[Risk factors and prognostic value of lymph node metastasis in patients undergoing curative resection for...

Objective: To investigate risk factors for postoperative lymph node metastasis in patients with intrahepatic cholangiocarcinoma (ICC) after curative resection. Methods: This retrospective case-series study consecutively enrolled 230 patients who underwent initial curative hepatectomy and were pathologically confirmed as ICC at Peking University People's Hospital between January 2015 and September 2025. The cohort comprised 120 men (52.2%) and 110 women (47.8%), with an age (M(IQR)) of 59 (14) years (range:31 to 83 years). Multivariable logistic regression was performed to identify independent risk factors for lymph node metastasis. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method and Cox proportional hazards models. Subgroup analyses based on lymph node status (N0, N1, and Nx) were conducted to explore the impact of lymphadenectomy extent and postoperative adjuvant therapy on prognosis across subgroups. Restricted cubic spline (RCS) analysis was used to assess the association between lymph node ratio (LNR) and survival outcomes. Results: Among the 230 ICC patients, 144 underwent lymphadenectomy, with a lymph node metastasis rate of 38.9% (56/144). Multivariable logistic regression identified carcinoembryonic antigen >4.7 μg/L (OR=5.895, P=0.030), preoperative radiological lymphadenopathy (OR=11.822, P=0.006), and large duct type histological subtype (OR=18.224, P=0.001) as independent risk factors for lymph node metastasis. Survival analyses showed that lymph node metastasis was associated with shortened OS and RFS (both P<0.01). In subgroup analyses of lymphadenectomy, retrieval of ≥6 lymph nodes prolonged RFS in the N1 group (P=0.004) but did not improve OS; in the N0 group, retrieval of <6 lymph nodes was associated with better OS and RFS compared with ≥6 nodes (both P<0.05). RCS analysis demonstrated a significant linear association between LNR and RFS (P=0.006), whereas no association was observed between LNR and OS (P=0.451). Regarding adjuvant therapy, adjuvant treatment improved OS in the overall cohort (P=0.039) but did not prolong RFS (P>0.05). In the N1 group, adjuvant therapy improved OS (P=0.031); in the N0 group, it improved RFS (P=0.031); however, no survival benefit was observed in the Nx group (both P>0.05). Conclusions: Elevated carcinoembryonic antigen, preoperative lymphadenopathy, and large duct type histological subtype are independent risk factors for postoperative lymph node metastasis in ICC. Lymph node status significantly affects prognosis. Patients with lymph node-positive disease may benefit from retrieval of ≥6 lymph nodes and postoperative adjuvant therapy, whereas excessive lymphadenectomy should be avoided in lymph node-negative patients, in whom adjuvant therapy mainly contributes to delaying recurrence.