Recently, several studies using animal models have demonstrated a relationship between platelets and metastasis of cancer.[9-11] The results

indicate that EHM tends to occur when platelet counts are high. There are several putative explanations, and one of them is a direct involvement of platelets: namely, platelets may assist implantation by forming a clot at the target organ and could induce immune escape by the tumor cells. Frequently, HCC occurs in patients with chronic liver compound screening assay disease and liver cirrhosis. Platelet counts often decrease with the development of liver disease.[12] As a result, the range of platelet counts in HCC patients is wide, meaning that HCC is a good candidate for examining the relationship between platelets and metastasis in human. In this study, we have sought to elucidate the role of platelets in metastasis by: (i) analyzing characteristics of EHM positive HCC patients at the time of the

tumor discovery (case–control study); and (ii) by analyzing risk factors of developing EHM in patients who received non-curative treatment for HCC (retrospective cohort study). AMONG 1721 CONSECUTIVE, newly diagnosed HCC patients who were admitted to Okayama University Hospital between January 1991 and August 2012, 1613 patients for whom the necessary data was available were selected for a case–control study of EHM positive and EHM negative patients. For a retrospective cohort study, we selected 803 EHM negative patients who received non-curative ABT-888 order treatment (637 patients treated by TACE and 97 patients by HAIC). Local ablation therapies had been applied to some of the HCC in 93 of the patients. Patients who developed EHM within the first 2 months were MCE considered to have already had EHM at initiation of therapy and were excluded

from the cohort (n = 1). Three hundred and ninety-five patients had a past history of curative treatment (182 RFA, 68 percutaneous ethanol injection therapy, 19 microwave coagulation therapy and 126 hepatectomy). Informed consent for the use of their clinical information was obtained from all patients in this study. The study protocol conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki, and it was approved by the ethics committee of our institute. In accordance with the American Association for the Study of Liver Diseases guidelines, HCC was diagnosed radiologically by at least two imaging modalities: hyperattenuation in the arterial phase and hypoattenuation in the portal phase on dynamic computed tomography (CT) and/or magnetic resonance imaging (MRI), and tumor staining on angiography. Fine-needle biopsy using abdominal ultrasonography (US) was performed as necessary in 276 patients for confirming the diagnosis. Vascular invasion was diagnosed macroscopically on the basis of dynamic CT/MRI or abdominal US.