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Page 8 of 15 Della Corte et al. Hepatoma Res 2022;8:5 https://dx.doi.org/10.20517/2394-5079.2021.103

Alternative ablative strategies are cryoablation and irreversible electroporation, both of which may be an
option in central liver tumors and tumors adjacent to sensitive structures (e.g., gallbladder, major bile ducts,
and bowel loops) due to their safer profile. However, data regarding their efficacy on ICC are extremely
[60]
scarce .

Factors affecting local tumor progression after ablation of ICC are size and superficial location . Higher
[59]
[61]
rates of local tumor progression in these settings are the result of under treatment due to technical
limitations (larger lesions) and possible damages to neighboring structures (in subcapsular lesions). Factors
[62]
affecting survival after ablation are albumin-bilirubin grade , tumor size, and presence of more than one
tumor .
[59]
One very frequently encountered complication after ablation of ICC is the development of a biliary abscess,
[63]
with an incidence rate ranging between 7% and 20% . Risk factors for the occurrence of this complication
are cholangiectasis (since thermal injury to the bile duct leads to contamination of ablation zone by enteric
bacteria) and presence of bilioenteric anastomosis (due to retrograde enteric bacterial contamination of the
biliary tract). For these reasons, pre-procedural care of these patients includes prophylactic antibiotic
therapy and palliation of biliary dilation whenever possible.

Transarterial chemoembolization
Conventional transarterial chemoembolization (cTACE) is the emulsion of chemotherapeutics and an oil-
based contrast agent (lipiodol) followed by an embolizing agent into the tumor-feeding artery .
[64]
Doxorubicin, cisplatin, mitomycin-C, and gemcitabine are the most commonly used drug
combinations [65,66] . In order to be eligible for TACE, good hepatic function (Child-Pugh Class A or B) and
performance status ECOG 0-2) are required. As for ablation, in patients with biliary dilation or bilioenteric
anastomosis, the increased risk of procedure-related development of biliary abscess justifies a pre-
procedural prophylactic antibiotic regimen . The ideal candidate for TACE is a patient with non-
[67]
resectable, multifocal disease not tolerating systemic chemotherapy. Another typical indication during
MDTs may be the presence of particularly hypervascular disease localization, wherein a good response to
intraarterial therapy may be expected.

Survival of ICC after cTACE has been shown to range from 12 to 25.2 months from diagnosis, and from 9.1
[68]
to 16.3 months from the procedure . The extreme variability in the results is a reflection of the variability
in patient-related variables, including tumor burden and previous therapies, as well as technical variables
including type of chemotherapeutic drug and number of treatment sessions. cTACE has a safe profile with
few adverse events. Post-embolization syndrome (i.e., transient nausea, abdominal pain, fever, and self-
limited increase in liver enzymes) is the most common side-effect.
[69]

Drug-eluting beads transarterial chemoembolization (DEB-TACE) is a relatively novel advance of TACE,
where local release of chemotherapeutic agents is mediated by pre-loaded beads obtaining both a
[70]
therapeutic and embolizing effect, with lower systemic drug exposure compared cTACE . Also in DEB-
TACE, efficacy of the procedure is extremely variable, with survival ranging from 8.6 to 30 months with
[68]
the same limitations described for cTACE.

[71]
DEB-TACE has been described with both doxorubicin and irinotecan; a study by Venturini et al. on 10
patients comparing DEB-TACE with doxorubicin and DEB-TACE with irinotecan showed no significant
differences between the two groups in terms of safety and efficacy.