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2019; 48: e245–e250

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INTERVENTIONAL ONCOLOGY
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Quarterly Medical Review

Percutaneous image-guided therapies of

primary liver tumors: Techniques and
outcomes

Mohamed Ben Ammar, Maud Nouri-Neuville, François H. Cornelis

Available online: 22 August 2019 AP–HP, Sorbonne université, hôpital Tenon, department of radiology, interventional
radiology/interventional oncology, 4, rue de la Chine, 75020 Paris, France

Correspondence:
François H. Cornelis, AP–HP, Sorbonne université, hôpital Tenon, department of
radiology, interventional radiology/interventional oncology, 4, rue de la Chine,
75020 Paris, France.
[email protected]

Summary
In this issue
Editorial: Interventional
Embolization and percutaneous ablations became well-established therapeutic options for hepa-
Oncology: the new pillar of tocellular carcinomas (HCC). All are performed under minimally invasive conditions using imaging
oncology. guidance. Selection of a technique over another follows guidelines but also patient's status and
Cornelis F.H., Lotz J.P.
(France)
availability of the techniques. The aim of this review is to present these techniques performed in
routine to treat HCC and to report the outcomes.
Percutaneous image-guided
ablation: from techniques
to treatments.
Ridouani F. et al. (USA)
Percutaneous image-guided Introduction
renal ablations: current
evidences for long term
Treatments of primary and secondary liver tumors have progressively gain acceptance worldwide.
oncologic efficacy. Image-guided procedures such as embolization and percutaneous ablations became well-estab-
Nouri-Neuville M. et al. lished therapeutic options. They allow to treat liver tumors under minimally invasive conditions
(France)
[1,2]. It may result in more rapid recovery, fewer complications, shorter hospital stays and reduced
Percutaneous Image-guided medical costs [3,4]. Selection of a technique over another follows guidelines, such as the Barcelona
therapies of primary liver
tumors: techniques and Clinic Liver Classification (BCLC) for hepatocelular carcinoma (HCC) [5] but also patient's status and
outcomes. local availability of the techniques. The aim of this review is to present the techniques performed
Ben Ammar M. et al. routinely in Interventional Radiology Departments.
(France)
Interventional oncologic
Transarterial chemoembolization
procedures for pain The rationale for transarterial hepatic chemoembolization (TACE) is the preferential blood supply of
palliation. HCC derived from the hepatic artery [6]. TACE is recognized as the primary treatment for BCLC stage
Filippiadis D.F. et al. (Greece,
B, asymptomatic, non-invasive and multinodular HCC and as an option to treat cholangiocarcinoma
France)
and metastases of colorectal cancer, neuroendocrine tumors, breast cancer or melanoma [1]. In
general, patients with unresectable disease involving less than 50% of the liver with well-
compensated cirrhosis (Child-Pugh score A or B) may be candidates [6]. The schedule of the
procedures is adaptated according to the individual response to treatment.
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© 2019 Elsevier Masson SAS. All rights reserved.
 M. Ben Ammar, M. Nouri-Neuville, F.H. Cornelis

The aim of this technique is to concomitantly perform both local The largest retrospective study of embolization included 322 HCC
embolization and chemotherapy. However, it requires that affer- patients and showed an overall survival of 21 months [10]. In a
ent arteries must be adequately selected to avoid damaging the study involving 112 patients [11], 1- and 2-year survival proba-
surrounding healthy parenchyma (figure 1). A precise planning bilities were 75% and 50% for with embolization using gelatin
using cone beam computed tomography and navigation soft- sponge particles, a resorbable embolic agent, and 82% and 63%
wares improves the outcomes [7]. The selective catheterization for conventional TACE (using doxorubicin as cytotoxic agent) and
of the hepatic artery is performed mainly via the femoral artery 63% and 27% for control (symptomatic treatment), respectively
followed by selective embolization of the hepatic artery (P = 0.009 for TACE vs. control). A meta-analysis assessing over-
branches feeding the tumor [8]. A solution, emulsion or sus- all survival for primary treatment of HCC (503 patients) [12]
pension of chemotherapy is injected intra-arterially. It is mixed showed a significant 2-year survival benefit associated with
with a water-soluble contrast medium and an embolic agent in TACE compared with conservative management (odds ratio
order to monitore the injection, to retain the drug in the tumor 0.53 [0.32–0.89], P = 0.017). Several studies compared conven-
and to exert embolic effects. The chemotherapy used in this tional TACE with DEB-TACE [1]. None of those found difference in
setting is doxorubicin mainly, cisplatin, epirubicin, mitoxan- complete response, overall response, or disease control rates
trone, or mitomycin C. Embolic agents can be spherical or between study arms but reported fewer side-effects in patients
non-spherical, calibrated or non-calibrated, resorbable or non- treated with DEB-TACE. Similarly, in a prospective randomized
resorbable. All of them induce or enhance tumour ischaemic trial including 101 patients with inoperable HCC [9], the authors
necrosis [9]. Conventional TACE use a solution for lipophilic drugs compared DEB-TACE and TAE with unloaded beads and found no
or an emulsion of the drug and ethiodized oil (Lipiodol, Guerbet, difference in time to progression, progression-free survival, or
France) [6]. The resulting emulsification procedure is operator- overall survival between groups. The median survival time was
dependent. Depending on the tumour size, vascularity, and 20.8 months in the DEB-TACE arm and 19.6 months in the TAE
fluoroscopic findings, a total volume of about 10–15 mL of arm, which was not signifiacant.
Lipiodol is injected mixed with a similar volume of drug. Alter- These treatments are generally considered to be well tolerated.
natively, drug eluting beads (DEB)-TACE is performed by inject- Major complications occur in only 4–7% of procedures and the
ing through the catether spherical embolic beads (in the 40–900 30-day mortality rate is of approximately 1% [13]. The most
micrometers range) loaded with the chemotherapeutic agent serious complications of TACE are liver abscess or liver infarction
[8]. These beads were developed to overcome the difficulty in and cholecystitis (about 2% of patients). However, a postembo-
obtaining reproducible emulsions with Lipiodol and to standard- lization syndrome occurs in up to 90% of patients and consists of
ize the size of occlusion marterial. As now the size of these a combination of fever, nausea, vomiting and abdominal pain. It
beads may be less than 100 micrometers, the embolic effects may last up to three days and justify to carefully follow the
may also be increased requiring supraselective embolization of patients after TACE. Other serious complications may occur:
the afferent vessels to the tumor. The bond between the beads nontarget embolization (i.e. inadvertent reflux of cytotoxic
and chemo allows slow and sustained release of the drug. Less drugs and/or embolic material into unintended territories); liver
systemic chemotherapy exposure than in conventional TACE has failure; tumor rupture (< 1% of cases) or biloma; and vessel
been reported. However, none of the agents used thus far has injury. TACE is infrequently associated with bone marrow sup-
been demonstrated to be clinically superior to others. No ran- pression and alopecia. With varying frequency, each intraarterial
domized clinical trial have been specifically conducted to date. therapy is associated with arterial sclerosis, dissection and
occlusion, which can render new procedure more challenging.

Transarterial radioembolization
Yttrium-90 (Y90) radioembolization is an emerging technique
Glossary aiming to enrich the therapeutic arsenal for the treatment of
liver tumors [8,14,15]. The indications include patients present-
BCLC Barcelona Clinic Liver Classification
CT computed tomography ing with BCLC stage B or C with portal vein tumoral thrombosis
DEB drug eluting beads HCC or progression after TACE. Patients must have ECOG status 0-
HCC hepatocelular carcinoma 2, and Child Pugh score A-B. In some studies, it has been also
MRI magnetic resonance imaging
MWA microwave ablation investigated for bridging patients to transplantation.
PET/CT positron emission tomography - computed tomography Y90 is a pure b-emitter which is incorporated into glass or resin
RFA radiofrequency ablation microspheres to be injected intraarterially [8]. Compared to
TACE transarterial hepatic chemoembolization
US ultrasound TACE, radioembolization requires a meticulous planning before
Y90 Yttrium-90 performing the treatment [14]. Therefore, a hepatic angiogra-
phy is combined with technetium-99m labelles macro-
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Percutaneous image-guided therapies of primary liver tumors: Techniques and
outcomes INTERVENTIONAL ONCOLOGY

Figure 1
Transarterial chemoembolization (TACE) of a 80 mm BCLC stage B hepatocellular carcinoma in a 60-year-old man
A. Axial contrast enhanced T1-weighted MR image showed the HCC (arrow).
B. A TACE was performed selecetively by injection microspheres loaded with doxorubicin.
C. A complete response was observed 1 month after TACE on an axial contrast enhanced T1-weighted MR image (arrowheads).
D. A portal vein embolization using gelfoam and coils (arrow) was decided to induce grow of the other side of the live.
E. The non-embolized side has grown on this axial contrast enhanced T1-weighted MR image.
F. A surgical resection of the right side was then performed 2 months after TACE.

aggregrated albumin scintigraphy 1–2 weeks prior to radioem- influencing the thermal conductivity), or the proximity to large
bolization to study the vascular supply of the tumor. The purpose vessels resulting in heat sink effect.
is to quantify liver-to-lung shunt and detect shunts to the RFA is recognized as one of the primary treatment of BCLC stage
gastrointestinal tract which are contraindication of radioembo- A (single tumor any size or up to 3 nodules < 3 cm with pre-
lization. If present, these shunts must be occluded. served liver function), and as an option to treat cholangiocarci-
However, recent studies have not already demonstrated any noma and metastases of colorectal cancer, neuroendocrine
benefits of radioembolization on overall survival compare to tumours, breast cancer or melanoma [1]. In general, patients
TACE, while it provides longer time to progression and better with unresectable disease involving less than 50% of the liver
safety profile [8,14,15]. with well-compensated cirrhosis (Child-Pugh score A or B) may
be candidates [6]. Therefore, a technique has to be select to
Percutaneous image-guided ablations adequately treat the tumor targeted while avoiding complica-
Percutaneous ablation of liver tumors can be achieved under tions based on the patients' and tumors' characteristics.
imaging guidance (US, CT-scan, MRI or PET/CT) using different Currently, RFA, MWA and in a lesser extent cryoablation are the
ablative techniques [3]. Chemical injection of alcool; heating by most frequently used techniques to treat liver tumor percuta-
radiofrequency ablation (RFA) or microwave ablation (MWA); neously in this setting. All these techniques present specific
cooling using cryoablation; and disrupting cell membranes by advantages and limits [16,20]. The resulting ablation zone
irreversible electroporation or electrochemotherapy are all differs substantially among the techniques in particular in the
effective tumoricid procedures [16–19] (figure 2). The resulting margins of ablation [21]. During RFA or MWA, temperature rises
volume of ablation depends of the technology, needle shape up to 100 8C, causing cell death by protein denaturation and cell
and the amount of energy locally delivered. Other factors may membrane dysfunction. Cryoablation use the Joule-Thompson
affect strongly the volume and/or the effectiveness of the effect to decrease temperature to less than -40 8C and cell death
ablation, such as the properties of the local tumor environment occurs mainly by crystal formation and osmotic shock. With all
(water content, cirrhotic versus non-cirrhotic parenchyma, all these techniques, an ablative margin of at least 5 mm is
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 M. Ben Ammar, M. Nouri-Neuville, F.H. Cornelis

Figure 2
Ultrasound guided liver microwave ablation (MWA) of a 20 mm BCLC stage A hepatocellular carcinoma in a 56-year-old man
A. Axial contrast enhanced T1-weighted MR image showed the tumor (arrowheads).
B. On ultrasound, the tumor was identified (arrowheads).
C. A microwave antenna was inserted in the tumor (arrowhead) and a subcapsular hydrodissection (arrow) was performed to displace the gallbladder in order to avoid any
complication.
D. Gas formation within the tumor and slight shrinkage of the tumor were observed during treatment (arrow).
E. Axial T1-weighted MR follow-up 3 months after MWA showed charred tissue (arrow) in the ablation zone.
F. No enhancement was observed after contrast injection on the axial contrast enhanced T1-weighted MR image.

recommended, as it has been associated with the best local group. A meta-analysis showed no difference between resec-
tumor control [22]. tion and percutaneous ablation with respect to overall survival
While a single applicator may be used to achieve this objective, up to 4 years for HCC up to 3 cm [26]. Although RFA was firstly
well-positioned overlapping ablations or multiple electrodes or introduced 20 years ago and appeared effective in long-term
probes activated simultaneously are used to increase the abla- evaluations [27], the advantage of MWA over RFA is to provide
tion volume and ensure the efficiency of ablation. Larger tumors higher energy within the tumor and be less sensitive to heat
(> 3 cm) and those with complex geometry or close contact with sink effect [28]. A recent single-center study of 75 patients
surrounding organs or sensitive tissue are more difficult to treat treated with MWA showed primary technique effectiveness of
and justify the development of the combined strategies dis- 93.7% in tumors 4 cm or smaller, and 75% in tumors greater
cussed later [23]. than 4 cm [29].
The mortality rate is low up to 0.3% [23] whereas the rate of
major complications is 2.2%. These complications justify further Combined therapies
improving image-guidance or using protective techniques such Recent studies have demonstrated that patients with large,
as hydro or carbodissection [3]. During the last decade, three unresectable HCC experienced significantly longer survival with
prospective randomized trials compared RFA and resection of combination therapy using both ablation and embolization
solitary HCC. Chen et al. [24] reported on 180 patients with when compared with patients who had undergone ablation
solitary < 5-cm HCC overall survival rates at 1, 2, 3, and 4 years of alone [28]. Performing ablation with embolization optimizes
96%, 82%, 71%, and 68% for ablation compared with 93%, outcomes by combining two different tumoricid method ensur-
82%, 73%, and 64% for resection. In another randomized trial ing adequate tumor destruction. Arterial embolization and sub-
on 230 patients [25] reported overall 1-, 2-, 3-, 4-, and 5-year sequent tumor constrast uptake may increase the efficiency of
survival rates for the ablation group of 87%, 76%, 70%, 66%, ablation by reducing heat sink but also by increasing the sensi-
and 55%, and 98%, 96%, 92%, 83%, and 76% for the surgical tivity of tumor cells to elevated temperatures, enhancing
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Percutaneous image-guided therapies of primary liver tumors: Techniques and
outcomes INTERVENTIONAL ONCOLOGY

potentially the efficacy of the ablation [23]. It also may help to embolic agents such as glue, microspheres, coils or plugs. This
improve tumor visualization by the retention of embolic mate- blockade of the portal blood supply induces the other side of the
rial. Improved overall survival was observed in patients present- liver to regrow and after several weeks, the non-embolized side
ing with 3- to 5-cm tumors. In a study including 139 patients has often grown enough so that surgery is a viable option. In
with recurrent HCC after resection [30], the 1-, 3-, and 5-year case of bilateral tumors, the future remnant liver may also be
overall survival rates were 94%, 69%, and 46% for the combi- preconditioned by resecting or ablating the tumors on this side.
nation therapy group (RFA +TACE) and 82%, 47%, and 36% for
the RFA alone group. In another study on 189 HCCs [31], overall Conclusion
survival and progression free survival rates to be signicantly Interventional Oncologic procedures performed in a daily prac-
better in the embolization-ablation group than in the group who tice such as embolization and percutaneous ablations allow to
underwent RFA alone. treat efficiently primary liver tumors under minimally invasive
Interventional radiologic procedures may be also used in com- conditions. It may result in more rapid recovery, fewer compli-
bination with surgery to enlarge the curative options [8]. To be cations, shorter hospital stays and reduced medical costs. Select-
considered as a suitable surgical candidate, a patient presenting ing the appropriate therapeutic option for the individual patient
with HCC must have enough functional liver remaining after the is mandatory justifying further clinical evaluations.
operation. Portal vein embolization is a procedure that induces
regrowth on one side of the liver before a planned hepatic Disclosure of interest: the authors declare that they have no competing
resection on the other side (figure 1). After selective catherer- interest.
ism of the portal vein, embolization is performed using various

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