Obstruction of the superior vena cava complicates many mediastinal diseases, often impeding blood flow through the superior vena cava and resulting in a collection of signs and symptoms. These signs and symptoms together constitute the superior vena cava syndrome (SVC syndrome), first described by William Hunter13 in 1757 as a complication of a saccular aortic aneurysm. Early case series reported about equal distribution of cases due to aortic aneurysms and thoracic neoplasms9,14. More recent series have reported that thoracic neoplasms account for the majority of SVC syndrome cases4,7,17,24,27,35.
The modern practice of medicine has seen increased use of semipermanent intravascular catheters. These catheters are placed in large central veins and are used for a variety of treatments, ranging from long-term antibiotics and chemotherapy to hyperalimentation and dialysis. Unfortunately, thrombosis occurs in up to 40% of patients with central catheters2,18,19, and a significant number of these patients progress to develop the SVC syndrome2,18. The increasing use of these catheters with their associated thromboses has resulted in more nonmalignant causes of the SVC syndrome. Despite many individual case reports or small case series describing these benign SVC syndromes, the exact prevalence remains undetermined. We conducted the current study to determine the prevalence of different etiologies of SVC syndrome and whether the varying etiologies presented with different signs and symptoms.
MATERIALS AND METHODS
Saint Thomas Hospital is a 455-bed, tertiary care hospital. This retrospective study was considered exempt by institutional review board guidelines. The medical records of all patients cared for at Saint Thomas Hospital between January 1, 1996, and November 30, 2001, were searched according to billing codes. All charts coded with an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) code of 453.2 (vena cava thrombosis) or 459.2 (compression of vein; stricture of vein; vena cava syndrome) were then reviewed to determine whether the patient had the SVC syndrome. Patient demographics (age and sex), etiology, and the method of diagnosing the SVC syndrome were collected from the records of each patient. The patient's initial presenting signs and symptoms were also recorded, along with other pertinent medical history, such as presence of venous access, medications, and prior medical history. The Saint Thomas Tumor Registry, which maintains records of every malignancy treated at Saint Thomas Hospital and affiliated clinics, was queried to obtain the total number of each tumor type treated for the study period. All procedures performed on the patient within 2 weeks of the diagnosis of SVC syndrome were collected. Any complications or concerns documented in either the physician or nursing notes were also recorded.
Data are presented as the means ± standard deviation unless otherwise noted. Chi-square analyses and the Fisher exact tests were performed to determine differences in signs and symptoms according to etiology. SPSS for Windows software (SPSS, Inc., Chicago, IL) was used for all calculations. All reported p values are 2-sided, with 0.05 used to determine significance.
The search of the medical records according to ICD-9 codes revealed 50 charts coded with 453.2 (vena cava thrombosis) and 166 charts coded with 459.2 (compression of vein; stricture of vein; vena cava syndrome) between January 1, 1996, and November 30, 2001. Of these, 10 were duplicates, resulting in 206 unique patients. Medical charts were available for 202 of the 206 patients. Medical records of the available 202 patients were reviewed and 78 cases of SVC syndrome were identified (Figure 1), with 42 occurring in female patients and 36 in males. The average age at the time of diagnosis was 57.7 ± 14.4 years. The remaining 124 patients had diagnoses other than SVC syndrome, including occlusion or thrombosis of the inferior vena cava and thrombosis or stricture of the subclavian or internal jugular vein.
Thoracic malignancies were present in 47 of the 78 patients (60%). However, 5 of these patients (6% of the overall total) also had a semi-permanent indwelling intravascular device. All 5 of these patients had lung cancer with at least some mediastinal pathology and are included in the malignant subgroup when comparing malignant and benign etiologies. The remaining 31 patients (40%) demonstrated no evidence of thoracic malignancy and were found to have other benign, mediastinal pathology resulting in the SVC syndrome.
Bronchogenic carcinomas accounted for 36 of the 47 cases (77%) of thoracic malignancy and 46% of all SVC syndrome cases. Cancers were almost equally divided between small cell (17 cases; 22%) and non-small cell lung cancer (19 cases; 24%) (Table 1). Lymphoma accounted for 6 cases (8% of the total) and germ cell tumors resulted in 2 SVC syndrome cases (3%). Although germ cell tumors are relatively rare, SVC syndrome developed in the highest percentage of these patients (see Table 1). Metastatic prostate cancer, thymic cancer, and adenocarcinoma of unknown primary each accounted for a single case.
The majority of benign causes (71%) involved the use of intravascular devices. A Port-a-Cath (Deltec, St. Paul, MN) was associated with 16 cases (21%), dialysis catheters with 4 cases (5%), and a pacemaker wire and Hickman catheter (CR Bard, Murray Hill, NJ) with a single case each. Fibrosing mediastinitis was the underlying disease in 6 cases (8%), and hematoma after aortic dissection repair, pseudotumor, and primary SVC thrombosis were each the etiology in 1 case.
The purpose for the placement of these infusion catheters varied widely. The Port-a-Cath was used to administer total parenteral nutrition in 4 patients (2 with Crohn disease, 1 with short-gut syndrome, and 1 with malnourishment after gastrectomy), chemotherapy in 4 patients (2 with breast cancer, 1 each with colon cancer and myeloma), and frequent antibiotic courses in 3 patients (2 with recurrent pulmonary infections and 1 with Felty syndrome). In the remaining 5 patients, the Port-a-Cath was not being used actively for infusion, but had previously been used for chemotherapy administration (3 for breast cancer, 1 each for colon cancer and lymphoma). The single Hickman catheter had been placed to administer antibiotics to an orthotopic heart transplant patient whose immunosuppression resulted in frequent infections.
Signs and Symptoms
The signs and symptoms on initial presentation are shown in Table 2. Regardless of etiology, face and/or neck swelling was the most frequent presenting sign, present in almost all cases, although upper extremity swelling was also present in the majority. More than half the patients had dyspnea at rest, and 50% had cough at presentation. Dilated chest collateral veins, although described as a hallmark of the syndrome, were present in just over one-third of the patients. Syncope, hoarseness, dizziness, and confusion were less common. Patients with malignancy were more likely to present with cough, dyspnea at rest, and shoulder pain. Hyponatremia and weight loss occurred exclusively in patients with malignancy.
Procedures and Complications
Eighty-one procedures were performed or attempted in the 78 cases of SVC syndrome. Procedures ranged from superior vena cava venograms and Port-a-Cath placements to bronchoscopy and coronary artery bypass grafting (Table 3). None of the 9 reported complications caused long-term morbidity or mortality, and the "complication" was an inability to finish the procedure in 5 cases.
Treatments for patients with benign etiologies differed drastically from treatments for patients with malignancies. Overall, 62% (29/47) of patients with malignancies received chemotherapy, either alone (n = 13, 28%) or combined with radiation (n = 16, 34%), including 22 of 36 patients with lung cancer, 5 of 6 with lymphoma, both patients with germ cell tumors, and 1 with thymic cancer. Radiation represented the lone treatment for an additional 8 patients with malignancies (17%), including 5 with lung cancer and 1 each with lymphoma, metastatic prostate cancer, and adenocarcinoma of unknown primary. Steroids were administered to 5 patients with lung cancer (as the sole treatment in 2, with chemotherapy and radiation in 2, and with radiation in 1). Only 6 patients (all with lung cancer) received long-term anticoagulation (3 in addition to chemotherapy and radiation, and 3 as the lone treatment). Four patients with lung cancer received comfort care measures with no additional therapies. One patient with lymphoma underwent thoracic surgery for lymph node resection and superior vena cava bypass grafting.
Most of the patients with intravascular devices presenting with SVC syndrome had the device removed (18/22, 82%). Two of the patients whose device was not removed received thrombolytics followed by long-term anticoagulation, 1 received only long-term anticoagulation, and 1 was simply observed. No further treatment was needed after removing the device in one-third of the patients (6/18). Six patients were treated with either anticoagulation (n = 3) or thrombolytics followed by anticoagulation (n = 3) after removal of the device. Venoplasty was performed after device removal in the remaining 6 patients (1 combined with thrombolytic treatment, 2 with long-term anticoagulation, and 2 before placement of an endovascular stent). Four of the 6 patients with fibrosing mediastinitis underwent venoplasty and stent placement, while 1 was treated only with anticoagulation, and 1 was observed until collaterals developed. The patients with pseudotumor and hematoma after surgery were treated with antibiotics and observation respectively, while anticoagulation was administered for treatment of the primary SVC thrombosis.
Analysis of 78 patients with SVC syndrome over 5 years revealed that malignancy was responsible for the syndrome in 60% of patients, while 40% had benign processes. Bronchogenic carcinoma was the most common malignant cause, while intravascular devices were responsible for the majority of benign etiologies. The most frequent symptom was facial and upper extremity swelling, occurring in almost all patients. Dilated collateral veins across the chest, however, were only present one-third of the time. Cough and dyspnea also occurred frequently, although more commonly in patients with malignancies.
Since the first description in 175713, the etiology of SVC syndrome has slowly evolved. In the early 20th century, cases of SVC syndrome were equally caused by aortic aneurysms and malignancies9,14. By the late 1900s, case series reported 80%-99% of cases being caused by thoracic malignancies, with bronchogenic carcinoma being the main etiology4,6,7,17,24,27,29,35. In our study, thoracic malignancy was the etiology in just over half of the cases of SVC syndrome, with bronchogenic carcinoma still being the most common. Despite previous reports that the majority of the bronchogenic carcinomas associated with the SVC syndrome were histologically small cell4-7,29,30,33, our results found non-small cell and small cell lung cancer to be about equally responsible, although a larger percentage of patients with small cell histology developed the SVC syndrome compared to those with non-small cell. The prevalence of SVC syndrome in patients with bronchogenic carcinoma has been reported to be 4%23, with up to 10% of patients with small cell carcinoma developing the syndrome30,33. We found similar results in our study.
Similar to the classic work by Schechter more than 50 years ago26, almost half of the cases in our study were due to benign causes. Most of these, however, were related to the presence of central indwelling intravascular devices and not from tuberculous mediastinitis or syphilitic aortic aneurysms, as in Schechter's study. In our study, intravascular devices alone accounted for over a quarter of cases, while possibly contributing, along with thoracic malignancy, in a few other patients. We believe this high prevalence of intravascular device-induced SVC syndrome is not unique to our patient population. Although the referral pattern of Saint Thomas Hospital may bias our data to favor benign etiologies, many previous reports obtained data primarily from radiation clinics or tertiary cancer referral centers4,6,24, likely over-representing malignant etiologies. Furthermore, many of today's medical treatments necessitate the use of such devices, often in patients with underlying conditions that increase the susceptibility for clot formation. The reported prevalence of central vein thrombosis and/or fibrosis with these devices ranges from 5% to 42%2,12,18,19,31, depending on the nature of the device and patient comorbidities. Thrombosis with or without subsequent fibrosis around these devices leads to obstruction of the superior vena cava. Accordingly, intravascular devices are becoming an increasingly common etiology of SVC occlusion. Reports indicate that 1%-14% of patients with these devices develop the SVC syndrome2,12,18,32, and the rate of development is estimated as 0.003% to 0.2% for each day the catheter resides in the superior vena cava2,32. Although prophylactic, low-dose anticoagulation is commonly prescribed to prevent clot formation, 4 of 22 patients (18%) with central vein intravascular devices in our study developed SVC syndrome despite being treated with low-dose Coumadin, and 2 additional patients (9%) developed the syndrome despite full anticoagulation and an international normalized ratio (INR) above 2.0.
Fibrosing mediastinitis was also found as a common benign cause of SVC syndrome in our study. Although 1 case occurred decades after mediastinal irradiation for lymphoma, the other 5 cases were likely a complication of prior histoplasmosis infection8,21. The high frequency of prior histoplasmosis infection in residents of middle Tennessee likely increased its prevalence in our study, but fibrosing mediastinitis remains a well-known cause of SVC syndrome3.
The signs and symptoms reported by the patients in our series are similar to those previously reported4,17,23,25. The majority of these arise from venous stasis, cerebral edema, or laryngeal edema. Venous stasis results in facial/neck and/or upper extremity swelling. Subsequently, dilated superficial chest collaterals may develop allowing venous blood to drain from the SVC distribution. Cerebral edema, resulting from reduced drainage of cerebral veins, may contribute to neurologic symptoms, including confusion, syncope, ischemic stroke, or headache. The etiology of the dyspnea is likely multifactorial. In 2004, Nguyen and Roarke22 reported the discovery of intrathoracic right to left shunting of blood in patients with SVC syndrome. This shunting results in systemic hypoxia, which produces dyspnea. Although dyspnea was common in the current study, hypoxia occurred in only a few patients. Pleural effusion probably results in some dyspnea, with lung cancer also contributing. This may explain the higher prevalence of dyspnea in patients with this malignancy. Although laryngeal edema is probably not a significant factor in causing dyspnea, it may contribute to the frequently reported cough. In addition, it is responsible for the infrequent hoarseness and dysphagia seen in these patients.
Many signs and symptoms, including cough, dyspnea at rest, chest pain, hyponatremia, and weight loss, were seen more frequently or exclusively in patients with malignancies. This suggests that although these conditions were previously described as signs and symptoms occurring in SVC syndrome4,17,35, they may be associated with malignancy and not with mechanical obstruction of the superior vena cava. In addition, a large percentage of the malignancies were bronchogenic carcinomas, which are more likely to occur in patients with underlying obstructive lung disease. This underlying obstructive lung disease may contribute to the cough and dyspnea. Dizziness is the only symptom more frequently found in patients with benign etiologies.
In the past, experts recommended against invasive procedures in patients with SVC syndrome because they were thought to be hazardous20,23. However, consider the results of a large analysis of all SVC cases in the literature since 19341: the authors found 1986 reported cases of SVC syndrome secondary to lung cancer. In these patients, 843 invasive diagnostic procedures were performed ranging from contrast venography and bronchoscopy to lymph node biopsy and thoracotomy. Only 10 complications were found, for a complication rate of 1.2%. We also found a low complication rate with invasive procedures performed in patients with both benign and malignant etiologies. None of the 5 complications of the 83 procedures in our study resulted in morbidity or mortality. Excess oozing was the most frequent complication, occurring after SVC venograms were performed, but none of these cases required any treatment other than direct pressure for a few minutes. Complications are often not documented in patient charts, and thus, when complication data are not collected prospectively it likely underestimates the true prevalence. However, despite this under-reporting of complications in retrospective reviews, our study results corroborate the data from other studies1,4,16,27,28,35 demonstrating that invasive procedures can be safely performed in patients with SVC syndrome, regardless of the etiology, and are often helpful in obtaining an accurate diagnosis and providing effective treatment.
The standard of care for treating SVC syndrome has evolved. It was once considered a medical emergency, and almost every patient received emergent radiation and chemotherapy27. As benign etiologies increase in prevalence, however, other therapeutic modalities have emerged. Initially, major operations were undertaken to construct venous tracts bypassing the superior vena cava15. Subsequently, less invasive approaches have been developed. The stenosis resulting from intravascular devices can sometimes be treated with anticoagulation and removal of the catheter. Alternatively, especially when fibrosis is present, treatment with balloon dilation and or stenting is effective15. Although definitive treatment should be directed at the underlying cause of the syndrome, the relative ease and safety of intravascular stenting has afforded its use even as palliative care in patients with terminal malignancy10,11,34.
Several conclusions can be drawn from this retrospective analysis of 78 cases of SVC syndrome. Although malignancy still accounts for the majority of cases, the prevalence of benign etiologies causing SVC syndrome is increasing, especially with the increasing use of intravascular devices. Bronchogenic carcinoma continues to be the most common malignant etiology, but lymphoma and germ cell tumors are not infrequently the cause. Not unexpectedly, the majority of patients present with face and upper extremity swelling, dyspnea, and cough. Only a third of patients, however, demonstrate dilated collateral chest veins. Invasive procedures for diagnostic and treatment purposes can be performed safely in these patients with few complications. Due to the minimal invasiveness and relative efficacy, intravascular stents are emerging as the preferred modality for both definitive treatment and palliation in patients with SVC syndrome.
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*Dr. Michael Rodriguez died unexpectedly on December 21, 2004.