Radiofrequency ablation for liver tumors: going multipolar?

Keywords::

• colorectal cancer
• liver neoplasm
• multipolar
• radiofrequency ablation

Surgical resection is the treatment option offering the best chance of a cure for patients with primary or secondary liver tumors. Improved imaging and surgical techniques, as well as effective neoadjuvant chemotherapy, have increased the number of patients receiving a radical resection for liver tumors. However, the majority of patients have irresectable disease upon presentation. Radiofrequency ablation (RFA) forms an attractive treatment option for patients with primary or secondary liver tumors. RFA, using heat to destroy tumor tissue, entered standard medical care in Western countries in the early 1990s. Interestingly, descriptions of local heat to destroy tumor tissue were already found in documentation from Egypt and early Greek civilization [1]. RFA uses a generator that delivers radiofrequency (RF) energy, sending a high-frequency alternating current from the tip of the RFA needle applicator into the liver. The ions of the tissue surrounding the needle applicator attempt to follow the direction of the current, resulting in frictional heat. A temperature of 45–50°C induces intracellular protein denaturation and dissolving of the lipid bilayers of the cell membranes. Commercially available RFA systems are designed to destroy tumor tissue through temperatures above 60°C. Since the RF energy decreases exponentially with increasing distance from the needle applicator, size and temperature reached are therefore dependent on electrical and thermal conductivity of the liver tissue. With most commercially available RFA devices, it is technically not feasible to achieve an RFA lesion above 4–5 cm in a single application. In most RFA systems, a closed electric circuit is formed by one single-needle applicator, from which a high-frequency alternating current moves through the tissue, the patient and grounding pads on the patient’s leg or arm. An alternative method is multipolar RFA, in which the alternating current moves from one needle applicator to another without the need for grounding pads. This way, the RF energy is exclusively applied to the target tissue [2].

Radiofrequency ablation is a safe technique, able to improve the disease-free and overall survival of patients with primary and metastatic liver metastases. Published 5-year survival rates after local ablation are 18–30% for tumors smaller than 4 cm [3]. Nevertheless, as with most techniques, there are some major disadvantages concerned with RFA. One of the major limitations is the fact that only a restricted size can be reached within one application. As temperature decreases with increasing distance from the needle applicator, the area of coagulative necrosis using a monopolar single-needle applicator is very small. Umbrella-shaped needle applicators with multiple tines have been developed to enlarge the ablative zone. Because the margin around a tumor should be 5–10 mm on all sides, only tumors up to 4–5 cm can be successfully ablated in one application. Having to use multiple applications for larger tumors makes RFA even more time-consuming than it already is. Local tumor progression (LTP), due to the outgrowth of residual tumor cells after RFA, is another major downside with occurrences varying from 2 to 60% in the literature [4]. It is not surprising that large tumor size is a very strong determinant of LTP. Another factor influencing LTP is the presence of large hepatic vessels. A great deal of conductive heat is lost owing to the presence of liver vasculature, the blood flow of which cools the heated tumor. This phenomenon is called the ‘heat sink effect’. The conductive heat loss is also dependent on the perfusion of the tumor, the amount of necrosis already present and whether or not the liver parenchyma is cirrhotic. All these factors make it difficult to predict the ablative size and shape of the generated lesion. Another disadvantage is the chance of severe (second- and third-degree) skin burns at the grounding pads. The incidence of severe skin burns increases up to 3.2% with the increasing power of the RF generators in order to attempt to ablate a larger volume. Furthermore, the chances of needle track seeding, where tumor cells attached to the needle applicator can be disseminated through the liver, especially with multitined umbrella shaped applicators, may result in new tumor formation somewhere along the applicator track [5].

A multipolar RFA system performs much better with regard to these disadvantages than monopolar systems, therefore we advocate the use of this system. The inability to create large ablative zones with the monopolar systems can be overcome by multiple overlapping ablations. Unfortunately, this technique is known to be associated with a higher risk of local recurrence due to seeding. The multipolar device allows multiple needle applicator placements at the same time (up to six), thereby limiting tumor spread and inaccurate ablation. Owing to the simultaneous application, an area is created inbetween the probes where heat is trapped and very little heat loss occurs. Therefore, more uniform energy distribution and larger ablation zones are achieved. In this way, the RFA procedure for large tumors takes approximately half the amount of time. Moreover, with the multipolar system, the needle applicators can be placed surrounding the tumor, further minimizing the chance of seeding. With the multipolar systems, the tissue is constantly monitored and the power is automatically adjusted to the resistance of the tissue in order to prevent early tissue dehydration and thereby loss of heat convection. When the procedure is not constantly monitored, there is a chance of heating the tissue too rapidly, thereby vaporizing or charring the tissue and, as a consequence, limiting ablation size. Another advantage of multipolar RFA systems is the fact that these systems do not use skin pads to close the electrical circuit, diminishing the risk of skin pad burns to zero. The conductive heat loss caused by the presence of large hepatic vessels (the so-called ‘heat sink effect’) prevents sufficient heat build-up in the tumor abutting vessels, leading to significantly more local tumor progression. A possibility for creating large ablation zones and limiting LTP is by applying vascular occlusion, which does reduce the heat sink effect. Prolonged stasis of blood flow leads to an increased chance of delayed venous thrombosis and the chance of damaging large vessels compromising perfusion of the liver. Therefore, vascular occlusion should not be used continuously for long intervals. In monopolar RFA systems, heat is produced by only one heat source, which is more prone to a scattered spread. Heat transfer relies on conduction, which is affected by the perfusion of the tumor, amount of tumor necrosis and the conditions and perfusion of surrounding liver parenchyma. The multipolar needle applicators are less susceptible to the ‘heat sink effect’ because the electrical current is moving from one needle applicator to the other, trapping heat between them. The fact that heat is generated between two needle applicators makes the lesion shape and size more predictable.

Series of RFA treatment of patients with large liver tumors with long-term results are lacking in the literature. A randomized trial to examine whether multipolar RFA devices do in fact perform better than monopolar ones will provide the highest level of scientific evidence. However, knowing the advantages stated above in increasing size and predictability of generated lesions with multipolar RFA, it seems logical to bypass that step and let the future focus be on further exploration of technical possibilities of the multipolar system.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.