Advertisement

Mechanical Thrombectomy for Trousseau Syndrome in a Terminally Ill Cancer Patient

Open ArchivePublished:December 18, 2018DOI:https://doi.org/10.1016/j.jpainsymman.2018.12.327

      Abstract

      Trousseau syndrome was first described by Armand Trousseau in 1865 and is characterized by hypercoagulation resulting from malignant tumors. This complication can markedly impact quality of life (QOL). This is the first report of a terminally ill patient who developed large-vessel occlusion stroke from Trousseau syndrome and underwent mechanical thrombectomy. A 75-year-old woman presented with Stage IV ovarian cancer. Goals of care were transitioned to palliative care. The patient was hospitalized with vertebral compression fracture and suddenly developed right hemiparesis and total aphasia during admission. Magnetic resonance imaging and angiography showed occlusion of Segment 1 of the left middle cerebral artery. We administered tissue-plasminogen activator, but symptoms remained unimproved. We performed mechanical thrombectomy based on medical indications and with the consent of her family. Thrombectomy improved symptoms dramatically. She was able to walk and talk with her family at discharge. She eventually died of respiratory failure on postoperative Day 98, but QOL remained high for those 98 days. Mechanical thrombectomy has the potential to markedly improve QOL in terminally ill patients with large-vessel occlusion associated with Trousseau syndrome.

      Key Words

      Introduction

      Terminally ill patients are often at risk of multiple complications. Knowing how aggressively to manage these complications is very challenging because no consensus has been reached regarding whether treatment should be withdrawn or withheld.
      • Lobo S.M.
      • De Simoni F.H.B.
      • Jakob S.M.
      • et al.
      Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective.
      • Chung G.S.
      • Yoon J.D.
      • Rasinski K.A.
      • Curlin F.A.
      US physicians' opinions about distinctions between withdrawing and withholding life-sustaining treatment.
      • Stiel S.
      • Krumm N.
      • Pestinger M.
      • et al.
      Antibiotics in palliative medicine--results from a prospective epidemiological investigation from the HOPE survey.
      • Mori I.
      • Shimada A.
      • Maeda I.
      • Morita T.
      • Tsuneto S.
      Interspecialty differences in physicians' attitudes, beliefs, and reasons for withdrawing or withholding hypercalcemia treatment in terminally ill patients.
      We have to make treatment decisions with due consideration of the benefits, risks, effects on comfort, preferences of the patient and family, and the course of any previous treatment.
      • Kangasala H.H.
      • Kosunen E.
      • Lammi U.-K.
      • et al.
      Decision making in terminal care: a survey of Finnish doctors' treatment decisions in end-of-life scenarios involving a terminal cancer and a terminal dementia patient.
      Trousseau syndrome is a common cause of ischemic stroke in cancer patients.
      • Shinohara T.
      • Tsumura M.
      • Hasegawa A.
      • Yamanaka Y.
      A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
      This syndrome was first reported by Armand Trousseau in 1865 and is characterized by hypercoagulation disorder in patients with malignancy.
      • Rak J.
      • Yu J.L.
      • Luyendyk J.
      • Mackman N.
      Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans.
      • Ikushima S.
      • Ono R.
      • Fukuda K.
      • et al.
      Trousseau's syndrome: cancer-associated thrombosis.
      This complication can markedly affect quality of life (QOL).
      Mechanical thrombectomy is an effective clot-removing treatment for patients with acute cerebral infarction due to large vessel occlusion (LVO). However, thrombectomy for Trousseau syndrome has only rarely been described,
      • Shinohara T.
      • Tsumura M.
      • Hasegawa A.
      • Yamanaka Y.
      A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
      • Matsumoto N.
      • Fukuda H.
      • Handa A.
      • et al.
      Histological examination of trousseau syndrome-related thrombus retrieved through acute endovascular thrombectomy: report of 2 cases.
      • Inoue S.
      • Fujita A.
      • Mizowaki T.
      • et al.
      Successful treatment of repeated bilateral middle cerebral artery occlusion by performing mechanical thrombectomy in a patient with trousseau syndrome.
      and no cases have yet been reported among terminally ill patients.
      This is the first report to describe the successful use of mechanical thrombectomy to rescue a terminally ill patient with LVO due to Trousseau syndrome. Mechanical thrombectomy dramatically improved patient QOL and activities of daily living.
      • Berkhemer O.A.
      • Fransen P.S.
      • Beumer D.
      • et al.
      A randomized trial of intraarterial treatment for acute ischemic stroke.
      • Campbell B.C.
      • Mitchell P.J.
      • Kleinig T.J.
      • et al.
      Endovascular therapy for ischemic stroke with perfusion-imaging selection.
      • Goyal M.
      • Demchuk A.M.
      • Menon B.K.
      • et al.
      Randomized assessment of rapid endovascular treatment of ischemic stroke.
      • Goyal M.
      • Menon B.K.
      • van Zwam W.H.
      • et al.
      Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.
      • Saver J.L.
      • Goyal M.
      • Bonafe A.
      • et al.
      Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.

      Case Description

      The patient was a 75-year-old woman who underwent chemoradiotherapy for Stage IV ovarian cancer (serous adenocarcinoma, high grade) as outpatient. Despite the chemoradiotherapy, the cancer progressed and showed metastasis to axillary, cervical, mediastinal, and supraclavicular lymph nodes. She developed severe adverse effects (gastrointestinal symptoms) that prevented continuation of chemoradiotherapy. We considered her treatment plan including hospice; however, she wished to spend peacefully the rest of her life at her home with her husband with palliative care follow-up as outpatient. Based on this wish, the goals of care were transitioned to palliative care, focusing on symptom alleviation and maintenance of QOL.
      However, after 43 days from this decision, the patient was admitted to our hospital with vertebral compression fracture. Sixteen days after admission, deep venous thromboses developed in bilateral soleal veins in association with immobility, and edoxaban was initiated at 30 mg/day. Palliative prognostic score was 1.0 and Palliative Prognostic Index was 2.5, indicating an estimated survival of a few months rather than weeks. On Day 21 of this admission, she suddenly developed right hemiparesis and total aphasia. National Institutes of Health Stroke Scale (NIHSS) score was 18, and blood examination showed an elevated concentration of D-dimer (6.5 μg/mL). Electrocardiography showed no atrial fibrillation. We performed magnetic resonance imaging and magnetic resonance angiography, followed by administration of tissue-plasminogen activator (t-PA) and performance of mechanical thrombectomy.
      Magnetic resonance imaging/magnetic resonance angiography showed occlusion of Segment 1 of the left middle cerebral artery (MCA) and Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) of 8 (Fig. 1). At 3.8 hours after onset, we administered t-PA (0.6 mg/kg), but symptoms remained unimproved. Based on the timing (i.e., within 8 hours), severity, and persistence of symptoms despite t-PA, and high Diffusion-Weighted Imaging–ASPECTS with LVO, thrombectomy was considered indicated. Given the rapid functional deterioration and failure of medical treatment, we held prompt but comprehensive discussions with the patient's oncologist, nurses, and family to discuss mechanical thrombectomy as a potential treatment option. The family also wanted their loved one to regain the capacity for communication. We considered that the potential benefit (improvement of neurological deficits) outweighed the risks (possibility of complications from treatment), determined that the procedure would be consistent with the patient's prestroke wish to spend peacefully with her husband, and obtained consent from her family on behalf of the patient. The prestroke mRS was 4 due to vertebral compression fracture; however, this state was considered temporary and predicted to recover to mRS 0 or 1. We thus concluded that thrombectomy would be appropriate, even in the setting of this terminally ill patient receiving best supportive care. We performed mechanical thrombectomy based on the medical indications and consent from the family.
      Figure thumbnail gr1
      Fig. 1MRI/MRA study on the development of right hemiparesis and aphasia including a) MR-DWI showing DWI-ASPECTS of 8, meaning that almost all areas of left MCA were not infarcted but represented penumbra and b) MRA showing that left MCA was occluded at the red circled point. ASPECTS = Alberta Stroke Program Early Computed Tomography Scores; DWI = diffusion-weighted imaging; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging. (For interpretation of the references to color in this figure legend, the reader is Referred to the web version of this article.)
      We made three attempts at passing using a stent-retrieval device (Trevo 3*20 mm; Stryker, Fremont, CA) and an aspiration device (Penumbra 5MAX ACE; Penumbra, Alameda, CA). The third attempt succeeded in removing three thrombi (3 mm, 4 mm, and 5 mm in diameter), and recanalized the occluded vessel. Thrombolysis in Cerebral Infarction scale classification was 2b, indicating complete filling of all the expected vascular territory, but with slower filling than normal (Fig. 2). The interval from onset to recanalization was 7.3 hours. Thrombus pathology included mainly fibrin, with no tumor cells (Fig. 3).
      Figure thumbnail gr2
      Fig. 2Angiographic findings for mechanical thrombectomy. a and b) Angiography before thrombectomy showing left M1 occlusion from an anteroposterior view (a) and lateral view (b). c and d) Angiography after thrombectomy showing recanalization of almost of all the occluded left M1 (TICI 2b). Anteroposterior view (c) and lateral view (d). M1 = middle cerebral artery segment 1; TICI = Thrombolysis in Cerebral Infarction scale.
      Figure thumbnail gr3
      Fig. 3Thrombi and macroscopic and microscopic findings. a) Three thrombi removed by thrombectomy are white in coloration, with diameters of 5 mm, 4 mm, and 3 mm. b and c) HE stains of thrombus. These thrombi consist of fibrin without tumor cells. Low-power field (b) and high-power field (c).
      Thrombectomy dramatically improved symptoms (NIHSS score 8), and the patient was discharged on postoperative Day 20, at which time she was able to walk and talk with her family (NIHSS score 5). After discharge, she continued to develop multiple asymptomatic infarctions despite optimal medical management, but no symptomatic infarctions were encountered. She died from respiratory failure on postoperative Day 98.

      Comment

      Terminally ill cancer patients frequently develop a number of severe complications.
      • Chang H.M.
      • Moudgil R.
      • Scarabelli T.
      • Okwuosa T.M.
      • Yeh E.T.H.
      Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: Part 1.
      • Hoang B.X.
      • Tran D.M.
      • Tran H.Q.
      • et al.
      Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain.
      • Lawlor P.G.
      • Bush S.H.
      Delirium in patients with cancer: assessment, impact, mechanisms and management.
      • Matsuo K.
      • Watanabe R.
      • Kanamori D.
      • et al.
      Associations between oral complications and days to death in palliative care patients.
      • Pene F.
      • Percheron S.
      • Lemiale V.
      • et al.
      Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit.
      • Ripamonti C.I.
      • Farina G.
      • Garassino M.C.
      Predictive models in palliative care.
      Management of these complications is challenging because no consensus has been reached on the optimal aggressiveness of treatment.
      • Lobo S.M.
      • De Simoni F.H.B.
      • Jakob S.M.
      • et al.
      Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective.
      • Chung G.S.
      • Yoon J.D.
      • Rasinski K.A.
      • Curlin F.A.
      US physicians' opinions about distinctions between withdrawing and withholding life-sustaining treatment.
      • Stiel S.
      • Krumm N.
      • Pestinger M.
      • et al.
      Antibiotics in palliative medicine--results from a prospective epidemiological investigation from the HOPE survey.
      Trousseau syndrome is one of the most common complications for patients with advanced cancers. This potentially life-threatening complication can cause not only physical dysfunction but also serious brain dysfunction such as aphasia and can markedly menace QOL for both patients and their families.
      Generally, the treatment of cerebral infarction including Trousseau syndrome has two aspects: improvement of symptoms and secondary prevention. Mechanical thrombectomy can improve symptoms and is effective for the treatment of acute ischemic stroke in patients with occlusion of the first segment of the MCA or the internal carotid artery if treatment is initiated within 6 hours.
      Four cases of thrombectomy for Trousseau syndrome have been reported.
      • Shinohara T.
      • Tsumura M.
      • Hasegawa A.
      • Yamanaka Y.
      A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
      • Matsumoto N.
      • Fukuda H.
      • Handa A.
      • et al.
      Histological examination of trousseau syndrome-related thrombus retrieved through acute endovascular thrombectomy: report of 2 cases.
      • Inoue S.
      • Fujita A.
      • Mizowaki T.
      • et al.
      Successful treatment of repeated bilateral middle cerebral artery occlusion by performing mechanical thrombectomy in a patient with trousseau syndrome.
      More reports are available if tumor embolism is included, but none have described cases involving terminally ill patients.
      • Chan Soon Kim M.
      • Hye-Ra Jung M.
      • Kyung-Hee Cho M.
      • et al.
      Forced-suction thrombectomy of an arterial tumor embolism due to metastatic melanoma.
      • Zander T.
      • Maynar J.
      • Lopez-Zarraga F.
      • et al.
      Mechanical thrombectomy in patients with tumour-related ischaemic stroke.
      • Tejada J.
      • Galiana A.
      • Balboa O.
      • et al.
      Mechanical endovascular procedure for the treatment of acute ischemic stroke caused by total detachment of a papillary fibroelastoma.
      Decision making in terminal care is very delicate and difficult. Some reports have described the decision-making process in the management of terminally ill cancer patients with complications such as hypercalcemia, infection, and dehydration.
      • Lobo S.M.
      • De Simoni F.H.B.
      • Jakob S.M.
      • et al.
      Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective.
      • Stiel S.
      • Krumm N.
      • Pestinger M.
      • et al.
      Antibiotics in palliative medicine--results from a prospective epidemiological investigation from the HOPE survey.
      • Mori I.
      • Shimada A.
      • Maeda I.
      • Morita T.
      • Tsuneto S.
      Interspecialty differences in physicians' attitudes, beliefs, and reasons for withdrawing or withholding hypercalcemia treatment in terminally ill patients.
      • Shimada A.
      • Mori I.
      • Maeda I.
      • et al.
      Physicians' attitude toward recurrent hypercalcemia in terminally ill cancer patients.
      However, to the best of our knowledge, no papers have examined mechanical thrombectomy for stroke associated with Trousseau syndrome at the end of life. The primary goal of medical care is to restore or maintain the patient's health as much as possible while also minimizing the risk of harm. From an ethical perspective, any treatment that does not provide benefit to the patient should be withheld or withdrawn, and the goal should be shifted to the alleviation of existing symptoms.
      • Buss M.K.
      • Rock L.K.
      • McCarthy E.P.
      Understanding palliative care and hospice: a review for primary care providers.
      • Strand J.J.
      • Kamdar M.M.
      • Carey E.C.
      Top 10 things palliative care clinicians wished everyone knew about palliative care.
      We have to consider many factors, such as the benefits, risks, wishes of the patient and their family, and the expertise available in local practices.
      Several randomized controlled trials have shown the efficacy of mechanical thrombectomy for acute ischemic stroke resulting from LVO.
      • Campbell B.C.
      • Mitchell P.J.
      • Kleinig T.J.
      • et al.
      Endovascular therapy for ischemic stroke with perfusion-imaging selection.
      • Goyal M.
      • Demchuk A.M.
      • Menon B.K.
      • et al.
      Randomized assessment of rapid endovascular treatment of ischemic stroke.
      • Goyal M.
      • Menon B.K.
      • van Zwam W.H.
      • et al.
      Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.
      • Saver J.L.
      • Goyal M.
      • Bonafe A.
      • et al.
      Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
      • Jovin T.G.
      • Chamorro A.
      • Cobo E.
      • et al.
      Thrombectomy within 8 hours after symptom onset in ischemic stroke.
      According to the 2015 American Heart Association/American Stroke Association Stroke Early Management Guidelines, patients ≥18 years old should undergo mechanical thrombectomy with a stent retriever if they show minimal prestroke disability, have a causative occlusion of the internal carotid artery or proximal MCA, have an NIHSS score ≥6, have a reassuring non–contrast-enhanced computed tomography of the head (ASPECTS ≥ 6), and can be treated within 6 hours of the last known time of a normal state.
      • Powers W.J.
      • Derdeyn C.P.
      • Biller J.
      • et al.
      2015 American Heart Association/American Stroke Association focused update of the 2013 Guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
      In our case, all the aforementioned conditions were met. From the perspective of stroke management, this patient was a suitable candidate for mechanical thrombectomy. The indications for mechanical thrombectomy are not restricted to a certain thrombus type. When considering the indication of mechanical thrombectomy in patients with Trousseau syndrome, comparing the prognoses of cancer and stroke is important. Thrombectomy is particularly indicated for patients with relatively good prognosis of cancer and poor prognosis of stroke. In this patient with ovarian cancer, estimated survival was a few months based on validated prognostic scores. On the other hand, in terms of the stroke, the high NIHSS score, elevated D-dimer concentration, and modified Rankin Scale score > 3 on previous discharge were all factors independently associated with poor prognosis of stroke.
      • Sorgun M.H.
      • Kuzu M.
      • Ozer I.S.
      • et al.
      Risk factors, biomarkers, etiology, outcome and prognosis of ischemic stroke in cancer patients.
      • Shin Y.W.
      • Lee S.T.
      • Jung K.H.
      • et al.
      Predictors of survival for patients with cancer after cryptogenic stroke.
      • Nam K.W.
      • Kim C.K.
      • Kim T.J.
      • et al.
      Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke.
      In this case, we predicted that stroke prognosis was poor even with the best medical treatment, because NIHSS score was 18, D-dimer was elevated and predicted modified Rankin Scale score at discharge was over 3. Comparing the prognoses of cancer and stroke, thrombectomy was considered potentially effective.
      We also considered the risks of treatment. Trousseau syndrome frequently recurs, because of the underlying hypercoagulable status associated with the underlying cancer. In fact, in two of four reported cases, LVO recurred after mechanical thrombectomy.
      • Shinohara T.
      • Tsumura M.
      • Hasegawa A.
      • Yamanaka Y.
      A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
      • Inoue S.
      • Fujita A.
      • Mizowaki T.
      • et al.
      Successful treatment of repeated bilateral middle cerebral artery occlusion by performing mechanical thrombectomy in a patient with trousseau syndrome.
      Thrombi in Trousseau syndrome mostly comprise fibrin, causing higher frictional resistance than other thrombi such as cardiogenic thrombus or atheroma.
      • Shinohara T.
      • Tsumura M.
      • Hasegawa A.
      • Yamanaka Y.
      A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
      • Gunning G.M.
      • McArdle K.
      • Mirza M.
      • et al.
      Clot friction variation with fibrin content; implications for resistance to thrombectomy.
      Thrombectomy can be challenging in the setting of higher frictional resistance and carries risks of events including vessel perforation, dissection, and hemorrhagic events. In our case, we needed three attempts because of the high friction resistance for fibrin, with subsequent achievement of a recanalization Thrombolysis in Cerebral Infarction scale classification of 2b.
      In situations where thrombectomy is required, little time is available because this treatment must be provided within a relatively narrow window of opportunity; however, confirming consent from the patient and/or family is considerably important.
      • Lobo S.M.
      • De Simoni F.H.B.
      • Jakob S.M.
      • et al.
      Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective.
      • Chung G.S.
      • Yoon J.D.
      • Rasinski K.A.
      • Curlin F.A.
      US physicians' opinions about distinctions between withdrawing and withholding life-sustaining treatment.
      • Wright A.A.
      • Keating N.L.
      • Ayanian J.Z.
      • et al.
      Family perspectives on aggressive cancer care near the end of life.
      • Gielen J.
      • Bhatnagar S.
      • Mishra S.
      • et al.
      Can curative or life-sustaining treatment be withheld or withdrawn? The opinions and views of Indian palliative-care nurses and physicians.
      • Hinkka H.
      • Kosunen E.
      • Metsanoja R.
      • Lammi U.-K.
      • Kellokumpu-Lehtinen P.
      Factors affecting physicians_ decisions to forgo life-sustaining treatment in terminal care.
      In addition, it is limited especially in outpatients because duration from onset to treatment can be longer than that in hospitalized patients.
      Finally, we should consider whether thrombectomy is consistent with the goals of care for the patient. The goal of care in this case was to improve QOL for the patient, especially to improve her ability to communicate, which was desired by both the patient and her family. Mechanical thrombectomy offered the possibility of achieving this goal.
      Based on these assessments, performing mechanical thrombectomy was considered appropriate in this case. In fact, mechanical thrombectomy dramatically improved activities of daily living and long-term QOL over the last months of life. Fig. 4 shows the improvements in functional prognosis and long-term QOL, indicating that thrombectomy benefited the patient.
      Figure thumbnail gr4
      Fig. 4Clinical course of the patient. This graph shows the temporal course of KPS, ADL, and CA125 (ovarian tumor marker). KPS and ADL deteriorated immediately after the development of Trousseau syndrome but showed marked improvement immediately after mechanical thrombectomy. If the patient had not undergone mechanical thrombectomy, KPS would have continued to deteriorate slowly (blue dotted line). The blue shaded region indicates the magnitudes of benefit in ADL and QOL that were considered to result from thrombectomy. ADL = activities of daily living; KPS = Karnofsky Performance Status; QOL = quality of life.
      In conclusion, we performed mechanical thrombectomy to treat a terminally ill cancer patient with LVO associated with Trousseau syndrome. The appropriateness of thrombectomy for terminally ill cancer patients should be determined quickly by an interdisciplinary team based on the benefits, risks, consent from the patient and/or family, and consistency with the patient's goals of care. Mechanical thrombectomy for Trousseau syndrome offers the potential to markedly improve QOL in terminally ill patients.

      Disclosures and Acknowledgments

      This research received no specific funding/grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest.
      Ethical approval: This study was approved by the ethics committee at the Seirei Hamamatsu General Hospital. An institutional review ethics committee determined that informed consent was not required.

      References

        • Lobo S.M.
        • De Simoni F.H.B.
        • Jakob S.M.
        • et al.
        Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective.
        Chest. 2017; 152: 321-329
        • Chung G.S.
        • Yoon J.D.
        • Rasinski K.A.
        • Curlin F.A.
        US physicians' opinions about distinctions between withdrawing and withholding life-sustaining treatment.
        J Relig Health. 2016; 55: 1596-1606
        • Stiel S.
        • Krumm N.
        • Pestinger M.
        • et al.
        Antibiotics in palliative medicine--results from a prospective epidemiological investigation from the HOPE survey.
        Support Care Cancer. 2012; 20: 325-333
        • Mori I.
        • Shimada A.
        • Maeda I.
        • Morita T.
        • Tsuneto S.
        Interspecialty differences in physicians' attitudes, beliefs, and reasons for withdrawing or withholding hypercalcemia treatment in terminally ill patients.
        J Palliat Med. 2016; 19: 979-982
        • Kangasala H.H.
        • Kosunen E.
        • Lammi U.-K.
        • et al.
        Decision making in terminal care: a survey of Finnish doctors' treatment decisions in end-of-life scenarios involving a terminal cancer and a terminal dementia patient.
        Palliat Med. 2002; 16: 195-204
        • Shinohara T.
        • Tsumura M.
        • Hasegawa A.
        • Yamanaka Y.
        A case of mechanical thrombectomy for middle cerebral artery occlusion with trousseau syndrome.
        J Neuroendovascular Ther. 2017; 11: 485-491
        • Rak J.
        • Yu J.L.
        • Luyendyk J.
        • Mackman N.
        Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans.
        Cancer Res. 2006; 66: 10643-10646
        • Ikushima S.
        • Ono R.
        • Fukuda K.
        • et al.
        Trousseau's syndrome: cancer-associated thrombosis.
        Jpn J Clin Oncol. 2016; 46: 204-208
        • Matsumoto N.
        • Fukuda H.
        • Handa A.
        • et al.
        Histological examination of trousseau syndrome-related thrombus retrieved through acute endovascular thrombectomy: report of 2 cases.
        J Stroke Cerebrovasc Dis. 2016; 25: e227-e230
        • Inoue S.
        • Fujita A.
        • Mizowaki T.
        • et al.
        Successful treatment of repeated bilateral middle cerebral artery occlusion by performing mechanical thrombectomy in a patient with trousseau syndrome.
        No Shinkei Gela. 2016; 44: 501-506
        • Berkhemer O.A.
        • Fransen P.S.
        • Beumer D.
        • et al.
        A randomized trial of intraarterial treatment for acute ischemic stroke.
        N Engl J Med. 2015; 372: 11-20
        • Campbell B.C.
        • Mitchell P.J.
        • Kleinig T.J.
        • et al.
        Endovascular therapy for ischemic stroke with perfusion-imaging selection.
        N Engl J Med. 2015; 372: 1009-1018
        • Goyal M.
        • Demchuk A.M.
        • Menon B.K.
        • et al.
        Randomized assessment of rapid endovascular treatment of ischemic stroke.
        N Engl J Med. 2015; 372: 1019-1030
        • Goyal M.
        • Menon B.K.
        • van Zwam W.H.
        • et al.
        Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.
        The Lancet. 2016; 387: 1723-1731
        • Saver J.L.
        • Goyal M.
        • Bonafe A.
        • et al.
        Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
        N Engl J Med. 2015; 372: 2285-2295
        • Chang H.M.
        • Moudgil R.
        • Scarabelli T.
        • Okwuosa T.M.
        • Yeh E.T.H.
        Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: Part 1.
        J Am Coll Cardiol. 2017; 70: 2536-2551
        • Hoang B.X.
        • Tran D.M.
        • Tran H.Q.
        • et al.
        Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain.
        J Pain Palliat Care Pharmacother. 2011; 25: 19-24
        • Lawlor P.G.
        • Bush S.H.
        Delirium in patients with cancer: assessment, impact, mechanisms and management.
        Nat Rev Clin Oncol. 2015; 12: 77-92
        • Matsuo K.
        • Watanabe R.
        • Kanamori D.
        • et al.
        Associations between oral complications and days to death in palliative care patients.
        Support Care Cancer. 2016; 24: 157-161
        • Pene F.
        • Percheron S.
        • Lemiale V.
        • et al.
        Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit.
        Crit Care Med. 2008; 36: 690-696
        • Ripamonti C.I.
        • Farina G.
        • Garassino M.C.
        Predictive models in palliative care.
        Cancer. 2009; 115: 3128-3134
        • Chan Soon Kim M.
        • Hye-Ra Jung M.
        • Kyung-Hee Cho M.
        • et al.
        Forced-suction thrombectomy of an arterial tumor embolism due to metastatic melanoma.
        Arch Neurol. 2012; 69: 272-273
        • Zander T.
        • Maynar J.
        • Lopez-Zarraga F.
        • et al.
        Mechanical thrombectomy in patients with tumour-related ischaemic stroke.
        Interv Neuroradiol. 2016; 22: 705-708
        • Tejada J.
        • Galiana A.
        • Balboa O.
        • et al.
        Mechanical endovascular procedure for the treatment of acute ischemic stroke caused by total detachment of a papillary fibroelastoma.
        BMJ Case Rep. 2013; : 1-3
        • Shimada A.
        • Mori I.
        • Maeda I.
        • et al.
        Physicians' attitude toward recurrent hypercalcemia in terminally ill cancer patients.
        Support Care Cancer. 2015; 23: 177-183
        • Buss M.K.
        • Rock L.K.
        • McCarthy E.P.
        Understanding palliative care and hospice: a review for primary care providers.
        Mayo Clin Proc. 2017; 92: 280-286
        • Strand J.J.
        • Kamdar M.M.
        • Carey E.C.
        Top 10 things palliative care clinicians wished everyone knew about palliative care.
        Mayo Clin Proc. 2013; 88: 859-865
        • Jovin T.G.
        • Chamorro A.
        • Cobo E.
        • et al.
        Thrombectomy within 8 hours after symptom onset in ischemic stroke.
        N Engl J Med. 2015; 372: 2296-2306
        • Powers W.J.
        • Derdeyn C.P.
        • Biller J.
        • et al.
        2015 American Heart Association/American Stroke Association focused update of the 2013 Guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2015; 46: 3020-3035
        • Sorgun M.H.
        • Kuzu M.
        • Ozer I.S.
        • et al.
        Risk factors, biomarkers, etiology, outcome and prognosis of ischemic stroke in cancer patients.
        Asian Pac J Cancer Prev. 2018; 19: 649-653
        • Shin Y.W.
        • Lee S.T.
        • Jung K.H.
        • et al.
        Predictors of survival for patients with cancer after cryptogenic stroke.
        J Neurooncol. 2016; 128: 277-284
        • Nam K.W.
        • Kim C.K.
        • Kim T.J.
        • et al.
        Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke.
        PLoS One. 2017; 12: e0172793
        • Gunning G.M.
        • McArdle K.
        • Mirza M.
        • et al.
        Clot friction variation with fibrin content; implications for resistance to thrombectomy.
        J NeuroInterventional Surg. 2017; 0: 1-5
        • Wright A.A.
        • Keating N.L.
        • Ayanian J.Z.
        • et al.
        Family perspectives on aggressive cancer care near the end of life.
        JAMA. 2016; 315: 284-292
        • Gielen J.
        • Bhatnagar S.
        • Mishra S.
        • et al.
        Can curative or life-sustaining treatment be withheld or withdrawn? The opinions and views of Indian palliative-care nurses and physicians.
        Med Health Care Philos. 2011; 14: 5-18
        • Hinkka H.
        • Kosunen E.
        • Metsanoja R.
        • Lammi U.-K.
        • Kellokumpu-Lehtinen P.
        Factors affecting physicians_ decisions to forgo life-sustaining treatment in terminal care.
        J Med Ethics. 2002; 28: 109