Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study

Abstract

Background: Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients.

Methods: We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort.

Results: Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS).

Conclusions: Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

Keywords: Intrahepatic cholangiocarcinoma; Liver resection; Lymph node dissection; Lymph node metastasis.

Figure 1

Flowchart of patients’ enrollment. ICC: intrahepatic cholangiocarcinoma.

Figure 2

Patients with different lymph node status of ICC. (a) A patient with clinically node-positive ICC received left hemi-hepatectomy and lymph node dissection. (b) A patient with clinically node-negative ICC underwent both liver resection and lymph node dissection based on suspicion of lymph node metastasis at multidisciplinary team discussion. Postoperative pathology confirmed no lymph node metastasis. (c) A patient with clinically node-negative ICC underwent liver resection only. Yellow arrows: tumor; red arrows: lymph node.

Figure 3

The lymph node dissection map of patients with suspected positive lymph nodes. Including: 1) Lymph nodes located around the hepatoduodenal ligament and the common hepatic artery (stations 12 and 8); 2) Retro-pancreatic lymph nodes (station 13, for right-sided tumors); and 3) Lymph nodes around the cardiac portion of the stomach and along the lesser curvature (station 7, for left-sided tumors).

Figure 4

Recurrence-free (a) and overall (b) survival of patients receiving lymph node dissection or not after propensity score matching (PSM). LND: lymph node dissection.

Figure 5

Recurrence-free (a) and overall (b) survival of patients with lymph node metastasis (LNM (+)) and no lymph node metastasis (LNM (-)). Recurrence-free (c) and overall (d) survival of patients with hepatectomy alone (non-LND) and LNM (-). LND: lymph node dissection.

Figure 6

(a-d) Recurrence-free survival of patients in total, with non-LND, LNM (-) and LNM (+) receiving postoperative adjuvant therapy or not after PSM. LND: lymph node dissection; LNM: lymph node metastasis; PSM: propensity score matching.

Figure 7

(a-d) Overall survival of patients in total, with non-LND, LNM (-) and LNM (+) receiving postoperative adjuvant therapy or not after PSM. LND: lymph node dissection; LNM: lymph node metastasis; PSM: propensity score matching.