Roles of contrast-enhanced ultrasonography in identifying volume change of benign thyroid nodule and optical time of secondary radiofrequency ablation

In the past few years, ultrasonography-guided radiofrequency ablation (RFA) was proved to be an effective and safe treatment for both benign and malignant thyroid tumor, with few complications using trans-isthmic approach and moving-shot technique [1‐4]. According to previous studies, a 50–80% volume reduction of thyroid nodule after 6 months [5], a 79–90% volume reduction after 2 years [6], and a 93% volume reduction after 4 years [7] could be observed postoperatively, with a longest and largest follow-up of 5 years reported [8].

Although satisfying volume reduction rate and symptomatic and/or cosmetic improvement could be achieved using RFA, previous studies had reported a recurrence rates of 5.6% for benign tumors, and all recurrent cases showed regrowth of incompletely treated nodule margin [7], which was considered as a reason of nodule recurrence after RFA [9].

Since a complete nodule margin is extremely important for prevention of nodular recurrence [10], in cases with incompletely treated nodule margin, a secondary RFA is should be necessary and beneficial. A secondary RFA was usually performed when symptom resolution was not achieved, residual tissue regrowth was noted or increasing vascularity was obviously observed. However, no consensus on the optimal itme to perform the secondary RFA was achieved due to lack of evidence. Thus, the current study was designed to analyze the dynamic change of nodular volume of benign thyroid tumors accessed using contrast-enhanced ultrasonography (CEUS) after RFA, and hopefully to offer evidence for time decision of secondary RFA.

The dynamic change of volume of benign thyroid nodule after RFA were assessed using CEUS in the present study. The main results of this study showed that 95.35% of nodular regrowth occurred in 12 months after RFA, with no statistical significance compared to the total rate of nodular regrowth. Treatments were effective with low complication rate, and no significant complications like procedure-related deaths occurred during up to 3-year follow-up.

Marginal recurrence of ablated thyroid nodule had been firstly reported by Baek and his colleagues [9]. However, primary purpose of RFA for benign thyroid nodule is to conduct effective debulking or to reduce pressure symptoms, rather than to ablate the entire nodule [5], which is considered to be technically difficult, because complications might be inevitable due to the existence of critical structures around the thyroid, such as oesophagus, trachea, vagus nerve, recurrent laryngeal nerve [22], sympathetic ganglion and blood vessels [23]. However, incompletely treated nodule margin could be a reason of the regrowth of thyroid nodule [5]. Therefore, thyroid nodule should have their margin treated as much as possible to minimize marginal recurrence.

Previous studies had identified several factors influencing marginal regrowth of nodule. Initial solidity and nodule volume affects treatment response. Huh et al. had suggested that RFA is effective in most thyroid nodules, however, large nodules require more energy in order to achieve complete ablation of peripheries [10]. Ha et al. suggested a moving-shot technique to minimize marginal recurrence [24]. Internal cooled electrode could also minimize thermal damage to the surrounding critical structures of thyroid [1]. Thus, the current study applied moving-shot technique and internal cooled electrode. Moreover, other influencing factors of nodule regrowth includes nodule nature, maximum temperature reached during ablation treatment, treatment modalities, energy type and post-procedural marginal vascularity [25, 26].

Monitoring Vv increase is important to identify nodule regrowth and symptom recurrence. The change in Vt was considered to consist of a Va decrease and a Vv increase. In the earlier period after RFA, Vt becomes smaller when Va decrease is greater than Vv increase. In the later period after RFA, Vt becomes larger when Vv increase exceeds Va decrease (regrowth). Vv increase might be masked by Va decrease if Vt is the only measured value. Thus, measurement of Vv had been recommended to detect regrowth and to provide evidence for a secondary RFA [27].

Up to date, no widely-accepted consensus on the optimal timing of secondary RFA exist. Our study found that 95.35% of nodular regrowth occurred in 12 months after RFA, and the rate showed substantial consistency with that on the 36th month postoperatively (Kappa = 0.656). Thus, the 12th month after RFA might be the optimal time for volume assessment to make the decision of secondary RFAs. On the other hand, it should also be noted that at 6th month postoperatively, 58.14% of nodular regrowth had been detected, which means for these patients, evaluation at 6th month was also important. However, negative results at 6th month postoperatively could not be considered as the final result, because there is still a good chance to detect nodular regrowth at next time point.

In the present study, CEUS was used to evaluate the dynamic change of thyroid benign nodules after RFA, because previous studies have suggested that the ablation zone can be more clearly visualized with CEUS than with color Doppler US [28]. Dynamic changes of nodular volume were also evaluated using CEUS in several our previous studies.

We have to admitted that there were still several limitations of our study. First, the nature of the retrospective, small -sampled study made it impossible to avoid selection bias. Second, we did not compare results from non-contrast ultrasound and contrast ultrasound because lack of a gold-standard method as reference. Besides, changes of nodular volume could not be assessed after a > 50% increase of Vt or Vv was firstly found because lack of subsequent data. Moreover, complexity of dynamic change of the volume, different time-volume curve of different nodules, and lack of data after secondary RFAs, made the data imbalanced, which is why quantitative compare (for example analysis of variance) could not be used. The interval of follow-up time points might also be inappropriate, lacking data after 9 months or 15 months, due to the retrospective nature of the study, as well as the cost-effective need in clinical routine. A further large volume, real world study with specifically designed follow-up time points might be more convincing in assessing the dynamic change of nodular volume after RFA. However, based on the existed results, we are still confident to conclude that the majority cases of regrowth occurred in 12 months after RFA.

CEUS was an effective and safe tool to monitor volume change of benign thyroid nodules after RFA. The majority cases of regrowth occurred in 12 months after RFA, thus, the 12th month after RFA might be the optimal time for volume assessment to make the decision of secondary RFAs.