Hyperlipidemia as a risk factor for Trousseau syndrome‑related cerebral infarction in patients with advanced gastrointestinal cancer

Tanaka,Toshimitsu; Suzuki,Hiroyuki; Miwa,Keisuke; Ushijima,Tomoyuki; Nagasu,Sachiko; Fukahori,Masaru; Ishii,Kaito; Nakamura,Toru; Iwamoto,Hideki; Masuda,Atsutaka; Sakaue,Takahiko; Koga,Hironori; Akagi,Yoshito; Murotani,Kenta; Torimura,Takuji

doi:10.3892/ol.2022.13437

Hyperlipidemia as a risk factor for Trousseau syndrome‑related cerebral infarction in patients with advanced gastrointestinal cancer

Authors:
- Toshimitsu Tanaka
- Hiroyuki Suzuki
- Keisuke Miwa
- Tomoyuki Ushijima
- Sachiko Nagasu
- Masaru Fukahori
- Kaito Ishii
- Toru Nakamura
- Hideki Iwamoto
- Atsutaka Masuda
- Takahiko Sakaue
- Hironori Koga
- Yoshito Akagi
- Kenta Murotani
- Takuji Torimura
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Affiliations: Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka 830‑0011, Japan, Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Biostatistics Center, Kurume University, Kurume, Fukuoka 830‑0011, Japan
Published online on: July 19, 2022 https://doi.org/10.3892/ol.2022.13437
Article Number: 318
Copyright: © Tanaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Trousseau syndrome‑related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome‑related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome‑related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58‑75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome‑related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome‑related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785‑27.513). Trousseau syndrome‑related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.

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1	Trousseau A: Phlegmasia alba dolens. Clin Med Hotel-dieu Paris. 3:654–712. 1865.
2	Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Francis CW, et al: Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 38:496–520. 2020. View Article : Google Scholar : PubMed/NCBI
3	Timp JF, Braekkan SK, Versteeg HH and Cannegieter SC: Epidemiology of cancer-associated venous thrombosis. Blood. 122:1712–1723. 2013. View Article : Google Scholar : PubMed/NCBI
4	Cohen AT, Katholing A, Rietbrock S, Bamber L and Martinez C: Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost. 117:57–65. 2017. View Article : Google Scholar : PubMed/NCBI
5	Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F and Girolami A: Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 100:3484–3488. 2002. View Article : Google Scholar : PubMed/NCBI
6	Lee AY: Epidemiology and management of venous thromboembolism in patients with cancer. Thromb Res. 110:167–172. 2003. View Article : Google Scholar : PubMed/NCBI
7	Prandoni P, Falanga A and Piccioli A: Cancer and venous thromboembolism. Lancet Oncol. 6:401–410. 2005. View Article : Google Scholar : PubMed/NCBI
8	Cestari DM, Weine DM, Panageas KS, Segal AZ and DeAngelis LM: Stroke in patients with cancer: Incidence and etiology. Neurology. 62:2025–2030. 2004. View Article : Google Scholar : PubMed/NCBI
9	Rickles FR: Mechanisms of cancer-induced thrombosis in cancer. Pathophysiol Haemost Thromb. 35:103–110. 2006. View Article : Google Scholar : PubMed/NCBI
10	Grisold W, Oberndorfer S and Struhal W: Stroke and cancer: A review. Acta Neurol Scand. 119:1–16. 2009. View Article : Google Scholar : PubMed/NCBI
11	Graus F, Rogers LR and Posner JB: Cerebrovascular complications in patients with cancer. Medicine (Baltimore). 64:16–35. 1985. View Article : Google Scholar : PubMed/NCBI
12	Khorana AA, Francis CW, Culakova E, Kuderer NM and Lyman GH: Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 5:632–634. 2007. View Article : Google Scholar : PubMed/NCBI
13	Schwarzbach CJ, Schaefer A, Ebert A, Held V, Bolognese M, Kablau M, Hennerici MG and Fatar M: Stroke and cancer: The importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 43:3029–3034. 2012. View Article : Google Scholar : PubMed/NCBI
14	Varki A: Trousseau's Syndrome: Multiple definitions and multiple mechanisms. Blood. 110:1723–1729. 2007. View Article : Google Scholar : PubMed/NCBI
15	Noble S and Pasi J: Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer. 102 (Suppl 1):S2–S9. 2010. View Article : Google Scholar : PubMed/NCBI
16	Wun T and White RH: Epidemiology of cancer-related venous thromboembolism. Best Pract Res Clin Haematol. 22:9–23. 2009. View Article : Google Scholar : PubMed/NCBI
17	Takano H, Nakajima K, Nagayoshi Y, Komazaki H, Suzuki J, Tanabe H, Niimi S, Isonishi S and Okamoto A: Clinical associations of Trousseau's syndrome associated with cerebral infarction and ovarian cancer. J Gynecol Oncol. 29:e672018. View Article : Google Scholar : PubMed/NCBI
18	Chen W, He Y and Su Y: Multifocal cerebral infarction as the first manifestation of occult malignancy: Case series of Trousseau's syndrome and literature review. Brain Circ. 4:65–72. 2018. View Article : Google Scholar : PubMed/NCBI
19	Kim SG, Hong JM, Kim HY, Lee J, Chung PW, Park KY, Kim GM, Lee KH, Chung CS and Bang OY: Ischemic stroke in cancer patients with and without conventional mechanisms: A multicenter study in Korea. Stroke. 41:798–801. 2010. View Article : Google Scholar : PubMed/NCBI
20	Chaturvedi S, Ansell J and Recht L: Should cerebral ischemic events in cancer patients be considered a manifestation of hypercoagulability? Stroke. 25:1215–1218. 1994. View Article : Google Scholar : PubMed/NCBI
21	Pinzon R, Drewinko B, Trujillo JM, Guinee V and Giacco G: Pancreatic carcinoma and Trousseau's syndrome: Experience at a large cancer center. J Clin Oncol. 4:509–514. 1986. View Article : Google Scholar : PubMed/NCBI
22	Brierley JD, Gospodarowicz MK and Christian Wittekind C: TNM Classification of Malignant Tumours. 8th edition. Wiley Publications; Hoboken, NJ: 2016
23	Araki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, Osawa H, Taguchi A, Tanizawa Y, Tobe K and Yoshioka N: Japanese clinical practice guideline for diabetes 2019. Diabetol Int. 11:165–223. 2020. View Article : Google Scholar : PubMed/NCBI
24	Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, Horio T, Hoshide S, Ikeda S, Ishimitsu T, et al: The Japanese society of hypertension guidelines for the management of hypertension (JSH 2019). Hypertens Res. 42:1235–1481. 2019. View Article : Google Scholar : PubMed/NCBI
25	Lipsy RJ: The National cholesterol education program adult treatment panel III guidelines. J Manag Care Pharm. 9 (Suppl 1):S2–S5. 2003. View Article : Google Scholar : PubMed/NCBI
26	KDIGO CKD Work Group, : KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. (Suppl 3):1–150. 2013.
27	Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K, Mayumi T, Murata A, Ikeda T, Ishikura H, et al: A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria. Crit Care Med. 34:625–631. 2006. View Article : Google Scholar : PubMed/NCBI
28	Puhr R, Heinze G, Nold M, Lusa L and Geroldinger A: Firth's logistic regression with rare events: Accurate effect estimates and predictions? Stat Med. 36:2302–2317. 2017.PubMed/NCBI
29	Zaorsky NG, Zhang Y, Tchelebi LT, Mackley HB, Chinchilli VM and Zacharia BE: Stroke among cancer patients. Nat Commun. 10:51722019. View Article : Google Scholar : PubMed/NCBI
30	Alloubani A, Nimer R and Samara R: Relationship between hyperlipidemia, cardiovascular disease and stroke: A systematic review. Curr Cardiol Rev. 17:e0511211890152021. View Article : Google Scholar : PubMed/NCBI
31	Dardiotis E, Aloizou AM, Markoula S, Siokas V, Tsarouhas K, Tzanakakis G, Libra M, Kyritsis AP, Brotis AG, Aschner M, et al: Cancer-associated stroke: Pathophysiology, detection and management (Review). Int J Oncol. 54:779–796. 2019.PubMed/NCBI
32	Lv J, Yang L, Guo R, Shi Y, Zhang Z and Ye J: Ox-LDL-induced microRNA-155 promotes autophagy in human endothelial cells via repressing the Rheb/mTOR pathway. Cell Physiol Biochem. 43:1436–1448. 2017. View Article : Google Scholar : PubMed/NCBI
33	Awkar N, Amireh S, Rai S, Shaaban H, Guron G and Maroules M: Association between level of tumor markers and development of VTE in patients with pancreatic, colorectal and ovarian Ca: Retrospective case-control study in two community hospitals. Pathol Oncol Res. 24:283–287. 2018. View Article : Google Scholar : PubMed/NCBI
34	Adam SS, Key NS and Greenberg CS: D-dimer antigen: Current concepts and future prospects. Blood. 113:2878–2887. 2009. View Article : Google Scholar : PubMed/NCBI
35	Tripodi A: D-Dimer testing in laboratory practice. Clin Chem. 57:1256–1262. 2011. View Article : Google Scholar : PubMed/NCBI
36	Bao L, Zhang S, Gong X and Cui G: Trousseau syndrome related cerebral infarction: Clinical manifestations, laboratory findings and radiological features. J Stroke Cerebrovasc Dis. 29:1048912020. View Article : Google Scholar : PubMed/NCBI
37	Taniguchi T, Kakkar AK, Tuddenham EG, Williamson RC and Lemoine NR: Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res. 58:4461–4467. 1998.PubMed/NCBI
38	Tsushima M, Metoki N, Hagii J, Saito S, Shiroto H, Yasujima M, Kato T, Kudo N, Toyama Y, Yokono Y, et al: D-Dimer and C-reactive protein as potential biomarkers for diagnosis of trousseau's syndrome in patients with cerebral embolism. J Stroke Cerebrovasc Dis. 29:1045342020. View Article : Google Scholar : PubMed/NCBI
39	Khorana AA, Kuderer NM, Culakova E, Lyman GH and Francis CW: Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 111:4902–4907. 2008. View Article : Google Scholar : PubMed/NCBI
40	Mulder FI, Candeloro M, Kamphuisen PW, Di Nisio M, Bossuyt PM, Guman N, Smit K, Büller HR and van Es N; CAT-prediction collaborators, : The khorana score for prediction of venous thromboembolism in cancer patients: A systematic review and meta-analysis. Haematologica. 104:1277–1287. 2019. View Article : Google Scholar : PubMed/NCBI
41	Donati MB and Lorenzet R: Thrombosis and cancer: 40 years of research. Thromb Res. 129:348–352. 2012. View Article : Google Scholar : PubMed/NCBI
42	Ikushima S, Ono R, Fukuda K, Sakayori M, Awano N and Kondo K: Trousseau's Syndrome: Cancer-associated thrombosis. Jpn J Clin Oncol. 46:204–208. 2016. View Article : Google Scholar : PubMed/NCBI
43	Noble S and Goa KL: Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer. Drugs. 54:447–472. 1997. View Article : Google Scholar : PubMed/NCBI
44	van Hell AJ, Haimovitz-Friedman A, Fuks Z, Tap WD and Kolesnick R: Gemcitabine kills proliferating endothelial cells exclusively via acid sphingomyelinase activation. Cell Signal. 34:86–91. 2017. View Article : Google Scholar : PubMed/NCBI
45	Sasaki R, Ohya Y, Hayashida S, Maeda Y, Murahashi S, Kumamoto S, Tsuji A, Shibata H, Kuramoto K, Hayashi H, et al: A case of Trousseau's syndrome due to intrahepatic cholangiocarcinoma with an extremely high level of CA19-9. Surg Case Rep. 6:752020. View Article : Google Scholar : PubMed/NCBI
46	Yamamoto R, Kato S, Takahashi M, Ono S, Sakurada T, Nagoshi S, Nisikawa K and Yakabi K: Trousseau syndrome accompanied by cholangiocellular carcinoma: Report of two. J Saitama Medical University. 40:131–134. 2014.
47	Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI
48	Nuver J, De Haas EC, Van Zweeden M, Gietema JA and Meijer C: Vascular damage in testicular cancer patients: A study on endothelial activation by bleomycin and cisplatin in vitro. Oncol Rep. 23:247–253. 2010.PubMed/NCBI
49	Walsh-McMonagle D and Green D: Low-molecular-weight heparin in the management of Trousseau's syndrome. Cancer. 80:649–655. 1997. View Article : Google Scholar : PubMed/NCBI
50	Yoshida K, Kimura T, Aburakawa Y, Suzuki Y, Kuroda K and Yahara O: Recurrent ischemic stroke in a patient with the trousseau syndrome treated with dabigatran. J Stroke Cerebrovasc Dis. 23:1724–1726. 2014. View Article : Google Scholar : PubMed/NCBI