원발성 간세포암종에서 부종양증후군의 발생 빈도와 임상적 의의
The Incidence and Clinical Significance of Paraneoplastic Syndromes in Patients with Hepatocellular Carcinoma
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목적: 원발성 간세포암종(이하 간암)은 고콜레스테롤혈증, 적혈구증가증, 고칼슘혈증 및 저혈당증 등의 부종양증후군이 동반될 수 있으나, 국내에서는 이에 대하여 보고된 바가 없다. 저자들은 간암 환자에서 부종양증후군의 발생과 이의 임상적 의의에 대하여 알아보고자 하였다. 대상과 방법: 1995년 1월부터 2002년 12월까지 경희대학교부속병원에서 처음으로 간암 진단을 받았던 환자 중 사망 시점이 명확하고 부종양증후군의 이차적인 발생 원인이 없었던 165명(남:여=133:32)을 대상으로 하였고, 이들의 의무기록을 후향적으로 조사하였다. 결과: 간암 질환 경과 중 부종양증후군은 전체적으로 43.6%에서 발생하였다. 고콜레스테롤혈증, 고칼슘혈증, 저혈당증이 단독으로 발생한 경우는 각각 14.5%, 7.8%, 12.7%였고, 적혈구증가증이 단독으로 발생한 경우는 없었으며, 2가지 이상이 발생한 경우는 8.5%였다. 고콜레스테롤혈증 발생 환자 31명 중 16명(51.6%), 적혈구증가증 발생 환자 5명 중 4명(80%)은 간암 진단 당시 이미 동반되어 있었으며, 고칼슘혈증이나 저혈당증은 각각의 13.6%, 3.3%만 동반되어 있었다. 부종양증후군이 발생하였던 환자는 나이가 다소 적었으며, 혈소판 수가 증가되어 있었고, AFP이 400 ng/mL 이상으로 증가한 경우가 많은 경향이 있었다. 종양 특성 면에서는 크기가 10 cm 이상인 경우, 양엽을 침범한 경우, 간문맥혈전증이 있는 경우가 유의하게 많았다. 생존분석 결과 고콜레스테롤혈증, 고칼슘혈증, 저혈당증이 Child-Pugh 등급 C와 문맥혈전증과 함께 유의한 나쁜 독립 예후인자로 판명되었다. 특히 고칼슘혈증이나 저혈당증은 발생 2주 이내에 대부분의 환자가 사망하였다. 결론: 부종양증후군은 간암이 진행된 경우에 적지 않게 발생하며, 특히 고콜레스테롤혈증, 저혈당증, 고칼슘혈증은 나쁜 예후를 시사하는 독립 인자로 생각된다.
Abstract
Background/Aims: Patients with hepatocellular carcinoma (HCC) may manifest paraneoplastic syndromes such as hypercholesterolemia, hypoglycemia, hypercalcemia and erythrocytosis. This study was aimed at evaluating the incidence and clinical significance of paraneoplastic syndromes in Korean HCC patients. Methods: The medical records of 165 HCC patients who were diagnosed and died in the Kyung Hee University Hospital, were reviewed retrospectively. The following variables were analyzed: age, gender, hepatitis markers, platelet, liver function test, α-fetoprotein (AFP), Child-Pugh score, tumor features, and the duration of their survival. Results: In total, paraneoplastic syndromes were presented in 43.6% of the HCC patients during the course of their disease. Hypercholesterolemia was solely presented in 14.5%, hypoglycemia in 12.7% and hypercalcemia in 7.8%. The patients who presented with more than 2 syndromes were 8.5%. While 80% of erythrocytosis (4/5) and 51.6% of hypercholesterolemia (16/31) was presented at the time of HCC diagnosis, hypoglycemia and hypercalcemia mainly occurred as terminal events. The patients with paraneoplastic syndromes were younger and had higher rates of portal vein thrombosis, bi-lobar tumor involvement and tumor more of more than 10 cm in diameter, compared to those patients without them. The proportion of patients with a serum AFP more than 400 ng/mL tended to be higher in the patients with paraneoplastic syndromes. The HCC patients with paraneoplastic syndromes, except for erythrocytosis, had a shorter survival than those patients without them. Conclusions: Paraneoplastic syndromes are not infrequently presented in HCC patients, especially at an advanced stage, and the survival of these patients is relatively shorter.
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