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Gavriilidis et al. Hepatoma Res 2023;9:23 https://dx.doi.org/10.20517/2394-5079.2023.26 Page 3 of 8

Figure 1. Kaplan-Meier analysis of overall survival (OS) relative to the number of lymph node metastasis. Proposed nodal status was as
follows: N0- 0 LNM; N1- 1-2 LNM; N2- 3 or more LNM. Adapted from Zhang et al. [14] .

The extent of lymphadenectomy for iCCA should be informed by an understanding of the patterns of liver
lymphatic drainage related to right versus left-sided iCCA. For example, tumors in the right hemi-liver
drain to the HDL (station 12), as well as the peripancreatic (station 13) and hepatic artery (station 8) and
celiac (stations 7/9) nodes. In contrast, tumors originating in the left hemi-liver primarily drain to nodes in
station 12, as well as to nodes also along the lesser curvature of the stomach (stations 1/3) [Figure 2]. As
[17]
such, “sidedness” is important to consider when performing LND for iCCA, as the liver is one of the largest
lymph-producing organs and lymphatic drainage plays a critical part in cancer dissemination .
[18]
Importantly, lymph node involvement beyond the primary nodal basins, such as disease within the celiac or
para-aortic lymph nodes, represents metastatic disease and curative-intent resection is generally
contraindicated as the risk of recurrence/systemic disease can be very high. In one study that evaluated the
effect of sidedness on the number and station of LNM, patients who underwent curative-intent surgery for
left hemi-liver iCCA had a greater number of lymph nodes resected and had a higher incidence of LNM
versus patients with iCCA in the right hemi-liver . However, there was no difference in the station and
[5]
number of LNM between right- versus left-sided tumors, nor in OS . In aggregate, a minimum of six
[5]
lymph nodes should be assessed and the extent and location of LND beyond the HDL should be dictated by
the location of the iCCA within the liver. By performing an adequate LND relative to number and location,
surgeons can better identify the extent of nodal disease and, therefore, better risk stratify patients relative to
prognosis, as well as gain information that may assist in decision making regarding adjuvant chemotherapy
and surveillance [2,11] .

Therapeutic index and lymphadenectomy
Notwithstanding the valuable staging and prognostic information that LND provides, the related
therapeutic benefit has been debated. Therapeutic index is a metric that can help define the survival benefit