Wang Han, Zhou Ying-Ying, Chen Hong-Zhen, Sheng Xia, Xia Chun-Yan, Qian You-Wen, Yu Hua, Cao Zhen-Yu, Cong Wen-Ming, He Miao-Xia, Dong Hui
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Yangpu, Shanghai, China; Department of Pathology, Changhai Hospital, Naval Medical University, Yangpu, Shanghai, China.
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Yangpu, Shanghai, China.
J Gastrointest Surg. 2025 Sep;29(9):102155. doi: 10.1016/j.gassur.2025.102155. Epub 2025 Jul 15.
The prognostic role of perineural invasion (PNI) in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains undefined. This multicenter study assessed the incidence, patterns, and clinical significance of PNI in cHCC-CCA.
This study included 307 patients with cHCC-CCA undergoing hepatectomy with curative intent. Three independent pathologists conducted histopathological assessments of the frequency (single/multiple), involved tumor components (HCC/CCA/intermediate cell carcinoma), and spatial distribution (intratumoral/intratumoral + peritumoral/peritumoral) of PNI. The impact of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis was further evaluated. Survival outcomes (recurrence-free survival [RFS], overall survival [OS], and early [≤2 years] and late [>2 years] RFS) were analyzed using Kaplan-Meier and Cox regression. Logistic regression identified the predictors of PNI.
Among 307 patients (median age, 52.7 years; 87.6% male), the prevalence of PNI was 16.0% (49 of 307). PNI-positive patients had significantly worse median RFS (0.21 vs 0.54 years; hazard ratio [HR], 2.003; P <.001) and OS (1.18 vs 2.56 years; HR, 2.213; P <.001) than PNI-negative patients. Early RFS differed significantly (P <.001), but late RFS did not (P =.443). Subgroup analysis showed that the worst RFS and early RFS were noted in patients with HCC-component PNI (P =.025; P =.024) and purely intratumoral PNI (P =.025; P =.024). PA-TACE improved the early RFS only in PNI-negative patients (P =.031). Elevated alkaline phosphatase (odds ratio [OR], 1.005; P =.029), macrovascular invasion (OR, 2.873; P =.003), microvascular invasion (OR, 2.291; P =.033), and absent tumor capsule (OR, 2.539; P =.014) independently predicted PNI. Multivariable analysis confirmed PNI as an independent risk factor for RFS (HR, 1.700; P =.002), OS (HR, 1.760; P =.001), and early RFS (HR, 1.749; P =.001).
PNI is a noteworthy pathological feature in cHCC-CCA, independently associated with early recurrence, inferior survival, and increased therapeutic challenge. Standardized pathological reporting of PNI status may improve prognostic stratification for patients with cHCC-CCA.
神经周围侵犯（PNI）在肝内胆管癌合并肝细胞癌（cHCC-CCA）中的预后作用尚不明确。这项多中心研究评估了cHCC-CCA中PNI的发生率、模式及临床意义。
本研究纳入307例接受根治性肝切除术的cHCC-CCA患者。三名独立病理学家对PNI的频率（单发/多发）、受累肿瘤成分（HCC/CCA/中间细胞癌）及空间分布（瘤内/瘤内+瘤周/瘤周）进行组织病理学评估。进一步评估术后辅助经动脉化疗栓塞（PA-TACE）对预后的影响。采用Kaplan-Meier法和Cox回归分析生存结局（无复发生存期[RFS]、总生存期[OS]以及早期[≤2年]和晚期[>2年]RFS）。Logistic回归分析确定PNI的预测因素。
在307例患者中（中位年龄52.7岁；87.6%为男性），PNI的发生率为16.0%（307例中的49例）。PNI阳性患者的中位RFS（0.21年对0.54年；风险比[HR]，2.003；P<.001）和OS（1.18年对2.56年；HR，2.213；P<.001）显著差于PNI阴性患者。早期RFS差异显著（P<.001），但晚期RFS无差异（P=.443）。亚组分析显示，HCC成分PNI患者（P=.025；P=.024）和单纯瘤内PNI患者（P=.025；P=.024）的RFS和早期RFS最差。PA-TACE仅改善了PNI阴性患者的早期RFS（P=.031）。碱性磷酸酶升高（比值比[OR]，1.005；P=.029）、大血管侵犯（OR，2.873；P=.003）、微血管侵犯（OR，2.291；P=.033）及无肿瘤包膜（OR，2.539；P=.014）独立预测PNI。多变量分析证实PNI是RFS（HR，1.700；P=.002）、OS（HR，1.760；P=.001）和早期RFS（HR，1.749；P=.001）的独立危险因素。
PNI是cHCC-CCA中一个值得关注的病理特征，与早期复发、较差的生存率及增加的治疗挑战独立相关。PNI状态的标准化病理报告可能改善cHCC-CCA患者的预后分层。
