Vascular and Interventional Radiology
Original Research
Optimum First-Line Treatment Technique for Benign Cystic Thyroid Nodules: Ethanol Ablation or Radiofrequency Ablation?
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OBJECTIVE. The purpose of this article is to compare the efficacy and safety of ethanol ablation and radiofrequency ablation (RFA) used as treatment of benign cystic thyroid nodules.
MATERIALS AND METHODS. Fifty-seven patients (44 women and 13 men) with benign cystic nodules (cystic portions > 90%) inducing pressure symptoms or cosmetic problems were treated with ethanol ablation (n = 36) or RFA (n = 21). Ethanol ablation was performed using 16- or 18-gauge needles with 95–99% ethanol, and RFA used a cooled-electrode RFA system and 17- or 18-gauge internally cooled electrodes. Of nine viscous nodules, five were treated with ethanol ablation and four with RFA, with all except for one nodule in the RFA group being treated only after evacuation of internal colloid material. Nodule volume, symptom score (0–10), cosmetic score (1–4), and complications were evaluated before and after treatment.
RESULTS. Both ethanol ablation and RFA resulted in significant decreases in nodule volume (p < 0.001), symptom score (p < 0.001), and cosmetic score (p < 0.001). There were no between-group differences in mean volume reduction (p = 0.15), decreases in symptoms (p = 0.53), cosmetic scores (p = 0.69), or therapeutic success rate (p = 0.61). However, the mean number of treatment sessions was significantly lower in the ethanol ablation than in the RFA group (p = 0.026). No serious complications were encountered in either group.
CONCLUSION. Ethanol ablation yielded similar results with fewer treatment sessions compared with RFA. Because ethanol ablation is also less expensive and simpler to perform than RFA, our findings suggest that ethanol ablation, rather than RFA, should be the first-line treatment technique for benign predominantly cystic thyroid nodules.
Keywords: cystic thyroid nodule, ethanol ablation, radiofrequency ablation, thyroid intervention, ultrasound
| Introduction |   |
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Sonography-guided ethanol ablation, an alternative to surgical or medical therapy, is a safe and effective technique for the treatment of thyroid nodules. Although ethanol ablation is less satisfactory when it is used to treat predominantly solid thyroid nodules [1], ethanol ablation is useful in the treatment of cystic thyroid nodules (cystic portions > 90%), affording volume reductions of 85–98.5% [2–8].
Radiofrequency ablation (RFA) has been used to treat various tumors [9–12] and has been reported to be effective in the treatment of thyroid nodules [13–19], including those that are either predominantly cystic or predominantly solid [16]. The use of RFA resulted in significantly greater reduction in the size of cystic nodules, compared with other forms of nodules, 1 and 3 months after ablation, but the difference at 6 months was not significant [16].
Although both ethanol ablation and RFA are effective in the treatment of cystic thyroid nodules, to the best of our knowledge, no study to date has compared these two techniques. We therefore compared the efficacy and safety of these two types of treatment in patients with cystic thyroid nodules.
| Materials and Methods | |
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This retrospective study was approved by our institutional review board, which waived the requirement for patient informed consent. However, informed consent for each procedure was obtained before the procedure for all patients.
We reviewed computerized medical records of 1,134 consecutive patients who underwent thyroid ethanol ablation and RFA from June 2002 through April 2008. The patients were referred to our radiologic intervention department from our thyroid center. Seventy-eight patients with cystic thyroid nodules were extracted from the computerized medical records. Among them, 16 patients with insufficient fine-needle aspiration cytology (FNAC) results were referred to surgery, and five patients refused treatment. Finally, 57 patients (44 women and 13 men) were included in this study. Of these, 36 patients (26 women and 10 men; mean age, 47.7 years) were treated with ethanol ablation, and 21 patients (18 women and three men; mean age, 42.5 years) were treated with RFA. All subjects treated with ethanol ablation or RFA have been included in the study because they fulfilled the following criteria: having a cystic nodule (cystic portions > 90%); reporting pressure symptoms or cosmetic problems; largest diameter of the nodule exceeding 2 cm; serum thyroid hormone and thyrotropin levels within normal limits; two separate ultrasound-guided FNAC examinations to rule out malignancy and to improve patient's clinical symptoms and cosmetic problems by aspiration of as much internal fluid as possible; fluid recurrence in the nodule after at least two aspiration sessions of FNAC; no history of minimally invasive treatment within 6 months; refusing or being ineligible for surgery; and undergoing follow-up for at least 6 months after treatment.
For referred patients, we explained the advantages and disadvantages of surgery and minimally invasive procedures to each patient. Patients desiring surgery were referred to a surgeon in our thyroid center, whereas patients requesting a minimally invasive procedure were referred to our radiologic intervention department. The latter patients were informed about the two minimally invasive procedures, ethanol ablation and RFA, and each chose a preferred treatment technique.
Ultrasound, ultrasound-guided FNAC, laboratory, and clinical results were evaluated before the ablation. Two radiologists performed ultrasound and ultrasound-guided FNAC using a 10-MHz linear probe and one of two real-time ultrasound systems (Prosound SSD-5000, Aloka; or Aplio SSA-770A, Toshiba Medical Systems). In all patients, FNAC included aspiration of internal fluid. We aspirated internal fluid first and then performed aspiration in the remaining solid portion or cyst wall. Sometimes viscous contents could not be aspirated using 21-gauge needles. After measurement of the three orthogonal diameters of each nodule (i.e., the largest diameter and two other mutually perpendicular diameters), the volume of each nodule was calculated using the following equation: V = ϖ abc / 6, where V is the volume, a is the largest diameter, and b and c are the other two diameters.
 View larger version (114K) | Fig. 1A —52-year-old woman with palpable right neck mass who complained of pain and who underwent ethanol ablation. Axial sonographic view shows transisthmic approach of needle. Initially, tip of electrode was located in central region of cystic portion. |
 View larger version (131K) | Fig. 1B —52-year-old woman with palpable right neck mass who complained of pain and who underwent ethanol ablation. Axial sonographic view shows that cystic contents of thyroid nodule had been almost completely removed. |
 View larger version (128K) | Fig. 1C —52-year-old woman with palpable right neck mass who complained of pain and who underwent ethanol ablation. Axial sonographic view shows injection of ethanol into cystic thyroid nodule. Transisthmic approach, through adequate amount of thyroid parenchyma, prevents leakage of ethanol to areas outside thyroid gland. |
Before treatment, patients were asked to rate symptoms on a 10-cm visual analog scale, and the physician recorded a cosmetic grading score (1, no palpable mass; 2, no cosmetic problem but palpable mass; 3, a cosmetic problem on swallowing only; and 4, a readily detected cosmetic problem).
Ethanol ablation and RFA were performed with patients in the supine position, with mild neck extension. All procedures used ultrasound guidance. To prevent serious hemorrhage, we carefully evaluated vascular structures along the approach route. The puncture site was anesthetized with 2% lidocaine, but no other anesthetic was used. To prevent unnecessary scar formation, the skin was not incised. The skin was punctured and target nodules were approached using a transisthmic approach method, both in ethanol ablation [7] and RFA [13, 14, 16, 20, 21]. In other words, the ethanol ablation needle or RFA electrode was inserted into the short axis of the nodule, from the isthmus, under a transverse ultrasound view (Figs. 1A and 2A). This method allows the needle or electrode to pass through an adequate amount of thyroid parenchyma [7, 13, 14, 16, 20, 21]. This approach has several advantages. The technique prevents a change in the position of the needle or electrode tip when the patient is swallowing or talking and also eliminates leakage of fluid (injected ethanol or ablated hot fluid of cystic portion of thyroid nodules) to areas outside the thyroid gland. Moreover, this approach allows clear continuous ultrasound monitoring of the relations of the nodule, the needle or electrode tip, and expected location of the recurrent laryngeal nerve, thus minimizing the risks of thermal injury to that nerve or the esophagus (Fig. 2A).
 View larger version (112K) | Fig. 2A —26-year-old woman with right lower neck bulging, discomfort, and pain who underwent radiofrequency ablation. Axial sonographic view shows transisthmic approach of radiofrequency electrode. Electrode tip was fixed in central portion of cystic nodule during ablation. |
 View larger version (111K) | Fig. 2B —26-year-old woman with right lower neck bulging, discomfort, and pain who underwent radiofrequency ablation. Axial sonographic view shows that entire nodule was filled with echogenic microbubble at end of ablation. Transisthmic approach through adequate amount of thyroid parenchyma prevents leakage of hot fluid to areas outside thyroid gland. |
Ethanol ablation—Ethanol ablation was performed as described elsewhere [7]. In brief, a 16- or 18-gauge needle was inserted into the nodule using a transisthmic approach method. After the needle tip was placed into the central portion of the cystic nodule, the internal nodular contents were aspirated to the maximal extent possible, followed by slow injection of 95–99% ethanol into the cystic space (Figs. 1A, 1B, and 1C). The volume of ethanol injected usually corresponded to 50% of the volume of aspirated fluid. If the cystic nodule contents were viscous, they were aspirated using a large-bore needle (16 gauge) attached to a 50-mL syringe or suction pump, followed by injection of ethanol after more than 90% of the viscous material had been removed [7]. After 10 minutes with the needle in place, the injected ethanol was completely removed, the needle was withdrawn, and the patient was observed for 30 minutes. If, during the follow-up periods, the cystic portion was more than 1 mL in volume or the patient's symptoms or cosmetic problems had not been completely resolved, an additional ethanol ablation was performed.
RFA—RFA was performed using a generator (Cool-Tip Radiofrequency System, Radionics) and internally cooled electrodes (7-cm length 17- or 18-gauge 1-cm active-tip; Well-Point Radiofrequency Electrodes, Taewoong Medical), without aspiration of internal fluid from 2002 through 2004 (five patients), but with aspiration from 2005 through 2008 (16 patients). Before the ablation, an IV access was obtained via the antecubital vein of the arm. No premedication was administered. In most patients, we made one puncture in each of the skin and thyroid capsule to prevent the leakage of hot fluid.
During ablation, the electrode was fixed in the central portion of the cystic nodule (Fig. 2A). If the nodule contained a focal solid portion, that portion was ablated first, and the electrode was next moved to the central cystic region of the nodule. Microbubbles forming during ablation gathered at the superficial region of each cystic nodule. Ablation was commenced with 30 W of radiofrequency power. The ablation procedure was performed under the internal cooling of the electrode. Usually, microbubbles formed within 5 seconds at 50–60 W of radiofrequency power. If a hyperechoic microbubble did not form at the electrode tip within 5–10 seconds, radiofrequency power was increased in 10-W increments up to 100 W. Ablation was terminated when the solid portion became hyperechoic and the cystic portion was full of echogenic bubbles (Fig. 2B). If the patient complained of pain during the procedure, we reduced radiofrequency power or stopped ablation. Complications during and after the procedure were evaluated with respect to clinical signs and symptoms. If, during the follow-up periods, the cystic portion was more than 1 mL in volume or patient symptoms or cosmetic problems were not completely resolved, an addition RFA was performed.
Ultrasound findings, laboratory data, symptom scores, cosmetic scores, and complications were evaluated in all patients during follow-up, in the same manner as before the ablation. Ultrasound examinations and evaluation of complications were performed after 1, 3, 6, and 12 months, whereas laboratory data and clinical symptoms were evaluated at 6 months after the procedure. However, the two physicians performing ultrasound during follow-up were not blind to the treatment techniques.
All statistical analyses were performed using the SPSS statistical software package (version 12.0 for Microsoft Windows, SPSS). Mann-Whitney and Fisher's exact tests were used to compare sex distribution, age, duration of follow-up, initial nodule volume, symptom score, and cosmetic score between the two groups before treatment. Wilcoxon's signed rank test was used to assess reductions in volume, symptom score, and cosmetic score in each group and to compare these parameters between groups, as well as to evaluate therapeutic success and differences in the number of treatment sessions between groups. The level of significance was defined as p less than 0.05.
| Results | |
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Before treatment, there were no significant differences between the ethanol ablation and RFA groups in any clinical or demographic parameter (Table 1). Changes in nodule volume, symptom score, and cosmetic score at each follow-up visit in the ethanol ablation group are shown in Figure 3. We observed significant decreases in nodule volume (p < 0.001), symptom score (p < 0.001), and cosmetic score (p < 0.001) between initial and last follow-up. The mean (± SD) number of treatment sessions was 1.19 ± 0.40 (range, 1–2 sessions), and the total ethanol ablation procedure time ranged from 15 to 45 minutes. Therapeutic success (volume reduction > 50%) was achieved in 34 (94.4%) of 36 patients.
Changes in nodule volume, symptom score, and cosmetic score at each follow-up visit in the RFA group are shown in Figure 4. This group also showed significant decreases in nodule volume (p < 0.001), symptom score (p < 0.001), and cosmetic score (p < 0.001) between initial and last follow-up. The mean number of treatment sessions was 1.67 ± 0.86 (range, 1–3 sessions). Therapeutic success (volume reduction > 50%) was achieved in 20 (95.2%) of 21 patients; treatment failure in a single patient was attributable to hemorrhage in the nodule during follow-up. Radiofrequency power ranged from 30 to 100 W, and ablation time ranged from 3 to 32 minutes.
The internal contents of the nodules were bloody in nature in most patients. However, nine patients (five treated by ethanol ablation and four treated by RFA) had viscous colloid material, which was removed before the procedure from all patients, except for a single patient in the RFA group. One patient with a nodule filled with a viscous colloid, which we did not aspirate before the ablation, achieved therapeutic success but showed insufficient volume reduction (54.04%), despite being treated with three RFA sessions and despite receiving medical attention over a 39-month follow-up period. The ablated mass was still palpable and very hard and did not change in size over a long period. This experience encouraged us to aspirate internal viscous nodule contents before RFA. Such contents can be aspirated using large-bore needles or a catheter connected to a suction pump [7]. After we changed our RFA procedure, we treated three patients with viscous cystic nodules. All three required a single session of RFA, with volume reduction at last follow-up (6, 6, and 11 months, respectively) of 98.02%, 97.64%, and 98.81%, respectively.
 View larger version (11K) | Fig. 3 —Efficacy of ethanol ablation. Graph shows thyroid nodule volumes, symptom scores, and cosmetic scores before ablation; 1, 3, and 6 months after ablation; and at last follow-up. Significant decreases in nodule volume (p < 0.001), symptom score (p < 0.001), and cosmetic score (p < 0.001) were observed between preablation figures and last follow-up data. |
We had three patients (two treated with ethanol ablation and one treated with RFA) with therapeutic failure because of intranodular bleeding. In these patients, ultrasound showed fluid in the treated nodules during follow-up, confirmed as hemorrhage by aspiration.
 View larger version (11K) | Fig. 4 —Efficacy of radiofrequency ablation. Graph shows thyroid nodule volumes, symptom scores, and cosmetic scores before ablation; 1, 3, and 6 months after ablation; and at last follow-up. Significant decreases in nodule volume (p < 0.001), symptom score (p < 0.001), and cosmetic score (p < 0.001) were observed between preablation figures and data from last follow-up. |
The therapeutic results in the two groups are compared in Table 2. There were no between-group differences in mean volume reduction (p = 0.15), decrease in symptom score (p = 0.53), decrease in cosmetic score (p = 0.69), or therapeutic success rate (p = 0.61), but the mean number of treatment sessions was significantly lower in the ethanol ablation group than in the RFA group (p = 0.026).
No serious complications, such as a voice change, skin burning, infection, or damage to the vital structures of the neck, were encountered in either group. During ethanol ablation, patients experienced only mild pain associated with needle puncture and removal. During RFA, most patients complained of pain and a burning sensation in the neck radiating to the head, shoulders, teeth, and chest, but these complaints were relieved by reducing radiofrequency power or by stopping ablation. Serum concentrations of triiodothyronine, free thyroxine, and thyrotropin were normal in all patients during follow-up.
| Discussion | |
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We have shown here that both ethanol ablation and RFA are effective and safe in the treatment of cystic thyroid nodules. Both treatment techniques improved patient symptoms and cosmetic problems related to the presence of thyroid nodules, and no major complication was associated with use of either procedure. However, the mean number of ethanol ablation treatments was significantly lower than the mean number of RFA treatments (p = 0.026).
As described in previous reports, we found that both ethanol ablation and RFA resulted in significant but similar volume reductions (93.08% vs. 92.19%) [2, 4, 5, 8, 16]. In both patients with therapeutic failure after ethanol ablation, hemorrhage in the nodules during follow-up was the cause of the failure.
The presence of colloid material in a nodule was also associated with slow volume reduction and a need for repeat treatment. This experience encouraged us to aspirate internal viscous nodule contents before RFA using large-bore needles or a catheter connected to a suction pump [7], and volume reduction was excellent (97.64–98.81%) with only a single session of RFA.
This study had several limitations, the principal limitation being the change made to the RFA procedure in the course of the study. With our initial RFA procedure, internal nodule contents were not aspirated, which may have reduced treatment efficacy and resulted in a requirement for a higher number of treatment sessions. The second limitation is selection bias, because this study was retrospective. The last limitation is the relatively small numbers of patients. Well-designed prospective blinded randomized studies with larger numbers of patients are required to further compare the efficacy and safety of ethanol ablation and RFA.
In conclusion, although both ethanol ablation and RFA were effective and safe treatment techniques, and repeat treatments were tolerable in all patients with benign cystic thyroid nodules, ethanol ablation required fewer treatment sessions. In addition, ethanol ablation is a less expensive and simpler procedure than is RFA, suggesting that ethanol ablation, rather than RFA, should be the first-line treatment technique for benign predominantly cystic thyroid nodules. These results may be useful in avoiding expensive trials or treatments in patients with benign cystic thyroid nodules that can be successfully managed in a simpler way.
Address correspondence to J. H. Baek ([email protected]).
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