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Page 6 of 12 Ruff et al. Hepatoma Res 2023;9:17 https://dx.doi.org/10.20517/2394-5079.2023.18

Figure 2. Lymph node drainage patterns for intrahepatic cholangiocarcinoma vary with tumor location. Left-sided cancers tend to drain
to lymph nodes along the lesser curvature of the stomach and then to the celiac nodal basin. Right-sided cancers preferentially drain to
portal/hilar lymph nodes and then to caval and peri-aortic lymph nodes [70] . This figure was reprinted with permission from reference
70.

[51]
patients who underwent curative-intent resection for ICCA . This study noted that 52.4% of patients had
at least one lymph node evaluated, 78.2% had 1-5 lymph nodes evaluated, and only 21.8% had at least six
lymph nodes evaluated. Over time, as the guidelines have changed, the number of patients who had at least
6 lymph nodes harvested increased. Still, these data suggest that patients are often under-staged. Of note,
while patients with higher T-category disease had an increased risk of lymph node metastases, the incidence
of lymph node metastases did not directly correlate with the T-category. In fact, the highest incidence of
lymph node metastases was noted among patients with T2a tumors. Therefore, T stage is not necessarily a
reliable predictor of nodal disease, a point that further emphasizes that lymphadenectomy should be
performed on all patients with ICCA to ensure adequate staging.

In a separate analysis of 603 patients from 15 high-volume institutions, Xu-Feng et al. investigated the
association between lymph node metastases and prognosis . Lymph node metastases were present in about
[52]
40% of patients who underwent surgical resection and an increasing number of lymph node metastases (0
vs. 1-2 vs. 3 or more) was associated with incrementally worse overall, disease-specific, and recurrence-free
survival. These data further emphasize the importance of an adequate lymphadenectomy for staging
purposes. In addition, this study highlighted the importance of lymph node metastasis location.
Specifically, among patients with at least six lymph nodes examined, individuals with lymph node
metastases beyond station 12 (hepatoduodenal ligament) had worse survival than patients with lymph node
metastases limited to station 12. The eighth edition of the American Joint Commission on Cancer staging
guidelines recommends sampling hepatoduodenal ligament, inferior phrenic, and gastrohepatic lymph
nodes for left-sided ICCA and hepatoduodenal ligament, peri-duodenal, and peri-pancreatic lymph nodes
for right-sided ICCA .
[52]

Clinical lymph node status should also be considered when deciding between upfront surgery versus
chemotherapy as the first line of treatment. Patients who have portal lymph node involvement may benefit
from receiving systemic chemotherapy with a re-staging scan prior to hepatectomy . This therapeutic
[30]
approach may provide a “test of time” to declare biology and help appropriately select patients who will
most likely benefit from a resection relative to an oncologic perspective. In particular, lymph node
involvement beyond the primary draining nodal basins (e.g., celiac or para-aortic lymph nodes) represents
metastatic disease, and these patients should be treated with systemic therapy and only offered surgery in