|Year : 2014 | Volume
| Issue : 7 | Page : 144-149
Ultrasonography-guided percutaneous radiofrequency ablation for cervical lymph node metastasis from thyroid carcinoma
Liping Wang1, Minghua Ge2, Dong Xu1, Liyu Chen1, Chaowen Qian1, Kaiyuan Shi1, Junping Liu1, Yong Chen1
1 Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou 310022, China
2 Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China
|Date of Web Publication||29-Nov-2014|
Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou 310022
Source of Support: None, Conflict of Interest: None
Purpose: The aim was to explore the efficacy and safety of ultrasonography-guided percutaneous radiofrequency ablation (RFA) for cervical lymph node metastases from thyroid carcinoma.
Materials and Methods: Eight patients with previous total thyroidectomy and radioiodine therapy were enrolled in this study. A total of 20 cervical lymph node metastases were confirmed by percutaneous biopsy. Participants underwent ultrasonography-guided RFA treatment for all confirmed metastatic lymph nodes. Contrast-enhanced ultrasound (CEUS) and sonoelastography were performed to rapidly evaluate treatment responses before and shortly after RFA. Routine follow-up consisted of conventional US, CEUS, sonoelastography, thyroglobulin level, and necessary fine needle aspiration cytology.
Results: All eight patients were successfully treated without obvious complications. Post-RFA CEUS showed that total metastatic lymph nodes were ablated. The sonoelastographic score of ablated area elevated significantly shortly after RFA (P < 0.001). With a mean follow-up of 9.4 ± 5.1 months, there were no evidences of recurrence at ablated sites; however, two new cervical recurrent lymph nodes occurred in one case, which was successfully ablated as well. The mass volume shrinkages of the ablated nodes were observed in all cases. We found that 5 treated lymph nodes disappeared, 4 were reduced more than 80%, 9 were reduced between 50% and 80%, and 2 were reduced less than 50%. At the last follow-up evaluation, the serum thyroglobulin levels had decreased in 6 of 8 patients.
Conclusion: Ultrasonography-guided percutaneous RFA for cervical lymph node metastasis of thyroid malignancy is a feasible, effective, and safe therapy. This procedure shows a nonsurgical therapeutic option for metastatic lymph nodes in patients with difficult reoperations or inoperations, it may reduce or delay a large number of highly invasive repeated neck dissections.
Keywords: Radiofrequency ablation, recurrent thyroid cancer, ultrasound
|How to cite this article:|
Wang L, Ge M, Xu D, Chen L, Qian C, Shi K, Liu J, Chen Y. Ultrasonography-guided percutaneous radiofrequency ablation for cervical lymph node metastasis from thyroid carcinoma. J Can Res Ther 2014;10, Suppl S3:144-9
|How to cite this URL:|
Wang L, Ge M, Xu D, Chen L, Qian C, Shi K, Liu J, Chen Y. Ultrasonography-guided percutaneous radiofrequency ablation for cervical lymph node metastasis from thyroid carcinoma. J Can Res Ther [serial online] 2014 [cited 2019 Aug 22];10:144-9. Available from: http://www.cancerjournal.net/text.asp?2014/10/7/144/145844
| > Introduction|| |
The thyroid gland is the most common site of all primary endocrine cancers globally, thyroid cancer (TC) incidence has increased greatly over recent decades, comprising 2.7% of all female cancers, ranking as the ninth most common cancer in women.  Papillary TC frequently spreads locally and recurs by metastasizing to local cervical lymph nodes. , When cervical lymph node metastasis detected, surgery, followed by radioactive iodine therapy and/or thyroid hormone therapy is still the mainstream standard treatment. Repeated operations are sometimes challenged to perform due to severe fibrosis and distortion of the normal tissue planes by scar formation and a higher rate of complications.
Ultrasonography-guided percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy that has been shown to provide promising results for local tumor control in a variety of organs, ,,, Recently, in addition, RFA has also been applied to benign thyroid tumors.  Although the RFA method for treatment of cervical recurrent TC has been firstly reported as early as 2001,  the subsequent similar reports are very limited. ,, Up to present, surgery is the gold standard for treatment for recurrent TCs in the central or lateral compartments of the neck, it seems that RFA modality treatment for the disease still fails to attract sufficient attention and the therapeutic outcomes still remain controversial. The present paper was designed to explore the feasibility, effectiveness, and safety of percutaneous RFA for cervical lymph node metastasis of TC. In this paper, we share our own detailed procedure technique for the treatment of cervical metastatic lymph nodes, which were rarely mentioned in published literatures. We have introduced more therapeutic evaluation methods than previous studies, especially contrast-enhanced ultrasound (CEUS) and sonoelastography, which were not reported in previous studies. ,,
| > Materials and methods|| |
The study was performed at our medical institution (Zhejiang Cancer Hospital, Hangzhou, China). Written informed consent was obtained from the patients and/or relatives, when appropriate, before treatment. Ethical approval was obtained from the Ethical Committees of Zhejiang Cancer Hospital.
Between January 2013 and August 2014, eight patients (seven women, one man; mean age, 43.6 ± 9.3 years; range, 30-58 years) were enrolled in this study. A total of 20 lymph node metastases were confirmed by percutaneous biopsy. Ultrasonography-guided RFA was performed for all confirmed metastatic lymph nodes. The demographic and clinical characteristics before and after RFA are summarized in [Table 1]. The mean number of operations before RFA was 2.25 (range, 1-3), and the interval between the last operation and RFA was 11.25 months (range, 1-24 months). The mean largest diameter of the initial tumors was 10.0 ± 6.1 mm (range, 3-22 mm), and the mean tumor volume was 0.206 ± 0.241 ml (range, 0.008-0.724 ml). All participants enrolled in this study for RFA had undergone total thyroidectomy and radioiodine therapy. Among them, two patients found 2 palpable lymph nodes in the neck, and six patients found 18 inpalpable lymph nodes in the neck by ultrasound during postoperative follow-up period.
|Table 1: Demographic and clinical characteristics regarding 8 patients treated with percutaneous radiofrequency ablation of 20 cervical metastatic LNs from thyroid carcinoma before and after RFA |
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All patients enrolled in the study had underwent out-patient RFA treatment at our department, two of the 20 recurrent lymph nodes in one patient were located in the surgical bed, and the other 18 metastatic lymph nodes were located in the lateral compartment of the neck. Supraclavicular lymph nodes and lymph nodes below the clavicle were excluded in our study. All enrolled patients were reviewed without risk of bleeding, with a normal platelet count and normal coagulation parameters.
Three orthogonal diameters of each metastatic lymph node (the largest diameter and two perpendicular diameters) were recorded. The volume of Lymph node was calculated with the equations V = π/6abc (where V is volume; a, the largest diameter; and band c, the other two perpendicular diameters), and percentage volume shrinkage ratio = ([initial volume-final volume] ×100)/initial volume.  Elasticity image of each ablated lymph node had been qualitatively scored for the proportion of stiff areas from score 1 to 5 (soft to stiff) on the basis of a newly defined system for lymph nodes. ,,
Devices for radiofrequency ablation
The RFA procedure was performed under real-time ultrasonographic guidance (model: LOGIQ E9, GE Health Care) with 10-MHz linear probe. A18-gauge 7-cm shaft length 0.5 cm straight fixed active-tip electrode with internally cooled (Star RF Electrode-Fixed, STARmed Co., Ltd., Korea) was connected to a radiofrequency generator (VRS01, STARmed Co., Ltd., Korea). The modified straight internally cooled electrode we used is specially developed for treating thyroid tumors. This modified electrode is shorter and thinner than the conventional electrode, and smaller active tips can easily penetrate small metastatic tumors through the surgical scar.  A peristaltic pump was used to perfuse chilled water (15°-20° C) at 80 mL/min through the perfusion port of the electrode to prevent tissue charring and to improve the radius of RF energy deposition.
Radiofrequency ablation procedure
The patients were placed in the supine position with the neck extended. Two grounding pads were attached to the waist. One radiologist performed the RFA procedure, and another radiologist guided the needle under real-time ultrasound, each of whom had more than 8 years of experience with RF ablation. Different from other reports, , our team use two kinds of drugs of Diazepam and Bucinperazine. Before and during RFA procedure, 250 ml normal saline (NS) mixed with 10 mg Diazepam Injection was administrated by continuous intravenous drip infusion via the antecubital vein. Diazepam is an anxiolytic-sedative drug useful in relieving anxiety and tension states that may be present before minor surgical procedures. Conscious sedation of high dosage was not recommended even in patients with intolerable pain because verbal communication with the patient is necessary to prevent injury of the nerve or major structures during the ablation session. Bucinperazine (50 mg) as analgesic agent was intramuscularly administered before the RFA. To prevent unnecessary scar formation, the skin was not incised, and only one electrode puncture of the skin was made in all patients.  To prevent serious hemorrhage, the vessels along the approach route were carefully evaluated. The vagus nerve in the lateral compartment of the neck was also carefully evaluated. 
If a metastatic lymph node is tightly adjacent to the vital structures, such as anterior cervical muscle group, carotid artery, jugular vein, trachea, esophagus, vagus nerve, and recurrent laryngeal nerve. The NS should be carefully injected between the vital structures and the tumor. The so-called "hydrodissection technique" could effectively protect vital structures from needle cutting and electrode heating injury. , For these reasons, our team had applied this technique to all cases in this study. But the total amount of NS injection should not exceed 30 ml, so as to avoid discomfort of neck constriction in the patient.
Continuous real-time US monitoring with gray scale and color Doppler imaging was performed to identify proper electrode position and assess microbubble formation during the RFA session. Sonoelastography and CEUS were performed before and immediately after the procedure to evaluate the therapeutic effect. Our team uses the "moving-shot" technique for ablating the metastatic lymph nodes, the technique has been popularly used to treat benign thyroid nodules and has recently been introduced to ablate recurrent TCs. ,,, Before starting RFA, the targeted lymph node should be divided into multiple conceptual ablation units, and RFA performed unit by unit by moving the electrode tip. These conceptual units are smaller at the periphery of the tumor and the portions adjacent to the vital structures and are larger in the central, safe portion of the tumor. Initially, the electrode tip is positioned in the deepest and most remote conceptual unit of the tumor to enable easy monitoring of the electrode tip without the disturbance caused by microbubbles. The electrode was moved within the targeted lymph node by tilting it upward or downward. When ablation in the peripheral unit was finished, the electrode was moved backward and in the superficial direction. For small tumors (≤5 mm), however, the electrode should be fixed to the center of the lymph node and not be moved during the procedure. ,, The RFA session in our study was started with 20 W of power, a transient hyperechoic zone did not form at the electrode tip within 5-10 s, radiofrequency power was increased in 5-10 W increments up to 35 W. If a patient could not tolerate pain during ablation, the power was reduced or turned off for several seconds. Ablation was terminated when all conceptual units had changed to transient hyperechoic zones. RFA was usually performed on both the metastatic tumor and the surrounding normal tissue. We carefully monitored patients for reports of symptoms and complications during and immediately after ablation. ,, All patients were successfully performed and discharged from the hospital after observation for 2-4 h at the post-procedure recovery room.
Clinical follow-up consisted of Conventional US, CEUS, sonoelastography, a checkup on thyroglobulin levels, and necessary fine needle aspiration cytology (FNAC) were similar to those performed before ablation. Follow-up examinations were performed 1, 3, 6, and 12 months after treatment and then every 6 months thereafter. We carefully evaluated changes of the ablated lymph node in the size, volume, intratumoral vascularity, and classification of sonoelastography. The serum thyroglobulin levels and the development of new metastatic tumors should be carefully assessed as well. A biopsy specimen of any suspicious or new lesion after RF ablation was obtained to evaluate the completeness of thermocoagulation.
Descriptive data were expressed as mean ± SD values. Statistical analysis was performed using SPSS statistical software (Version 19.0; SPSS, Chicago, IL). The Wilcoxon signed rank test was used to compare largest diameter, volume, sonoelastographic score and serum thyroglobulin levels before RFA and at each follow-up visit. A difference with P < 0.05 was considered as statistically significant.
| > Results|| |
The procedures were well tolerated in all 8 patients to completion without obvious bleeding or/and serious complications. Although some patients suffered a burning sensation, pain, or both, the symptoms were relieved with a reduction in radiofrequency power output or stopping the ablation for several seconds. In 20 RFA sessions, the mean maximum power output of RF procedure was 30W (range, 20-35 W), and mean active time of ablation was 2.7 min (range, 0.5-6 min).
The radiologic assessments were achieved by consensus of both RFA operators and another radiologist who did not perform any of the procedures. After and during the follow-up period, the treated lymph nodes demonstrated increased echogenicity in the tumor and surrounding soft tissue, and the absence of intratumoral color Doppler signals in comparison with the previous treatment. Completeness of RF ablation was assessed by the presence of contrast enhancement in the lymph node: Lack of enhancement was deemed to indicate complete ablation and no evidence of local progression, while residual enhancement or appearance of the foci of enhancement in the lymph node that was previously considered to be completely ablated was deemed to indicate incomplete ablation or local progression, respectively.  Post-RFA CEUS showed that totally 20 cervical metastatic lymph nodes were once ablated, and no recurrent tumors found in the ablated area during the follow-up period. Shortly after RFA procedure, the mean sonoelastographic score of ablated area elevated was 4.80 ± 0.41, which was significantly shortly after RFA procedure (P < 0.001). The mean score at the last follow-up was slightly decreased (4.75 ± 4.44), but no statistical significance was found (P > 0.74).
After RFA, five metastatic lymph nodes finally completely disappeared (5/20, 25%) and four lymph nodes remained as small scarlike lesions. By the last follow-up visit, the mean largest diameter of the 20 treated lymph nodes had decreased significantly from 10.0 ± 6.1 mm to 5.65 ± 4.66 mm (P < 0.001). Of the 20 treated lymph nodes, the volume shrinkage ratio ranged from 25% to 100%, and the mean volume had decreased significantly from 0.206 ± 0.241 ml to 0.056 ± 0.080 ml (P < 0.001), namely the mean volume shrinkage ratio was 76.9% ± 21.2% during the last follow up visit.
At the last follow-up visit, the serum thyroglobulin levels had decreased in 6 of 8 patients and had slightly increased in two cases. The mean serum thyroglobulin level decreased from 7.7 ± 5.5 ng/ml to 3.4 ± 4.3 ng/ml, but the difference was not statistically significant (P = 0.05).
During post-RFA follow-up period, two new recurrent cervical lymph nodes in one patient were detected by US and confirmed using US-guided FNAC, but there was no evidence of recurrence at the initial treatment site. The patient had received a repeated RFA treatment, and then two ablated recurrent metastases in the neck were also enrolled for further observation.
Treatment outcome after RFA is summarized in [Table 2].
|Table 2: Outcomes of radiofrequency ablation regarding 8 patients treated with percutaneous radiofrequency ablation of 20 cervical metastatic LNs from thyroid carcinoma |
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| > Discussion|| |
US-guided thermal energy is deployed very precisely and in a highly predictable way, and small ablation volumes can be obtained, thus theoretically minimizing risks of burning undesired structures.  US-guided Laser ablation has been reported as an effective form of thermal ablation technique for the treatment of nodal metastases in papillary TC. , Our initial results show that RFA under ultrasound guidance is also feasible, effective, and safe for the treatment of cervical lymph nodal metastases from thyroid carcinoma and that this procedure can potentially reduce a large number of radical neck dissections in selected patients.
In our study, the lymph nodes that were successfully treated by RFA method decreased in volume (by approximately 76.9%, at last follow-up visit) and became hyperechoic. Reported in previous studies, RF ablation of recurrent TCs in the neck resulted in a mean volume reduction of 56% to 93%, ,, with 42-58% of nodules completely disappearing. ,,, Baek et al.  reported freedom from recurrence in 9 of 10 patients, but one patient had newly developed metastatic tumors, and one patient had been incompletely treated. In comparison with our study, no incompletely treated tumors were found in all previously treated lesion of 8 patients, but one patient developed two distant metastases in ipsilateral neck during the follow-up period. However, a relatively less satisfactory result was reported in an RFA treatment for inoperable symptomatic recurrent TCs, Of 16 sessions, tumor ablation was complete in 6, incomplete in 9, and failed in 1. Incomplete or failed ablation was analyzed by the author due to intolerable pain, severe calcified lesion, or a tumor encasement of major vessels.  It is, however, worth stressing that the mean diameter of ablated tumors in our series (10 mm) was smaller compared with that in the study by Park et al.  (29 mm). We considered that application for smaller lesions in our present study may provide more favorable results.
Careful RFA applications in the hands of an experienced interventional ultrasound team likely led to the fact that there were no complications in our present study. Nevertheless, one potential risk of this technique is nerve damage caused by thermal injury. Changes in voice tone that can occur following RFA are some of the most serious complications caused by injury to the recurrent laryngeal nerve. Changes in voice tone have been reported in 7% (3 of 45) of RFA patients. ,,, We believe that this risk can be mitigated by using low power and prolonging the time of the procedure to have a better control of the energy deployment. , Another method to avoid thermal nerve injury in these cases is to inject a bolus of NS between the targeted lymph node and the expected location of the nerve, which will serve as a protective thermal barrier to RF energy.
The best methodology for evaluating tumor response after thermal ablation is still debated. CEUS can provides good visualisation of vascular modifications after thermoablation, CEUS in percutaneous ablative treatment and in surgery has been reported as an effective utility for assessing local control of tumor, and the utility is particularly very helpful in monitoring the immediate result of the ablation procedure. , In our practice, we applied CEUS as an important mean to evaluate the effectiveness of thermoablation immediately after the procedure and during the follow-up period. Elastographic scores were determined on the distribution and percentage of the lymph node area with high elasticity (hard), with score 1 being an absent or very small hard area to score 5, a hard area occupying the entire lymph node.  An elastography score ≥3 was reported as an independent significant factor to predict a metastatic lymph node involvement.  In our study, the vast majority of biopsy-proven positive lymph nodes were accord with this rule, but 2 lymph nodules (2/20) in two patients demonstrated the sonoelastography score 2 because metastatic papillary thyroid carcinoma had a considerable proportion of cystic degeneration. Thermal coagulation can results in elevated stiffness in treated lesion, the use of sonoelastography technique has been suggested to portray tissue elasticity for the evaluation of tissue ablation procedures over the past decade. , It was observed in our study that the sonoelastographic score after RFA procedure in ablated area elevated significantly (P < 0.001), the visual change of tissue elasticity in the necrotic areas after ablation had been perceived from its hardness. A declining trend of sonoelastographic score was also observed with the passage of time, but no statistical significance was found (P > 0.05). Of course, it needs to be noted that sonoelastography has a certain subjectivity, doctor's skill and experience have potential influence on the accuracy of the results. In a series of studies, the serum thyroglobulin (Tg) levels had been proved as a effective indicator to predict a successful control of recurrent TC in the majority of patients, the patients in which local control was not achieved or who developed disease progression had elevated serum levels of thyroglobulin (Tg), whereas all patients with negative serum levels of thyroglobulin (Tg) were found to have local control ,, in our study, a similarly decreasing trend in the serum thyroglobulin levels was found.
Some limitations of our study should be taken into account. First, all of the RF ablated lymph node metastases were histologically well-differentiated tumors with relatively indolent nature, not poorly differentiated tumors. We have not demonstrated the treatment effect of RF ablation in those metastatic lymph nodes of poorly differentiated types, However, it was deemed that RF procedure of poorly differentiated tumors could result in poor long-term clinical results, because they usually show rapid regrowth and poor prognosis.  Secondly, we reported only data about a relatively short follow-up period in a small number of patients who affected by the slowly growing disease. In addition, radioactive iodine had already been used in all cases before RFA procedures, the tumor activity of the metastases had been partly inhibited, the RF treatment results of metastatic lymph node without radioactive iodine therapy still needs further explore. So far, only a small amount of similar literatures based on a small samples and short-term data have been found, our team believes that RFA procedure as a treatment alternative to surgery for the patient with numerous metastatic lymph nodes still need to be cautious.
In summary, we have demonstrated that ultrasonography-guided RFA may represents a new option in the treatment of cervical lymph node metastasis from thyroid carcinoma. This procedure appears to be a feasible, effective and safe therapy and may allow us to treat completely or to avoid unnecessary surgery in a high number of selected patients.
| > Acknowledgements|| |
The authors alone are responsible for the content and writing of this article.
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[Table 1], [Table 2]