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Bale et al. Hepatoma Res 2023;9:44 https://dx.doi.org/10.20517/2394-5079.2023.71 Page 3 of 13

[20]
clinical trials .

Locoregional treatment
[21]
Locoregional treatments (LRTs) include hepatic arterial infusion of chemotherapy (HAI) , transarterial
[25]
chemoembolization (TACE) , radioembolization (TARE) [23,24] , and radiation therapy (RT) .
[22]
Reported median OS and median PFS after HAI ranged from 10.1-31.1 months and 5-11.8 months,
[27]
respectively . One recent cohort study reported that HAI floxuridine chemotherapy achieved similar OS
[26]
in patients with multifocal iCCA compared with RX. In particular, 5-year OS among patients with 4 or
more lesions was 5.0% (95%CI: 1.7%-14.3%) in the HAIP group compared with 6.8% (95%CI: 1.8%-25.3%)
in the RX group. In turn, treatment of multifocal iCCA with RX should be considered with care as the risk
of complications with major liver resection can be high. Moreover, evidence for the treatment of iCCA with
LRT is scarce. The reported median OS for TACE, TARE, and RT ranged from 6-30 months, 5.7-33.6
months, and 7-39.5 months, respectively . However, despite a low level of evidence and a wide variability
[26]
in outcomes, these treatments are safe and feasible and can be reasonable alternatives or adjuncts to
systemic therapy for some patients with unresectable disease.

Thermal ablation is regarded as a potentially local curative treatment option. In this narrative review, we
summarized the most relevant articles related to conventional, US- or CT-guided, percutaneous thermal
ablation for iCCA that were published between 2000 and 2023. In addition, we highlight studies reporting
the application of sophisticated stereotactic planning and guidance techniques.

PERCUTANEOUS ABLATION
Techniques
Radiofrequency ablation (RFA) and microwave ablation (MWA) are minimally invasive procedures for the
local curative treatment of liver tumors. The objective is to obliterate the entire tumor, including a margin
of safety that is 0.5-1 cm [28-31] ; the needle tract should also be cauterized during probe removal to avoid
tumor seeding. The principle of RFA is based on high-frequency alternating electrical current that is emitted
[32]
by the tip of the RFA electrode, which causes frictional heat in the surrounding tissue . Cell death is
achieved at temperatures of 60-100 °C. Microwave ablation (MWA) is considered a valid alternative to RFA.
Direct heating in the tissue volume around the antenna is induced by an oscillating electromagnetic field.
Compared with RFA, MWA is less susceptible to the heat sink effect, and larger and more predictable
ablation zones can be achieved in a shorter time . Interventional radiologists typically perform RFA and
[33]
MWA percutaneously under computed tomography (CT) or ultrasound (US) guidance . Additionally,
[28]
[31]
thermal ablation can be performed during open or laparoscopic liver surgery .
[34]
Exclusion criteria and complications
In most studies, exclusion criteria for conventional single probe RFA and MWA include severe
coagulopathy, severe thrombocytopenia, vascular invasion, large tumor size (> 3 or > 5 cm), multiple
hepatic lesions (> 3-5), progressive extrahepatic metastases, or poor performance status [28,29,31,34,35] .

Both RFA and MWA are well tolerated. Post-ablation syndrome is common and characterized by fever and
flu-like symptoms. Major complications after thermal ablation of iCCA include bleeding, liver abscess,
biloma, biliary stricture, hepatic failure, pleural effusion, ascites, and tumor seeding. Minor complications
include elevated liver function tests, thrombocytopenia, portal vein thrombosis, asymptomatic pleural
effusions, or hematomas.