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肝细胞癌完全病理缓解的肝移植受者中肿瘤标志物的表达模式

Expression Patterns of Tumor Markers in Liver Transplant Recipients Showing Complete Pathological Response of Hepatocellular Carcinoma.

作者信息

Kim Min-Jae, Kang Woo-Hyoung, Hwang Shin, Ahn Chul-Soo, Moon Deok-Bog, Ha Tae-Yong, Song Gi-Won, Jung Dong-Hwan, Park Gil-Chun

机构信息

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

出版信息

J Clin Med. 2022 Oct 6;11(19):5897. doi: 10.3390/jcm11195897.

Abstract

Complete pathological response (CPR) is achieved with various pretransplant locoregional treatments for hepatocellular carcinoma (HCC). This study aimed to investigate pretransplant expression of HCC tumor markers in liver transplantation (LT) recipients showing CPR. For the CPR group, 166 patients were selected from a single-institution LT database. Two control groups of 332 patients without HCC and 184 patients with partial pathological response (PPR) were also selected. The model for end-stage liver disease score in the CPR group was 11.5 ± 7.7. The number of transcatheter arterial chemoembolization sessions before LT was one in 68 patients (14.0%), two in 38 patients (22.9%), and three or more in 60 patients (36.1%). A solitary non-viable tumor was identified in 120 (86.4%) of the explant livers and the largest tumor size was 2.4 ± 1.3 cm. Living-donor and deceased-donor LTs were performed in 152 (91.6%) and 14 (8.4%) patients, respectively. The median levels of α-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) measured within two weeks before LT were 4.2 ng/mL and 20 mAU/mL, respectively. These tumor marker levels were comparable to those in the no-HCC control group, but much lower than those in the PPR group (p < 0.001). Receiver operating characteristic curve analysis of AFP and PIVKA-II showed no definite cutoff values for CPR in the cohort of CPR and no-HCC patients, but significant cutoffs of 6.5 ng/mL for AFP and 29 mAU/mL for PIVKA-II were obtained in the cohort of CPR and PPR patients. The 1-, 3- and 5-year HCC recurrence and overall patient survival rates of the CPR group were 5.1% and 93.3%, 7.6% and 89.6%, and 7.6% and 89.6%, respectively. These tumor recurrence rates were much lower than those in the PPR group (p < 0.001). In conclusion, the present study results suggest that normalizing AFP and PIVKA-II after locoregional treatment is indicative of CPR. However, some CPR patients showed high expression of tumor markers; thus, pretransplant values of HCC tumor markers should be interpreted with caution.

摘要

通过对肝细胞癌(HCC)进行各种移植前局部区域治疗可实现完全病理缓解(CPR)。本研究旨在调查在肝移植(LT)受者中出现CPR时HCC肿瘤标志物的移植前表达情况。对于CPR组,从单机构LT数据库中选取了166例患者。还选取了两个对照组,分别为332例无HCC患者和184例部分病理缓解(PPR)患者。CPR组的终末期肝病模型评分是11.5±7.7。LT前经动脉化疗栓塞术的次数,68例患者(14.0%)为1次,38例患者(22.9%)为2次,60例患者(36.1%)为3次或更多次。在120例(86.4%)切除的肝脏中发现单个无活性肿瘤,最大肿瘤大小为2.4±1.3cm。分别有152例(91.6%)和14例(8.4%)患者接受了活体供体和尸体供体LT。LT前两周内测得的甲胎蛋白(AFP)和维生素K缺乏或拮抗剂-II诱导蛋白(PIVKA-II)的中位水平分别为4.2ng/mL和20mAU/mL。这些肿瘤标志物水平与无HCC对照组相当,但远低于PPR组(p<0.001)。对AFP和PIVKA-II进行的受试者工作特征曲线分析显示,在CPR组和无HCC患者队列中,对于CPR没有明确的临界值,但在CPR组和PPR患者队列中,AFP的临界值为6.5ng/mL,PIVKA-II的临界值为29mAU/mL。CPR组1年、3年和5年的HCC复发率和患者总生存率分别为5.1%和93.3%、7.6%和89.6%、7.6%和89.6%。这些肿瘤复发率远低于PPR组(p<0.001)。总之,本研究结果表明,局部区域治疗后AFP和PIVKA-II恢复正常表明出现了CPR。然而,一些CPR患者显示肿瘤标志物高表达;因此,对HCC肿瘤标志物的移植前值应谨慎解读。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9c/9573247/11230484b830/jcm-11-05897-g001.jpg

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