BCLC 0/A期肝细胞癌根治性切除术后复发评分预警系统的建立及其预测价值分析

刘胜; 唐豪佑; 杨洋; 曾新; 黄孝彬; 顾秋红; 李建水

doi:10.3969/j.issn.1001-5256.2021.09.022

BCLC 0/A期肝细胞癌根治性切除术后复发评分预警系统的建立及其预测价值分析

DOI: 10.3969/j.issn.1001-5256.2021.09.022

1.
川北医学院附属医院肝胆外二科，四川南充 637000
2.
德阳市人民医院重症医学科，四川德阳 618000

基金项目:

四川省南充市科学技术局2019市校合作科研项目 (18SXHZ0332)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：刘胜负责课题设计，资料分析，撰写论文; 唐豪佑、杨洋、曾新、黄孝彬、顾秋红参与收集数据和分析，修改论文; 李建水负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
李建水，ljs2005doctor@126.com

中图分类号: R735.7
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出版历程
- 收稿日期: 2021-01-05
- 录用日期: 2021-03-01
- 出版日期: 2021-09-20

Establishment and predictive value of an early warning system for recurrence after radical resection of BCLC stage 0/A hepatocellular carcinoma

1.
Second Department of Hepatobiliary Surgery, Affiliated Hospital of Chuanbei Medical College, Nanchong, Sichuan 637000, China
2.
Department of Critical Care Medicine, Deyang People's Hospital, Deyang, Sichuan 618000, China

Research funding:

The 2019 Scientific Research Project of City-University Cooperation in Nanchong Bureau of Science & Technology of Sichuan Province (18SXHZ0332)

摘要

摘要: 目的建立BCLC 0/A期肝细胞癌(HCC)根治性切除术后复发评分预警系统(PLC-EWSPRS)并对其预测价值进行分析。方法回顾性分析川北医学院附属医院2009年1月—2015年1月行根治性切除的232例BCLC 0/A期HCC患者的临床资料。根据电话或门诊资料随访术后5年内是否复发分为复发组(103例)和非复发组(129例)。符合正态分布的计量资料两组间比较采用t检验; 非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间采用χ²检验或Fisher精确法检验。将差异具有统计学意义的指标纳入二元logistic回归分析，探讨BCLC 0/A期HCC术后复发的危险因素。将独立危险因素赋值为2分，危险因素赋值为1分，建立PLC-EWSPRS系统。采用受试者工作特征(ROC)曲线下面积(AUC)评估其诊断效能。结果两组患者术前AST(Z=3.864, P＜0.001)、ALT(Z=4.587, P＜0.001)复发组明显高于非复发组，术前Alb(t=-5.628, P＜0.001)复发组明显低于非复发组; 复发组HBsAg阳性、包膜侵犯、微血管侵犯(MVI)、肿瘤直径≥5 cm、肝硬化(中重度)、非R0切除、5年死亡数所占比例均显著高于非复发组(χ²值分别为35.539、22.325、13.398、7.130、4.312、4.034、18.527，P值均＜0.05)。回归分析显示：术前Alb＜40 g/L(OR=5.796，P＜0.001)、术前ALT≥40 U/L(OR=3.029，P=0.002)、MVI(OR=3.981，P=0.003)、HBsAg阳性(OR=7.829，P＜0.001)、包膜侵犯(OR=5.357，P＜0.001)、非R0切除(OR=3.048，P=0.018)均为根治性切除的BCLC 0/A期HCC术后5年复发的独立危险因素。根据PLC-EWSPRS系统拟定的赋分标准，复发组最低分2分，最高分14分; 非复发组最低分0分，最高分11分，复发组分值明显高于非复发组，两组患者分值比较差异具有统计学意义(P＜0.05)。ROC曲线分析结果显示，预测根治性切除的BCLC 0/A期HCC者术后5年内复发的AUC(95%CI)为0.918(0.883~0.953)，P＜0.001;亚组预测低、中、高分数段术后5年内复发的AUC(95%CI)分别为：0.796(0.695~0.896)，P=0.002;0.859(0.791~0.927)，P＜0.001;0.944(0.839~1.000)，P=0.044。结论 PLC-EWSPRS对BCLC 0/A期HCC患者术后5年复发具有良好的预测价值，对根治性切除的BCLC 0/A期HCC患者术后复查及治疗策略的制订具有重要的指导意义。
- 癌，肝细胞 /
- 肝切除术 /
- 复发 /
- 危险因素
Abstract: Objective To establish an Early Warning System for Recurrence Scoring after Radical Resection of BCLC stage 0/A Primary Liver Cancer (PLC-EWSPRS), and to investigate its predictive value. Methods A retrospective analysis was performed for the clinical data of 232 patients with BCLC stage 0/A liver cancer who underwent radical resection in Affiliated Hospital of Chuanbei Medical College from January 2009 to January 2015, and according to the presence or absence of recurrence within 5 years after surgery based on telephone or outpatient follow-up data, the patients were divided into recurrence group with 103 patients and non-recurrence group with 129 patients. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or Fisher's exact test was used for comparison of categorical data between groups. The indices with statistical significance were included in the binary logistic regression analysis to investigate the risk factors for recurrence of BCLC stage 0/A liver cancer after surgery. Two points were assigned for independent risk factors and one point was assigned for risk factors to establish the PLC-EWSPRS system. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic efficiency of this system. Results Compared with the non-recurrence group, the recurrence group had significantly higher levels of aspartate aminotransferase and alanine aminotransferase (ALT) and a significantly lower level of albumin (Alb) before surgery (Z=3.864 and 4.587, t=-5.628, all P < 0.001), as well as a significantly higher proportion of patients with positive HBsAg, capsular invasion, microvascular invasion (MVI), tumor diameter ≥5 cm, liver cirrhosis (moderate-to-severe), non-R0 resection, or death within 5 years (χ²=35.539, 22.325, 13.398, 7.130, 4.312, 4.034, and 18.527, all P < 0.05). The regression analysis showed that preoperative Alb < 40 g/L (odds ratio [OR]=5.796, P < 0.001), preoperative ALT ≥40 U/L (OR=3.029, P=0.002), MVI (OR=3.981, P=0.003), positive HBsAg (OR=7.829, P< 0.001), capsular invasion (OR=5.357, P< 0.001), and non-R0 resection (OR=3.048, P=0.018) were independent risk factors for recurrence of BCLC stage 0/A liver cancer within 5 years after surgery. According to the assignment criteria of the PLC-EWSPRS system, the recurrence group had the lowest score of 2 points and the highest score of 14 points, while the non-recurrence had the lowest score of 0 point and the highest score of 11 points, and the recurrence group had a significantly higher score than the non-recurrence group (P < 0.05). The ROC curve analysis showed that the PLC-EWSPRS system had an AUC of 0.918 (95% confidence interval [CI]: 0.883-0.953, P < 0.001) in predicting recurrence within 5 years after surgery in patients with BCLC stage 0/A liver cancer undergoing radical resection, and subgroup analysis showed that the system had an AUC of 0.796 (95% CI: 0.695-0.896, P=0.002), 0.859 (95% CI: 0.791-0.927, P < 0.001), and 0.944 (95% CI: 0.839-1.000, P=0.044), respectively, in predicting recurrence within 5 years after surgery in patients with a low score of 0-5 points, a moderate score of 6-10 points, and a high score of 11-14 points. Conclusion The PLC-EWSPRS system has a good value in predicting the recurrence of BCLC stage 0/A liver cancer within 5 years after surgery and thus has important guiding significance for postoperative reexamination and treatment strategy for patients with BCLC stage 0/A liver cancer undergoing radical resection.
- Carcinoma, Hepatocellular /
- Hepatectomy /
- Recurrence /
- Risk Factors

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图 1 PLC-EWSPRS预测术后5年复发的ROC曲线

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图 2 PLC-EWSPRS预测术后5年死亡的ROC曲线

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表 1 术后5年内复发组与非复发组相关基线资料、并发症及结局的比较

项目	复发组(n=103)	非复发组(n=129)	统计值	P值
住院时间(d)	9.84±3.98	10.23±4.72	t=-0.666	0.506
年龄(岁)	50.36±12.05	52.28±12.99	t=-1.155	0.249
体质量(kg)	56.94±4.85	56.68±6.70	t=0.337	0.745
OS(月)	18.0(8.0~31.0)	25.0(15.5~40.5)	Z=-2.880	0.004
术前RBC(10⁹/L)	4.63±0.68	4.53±0.59	t=1.166	0.245
术前WBC(10⁹/L)	5.57±1.63	5.60±2.02	t=-0.438	0.662
术前PLT(10⁹/L)	144(101~203)	138(92~200)	Z=0.445	0.656
术前TBil(μmol/L)	14.7(11.7~19.3)	13.6(10.1~18.0)	Z=1.666	0.096
术前DBil(μmol/L)	4.8(3.5~6.4)	4.5(3.6~5.8)	Z=0.975	0.330
术前ALT(U/L)	51(39~63)	39(30~52)	Z=4.587	＜0.001
术前AST(U/L)	44(33~65)	34(25~51)	Z=3.864	＜0.001
术前Alb(g/L)	39.08±4.19	42.34±4.53	t=-5.628	＜0.001
男性[例(%)]	84(81.6)	102(79.1)	χ²=0.222	0.637
HBsAg阳性[例(%)]	87(84.5)	60(46.5)	χ²=35.539	＜0.001
包膜侵犯[例(%)]	48(46.6)	23(17.8)	χ²=22.325	＜0.001
肿瘤直径≥5 cm[例(%)]	86(83.5)	88(68.2)	χ²=7.130	0.008
MVI[例(%)]	32(31.1)	15(11.6)	χ²=13.398	＜0.001
R0切除[例(%)]	79(76.7)	112(86.8)	χ²=4.034	0.045
低分化程度[例(%)]	40(38.8)	53(41.1)	χ²=0.121	0.728
肿瘤数≥2个[例(%)]	11(10.7)	15(11.6)	χ²=0.052	0.820
5年死亡数[例(%)]	51(49.5)	29(22.5)	χ²=18.527	＜0.001
肝硬化(中重度)[例(%)]	34(33.0)	27(20.9)	χ²=4.312	0.038
BCLC分期[例(%)]
0期	9(8.7)	8(6.2)	χ²=0.543	0.461
A期	94(91.3)	121(93.8)
并发症[例(%)]
肺部感染	8(7.8)	8(6.2)	χ²=0.219	0.640
腹腔感染	3(2.9)	2(1.6)		0.841
腹腔出血	2(1.9)	7(5.4)		0.172
腹腔积液	81(78.6)	88(68.2)	χ²=3.146	0.076
胸腔积液	9(8.7)	5(3.9)	χ²=2.387	0.122
复发部位[例(%)]
肝	86(83.5)
肺	5(4.9)
肝肺	3(2.9)
肝脑	1(1.0)
腹腔	5(4.9)
骨	1(1.0)
淋巴结	2(1.9)

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表 2 BCLC 0/A期HCC患者行根治性切除术5年复发的logistic单因素分析

项目	B值	SE	Wald	P值	OR(95%CI)
术前Alb(＜40 g/L)	1.563	0.286	29.804	＜0.001	4.774(2.724~8.368)
术前ALT(≥40 U/L)	1.045	0.278	14.093	＜0.001	2.843(1.648~4.906)
MVI	1.231	0.348	12.551	＜0.001	3.425(1.733~6.769)
HBsAg阳性	1.833	0.324	31.955	＜0.001	6.253(3.312~11.806)
肿瘤直径(≥5 cm)	0.857	0.326	6.921	0.009	2.357(1.244~4.464)
包膜侵犯	1.392	0.303	21.073	＜0.001	4.022(2.220~7.287)
肝硬化(中重度)	0.621	0.301	4.255	0.039	1.862(1.031~3.360)
非R0切除	0.694	0.349	3.944	0.047	2.001(1.009~3.970)

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表 3 BCLC 0/A期HCC患者行根治性切除术5年复发的logistic多因素分析

项目	B值	SE	Wald	P值	OR(95%CI)
常量	-4.598	0.661	48.371	＜0.001	0.010
术前Alb(＜40 g/L)	1.757	0.376	21.826	＜0.001	5.796(2.773~12.113)
术前ALT(≥40 U/L)	1.108	0.366	9.175	0.002	3.029(1.479~6.204)
MVI	1.382	0.463	8.922	0.003	3.981(1.608~9.856)
HBsAg阳性	2.058	0.413	24.884	＜0.001	7.829(3.488~17.574)
肿瘤直径(≥5 cm)	0.606	0.410	2.187	0.139	1.833(0.821~4.091)
包膜侵犯	1.678	0.411	16.668	＜0.001	5.357(2.393~11.992)
肝硬化(中重度)	0.406	0.406	1.001	0.317	1.502(0.677~3.329)
非R0切除	1.115	0.473	5.552	0.018	3.048(1.206~7.704)

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表 4 两组患者PLC-EWSPRS评分的分布及复发差异分析

分值分段(复发率)	分值	各分值病例分布[例(%)]		分值段病例分布[例(%)]		χ²值	P值
分值分段(复发率)	分值	复发组(n=103)	非复发组(n=129)	复发组(n=103)	非复发组(n=129)	χ²值	P值
低分段(0~5)	0	0	5(3.9)			91.502	＜0.001
(9.8%)	1	0	15(11.6)
	2	2(1.9)	8(6.2)
	3	2(1.9)	18(14.0)
	4	2(1.9)	18(14.0)
	5	4(3.9)	28(21.7)	10(9.7)	92(71.3)
中分段(6~10)	6	14(13.6)	16(12.4)
(68.2%)	7	10(9.7)	14(10.9)
	8	25(24.3)	1(0.8)
	9	12(11.7)	2(1.6)
	10	14(14.6)	2(1.6)	75(72.8)	35(27.1)
高分段(11~14)	11	2(1.9)	2(1.6)
(90.0%)	12	8(7.8)	0
	13	6(5.8)	0
	14	2(1.9)	0	18(17.5)	2(1.6)

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