Superior Vena Cava Syndrome (SVCS)

The 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.[8]

Obstruction of the 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 thin-walled SVC. Complete SVC obstruction is the result of intravascular thrombosis in combination with extrinsic pressure. Incomplete SVC obstruction is more often secondary to extrinsic pressure without thrombosis. Other causes include compression by intravascular arterial devices. The incidence is on the rise, in line with the increased use of endovascular devices.[6]

An obstructed SVC initiates collateral venous return to the heart from the upper half of the body through four principal pathways. The first and most important pathway is the azygous venous system, which includes the azygos vein, the hemiazygos 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 SVC is present. Venous pressure as high as 200-500 cm H2O has been recorded in patients with severe SVCS.

More than 80% of cases of SVCS are caused by malignant mediastinal tumors.[9, 10, 11] Bronchogenic carcinomas account for 75-80% of all these cases, with most of these being small-cell carcinomas.[5] Non-Hodgkin lymphoma (especially the large-cell type) account for 10-15%. Causes of SVCS appear similar to the relative incidence of primary lung and mediastinal tumors. Rare malignant diagnoses include Hodgkin disease, metastatic cancers,[12] primary leiomyosarcomas of the mediastinal vessels, and plasmocytomas.[13, 14, 15]

Nonmalignant conditions that can cause SVCS include the following:

• Mediastinal fibrosis
• Vascular diseases, such as aortic aneurysm, vasculitis, and arteriovenous 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
• Thrombosis related to the presence of central vein catheters

These account for approximately 22% of cases of SVCS.[13, 16, 17, 18]

United States statistics

SVCS develops in 5-10% of patients with a right-side malignant intrathoracic mass lesion. In 1969, Salsali and Cliffton observed SVCS in 4.2% of 4960 patients with lung cancer; 80% of the tumors inducing SVCS were of the right lung.[19] In five large series of small-cell lung cancer, 9-19% of patients demonstrated SVCS. In 1987, Armstrong and Perez found SVCS in 1.9% of 952 patients with lymphoma.[20]

Age-, sex-, and race-related demographics

Malignant causes of 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 SVC in the pediatric age group is rare and has a different etiologic spectrum.

Malignant causes of SVCS are most commonly observed in males because of the high incidence of lung cancer in this population. In contrast, cases related to benign causes show no sex-related differences in frequency.

The frequency of SVCS in different races depends largely on the frequency of lung cancer and lymphomas in these populations.

Survival in patients with SVCS depends mainly on the course of the underlying disease. No mortality, per se, results directly from mild venous congestion.

In patients with benign SVCS, life expectancy is unchanged. If SVCS is secondary to a malignant process, patient survival correlates with tumor histology. Patients with signs and symptoms of laryngeal and cerebral edema have the most life-threatening manifestations of SVCS 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 SVCS survive for only about 30 days.[7]  Survival for those who do not respond to treatment is similar.

Early in the clinical course of superior vena cava syndrome (SVCS), partial obstruction of the superior vena cava (SVC) may be asymptomatic, but more often, minor symptoms and signs are overlooked.

As the syndrome advances toward total SVC obstruction, the classic symptoms and signs become more obvious. Dyspnea is the most common symptom, observed in 63% of patients with SVCS.[8, 21] 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.[8, 21, 22]

The characteristic physical findings of SVCS include venous distention 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.

Complications of SVCS may include the following:

• Laryngeal edema
• Cerebral edema
• Decreased cardiac output with hypotension
• Pulmonary embolism (when an associated thrombus is present)

Patients presenting with overt superior vena cava syndrome (SVCS) may be diagnosed by means of physical examination alone. However, subtle presentations necessitate diagnostic imaging.

Chest radiography

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 et al in 1981 had normal findings on chest radiography.[16]

Computed tomography

Computed tomography (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.[8] 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. (See the images below.)

Superior vena cava syndrome (case 1). Patient was 35-year-old man with 3-year history of progressive upper-extremity and fascial swelling. Patient had undergone treatment for histoplasmosis in the past. CT shows narrowed superior vena cava with adjacent calcified lymph nodes and posterior soft-tissue thickening.

Superior vena cava syndrome (case 1, continued). Sonogram shows markedly damped venous waveform with complete loss of normal venous pulsatility and minimal respiratory variation.

SPECT

Gallium single-proton emission CT (SPECT) may be of value in select cases.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) has not yet been sufficiently investigated in this setting, but it appears promising. It has several potential advantages over CT, in that it provides images in several planes of view, allows direct visualization of blood flow, and does not require iodinated contrast material (an especially important characteristic when stenting is anticipated).[17]

MRI is an acceptable alternative for patients with renal failure or those with contrast allergies. Potential disadvantages include increased scanning time with attendant problems in patient compliance and increased cost.

Venography

Invasive contrast venography is the most conclusive diagnostic tool (see the image below). It precisely defines the etiology of obstruction. It is especially important if surgical management is being considered for the obstructed vena cava.

Superior vena cava syndrome (case 1, continued). Venogram shows almost complete occlusion of superior vena cava with dramatic collateral drainage through left superior intercostal vein.

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 achieved with contrast venography, they demonstrate potency and flow patterns.[23]

Most patients with SVCS present before the primary diagnosis is established. Controversy often arises in the treatment of these patients with 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 SVCS. Sputum cytologic results are diagnostic in 68% of the cases, whereas biopsy of a palpable supraclavicular node is positive in 87%.[24] Bronchoscopy has a 60% success rate, whereas thoracotomy is 100% successful.[24] Open biopsy is rarely needed for diagnosis. Dosios et al showed that cervical mediastinoscopy and anterior mediastinoscopy are effective in establishing a histologic diagnosis.[25]

In the management of superior vena cava syndrome (SVCS), the goals are to relieve symptoms and to attempt cure of the primary malignant process. Only a small percentage of patients with rapid-onset obstruction of the superior vena cava (SVC) are at risk for life-threatening complications.[14]

Patients with clinical SVCS often gain significant symptomatic improvement from conservative treatment measures, including elevation of the head of the bed and supplemental oxygen.[24] 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 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, reviews suggest that SVC obstruction alone rarely represents an absolute emergency that necessitates treatment without a specific diagnosis.[5, 26]

The fractionation schedule for radiotherapy usually includes two to four large initial fractions of 3-4 Gy, followed by daily delivery of conventional fractions of 1.5-2 Gy, up to a total dose of 30-50 Gy. 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 SVC obstruction in 70% of patients with lung carcinoma and in more than 95% of those with lymphoma.

In patients with 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.[27]

Chemotherapy may be preferable to radiation for patients with chemosensitive tumors.[27] In 1983, Maddox et al reported on 56 patients with small-cell lung cancer who presented with SVCS. Correction of 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.[28]

The most extensive experience with management of SVCS 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.[29] All patients achieved complete relief of SVCS symptoms within 2 weeks of the institution of any type of treatment. No treatment modality appeared to be superior in achieving clinical improvement.

When SVCS is due to thrombus around a central venous catheter, patients may be treated with thrombolytics (eg, streptokinase, urokinase, or recombinant tissue-type plasminogen activator) or anticoagulants (eg, heparin or oral anticoagulants). Removal of the catheter, if possible, is another option, and it should be combined with anticoagulation to prevent embolization.[8, 18] . These agents are most effective when patients are treated within 5 days after the onset of symptoms.

In a 1988 report, Adelstein et al discussed prophylaxis against embolic events in the presence of SVC obstruction in the management of 25 patients with malignant SVCS.[30] Ten patients were retrospectively reviewed after having been diagnosed clinically without venography and treated without anticoagulation. Five thromboembolic complications occurred, two of which proved fatal.

Fifteen patients were prospectively evaluated by means of angiography and then treated with anticoagulants.[30] Angiographic evidence of intraluminal subclavian vein or SVC thrombosis was found in five of these patients, and no thromboembolic complications occurred. Of the 20 patients who were ultimately given anticoagulation therapy, two had fatal intracranial hemorrhages. The authors suggested that randomized prospective trials would be needed to determine the roles of venography and anticoagulation in the management of SVCS.

Admit the patient to the hospital if symptoms of SVCS are moderate to severe or if a patient requires the administration of thrombolytic therapy or anticoagulation. Transfer may be required for further diagnostic evaluation and surgical intervention.

Oxygen supplementation may be provided if needed. Antiemetics may be provided as needed to prevent nausea and vomiting. If a patient has been started on steroids, the steroids should be tapered slowly, depending on the patient's condition.

Surgical bypass

Surgical bypass of the SVC may be a useful way to palliate symptoms in carefully selected patients with SVCS. Indications for proceeding with such procedures are not fully 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.[31, 32]

Stenting

The principal options for endovascular therapy today are stenting, percutaneous transluminal angioplasty (PTA), thrombolysis, or some combination thereof. In most patients with SVCS, stenting of the SVC provides rapid symptomatic relief within few days (see the images below).

Superior vena cava syndrome (case 1, continued). Palmaz P308 stent mounted on 12-mm balloon was deployed in superior vena cava after it was predilated to 8 mm. Stent was subsequently dilated to 14 mm.

Superior vena cava syndrome (case 1, continued). Venogram obtained after stenting shows widely patent superior vena cava with no collateral drainage. Pressure measurements after stenting showed 1- to 2-mm residual gradient.

Superior vena cava syndrome (case 1, continued). Sonogram obtained 1 year after stenting shows near-normal venous pulsatility and respiratory phasicity. Patient experienced complete resolution of symptoms.

SVC stenting may provide relief of severe symptoms for patients while the histologic diagnosis of the malignancy causing the obstruction is being actively pursued.[17, 26, 32] It may also be indicated in patients in whom chemotherapy or radiation has failed.[33, 34, 35]

There is growing support for recommending stenting as a first-line treatment to be performed early in the management of SVCS.[33, 34, 35] A 2008 study by Rizvi et al concluded that stenting should be considered first-line therapy for SVCS of benign origin, with open surgical reconstruction still a good option if endovascular repair fails or is unsuitable.[36]

A 2016 study by Breault et al reported that the use of percutaneous endovascular techniques to treat benign SVCS yielded good long-term patency, with recurrences easily addressable by repetition of the procedure.[37]

A 2017 review by Sfyroeras et al examined the results of open (four studies; N = 87) and endovascular (nine studies; N = 136) treatment of benign SVCS.[38] Endovascular interventions included percutaneous transluminal angioplasty (PTA) and stenting (73.6%); PTA only (17.3%); and thrombolysis, PTA, and stenting (9%). Open procedures included spiral saphenous interposition graft, other vein graft, PTFE graft, and human allograft.

In this review, the technical success rate in the endovascular group was 95.6%, the 30-day mortality was 0%, 97.3% of patients reported symptom regression, and 26.9% underwent secondary procedures (58 secondary procedures in total).[38] The 30-day mortality in the open group was 0%, 93.5% of patients reported symptom regression, and 28.4% underwent secondary procedures (33 secondary procedures in total).

The use of endovascular therapy for SVCS of malignant origin has been discussed by del Río Solá et al.[39]

A systematic review and meta-analysis by Azizi et al (38 articles; N = 2200) reported high technical success rates, low restenosis rates, and low recurrence rates after endovascular therapy for SVCS.[40]  These findings lent further support to the paradigm of endovascular therapy as a first-line treatment for SVCS of either malignant or benign origin.

Cases of excimer laser removal of pacemaker leads followed by venoplasty and stenting have been reported.[41]

Consultations to be considered include the following:

• Thoracic surgeon
• Hematologist/oncologist
• Radiation therapist
• Interventional radiologist

Carefully monitor the patient's symptoms and the adverse effects of the administered treatment. Patients should notify the physician immediately if any change in symptoms occurs.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

These agents reduce swelling in patients with cerebral or laryngeal edema.

Dexamethasone (Decadron, Dexasone)

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.

Class Summary

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.

Urokinase (Abbokinase)

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

Class Summary

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 (Coumadin)

Inhibits synthesis of vitamin K–dependent coagulation factors (factors II, VII, IX, X).