Ethanol and Radiofrequency Thyroid Ablation Move toward Mainstream Treatment for Benign Thyroid Nodules-Solitary or Combined Treatment, Neuromonitoring, and Shared Decision-Making?

This article refers to:

Comparison of the Effectiveness of Ethanol and Radiofrequency Ablation in the Treatment of Thyroid Nodules and Their Effects on Cosmetic Scoring

Thyroid nodules are common in the adult population with a prevalence of up to 30% at ultrasound examination. Minimally invasive techniques using image-guided thyroid ablation procedures, such as ethanol ablation (EA), radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), and high-intensity focused ultrasound (HIFU), have been increasingly proposed as treatment options for benign lesions that cause symptoms or cosmetic concern [1,2]. Thyroid ablation can change the natural history of benign thyroid lesions that keep growing over time to prevent or control symptoms and to reduce the need for surgery and avoid surgical complications. In cystic thyroid lesions, aspiration and EA are the most effective and least expensive treatments. RFA may be considered for cystic lesions that relapse after EA or have a significant residual solid component following drainage and EA [2].

Given the minimally invasive thyroid ablation procedures, specifically the EA and RFA, has gained increasing acceptance among clinicians and patients as the mainstream treatment for benign thyroid nodules, we acknowledge the importance of the study recently published in the Journal of Investigative Surgery [3] which evaluates the volumes and cosmetic scores of biopsy-proven benign mixed-type and spongy-type thyroid nodules before and after EA and RFA treatment and compared the safety and efficacy among the treatments. Fifty patients received EA treatment and 46 patients who received RFA treatment were included in the study. Nodule volumes obtained before, three months after, and six months after treatment were recorded. Similarly, the cosmetic scores were obtained before and six months after treatment for all patients. The study shows that RFA is more successful in reducing cosmetic scores in patients with mixed-type and spongy-type thyroid nodules, and both techniques are similarly effective in volume reduction. The major strength of the commented study is that they compare the safety, efficacy, and cosmetic outcome of the popular EA and RFA treatments. In this regard, this article is original and can draw interest from the readers of different disciplines (i.e. endocrine surgeons, head and neck surgeons, radiologists, and endocrinologists).

However, there are several concerns that need to be mentioned and discussed. In this study, EA or RFA procedure was performed randomly in a single session without any distinction between mixed-type and spongy-type nodules. In a previous study, the size of the solid components of cystic thyroid lesions can be a negative factor in the technical efficacy of EA [4]. The combined use of EA and RFA has been shown to be effective and reduce incomplete treatment [5]. Solitary RFA treatment and EA/RFA combined treatment will be the main options for the therapy of mixed-type and spongy-type thyroid nodules, and the comparison of their treatment outcomes will also be the trend of future studies.

Moreover, the commented study described the transient loss of voice developed due to edema in three patients who underwent EA and thermal injury in four patients who underwent RFA, and all of them recovered at the end of the first month. What the author did not mention in detail is that the mechanism or etiology for voice loss should be different in the two treatments, and the possible mechanism should be elucidated in both groups. Ethanol acts by denaturing proteins, extracting fatty substances, and precipitating the lipoproteins and mucoproteins [6]. The recurrent laryngeal nerve (RLN) injury in the EA technique is usually caused by the spillage of ethanol outside the lesion [7], direct contact between ethanol and RLN is essential for nerve injury. The thermal injury of RLN in the RFA technique is different, the lateral thermal spread may cause protein denaturation even into endoneurium without direct contact between the device and RLN, and result in more risk of irreversible RLN injury.

To reduce the RLN injury during EA and RFA, the intraoperative neuromonitoring (IONM) system, a technique that has been widely used in open and remote thyroid surgeries, showed great potential. Early detection of RLN injury during thyroid surgery has been generally agreed to identify and stop the harmful surgical steps, and improve surgeons’ skill to avoid similar harmful steps in future operations. This concept can also be applied to thyroid ablation treatments. IONM consists of three essential parts, stimulator, recorder, and monitoring system. Lee et al. [8] conducted an animal study to develop a RFA device combined with a stimulating electrode to monitor the RLN status. In addition, an accelerometer sensor to install on the skin of the front neck, making it possible for patients to perform RLN monitoring under non-general anesthesia. Zhang et al. [9] designed a pre-prototype combined stimulating and recording endotracheal tube that continually delivered current from the tube edge and monitored the RLN function in an animal study. However, these studies also showed some shortcomings [10], such as the inability to complete monitor vagus nerve and RLN, and the stability of the recorder (i.e. EMG tube and accelerometer sensor) is insufficient. Even though more future researches on novel EMG tube are still expected to improve the current limitations, a monitored thyroid ablation will be a safe option for patients with recurrent thyroid lesions, tumors adjacent to the RLN, and RLN with anatomical variations, specifically the non-recurrent or ventrally displaced nerves.

In the selection of EA and RFA, a balance between cost and treatment response should be achieved for different thyroid nodule types. Furthermore, several factors should be considered when weighing between observation, surgery, and thyroid ablation for benign thyroid nodules. Although this commented study provides excellent evidence that EA and RFA are effective in volume reduction for benign thyroid nodules and reducing the cosmetic scores, patients have to be counseled about the cost and treatment response of the ablation therapy for the appropriate thyroid nodule type. Future studies are needed to understand the long-term cost-effectiveness of adopting EA and RFA as mainstream treatments for benign thyroid nodules. Current clinical decisions might be made after a shared decision-making process between clinicians and patients.

Authors’ contribution

All the authors conform the Journal and the International Committee of Medical Journal Editors (ICMJE) criteria for authorship, contributed to the intellectual content of the study and gave approval for the final version of the article.

Disclosure statement

The authors have no proprietary, financial, professional or other personal interest of any nature in any product, service or company. The authors alone are responsible for the content and writing of the paper.