We retrospectively enrolled patients with PTC who underwent TA as first-line treatment at China-Japan Friendship Hospital between April 2018 and December 2023.

The inclusion criteria were:

The exclusion criteria comprised:

After applying these criteria, 113 patients were included in the final analysis (Figure 1). All patients included in the study declined surgical intervention due to either medical contraindications (e.g., poor general condition precluding general anesthesia) or personal preference (such as the desire to preserve thyroid function or refusal to accept surgical scarring).

All patients underwent comprehensive ultrasound (US) evaluation before and after ablation (Nanjing ECO Microwave System or Surgnova Radiofrequency Ablation System) using high-resolution US scanners GE LOGIQ E9 (GE Healthcare, USA) or Aplio 500 (Toshiba, Japan) equipped with linear transducers. The largest tumor or metastatic lymph node was identified as the index lesion. When extrathyroidal extension was present, the tumor with invasion was designated as the index lesion. Tumor characteristics were described based on the index lesion. All patients underwent comprehensive evaluation during and within 24 hours after the ablation procedure, including US, contrast-enhanced ultrasound (CEUS), and physical examination, to assess the ablation outcomes and detect potential complications. The procedure was immediately terminated if intolerable adverse reactions or complications occurred during treatment, and ablation was performed again after symptom resolution. Follow-up was conducted every 3 months in the first year, every 6 months from years 2 to 4, and annually thereafter. The follow-up contents include ultrasound examinations, thyroid function tests, and annual chest CT scans. When suspicious nodules are detected on ultrasound, patients are advised to undergo FNA or close monitoring. CEUS is employed to evaluate suspicious lymph nodes and any newly emerging nodules within the ablation zone. The definitive diagnosis is ultimately based on FNA results. For recurrent tumors, multidisciplinary team evaluation determined subsequent treatment (repeat ablation or surgical resection).

All ablation procedures were performed by radiologists with over 3 years of specialized experience in thyroid nodule ablation. The detailed procedural steps were consistent with our previous study (15, 16). Here, we primarily focus on describing the technical nuances of the hydrodissection technique.

An 18-G core needle connected to an extension tube and normal saline (NS) was used. Under real-time ultrasound guidance, the puncture needle was advanced layer by layer to the target position, with the tip appropriately placed within the fascial space. NS was then injected. If swelling of the surrounding soft tissues was observed, the needle tip was considered improperly positioned and was adjusted until the fascial space expanded upon NS injection, appearing as an anechoic area on ultrasound. During the ablation procedure, NS was continuously injected to maintain an adequate width of the isolation zone (at least 5 mm). The purpose of hydrodissection was to separate the lesion from adjacent critical structures and organs, thereby reducing the risk of complications. During lymph node ablation, hydrodissection was similarly performed to create a fluid barrier surrounding the target lymph node, with complete circumferential isolation as the optimal endpoint.

Given the nonsurgical nature of thermal ablation (with consequent absence of pathological specimens), and distinct from the surgical-pathological criteria used in the ATA risk stratification system, we established the following sonographic definition of uETE: (1) on ultrasound examination, the tumor shows a tendency to breach the capsule but can be effectively isolated from adjacent soft tissues by hydrodissection. which specifically characterized by the presence of interrupted or defective capsular echoes adjacent to the tumor, (2) but after isolation, a separation of at least 5 mm is maintained between the tumor and surrounding important structures as opposed to mere soft tissue edema (Figure 2). Technical success was achieved when the tumor was entirely encompassed by the ablation zone with a minimum 2-mm safety margin (except at the capsular interface). Complete ablation was confirmed by immediate post-procedural CEUS demonstrating no enhancement within the treated area; any residual enhancement prompted additional ablation. RFS was measured from the date of confirmed complete ablation until either disease recurrence or death from any cause. Disease recurrence encompassed: (1) pathologically-confirmed local recurrence (tumor regrowth within or adjacent to the ablation zone), (2) new primary tumors (distinct from the ablation site), (3) emergence of new lymph node metastases, or (4) distant metastasis. Procedure-related complications encompassed both immediate adverse events and subsequent occurrences with probable treatment association, where complications persisting beyond 6 months were designated as permanent (17, 18). Assessment of major complications (hoarseness or permanent·vocal cord paralysis) and minor complications (choking cough, hematoma, shoulder pain). The tumor volume was calculated using the following formula: V=πabc/6, where V represents the volume, A is the largest diameter, B and C are the other two perpendicular diameters.

Continuous variables were compared using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Fisher’s exact test, chi-square test or continuity-corrected chi-square test. The Kolmogorov-Smirnov test was used for normality testing. Survival curves were generated by Kaplan-Meier method and compared using log-rank test. A p-value <0.05 was considered statistically significant. Univariate and multivariate regression analyses (Cox regression and logistic regression) were performed to identify prognostic factors, with variables showing p<0.1 in univariate analysis included in multivariate analysis. All analyses were conducted using SPSS (version 25.0, Chicago, USA) and R software (version 4.1.1).

After applying the inclusion and exclusion criteria, a total of 113 patients were enrolled in this study. Their demographic and tumor characteristics are summarized in Table 1. Among them, 94 patients (83.2%) harbored BRAF mutations, while 19 (16.8%) were BRAF wild-type. The median number of ablated nodules was 2 (IQR: 2, 4), and the median number of intrathyroidal tumors was 1 (IQR: 1, 2). The median volume of the index lesion was 0.30 cm³ (IQR: 0.11, 1.05). Regarding tumor characteristics, 77.0% (87/113) of index lesions showed no calcification, while 23.0% (26/113) exhibited calcifications. On CEUS, 48.7% (55/113) demonstrated hyperenhancement, 5.3% (6/113) showed isoenhancement and 46.0% (52/113) presented with hypoenhancement or no enhancement. Lymph node metastasis was observed in 55.8% (63/113) of patients, with a median of 2 metastatic lymph nodes (IQR: 1, 3) and a median maximum diameter of 0.90 cm (IQR: 0.70, 1.45). Additionally, 48.7% (55/113) of patients exhibited uETE, with specific invasion sites detailed in Table 2. The median ablation time was 150.0 seconds (IQR: 98.00, 301.00). The mean ablation power was 30–40 W.

A total of 380 nodules, including 194 PTC nodules and 186 metastatic lymph nodes, underwent ablation treatment. Among the 113 patients, 118 ablation sessions were performed, with 108 (95.6%) underwent single ablation session and 5 patients (4.4%) requiring a second session due to either loss of visualization during continuous separating fluid injection in cases with multiple lesions or procedure-related complications. Post-treatment CEUS confirmed the absence of enhancement within all ablation zones, resulting in 100% technical success and complete ablation rates.

The median follow-up duration was 45.7 months (95% CI: 34.6–48.7). By the end of follow-up, 18 patients (15.9%) had developed tumor recurrence. Notably, all recurrences manifested as new primary tumors rather than local recurrence. The mean RFS was 70.8 ± 2.8 months, with 1-, 2-, 3-, and 5-year recurrence-free survival rates of 95.6% (95% CI: 91.9%–99.4%), 89.5% (95% CI: 83.8%–95.6%), 83.7% (95% CI: 76.2%–91.9%) and 79.8% (95% CI: 71.1%–89.5%). The survival curve is presented in Figure 3. Univariate and multivariate analyses (Table 3) identified metastatic lymph node diameter as an independent risk factor for RFS (HR: 3.20, 95% CI: 1.32–7.76, p < 0.05).

By the end of follow-up, 24 patients (21.2%) had experienced procedure-related complications (Table 4). Major complications occurred in 21 (18.6%) patients, while minor complications in 8 (7.1%). To elaborate in detail, the most frequent complication was hoarseness (18.6%, 21/113), including 2 cases (1.8%) of permanent vocal cord paralysis. Other complications included choking cough [occurs concomitantly with hoarsenes (4.4%, 5/113)], hematoma formation (1.8%, 2/113) and shoulder pain (0.9%, 1/113). All complications except permanent hoarseness resolved completely within 3 months post-procedure. Univariate and multivariate analyses (Table 5) revealed that number of ablation sessions was independently associated with complication occurrence (OR: 13.54, 95% CI: 1.14–160.19, p < 0.05).