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Page 6 of 14 Afyouni et al. Hepatoma Res 2023;9:28 https://dx.doi.org/10.20517/2394-5079.2023.29

[48]
diffusion restriction in ICC was a standalone predictive parameter for the outcome . The ADC value of the
[49]
ICC has been demonstrated by Zhou et al. to be significantly linked with microvascular invasion (MVI) .
Ma et al. suggested some quantitative and qualitative MRI features from preoperative DCE-MR images to
[46]
evaluate MVI before surgery . Their finding showed that MVI of ICC is correlated with six MR
characteristics, including two quantitative parameters (arterial phase edge enhancement ratio and
maximum tumor diameter) and four qualitative features (tumor morphology, intrahepatic duct dilatation,
arterial phase enhancement pattern, and visible hepatic artery penetration sign).

Another critical predictor of outcome in ICC patients is LNM [50,51] . In light of the fact that neoadjuvant
therapy can increase the survival of ICC with LNM and LN dissection did not improve chances of
[52]
survival in ICC without LNMs, it is crucial to identify LNM by imaging before surgery .
[53]

However, there are still concerns about preoperative imaging to detect LNM accurately, particularly for
periductal infiltrating ICC subtypes [54,55] .

The size, shape, and necrosis are key imaging characteristics in the detection of LNM [56-58] , and
micrometastases are frequently missed in the imaging of normal-sized LNs [56,59,60] . Additionally, individuals
with primary sclerosing cholangitis (PSC), where slightly enlarged lymph nodes are a frequent sign, can
experience false-positive cases .
[61]

[62]
T1- and T2-weighted fat-suppressed images are very useful for the diagnosis of lymphadenopathy .
Zhou et al. reported that the ADC value of the primary ICC lesion, particularly when combined with the
[63]
diameter of the largest LN > 1 cm, can be helpful for the preoperative detection of LNM .
In this regard, also, Ji et al. proposed a nomogram to predict LNM using preoperative CA19-9 and eight LN
CT-based quantitative features . Another study by Meng and associates suggested a nomogram that used
[64]
preoperative CA19-9 levels, the location of the original tumor, the size of the LNs on CT, and the growth
trend of the tumor to forecast LNM in ICC .
[65]

While CT and MRI have poor sensitivity and specificity in detecting metastases in ICC, the ability of PET to
measure metabolic activity makes it superior. In particular, PET can resolve spatial and temporal
information when combined with CT. In a recent meta-analysis, PET/CT was reported to detect ICCs with
[66]
95% sensitivity and 93% specificity . This technique may also improve nodal staging and identification of
[67]
distant metastasis, altering the clinical treatment of 17%-30% of patients .
PET/CT may also aid in stratifying patients relative to prognosis. Specifically, SUVmax has been associated
with overall survival and recurrence. Ma et al. reported that SUVmax values above 8 were associated with
decreased survival. In contrast, tumors with low SUVmax had a more favorable prognosis, were more likely
not to be associated with metastatic disease, and had a more favorable prognosis following surgical
resection .
[68]

PET/MRI is another imaging modality increasingly used for cancer detection and staging. Kirchner et al.
reported that PET/MRI with the liver-specific contrast agent gadobenate dimeglumine assisted in ICC
detection and diagnosis. PET/MRI classified tumors as malignant or benign with 98% and 100%
accuracy . Nonetheless, ICC-specific PET/MRI investigations are needed to determine its role in diagnosis
[69]
and staging.