We observed a clear relationship between platelet counts and EHM of HCC in the case–control study. However, it was unclear

whether high platelet counts promoted EHM or were a consequence of EHM. In cancer patients, the presence of infectious disease and cytokine production by cancer cells may cause an elevation of platelet counts. To eliminate these uncertainties, we performed a retrospective cohort study, and here also we observed that high platelet counts floated as a risk factor for EHM. Platelet MLN0128 purchase count also correlated with the appearance of portal vein tumor thrombosis (PVTT) in our preliminary analysis, indicating the importance of platelets in various clinical aspects. The elevation of DCP, the presence of vascular invasion and multiple nodules of HCC can be considered as risk factors of EHM associated with high malignant potential of HCC. The marker DCP is associated with portal vein invasion and tumor angiogenesis,[13] and it also correlates with PCI-32765 autologous HCC cell proliferation in vitro through the DCP Met–STAT3 signaling pathway.[14] Moreover, portal vein invasion is a major cause of intrahepatic metastasis.[15] All of these markers are so-called tumor factors that are characteristic of HCC. In contrast, high platelet count is the only risk factor for EHM other than tumor factors. There are several reports that platelets contribute to tumor metastasis.[9-11]

P-selectin mediates the aggregation of activated platelets and tumor cells,[16] whereby the platelets can then defend the aggregated tumor cells by forming a physical barrier against attack of circulating immune-competent cells.[17] Surviving tumor cells arrest within the microvasculature of distant organs and then subsequently exit from the blood circulation and form metastatic lesions. There are some reports that

high platelet counts correlate with poor prognosis in cancers of several organs, including the uterus, kidney, brain, pancreas, lung, colon learn more and breast.[18-24] It is well known that liver function correlates with platelet counts, where platelet counts decline with advancement of liver functional impairment.[12] Addario et al. reported that HCC patients with better hepatic function show an increased risk for metastases.[25] The results of these reports suggested an indirect relationship between platelet counts and EHM of HCC, and we have confirmed that relationship in the present study. In addition, high platelet counts (>10 × 104/μL) were significantly associated with the presence of PVTT in both the case–control study (P < 0.001) and the retrospective cohort study (P < 0.001). High platelet counts may be associated with the appearance of PVTT. In this study, the frequency of EHM was high in patients of Child–Pugh A. Similar result was reported by Addario et al. as described previously.