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Mesothelioma and Internal Carotid Artery Occlusion: Acute Ischemic Stroke and Efficacy of Emergency Carotid Thrombectomy
Mesothelioma and Internal Carotid Artery Occlusion: Acute Ischemic Stroke and Efficacy of Emergency Carotid Thrombectomy Emanuele Ferrero,1 Michelangelo Ferri,1 Andrea Viazzo,1 Andrea Gaggiano,2 Giuseppe Berardi,1 Salvatore Piazza,1 Pia Cumbo,1 and Franco Nessi,1 Turin, Asti, Italy
We report the case of a 54-year-old man with acute stroke caused by left internal carotid artery (ICA) occlusion secondary to pleural mesothelioma, discovered later. The cranial computed tomography scan revealed a left hemisphere ischemic lesion. At neurological examination, the modified National Institutes of Health Stroke Scale (mNIHSS) score was 9. The carotid duplex scan (DS) showed a complete thrombotic occlusion of the left ICA. The patient underwent emergency carotid thrombectomy. The screening tests revealed thrombocytosis, hyperfibrinogenemia, increased C-reactive protein values, and multiple left pleural mesothelioma nodularity confirmed at the immunohistochemical investigation. After surgery, the patient’s neurological symptoms improved, with an mNIHSS score of 3. At 30 and 120 days, the DS follow-up showed regular patency of the ICA.
INTRODUCTION The natural history of acute internal carotid artery (ICA) occlusions with serious neurological symptoms is rare and generally results in high rates of morbidity and mortality. Acute ischemic stroke could result from cardioembolic or atherothrombotic occlusion of the ICA and also from spontaneous internal carotid dissection; only 2% to 12% of patients with severe neurological deficits have a good prognosis, whereas 40% to 60% will have severe neurological disability and 16% to 55% will die.1
CASE REPORT A 54-year-old man with acute stroke was referred to our hospital, presenting with symptoms that had started at 1 Vascular and Endovascular Surgery Unit, Mauriziano Umberto I Hospital, Turin, Italy. 2 Vascular and Endovascular Surgery Unit, Cardinal Massaia, Asti, Italy.
Correspondence to Emanuele Ferrero, Vascular and Endovascular Surgery Unit, Mauriziano Umberto I Hospital, Largo Turati 62, 10128 Turin, Italy, E-mail: [email protected] Ann Vasc Surg 2010; 24: 257.e9-257.e12 DOI: 10.1016/j.avsg.2009.11.001 Ó Annals of Vascular Surgery Inc. Published online: December 25, 2009
06:00 with mental confusion and release of urine; at 06:30, he arrived at our hospital. Immediately, a cerebral computed tomography (CT) scan was performed, and it revealed the presence of a recent left ischemic lesion in the frontoparietal corticosubcortical region (Fig. 1). No obliterative diseases of the aorta arch and truncus brachiocephalicus were detected on the CT scan. On neurological examination, the presence of mental confusion and mnesic weakness was noted. The patient was drowsy and presented with mixed aphasia, slight right facial deficit, no brachial or crural stenic deficit, increased deep tendon reflexes, and no dysphagia; the modified National Institutes of Health Stroke Scale (mNIHSS) score was 9. All preoperative examinations were performed, and the electrocardiogram and the echocardiograms revealed no abnormalities. The carotid duplex scan was performed and showed the perviousness of the common left carotid artery and of the external carotid artery. Instead a complete thrombotic occlusion of the left ICA was detected (Fig. 2), with no evidence of atherosclerotic plaques or dissections associated. The patient underwent emergency carotid surgery that started at 13:30 under general anesthesia with use of an INVOS Cerebral Oximeter to monitor changes in cortical blood oxygen saturation. At skin incision, immediate administration of heparin (50 IU/kg intravenous) was performed; prior to cross-clamping, the ICA stump pressure was measured (0 mm Hg) and a standard CEA was performed. Intraoperatively on opening of the ICA, a thrombus was found (Fig. 3). A thrombectomy (TA)
257.e9
257.e10 Case reports
Annals of Vascular Surgery
Fig. 3. Intraoperative thrombus detection.
Fig. 1. Left ischemic lesion detected on the preoperative cerebral CT scan.
Fig. 4. Thrombus 6 cm long.
Fig. 2. Complete thrombotic occlusion of the ICA detected on duplex scan. with a Fogarty catheter (2Fr) to retrieve the carotid thrombus (6 cm long) was undertaken (Fig. 4). No carotid plaque or associated stenosis was detected. A good back flow was restored after removal of the thrombus. Clamp time of the carotid artery was 2 minutes, because after Fogarty use, partial clamping of the carotid arteriotomy was performed, to ensure the cerebral perfusion during artery suture. The intraoperative angiographic control (Fig. 5) showed complete patency in the proximal and the next part of the distal intracranial carotid artery in the absence of residual thrombosis; it also showed the patency of the left middle cerebral artery (MCA). At declamping, use of the INVOS Cerebral Oximeter had improved cerebral oxygenation (from 58 to 65). There were no hemodynamic instabilities during the procedure or during reperfusion. The day after surgery at neurological examination, the patient was alert and cooperative, responding correctly to simple questions or questions
involving long-term memory but he was unable to show a temporal orientation; he also had serious difficulties in calculation and confused right with left, and he had asymmetry in the standing position, light hyposthenia, nuanced facial asymmetry with right eyelid ptosis, and an mNIHSS score of 3. After surgery, the patient underwent screening tests to identify the genesis of internal carotid thrombosis; thrombophilia tests were negative but the patient presented with thrombocytosis (platelet count, 721,000/mL) and hyperfibrinogenemia (fibrinogen concentration, 603 mg/dL), and C-reactive protein (CRP) values were increased to 0.04 g/L (reference range, <0.005 g/L).The postoperative total body CT scan showed an ischemic injury in the subacute phase in the left frontoparietal corticosubcortical region in the brain, and another, smaller lesion with similar characteristics was detectable in the early occipital region, cortical-subcortical (Fig. 6). The lung CT scan showed the presence of multiple left nodules on the parietal pleura, but no infiltration/involvement of the tumor into the supra-aortic vessels or postoperative edema was noted. The morphological and immunohistochemical investigation results suggested a mesothelioma. The multidisciplinary team recommended chemotherapy
Vol. 24, No. 2, February 2010
Case reports 257.e11
neurological symptoms, the brachial and crural functions had totally recovered, and the mNIHSS score was 3. The duplex scan follow-up at 30 and 120 days showed regular patency of the carotid artery without thrombosis or residual flaps.
DISCUSSION
Fig. 5. Carotid angiographic scan control after CEA.
Fig. 6. Left ischemic lesion detected on the postoperative cerebral CT scan. after review of the case, and the patient started cancer therapy. After surgery, no antithrombotic therapy was done, but the patient underwent antiplatelet therapy.
RESULTS Thirty days after surgery and rehabilitation, the patient presented with a marked improvement in
Even if the natural history of acute ICA occlusion with serious neurological symptoms is unfavourable,2 and traditionally this kind of patient is not a candidate for intervention, some patients with stroke due to sudden occlusion of the ICA could undergo surgery to restore carotid patency and to rescue brain tissue not yet irreversibly damaged.3 In this case, therapy consists of emergency carotid TA or, alternatively, endovascular thrombolytic treatment and/or mechanical revascularization, with or without stent placement.4,5 Although cases of emergency TA have been reported as technically successful, the clinical benefit is controversial.1,6,7 Generally, acute ICA occlusion results from a cardioembolic or an atherothorombotic event, but it can be also secondary to a malignancy.8,9 In patients with cancer, generally the thrombosis may be the first manifestation of malignancy; thrombocytosis is common in association with carcinomas of the lung, gastrointestinal tract, breast, ovary, and uterus,10 and it has a high prevalence during the course of a malignant mesothelioma.11 As Ustu¨ndag˘ et al.8 reported, mesothelioma cells and cell lines have been shown to secrete a pleiotropic cytokine, interleukin 6 (IL-6), which potentiates the production of platelets by inducing megakaryocytopoiesis12; this may be because of the malignancyrelated effect of IL-6 on platelet functions or the basal functional changes occurring in platelets produced through IL-6estimulated megakaryocytopoiesis. Our patient’s high CRP level may reflect an elevated serum IL-6. Hyperfibrinogenemia in the patient may also act as a partial contributing factor in ICA occlusion, in concert with activation of coagulation pathways by substances secreted by tumor tissue. Mesothelioma cells had been found to release procoagulant materials in vitro, which may shift the hemostatic balances to a tendency toward thrombosis.13 Generally, a thromboembolic event in mesothelioma consists of deep venous thrombosis and pulmonary embolus, but it can include arterial clots; moreover, the thromboembolic event incidence rate in mesothelioma patients is higher than that in other cancer patients.14 There are only two reports of ICA occlusion in patients with malignant mesothelioma in the literature,8-15 and this is the
257.e12 Case reports
first case in which an emergency TA was performed on a patient with mesothelioma with complete recovery of neurological deficits. This report demonstrates that, combined with hyperfibrinogenemia, malignant pleural mesothelioma and thrombocytosis may result in a major vascular occlusion. Besides, even if this is an anecdotic case, the authors can assert that restoration of blood flow in an acutely occluded ICA can only be achieved in the acute stage with good results even in patients with malignancy, but the timeliness of diagnosis and treatment remains essential. REFERENCES 1. Meyer FB, Sundt TM, Jr, Piepgras DG, et al. Emergency carotid endarterectomy for patients with acute carotid occlusion and profound neurological deficits. Ann Surg 1986;203:82-89. 2. Adams HP, Jr, Bendixen BH, Leira E, et al. Antithrombotic treatment of ischemic stroke among patients with occlusion or severe stenosis of the internal carotid artery: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999;13:122-125. 3. Weis-Mu¨ller BT, Huber R, Spivak-Dats A, et al. Indication for emergent revascularisation of acute carotid occlusion. Chirurg 2007;78:1041-1048 [in German]. 4. Mocco J, Tawk RG, Jahromi BS, et al. Endovascular intervention for acute thromboembolic stroke in young patients: an ideal population for aggressive intervention? J Neurosurg 2009;110:30-34.
Annals of Vascular Surgery
5. Miyamoto N, Naito I, Takatama S, et al. Urgent stenting for patients with acute stroke due to atherosclerotic occlusive lesions of the cervical internal carotid artery. Neurol Med Chir (Tokyo) 2008;48:49-55. discussion, 55-56. 6. Kasper GC, Wladis AR, Lohr JM, et al. Carotid thromboendarterectomy for recent total occlusion of the internal carotid artery. J Vasc Surg 2001;33:242-249. discussion, 249-250. 7. Brandl R, Brauer RB, Maurer PC. Urgent carotid endarterectomy for stroke in evolution. Vasa 2001;30:115-121. 8. Ustu¨ndag˘ Y, Can U, Benli S, et al. Internal carotid artery occlusion in a patient with malignant peritoneal mesothelioma: is it a sign of malignancy-related thrombosis? Am J Med Sci 2000;319:265-267. 9. Bell WR, Starksen NF, Tong S, et al. Trousseau’s syndrome. Devastating coagulopathy in the absence of heparin. Am J Med 1985;79:423-430. 10. Bick RL. Coagulation abnormalities in malignancy: a review. Semin Thromb Hemost 1992;18:353-372. 11. Chahinian AP, Pajak TF, Holland JF, et al. Diffuse malignant mesothelioma. Ann Intern Med 1982;96:746-755. 12. Nakano T, Chahinian AP, Shinjo M, et al. Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma. Br J Cancer 1998;77: 907-912. 13. Nakano T, Fuji J, Tamura S, et al. Thrombocytosis in patients with malignant pleural mesothelioma. Cancer 1986;58: 1699-1701. 14. Nguyen D, Lee SJ, Libby E, et al. Rate of thromboembolic events in mesothelioma. Ann Thorac Surg 2008;85: 1032-1038. 15. Fazekas T, Tiszlavicz L, Ungi I. Primary malignant pericardial mesothelioma. Orv Hetil 1991;132:2677-2680 [in Hungarian].
We report the case of a 54-year-old man with acute stroke caused by left internal carotid artery (ICA) occlusion secondary to pleural mesothelioma, discovered later. The cranial computed tomography scan revealed a left hemisphere ischemic lesion. At neurological examination, the modified National Institutes of Health Stroke Scale (mNIHSS) score was 9. The carotid duplex scan (DS) showed a complete thrombotic occlusion of the left ICA. The patient underwent emergency carotid thrombectomy. The screening tests revealed thrombocytosis, hyperfibrinogenemia, increased C-reactive protein values, and multiple left pleural mesothelioma nodularity confirmed at the immunohistochemical investigation. After surgery, the patient’s neurological symptoms improved, with an mNIHSS score of 3. At 30 and 120 days, the DS follow-up showed regular patency of the ICA.
INTRODUCTION The natural history of acute internal carotid artery (ICA) occlusions with serious neurological symptoms is rare and generally results in high rates of morbidity and mortality. Acute ischemic stroke could result from cardioembolic or atherothrombotic occlusion of the ICA and also from spontaneous internal carotid dissection; only 2% to 12% of patients with severe neurological deficits have a good prognosis, whereas 40% to 60% will have severe neurological disability and 16% to 55% will die.1
CASE REPORT A 54-year-old man with acute stroke was referred to our hospital, presenting with symptoms that had started at 1 Vascular and Endovascular Surgery Unit, Mauriziano Umberto I Hospital, Turin, Italy. 2 Vascular and Endovascular Surgery Unit, Cardinal Massaia, Asti, Italy.
Correspondence to Emanuele Ferrero, Vascular and Endovascular Surgery Unit, Mauriziano Umberto I Hospital, Largo Turati 62, 10128 Turin, Italy, E-mail: [email protected] Ann Vasc Surg 2010; 24: 257.e9-257.e12 DOI: 10.1016/j.avsg.2009.11.001 Ó Annals of Vascular Surgery Inc. Published online: December 25, 2009
06:00 with mental confusion and release of urine; at 06:30, he arrived at our hospital. Immediately, a cerebral computed tomography (CT) scan was performed, and it revealed the presence of a recent left ischemic lesion in the frontoparietal corticosubcortical region (Fig. 1). No obliterative diseases of the aorta arch and truncus brachiocephalicus were detected on the CT scan. On neurological examination, the presence of mental confusion and mnesic weakness was noted. The patient was drowsy and presented with mixed aphasia, slight right facial deficit, no brachial or crural stenic deficit, increased deep tendon reflexes, and no dysphagia; the modified National Institutes of Health Stroke Scale (mNIHSS) score was 9. All preoperative examinations were performed, and the electrocardiogram and the echocardiograms revealed no abnormalities. The carotid duplex scan was performed and showed the perviousness of the common left carotid artery and of the external carotid artery. Instead a complete thrombotic occlusion of the left ICA was detected (Fig. 2), with no evidence of atherosclerotic plaques or dissections associated. The patient underwent emergency carotid surgery that started at 13:30 under general anesthesia with use of an INVOS Cerebral Oximeter to monitor changes in cortical blood oxygen saturation. At skin incision, immediate administration of heparin (50 IU/kg intravenous) was performed; prior to cross-clamping, the ICA stump pressure was measured (0 mm Hg) and a standard CEA was performed. Intraoperatively on opening of the ICA, a thrombus was found (Fig. 3). A thrombectomy (TA)
257.e9
257.e10 Case reports
Annals of Vascular Surgery
Fig. 3. Intraoperative thrombus detection.
Fig. 1. Left ischemic lesion detected on the preoperative cerebral CT scan.
Fig. 4. Thrombus 6 cm long.
Fig. 2. Complete thrombotic occlusion of the ICA detected on duplex scan. with a Fogarty catheter (2Fr) to retrieve the carotid thrombus (6 cm long) was undertaken (Fig. 4). No carotid plaque or associated stenosis was detected. A good back flow was restored after removal of the thrombus. Clamp time of the carotid artery was 2 minutes, because after Fogarty use, partial clamping of the carotid arteriotomy was performed, to ensure the cerebral perfusion during artery suture. The intraoperative angiographic control (Fig. 5) showed complete patency in the proximal and the next part of the distal intracranial carotid artery in the absence of residual thrombosis; it also showed the patency of the left middle cerebral artery (MCA). At declamping, use of the INVOS Cerebral Oximeter had improved cerebral oxygenation (from 58 to 65). There were no hemodynamic instabilities during the procedure or during reperfusion. The day after surgery at neurological examination, the patient was alert and cooperative, responding correctly to simple questions or questions
involving long-term memory but he was unable to show a temporal orientation; he also had serious difficulties in calculation and confused right with left, and he had asymmetry in the standing position, light hyposthenia, nuanced facial asymmetry with right eyelid ptosis, and an mNIHSS score of 3. After surgery, the patient underwent screening tests to identify the genesis of internal carotid thrombosis; thrombophilia tests were negative but the patient presented with thrombocytosis (platelet count, 721,000/mL) and hyperfibrinogenemia (fibrinogen concentration, 603 mg/dL), and C-reactive protein (CRP) values were increased to 0.04 g/L (reference range, <0.005 g/L).The postoperative total body CT scan showed an ischemic injury in the subacute phase in the left frontoparietal corticosubcortical region in the brain, and another, smaller lesion with similar characteristics was detectable in the early occipital region, cortical-subcortical (Fig. 6). The lung CT scan showed the presence of multiple left nodules on the parietal pleura, but no infiltration/involvement of the tumor into the supra-aortic vessels or postoperative edema was noted. The morphological and immunohistochemical investigation results suggested a mesothelioma. The multidisciplinary team recommended chemotherapy
Vol. 24, No. 2, February 2010
Case reports 257.e11
neurological symptoms, the brachial and crural functions had totally recovered, and the mNIHSS score was 3. The duplex scan follow-up at 30 and 120 days showed regular patency of the carotid artery without thrombosis or residual flaps.
DISCUSSION
Fig. 5. Carotid angiographic scan control after CEA.
Fig. 6. Left ischemic lesion detected on the postoperative cerebral CT scan. after review of the case, and the patient started cancer therapy. After surgery, no antithrombotic therapy was done, but the patient underwent antiplatelet therapy.
RESULTS Thirty days after surgery and rehabilitation, the patient presented with a marked improvement in
Even if the natural history of acute ICA occlusion with serious neurological symptoms is unfavourable,2 and traditionally this kind of patient is not a candidate for intervention, some patients with stroke due to sudden occlusion of the ICA could undergo surgery to restore carotid patency and to rescue brain tissue not yet irreversibly damaged.3 In this case, therapy consists of emergency carotid TA or, alternatively, endovascular thrombolytic treatment and/or mechanical revascularization, with or without stent placement.4,5 Although cases of emergency TA have been reported as technically successful, the clinical benefit is controversial.1,6,7 Generally, acute ICA occlusion results from a cardioembolic or an atherothorombotic event, but it can be also secondary to a malignancy.8,9 In patients with cancer, generally the thrombosis may be the first manifestation of malignancy; thrombocytosis is common in association with carcinomas of the lung, gastrointestinal tract, breast, ovary, and uterus,10 and it has a high prevalence during the course of a malignant mesothelioma.11 As Ustu¨ndag˘ et al.8 reported, mesothelioma cells and cell lines have been shown to secrete a pleiotropic cytokine, interleukin 6 (IL-6), which potentiates the production of platelets by inducing megakaryocytopoiesis12; this may be because of the malignancyrelated effect of IL-6 on platelet functions or the basal functional changes occurring in platelets produced through IL-6estimulated megakaryocytopoiesis. Our patient’s high CRP level may reflect an elevated serum IL-6. Hyperfibrinogenemia in the patient may also act as a partial contributing factor in ICA occlusion, in concert with activation of coagulation pathways by substances secreted by tumor tissue. Mesothelioma cells had been found to release procoagulant materials in vitro, which may shift the hemostatic balances to a tendency toward thrombosis.13 Generally, a thromboembolic event in mesothelioma consists of deep venous thrombosis and pulmonary embolus, but it can include arterial clots; moreover, the thromboembolic event incidence rate in mesothelioma patients is higher than that in other cancer patients.14 There are only two reports of ICA occlusion in patients with malignant mesothelioma in the literature,8-15 and this is the
257.e12 Case reports
first case in which an emergency TA was performed on a patient with mesothelioma with complete recovery of neurological deficits. This report demonstrates that, combined with hyperfibrinogenemia, malignant pleural mesothelioma and thrombocytosis may result in a major vascular occlusion. Besides, even if this is an anecdotic case, the authors can assert that restoration of blood flow in an acutely occluded ICA can only be achieved in the acute stage with good results even in patients with malignancy, but the timeliness of diagnosis and treatment remains essential. REFERENCES 1. Meyer FB, Sundt TM, Jr, Piepgras DG, et al. Emergency carotid endarterectomy for patients with acute carotid occlusion and profound neurological deficits. Ann Surg 1986;203:82-89. 2. Adams HP, Jr, Bendixen BH, Leira E, et al. Antithrombotic treatment of ischemic stroke among patients with occlusion or severe stenosis of the internal carotid artery: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999;13:122-125. 3. Weis-Mu¨ller BT, Huber R, Spivak-Dats A, et al. Indication for emergent revascularisation of acute carotid occlusion. Chirurg 2007;78:1041-1048 [in German]. 4. Mocco J, Tawk RG, Jahromi BS, et al. Endovascular intervention for acute thromboembolic stroke in young patients: an ideal population for aggressive intervention? J Neurosurg 2009;110:30-34.
Annals of Vascular Surgery
5. Miyamoto N, Naito I, Takatama S, et al. Urgent stenting for patients with acute stroke due to atherosclerotic occlusive lesions of the cervical internal carotid artery. Neurol Med Chir (Tokyo) 2008;48:49-55. discussion, 55-56. 6. Kasper GC, Wladis AR, Lohr JM, et al. Carotid thromboendarterectomy for recent total occlusion of the internal carotid artery. J Vasc Surg 2001;33:242-249. discussion, 249-250. 7. Brandl R, Brauer RB, Maurer PC. Urgent carotid endarterectomy for stroke in evolution. Vasa 2001;30:115-121. 8. Ustu¨ndag˘ Y, Can U, Benli S, et al. Internal carotid artery occlusion in a patient with malignant peritoneal mesothelioma: is it a sign of malignancy-related thrombosis? Am J Med Sci 2000;319:265-267. 9. Bell WR, Starksen NF, Tong S, et al. Trousseau’s syndrome. Devastating coagulopathy in the absence of heparin. Am J Med 1985;79:423-430. 10. Bick RL. Coagulation abnormalities in malignancy: a review. Semin Thromb Hemost 1992;18:353-372. 11. Chahinian AP, Pajak TF, Holland JF, et al. Diffuse malignant mesothelioma. Ann Intern Med 1982;96:746-755. 12. Nakano T, Chahinian AP, Shinjo M, et al. Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma. Br J Cancer 1998;77: 907-912. 13. Nakano T, Fuji J, Tamura S, et al. Thrombocytosis in patients with malignant pleural mesothelioma. Cancer 1986;58: 1699-1701. 14. Nguyen D, Lee SJ, Libby E, et al. Rate of thromboembolic events in mesothelioma. Ann Thorac Surg 2008;85: 1032-1038. 15. Fazekas T, Tiszlavicz L, Ungi I. Primary malignant pericardial mesothelioma. Orv Hetil 1991;132:2677-2680 [in Hungarian].