Background. Paraneoplastic syndromes (PNS) such as hypercalcaemia, hypercholesterolaemia, and erythrocytosis have been described in hepatocellular carcinoma (HCC). Aims. (1) To examine the prevalence, clinical characteristics, and survival of PNS in HCC patients and (2) to evaluate the extent to which each individual PNS impacts on patient survival. Methods. We prospectively evaluated the prevalence, clinical characteristics, and survival of PNS among 457 consecutive HCC patients seen in our department over a 10-year period and compared them with HCC patients without PNS. Results. PNS were present in 127 patients (27.8%). The prevalence of paraneoplastic hypercholesterolemia, hypercalcemia, and erythrocytosis 24.5%, 5.3%, and 3.9%, respectively. Patients with PNS had significantly higher alpha-fetoprotein levels, more advanced TNM stage, and shorter survival. Among the individual PNS, hypercalcemia and hypercholesterolemia were associated with more advanced disease and reduced survival but not erythrocytosis. On multivariate analysis, the presence of PNS was not found to be an independent prognostic factor for reduced HCC survival. Conclusion. PNS are not uncommon in HCC and are associated with poor prognosis and reduced survival due to their association with increased tumor burden. However, they do not independently predict poor survival. Individual PNS impact differently on HCC outcome; paraneoplastic hypercalcemia in particular is associated with poor outcome. 1. Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and is associated with significant mortality [1]. Symptomatic HCC patients often present with constitutional symptoms such as malaise, anorexia and weight loss in association with abdominal discomfort or an abdominal mass. Occasionally, patients may present with atypical features due to paraneoplastic manifestations of HCC. The paraneoplastic syndromes (PNS) which have been associated with HCC include hypercholesterolemia, hypercalcemia, erythrocytosis, hypoglycemia, demyelinating disease, pemphigus, polyarthritis, encephalomyelitis, and thrombocytosis [2–10]. The most common PNS associated with HCC are hypercholesterolemia, hypercalcemia, hypoglycemia, and erythrocytosis [11]. There is very little literature on PNS in HCC. Previous studies have suggested that HCC patients with PNS have more advanced disease, higher alpha-fetoprotein (AFP) levels, and poorer survival compared to those without [11–14]. In a study of PNS in patients with HCC in Taiwan [12], the presence of PNS was found to be an independent
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