Ultrasound guided thermal ablation

Various methods of tissue ablation using thermal effects, thermoablation, have been used in routine clinical practice since the 1970s. Thermoablation is an alternative therapy for benign symptomatic thyroid nodules and symptomatic thyroid cysts. The rate of hypothyroidism after thermal ablation of a hyperfunctional thyroid nodule is less than 0.01%.

Various methods of tissue ablation by thermal effects, thermoablation, have been used in routine clinical practice since as early as the 1970s, and are currently considered established therapies in some cases in the treatment of liver, lung, spleen, bone, and prostate tumors. The principle of operation is the ablative destruction of tissue by heat. Thermal ablation of thyroid nodules does not compete with established procedures for the treatment of benign thyroid diseases such as drug therapy, radioiodine therapy or thyroidectomy, but should rather be seen as a useful complement to existing therapeutic modalities.

Basics of thermal ablation

The goal of thermoablation of thyroid nodules is irreversible coagulation necrosis of the thyroid nodule with subsequent volume reduction. During thermal ablation of thyroid nodules, a temperature of at least 60°C is aimed for in the ablation zone. At ablation temperatures of 60°C, the thermal effect occurs almost immediately and irreversible damage to the node subsequently occurs. Vessels with a diameter of less than 3 mm are destroyed by the heat (“thermal embolization” of the vessels). This is a desired effect, as it destroys the intrathyroidal vessels supplying the nodule. This effect does not occur with vessels larger than 4 mm in diameter. In these cases, there is a loss of energy, also called “heat sink”.

Radiofrequency ablation (RFA)

Radiofrequency ablation involves placing a probe percutaneously into the nodule. The probe is connected to a radio frequency alternating current generator. A current flows between two electrodes in the area of the active tip. The large local current density in a small area creates ionic friction energy (heat), which forms the ablation zone.

RFA of benign thyroid nodules

Metanalyses [1,2] have examined the effect of RFA on thyroid nodules. The meta-analyses showed a statistically significant improvement in outcome (volume, symptomatology, cosmesis, medication requirements). The average volume reduction after RFA was 8.9 ml [2] to 9.77 ml [1]. The outcome was dependent on nodal morphology [3]. In the monocentric randomized trials, the volume reduction of primary cystic thyroid nodules was 87% to 93% [4,5] and in the randomized case-control study of solid nodules at 6 months was 49.1% ± 19.5% compared with the control group [6]. In the randomized prospective study, the smaller a thyroid nodule, the greater the relative volume reduction [7]. In this regard, RFA was performed once or more, unilaterally or bilaterally, for benign cold or hyperfunctional thyroid nodules [3,8–14]. RFA is also possible after a lobectomy has been performed [15]. In the case of thyroid cysts with viscous colloid, RFA can be performed after aspiration of the viscous cyst contents. After thermal ablation of thyroid cysts, recurrences are very rare, thyroid cysts can be treated very well with thermal ablation [16]. Even after a preceding ethanol injection, further significant volume reduction is achieved by RFA [17,18]. Monopolar RFA of hyperfunctional thyroid nodules with decreased TSH requires multiple RFA treatments. After a single RFA of hyperfunctional nodules, 50% to 67% of patients were still hyperthyroid [13,21,22]. With bipolar RFA of hyperfunctional thyroid nodules, only 10% are still hyperfunctional after a single treatment. This is explained by the remaining rim of the hyperfunctional node to spare thermo-sensitive structures. Bipolar RFA is superior to monopolar RFA in the treatment of hyperfunctioning thyroid glands [11,19,20].

Because only the hyperfunctional portion of the nodule is destroyed, the rate of hypothyroidism is less than 1%, whereas the rate of hypothyroidism with lifelong levothyroxine use after radioiodine therapy is 10% in the first year.

In a thyroid nodule with Thy 2 classification in fine needle aspiration, there was volume depletion of 67% in the observation period of 24 months. Only in Thy3 classification, volume increase occurred in two of six thyroid nodules. In the two thyroid nodules, follicular carcinoma and microfollicular neoplasia were found histologically postoperatively [23]. In a long-term study over 4 years, volume increase after RFA was found in the marginal area of the nodule with a frequency of 5.6% [3]. The Italian expert committee recommends RFA for hyperfunctional thyroid nodules and for non-hyperfunctional thyroid nodules larger than 20 ml if patients refuse surgical therapy or radioiodine therapy [24]. The Italian Medical Radiological Society recommends RFA for all benign thyroid nodules [25]. There is a significant decrease in echogenicity and Doppler signal within the ablation zone after bipolar RFA with “multi-shot” technique [26,27]. The Korean Task Force (KSThR) recommends RFA with “moving-shot” technique for all benign thyroid nodules regardless of size if the thyroid nodule causes clinical symptoms [28]. Successful ablation of thyroid nodules is possible with both shot techniques and with monopolar and bipolar RFA probes [26,27,29].

Complications after RFA are rare [8,22,25,28,30]. In the retrospective analysis with four centers from Korea, the complication rate was 0.2% after 2616 treatments [31], and in the retrospective multicenter study with 13 thyroid centers, the overall complication rate was 3.3%, with permanent complications (hypothyroidism and thyroid nodal rupture) documented in only 2 patients. In long-term studies over four years, the complication rate was 3.6% [3]. Bipolar RFA also show low complication rates [26,27]. Compared to thyroidectomy for benign multifocal thyroid nodules, the complication risks of RFA are lower [32].

RFA of lymph node metastases or local recurrences of thyroid carcinoma.

In some cases, surgery or radioiodine therapy after thyroidectomy cannot be performed for known metastases of well-differentiated papillary thyroid carcinoma. After RFA of local recurrences or lymph node metastases, there was a significant volume reduction of metastases from 53% to 95% and a decrease in tumor maker thyroglobulin [33–37]. Posttherapeutic control by biopsy showed no evidence of residual malignant tissue and no evidence of recurrence of the treated side after RFA [38–40]. Also in the case series with well-differentiated papillary and follicular thyroid carcinoma recurrences, long-term follow-up after RFA showed no evidence of progression [41]. Also, in combination with radioiodine therapy, RFA was shown in a prospective study to successfully destroy thyroid remnants after thyroidectomy [42]. Therefore, the expert committees recommend palliative RFA for recurrences and metastases of well-differentiated thyroid carcinoma when surgical therapy or radioiodine therapy are not possible or are refused by the patient [24,25,28].

The complication rate of RFA of metastases and local recurrences was approximately 7%, and life-threatening complications were not observed [25,36]. In direct comparison with reoperation for local recurrence, lower complication rates were found with RFA for the same effectiveness [40].

Microwave ablation (MWA)

In MWA, a microwave probe is inserted percutaneously into the thyroid nodule. A microwave field is generated in the area of the active tip. Excitation of dipole compounds (tissue water, molecules) attenuates the electromagnetic wave. The attenuation of the electromagnetic wave is converted into heat (ablation energy).

MWA of benign thyroid nodules

Already with the first prospective study, a volume reduction of 46 ± 30% after 9 months was achieved in benign thyroid nodules using cooled MWA [43]. In the retrospective work with 222 patients and 477 nodes, the volume reduction was 41%. Volume reduction was dependent on nodal morphology. Cystic nodules were found to have an 80% volume reduction, echocomplex nodules were found to have a 72% volume reduction, and solid nodules were found to have a 27% volume reduction [44]. The uncooled MWA probes showed a significant volume reduction of over 50% after just 3 months [45,46]. In combination with radioiodine therapy, the radioiodine activity required for radioiodine therapy was significantly reduced in very large strumen, with a volume reduction of 30% [47,48]. Scintigraphy can be used for early verification of the effectiveness of thermal ablation before volumetric progress monitoring is possible [45–48]. Using MWA, benign cold or hyperfunctional thyroid nodules have been successfully treated [49]. Due to the thicker MWA probe, a small capsular hemorrhage of the thyroid gland smaller than 1 mm was found in 4 of 11 patients [43], with the uncooled MWA probes a superficial small hematoma was found in all patients [45]. Life-threatening or permanent complications did not occur in any study [43–45,50,51].

MWA of lymph node metastases or local recurrences of thyroid carcinoma.

In this prospective study of 17 patients with local recurrence of papillary thyroid carcinoma, one or up to four MWAs were performed. Volume reduction was 91 ± 14% after 18 months. In 30% of cases, no local recurrence was detected after treatment, and there were no life-threatening or permanent complications [52]. In another study, 21 stage T1N0M0 papillary microcarcinomas were treated by MWA. All microcarcinomas could be completely ablated using one MWA session. After 11 months of follow-up, no local recurrence was found [53]. No life-threatening or permanent complications occurred.

Highly focused ultrasound

In HIFU, thermal ablation is performed non-invasively. The ultrasound probe operates at 2 MHz and is curved inward (concave). This results in a focusing and targeted bundling of the ultrasound through the skin into the thyroid nodule. Ablation involves heating a volume the size of a grain of rice to about 85°C. The advantage of this non-invasive thermoablative procedure is that there is no risk of infection. The concavity of the ultrasonic head simultaneously determines the degree of focus and thus also the depth at which the thermal effect occurs.

HIFU of benign thyroid nodules

In the 2011 feasibility study, 25 patients were treated with HIFU for multinodular goiter for the first time. 16 patients showed significant changes on ultrasound and in 17 thyroid nodules changes such as necrosis were found in the subsequent histopathological evaluation [54]. Scintigraphy can be used for early verification of the effectiveness of thermal ablation before volumetric progress monitoring is possible [55,56]. HIFU has been used to successfully treat benign cold, indifferent or hyperfunctional thyroid nodules [55,56]. The volume reduction after 3 months was 49 to 55% after a single HIFU treatment. In a prospective study with 20 patients, the volume reduction was 49% [57].

Pretherapeutically, the median nodule volume was 5 ml; in addition, safety distances were defined by the system, thus marginal areas of the thyroid nodule were outside the ablation zone [56–59]. Life-threatening or permanent complications after HIFU did not occur, and immunogenic autoimmune thyroidopathy is also not induced by HIFU in the thyroid gland [54–59]. Knowledge of the various techniques (RFA, MWA, HIFU) with their advantages and disadvantages is elementary for individual therapy using thermal ablation. These can be learned at the DZTA – Deutsches Zentrum für Thermoablation e.V. (German Center for Thermoablation).

The costs for the therapy are covered by some health insurance companies from Switzerland. Requests from Switzerland can therefore be sent to the German Center for Thermaoblation e.V..

Take-Home-Messages

• Thermoablation is an alternative therapy for benign symptomatic thyroid nodules and symptomatic thyroid cysts.
• The rate of hypothyroidism after thermal ablation of a hyperfunctional thyroid nodule is less than 0.01%.
• A conclusive fine-needle biopsy is required before thermal ablation of a hypofunctional node.
• The different techniques RFA, MWA, LASER and HIFU can be used in the
  German Center for Thermoablation e.V.

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