Successful Treatment in a Case of Massive Hepatocellular Carcinoma with Paraneoplastic Syndrome

Abstract

Paraneoplastic syndromes of hepatocellular carcinoma (HCC) are not uncommon. However, the prognosis is poor and follow-up and improvement of paraneoplastic syndromes with treatment have been reported rarely. We report a successful case in an aged man of a massive HCC with paraneoplastic syndrome, treated by combined intraarterial chemotherapy and hepatic resection. Paraneoplastic syndrome (erythrocytosis and hyperlipidemia) was monitored throughout the treatment and erythropoietin (EPO) mRNA also was analyzed in the resected liver. The hemoglobin level and serum levels of EPO and total cholesterol (T-cho) decreased dramatically with treatment, along with a decrease in serum levels of α-fetoprotein and protein induced by vitamin vitamin K absence II (PIVKA-II). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that the residual cancer expressed EPO RNA but the nontumor tissue did not. This was a rare case of paraneoplastic syndrome of HCC that was treated successfully. This case indicates that paraneoplastic syndrome reflected tumor progression and that serum levels of both EPO and T-cho might be used as tumor markers.

Paraneoplastic Polyarthritis in Hepatocellular Carcinoma Treated With Lenvatinib

“…Resolution of HCC-associated PNS has only been documented with locoregional treatment. (1) Rheumatic PNSs are rare and symptoms are acute in onset and associated with asymmetric synovitis manifesting with pain disproportionate to the physical exam, swelling, and stiffness in small and large joints. (2) Most cases are seronegative with elevated inflammatory markers and poor response to steroids and disease-modifying antirheumatic drugs.…”

“…Arani Sathiyapalan, 1 Kimberly Legault, 2 Christian B. van der Pol, 3 and Brandon M. Meyers 1 P araneoplastic syndromes (PNSs) are clinical manifestations distant from the primary malignancy. They are associated with advanced disease and poor survival.…”

ARID1A loss in adult hepatocytes activates β-catenin-mediated erythropoietin transcription

“…Lastly, some liver cancer studies have identified pathological erythrocytosis and/or hepatic vascular lesions, potentially with EPO production and peliosis. However, the molecular mechanisms underlying these pathological observations are still poorly understood ( Matsuyama et al, 2000 ; Bunn, 2013 ; Ke et al, 2017 ; Hoshimoto et al, 2009 ; Tsuchiya et al, 2009 ; Vik et al, 2009 ). Our study contributes molecular clues by indicating that this is not linked to CTNNB1/ARID1A mutations, but more likely attributed to the hypoxia frequently found in cancers.…”

Erythrocytosis in hepatocellular carcinoma portends poor prognosis by respiratory dysfunction secondary to mitochondrial DNA mutations

“…Our data have demonstrated that both HIF‐1α and HIF‐2α proteins are stabilized in tumor tissues from HCC patients with erythrocytosis, secondary to up‐regulation of EPO. These findings support previous clinical reports of paraneoplastic erythrocytosis associated with elevated EPO levels in HCC . In contrast to hypoxia‐induced HIF‐α expression, the sustained HIF‐α expression and EPO secretion in the HCC cells from patients with erythrocytosis independent of tumor microenvironment, which was induced by “pseudo‐hypoxia,” encouraged us to focus on potential intrinsic causes presented in the HCC cells.…”