Abstract
Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in ex vivo culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression.
Highlights
Human cancers are associated with frequent intravascular embolism (Noble and Pasi, 2010), which could be either symptomatic or asymptomatic, occurring before or after the cancer diagnosis (Viale, 2005; Elyamany et al, 2014)
We examined patient blood samples including those from pancreatic cancer patients for additional abnormalities that could be explored as etiologic factors or warning biomarkers of cancer-associated vascular embolism
Suspecting additional contributory factors of vascular occlusion, we examined whether certain features in cancer patient peripheral blood samples could serve as sentinels of cancerassociated vascular embolism
Summary
Human cancers are associated with frequent intravascular embolism (Noble and Pasi, 2010), which could be either symptomatic or asymptomatic, occurring before or after the cancer diagnosis (Viale, 2005; Elyamany et al, 2014). Pancreatic cancer is found to have the highest incidence; from 17 to 57% of the patients suffering from embolic events (Khorana and Fine, 2004; Shah and Saif, 2010). As. Circulating Fatty Objects a cancer complication, the embolism is often fatal, accounted for the second leading cause of cancer mortality (Pruemer, 2005; Sheth et al, 2017). Delineating the mechanism of vascular embolism in cancer progression and metastasis will help improve patient survival. The aim of this study is to search for additional abnormalities which may contribute to cancerassociated vascular embolism
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