Radiologic stages of vena cava obstruction. The Stanford classification system for superior vena cava (SVC) syndrome was developed to assist in identifying patients at risk of substantial airway or cerebral compromise and therefore warranting rapid intervention. A: Stanford type I: mild SVC obstruction, with vessel obstruction of less than 90%. B: Stanford type II: high-grade SVC stenosis (grade of stenosis 90 –100%). C: Stanford type III: complete SVC obstruction and prominent flow through collateral veins, but without involvement of the mammary and epigastric veins. D: Stanford type IV: complete SVC obstruction and prominent flow through collateral veins and the mammary and epigastric veins. (Adapted from Reference 26, with permission). 

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... they are non-collapsing if above the heart level. Consecutive signs of decreased venous flow are cyanosis and plethora. Furthermore, edema of the larynx or pharynx may adversely affect their function and lead to complaints including hoarseness, cough, stridor, dyspnea, and dysphagia. Figure 1 shows the most frequent signs and symptoms in SVCS. Patients with SVCS can, rarely, develop life-threatening complications such as cerebral edema, causing headache, dizziness, confusion, and eventually coma or compromised hemodynamics, if SVC obstruction impairs venous return to the right atrium. Hemodynamic alterations can also be caused by direct compression of the heart by a mediastinal mass. Blurred vision or conjunctival suffusion may indi- cate imminent papilledema. Another rare complication of SVCS is esophageal varices, which occasionally cause variceal bleeding, especially in chronic SVCS. As a consequence of the increased cervical venous pressure, subcutaneous vessels may distend, providing collateral circulation to the lower torso and finally to the inferior vena cava. The most important collateral pathway to the inferior vena cava is via the azygos/hemiazygos veins and intercostal veins. Other collateral pathways include the internal mammary veins and their tributaries and conjunctions to the superior and inferior epigastric veins, and the long thoracic veins, which discharge into the femoral and vertebral veins. Unfortunately, it requires several weeks to develop a sufficient collateral vascular network, so it stands to reason that clinical manifestations of SVCS may vary and do not exclusively depend on the degree of vascular obstruction, but also on the rapidity of onset. Approxi- mately one third of all SVCS patients develop clinical signs and symptoms of SVC obstruction within a 2-week period, but sometimes it can take longer. In summary, facial edema, dilated head, neck, and chest veins, dyspnea, cough, and in some cases, orthopnea are the most common symptoms of SVCS. Although the clinical appearance of SVCS can be striking at times (see Fig. 1) and the patient may appear severely distressed, SVCS itself is rarely fatal. Only when severe cerebral edema or hemodynamic alterations complicate the course of SVCS is a patient at high risk of dying. Usually, the clinical diagnosis of SVCS is based on a quite clear clinical presentation, with a combination of the aforementioned signs and symptoms. A careful physical examination can rule out common differential diagnoses that may mimic SVCS, including congestive heart failure and Cushing syndrome (eg, by ectopic production of ad- renocorticotropic hormone). Physical examination should include a careful evaluation of central nervous functions, because neurologic alteration may be subtle, although al- ready indicating imminent cerebral edema and, thus, a life-threatening complication and the need for immediate therapeutic intervention. Additionally, appraisal of respiratory function and hemodynamics is needed to determine the patient’s risk of adverse outcome. Taking a detailed history of the current medical condition is equally important, and it should include onset and duration of symptoms and medical history, with emphasis on malignant conditions and recent intravascular procedures, including central venous lines. Generally, symptoms develop over a period of several weeks, and their severity increases with duration of SVC obstruction. Of interest, formation of venous collaterals may improve clinical manifestations of SVCS in some cases. In conclusion, patient history and a close physical examination constitute a solid basis for adequate management of patients with SVCS. The severity of symptoms determines the required diagnostic procedures and the acuteness of therapeutic interventions. According to Yu and colleagues, 25 hemodynamic symptoms (facial swelling) are most frequent, followed by respiratory symptoms (dyspnea, cough). Common symptoms are displayed in Table 2. The diagnosis of a large mediastinal mass can be made on a conventional chest radiograph. For a more detailed visualization of the SVC and its surrounding structures, a chest computed tomogram (CT) with intravenous contrast medium in the venous phase is recommended. Alternatively, magnetic resonance imaging (MRI) with MRI phlebocavography can be performed. Both CT and MRI can be used to diagnose the underlying pathology, including tumor mass size and localization. SVC diameter and length of SVC stenosis/occlusion can be determined, which constitutes a solid basis for planning endovascular treatment. Alternatively, a conventional phlebocavography with si- multaneous intravenous contrast injection from both upper extremities can be performed. Since this is usually done in the angiography suite, venous pressure gradient measure- ments and stenting can be performed at the same time. The radiologic stages of vena cava obstruction, as suggested by Stanford and colleagues, 26 are displayed in Figure 2. The treatment of SVCS is determined by the underlying disease, so the cornerstone of the treatment of thoracic malignancies is accurate diagnosis, and in the case of malignancy an exact determination of tumor extension and stage. In lung cancer, the presence of SVCS usually indi- cates an extensive mediastinal tumor mass. In addition to morphological imaging modalities such as CT or MRI, positron emission tomography (a molecular imaging modality), provides further information on node status and mediastinal involvement. Additionally, a cranial CT or preferably a cranial MRI and, if necessary, a bone scin- tigraphy 27 may complete the staging procedures. However, to clarify the nature of the underlying disease, biopsies have to be obtained for histological and/or cytological examination. A diagnostic bronchoscopy, either in flexible or rigid technique, can detect endoluminal tumor growth, as well as tumor infiltration of central and peripheral airways, and obtain tumor tissue samples, via forceps or flexible cryo- probe. 28 In addition, cytological methods such as protected specimen brush, bronchial washing, or bronchoalveolar lavage tend to increase the diagnostic yield. Conventional mediastinoscopy is limited to paratracheal lymph nodes (2R, 2L, 4R, and 4L), pretracheal nodes (stations 1 and 3), and anterior subcarinal nodes (station 7). Newer techniques such as video-assisted mediastinoscopic lymphadenectomy allow better visualization and more extensive sampling. 29 Even if a complete mediastinal lymphadenectomy is performed, not all lymph nodes can be assessed. To avoid bleeding complications in SVCS, less invasive diagnostic methods are preferred. Mediastinal lymph nodes can be biopsied under conventional anatomical or CT-based localization or newer imaging methods. Endobronchial ultrasound guided fine- needle aspiration biopsy of mediastinal lymph nodes has a high diagnostic accuracy and offers an alternative and less invasive technique for biopsy of mediastinal lymph nodes, as compared to mediastinoscopy. 30 Endobronchial ultrasound can overcome the limitations of mediastinoscopy in assessing lymph node stations 2, 3, 4, 7, 10, and 11, and is preferred in terms of safety and costs. Sputum cytology, pleural fluid cytology, and biopsy of peripheral enlarged lymph nodes (eg, supraclavicular) are recommended if these are present and might be diagnostic in up to two thirds of cases. 31 Treatment of the underlying disease strongly depends on histology type, staging of the disease, previous treatments, and overall prognosis. Novel molecular biological targets such as epidermal growth factor receptor tend to give further important information on treatment options. If, after obtaining medical history, clinical assessment, and chest imaging, malignant SVCS is probable, management depends on the presence or absence of grade 4 symptoms (ie, critical issues for the patient, such as threatened air- way, cardiac compression, and/or hypotension or syncope without preceding factors) (Table 3). If the patient presents with grade 4 symptoms, venogram and urgent stenting should be considered. If thrombosis is present, the patient might benefit directly from thrombolytic agents. A threatened airway should immediately be protected. All other stages prompt tissue biopsy and staging, which should be done without relevant delay. Early multidisciplinary planning improves the management of SVCS. If neurologic symptoms are present, brain metastases should be excluded with imaging (preferably contrast-enhanced MRI, alterna- tively contrast-enhanced CT). After biopsy and staging, a tumor-specific and stage-specific treatment plan should be developed depending on the tumor entity and symptoms, and, in the case of malignancy, on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale score ( Figure 3 summarizes a treatment algorithm for the management of malignant SVCS. Although the prognosis of most malignancies causing SVCS is poor, most of the underlying conditions may respond well to chemotherapy, radiation therapy or combined chemotherapy and radiation therapy; several months of survival can be seen in properly treated patients. As SVCS might be the first manifestation of a thoracic malignancy, even in advanced-stage malignancies all therapeutic options, including invasive ventilation, should be considered, as they might gain several months of survival. The primary goal in SVCS management is alleviation of symptoms and treatment of the underlying disease. We recommend that the patient’s head be raised to decrease hydrostatic pressure and head and neck edema, though ...