• Xu-Feng Zhang, Feng Xue, Ding-Hui Dong, Matthew Weiss, Irinel Popescu, Hugo P Marques, Luca Aldrighetti, Shishir K Maithel, Carlo Pulitano, Todd W Bauer, Feng Shen, George A Poultsides, Oliver Soubrane, Guillaume Martel, KoerkampBas GrootBGDepartment of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands., Endo Itaru, Yi Lv, and Timothy M Pawlik.
• Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
• Ann. Surg. 2021 Dec 1; 274 (6): e1187-e1195.

ObjectivesTo determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC).BackgroundImpact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined.MethodsData on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival.ResultsAmong 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003).ConclusionStandard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC.Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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