切换至 "中华医学电子期刊资源库"
高级检索
中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (02) : 151 -157. doi: 10.3877/cma.j.issn.2095-3232.2024.02.006

临床研究

微血管侵犯及手术切缘对肝细胞癌患者术后生存预后的影响
王礼光1, 严庆2, 廖珊2, 符荣党2, 陈焕伟3,†()   
  1. 1. 5240001　广东省湛江市，广东医科大学第一临床学院
    2. 528010　广东省佛山市第一人民医院肝脏胰腺外科
    3. 5240001　广东省湛江市，广东医科大学第一临床学院；528010　广东省佛山市第一人民医院肝脏胰腺外科
  • 收稿日期:2023-12-27 出版日期:2024-04-10
  • 通信作者: 陈焕伟
  • 基金资助:
    广东省自然科学基金重点项目(2020A1515110073); 广东省科学技术奖培育项目(2020001003307); 肝癌的微创诊疗技术及基础研究创新平台建设(2016AG100561)

Effect of microvascular invasion and surgical margin on postoperative survival and prognosis of patients with hepatocellular carcinoma

Liguang Wang1, Qing Yan2, Shan Liao2, Rongdang Fu2, Huanwei Chen3,†()   

  1. 1. The First Clinical Medical College of Guangdong Medical University, Zhanjiang 524001, China
    2. Department of Hepatobiliary and Pancreatic Surgery, the First People's Hospital of Foshan, Foshan 528010, China
    3. The First Clinical Medical College of Guangdong Medical University, Zhanjiang 524001, China; Department of Hepatobiliary and Pancreatic Surgery, the First People's Hospital of Foshan, Foshan 528010, China
  • Received:2023-12-27 Published:2024-04-10
  • Corresponding author: Huanwei Chen
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

王礼光, 严庆, 廖珊, 符荣党, 陈焕伟. 微血管侵犯及手术切缘对肝细胞癌患者术后生存预后的影响[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 151-157.

Liguang Wang, Qing Yan, Shan Liao, Rongdang Fu, Huanwei Chen. Effect of microvascular invasion and surgical margin on postoperative survival and prognosis of patients with hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(02): 151-157.

目的

探讨微血管侵犯（MVI）及手术切缘对肝细胞癌（HCC）术后生存预后的影响。

方法

回顾性分析2016年1月至2020年12月佛山市第一人民医院收治的513例HCC肝切除患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男419例，女94例；年龄25～86岁，中位年龄54岁。MVI分为3个等级：M0（无MVI组）、M1（低危组）、M2（高危组）。肿瘤切缘分为窄切缘（<1 cm）、宽切缘（≥1 cm）。采用χ2检验及Logistic回归多因素分析HCC患者MVI发生的影响因素。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

单因素分析显示，AFP、肿瘤直径、肿瘤数目、CNCL与HCC患者MVI发生有关（χ2=28.068，29.657，4.375，10.208；P<0.05）。Logistic回归多因素分析显示，AFP、肿瘤直径是HCC患者MVI发生的独立影响因素（OR=0.408，0.394；P<0.05）。M0组术后1、2、3年无瘤生存率分别为79.6%、71.0%、63.4%，M1组相应为59.6%、48.0%、43.3%，M2组相应为31.0%、27.5%、25.2%，差异有统计学意义（χ2=61.889，P<0.05）。M0组术后1、2、3年总体生存率分别为97.3%、88.2%、84.6%，M1组相应为87.0%、71.5%、66.1%，M2组相应为79.3%、61.9%、52.6%，差异有统计学意义（χ2=44.138，P<0.05）。对于MVI阴性患者，宽切缘组术后1、2、3年无瘤生存率分别为82.6%、70.7%、65.4%，而窄切缘组相应为79.4%、64.7%、60.5%，差异无统计学意义（χ2=0.983，P>0.05）；宽切缘组术后1、2、3年总体生存率分别为97.5%、89.6%、85.2%，而窄切缘组相应为97.1%、86.0%、82.8%，差异无统计学意义（χ2=0.051，P>0.05）。对于MVI阳性患者，宽切缘组术后1、2、3年无瘤生存率分别为58.1%、45.4%、40.3%，而窄切缘组相应为42.9%、37.3%、36.1%，差异有统计学意义（χ2=4.874，P<0.05）；宽切缘组术后1、2、3年总体生存率分别为88.8%、71.9%、64.3%，窄切缘组相应为82.6%、64.8%、61.0%，差异有统计学意义（χ2=4.604，P<0.05）。

结论

肿瘤大小、AFP是HCC患者发生MVI的独立危险因素。MVI分级越高，患者预后越差。对于MVI阳性患者，肿瘤切缘宽者长期预后优于切缘窄者；而对于MVI阴性患者，肿瘤切缘对预后无明显影响。

关键词: 癌，肝细胞, 微血管侵犯, 肝切除术, 手术切缘, 生存分析, 预后
Objective

To evaluate the effect of microvascular invasion (MVI) and surgical margin on postoperative survival and prognosis of hepatocellular carcinoma (HCC) patients.

Methods

Clinical data of 513 patients with HCC admitted to the First People's Hospital of Foshan from January 2016 to December 2020 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 419 patients were male and 94 female, aged from 25 to 86 years, with a median age of 54 years. MVI was divided into three grades: M0 (non-MVI group), M1 (low-risk group) and M2 (high-risk group). The tumor surgical margin was divided into narrow surgical margin (<1 cm) and wide surgical margin (≥1 cm). The influencing factors of MVI in HCC patients were identified by Chi-square test and Logistic regression analysis. Survival analysis was conducted by Kaplan-Meier method and Log-rank test.

Results

Univariate analysis showed that AFP, tumor diameter, number of tumors and China liver cancer (CNLC) staging system were correlated with the incidence of MVI in HCC patients (χ2=28.068, 29.657, 4.375, 10.208; P<0.05). Multivariate Logistic regression analysis showed that AFP and tumor diameter were the independent influencing factors of MVI in HCC patients (OR=0.408, 0.394; P<0.05). In the M0 group, the postoperative 1-,2- and 3-year disease-free survival rates were 79.6%, 71.0% and 63.4%, and 59.6%, 48.0% and 43.3% in the M1 group, and 31.0%, 27.5% and 25.2% in theM2 group, respectively. The differences were statistically significant (χ2=61.889, P<0.05). In the M0 group, the postoperative 1-, 2- and 3-year overall survival rates were 97.3%, 88.2% and 84.6%, 87.0%, 71.5% and 66.1% in the M1 group, and 79.3%, 61.9% and 52.6% in the M2 group, respectively. The differences were statistically significant (χ2=44.138, P<0.05). For MVI-negative patients, the postoperative 1-,2- and 3-year disease-free survival rates in the wide margin group were 82.6%, 70.7% and 65.4%, and 79.4%, 64.7% and 60.5% in the narrow margin group, with no statistical significance (χ2=0.983, P>0.05). In the wide margin group, the 1-, 2- and 3-year overall survival rates were 97.5%, 89.6% and 85.2%, and 97.1%, 86.0% and 82.8% in the narrow margin group, with no statistical significance (χ2=0.051, P>0.05). For MVI-positive patients, the postoperative 1-, 2- and 3-year disease-free survival rates in the wide margin group were 58.1%, 45.4% and 40.3%, and 42.9%, 37.3% and 36.1% in the narrow margin group. The differences were statistically significant (χ2=4.874, P<0.05). In the wide margin group, the postoperative 1-, 2- and 3-year overall survival rates were 88.8%, 71.9% and 64.3%, and 82.6%, 64.8% and 61.0% in the narrow margin group. The differences were statistically significant (χ2=4.604, P<0.05).

Conclusions

Tumor size and AFP are the independent risk factors for MVI in HCC patients. The higher the MVI grade, the worse the prognosis. For patients with positive MVI, long-term prognosis of patients with wide surgical margin is better than that of those with narrow surgical margin. However, for patients with negative MVI, tumor surgical margin exerts no significant effect upon clinical prognosis.

Key words: Carcinoma, hepatocellular, Microvascular invasion, Hepatectomy, Surgical margin, Survival analysis, Prognosis
表1 不同分级MVI的HCC患者术前一般资料比较（例）
参数 M0组 M1组 M2组 χ2值 P值
性别（男/女） 257/75 109/14 53/5 4.331 0.115
年龄（≤50岁/>50岁） 117/215 55/68 27/31 5.052 0.080
Plt（<100×109/L/≥100×109/L） 17/315 4/119 4/54 1.253 0.534
AFP（<400 μg/L/≥400 μg/L） 252/80 65/58 31/27 28.075 0.001
HBV-DNA定量（≤104 cps/ml />104 cps/ml） 161/171 55/68 31/27 1.249 0.536
肝硬化（有/无） 287/45 107/16 55/3 3.219 0.200
肿瘤直径（≤5 cm/>5 cm） 215/117 50/73 22/36 29.775 0.001
肿瘤数目（单发/多发） 304/28 111/12 44/14 13.031 0.001
CNLC分期（Ⅰ/Ⅱ） 317/15 113/10 46/12 19.498 0.001
术中输血 40 13 8 0.413 0.813
Clavien并发症Ⅲ级以上 30 18 6 2.989 0.224
表2 HCC患者MVI发生影响因素的单因素分析（例）
因素 MVI阴性 MVI阳性 χ2值 P值
性别（男/女） 257/75 162/19 3.316 0.071
年龄（≤50岁/>50岁） 117/215 82/99 2.282 0.115
Plt（<100×109/L/≥100×109/L） 315/17 173/8 1.124 0.725
AFP（<400 μg/L/≥400 μg/L） 252/80 85/96 28.068 0.001
HBV-DNA定量（≤104 cps/ml />104 cps/ml） 161/171 86/95 0.045 0.832
肝硬化（有/无） 287/45 162/19 1.003 0.317
肿瘤直径（≤5 cm/>5 cm） 215/117 72/109 29.657 0.001
肿瘤数目（单发/多发） 304/28 155/26 4.375 0.036
CNLC分期（Ⅰ/Ⅱ） 317/15 159/22 10.208 0.001
表3 HCC患者MVI发生影响因素的Logistic多因素回归分析
因素 b SE（b） Wald χ2 OR 95% CI P值
AFP≥400 μg/L 0.897 0.204 19.374 0.408 0.274～0.608 0.001
肿瘤直径>5 cm 0.931 0.199 21.852 0.394 0.267～0.582 0.001
肿瘤数目多发 0.066 0.598 0.012 0.937 0.290～3.025 0.913
CNLC Ⅱ期 0.797 0.687 1.344 0.451 0.117～1.734 0.246
图1 MVI分级对HCC患者术后生存影响的Kaplan-Meier生存曲线注：MVI为微血管侵犯，HCC为肝细胞癌；M0为无MVI，M1为癌旁1 cm肝组织不超过5个MVI，M2为癌旁1 cm肝组织多于5个MVI或MVI出现在距离肿瘤超过1 cm肝实质
图2 MVI阳性组肿瘤切缘对HCC患者术后生存影响的Kaplan-Meier生存曲线注：MVI为微血管侵犯，HCC为肝细胞癌
[1]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2]
Wang M, Wang Y, Feng X, et al. Contribution of hepatitis B virus and hepatitis C virus to liver cancer in China north areas: experience of the Chinese National Cancer Center[J]. Int J Infect Dis, 2017(65):15-21.
[3]
Chen HW, Liao S, Wan-Yee L, et al. Prognostic impact of hepatic resection for hepatocellular carcinoma: the role of the surgeon in achieving R0 resection-a retrospective cohort study[J]. Int J Surg, 2015(13):297-301.
[4]
夏永祥, 张峰, 李相成, 等. 原发性肝癌10 966例外科治疗分析[J]. 中华外科杂志, 2021, 59(1):6-17.
[5]
罗发, 严庆, 陈焕伟. 腹腔镜肝切除治疗肝细胞癌的安全性和长期疗效观察[J]. 岭南现代临床外科, 2022, 22(5):441-445.
[6]
丛文铭, 吴孟超. 努力提高我国肝癌微血管侵犯的精细化诊断和个体化治疗水平[J]. 中华肝胆外科杂志, 2019, 25(10):721-724.
[7]
丛文铭, 步宏, 陈杰, 等. 原发性肝癌规范化病理诊断指南(2015版)[J]. 临床与实验病理学杂志, 2015, 31(3):241-246.
[8]
中华人民共和国国家卫生健康委员会医政医管局.原发性肝癌诊疗指南(2022年版)[J].中国实用外科杂志, 2022, 42(3):241-273.
[9]
Erstad DJ, Tanabe KK. Prognostic and therapeutic implications of microvascular invasion in hepatocellular carcinoma[J]. Ann Surg Oncol, 2019, 26(5):1474-1493.
[10]
Xu X, Zhang HL, Liu QP, et al. Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma[J]. J Hepatol, 2019, 70(6):1133-1144.
[11]
Hong SB, Choi SH, Kim SY, et al. MRI features for predicting microvascular invasion of hepatocellular carcinoma: a systematic review and meta-analysis[J]. Liver Cancer, 2021, 10(2):94-106.
[12]
Zeng J, Zeng J, Wu Q, et al. Novel inflammation-based prognostic nomograms for individualized prediction in hepatocellular carcinoma after radical resection[J]. Ann Transl Med, 2020, 8(17):1061.
[13]
Hu H, Qi S, Zeng S, et al. Importance of microvascular invasion risk and tumor size on recurrence and survival of hepatocellular carcinoma after anatomical resection and non-anatomical resection[J]. Front Oncol, 2021(11):621622.
[14]
谢伟选, 柏杨, 方征, 等. 肝细胞癌微血管侵犯的危险因素及其对预后的影响分析[J]. 中国普通外科杂志, 2022, 31(7):890-895.
[15]
Margonis GA, Sergentanis TN, Ntanasis-Stathopoulos I, et al. Impact of surgical margin width on recurrence and overall survival following R0 hepatic resection of colorectal metastases: a systematic review and meta-analysis[J]. Ann Surg, 2018, 267(6):1047-1055.
[16]
熊书名, 郭飞宇, 杨军, 等. AFP在肝癌术后患者生存预后中的价值[J/OL]. 中华肝脏外科手术学电子杂志, 2019, 8(5):444-447.
[17]
Imura S, Teraoku H, Yoshikawa M, et al. Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria[J]. Int J Clin Oncol, 2018, 23(1):98-103.
[18]
Yang P, Si A, Yang J, et al. A wide-margin liver resection improves long-term outcomes for patients with HBV-related hepatocellular carcinoma with microvascular invasion[J]. Surgery, 2019, 165(4):721-730.
[19]
Chen ZH, Zhang XP, Feng JK, et al. Actual long-term survival in hepatocellular carcinoma patients with microvascular invasion:a multicenter study from China[J]. Hepatol Int, 2021, 15(3):642-650.
[20]
Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma:a prospective randomized trial[J]. Ann Surg, 2007, 245(1):36-43.
[21]
Han J, Li ZL, Xing H, et al. The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study[J]. HPB, 2019, 21(8):962-971.
[22]
焦作义, 俞泽元. 原发性肝癌外科治疗进展[J/OL]. 中华肝脏外科手术学电子杂志, 2016, 5(5):281-284.
[23]
Zhou JM, Zhou CY, Chen XP, et al. Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: a prospective cohort study[J]. World J Gastrointest Oncol, 2021, 13(12):2190-2202.
[24]
Nitta H, Allard MA, Sebagh M, et al. Ideal surgical margin to prevent early recurrence after hepatic resection for hepatocellular carcinoma[J]. World J Surg, 2021, 45(4):1159-1167.
[1] 薛雨柔, 孔洁, 朱龙玉, 韩慧娜, 张钧, 刘志坤. 局部治疗在乳腺癌术后孤立性局部区域复发中的作用[J]. 中华乳腺病杂志(电子版), 2024, 18(01): 18-24.
[2] 王旭, 钱航, 刘军, 时志斌, 党晓谦, 刘瑞宇. 肱骨近端骨折合并肩袖损伤对半肩关节置换术后的影响[J]. 中华关节外科杂志(电子版), 2024, 18(01): 8-16.
[3] 刘政宏, 王凤力, 吉亚君, 高佳. 胃癌中ELK3蛋白的表达与临床病理特征和预后的关系研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 155-159.
[4] 张琳, 李婷. CRIP1在胃癌中的表达及与临床病理指标和预后的关系研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 171-175.
[5] 杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[6] 朱显钟, 李金雨, 于忠英, 温路生. 淋巴结平均直径与无淋巴结转移肾癌病理特征及预后关系研究[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 146-151.
[7] 朱迎, 赵征, 许达, 陆录, 殷保兵. 免疫检查点抑制剂治疗肝细胞癌的进展与展望[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 5-10.
[8] 张占国. 靶向免疫治疗时代的肝癌肝切除术再思考[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 11-15.
[9] 洪汉崟, 陈志坚, 池小斌, 陈剑伟, 俞建达, 陈永标. 鞘外法和鞘内法Glisson蒂阻断在腹腔镜解剖性肝切除中应用的对比研究[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 21-26.
[10] 孙振, 谭天华, 郑洋洋, 李喆, 宋京海. 基于术前纤维蛋白原与白蛋白比值构建肝癌微血管侵犯的预测模型[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 27-32.
[11] 黄金灿, 王迪, 崔松平, 陈晴, 吕少诚, 贺强, 郎韧. 预后营养指数对交界可切除胰腺癌患者术后预后的预测价值[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 51-56.
[12] 沈佳佳, 何经雄, 王芳, 江艺, 潘凡, 张小进. ICG荧光引导腹腔镜射频消融在合并严重大结节肝硬化小肝癌患者治疗中的应用[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 68-71.
[13] 张宇, 余灵祥, 杨永平, 赵德希, 刁广浩, 杨木易, 赵亮, 刘佳, 李鹏, 张宁, 任辉. 原发性肝癌Ⅲa期降期后肝切除临床疗效分析[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 78-82.
[14] 严帅, 岳志强, 赵江华, 陈琳, 吴金柱. 初始不可切除肝癌患者靶向免疫联合治疗后手术切除临床疗效[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 83-87.
[15] 冯军, 艾麦提·牙森, 梁润斌, 廖志洪, 赵超尘, 谢嘉奋, 朱灿华, 罗燕君, 汪国营. 肝癌肝移植术前应用PD-1抑制剂后发生急性排斥反应一例并文献复习[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 88-92.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号