic syndrome.
UROKINSE (Abbokinase)

Converts plasminogen to plasmin, which degrades fibrin clots, fibrinogen, and other plasma proteins.

Anticoagulants
In superior vena cava syndrome (SVCS), these agents are used mainly to prevent pulmonary embolism from superior vena cava (SVC) thrombus.
Heparin

Inhibits thrombosis by inactivating activated factor X and inhibiting conversion of prothrombin to thrombin. Warfarin Inhibits synthesis of vitamin Kdependent coagulation factors (factors II, VII, IX, X). Prognosis The survival of patients with superior vena cava syndrome (SVCS) depends mainly on the course of the underlying disease. Untreated patients and those not responding to treatment survive approximately 30 days.

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