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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 ›› 2026, Vol. 15 ›› Issue (03) : 386 -391. doi: 10.3877/cma.j.issn.2095-3232.2026.03.013

临床研究

肝癌肿瘤出芽与患者临床病理特征关系及其对切除术后复发影响
张文华1, 陈宇凡1, 林松茸1, 江艺2, 江哲龙2,†()   
  1. 1　363000　福建省漳州市，第九〇九医院（厦门大学附属东南医院）普通外科
    2　350001　福州，第九〇〇医院肝胆外科
  • 收稿日期:2025-10-12 出版日期:2026-06-10
  • 通信作者: 江哲龙
  • 基金资助:
    福建省自然科学基金(2023J011348)

Relation between tumor budding and clinicopathological characteristics in patients with hepatocellular carcinoma and its impact on post-hepatectomy recurrence

Wenhua Zhang1, Yufan Chen1, Songrong Lin1, Yi Jiang2, Zhelong Jiang2,†()   

  1. 1 Department of General Surgery, the 909th Hospital (Southe Hospital to Xiamen University), Zhangzhou, 363000, China
    2 Department of Hepatobiliary Surgery, the 900th Hospital, Fuzhou 350001, China
  • Received:2025-10-12 Published:2026-06-10
  • Corresponding author: Zhelong Jiang
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引用本文：

张文华, 陈宇凡, 林松茸, 江艺, 江哲龙. 肝癌肿瘤出芽与患者临床病理特征关系及其对切除术后复发影响[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(03): 386-391.

Wenhua Zhang, Yufan Chen, Songrong Lin, Yi Jiang, Zhelong Jiang. Relation between tumor budding and clinicopathological characteristics in patients with hepatocellular carcinoma and its impact on post-hepatectomy recurrence[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(03): 386-391.

目的

探讨肝癌病理组织中肿瘤出芽与患者临床病理特征的关系及其对切除术后复发的影响。

方法

回顾性分析2020年1月至2021年12月厦门大学附属东南医院收治的107例接受肝癌切除患者临床病理资料。其中男58例，女49例；年龄（60±6）岁。患者均知情同意，符合医学伦理学规定。根据术后病理结果分析癌组织中肿瘤出芽与患者临床病理特征的关系。根据是否出现肿瘤复发分为复发组（39例）和无复发组（68例）。肿瘤出芽与临床病理特征相关性分析采用χ2检验。采用Cox单因素和多因素分析肝癌复发的影响因素。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

高级别肿瘤出芽患者肿瘤最大径≥5 cm、肿瘤多发、微血管侵犯（MVI）、包膜不完整、中低分化、静脉侵犯、TNM分期Ⅲ~Ⅳ期百分比明显高于低级别肿瘤出芽患者（χ2=7.666，9.805，12.022，6.847，4.142，6.538，4.503；P<0.05）。Cox单因素分析发现肿瘤多发（HR=3.155，95%CI：1.074~9.267）、MVI（HR=2.791，95%CI：1.516~5.048）、包膜不完整（HR=4.903，95%CI：1.266~5.984）、高级别肿瘤出芽（HR=6.406，95%CI：1.349~8.071）、TNM分期Ⅲ~Ⅳ期（HR=4.102，95%CI：1.698~5.807）与术后复发相关（P<0.05）。Cox多因素回归分析显示，肿瘤多发（HR=3.342，95%CI：1.840~5.049）、MVI（HR=5.722，95%CI：1.928~7.387）、包膜不完整（HR=3.693，95%CI：1.492~6.427）、高级别肿瘤出芽（HR=4.556，95%CI：1.912~7.908）、TNM分期Ⅲ~Ⅳ期（HR=4.470，95%CI：1.846~7.631）是肝癌术后复发的危险因素（P<0.05）。随访时间9~57个月，中位随访时间39个月。生存分析显示，高级别肿瘤出芽患者术后1、3、5年累积复发率分别为8.53%、78.65%、86.71%，低级别患者相应为0、18.62%、31.36%，差异有统计学意义（χ2=14.039，P<0.001）。

结论

肝癌患者中高级别肿瘤出芽与肿瘤最大径≥5 cm、肿瘤多发、MVI、包膜不完整、中低分化、静脉侵犯、TNM分期Ⅲ~Ⅳ期等不良病理学特征相关，高级别肿瘤出芽是肝癌患者术后复发的独立危险因素，高级别肿瘤出芽患者术后复发率高，预后差。

关键词: 癌，肝细胞, 肿瘤出芽, 临床病理特征, 肿瘤复发
Objective

To investigate the relation between tumor budding in pathological specimens of patients with hepatocellular carcinoma and clinicopathological characteristics, and its impact on the recurrence after hepatectomy.

Methods

A retrospective analysis was performed on the clinicopathological data of 107 patients who underwent hepatectomy for hepatocellular carcinoma in Southe Hospital to Xiamen University from January 2020 to December 2021. There were 58 males and 49 females; the age was (60±6) years. The informed consents of all patients were obtained and the local ethical committee approval was received. Based on postoperative pathological findings, the relation between tumor budding in cancer tissue and clinicopathological characteristics was analyzed. According to whether tumor recurrence occurred, patients were divided into a recurrence group (n=39) and a non-recurrence group (n=68). The correlation between tumor budding and clinicopathological characteristics was analyzed using the χ2 test. Cox univariate and multivariate analyses were used to identify factors associated with recurrence of hepatocellular carcinoma. Recurrence-free survival was analyzed using the Kaplan-Meier method and the Log-rank test.

Results

Compared with low-grade tumor budding, patients with high-grade tumor budding had higher proportions of maximum tumor diameter ≥ 5 cm, multiple tumors, microvascular invasion (MVI), incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stage Ⅲ-Ⅳ (χ2=7.666, 9.805, 12.022, 6.847, 4.142, 6.538, 4.503; P < 0.05). Cox univariate analysis showed that multiple tumors (HR=3.155, 95%CI: 1.074-9.267), MVI (HR=2.791, 95%CI: 1.516-5.048), incomplete capsule (HR=4.903, 95%CI: 1.266-5.984), high-grade tumor budding (HR=6.406, 95%CI: 1.349-8.071), and TNM stage Ⅲ-Ⅳ (HR=4.102, 95%CI: 1.698-5.807) were associated with postoperative recurrence (P < 0.05). Cox multivariate regression analysis indicated that multiple tumors (HR=3.342, 95%CI: 1.840-5.049), MVI (HR=5.722, 95%CI: 1.928-7.387), incomplete capsule (HR=3.693, 95%CI: 1.492-6.427), high-grade tumor budding (HR=4.556, 95%CI: 1.912-7.908), and TNM stageⅢ-Ⅳ (HR=4.470, 95%CI: 1.846-7.631) were risk factors for postoperative recurrence of hepatocellular carcinoma (P < 0.05). The follow-up duration ranged from 9 to 57 months, with a median follow-up of 39 months. Survival analysis showed that the cumulative recurrence rates at 1, 3, and 5 years after surgery were 8.53%, 78.65%, and 86.71% in the high-grade tumor budding group, and 0, 18.62%, and 31.36% in the low-grade group, with a statistically significant difference (χ2=14.039, P < 0.001).

Conclusions

In patients with hepatocellular carcinoma, high-grade tumor budding is correlated with adverse pathological features, including maximum tumor diameter ≥5 cm, multiple tumors, MVI, incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stageⅢ-Ⅳ.High-grade tumor budding is an independent risk factor for postoperative recurrence, and patients with high-grade tumor budding have a higher postoperative recurrence rate and a poorer prognosis.

Key words: Carcinoma,hepatocellular, Tumor budding, Clinicopathological features, Tumor recurrence
图1 肝癌组织病理检查图（HE，×200） 注：a为低级别肿瘤出芽；b为高级别肿瘤出芽
表1 肿瘤出芽与肝癌临床病理特征相关性（例）
临床病理特征 低级别肿瘤出芽 高级别肿瘤出芽 χ2值 P值
年龄>60岁 39 18 0.031 0.860
男性 37 21 1.710 0.191
饮酒史 27 9 0.868 0.352
乙肝 47 17 1.367 0.242
Child-Pugh分级B级 21 13 1.277 0.258
AFP≥400 μg/L 63 23 3.448 0.063
腹腔镜手术 47 18 0.770 0.380
解剖性肝切除 48 19 0.518 0.472
肿瘤位于右肝 37 21 1.710 0.191
肿瘤最大径≥5 cm 18 17 7.666 0.006
肿瘤多发 8 12 9.805 0.002
MVI 19 20 12.022 0.001
包膜不完整 12 13 6.847 0.009
中低分化 27 19 4.142 0.042
静脉侵犯 5 8 6.538 0.011
TNM分期Ⅲ~Ⅳ期 13 12 4.503 0.034
表2 肝癌术后复发Cox单因素分析
因素 b SE(b) Wald χ2 HR 95%CI P值
年龄>60岁 -0.750 0.688 1.188 0.472 0.123~1.819 0.276
男性 -0.716 0.475 2.271 0.489 0.192~1.240 0.132
饮酒史 0.713 0.417 2.925 2.042 0.813~3.490 0.136
乙肝 0.939 0.517 3.301 2.559 0.744~3.848 0.240
Child-Pugh分级B级 0.263 0.560 0.220 1.301 0.434~3.900 0.639
AFP≥400 μg/L 0.233 0.814 0.082 1.263 0.256~6.231 0.775
腹腔镜手术 0.395 0.613 0.416 1.485 0.447~4.938 0.519
解剖性肝切除 -0.293 0.541 0.294 0.746 0.258~2.152 0.587
肿瘤位于右肝 1.124 0.876 1.648 3.079 0.876~4.980 0.098
肿瘤最大径≥5 cm 0.807 0.624 1.672 2.242 0.659~7.623 0.196
肿瘤多发 1.149 0.550 4.367 3.155 1.074~9.267 <0.001
MVI 1.026 0.654 2.463 2.791 1.516~5.048 0.017
包膜不完整 1.502 0.688 4.768 4.903 1.266~5.984 <0.001
中低分化 1.119 0.804 1.939 3.063 0.741~5.966 0.549
静脉侵犯 0.760 0.674 1.273 2.140 0.512~3.753 0.276
高级别肿瘤出芽 1.857 0.946 3.855 6.406 1.349~8.071 <0.001
TNM分期Ⅲ~Ⅳ期 1.411 0.860 2.694 4.102 1.698~5.807 <0.001
动脉化疗栓塞 0.857 0.694 1.523 2.356 0.604~9.185 0.217
术后靶向治疗 0.776 0.404 3.691 2.174 0.815~3.607 0.335
表3 肝癌术后复发Cox多因素分析
因素 β SE(b) Wald χ2 HR 95%CI P值
肿瘤多发 1.206 0.937 1.659 3.342 1.840~5.049 0.021
MVI 1.774 0.809 4.810 5.722 1.928~7.387 <0.001
包膜不完整 1.306 0.821 2.532 3.693 1.492~6.427 0.014
高级别肿瘤出芽 1.516 1.031 2.164 4.556 1.912~7.908 <0.001
TNM分期Ⅲ~Ⅳ期 1.497 0.795 3.548 4.470 1.846~7.631 <0.001
图2 不同级别肿瘤出芽患者复发风险曲线
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