Anesth Analg 2004;98:806-809
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000103260.45058.B1
NEUROSURGICAL ANESTHESIA
Perioperative Stroke Caused by Arterial Tumor Embolism
Douglas V. Brown, MD*,
L. Penfield Faber, MD
, and
Kenneth J. Tuman, MD*
Departments of *Anesthesiology and Cardiovascular and Thoracic Surgery, Rush Medical College, Rush University Medical Center, Chicago, Illinois
Address correspondence and reprint requests to Douglas V. Brown, MD, Department of Anesthesiology, Rush Medical College, Rush University Medical Center, 1653 W. Congress Pkwy., Suite 739, Chicago, IL 60612. Address e-mail to douglas_brown{at}rush.edu
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Abstract
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Rarely, cancer invades a pulmonary vein and subsequently embolizes to the cerebral circulation, causing a stroke. Tumor embolism typically involves large, centrally located lung tumors. We report a case of immediate postoperative stroke caused by an arterial tumor embolism during pulmonary resection of metastatic sarcoma. This case is unique because the resected lesions were smaller than those previously associated with tumor embolism and unusual in that the tumors were peripherally located. Tumor embolization should be considered in the differential diagnosis of stroke after lung cancer surgery even with small, peripherally located pulmonary malignancies.
IMPLICATIONS: We present a case of stroke diagnosed in the recovery room after lung cancer resection. The cause of the stroke was tumor that embolized from the lung to the middle cerebral artery. Tumor embolism should be considered in the differential diagnosis of immediate postoperative stroke after lung cancer surgery.
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Introduction
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Perioperative stroke occurs uncommonly and usually results from embolic or thrombotic events. Rarely, during pulmonary surgery, a fragment of tumor that has invaded a pulmonary vein can embolize and result in cerebral infarction. Large, centrally located, primary or secondary pulmonary tumors are typically responsible for tumor arterial embolism (1). We report a case of arterial tumor embolism causing a stroke that presented in the recovery room immediately after pulmonary resection of metastatic sarcoma. This is only the third report of such a case (2,3) and the sixth reported case of arterial tumor embolism to any location during pulmonary resection of metastatic sarcoma (2–6). This case is unique because the resected lesions were small and peripherally located, and it suggests that tumor embolization should be included in the differential diagnosis of perioperative stroke even with peripherally located pulmonary malignancies.
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Case Report
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A 45-yr-old man was diagnosed with sarcoma (malignant fibrous histiocytoma) of the left leg. After staging for metastatic disease was negative, en bloc resection of the soft tissue sarcoma from the left thigh and prophylactic rodding of the left femur were performed, followed by local external beam irradiation. Four months later, chest computerized tomography (CT) revealed bilateral peripheral pulmonary nodules. Evaluation for extrathoracic involvement was negative. The patient presented for a right thoracotomy and resection of five right lung nodules. It was anticipated that the nodules in the contralateral lung would be surgically excised several weeks later. The patient’s medical history was negative; he was active without symptoms of cardiac or respiratory pathology. Preoperative vital signs and laboratory results included arterial blood pressure of 124/80 mm Hg, heart rate of 82 bpm in sinus rhythm, and hemoglobin of 14.4 g/dL.
A peripheral venous catheter, radial arterial catheter, and thoracic epidural catheter were placed. Anesthesia was induced, and the trachea was intubated with a left 41F double-lumen endobronchial tube. Anesthesia was maintained with a small concentration of isoflurane delivered in 100% oxygen, and the epidural catheter was dosed with 2% lidocaine. A right thoracotomy was performed. Palpated lung nodules were excised with multiple wedge resections and a lower lobe segmentectomy. Surgical pathology confirmed the lung nodules as malignant fibrous histiocytoma. The largest of these tumor nodules measured 2.2 x 1.7 x 1.5 cm.
The patient’s arterial blood pressure was stable throughout the procedure; the lowest intraoperative arterial blood pressure was 95/60 mm Hg, and no vasopressors were used. Oxygen saturation remained at or more than 94%, even during one-lung ventilation. The endotracheal tube was removed while the patient was still somnolent but following simple commands, including eye opening and head lift. Thirty minutes after arrival in the postanesthesia recovery area, right-sided weakness was noted. Neurologic assessment revealed flaccid right hemiplegia, right lower facial paresis, expressive aphasia, right-sided neglect, and right-sided hyperreflexia and toe extension to plantar stimulation. Neurological consultation was obtained. Brain CT was consistent with early cerebral infarction in the left middle cerebral artery (MCA) distribution, without evidence of intracranial bleed, cerebral metastasis, or midline shift. Transesophageal echocardiography (TEE) did not demonstrate a source of embolism (left atrial or appendage thrombus, patent foramen ovale or other intracardiac shunt, valvular vegetation, or aortic debris). Heart function was normal. Carotid ultrasound demonstrated normal arterial flow without significant stenosis. Lower extremity venous Doppler study was normal. Laboratory tests for evidence of hypercoagulability (including prothrombin time, partial thromboplastin time, anticardiolipin antibodies, lupus anticoagulant, protein C and protein S levels and activity, factor V Leiden, and prothrombin gene mutation 20210) were all normal. The patient’s neurologic condition did not change on postoperative Day 2; brain CT showed diffuse low density throughout the entire territory of the left MCA, consistent with infarction and significant cerebral swelling. On the third postoperative day, his pupils dilated bilaterally. Although treatment for increased intracranial pressure was initiated, CT demonstrated transtentorial herniation. After brain death was confirmed, supportive measures were withdrawn, and the patient died.
Autopsy pathology revealed a 6-mm-long tumor embolus in the left MCA. The heart was normal, without evidence of thrombus. Neither surgical nor autopsy pathology identified tumor involvement of the pulmonary veins. Tumor emboli were not found elsewhere in the body.
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Discussion
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Perioperative stroke is unusual. Excluding cardiac, carotid, neck, and intracranial procedures, the incidence of perioperative stroke is 0.04% to 0.2% (7–10). Perioperative stroke risk factors include a previous cerebrovascular event, peripheral vascular disease, chronic obstructive pulmonary disease, hypertension, smoking, nonsinus cardiac rhythm, and advanced age (8–11). Although the exact mechanisms of perioperative stroke are uncertain, it is believed that cardiogenic emboli are responsible in a large portion of such occurrences. This is supported by the commonness in many perioperative stroke patients of conditions related to cardiac emboli, including atrial fibrillation, recent discontinuation of anticoagulants, perioperative myocardial infarction, and subacute bacterial endocarditis. Emboli originating from the vasculature supplying the brain are less frequently responsible for causing perioperative stroke. Intraoperative and postoperative hypotension and hypoxia are rarely responsible for postoperative strokes (10,11), and intracranial hemorrhage is an unusual cause of neurologic deficit in the perioperative setting (8,9,11).
Perioperative stroke tends to present in the early postoperative period. In one series, 53% of strokes occurred within 24 hours of surgery (9). Another report found that the mean onset of perioperative stroke was 2 days after surgery, and 16% of cerebral infarcts occurred during surgery (11).
Although the presence of cancer has not been identified as a risk factor for perioperative stroke, ischemic and hemorrhagic central nervous system lesions are common in nonsurgical cancer patients with advanced malignancy. Graus et al. (2) found such central nervous system lesions in 14.6% (500 of 3426) of cancer patients at autopsy. Although most cerebral hemorrhages were attributed to coagulation disorders, 60 patients (including 4 with primary sarcomas) hemorrhaged into a cerebral metastasis. Spontaneous tumor embolus was responsible for 12 cases of cerebral infarction in this study.
Although systemic embolism of atrial myxoma before surgical resection is common (12,13), clinically significant arterial tumor embolus from other tumors is rare. Xiromeritis et al. (14) identified 104 reported cases of nonmyxomatous arterial tumor emboli. Primary lung cancer (46 patients) and metastatic lung cancer (33 patients) were responsible for most of these cases. The most common of the metastatic lung neoplasms was sarcoma, which accounted for 14 cases. The other etiologies of arterial tumor embolism included primary tumor of the aorta, direct tumor invasion of the aorta, and paradoxical embolism through a patent foramen ovale.
The mechanism of primary and metastatic lung cancer embolism is considered to involve tumor that invades and propagates within a pulmonary vein. When a tumor fragment breaks off in the pulmonary vein, it travels through the left heart and subsequently lodges in a systemic artery. Infarction results when the tumor fragment is large enough to occlude the tissue’s arterial perfusion. Arterial tumor embolism from the pulmonary vein can occur in two settings. The embolism can occur either perioperatively or spontaneously. Arterial embolism related to thoracic surgery is likely due to manipulation of the pulmonary hilum or division of the pulmonary vein, which dislodges tumor from the pulmonary vein. The other scenario of tumor embolization occurs in the absence of pulmonary surgery and is assumed to result from spontaneous fragmentation of propagated tumor within a pulmonary vein (15,16). Of the 79 reported cases of arterial tumor embolism from the pulmonary vasculature summarized by Xiromeritis et al. (14), 43 occurred spontaneously and 36 were associated with thoracic surgery.
Whyte et al. (1) reviewed 28 cases of perioperative arterial tumor embolism. Six of these cases involved metastatic lung cancer, and five of these were sarcomas. In most cases, tumor was palpated in the pulmonary vein during surgical dissection. Large and centrally located tumors were most often responsible for arterial tumor emboli (1). The smallest reported tumor diameter related to arterial emboli was 3 cm (5). Although they are more common with central hilar tumors, peripheral tumors may also involve the pulmonary veins and cause arterial emboli (17). Most tumor emboli occur during surgery; a few occur in the early postoperative period. The delayed occurrence of these emboli may be due to tumor fragments that remain loosely adherent to the site of pulmonary vein ligation and then embolize after surgery with coughing or other movement, or perhaps emboli are temporarily detained in the left ventricular trabeculations or chordae tendineae. Also, some instances of delayed emboli may be attributed to delayed recognition of the embolism’s clinical sequelae. Almost all sites of arterial embolization have been reported. The distribution of sites where arterial emboli lodge is similar to that of atherosclerotic emboli, although the larger tumor emboli may occlude arteries at more proximal locations (18). In the review of Whyte et al. (1), tumor embolization to the carotid or cerebral arteries occurred in half of the cases, and tumor embolization to multiple sites occurred in approximately one-third of patients. Consistent with the perioperative stroke literature (11), Xiromeritis et al. (14) found the vast majority of tumor emboli to the cerebral/carotid vasculature lodged in the MCA.
In cases of tumor embolism, pulmonary vein involvement by cancer is often first identified during surgery. When tumor invades the pulmonary vein, avoidance of unnecessary lung manipulation and early ligation of the pulmonary vein are suggested to prevent detachment and subsequent embolization of tumor (4). Unfortunately, even with these precautions, arterial tumor emboli occur (19,20). The extent of pulmonary vein involvement is difficult to access by palpation, and ligation through the tumor allows for embolization of the proximal portion of the tumor (19,20). Also, surgical palpation does not always identify existing tumor in the pulmonary vein, so that the recommended precaution of early pulmonary vein ligation is not performed (1,21). Because of the importance of diagnosing the presence and the extent of pulmonary vein tumor, preoperative testing is appropriate for tumors considered to be at high risk for pulmonary vein invasion. Although there is no consensus, large, central tumors and peripheral tumors larger than 5 cm in diameter might be classified as high risk (1,17). Vascular contrast enhancement with chest CT will demonstrate the pulmonary vein filling defect characteristic of pulmonary vein tumor. Alternatively, magnetic resonance imaging (MRI) can identify pulmonary vein involvement. Echocardiography can be used to detect proximal pulmonary vein involvement. For this purpose, TEE may be more sensitive than transthoracic echocardiography (22). If preoperative testing identifies tumor involvement of the proximal pulmonary vein, a left atrial cuff may be resected along with the lung to prevent tumor embolism, and if tumor involves the left atrium, cardiopulmonary bypass may be implemented to facilitate complete intravascular tumor resection (17,23,24). Intraoperative TEE is appropriate for assessing the adequacy of tumor resection and monitoring for intraoperative embolization when pulmonary vein tumor involvement is identified before surgery by CT, MRI, or echocardiography and also for determining the extent of pulmonary vein or atrial involvement when an intravascular tumor is first identified during surgery by palpation (1,19).
Our patient is only the sixth reported case of perioperative tumor embolism related to metastatic sarcoma and the third reported case with cerebral infarction. This case is unique in that the resected tumors were small. The largest of these measured 2.2 cm in diameter. Arterial tumor embolus has not yet been associated with a tumor <3 cm in diameter. It is unusual that pathologic examination did not demonstrate pulmonary vein invasion. It is speculated that this small embolus was released in its entirety. Although tumor emboli to the cerebral circulation are rare, the possibility of such an event should be included in the differential diagnosis of perioperative strokes in patients with malignancies involving the lung.
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Accepted for publication October 10, 2003.
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Abstract
Introduction
