Objectives: The aim of this study was to evaluate the success rate in ultrasonography-guided ethanol ablation (EA) of benign, predominantly solid thyroid nodules and to assess the value of colour Doppler ultrasonography in prediction of its success.
Methods: From January 2008 to June 2009, 30 predominantly solid thyroid nodules in 27 patients were enrolled. Differences in the success rate of EA were assessed according to nodule vascularity, nodule size, ratio of cystic component, amount of injected ethanol, degree of intranodular echo-staining just after ethanol injection and the number of EA sessions.
Results: On follow-up ultrasonography after EA for treatment of thyroid nodules, 16 nodules showed an excellent response (90% or greater decrease in volume) and 2 nodules showed a good response (50–90% decrease in volume) on follow-up ultrasonography. However, 5 nodules showed an incomplete response (10–50% decrease in volume) and 7 nodules showed a poor response (10% or less decrease in volume). Statistical analysis revealed a significant association of nodule vascularity (p=0.002) and degree of intranodular echo-staining just after ethanol injection (p=0.003) with a successful outcome; however, no such association was observed with regard to nodule size, ratio of cystic component, amount of infused ethanol and the number of EA sessions. No serious complications were observed during or after EA.
Conclusion: The success rate of EA was 60%, and nodule vascularity and intranodular echo-staining on colour Doppler ultrasonography were useful in predicting the success rate of EA for benign, predominantly solid thyroid nodules.
Technique of ethanol ablation
Written informed consent was obtained from all patients prior to each EA. EA was performed on an out-patient basis by a radiologist according to the following method. The operator used an empty 10-ml plastic syringe attached to either a conventional 21- or 23-gauge needle (23 gauge for a purely solid nodule or a predominantly solid nodule with a smaller cystic component, and 21 gauge for a predominantly solid nodule with a larger cystic component). During the entire procedure, the operator manoeuvred the ultrasonography probe with his left hand and the syringe–needle unit with his right hand. The ultrasonography probe was adjusted for centring the target nodule on the ultrasonography monitor.
The needle was inserted rapidly almost perpendicular to the neck while the operator applied positive pressure to the syringe piston using the thumb of his right hand in order to prevent an influx of blood into the needle lumen. The method of ethanol instillation differed according to whether the nodule was purely solid or predominantly solid. In the case of a purely solid nodule, absolute ethanol (99.9%) injection was administered directly.
Adequate coverage of the target nodule, as indicated by its echogenicity (called intranodular echo-staining), was achieved by adjusting the injection of ethanol under ultrasonography guidance; the needle–syringe unit was then rapidly withdrawn and the procedure was completed. In cases where the predominantly solid nodule contained a cystic component, the cystic component was punctured and almost completely aspirated, and an appropriate amount of ethanol was instilled. After replacement of the needle into the solid component of the target nodule by adjustment of the needle position, an appropriate amount of ethanol, which was in proportion to nodule size and echo-staining of the solid portion of the nodule, was infused. A single-puncture technique was used with no local anaesthesia. In all cases the amount of injected ethanol did not exceed 10ml. Any patient experiencing a sensation of drunkenness after EA was not allowed to drive herself/himself home. Additional EA was performed 1–2 months after the initial EA when the outcome of EA was determined to be unsuccessful on follow-up ultrasonography. The amount of infused ethanol, degree of intranodular echo-staining just after ethanol injection and presence of pain or other complications during or after the procedure were recorded for each patient.
Nodule volume was calculated during the latest thyroid ultrasonography before EA and during the final follow-up thyroid ultrasonography after EA. The difference in nodule volume was used as a criterion for determination of the success or failure of EA for treatment of thyroid nodules.
The other factor was the absence of, or marked reduction in, nodule vascularity. The outcome of EA was classified as follows, according to the decrease in nodule volume and nodule vascularity: poor response ( <10% decrease in volume, regardless of nodule vascularity), incomplete response (10–50% decrease in volume, regardless of nodule vascularity), good response (50–90% decrease in volume and decreased vascularity) and excellent response (> 90% decrease in volume and scanty vascularity). On real-time colour Doppler ultrasonography, nodule vascularity on the same-day ultrasonography, just before ethanol injection, and that of the last follow-up ultrasonography after EA were compared. Also, nodule volume measured on the same-day ultrasonography just before ethanol injection and that of the last follow-up ultrasonography after EA were compared. Furthermore, the success rate of EA was compared across the nodule size, ratio of the cystic component, amount of infused ethanol, degree of intranodular echo-staining by injected ethanol and the number of sessions of EA. Intranodular echo-staining was roughly estimated on the basis of real-time ultrasonography just after EA and classified as follows: no staining (nearly complete washout of injected ethanol), poor staining ( <10% of the injected area), mild staining (10–50% of the injected area) and moderate staining ( > 50% of the injected area) (Figure 1).
Owing to its ease of use, safety, low cost and effectiveness, EA is the first-choice tool for use in the treatment of benign cystic thyroid nodules [17–26].
However, the efficacy and results of EA for the treatment of solid or predominantly solid thyroid nodules have been variable according to studies (Table 1) [2–14]. RFA or laser ablation has recently become a safe modality for use as an appropriate alternative to clinical follow-up, radioiodine therapy, surgery and EAtreatment of benign solid thyroid nodules [27–30]. RFA has proven to be a feasible and effective tool for treatment of solid nodules; however, its disadvantage lies in the high cost when compared with EA. Baek et al  suggested that RFA for the treatment of benign, predominantly solid thyroid nodules is effective for the reduction of nodule volume and relief of nodule-related clinical problems; they demonstrated a high success rate (100%) and a high mean volume reduction rate (79.7%) during a 6-month period of ultrasonography follow-up. In the present study, the mean success rate (60%) and volume reduction rate (64.3%) of EA were lower than those reported by Baek et al .
In this study, a significant relationship was observed between nodule vascularity and the success rate of EA. EA of predominantly solid thyroid nodules with high vascularity on colour Doppler ultrasonography showed worse results than those with low vascularity. In addition, venous washout of injected ethanol was frequently observed during EA of solid thyroid nodules with high vascularity. We found that poor venous washout of injected ethanol during EA was closely related to good intranodular echo-staining and good results, whereas moderate venous washout was closely related to poor intranodular echo-staining and poor results. Consequently, intranodular echo-staining is closely related to the success rate of EA. It may be hypothesised that effective ethanol ablation is possible only when the ethanol stays within the thyroid nodule and there is no venous washout of the injected ethanol. A long stay of ethanol with little washout can have an effect on sclerotic mechanisms of ethanol, which include coagulative necrosis, small-vessel thrombosis and haemorrhagic infarction . Therefore, EA may become the first-line treatment when a symptomatic solid thyroid nodule shows low- or isovascularity in colour Doppler ultrasonography.
Only one or two EA sessions were conducted for each nodule in this study. We restricted additional EA sessions in case of a significant appearance of venous washout of the injected ethanol during the procedure or poor intranodular echo-staining immediately after ethanol injection; therefore, no more than two EA sessions were conducted. Furthermore, depending on nodule vascularity, degree of intranodular echo-staining and an unsuccessful result on follow-up ultrasonography, an additional EA session or RFA can be decided upon; thus, three or more EA sessions can be avoided.
The fact that EA of large solid thyroid nodules is less successful than EA of small ones is generally accepted [5, 8, 9, 14, 24]; however, other studies have demonstrated safe and effective techniques for treatment of large (.30ml) hyperfunctioning nodules . Some investigators have emphasised that a higher dose of ethanol per session is more important than nodule size and could be significantly related to EA success . However, we believe that intranodular echo-staining of the injected ethanol with no washout is more important than nodule size or the amount of ethanol injected per session.
Kim et al  insisted that the volume of instilled ethanol showed significant correlation with the volume reduction rate of cysts, but not that of solid nodules. The percentage of cystic components in the thyroid nodule has been shown to be closely associated with successful EA . However, in the present study, nodules with a higher percentage of cystic components did not show good results in comparison with nodules with a lower percentage of cystic components. If the procedure were applied to predominantly solid thyroid nodules with low vascularity and high echo-staining without venous washout, we could expect a higher success rate before and during EA. Using this guideline for the selection of thyroid nodules, we could improve the therapeutic results of benign predominant thyroid nodules by choosing the most efficient therapeutic modality.
Ablation mechanisms of ethanol include coagulative necrosis and small-vessel thrombosis with haemorrhagic infarction . An ablated portion of the nodule is replaced by a granulation tissue, followed by progressive shrinkage. Except for transient neck pain and discomfort, there was no occurrence of serious complications of EA in our study. We think that the most serious complication is necrosis of the adjacent normal soft and nerve tissue by leakage of injected ethanol [11, 15, 32]. To avoid complications, substantial experience and a precise ultrasound-guided injection are required. For reduction of side effects, the amount of ethanol injected during each session did not exceed 10 ml in our study. There is no definite guideline for an adequate amount of ethanol injected; in other studies, the maximum amount of ethanol injected per session varied from 7 to 14ml without serious complication [9, 11, 12].
There were several limitations to our study. First, the sample size was small and the range of nodule sizes or configurations broad. Therefore, large-scale studies are recommended in the future. Second, objective quantification of nodule vascularity, intranodular echo-staining and venous washout of injected ethanol was not performed. These were estimated and subsequently classified by the ultrasonography operator. Finally, a thyroid scan was not performed before EA.
In summary, the success rate of EA was 60%, and EA of predominantly solid nodules was more effective in less vascular and more echo-staining thyroid nodules than in more vascular and less echo-staining ones.
Therefore, colour Doppler ultrasonography may be an useful tool for the prediction of treatment outcomes for EA of benign, predominantly solid thyroid nodules.