Long-Term Outcome of Microwave Ablation for Benign Thyroid Nodules: A 48-Month Follow-up Study

Purpose The short-term effects of microwave ablation (MWA) in the treatment of benign thyroid nodules (BTNs) were satisfactory in previous studies. However, as a slowly progressing disease, the long-term ecacy of MWA for BTNs at present is not clear. Our study aim was to assess the long-term results of MWA for BTNs after a 48-month follow-up. Methods From June 2015 to September 2017, 148 patients had 148 BTNs lesions. All patients were from China-Japan Union Hospital of Jilin University. Careful ultrasound examinations were performed 1 day, 1 month, 3 months, 6 months, 12 months, and every 6 months after MWA. The volume, volume reduction rate (VRR) recurrence rate of the ablated area and thyroid function were recorded.


Introduction
In recent years, the detection rate of thyroid nodules has been as high as 65%, and more than 90% of nodules are benign [1,2]. Only a few of these benign nodules require treatment. Although surgery is a widely used and effective treatment regimen, it is traumatic, results in a slow recovery, and affects the appearance of the patient. Moreover, some patients must be placed on long-term thyroid hormone replacement therapy after surgery [3][4][5]. Therefore, in recent years, a huge number of scholars have sought minimally invasive treatment methods to treat benign thyroid nodules (BTNs).
One such method is microwave ablation (MWA), which has demonstrated good results in the treatment of benign and malignant thyroid tumours in recent years [6][7][8]. The short-term effects of MWA in the treatment of BTNs have been veri ed by some scholars [9][10][11][12]. However, as a slowly progressing disease, the real e cacy of MWA treatment for BTNs should be demonstrated over long-term follow-up. Therefore, this study aimed to clarify the e cacy of MWA in the treatment of BTNs through at least 48 months of follow-up.

Study oversight
This retrospective study was approved by the Ethics Committee of the China-Japan Union Hospital of Jilin University, and all patients signed an informed consent form before undergoing MWA. All patients were con rmed to have BTNs by core-needle biopsy (CNB).

Patients
The inclusion criteria were as follows: (1)   Pre-MWA procedures Image collection included observing and recording the size, location, composition, echogenicity, margin, shape, echogenic foci, blood ow, etc., of the lesion. All images were collected by a senior doctor (with more than 10 years of experience in thyroid ultrasound examination). Contrast-enhanced ultrasonography (CEUS) was performed before MWA to obtain the scope and blood supply of the nodules and to design a corresponding MWA plan, which was designed by two experienced doctors (with over 5 years of experience in MWA). The volume of the lesion was calculated using V =πabc∕6 (V: volume, a: maximum diameter, b and c: the other two perpendicular diameters). A thyroid function test was performed before MWA and 1 month, 6 months, 12 months, and every 12 months thereafter.
Symptom scores and cosmetic scores were evaluated before and after MWA. We used a visual analogue scale (with scores ranging from 0 to 10) to evaluate neck compression symptoms and dysphagia. The experienced physician evaluated the cosmetic appearance with a score from 1 to 4: 1: no palpable mass; 2: palpable but invisible mass; 3: cosmetic problems when swallowing; 4: cosmetic problems (6, 10).

MWA procedure
The patient was laid supine with the neck fully exposed, and local in ltration anaesthesia with 1% lidocaine was administered. For lesions close to the high-risk area, e.g., near the trachea, oesophagus, recurrent laryngeal nerve and neck vasculature, normal saline was used as an isolation uid to separate the high-risk area from the lesion to prevent damage to the surrounding important organs or tissues.
Following the use of Teng's puncture method (13), the ablation antenna was implanted into the thyroid nodule. On the MWA instrument, ablation mode was initiated with 25 W-30 W power. Using moving-shot techniques (14) during MWA, according to the volume, location and blood supply of the nodule, ablation was performed layer by layer from the upper pole to the lower pole or from the lower pole to the upper pole of the thyroid, following the "from far to near" or "from deep to shallow" principle (14). When the MWA process was performed near the recurrent laryngeal nerve, the operator verbally communicated intermittently with the patient to quickly detect any hoarseness. During the MWA process, the isolation uid should be quickly replenished if it is absorbed.
A CEUS examination was performed immediately after MWA. If the ablation range was satisfactory, i.e., the "black hole" without contrast lling completely covered the tumour, the ablation was considered complete; if the ablation range was not satisfactory, i.e., CEUS showed contrast lling in nodules, supplemental ablation was performed.

Follow-up
Careful ultrasound examinations were performed 1 day, 1 month, 3 months, 6 months, 12 months, and every 6 months after MWA. The volume and volume reduction rate (VRR) of the MWA area were observed and recorded, the latter using the following formula: VRR (%) = ([initial volume-nal volume] × 100%)/initial volume. Recurrence was de ned as abnormal nodular echo found in the internal or marginal ablation area, nodular echo gradually growing or abundant blood ow signals inside during follow-up, and then it was con rmed as a BTN by CNB.
Statistical analysis SPSS 20.0 was used for statistical analysis. The size of the nodule and the age of the patient were described using the mean ± standard deviation (SD). The volume changes before and after MWA were measured by the paired samples t-test. P < 0.05 was considered to indicate statistical signi cance.

Result
Lesion characteristics A total of 148 lesions were con rmed by CNB pathology to be BTNs. Among them, 81 were located in the right lobe, and 67 were located in the left lobe. The average maximum diameter of the nodules was Of the two patients (1.35%) who had bleeding during MWA, 5 minutes of compression stopped the bleeding for one but not for the other, as con rmed by colour Doppler ultrasound at the bleeding site. For the other patient, the bleeding site was burned for 1 minute with an ablation power of 40 W, successfully stopping the bleeding. Neither of the patients who had bleeding required surgical haemostasis.
Two patients (1.35%) experienced earache or toothache on the same side as the lesion during MWA, and the pain was relieved within two hours after MWA.
One patient (0.68%) had hoarseness after MWA and recovered 3 months after MWA. The nodule of this patient was larger than that of the other patients, measuring 5.8 cm×3.5 cm×4.6 cm for a volume of 48.9 cm 3 , and was located adjacent to the dorsal thyroid gland.
Two patients (1.35%) had recurrence after MWA. Two recurrent nodules showed regrowth at the marginal region of the previous nodule at the 18-month and 24-month follow-ups. Both of them showed BTN diagnosis by CNB and performed a second MWA procedure. After the secondary procedure, two nodules decreased in size and did not recur during the follow-up period, which continued for more than 24 months and 30 months.
All 148 patients underwent thyroid function examination before MWA and 1 month, 6 months, 12 months, and every 12 months after MWA, and none showed signi cant variation in thyroid function after MWA compared with before MWA.

Discussion
In this study, 148 nodules in 148 patients were treated with MWA, and the patients were followed-up for 48 months. The long-term follow-up results of the study showed that MWA was effective and safe for the treatment of BTNs. Cheng [6] and Yue [20] reported the treatment of BNTs by MWA and achieved good results, but their follow-up time was less than 12 months. However, BNTs are a slowly progressing disease, and short-term follow-up may not be enough to accurately judge recurrence after MWA. Although Lim [15] treated BNTs with RFA and conducted long-term follow-up, the long-term e cacy of MWA treatment for BTNs at present is not clear.
In this study, MWA was used to treat BTNs, achieving good therapeutic effects for long-term follow-up. After 48 months of follow-up after MWA, the nodule volume was signi cantly reduced, with a VRR of 96.9±2.5% (range: 90.4-100%). In previous research [4,6,9,10,[20][21][22][23][24][25], the follow-up duration after MWA and RFA was 6-12 months, and the mean VRR of the nodules was 45.99%-85.97% and 57.10%-84.79%, respectively, lower than that in our study. We think this is due to the short follow-up period. In Lim's study [15], BTNs were treated with RFA and were followed up for 4 years, and the mean VRR was 93.4±11.7%, similar to the value obtained in our study. Moreover, the treatment of BTNs by MWA in this study signi cantly alleviated the patients' symptoms and cosmetic problems.
Our study revealed a recurrence rate of 1.35% (2/148), which was lower than that in Cheng's and Lim's study, in which the recurrence rates were 7.7% (51/664) and 5.6% (7/126), respectively [6,15]. We hypothesize three reasons for the low recurrence rate after MWA in this study. First, the application of CEUS helped in quickly detecting the presence of residual nodules after MWA and in minimizing or avoiding recurrence through timely supplemental ablation. Second, during MWA, the supplying blood vessel was usually located at the edge of the nodule; thus, the marginal area of the nodule should be fully ablated. Third, careful planning before MWA and strict implementation of the plan during MWA were crucial for preventing recurrence after MWA.
This study showed that MWA was safe for treating BTNs. Five patients (3.38%) in this study had complications in the peri-MWA period, which was similar to Lim's study [15], and the overall complication rate in Lim's study was 3.6% (4/111).
In our study, two patients (1.35%) experienced bleeding during the MWA procedure, lower than previous studies on MWA for the treatment of BTNs, such as studies by Liu and Korkusuz, who found bleeding risk rates of 3.4% and 7.1%, respectively [11,16]. The lower bleeding risk rate in this study was attributed to the following reasons. First, careful observation with colour Doppler prior to puncture could avoid some bleeding, which was caused by damage to the small blood vessels during the puncture process. Second, colour Doppler ultrasound was used to locate the bleeding site quickly and accurately, and MWA could be used to perform haemostasis with 1 minute of ablation at a power of 40 W.
One patient (0.68%) experienced hoarseness that recovered after 3 months, which was lower than Zhi Xi's [3] study (3.6%) and Cheng's [6] report (5.8%). Our experience shows that the treatment of BTNs should comprise full ablation under the premise of safety. Therefore, when ablating BTNs, heat injury of the peripheral nerves should be avoided as much as possible. If the duration of ablation is too long, it is important to quickly replenish the isolation liquid to avoid nerve injury [17][18][19].
Our study also demonstrated other advantages. The thyroid function of all 148 patients was reviewed 48 months after MWA, showing no signi cant variation compared with that before MWA. This shows that MWA does not cause hypothyroidism in patients, which is a very important advantage of MWA for BTNs.
This research also has some limitations. First, this research had a small sample size. Second, this study was conducted at a single centre; future studies should involve a multicentre, larger sample to further verify the results. Finally, although CNB was performed for all 148 nodules in this study to reduce the occurrence of false negatives, this cannot be completely avoided.
In conclusion, over long-term follow-up, MWA for the treatment of BTNs is effective and safe and is expected to be a potential rst-line treatment.