Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node negative intrahepatic cholangiocarcinoma

Published:October 31, 2022DOI:


      • Nodal metastases drive the prognosis of intrahepatic cholangiocarcinoma
      • Lymphadenectomy is essential for staging of surgical intrahepatic cholangiocarcinoma
      • In clinically node-negative patients, lymphadenectomy provides a survival benefit
      • The benefit of lymphadenectomy is significant in early tumors and healthy livers


      Background & Aims

      Lymph nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (ICC), but the need to perform lymphadenectomy in clinically node-negative (cN0) patients is still under debate. Aim of this study is to determine whether adequate lymphadenectomy improves long-term outcomes in cN0 patients undergoing liver resection for ICC.


      Retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 ICC at five tertiary referral Centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weighting (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW-weighted regression.


      The study includes 706 cN0 patients who underwent curative surgery for intrahepatic cholangiocarcinoma. Four-hundred seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR: 18-77), median overall survival was 39 months (IQR: 23-109) and median recurrence-free survival was 23 months (IQR: 8-74). After stratifying according to nodal status at final pathology, node-positive patients had longer overall survival (28 months vs 23, HR=1.82; 95%CI: 1.14-2.90; p=0.023) and disease free survival (13 months vs 9, HR=1.35; 95%CI: 1.14-1.59; p=0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less advanced tumors (solitary tumors, tumor size < 5 cm, Ca19.9 <200 U/mL).

      Conclusions and Relevance

      Adequate lymphadenectomy provided better survival outcomes for cN0 patients who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 intrahepatic cholangiocarcinoma.


      Lymphadenectomy (LND) is essential for the surgical staging of intrahepatic cholangiocarcinoma (ICC). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of LND on survival of clinically node-negative (cN0) patients is still under debate.
      In this large retrospective study on cN0 patients who underwent surgical resection for ICC, we show that performing an adequate LND by retrieving 6 or more lymph nodes significantly improves survival and lowers the risk of tumor recurrence.
      Lymphadenectomy during surgical resection of ICC is actually underperformed by the surgical community, resulting in inadequate staging and possibly in worse long-term outcomes. The results of this study empower surgeons and clinicians in claiming an adequate lymphadenectomy even in cN0 patients.
      Since patients with no chronic liver disease and with less advanced tumors are those who receive a significant benefit from LND, our results might guide decision making in patients at high-risk for postoperative complications.

      Graphical abstract



      Intrahepatic cholangiocarcinoma (iCC), lymph node (LN), clinically node-positive (cN+), clinically node-negative (cN0), 18F-FDG positron emission tomography (PET), “adequate” lymphadenectomy (AD-LND), “non-adequate” lymphadenectomy (NAD-LND), recurrence-free survival (RFS), overall survival (OS), interquartile range (IQR), inverse probability of treatment weights (IPTW)
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