Background/aims: Hepatocellular carcinoma patients with paraneoplastic syndromes usually have a larger tumor volume and a higher serum alpha-fetoprotein. Whether the presence of paraneoplastic syndromes, such as hypercholesterolemia, hypoglycemia, hypercalcemia, and erythrocytosis in hepatocellular carcinoma patients is a significant prognostic factor in patients' survival is of clinical interest.
Methodology: We evaluated the occurrence of paraneoplastic syndromes in 903 hepatocellular carcinoma patients; 179 (20%) patients developed paraneoplastic syndromes either upon diagnosis or during follow-up, 179 age-sex-tumor volume-matched hepatocellular carcinoma patients without paraneoplastic syndromes were selected as controls. Serum liver biochemistry, alpha-fetoprotein, clinical Child-Pugh's score, tumor image studies, histological features, accessibility to treatment, and survival were recorded and compared between patients with and without paraneoplastic syndromes. Prognostic factors in patients' survival were analyzed. The clinical course and survival of hepatocellular carcinoma patients with different paraneoplastic syndromes were also compared.
Results: Multivariate Cox regression analysis revealed Child-Pugh's grade C, ineligibility for active treatment, serum alpha-fetoprotein > 10,000 ng/mL, main portal vein tumor thrombosis, and the presence of paraneoplastic syndromes were all independent unfavorable prognostic factors for survival. The median survival from the occurrence of paraneoplastic manifestation to death was only 36 days. Patients with different paraneoplastic syndromes had similar clinical characteristics in Child-Pugh's score, serum alpha-fetoprotein level, tumor volume, prevalence of main portal vein tumor thrombosis, and accessibility for active treatment upon diagnosis. However, erythrocytosis and hypercholesterolemia usually developed earlier in the clinical course, whilst hypoglycemia and hypercalcemia were usually terminal events. Hepatocellular carcinoma patients with erythrocytosis tended to have a longer survival than patients with other paraneoplastic syndromes.
Conclusions: The presence of paraneoplastic syndromes in hepatocellular carcinoma patients is an unfavorable prognostic factor, excluding the occurrence of erythrocytosis.