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Ohtsuka et al. Hepatoma Res 2024;10:18 https://dx.doi.org/10.20517/2394-5079.2024.04 Page 3 of 6

lesser omentum [Supplementary Table 1]. Characteristically, 7 of the 11 patients with LNM associated with
the lesser omentum had a replaced or an accessory LHA (aberrant LHA) arising from the left gastric artery
[9]
(LGA). The aberrant LHA typically runs to the right through the cranial part of the lesser omentum , the
anterior surface of the Spiegel lobe, reaching close to the Arantius’ ligament (ligamentum venosum) and
finally entering the liver at the left-back of the umbilical portion of the left portal vein [10,11] [Figure 1]. In such
cases, metastatic LNs were present along the aberrant LHA [Figure 2], and histological examination
evidenced the presence of LVs and LNs around the aberrant LHA [Figure 3]. On the other hand, aberrant
LHA was found in 8 patients with LNM. Of these, five patients had LNM in the hepatoduodenal ligament,
but four of these five patients also had LNM associated with the lesser omentum. In other words, only one
patient with aberrant LHA had LNM only in the hepatoduodenal ligament. In contrast, of 15 patients with
LNM and no aberrant LHA, only 4 had LNM associated with the lesser omentum, which was significantly
less frequent than in patients with aberrant LHA (P < 0.01 by Fischer’s probability test), and the remaining
11 patients had LNM only in areas other than the lesser omentum.

PATHWAY OF LYMPHATIC SPREAD FROM LEFT-SIDED ICC
In principle, the LVs and LNs should be accompanied by blood vessels. The aberrant LHA is a remnant of
the left embryonic artery (LEHA) that originated from the LGA in early human fetal life, which regresses
and eventually disappears under normal conditions. Normally, the LVs, LNs, and nerves are present along
the embryonic artery . Although the exact fate of the LVs and LNs along LEHA after the disappearance of
[12]
[12]
this artery has not been determined, these may remain even after the embryonic artery has disappeared .
In other words, the pathway to the left gastric nodes through the lesser omentum would also follow the
principle that LVs travel along the blood vessels. Indeed, it is often experienced that there are some LNs
close to the liver along the aberrant LHA [Figure 4] that are different from the hilar LNs.

Thus, most of the lymphatic spread from the ICC of the left-sided liver is thought to be through the portal
lymphatic pathway in the liver and followed by pathways along the blood vessels according to the principle:
the left and proper hepatic arteries, which are remnants of the middle embryonic artery at the
[5,6]
hepatoduodenal ligament , and LEHA that is left as the aberrant LHA or even disappears during
development. In the former pathway, LNs along the proper hepatic artery act as the first LN station. Then,
these LNs connect with those along the CHA and reach the LNs around the CEA. In the latter pathway, LNs
along the aberrant LHA or along the assumed LEHA run serve as the first LN station [Figure 4]. These LNs
directly connect with those along the LGA and reach the LNs around the CEA, and do not reach the
perigastric lymph nodes along the lesser curvature because of the opposite direction of lymph flow
[Figure 1].

ROLE OF LND ALONG THE LEFT EMBRYONIC HEPATIC ARTERY
In ICC, LND itself has not been widely adopted [13,14] because of the reported dismal prognosis of ICC
patients with LNM and the lack of effective adjuvant therapy for such patients. However, recent reports of
the usefulness of adjuvant therapy with capecitabine or S-1 for biliary tract cancers have increased the
[16]
[15]
importance of LND for accurate staging. In fact, several reports [13,17-19] have shown the necessity of LND for
accurate nodal staging of ICC, since accurate staging is not always possible preoperatively, even by using
MDCT, MRI, and PET scans. The current AJCC/UICC staging manuals recommend routine regional
[1,2]
LND as part of the surgical treatment of ICC patients for complete pathologic staging. Although, in these
reports, the number of retrieved lymph nodes for accurate staging is emphasized, it is not clear which
regional lymph nodes should be dissected. Zhang et al. argue that adequate LND with the inclusion of the
defined lymph nodes beyond lymph nodes in the hepatoduodenal ligament is important for optimal nodal
[13]
staging . Meanwhile, Kim et al. noted that only LND in the hepatoduodenal ligament and along the