title: Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver.
abstract: Oxaliplatin-based chemotherapy plays a central role in the treatment of patients with colorectal liver metastasis (CRLM). This treatment, however, has been associated with hepatic sinusoidal obstruction syndrome (SOS), a clinically important adverse effect characterized by a bluish hue of the liver, splenomegaly and thrombocytopenia, resulting in liver dysfunction. The significant association between the sinusoidal endothelium and platelets has suggested that oxaliplatin-based chemotherapy affects platelets in the liver. This study compared platelet counts in patients who did and did not receive oxaliplatin-based neoadjuvant chemotherapy (NAC). The peripheral blood platelet count was significantly lower in the NAC group (n=17) compared to that in the non-NAC, or control group (n=15) (P<0.05). The spleen index was also higher in the NAC group, although the difference was not significant. However, the spleens of the patients in the NAC group were significantly enlarged following treatment (P<0.01). Immunostaining for the platelet surface marker CD42b (glycoprotein Ib), revealed more platelets in the liver in the NAC compared to the control group, particularly in the centrilobular zone III, adjacent to the hepatic central vein and in contact with hepatocytes (P<0.01). The platelets present in the spaces of Disse, referred to as extravasated platelet aggregation (EPA), secrete a number of growth factors, including transforming growth factor-β, vascular endothelial growth factor-A, plasminogen activator inhibitor-1 and thromboxane A2. In conclusion, EPA may play an important role in the development of hepatic SOS. Moreover, antiplatelet drugs may prevent the onset of SOS and hepatic injury in patients treated with oxaliplatin-based chemotherapy for CRLM.
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakanuma
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Matoba
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Seisho
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Nakagawara
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Division of Cancer Medicine, Department of Gastroenterologic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Pathology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
keywords: colorectal liver metastasis; extravasated platelet aggregation; oxaliplatin; sinusoidal obstruction syndrome