Superior vena cava syndrome (SVCS) is an array of symptoms caused by the impairment of blood flow through the superior vena cava (SVC) to the right atrium. Symptoms that prompt suspicion of this syndrome include dyspnea, coughing, and swelling of the face, neck, upper trunk and extremities. In rare instances, patients may complain of hoarseness, chest pain, dysphagia, and hemoptysis. Physical signs that may be noted on presentation are neck vein distention, thoracic vein distention, edema of the face or upper extremities, plethora, and tachypnea. Rarely, cyanosis, Horner's syndrome, and a paralyzed vocal cord may also be present.

SVCS is usually a sign of locally advanced bronchogenic carcinoma. Survival depends on the status of the patient's disease. When small cell bronchogenic carcinoma is treated with chemotherapy, the median survival times with or without SVCS are almost identical (42 weeks or 40 weeks). The 24-month survival is 9% in patients without SVCS and 3% in those with the syndrome. When the malignancy is treated with radiation therapy, 46% of patients who have non-small cell lung cancer experience relief of symptoms compared with 62% of patients who have small cell bronchogenic carcinoma. The 2-year survival of 5% is almost the same for both groups.

Most non-Hodgkin's lymphoma patients with SVCS respond to appropriate chemotherapy or to combined modality regimens.

ETIOLOGY/PHYSIOLOGY

Since superior vena cava syndrome (SVCS) was first described by William Hunter in 1757, the spectrum of underlying conditions associated with it has shifted from tuberculosis and syphilitic aneurysms of the ascending aorta to malignant disorders. Almost 95% of SVCS cases described in published modern series are due to cancer; the most common cause is small cell bronchogenic carcinoma, followed by squamous cell carcinoma of the lung, adenocarcinoma of the lung, non-Hodgkin's lymphoma, and large cell carcinoma of the lung. A nonmalignant cause of SVCS in cancer patients is thrombosis that is associated with intracaval catheters or pacemaker wires. A rare cause of SVCS is fibrosing mediastinitis, either idiopathic or associated with histoplasmosis.Additional rare causes of SVCS include metastatic germ cell neoplasms, metastatic breast cancer, colon cancer, Kaposi's sarcoma, esophageal carcinoma, fibrous mesothelioma, Bechet's syndrome, thymoma, substernal thyroid goiter, Hodgkin's disease, and sarcoidosis.

Knowledge of the anatomy of the superior vena cava (SVC) and its relationship to the surrounding lymph nodes is essential to understanding the development of the syndrome. The SVC is formed by the junction of the left and right brachiocephalic veins in the mid-third of the mediastinum. The SVC extends caudally for 6-8 centimeters, terminating in the superior right atrium, and extends anteriorly to the right mainstem bronchus. The SVC is joined posteriorly by the azygos vein as it loops over the right mainstem bronchus and lies posterior to and to the right of the ascending aorta. The mediastinal parietal pleura is lateral to the SVC, creating a confined space, and the SVC is adjacent to the right paratracheal, azygous, right hilar, and subcarinal lymph node groups. The vessel itself is thin-walled, and the blood flowing therein is under low pressure. Thus, when the nodes or ascending aorta enlarge, the SVC is compressed, blood flow slows, and complete occlusion may occur.

The severity of the syndrome depends on the rapidity of onset of the obstruction and its location. The more rapid the onset, the more severe the symptoms because the collateral veins do not have time to distend to accommodate an increased blood flow. If the obstruction is above the entry of the azygos vein, the syndrome is less pronounced because the azygous venous system can readily distend to accommodate the shunted blood with less venous pressure developing in the head, arms, and upper thorax. If the obstruction is below the entry of the azygos vein, more florid symptoms and signs are seen because the blood must be returned to the heart via the upper abdominal veins and the inferior vena cava, which requires higher venous pressure.

ASSESSMENT/DIAGNOSIS

Once superior vena cava syndrome (SVCS) is recognized, prompt clinical attention is important. A diagnosis should be established prior to initiating therapy for the following reasons:

• 75% of patients have symptoms and signs for longer than 1 week before seeking medical attention,
  
• cancer patients diagnosed with SVCS do not die of the syndrome itself but from the extent of their underlying disease, and
  
• 3%-5% of the patients diagnosed with SVCS do not have cancer.

In the absence of tracheal obstruction, SVCS is unlikely to be a life- threatening oncologic emergency and treatment prior to definitive diagnosis is not justified.

The initial evaluation of the patient should include a chest radiograph to look for mediastinal masses and associated findings, such as pleural effusion, lobar collapse, or cardiomegaly. Computed tomography (CT) scanning of the thorax yields the most useful diagnostic information and can define the anatomy of the involved mediastinal nodes. Venous patency and the presence of thrombi are assessed by using contrast and rapid scanning techniques.[2] Depending on local expertise, contrast or nuclear venography, magnetic resonance imaging, and ultrasound may be valuable in assessing the site and nature of the obstruction.

If bronchogenic carcinoma is suspected, a sputum specimen should be obtained. If the sputum specimen is negative, a biopsy specimen should be taken from the most accessible site that is clinically involved with disease. The biopsy approach depends on the working diagnosis, the location of the tumor, the physiologic status of the patient, and the expertise available at the facility. It may include bronchoscopy, biopsy of palpable cervical or supraclavicular lymph nodes, needle biopsy of a lung mass or mediastinal nodes using either CT or ultrasound guidance, mediastinoscopy, mediastinotomy, median sternotomy, video-assisted thoracoscopy, and conventional thoracotomy. The biopsy findings will help the clinician to plan appropriate treatment.

TREATMENT OPTIONS

The treatment of superior vena cava syndrome (SVCS) depends on the etiology of the obstruction, the severity of the symptoms, the prognosis of the patient, and patient preferences and goals for therapy. Radiation therapy or chemotherapy should be withheld until the etiology of the obstruction is clear. The treatments discussed here will focus on superior vena cava (SVC) obstruction caused by a malignant tumor. Since the treatment of malignant obstruction may depend on tumor histology, a histologic diagnosis, if not made earlier, should be made prior to initiation of treatment. Unless there is airway obstruction or cerebral edema, there appears to be no detriment in outcome when treatment is delayed for the assessment. The following treatment approaches can be used for SVCS.

Medical management

A patient with sufficient collateral blood flow and minimal symptoms may not need treatment. If the lesion is above the azygous vein or if the onset of SVC occlusion is slow enough to allow sufficient collateral circulation, the symptoms and signs may stabilize and the patient may be comfortable enough to forego further therapy. Short-term palliation of a symptomatic patient who does not want aggressive treatment may be achieved by elevating the head and using corticosteroids and diuresis. Although potentially useful to treat respiratory compromise, there are no definitive studies that prove the effectiveness of steroids. Diuretics may give symptomatic relief of edema but can ultimately cause systemic complications, such as dehydration.

Radiation therapy

If the obstruction of the superior vena cava is caused by a tumor that is not sensitive to chemotherapy, radiation therapy should be given. Treatment with larger fractions of radiation is thought to be beneficial in developing a rapid response. However, one study shows that there is no obvious need for large radiation fraction sizes for the first few radiation treatments as was previously believed. Many fractionation schemes have been used, with doses ranging from 30 Gy in 10 fractions to 50 Gy in 25 fractions. In one study, more than 90% of the patients achieved a partial or complete response with a 3-week regimen of 8 Gy given once a week for a total dose of 24 Gy.

Chemotherapy

Chemotherapy is the treatment of choice for sensitive tumors such as lymphoma or small cell lung cancer. SVCS does not appear to be an independent prognostic factor, and its presence should not be used to change the treatment approach. Rapid initiation of chemotherapy can result in complete and partial response rates of the SVCS of more than 80% in small cell lung cancer patients.

Thrombolysis

It has been suggested that SVCS arises when a thrombus forms in a partially occluded vein. In patients with a documented thrombus in the SVC, treatment may include thrombectomy, with or without tissue plasminogen activator (TPA) or other thrombolytic agents such as streptokinase or urokinase.

Stent placement

There have been several small studies using an intravascular expandable stent to reopen the occluded SVC. The reported response rates have been about 90% or greater. There is no agreement on the need for anticoagulant therapy after stent placement. In one series that used anticoagulant therapy for patients as part of the treatment protocol, there were reports of reocclusion after this therapy was stopped. However, in another study, 17 cancer patients who were treated with stents and who did not have anticoagulant therapy had no occlusions.

Surgery

Surgical bypass of an obstructed SVC is more appropriate for patients with a benign obstruction than with a malignant obstruction, although surgical bypass has also been used for patients with malignant obstructions.