Superior and Inferior Vena Caval Syndromes Body_ID: HC010083

The superior vena caval syndrome is usually caused by neoplasms that compress or invade the superior vena cava (e.g., bronchogenic carcinoma or mediastinal lymphoma). The resulting obstruction produces a characteristic clinical complex including marked dilation of the veins of the head, neck, and arms with cyanosis. Pulmonary vessels can also become compressed, inducing respiratory distress.

Body_ID: P010163The inferior vena caval syndrome can be caused by neoplasms that compress or invade the inferior vena cava (IVC) or by a thrombus from the hepatic, renal, or lower extremity veins that propagates upward. Certain neoplasms-particularly hepatocellular carcinoma and renal cell carcinoma-show a striking tendency to grow within veins, and these may ultimately occlude the IVC. IVC obstruction induces marked lower extremity edema, distention of the superficial collateral veins of the lower abdomen, and-with renal vein involvement-massive proteinuria. Robbins basic pathology

Superior Vena Cava Syndrome

Superior vena cava syndrome (SVCS) is the clinical manifestation of superior vena cava (SVC) obstruction, with severe reduction in venous return from the head, neck, and upper extremities. Malignant tumors, such as lung cancer, lymphoma, and metastatic tumors, are responsible for the majority of SVCS cases. With the expanding use of intravascular devices (e.g., permanent central venous access catheters,

pacemaker/defibrillator leads), the prevalence of benign causes of SVCS is increasing. Lung cancer, particularly of small cell and squamous cell histologies, accounts for approximately 85% of all cases of malignant origin. In young adults, malignant lymphoma is a leading cause of SVCS. Hodgkin's lymphoma involves the mediastinum more commonly than other lymphomas but rarely causes SVCS. When SVCS is noted in a young man with a mediastinal mass, the differential diagnosis is lymphoma vs primary mediastinal germ cell tumor. Metastatic cancers to the mediastinum, such as testicular and breast carcinomas, account for a small proportion of cases. Other causes include benign tumors, aortic aneurysm, thyromegaly, thrombosis, and fibrosing mediastinitis from prior irradiation or histoplasmosis.

Patients with SVCS usually present with neck and facial swelling (especially around the eyes), dyspnea, and cough. Other symptoms include hoarseness, tongue swelling, headaches, nasal congestion, epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope, and lethargy. Bending forward or lying down may aggravate the symptoms. The characteristic physical findings are dilated neck veins, an increased number of collateral veins covering the anterior chest wall, cyanosis, and edema of the face, arms, and chest. More severe cases include proptosis, glossal and laryngeal edema, and obtundation. The clinical picture is milder if the obstruction is located above the azygos vein.

Signs and symptoms of cerebral and/or laryngeal edema, though rare, are associated with a poorer prognosis and require urgent evaluation. Seizures are more likely related to brain metastases

than to cerebral edema from venous occlusion. Patients with small cell lung cancer and SVCS have a higher incidence of brain metastases than those without SVCS.

Cardiorespiratory symptoms at rest, particularly with positional changes, suggest significant airway and vascular obstruction and limited physiologic reserve. Cardiac arrest or respiratory failure can occur, particularly in patients receiving sedatives or undergoing general anesthesia.

The diagnosis of SVCS is a clinical one. The most significant chest radiographic finding is widening of the superior mediastinum, most commonly on the right side. Pleural effusion occurs in only 25% of patients, often on the right side. However, a normal chest radiograph is still compatible with the diagnosis if other characteristic findings are present. CT provides the most reliable view of the mediastinal anatomy. The diagnosis of SVCS requires diminished or absent opacification of central venous structures with prominent collateral venous circulation. MRI has no advantages over CT. Invasive procedures, including bronchoscopy, percutaneous needle biopsy, mediastinoscopy, and even thoracotomy, can be performed by a skilled clinician without any major risk of bleeding. For patients with a known cancer, a detailed workup usually is not necessary, and appropriate treatment may be started after obtaining a CT scan of the thorax. For those with no history of malignancy, a detailed evaluation is essential to rule out benign causes and determine a specific diagnosis to direct the appropriate therapy.

Superior Vena Cava Syndrome: Treatment

The one potentially life-threatening complication of a superior mediastinal mass is tracheal obstruction. Upper airway obstruction demands emergent therapy. Diuretics with a low-salt diet, head elevation, and oxygen may produce temporary symptomatic relief. Glucocorticoids may be useful at shrinking lymphoma masses; they are of no benefit in patients with lung cancer.

Radiation therapy is the primary treatment for SVCS caused by non-small cell lung cancer and other metastatic solid tumors. Chemotherapy is effective when the underlying cancer is small cell carcinoma of the lung, lymphoma, or germ cell tumor. SVCS recurs in 10–30% of patients; it may be palliated with the use of intravascular self-expanding stents (Fig. 270-1). Early stenting may be necessary in patients with severe symptoms; however, the prompt increase in venous return after stenting may precipitate heart failure and pulmonary edema. Surgery may provide immediate relief for patients in whom a benign process is the cause.

Clinical improvement occurs in most patients, although this improvement may be due to the development of adequate collateral circulation. The mortality associated with SVCS does not relate to caval obstruction, but rather to the underlying cause.

SVCS and Central Venous Catheters in Adults

The use of long-term central venous catheters has become common practice in patients with cancer. Major vessel thrombosis may occur. In these cases, catheter removal should be combined with anticoagulation to prevent embolization.

SVCS in this setting, if detected early, can be treated by fibrinolytic therapy without sacrificing the catheter. The routine use of low-dose warfarin or low molecular weight heparin to prevent thrombosis related to permanent central venous access catheters in cancer patients is not recommended.

Harrison

SUPERIOR VENA CAVA SYNDROMEIssues at the Time of AdmissionClinical PresentationSuperior vena cava syndrome (SVCS) is the oncologic emergency most likely to be the first symptom of cancer. As many as half of the patients with SVCS do not have a pre-existing cancer diagnosis. SVCS is a clinical diagnosis. Patients complain of dyspnea, and present with facial and upper extremity swelling. Occasionally, patients may complain of cough, chest tightness, or other symptoms caused by the tumor in the thorax. Physical findings typically consist of venous distention across the upper chest and neck, facial edema and plethora. Arm edema is present in approximately 15% of patients. Patients may have other physical findings caused by the mass within the thorax, including signs of airway obstruction, pleural effusion, or volume loss.Differential DiagnosisSVCS is usually due to cancer in the modern era, but nonmalignant causes are still found in about 15% of patients. Thrombosis around central lines is a common event that may cause SVCS. Histoplasmosis and other chronic inflammatory diseases cause the remainder of the benign cases.P.923

Most cases of malignant SVCS are caused by lung cancer, usually small cell lung cancer. It has been estimated that SVCS occurs in more than 20% of patients with small cell lung cancer. Non-Hodgkin's lymphomas account for 7%–10% of cases of SVCS, and breast cancer for another 10%. Rare causes include germ cell tumors of the mediastinum, thymoma, and Hodgkin's disease.Chest x-rays are abnormal in 85% of cases of SVCS. Superior mediastinal widening is seen in the majority of cases, and right hilar mass or pleural effusions are common findings. Anterior mediastinal mass should be a clue to thymoma, lymphoma, or germ cell tumor. Cardiomegaly is occasionally seen.CT of the thorax is the most important diagnostic tool. In addition to demonstrating the anatomy of SVCS, it accurately guides both biopsy and radiation therapy. MRI is not clearly superior to CT for this purpose and is much less widely used.Because SVCS is often the first sign of cancer, priority should be given to making a tissue diagnosis. Sputum cytology and fine needle aspiration are the most commonly used and highest yield techniques. The yield of sputum cytology in suspected lung cancer might be as high as 50%. Lymph nodes in the supraclavicular and axillary areas should be sought; fine needle aspiration biopsy of these is useful when they are present. If pleural effusion is present, thoracentesis may produce a histologic diagnosis. Bronchoscopy can be safely performed if the patient is suspected of having lung cancer, and has a high yield in SVCS (about 50%).If these less invasive procedures are not helpful diagnostically, it may be necessary to obtain tissue from within the thorax. The safest technique is CT-guided fine needle aspiration biopsy.

Either mediastinoscopy or limited anterior thoracotomy can be safe and highly effective ways to establish a diagnosis. Neither procedure is associated with a significant increase in serious complications in patients with SVCS, although rare patients do require additional surgical intervention.Although as many as half of all patients with SVCS have some thrombus in association with the obstruction to blood flow, the identification of thrombus is of no clinical or therapeutic significance (see the section on “Issues During the Course of Hospitalization†below). Venography may be performed as part� of the evaluation to identify candidates for vascular stenting.Initial TherapyRoutine care of patients with SVCS includes bed rest with elevation of the head of the bed, oxygen therapy as indicated, and other comfort measures for relief of pain and cough. Steroids and diuretics have been used for symptom management, although no clear data support their benefit.Anticoagulation is controversial. The routine use of heparin or warfarin anticoagulation has not been shown to hasten the relief of symptoms, and thrombolysis is risky and without proven benefits. Life threatening pulmonary embolization is highly unusual in patients with SVCS, and anticoagulation may delay efficient diagnosis and treatment. In contrast, when SVCS in cancer patients is caused by thrombosed central lines, this entity is quite effectively treated with local thrombolysis followed by heparin and warfarin. Removal of the catheter is necessary only if the clot fails to lyse. The use of angioplasty has been reported, although the expertise and experience necessary to safely perform this procedure is not widely available.Vascular stenting as initial therapy for SVCS is also controversial. Insertion of a stent produces rapid relief of

symptoms for 95% of patients with SVCS due to lung cancer (9). Long-term complications of stent placement, including rates of thrombosis or reocclusion rates, have not been well established. Whether cancer patients with superior vena cava stents should all receive anticoagulation remains an unanswered question. Most experts recommend that stents be the initial therapy when patients have recurred after radiation treatment of SVCS, when patients have SVCS due to cancers that are not likely to respond to radiation and chemotherapy, or when radiation therapy might be uniquely burdensome. There are no cost comparison studies and no long-term follow-up studies of stent placement.SVCS caused by small cell lung cancer and by lymphoma is treated with chemotherapy, and clinical resolution occurs just as rapidly as with radiation therapy. Radiation therapy is the primary treatment for all other malignant causes, although chemotherapy is increasingly used concurrently for diseases such as non-small cell lung cancer. Radiation and/or chemotherapy of SVCS in non-small cell lung cancer results in relief of symptoms for more than 60% of patients. The initiation of either chemotherapy or radiation therapy should be prompt, but SVCS is not so urgent as to mandate treatment immediately (i.e., especially prior to making an accurate tissue diagnosis).Issues During the Course of HospitalizationThe signs and symptoms of patients with SVCS begin to resolve in 5–7 days after the start of treatment. Resolution of symptoms is not necessarily accompanied by radiographic change; thus, there is no indication to follow the chest x-ray frequently. Complications of radiation therapy include esophagitis, bone marrow suppression, fatigue, and mild immunosuppression. These side effects are treated expectantly.

Patients who have large lung cancers are at risk of developing bronchial obstruction or pneumonia during treatment. Clinically apparent pulmonary embolism as a complication of SVCS is rare, but should be treated conventionally if it occurs (Chapter 53). Most patients with SVCS should receive prophylaxis for deep venous thrombosis while they are at bedrest.Patients may fail to respond to treatment because of formation of thrombus, refractoriness of the primary tumor, P.924

or hemorrhage or edema around the primary tumor that further occlude the vena cava. The assumption that treatment is failing should not be made until at least two weeks of radiation therapy has been delivered, since responses to radiation may still occur. The evaluation of patients with poor responses should include repeat chest CT and possibly venography.Patients whose SVCS recurs after an initial response, and patients who have failed to respond to radiation, are candidates for vascular stent or surgical intervention. Several types of vascular stents have been developed. Stenting is clearly less invasive than surgical options (such as thoracotomy with vascular excision and grafting or SVC bypass), although individual anatomy may not always permit stent placement. Complications of stents and grafts include infection, stent migration, mediastinitis, graft failure, perforation, and thrombosis. Patients must be carefully selected, and the extent of institutional expertise considered.Discharge IssuesPatients who are physiologically stable while being treated for SVCS may be discharged home. Outpatient radiation therapy and chemotherapy may be augmented by home nursing visits if

necessary. The response to treatment is followed clinically. Repeated imaging of the tumor is planned as needed to evaluate further therapy. Analgesia for esophagitis should be offered prophylactically; the patient's oral intake and hydration may require monitoring once esophagitis occurs.The prognosis of SVCS depends on the cause. Small cell lung cancer and lymphoma are highly responsive to initial therapy, potentially curable, and often accompanied by durable remissions. Non-small cell lung cancer is much less responsive, and relapse is common. Seventeen percent of small cell lung cancer patients and 19% of non-small cell lung cancer patients experienced recurrence of SVCS after treatment (9). SVCS caused by other cancers responds variably, depending on whether effective treatment is available. Thymoma has a variable natural history, and survival may be long even when treatment is relatively ineffective. Extragonadal germ cell tumors are treatment-responsive, but have a much worse prognosis than testicular germ cell tumors.

Superior vena cava (SVC) obstructionA. Epidemiology and etiology1. Malignant etiologies(85% to 95% of cases)

Lung cancer (about half of the small cell type) accounts for 80% of cases of SVC obstruction. SVC syndrome develops in about 5% of patients with lung cancer.

Malignant lymphoma accounts for 15% of cases of SVC obstruction. Nearly all cases have high-grade histology. Hodgkin lymphoma or low-grade nodular lymphomas rarely cause SVC obstruction.

Other etiologies. Metastatic disease (most commonly the result of breast adenocarcinoma or testicular seminoma), sarcomas, and other malignancies, such as gastrointestinal tumors, transitional cell carcinomas and melanomas, account for the small remainder of cases.

2. Benign etiologies(<15% of cases)

Mediastinal fibrosiso Idiopathic fibrosing mediastinitiso Histoplasmosis (in endemic regions), actinomycosiso Tuberculosis and pyogenic infectionso Associated with Riedel's thyroiditis, retroperitoneal

fibrosis, sclerosing cholangitis, and Peyronie's diseaseo After radiation therapy (RT) to the mediastinum

Thrombosis of vena cavao Long-term central venous catheterization, transvenous

pacemakers, balloon-tipped pulmonary artery catheters, peritoneal venous shunting

o Polycythemia vera, paroxysmal nocturnal hemoglobinuria

o Behçet's syndromeo Idiopathic

Benign mediastinal tumorso Aneurysm of aorta or right subclavian arteryo Dermoid tumors, teratomas, thymomao Goiter, sarcoidosis

B. Pathogenesis1. Obstruction and thrombosis

Tumors growing in the mediastinum compress the thin-walled vena cava, leading to its collapse. Venous thrombosis because of stasis or vascular tumor invasion often appears to be responsible for acute-onset SVC syndrome.2. Collateral circulationVena cava obstruction caused by malignancy often progresses too rapidly to develop sufficient collateral circulation, which might alleviate the syndrome. If the obstruction occurs above the azygos vein, the obstructed SVC could then drain into the azygos system. The azygos vein, however, is frequently obstructed by malignancy below its origin.3. Incompetent internal jugular vein valvesa rare occurrence, cause a dire emergency that is manifested by the filling of these veins. Patients who present with this finding die within hours or days of massive cerebral edema unless treatment is immediately instituted.C. DiagnosisThe diagnosis is usually based on the clinical findings and the presence of a mediastinal mass. SVC syndrome rarely has to be treated before a histological diagnosis is made.1. Symptomsof SVC syndrome are present for less than 2 weeks before diagnosis in 20% of patients and for more than 8 weeks in 20%.P.574

The most common presenting symptoms are shortness of breath (50% of patients), neck and facial swelling (40%), and swelling of trunk and upper extremities (40%). Sensations of choking, fullness in the head, and headache are also frequent complaints. Chest pain, cough,

lacrimation, dysphagia, hallucinations, and convulsions are less frequent.

SVC obstruction may occasionally be accompanied by spinal cord compression, usually involving the lower cervical and upper thoracic vertebrae. The SVC syndrome consistently precedes spinal cord compression in these cases. The coexistence of these two complications should be seriously suspected in patients with upper back pain.

2. Physical findingsThe most common physical findings are thoracic vein distention (65%), neck vein distention and edema of face (55%), tachypnea (40%), plethora of the face and cyanosis (15%), edema of upper extremities (10%), and paralysis of vocal cords and Horner's syndrome (3%). Veins in the antecubital fossae are distended and do not collapse when elevated above the level of the heart. Retinal veins may be dilated on funduscopic examination. Dullness to percussion over the sternum may be present. Laryngeal stridor and coma are grave signs.3. Radiographs

Chest radiograph demonstrates a mass in more than 90% of patients. The mass is located in the right superior mediastinum in 75% of cases and is combined with a pulmonary lesion or hilar adenopathy in 50%. Pleural effusions are present in 25% of cases, nearly always on the right side.

Chest computed tomography (CT) scan. Contrast-enhanced CT can pinpoint the area of obstruction, the degree of occlusion, and the presence of collateral veins. CT scans show absence of contrast in central venous structures with

opacification of collateral routes. It can guide fine-needle aspiration.

Superior venocavogram. Digital subtraction angiography demonstrates the exact site of obstruction and is the procedure of choice in planning stenting procedures. This information is rarely needed for localization of RT ports.

Magnetic resonance imaging (MRI) scans of the cervical and upper thoracic vertebrae should be planned in patients with SVC syndrome and back pain, particularly in the presence of Horner's syndrome or vertebral destruction on plain films.

4. Histological diagnosisis important for identifying malignancies that must be treated with cytotoxic agents to improve survival (e.g., lymphoma, small cell lung cancer). After RT is started, tissue diagnosis is difficult to interpret due to nondescript necrosis from radiation. Likewise, steroids can affect histology if the underlying diagnosis is lymphoma.

Cytology of sputum is positive in 67% of patients and of pleural effusion fluid in nearly all patients with SVC syndrome.

Bronchoscopy and bronchial brushings are positive in 60% of patients. Bronchoscopy and bronchial biopsy are rarely associated with serious complications when performed by experienced endoscopists.

Lymph node biopsy of palpable nodes can be helpful. Biopsy of palpable scalene nodes in patients with SVC syndrome reveals tumor in 85% of cases; biopsy of

nonpalpable, scalene nodes reveals tumors in only 30% to 40% of cases.

Transthoracic fine-needle aspiration can be attempted for peripheral lesions that cannot easily be approached by bronchoscopy or in whom bronchoscopy results are nondiagnostic. The risk for pneumothorax is small but real.

Minithoracotomy nearly always results in a definitive histological diagnosis. Bleeding points are usually visualized and can be controlled. Limited anterior thoracotomy should be considered in patients with

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early SVC syndrome and without productive cough, diagnostic bone marrow evaluation, pleural effusion, or palpable lymphadenopathy.

Mediastinoscopy with biopsy risks hemorrhage and other complications. However, when mediastinoscopy is performed on a highly selected group of patients, positive results are obtained in 80% of cases.

Bone marrow biopsy is helpful in patients suspected of having small cell lung cancer or lymphoma, especially in patients with cytopenia or leukoerythroblastic blood smear.

D. ManagementThere is little clinical or experimental evidence that unrelieved SVC syndrome is life-threatening. Emergency treatment is indicated only in the presence of cerebral dysfunction, decreased cardiac output, or upper airway obstruction.1. Supportive therapy

Airway obstruction should be corrected and hypoxia treated by oxygen administration. Corticosteroids reduce brain edema and improve the obstruction by decreasing the inflammatory reaction associated with the tumor and early RT. Diuretics may be helpful.2. StentingPercutaneous placement of self-expanding metal endoprostheses gives rapid symptomatic relief in 90% to 100% of patients. When available, stenting is the procedure of choice, especially in the setting of recurrent SVC obstruction after RT. Complications are infrequent, but interventional radiologists experienced in stent placement are not universally available.3. RTThe total dose of RT varies between 3,000 and 5,000 cGy, depending on the general condition of the patient, severity of the symptoms, anatomic site, and histological type of underlying malignant tumor. Symptoms may resolve dramatically even without establishment of patency of the SVC.

Response. Improvement is evident within 3 to 7 days for most patients. Complete response is observed in about 75% of patients with lymphoma and in 25% with lung cancer. Virtually all patients with lymphoma have at least a partial response, whereas about 15% of patients with lung cancer experience no real benefit from treatment.

Median survival is about 10 months for small cell lung cancer, and 3 to 5 months for other types of lung cancer.

Local relapse and recurrent SVC syndrome occur in 15% to 20% of patients but rarely after RT for lymphoma.

4. Chemotherapy

is indicated in patients with malignant lymphoma or with small cell lung cancer. Chemotherapy is used in combination with RT in these conditions.5. Anticoagulants and antifibrinolytic agentsmay be helpful if the underlying cause of the SVC thrombosis is an indwelling catheter. These agents rarely result in disappearance of caval thrombosis but may be used in conjunction with stent placement.6. Surgical decompressionof acute SVC obstruction and incompetence of jugulosubclavian valves consists of reconstructing or bypassing the SVC using a spiral saphenous vein graft or left saphenoaxillary vein bypass, which can be done under local anesthesia.

Superior vena cava (SVC) obstruction with airway compromiseSVC obstruction is not an emergency unless there is tracheal compression with airway compromise: usually there is time to plan optimal treatment, and this is to be preferred, rather than rushing into therapy which may not be beneficial.[diskette]11 Causes: Typically lung cancer; rarely from causes of mediastinal enlargement (eg germ cell tumour); lymphadenopathy (lymphoma); thymus malignancy; thrombotic disorders (eg Behçet's or nephrotic syndromes); thrombus around an IV central line; hamartoma; ovarian hyperstimulation (OHCS p75); fibrotic bands (lung fibrosis after chemotherapy). Signs &; symptoms: Dyspnoea; orthopnoea; swollen face &; arm; cough; plethora/cyanosis; headache; engorged veins. Pemberton's test: On lifting the arms over the head for >1min, there is ↑ facial plethora/cyanosis, JVP↑ (non-pulsatile), and inspiratory stridor. Tests: Sputum cytology, CXR, CT, venography.

Management: Get a tissue diagnosis if possible, but bronchoscopy may be hazardous. Give dexamethasone 4mg/6h PO. Consider balloon venoplasty and SVC stenting,[diskette]12 eg prior to radical or palliative chemo- or radiotherapy (depending on tumour type).

Superior Vena Cava Syndrome (10)Obstruction of the superior vena cava is usually caused by extrinsic compression. The majority of cases are associated with bronchogenic carcinoma (especially small-cell carcinoma), lymphoma, and metastatic disease. The earliest manifestation is asymptomatic, unexplained distention of the neck veins. Late signs include swelling of the face, neck, and upper extremities, plethora, shortness of breath, and persistent headache. Although the condition is rarely fatal, increased intracranial pressure and thrombosis leading to neurologic deficits may ensue. The clinical diagnosis is reinforced by the finding of a mass on chest radiography in the right superior mediastinum or hilar area. Chest CT with careful evaluation of the vasculature should be performed.At one time, it was considered essential to treat the mass immediately with emergency radiotherapy. Now, the view is one of urgency rather than emergency. The first task is to consider whether a tissue diagnosis should be obtained before radiotherapy is instituted (see Chapter 44) because a host of tumors with different degrees of radiosensitivity may be responsible for the condition. Although many malignancies respond within 1 week to radiation, some may respond better to chemotherapy, and occasionally a nonmalignant process that would not benefit from radiation is the cause (e.g., tuberculous

adenopathy, substernal goiter). When a tissue diagnosis will alter therapy, invasive study to obtain tissue should proceed. If a small-cell carcinoma or lymphoma is found, chemotherapy might be placed ahead of radiation as the treatment of choice (see Chapters 53 and 84).Optimal therapy depends on the underlying diagnosis, prior treatment, and overall clinical status of the patient. Diuretics and corticosteroids can occasionally diminish local symptoms, but the effect is transient, and these agents are no substitute for more-definitive therapy. The use of heparin provides no benefit. The occurrence of superior vena cava syndrome does not worsen the prognosis (if adjusted for stage of disease), particularly in cases of small-cell lung cancer.