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Collected Research

Objective: 
To determine the number of total thyroidectomies per surgeon per year associated with the lowest risk of complications.

Background: 
The surgeon volume-outcome association has been established for thyroidectomy; however, a threshold number of cases defining a "high-volume" surgeon remains unclear.

Methods: 
Adults undergoing total thyroidectomy were identified from the Health Care Utilization Project-National Inpatient Sample (1998-2009). Multivariate logistic regression with restricted cubic splines was utilized to examine the association between the number of annual total thyroidectomies per surgeon and risk of complications.

Is There a Minimum Number of Thyroidectomies a Surgeon Should Perform to Optimize Patient Outcomes?

Radiofrequency ablation (RFA) seems to achieve a significantly larger nodule volume reduction rate (VRR) than laser ablation (LA) in benign nonfunctioning thyroid nodules (BNTNs).

Objective: 
To compare the efficacy and safety of both treatments at 12-month follow-up in patients with solid or predominantly solid BNTN.

Methods: 
This was a single-center, 12-month, randomized, superiority, open-label, parallel-group trial conducted in an outpatient clinic. Sixty patients with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems were randomly assigned (1:1 ratio) to receive either a single session of RFA or LA. Twenty-9 patients per group completed the study. The main outcome measures were VRR and proportion of nodules with more than 50% reduction (technical success rate).

Laser Ablation Versus Radiofrequency Ablation for Thyroid Nodules: 12-Month Results of a Randomized Trial (LARA II Study)

Background: Ultrasound-guided thermal ablations have become one of the main options for treating benign thyroid nodules. To determine efficacy of thermal ablation of benign thyroid nodules, we performed a meta-analysis of studies with long-term follow-up of more than 3 years.

Methods: Databases were searched for studies published up to August 25, 2019, reporting patients with benign thyroid nodules treated with thermal ablation and with follow-up data of more than 3 years. Data extraction and quality assessment were performed according to PRISMA guidelines. The analysis yielded serial volume reduction rates (VRRs) of ablated nodules for up to 3 years or more, and adverse effect of ablation during follow-up. Radiofrequency ablation (RFA) and laser ablation (LA) were compared in a subgroup analysis.

Results: The pooled VRRs for ablated nodules showed rapid volume reduction before 12 months, a plateau from 12 to 36 months, and more volume reduction appearing after 36 months, demonstrating long-term maintenance of treatment efficacy. Thermal ablation had an acceptable complication rate of 3.8%. Moreover, patients undergoing nodule ablation showed no unexpected delayed complications during the follow-up period. In the subgroup analysis, RFA was shown to be superior to LA in terms of the pooled VRR and the number of patients who underwent delayed surgery.

Long-Term Results of Thermal Ablation of Benign Thyroid Nodules: A Systematic Review and Meta-Analysis

Background: Nearly 20 years after the first feasibility study, minimally invasive ultrasound (US)-guided therapeutic techniques are now considered as a safe and effective alternative to surgery for symptomatic benign thyroid nodules. Radiofrequency ablation (RFA) is one of the most widely used treatment in specialized thyroid centers but, due to the relatively recent introduction into clinical practice, there are limited long-term follow-up studies. Aim of our work was to review the outcomes of RFA on solid nonfunctioning and on autonomous thyroid nodules (AFTN) on a long-time period for assessing the results in term of efficacy, complications, and costs and to compare them to the current indications of RFA.

Methods: A systematic review was performed using EMBASE and Medline library data between 2008 and 2021. Seventeen studies evaluated RFA for the treatment of benign solid (nonfunctioning or autonomous) thyroid nodules, with an at least 18 months of follow-up. Data extraction and quality assessment were performed by two endocrinologist according to PRISMA guidelines. Anthropometric data, safety and efficacy parameters were collected.

Results: The majority of the studies was retrospective study and reported 933 nodules, mostly solid. Baseline volume ranged between 6.1 ± 9.6 and 36.3 ± 59.8 ml. Local analgesia was used and the time duration of the treatment was between 5 ± 2 and 22.1 ± 10.9 min. The volume reduction rate at 12 months ranged from 67% to 75% for the nodule treated with a single procedure and reached to 93.6 ± 9.7% for nodules treated with repeat ablations. The regrowth rate at 12 months ranged from 0% to 34%.

Long-Term Results of Ultrasound-Guided Radiofrequency Ablation of Benign Thyroid Nodules: State of the Art and Future Perspectives-A Systematic Review

Background: Monopolar radiofrequency ablation is currently deemed an exotic treatment option for benign thyroid nodules in many central European countries. The aim of this study was to evaluate prospectively the safety and efficacy of this method in a large patient cohort following its introduction in Austria.

Methods: Peri- and post-interventional complications were analyzed for 277 patients. Efficacy was determined for 300 and 154 nodules at 3 and 12 months post treatment, respectively. All treatments were performed with an internally cooled 18G radiofrequency electrode using a free-hand, “moving-shot” technique following subcutaneous and local perithyroidal anesthesia.

Results: Mean patient age (SD) was 52 ± 12.9 years (75% female), and overall mean baseline nodule volume (SD) was 13.8 ± 15.9 mL. Nodules were visible in 62.8% of patients, 40% had a symptom score ≥4 on a 10-point visual analogue scale, and 14.4% had hyperthyroidism. Mean overall nodule volume reduction rates (VRR) at 3 and 12 months were 68 ± 16% and 82 ± 13%, respectively (p < 0.001). At 12 months, 81% of nodules exhibited a VRR of ≥70%, with 10%, 6%, and 2% of nodules showing VRRs of 60–70%, 50–60%, and ≤50%, respectively. Subgroup analysis according to baseline nodule size (≤10 mL to >30 mL) or baseline nodule composition (solid, mixed, cystic) revealed significantly higher VRRs for smaller and cystic nodules. Moreover, nodule shrinkage was accompanied by significantly improved symptom and cosmetic scores after 3 and 12 months (p < 0.001). Of 32 hyperthyroid patients, 27 (84%) were euthyroid, four had subclinical hyperthyroidism, and one had subclinical hypothyroidism at last follow-up. Post-procedural complications were absent in 83% of patients, minimal in 12.9%, moderate and reversible in 3.2% (1.8% voice change, 0.7% hyperthyroidism, 0.3% wound infection treated with antibiotics, 0.3% epifascial hematoma), and irreversible in 0.7% (one case with hypothyroidism and one with a wound infection treated by surgery).

In summary, the results of the present study are consistent with the existing literature and confirm the safety of RFA in general and the efficacy of a single treatment course of monopolar RFA in a large central European cohort. The results also provide some potentially significant data for future discussions regarding possible selection criteria for patients with thyroid nodules that could be treated with RFA.

Monopolar Radiofrequency Ablation of Thyroid Nodules: A Prospective Austrian Single-Center Study

Benign thyroid nodules are exceedingly common in the adult population. Only a small percentage of nodules are toxic or autonomously functioning thyroid nodules (AFTNs). The options clinicians have for treating the symptoms of hyperthyroidism include anti-thyroidal medications, radioactive iodine, or surgery. Depending on the patient population treated, these options may not be suitable or have inherent risks that are undesirable to the patient. On the other hand, untreated hyperthyroidism can lead to osteoporosis, atrial fibrillation, emotional lability, and neurological consequences. Thus, we present a review of two novel safe and effective approaches for treating AFTN; one surgical (transoral endoscopic thyroid surgery) and one non-surgical (radiofrequency ablation), as a means for expanding our treatment armamentarium.

Radiofrequency ablation (RFA) is a novel minimally invasive approach that is a potential alternative to surgery for treating symptomatic benign nodules (43) as well as AFTN (44). This approach eliminates the need for a general anesthetic, an incision, radioactive iodine, or prolonged ATD treatment, making it an attractive non-surgical option. With the use of local anesthesia, the RFA probe is introduced into the midline of the anterior neck at the level of the isthmus, and the nodule is approached using the moving shot technique under ultrasound guidance (45). This causes tissue necrosis and fibrosis by introducing a high frequency alternating current, which raises tissue temperatures to 60 to 100 C (46). Over time, there is progressive shrinkage of the ablated nodule. In benign nodules, the volume of the nodule is thought to decrease between 50 and 80% for most patients, although this is operator and tumor dependent (47, 48).

RFA has been offered to patients internationally since 2000 and has been used to treat primary and metastatic tumors of the liver, lung, bone, and kidney and to ablate aberrant conduction pathways in the heart (49–53). More recently, RFA has been applied to the head and neck, particularly for thyroid nodules. While the early results have been promising internationally, there is little North American data (47, 48, 54–61). The current international recommendations for treating benign thyroid nodules include patients who are symptomatic or those who have a disfiguring goiter or a nodule that exceeds 2 cm, or if an AFTN is present (43, 44, 57). Prior to RFA treatment of AFTN, confirmation that the nodule is benign on at least one US-guided FNA or core biopsy is recommended, unless there are concerning features on ultrasound in which case two biopsies should be obtained (43, 44). Nodules that are benign on FNA but that have suspicious US features (EU-TIRADS 5), the latest European Thyroid Association Guidelines strongly recommend (moderate quality evidence) against thyroid ablation to avoid potential delay in treatment of a malignant lesion (62).

Novel Approaches for Treating Autonomously Functioning Thyroid Nodules

Purpose: To confirm the efficacy of ultrasound (US) guided radiofrequency ablation (RFA) in the treatment of benign thyroid nodules, we evaluated as primary outcome the technical efficacy and clinical success in a single center dataset. The secondary outcome was to find a correlation between nodules’ pre-treatment features and volume reduction rate (VRR) ≥75% at 12 months after RFA and during follow-up period.

Methods: This retrospective study included 119 consecutive patients (99 females, 20 males, 51.5 ± 14.4 years) with benign thyroid nodules treated in our hospital between October 2014 and December 2018 with a mean follow-up of 26.8 months (range 3–48). Clinical and US features before and after RFA were evaluated by a US examination at 1, 3, 6, 12 months and annually thereafter up to 48 months.

Results: The median pre-treatment volume was 22.4 ml; after RFA we observed a statistically significant volume reduction from the first month (11.7 ml) to the last follow-up (p < 0.001 for all follow-up times). The median VRR was 47.1, 55.3, 61.2, 67.6, 72.8, 71.3, and 62.9% at 1, 3, 6, 12, 24, 36, and 48 months of follow-up respectively, showing a progressive significant improvement up to 24 months (VRRs 1 vs 3 months, 3 vs 6 months and 6 vs 12 months p < 0.001, 12 vs 24 months p = 0.05) while no differences at 24 vs 36 and 36 vs 48 months were observed. Symptoms improved significantly (complete resolution 64.35%, partial resolution 35.65%), and neck circumference was reduced as compared to pre-treatment (p < 0.001). Lower pre-treatment neck circumference (37.5 vs 36.0 cm, p = 0.01) was a positive predictor of VRR ≥75% at 12 months. Macrocystic echostructure (HR 2.48, p 0.046) and pre-treatment volume >22.4 ml (HR 0.54, p 0.036) were found to be independent positive and negative predictors of VRR ≥75% respectively. One-month post RFA VRR ≥50% represented the best positive predictor of technical success.

Predictor Analysis in Radiofrequency Ablation of Benign Thyroid Nodules: A Single Center Experience

Ultrasound (US) features of solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape are suspicious characteristics for thyroid nodules. An US based Thyroid Imaging Reporting and Data System (TI-RADS) is classified based on the number of aforesaid features. TI-RADS category 3 included nodules without any suspicious features, and categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features. The purpose of the study was to prospectively validate the effectiveness of the TI-RADS. 

Methods: 
From October 2011 to June 2013, we prospectively categorized 3980 thyroid nodules (3752 benign and 228 malignant lesions) in 2921 patients using TI-RADS classification. TI-RADS categories 2 and 3 were considered as benign whereas TI-RADS categories 4 and 5 as malignant. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were calculated. Results: Of the 3980 nodules, 2953 nodules were TI-RADS category 2 (0% malignancy), 466 nodules TI-RADS category 3 (1.3% malignancy), 186 nodules TI-RADS category 4a (4.8% malignancy), 165 nodules TI-RADS category 4b (30.3% malignancy), 188 nodules TI-RADS category 4c (75.5% malignancy), and 22 nodules TI-RADS category 5 (95.5% malignancy). The sensitivity, specificity, PPV, NPV and accuracy were 97%, 90%, 40%, 99%, and 91%, respectively.

Prospective validation of an ultrasound-based thyroid imaging reporting and data system (TI-RADS) on 3980 thyroid nodules

Benign thyroid nodules (BTNs) are commonly found in the general population. They are usually asymptomatic and their incidence has increased as a result of wide‐spread use of ultrasound. Benign nodules are typically monitored clinically until they increase in size, resulting in compressive symptoms warranting surgery. However, although surgery is generally well‐tolerated and of low‐risk, it is associated with a small risk for several complications including hypothyroidism, nerve injury, hematoma, injury to other structures and wound infection. Recently, newer image‐guided ablation techniques including radiofrequency ablation (RFA) have been introduced. RFA has a similar safety profile when compared to surgery and has shown promising results in challenging surgical candidates. Though several studies have been published in Asian and European countries on the efficacy of RFA, limited data is available on the North American population. The aim of the study is to review the current literature establishing the clinical outcomes and safety of RFA for benign nodules.

RFA and benign thyroid nodules: Review of the current literature

Radiofrequency ablation (RFA) is a relatively novel procedure in the management of benign nodular
goiter. This study was conducted to evaluate the safety and efficacy of ultrasound (US)-guided percutaneous RFA for benign symptomatic thyroid nodules as an alternative to surgery.

Methods 
The study involved patients for whom a fine needle aspiration biopsy had proved a diagnosis of benign
nodular goiter and had nodule-related symptoms such as dysphagia, cosmetic problems, sensation of foreign body in the neck, hyperthyroidism due to autonomous nodules or fear of malignancy. Percutaneous RFA was performed as an outpatient procedure under local anesthesia. The primary outcome was an evaluation of the changes in symptom scores (0–10) for pain, dysphagia and foreign body sensation at the 1st, 3rd, and 6th months after the RFA procedure. Secondary outcomes were assessing volume changes in nodules, complication rates, and changes in thyroid function status. 

Results 
A total of 33 patients (24 % female, 76 % male) and a total of 65 nodules were included into the study.
More than one nodule was treated in 63.6 % of the patients. We found a statistically significant improvement from baseline to values at the 1st, 3rd, and 6th months, respectively.

Radiofrequency Ablation of Benign Symptomatic Thyroid Nodules: Prospective Safety and Efficacy Study

Radiofrequency ablation (RFA) is a thermal ablation technique widely used for the management of benign thyroid nodules. To date, five academic societies in various countries have reported clinical practice guidelines, opinion statements, or recommendations regarding the use of thyroid RFA. However, despite some similarities, there are also differences among the guidelines, and a consensus is required regarding safe and effective treatment in Asian countries. Therefore, a task force was organized by the guideline committee of the Asian Conference on Tumor Ablation with the goal of devising recommendations for the clinical use of thyroid RFA. The recommendations in this article are based on a comprehensive analysis of the current literature and the consensus opinion of the task force members.

Radiofrequency Ablation of Benign Thyroid Nodules:

Radiofrequency ablation (RFA) is used in the United States to treat benign thyroid nodules; however, experience with treating cervical recurrence/persistence of papillary thyroid cancer (PTC) is limited.

Objective
To evaluate the efficacy RFA for the treatment of cervical recurrence/persistence of PTC in the United States.

Although it is well recognized that surgery is the treatment of choice for recurrent thyroid cancer in the neck, some patients are not surgical candidates, or may not want to undergo repeat surgeries after their initial resection. While active surveillance is an option for selected patients, many patients have anxiety with this approach and may choose intervention despite no progression in tumor kinetics or size [30, 31]. RFA is emerging as an alternative option for these patients.

RFA is minimally invasive and has a lower complication rate than surgery; however, use in recurrent cervical PTC recurrence is still limited in the United States [12-14, 17]. The results of our study are illustrative of the real-world outpatient application and results using this technique.

Technical success has traditionally been defined as a 50% volume reduction in the thermal ablation literature with regards to benign thyroid nodules; however, in case of malignancy, treatment should be with curative intent. Therefore, we have defined complete success as a 100% volume reduction that mimics the results after surgery, and have recognized that a near-complete response of 90% volume reduction is likely to be clinically similar to a complete response, as the remaining tissue may not be viable or may have only microscopic disease that can be monitored. This is further supported by the low post procedure Tg levels in these patients.

Radiofrequency Ablation of Cervical Thyroid Cancer Metastases—Experience of Endocrinology Practices in the United States

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