간세포암 환자의 치료에 있어 수술적 절제술과 간동맥 화학색전술 치료요법에 따른 생존율 비교 연구

Abstract

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma has been improved rapidly due to the recent advancement of various imaging tests and operative techniques. However, as the rate of early detection of hepatocellular carcinoma is still low, the percentage of cases of hepatocellular carcinoma diagnosed with advanced cancer with very poor prognosis remains high in reality. At an early stage of hepatocellular carcinoma, it can be treated adequately using operative or non-operative methods, or the survival rates of the patients could be increased. This study attempted to investigate the stages of the patients with hepatocellular carcinoma at the first diagnosis along with their liver functions, and the differences in the survival rates and survival periods between the group who underwent surgical resection and the Transcatheter Arterial Chemoembolization group who treated with transcatheter arterial chemoembolization (TACE) which was a non-operative method were investigated and compared. Further, statistical significances in the survival periods were examined by controlling prognostic factors affecting the survival rates of the patients with hepatocellular carcinoma. MATERIAL AND METHOD: The subjects of this study were 192 patients diagnosed with primary hepatocellular carcinoma and treated for the disease between January 1, 2001 and December 31, 2004 at Ajou University Hospital. When the diagnosis of hepatocellular carcinoma was firstly made, their stages and Child-Pugh classification were examined, the survival rates of hepatocellular carcinoma patients according to the treatment methods were calculated, and after controlling the prognostic factors which might affect the survival rates of the patients, its relations to survival periods were investigated. RESULT: Mean age of the 192 patients was 57 years, and the number of male patients was 3.2 times greater than that of female patients. Survived patients until December 31, 2004, the end of follow-up period, were 85 (44.3%) and the number of patients died was 107 (55.7%). Of the total subject patients, the 1, 2, and 3 year survival rates were to be 56.4%, 42.0%, and 35.8%, respectively, and median survival period was 18 months. When it was looked into according to the treatment methods, the patient group who underwent surgical resection (86 people) accounted for 44.8%; their 1, 2, and 3 year survival rates were to be 77.7%, 67.5%, and 64.4%, respectively, with median survival period of 16 months. For the group who had TACE (106 people), these patients accounted for 55.2% of the total patients, and the 1, 2, and 3 year survival rates were 40.1%, 25.0%, and 18.9%, respectively, and median survival period was 7 months. Taken together, the median survival period of the surgical resection group was 9 months longer than that of the TACE group (P<0.001). In addition, among the patients who underwent surgical resection, Child-Pugh classes A, B and C groups accounted 57%, 38%, and 5%, respectively. With regard to the survival rates according to treatment methods of the Child-Pugh Class A group, in which their liver function was adequate for operation, no statistically significant difference(P=0.0817) in survival rates was found between the surgical resection group and the TACE group among patients included the stage Ⅰ and Ⅱ groups, also the stage Ⅲ group showed no significant differences in the survival rates (P=0.2377); the results can be concluded that there are no statistically significant differences in the survival rates according to treatment methods if the patients with hepatocellular carcinoma maintain good liver function and remain in an early stage. In the results of the analysis of the survival rates according to the modified UICC staging, the survival rates of the surgical resection group were higher than that of the TACE group, and there were statistically significant differences in the survival rates according to treatment methods among the different stage groups(P<0.001), showing that the survival rates and survival periods of the patients with hepatocellular carcinoma were statistically significantly lower with their stages increased. Significant prognostic factors in the survival rate of hepatocellular carcinoma were found to be treatment methods, liver cirrosis, Child-Pugh Class, serum alpha-fetoprotein (AFP), the presence or absence of serum ascites, the Modified UICC staging, and so on. In the analysis conducted after controlling the above variables, there were statistically significant differences between the treatment methods of surgical resection and TACE. CONCLUSIONS: In most cases, the treatment of hepatocellular carcinoma was attempted in limited cases where liver function was intact, and there were no statistically significant differences in the survival rates according to treatment methods if the patients with hepatocellular carcinoma maintain good liver function and remain in an early stage. In expecting survival rate, the degree of liver function and stages of the cancer were found to be significant prognostic factors. In regard to the differences in survival rates between the TACE group in which the subjects had advanced cancers so that operation was not possible and the surgical resection group, the survival period of the surgical resection group was found to be longer than that of the TACE group.

목적: 최근 각종 영상 진단법의 발달 및 수술 술기의 발전으로 인하여 간세포암의 예후는 비약적으로 향상되었다. 그러나 아직도 조기 간암의 발견율은 낮으며 예후가 불량한 진행암의 상태로 진단되는 간세포암이 훨씬 더 많은 실정이다. 간암의 병기가 낮은 경우에는 수술적 치료 및 비수술적 초기 치료로 완치 시키거나 환자의 생존율을 높일 수 있다. 본 연구는 간세포암 환자에서, 최초 진단시에 간기능의 상태와 병기가 어느 정도 진행 되었는지에 대해 조사하고, 간 절제술 요법으로 치료를 받은군과 비수술적 치료요법인 간동맥 화학색전술 (transcatheter arterial chemoembolization : TACE)로 치료 받은 환자군 사이에 생존율과 생존기간에 차이가 있는지를 비교 연구하고자 하였으며, 간세포암 환자의 생존율에 영향을 미치는 예후인자들을 통제하여 생존기간의 통계학적 유의성을 파악해 보고자 하였다. 대상 및 방법: 본 연구는 아주대학교 의과대학 부속 병원에 내원하여 2001년 1월 1일부터 2004년 12월 31일 까지, 원발성 간세포암으로 진단 및 치료를 받은 환자 192명을 대상으로 하여, 간세포암의 최초 진단시 병기(stage)와 Child-Pugh분류에 대해 조사하고, 치료법에 따른 간세포암 환자들의 생존율을 구하였으며, 생존율에 영향을 미칠 수 있는 예후 인자들을 통제하고 생존기간과의 연관성을 조사 하였다. 결과: 대상환자 192명의 평균 연령은 57세 였으며 남자가 여자보다 3.2배 많았다. 추적종료 시점인 2004년 12월 31일 까지 생존한 환자는 85명(44.3%)이었으며 사망한 환자는 모두 107명(55.7%)였다. 전체 대상 환자의 1, 2, 3년 생존율은 각각 56.4%, 42.0%, 35.8%이었으며, 중앙 생존기간은 18개월 이었다. 치료요법별로 보면, 간 절제술(86명)을 시행받은 환자군은 44.8% 였으며 1, 2, 3년 생존율은 각각 77.7%, 67.5%, 64.4%, 중앙생존기간은 16개월 이었고, 간동맥 화학색전술(106명)을 시행받은 환자군은 55.2% 였으며, 1, 2, 3년 생존율은 각각 40.1%, 25.0%, 18.9%, 중앙생존기간은 7개월 이었다. 간 절제술을 받은 환자군의 경우가 간동맥 화학색전술을 시행한 환자보다 중앙생존기간이 9개월이 더 길었고 통계학적으로 유의하였다 (P<0.001). 간 절제술을 시행받은 환자는 Child-Pugh A, B등급의 경우가 각각 57%와 38%이었으며 C등급의 경우는 5%이었다. 수술이 가능한 간기능 상태인 Child-Pugh Class A군의 환자들만을 대상으로 하여, 치료요법별로 생존율을 분석한 결과를 보면, 병기 Ⅰ, Ⅱ기 군에서 간동맥 화학색전술과 간 절제술을 시행한 환자들 사이에 생존율에 있어서 통계학적으로 유의한 차이가 없었으며 (P=0.0817) 또한 병기 Ⅲ군에서도 생존율에 의미있는 차이가 발견되지 않아 (P=0.2377) 간기능 상태가 양호하고, 조기 발견되어 병기가 낮은 간세포암 환자들은 치료방법에 따른 생존율에 있어 통계학적으로 유의한 차이가 없었다. Modified UICC 병기에 따라 생존율을 분석한 결과에서 보면 간동맥 화학색전술군에 비해 간 절제술군의 생존율이 높게 나타났으며 각 병기 단계별로 치료요법에 따른 생존율에 통계학적으로 유의한 차이가 있었다 (P<0.001). 병기 단계가 높아 질수록 간세포암 환자의 생존율과 생존기간은 통계학적으로 유의하게 낮았다. 간세포암의 생존율에 통계학적으로 유의하게 영향을 미치는 인자는 치료방법, 간경변, Child-Pugh Class, 혈청 알파태아단백치(AFP), 복수의 유무, Modified UICC 병기 분류 등이었다. 이들 변수들을 통제하고 시행한 분석에서 간 절제술과 간동맥 화학색전술은 통계학적으로 유의한 차이가 있었다. 결론: 간 절제술의 경우 대부분의 간세포암 환자가 간기능이 잘 유지된 경우에 치료가 시행 되었으며, 간기능 상태가 양호하고, 조기 발견되어 병기가 낮은 간세포암 환자들은 치료방법에 따른 생존율에 있어 통계학적으로 유의한 차이가 없었다. 생존율을 예측하는데 있어 간기능의 정도와 병기는 매우 중요한 예후 인자 이었으며, 진행된 간세포암을 대상으로 수술이 불가능한 경우에 시행되는 간동맥 화학색전 시술과 간 절제술의 생존율 차이에 있어서는 간 절제술을 받은 환자군의 경우가 생존기간이 더 길었다.