aula de radiofrequencia em nódulos tireoidianos

Dr. Leonardo G. Rangel

Thermal Ablation of Thyroid Nodules

Head and Neck SurgeonMD , PHDUERJ

New Technique

❖ You have to answer 3 questions :

❖ What for ?

❖ How does it work ?

❖ When will I use it ?

Abraham Maslow

“If the only tool you have is a Hammer, you tend too see every problem as a Nail

Psychologist - 1908-1970

Background

between 2 factor variables was estimated usingv2 analysis.

The Spearman correlation test was used toanalyze the association between PTC tumor sizeand stage. Statistical analysis was performed usingSAS version 9.1 (SAS Institute, Cary, NC). All testswere two-sided and a P value <.05 was consideredstatistically significant.

RESULTS

Incidence trends for all thyroid malignancies:1973–2006. From 1973 to 2006, a statisticallysignificant increase occurred in the age-adjustedincidence rate of thyroid carcinoma from 4.3 casesper 100,000 in 1973–1974 to 11.1 cases per 100,000 in2005–2006, representing a 2.6-fold increase (Fig 1)(P < .0001). PTC had the largest increase in age-adjusted incidence rates with 2.88 per 100,000 in1973-1974 to 9.25 per 100,000 in 2005–2006, repre-senting a 3.2-fold increase (P < .0001). Medullary(0.13 per 100,000 in 1973–1974 to 0.21 per 100,000in 2005–2006) and follicular (0.91 per 100,000 in1973–1974 to 1.08 per 100,000 in 2005–2006) carci-nomas displayed more modest but statisticallysignificant increases in age-adjusted incidence rates(P < .0005). No increase in anaplastic cancer wasnoted (0.11 per 100,000 in 1973–1974 to 0.08 per100,000 in 2005–2006) (P > .05).

PTC: 1983–2006. As mentioned previously, PTChad the greatest increase in age-adjusted incidencerates with 2.88 per 100,000 in 1973–1974 to 9.25 per100,000 in 2005–2006 representing a 3.2-fold in-crease (P < .0001). This change in incidence of PTCaccounted for 96% of the overall increase in thyroidcancer (net increase in PTC of 6.37 per 100,000

divided by a combined increase in PTC, follicularthyroid carcinoma, and medullary thyroid carci-noma of 6.62 per 100,000). When we analyzed thisincrease in PTC incidence based on tumor size, wefound an increase in age-adjusted incidence ratesin each tumor size category of PTC. The largest in-crease was among the microPTC (#1 cm) neo-plasms (Fig 2). MicroPTC (#1 cm) increased441% between 1983 and 2006, or 19.3%/year(0.79 per 100,000 in 1983–1984 to 3.48 per100,000 in 2005–2006; P < .0001). This increasewas followed by a 12.3%/year increase in 1.1–2-cmneoplasms (0.91 per 100,000 in 1983–1984 to 2.57per 100,000 in 2005–2006; P < .0001), a 10.3%/year increase in 2.1–5-cm neoplasms (0.92 per100,000 in 1983–1984 to 2.19 per 100,000 in2005–2006; P < .0001), and lastly a 12.0%/yearincrease in neoplasms >5-cm (0.12 per 100,000in 1983–1984 to 0.33 per 100,000 in 2005–2006;P < 0.0001).

A correlation was found between PTC tumorsize and Stage A classification (Table I) (Spearmancorrelation coefficient 0.285; P < .0001). For mi-croPTC (#1 cm), 81% of neoplasms were localizedand confined to the thyroid. Of the microPTCcases, 17.7% exhibited regional lymph node metas-tases and 1.3% demonstrated distant metastaticmetastases. As we examined the other tumor sizecategories, a trend emerged showing that as tumorsize increased so did the overall stage and the like-lihood of distant metastatic disease. Thus, asshown in Table I, patients with neroplasms >5 cmin size had both the greatest rate of regional lymphnode metastases (51.6%) and distant metastases(12.1%).

Fig 1. Trends in incidence of overall thyroid cancer cases(1973–2006). Data are age-adjusted to 2000 U.S. Censusand stratified by histological subtype with 95% CI.

Fig 2. PTC incidence rates by tumor size (1983–2006).Data are age-adjusted to the 2000 U.S. Census with95% CI.

SurgeryVolume 148, Number 6

Cramer et al 1149

Analysis of the rising incidence of thyroid cancer using the Surveillance, Epidemiology and End Results national cancer data registry

John D. Cramer, et al. Surgery, 2010

BackgroundFinally, the type of surgical resection for PTC

demonstrated an increase in the percentage ofpatients who underwent total thyroidectomy per-formed over time (27% in 1987–1988 to 82.6% in2005–2006; P < .0001) (Fig 3). Thus, a downwardtrend in the percentage of partial thyroidectomiesperformed over time was observed (20.5% in1987–1988 to 13.5% in 2005–2006; P < .0001).Prior to 1987, the most common operative designa-tion was surgery NOS that has decreased over time(96% in 1983–1984 to 0.8% in 2005–2006; P <.0001), reflecting possibly coding disparities inthe SEER database during earlier collectionperiods.

Finally, the type of operative resection for PTCshowed an increase in the rate of total thyroidectomyperformedover time (0.95 per 100,000 in 1987–1988to 1.63 per 100,000 in 2005–2006; P < .0001) (Fig 3).The rate of partial thyroidectomies performedover time remained unchanged (0.74 per 100,000in 1987–1988 to 1.25 per 100,000 in 2005–2006;P < .97). Prior to 1987, the most common operativedesignation was NOS that has decreased over time(3.2 per 100,000 in 1983–1984 to 0.29 per 100,000in 2005–2006; P < .0001), again reflecting possiblycoding disparities in the SEER database duringearlier collection periods.

Adjuvant therapies for all PTC tumors: (1983–2006). We queried the SEER database looking forthe use of adjuvant therapy for thyroid malignan-cies. One limitation of this query is that the SEERdatabase only captures those patients who receivedradiation therapy within 4 months of operation.A total of 33,886 cases of PTC were included in theSEER database. Most PTC received no form ofadjuvant radiation therapy (53.6%; n = 18,178).Among the 46.4% of patients who received someform of adjuvant radiation therapy for PTC, thedistribution was as follows: radioisotope therapy(I-131) (37.1%; n = 12,580), radiation therapy des-ignated as ‘‘other’’ with no additional informationavailable (3%; n = 1,023), external beam radiationtherapy (2.3%; n = 765), and radioactive implants(1.4%; n = 471). Remaining forms of radiationtherapy designations (combination of beam, im-plants and isotopes, and radiation therapy NOS)

represented only 1.1% of the postoperative popu-lation; n = 373). Cases also were present in whichtherapies were recommended but potentially notgiven (1.1%; n = 381), were refused (0.16%; n =54), or were unknown (0.18%; n = 61).

DISCUSSION

Our findings demonstrate that thyroid cancer isincreasing rapidly and that this increase in age-adjusted incidence can be accounted for primarilyby PTC, which accounts for 96% the overallincrease in the general incidence of thyroid carci-noma. These findings agree with several previousstudies that PTC is responsible for the generalincrease in the incidence of thyroid cancer.1,2 In-terestingly, in our current review, follicular andmedullary types of thyroid cancer also show a smallbut statistically significant increase, although thisincrease accounted for only 4% of the overall in-crease in thyroid cancer. The purpose of our studywas to determine whether the increase in thyroidcancer reflected a shift toward cancers at earlierstages or an increase in cancers of all stages.When looking at tumor size, our findings show asignificant increase in PTC of all size categories(#1 cm, 1.1–2 cm, 2.1–5 cm, >5 cm).

Table I. Correlation of SEER stage A classification to PTC tumor size (1983–2006)

Tumor size Localized n (%) Regional n (%) Distant n (%) Total

<1 cm 8,607 (81.0%) 1,886 (17.7%) 136 (1.3%) 10,629 (100%)1.1–2 cm 5,356 (59.0%) 3,493 (38.5%) 223 (2.5%) 9,072 (100%)2.1–5 cm 4,381 (50.5%) 3,903 (45.0%) 387 (4.5%) 8,671 (100%)>5 cm 382 (36.3%) 543 (51.6%) 127 (12.1%) 1,053 (100%)

Fig 3. Surgical therapy for papillary thyroid cancers(1983–2006). Data are age-adjusted to 2000 U.S. Censuswith 95% CI.

SurgeryDecember 2010

1150 Cramer et al

Analysis of the rising incidence of thyroid cancer using the Surveillance, Epidemiology and End Results national cancer data registry

John D. Cramer, et al. Surgery, 2010

Let’s do the Math❖ Total Incidence of Thyroid Cancer = 11,1 : 100.000❖ Total of Thyroidectomies in 2006 : 93.000❖ US population aprox. 300.000.000

❖ So….❖ 33,300 new cases in 2005-2006❖ only 35,8% of the cases where operated on Cancer❖ if you take Microcarcinoma and Incidentalomas

Other Issues ❖ nontoxic goiter

❖ compressive symptoms 28% to 36%❖ cosmetic symptoms 17% to 69%

❖ Hyperfunctioning nodules

❖ Cardiac effects

❖ Bone alterations

❖ RAI

Watt T, Groenvold Eur J Endocrinol 2006;154:501–510

Is there another way ?

Treatment of the Nodule❖ Aspiration

❖ Chemical Ablation

❖ Ethanol Ablation

❖ Tetracycline

❖ Thermal Ablation

❖ Laser Ablation

❖ Radiofrequency Ablation

❖ Microwave Ablation

Treatment of the Nodule

❖ Thermal Ablation

❖ Radiofrequency Ablation

Eur Radiol (2008) 18: 1244–1250DOI 10.1007/s00330-008-0880-6 HEAD AND NECK

Woo Kyoung JeongJung Hwan BaekHyunchul RhimYoon Suk KimMin Sook KwakHyun Jo JeongDucky Lee

Received: 30 June 2007Revised: 19 December 2007Accepted: 15 January 2008Published online: 20 February 2008# European Society of Radiology 2008

Radiofrequency ablation of benign thyroidnodules: safety and imaging follow-upin 236 patients

Abstract This study evaluated thesafety and volume reduction of ultra-sonography (US)-guided radiofre-quency ablation (RFA) for benignthyroid nodules, and the factors af-fecting the results obtained. A total of302 benign thyroid nodules in 236euthyroid patients underwent RFAbetween June 2002 and January 2005.RFA was carried out using an inter-nally cooled electrode under localanesthesia. The volume-reductionratio (VRR) was assessed by US andsafety was determined by observing

the complications during the follow-up period (1–41 months). The corre-lation between the VRR and severalfactors (patient age, volume andcomposition of the index nodule) wasevaluated. The volume of indexnodules was 0.11–95.61 ml (mean,6.13±9.59 ml). After ablation, thevolume of index nodules decreased to0.00–26.07 ml (mean, 1.12±2.92 ml)and the VRR was 12.52–100% (mean,84.11±14.93%) at the last follow-up.AVRR greater than 50% wasobserved in 91.06% of nodules, and27.81% of index nodules disappeared.The complications encountered werepain, hematoma and transient voicechanges. In conclusion, RFA is a safemodality effective at reducing volumein benign thyroid nodules.

Keywords Radiofrequency ablation .Thyroid nodule . Thyroid ultrasound .Intervention

Introduction

Thyroid nodules were found in 4–8% of adults by means ofpalpation, in 10–41% by means of ultrasonography (US),and in 50% by means of a pathologic examination atautopsy [1]. Most thyroid nodules are benign [2] but somenodules require treatment for cosmetic reasons, subjectivesymptoms or anxiety about a malignant change [3, 4]. Thetreatment for benign thyroid nodules consists of two parts:surgery and levothyroxine medication However, both

surgery and medication have drawbacks. Although surgeryis curative, it has problems, including general anesthesia,scar formation and iatrogenic hypothyroidism. In addition,the efficacy of thyroid hormone-suppressive therapy is stillcontroversial [5]. Therefore, non-surgical minimally inva-sive modalities, such as ethanol ablation and interstitiallaser photocoagulation (ILP), have been attempted, yield-ing good results [6–20].

Radiofrequency ablation (RFA) is a minimally invasivetechnique that has been used to treat benign and malignant

W. K. JeongDepartment of Radiology,Asan Medical Center,College of Medicine,University of Ulsan,Seoul, South Korea

J. H. Baek (*) . Y. S. Kim .M. S. Kwak . H. J. JeongDepartment of Radiology, Thyroidcenter, Daerim St. Mary’s Hospital,#978-13 Daerim-dong,Youngdeunpo-gu,Seoul, 150-070, South Koreae-mail: [email protected].: +82-2-8299363Fax: +82-2-8299166

H. RhimDepartment of Radiology,Samsung Medical Center,Sungkyunkwan UniversitySchool of Medicine,Seoul, South Korea

D. LeeDepartment of Internal Medicine,Thyroid center,Daerim St. Mary’s Hospital,Seoul, South Korea

VRR

Before ablation, the largest diameter recorded was 0.6–10 cm (mean, 2.44±1.36 cm) and the volume of indexnodules was 0.11–95.61 ml (mean, 6.13±9.59 ml). Afterablation, the largest diameter recorded was 0.00–5.70 cm(mean, 1.01±1.00 cm) and the volume of the nodules was0.00–26.07 ml (mean, 1.12±2.92 ml) at the last follow-up.The VRR was 12.52–100% (mean, 84.11±14.93%) at thelast follow-up. The mean VRR at 1, 3 and 6 months afterablation was 58.20%, 74.41% and 84.79%, respectively.The changes in the volume of the nodule before ablation,and at each follow-up are summarized in Table 1.

A volume reduction greater than 50% was observed in91.06% (n=275), and 84 (27.81%) index nodules haddisappeared on the follow-up US. There was no patient inwhich the volume increased after ablation at the lastfollow-up.

Safety

The patients complained of various degrees of pain at theablated site, or pain radiating to the head, ear, shoulder, orteeth. The pain decreased when the generator output wasreduced or turned-off during ablation and was easilycontrolled by oral analgesics during admission. However,13 patients (5.5%) required analgesics for more than2 days.

Immediately after ablation, extra-thyroidal hematomadeveloped in five patients (2.1%) but was resolved within 1month using conservative treatment. There was no intra-thyroidal or intra-nodular hematoma formation. Threepatients (1.3%) complained of voice changes, all recover-ing within 2 months without specific treatment. There wereno serious complications, such as esophageal perforation,tracheal injury or skin burn. One day after ablation, thyroidfunction tests were performed on all patients. The serumtriiodothyronine and free thyroxine were within normallimits, but the TSH had decreased in three patients 1 dayafter ablation without any thyrotoxicosis symptoms (0.017,0.087, and 0.053, respectively; normal range 0.4–4 mU/l).

However, they had normalized at the subsequent 1-monthfollow-up.

Factors related to the VRR

Multiple linear regression analysis between the VRR andthe patient’s age and index volume showed that thecorrelation coefficient was 0.036 (P=0.884), and the Pvalue of these factors was 0.891 and 0.623, respectively.Therefore, the VRR was not associated with the patient’sage or index volume statistically.

One and three months after ablation, the mainly cysticnodules decreased in size more than the other types (P=0.000 and 0.007, respectively) but there was no significantdifference between the types of nodules at the 6-monthfollow-up (P=0.621). There was no correlation betweenthe VRR and the composition of the nodule after 6 months(Fig. 4).

Table 1 The changes in volume before RFA and at each follow-up

Initial 1 month later 3 months later 6 months later Last follow-up

No. of nodules 302 247 155 140 302Volume (ml)a 0.11–95.61

(6.13±9.59)0.00–40.30(2.53±4.40)

0.00–24.17(2.00±3.24)

0.00–30.11(1.54±4.38)

0.00–26.07(1.12±2.92)

Largest diameter (cm)a 0.6–10.00(2.44±1.36)

0.00–7.00(1.73±1.03)

0.00–5.20(1.60±0.97)

0.00–6.00(1.26±1.07)

0.00–5.70(1.01±1.00)

Volume reduction rate (%) 58.20 74.41 84.79 84.11aMean ±standard deviation in parentheses

Fig. 4 Graph shows the correlation between mean volumepercentage of remnant nodule and composition of the thyroidnodule at 1, 3 and over 6 months after RFA

1248

Retrospective / No Control Group

2008

The LaryngoscopeVC 2013 The American Laryngological,Rhinological and Otological Society, Inc.

Systematic Review

Radiofrequency Ablation for Treatment of Benign Thyroid Nodules:Systematic Review

Colin W. Fuller, MD, MS; Shaun A. Nguyen, MD, MA; Shivangi Lohia, MD; M. Boyd Gillespie, MD, MSc

Objective: To summarize the literature published to date on the use of radiofrequency ablation (RFA) in the treatmentof benign thyroid nodules, to evaluate the effectiveness of this treatment, and to attempt an evaluation of factors that mayinfluence treatment outcome.

Study Design: Systematic review with meta-analysis.Methods: Systematic literature search was performed by two separate authors in four commonly used literature data-

bases. Trials included in meta-analysis included only those presenting prospective data. Meta-analysis compared pretreatmentvalues to post-treatment outcomes.

Results: Of 46 full-text articles identified, nine articles satisfied inclusion criteria. Two of these articles were randomizedcontrolled trials comparing RFA to placebo or to some other treatment. One article was a randomized controlled trial compar-ing one RFA treatment to two treatments. The remaining six articles were noncontrolled, prospective observational studies.All analyzed outcomes showed statistically significant improvements from baseline to final follow-up, including reduction innodule size, improvement of symptom and cosmetic scores, and withdrawal from methimazole. Improvement in nodule sizeremained significant in both “hot” and “cold” nodule subgroups. Twelve adverse events were identified across all studies outof 306 total treatments. Two of these events qualified as significant adverse events. None of these events resulted in hospital-ization or death.

Conclusions: Radiofrequency ablation is a safe and effective treatment for symptomatic thyroid nodules that are con-firmed benign. However, the paucity of level 1 evidence comparing RFA to surgical or to other nonsurgical treatment modal-ities is concerning.

Key Words: Radiofrequency catheter ablation; thyroid nodule; systematic review; meta-analysis.Level of Evidence: NA

Laryngoscope, 124:346–353, 2014

INTRODUCTIONThyroid nodules are very common in the adult pop-

ulation with a prevalence of 20% to 76%.1 Although themajority of nodules are benign, many require interven-tion due to compressive symptoms, cosmetic concerns, orthe presence of hyperfunctioning thyroid tissue. Largenodules may arise from nodular goiter, causing dyspha-gia, dyspnea, and dysphonia due to local mass effect onimportant anatomical structures in the head and neckinvolved in swallowing, phonation, and breathing. Inextreme cases, nodular goiter may even lead to airwayobstruction requiring emergent surgical intervention.

Goiter may also cause significant cosmetic concerns.2

Prevalence of compressive and cosmetic symptoms inpatients with nontoxic goiter has been reported from28% to 36% and 17% to 69%, respectively.3

Hyperfunctioning nodules are relatively rare amongbenign nodules4; however, a subset may cause subclini-cal or overt hyperthyroidism.5 Although the majority ofpatients are adequately controlled with currently avail-able medical interventions, a small number may haveprogression of hyperthyroidism. However, even subclini-cal hyperthyroidism may adversely affect the cardiovas-cular and skeletal systems,6 leading patients andphysicians to employ definitive treatment with radioac-tive iodine and/or surgery.

Neither of these strategies, however, is withoutrisks. Radioactive iodine (RAI) therapy specifically, whenused to treat any cause of hyperthyroidism, may causetransient thyrotoxicosis, and although this risk can beameliorated by pretreatment antithyroid medications,such a pretreatment regimen may also be associatedwith reduced RAI treatment success.7 Additionally, themajority of patients undergoing RAI and virtually allpatients undergoing total thyroidectomy will have resid-ual hypothyroidism following treatment.

From the Department of Otolaryngology–Head and Neck Surgery,Medical University of South Carolina, Charleston, South Carolina,U.S.A.

Editor’s Note: This Manuscript was accepted for publicationAugust 26, 2013.

The authors have no funding, financial relationships, or conflictsof interest to disclose.

Send correspondence to Colin Fuller, MD, Clinical Research Fel-low, Department of Otolaryngology–Head and Neck Surgery, MedicalUniversity of South Carolina, 135 Rutledge Ave. MSC 550, Charleston,SC 29425-5500. E-mail: [email protected]

DOI: 10.1002/lary.24406

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346

to detect the OR of requiring methimazole before andafter treatment. The results were statistically signifi-cant with an OR of 40.34 (95% CI: 7.78 to 209.09)(Fig. 4).

Adverse EventsAdverse events (AEs) of treatment were tallied and

grouped as either serious or nonserious. Serious AEs(SAEs) were defined as any adverse event that was fatal,life threatening, resulted in significant or persistent dis-ability or incapacity, or resulted in hospitalization, orany adverse event categorized as a SAE by the originalstudy authors. A summary of all AEs is expressed inFigure 5.

Across all articles, there were two AEs that couldhave been considered serious.18,22 One subject sufferedendoscopy-confirmed vocal fold palsy persistent at 1-month follow-up. The subject was subsequently lost tofollow-up, and therefore resolution could not be con-firmed. The remaining SAE was a case of intraoperativediffuse glandular hemorrhage. The RFA procedure wasdiscontinued. The article’s description of this eventmakes no reference to any airway distress, and the only

intervention required was a 3-day course of oral analge-sics. No hematoma was evident on ultrasound 1 monthlater. The same complication occurred in a subsequentPEI treatment for the same subject. There were no fatalor life-threatening complications, nor any AEs requiringhospitalization in any included trials.

Nonserious AEs were any other untoward effects oftreatment not controllable with over-the-counter analge-sics. Intraoperative pain and discomfort that did notresult in discontinuation of the procedure was alsoexcluded. Eleven nonserious AEs satisfied these criteria,including self-limiting fever,19 edema requiring a singledose of betamethasone,24 first-degree burn at the site ofelectrode insertion,22 and hematoma.22

DISCUSSIONThis meta-analysis has some important limitations.

The lack of a control arm is one limitation, due to thedeficiency of controlled trials uncovered in the literature.This most especially limits the applicability of the moresubjective elements of the analysis, such as symptomscore and cosmetic score. Again, this systematic reviewunderlines the need for higher-quality research directly

Fig. 2. Nodule volume change. (A) Pooled nodule volume change. (B) Hot nodule subgroup volume change. (C) Cold nodule subgroup vol-ume change. CI 5 confidence interval; IV 5 inverted variance; SD 5 standard deviation.


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3cm x 3cm x 2cm = 9,4 cm3 = 9,4 ml3cm x 3cm x 3cm =14,2cm3=14,2ml











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comparing RFA, PEI, and PLA for the various benignthyroid nodules that may require intervention. Addition-ally, the articles that satisfied our inclusion criteria hadsome overlap in authorship, with seven of the nine stud-ies deriving from one of two author groups. Therefore,the data available for meta-analysis may not be as rigor-ous and generalizable as data from a higher number ofindependent centers. Operator experience has been sug-gested as a factor affecting treatment efficacy,18 and thusthe generalizability of the results may be reduced by therelatively high level of RFA experience in these twoauthor groups compared to the average practicing endo-crinologist, surgeon, or radiologist. Furthermore, occultbias not detected by the authors of this meta-analysismight be magnified by its repeated presence in the data.

However, the lack of variety in authorship may beevidence that the technique is relatively underutilized inmany regions where its introduction or expansion wouldlead to better patient care. Although the authors do notpresently submit survey data to this effect, it is ourbelief that there is sufficient evidence to supportexpanded use of radiofrequency techniques to treat goi-ter and AFTNs in the United States.

At least 60,000 thyroidectomies, hemithyroidecto-mies, and partial thyroidectomies are performed in theUnited States each year, based on a study of 2009 data.8

Based on the same data, nontoxic nodular goiter is theindication in 36% of cases, making it the most commonindication for this procedure. The subset of these proce-dures for which consideration of RFA might prove

Fig. 3. Symptom and cosmetic score change. (A) Visual analog scale score change. Values scored on a 10-point scale (0–10) of severity ofsymptoms related to neck mass. (B) Physician-rated cosmetic score change. Values scored on a 4-point scale (1–4). (C) Combined symp-tom/cosmetic scale score change. Values scored on a 6-point scale (0–6) describing the severity of three symptoms (pressure, dysphagia,cosmesis), each scored independently from 0 to 2. CI 5 confidence interval; IV 5 inverted variance; SD 5 standard deviation.

Fig. 4. Change in requirement of methimazole. CI 5 confidence interval; M-H 5 Mantel-Haenszel odds ratio. [Color figure can be viewed inthe online issue, which is available at wileyonlinelibrary.com.]


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Symptoms

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comparing RFA, PEI, and PLA for the various benignthyroid nodules that may require intervention. Addition-ally, the articles that satisfied our inclusion criteria hadsome overlap in authorship, with seven of the nine stud-ies deriving from one of two author groups. Therefore,the data available for meta-analysis may not be as rigor-ous and generalizable as data from a higher number ofindependent centers. Operator experience has been sug-gested as a factor affecting treatment efficacy,18 and thusthe generalizability of the results may be reduced by therelatively high level of RFA experience in these twoauthor groups compared to the average practicing endo-crinologist, surgeon, or radiologist. Furthermore, occultbias not detected by the authors of this meta-analysismight be magnified by its repeated presence in the data.

However, the lack of variety in authorship may beevidence that the technique is relatively underutilized inmany regions where its introduction or expansion wouldlead to better patient care. Although the authors do notpresently submit survey data to this effect, it is ourbelief that there is sufficient evidence to supportexpanded use of radiofrequency techniques to treat goi-ter and AFTNs in the United States.

At least 60,000 thyroidectomies, hemithyroidecto-mies, and partial thyroidectomies are performed in theUnited States each year, based on a study of 2009 data.8

Based on the same data, nontoxic nodular goiter is theindication in 36% of cases, making it the most commonindication for this procedure. The subset of these proce-dures for which consideration of RFA might prove

Fig. 3. Symptom and cosmetic score change. (A) Visual analog scale score change. Values scored on a 10-point scale (0–10) of severity ofsymptoms related to neck mass. (B) Physician-rated cosmetic score change. Values scored on a 4-point scale (1–4). (C) Combined symp-tom/cosmetic scale score change. Values scored on a 6-point scale (0–6) describing the severity of three symptoms (pressure, dysphagia,cosmesis), each scored independently from 0 to 2. CI 5 confidence interval; IV 5 inverted variance; SD 5 standard deviation.

Fig. 4. Change in requirement of methimazole. CI 5 confidence interval; M-H 5 Mantel-Haenszel odds ratio. [Color figure can be viewed inthe online issue, which is available at wileyonlinelibrary.com.]


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Adverse Effects

Serious :2/277 (no death)

Non-Serious:10/277

No RCT

Few Control groups

❖ Indications

❖ Benign nodules

❖ with clinical Symptoms

❖ Esthetic problem

❖ Autonomous nodule

❖ Malignant nodules

❖ Recurrent malignancy (in the bed or neck)

Korean Journal of Radiology

Review Article ^http://dx.doi.org/10.3348/kjr.2012.13.2.117 .pISSN 1229-6929 • elSSN 2005-8330Korean J Radiol 2012;13(2):117-125 J

Radiofrequency Ablation of Benign Thyroid Nodules andRecurrent Thyroid Cancers: Consensus Statement andRecommendationsDong Gyu Na, MD^ Jeong Hyun Lee, MD\ So Lyung Jung, MD^ Ji-hoon Kim, MU\ Jin Yong Sung, MD^Jung Hee Shin, MD^ Eun-Kyung Kim, MD^ Joon Hyung Lee, MD^ Dong Wook Kim, MD^Jeong Seon Park, MD'°, Kyu Sun Kim, MD', Seon Mi Baek, MD", Younghen Lee, MD", Semin Chong, MD",Jung Suk Sim, MD", Jung Yin Huh, MD^ Jae-Ik Bae, MD", Kyung Tae Kim, MD'',Song Yee Han, MD'', Min Young Bae, MD", Yoon Suk Kim, MD'°, Jung Hwan Baek, MD';for Korean Society of Thyroid Radiology (KSThR), Korean Society of Radiology'Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736,Korea; ^Department of Radiology, Human Medical Imaging & Intervention Center, Seoul 137-902, Korea; 'Department of Radiology, Seoul St.Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea; "Department of Radiology, Seoul National UniversityCollege of Medicine, Seoul 110-744, Korea, 'Department of Radiology and Thyroid Center, Daerim St. Mary's Hospital, Seoul 150-070, Korea;'Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710,Korea; 'Department of Radiology, Yonsei Univsersity College of Medicine, Seoul 120-752, Korea; 'Department of Radiology, Dong-A UniversityMedical Center, Busan 602-713, Korea; 'Department of Radiology, Busan Paik Hospital, Inje University College of Medicine, Busan 633-165, Korea;'"Department of Radiology, Hanyang University College of Medicine, Hanyang University Hospital, Seoul 133-792, Korea, "Department ofRadiology, Haeundae Healings Hospital, Busan 613-101, Korea; '^Department of Radiology, Ansan Hospital, Korea University Medical College,Ansan 425-707, Korea; "Department of Radiology and Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine,Seoul 156-755, Korea; '"Department of Radiology, Mothers' Clinic, Seongnam 463-821, Korea; '^Department of Radiology, CHA University Collegeof Medicine, Gangnam CHA Hospital, Seoul 135-081, Korea; "Department of Radiology, Ajou University School of Medicine, Suwon 443-721,Korea; "Department of Radiology, UNMEC Clinic, Daegu 704-910, Korea; "Department of Radiology, Dr. Han's Breast Clinic, Seoul 135-892, Korea;"Department of Radiology, Myung Jindan Health Care Center, Seoul 157-927, Korea; ^"Department of Radiology, Thyroid Clinic, Philip MedicalCenter, Seoul 150-042, Korea

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery inpatients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society ofThyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. Theserecommendations are based on a comprehensive analysis of the current literature, the results of muLticenter studies, andexpert consensus.Index terms: Thyroid, radiofrequency; Thyroid, ethanol; Thyroid, US; Thyroid, nodules; Thyroid, recurrent cancers; Thyroid,intervention

Received November 3, 2011; accepted after revision January 13, 2012.Corresponding author: Jung Hwan Baek, MD, Department of Radiology and Research Institute of Radiology, University of Ulsan Collegeof Medicine, Asan Medical Center, 88 Oylimpic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.• Tel: (822) 3010-4352 • Fax: (822) 476-0090 • E-mail: [email protected] is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (ht tp: / /creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium,provided the original work is properly cited.

kjronline.org Korean J Radiol 13(2), Mar/Apr 2012 117

2012

Korean Journal of Radiology

Review Article ^http://dx.doi.org/10.3348/kjr.2012.13.2.117 .pISSN 1229-6929 • elSSN 2005-8330Korean J Radiol 2012;13(2):117-125 J

Radiofrequency Ablation of Benign Thyroid Nodules andRecurrent Thyroid Cancers: Consensus Statement andRecommendationsDong Gyu Na, MD^ Jeong Hyun Lee, MD\ So Lyung Jung, MD^ Ji-hoon Kim, MU\ Jin Yong Sung, MD^Jung Hee Shin, MD^ Eun-Kyung Kim, MD^ Joon Hyung Lee, MD^ Dong Wook Kim, MD^Jeong Seon Park, MD'°, Kyu Sun Kim, MD', Seon Mi Baek, MD", Younghen Lee, MD", Semin Chong, MD",Jung Suk Sim, MD", Jung Yin Huh, MD^ Jae-Ik Bae, MD", Kyung Tae Kim, MD'',Song Yee Han, MD'', Min Young Bae, MD", Yoon Suk Kim, MD'°, Jung Hwan Baek, MD';for Korean Society of Thyroid Radiology (KSThR), Korean Society of Radiology'Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736,Korea; ^Department of Radiology, Human Medical Imaging & Intervention Center, Seoul 137-902, Korea; 'Department of Radiology, Seoul St.Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea; "Department of Radiology, Seoul National UniversityCollege of Medicine, Seoul 110-744, Korea, 'Department of Radiology and Thyroid Center, Daerim St. Mary's Hospital, Seoul 150-070, Korea;'Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710,Korea; 'Department of Radiology, Yonsei Univsersity College of Medicine, Seoul 120-752, Korea; 'Department of Radiology, Dong-A UniversityMedical Center, Busan 602-713, Korea; 'Department of Radiology, Busan Paik Hospital, Inje University College of Medicine, Busan 633-165, Korea;'"Department of Radiology, Hanyang University College of Medicine, Hanyang University Hospital, Seoul 133-792, Korea, "Department ofRadiology, Haeundae Healings Hospital, Busan 613-101, Korea; '^Department of Radiology, Ansan Hospital, Korea University Medical College,Ansan 425-707, Korea; "Department of Radiology and Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine,Seoul 156-755, Korea; '"Department of Radiology, Mothers' Clinic, Seongnam 463-821, Korea; '^Department of Radiology, CHA University Collegeof Medicine, Gangnam CHA Hospital, Seoul 135-081, Korea; "Department of Radiology, Ajou University School of Medicine, Suwon 443-721,Korea; "Department of Radiology, UNMEC Clinic, Daegu 704-910, Korea; "Department of Radiology, Dr. Han's Breast Clinic, Seoul 135-892, Korea;"Department of Radiology, Myung Jindan Health Care Center, Seoul 157-927, Korea; ^"Department of Radiology, Thyroid Clinic, Philip MedicalCenter, Seoul 150-042, Korea

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery inpatients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society ofThyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. Theserecommendations are based on a comprehensive analysis of the current literature, the results of muLticenter studies, andexpert consensus.Index terms: Thyroid, radiofrequency; Thyroid, ethanol; Thyroid, US; Thyroid, nodules; Thyroid, recurrent cancers; Thyroid,intervention

Received November 3, 2011; accepted after revision January 13, 2012.Corresponding author: Jung Hwan Baek, MD, Department of Radiology and Research Institute of Radiology, University of Ulsan Collegeof Medicine, Asan Medical Center, 88 Oylimpic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.• Tel: (822) 3010-4352 • Fax: (822) 476-0090 • E-mail: [email protected] is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (ht tp: / /creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium,provided the original work is properly cited.

kjronline.org Korean J Radiol 13(2), Mar/Apr 2012 117

Benign Nodule Recurrent CancerBenign cytology ( twice ) diagnosis of recurrence

US features (nodule and Neck) US features (surrounding structures)Nodule Volume Tumor VolumeSymptom Score Lab tests (TG,anti-TG)Cosmetic Score CT (selected Cases)

Laboratory TestsCT, MRI (selected cases)

mCT Technetium (hot nodule)

2012

Case Workup

VASCULAR AND INTERVENTIONAL RADIOLOGY

Vascular and interventional radiology radiofrequency ablationof benign thyroid nodules and recurrent thyroid cancers:literature review

Irene Chiara De Bernardi • Chiara Floridi • Alessandra Muollo •

Roberta Giacchero • Gian Lorenzo Dionigi • Alfonso Reginelli • Gianluca Gatta •

Vito Cantisani • Roberto Grassi • Luca Brunese • Gianpaolo Carrafiello

Received: 27 April 2014 / Accepted: 30 April 2014 / Published online: 14 June 2014! Italian Society of Medical Radiology 2014

Abstract Thermal radiofrequency ablation is a relativelynew, minimally invasive modality employed as an alter-

native to surgery in patients with benign thyroid nodules

and recurrent thyroid cancers. Different recommendationsare necessary for the optimal use of radiofrequency abla-

tion for thyroid nodules. These recommendations are based

on a comprehensive analysis of the current literature, theresults of multicenter studies, and expert consensus.

Keywords Thyroid ! US ! CEUS ! Radiofrequency !Ablation ! Thyroid nodules ! Thyroid recurrent cancers !Intervention radiology

Introduction

Thyroid nodules are very common in the adult population

with a prevalence of 20–76 % [1]. The incidence of thyroid

nodules has increased with the recently increased use ofthyroid ultrasonography (US) [1]. Although most thyroid

nodules are benign and do not require treatment, some

benign nodules may require treatment for associatedsymptoms and/or because of cosmetic problems [2, 3]. As

curative surgery has several drawbacks and the efficacy of

thyroid hormone-suppressive therapy has not yet beendetermined, nonsurgical, minimally invasive treatment

modalities, such as ethanol ablation (EA), percutaneous

laser ablation, and radiofrequency (RF) ablation, have beenused to treat thyroid nodules [2–7].

Thermal ablation using radiofrequency is a new, mini-

mally invasive modality that may be an alternative tosurgery in selected patients with benign thyroid nodules

and recurrent thyroid cancers [8].

This paper provides information regarding the basicprinciples, indications, devices, and techniques that have

been especially designed to optimize thyroid RF ablation,

as well as the clinical results and complications.

Principles of radiofrequency ablation (RFA)

RF ablation uses the heat generated from high-frequencyalternating electric current oscillating between 200 and

1,200 kHz [2, 9]. Application of RF power to tissue agi-

tates tissue ions as they attempt to follow the changes indirection of the alternating current. Such agitation creates

frictional heat around the electrode [2, 9]. Although this

heat creates immediate damage to tumor tissue, the damageis significant only in regions very close to (thus, within a

few mm of) the electrode. Simultaneously, tumor tissue

more remote from the electrode is heated slowly, viathermal conduction from the hot region adjacent to the

electrode [10–12].

I. C. De Bernardi (&) ! C. Floridi ! A. Muollo !G. L. Dionigi ! G. CarrafielloUniversity of Insubria, Varese, Italye-mail: [email protected]

R. GiaccheroUniversity of Milan, Milan, Italy

A. Reginelli ! G. GattaSecond University of Naples, Naples, Italy

V. CantisaniUniversity of Rome ‘‘La Sapienza’’, Rome, Italy

R. GrassiDepartment of Radiology, Second University of Naples,Caserta, Italy

L. BruneseUniversity of Molise, Campobasso, Italy

123

Radiol med (2014) 119:512–520

DOI 10.1007/s11547-014-0411-2

❖ Indications

❖ Benign nodules (3 Groups)

❖ “Symptomatic patients"

❖ “Cosmetic Problems"

❖ "Thyrotoxicosis

❖ Malignant nodules (exceptional cases)

❖ Recurrent malignancy (in the bed or neck)

2014

VASCULAR AND INTERVENTIONAL RADIOLOGY

Vascular and interventional radiology radiofrequency ablationof benign thyroid nodules and recurrent thyroid cancers:literature review

Irene Chiara De Bernardi • Chiara Floridi • Alessandra Muollo •

Roberta Giacchero • Gian Lorenzo Dionigi • Alfonso Reginelli • Gianluca Gatta •

Vito Cantisani • Roberto Grassi • Luca Brunese • Gianpaolo Carrafiello

Received: 27 April 2014 / Accepted: 30 April 2014 / Published online: 14 June 2014! Italian Society of Medical Radiology 2014

Abstract Thermal radiofrequency ablation is a relativelynew, minimally invasive modality employed as an alter-

native to surgery in patients with benign thyroid nodules

and recurrent thyroid cancers. Different recommendationsare necessary for the optimal use of radiofrequency abla-

tion for thyroid nodules. These recommendations are based

on a comprehensive analysis of the current literature, theresults of multicenter studies, and expert consensus.

Keywords Thyroid ! US ! CEUS ! Radiofrequency !Ablation ! Thyroid nodules ! Thyroid recurrent cancers !Intervention radiology

Introduction

Thyroid nodules are very common in the adult population

with a prevalence of 20–76 % [1]. The incidence of thyroid

nodules has increased with the recently increased use ofthyroid ultrasonography (US) [1]. Although most thyroid

nodules are benign and do not require treatment, some

benign nodules may require treatment for associatedsymptoms and/or because of cosmetic problems [2, 3]. As

curative surgery has several drawbacks and the efficacy of

thyroid hormone-suppressive therapy has not yet beendetermined, nonsurgical, minimally invasive treatment

modalities, such as ethanol ablation (EA), percutaneous

laser ablation, and radiofrequency (RF) ablation, have beenused to treat thyroid nodules [2–7].

Thermal ablation using radiofrequency is a new, mini-

mally invasive modality that may be an alternative tosurgery in selected patients with benign thyroid nodules

and recurrent thyroid cancers [8].

This paper provides information regarding the basicprinciples, indications, devices, and techniques that have

been especially designed to optimize thyroid RF ablation,

as well as the clinical results and complications.

Principles of radiofrequency ablation (RFA)

RF ablation uses the heat generated from high-frequencyalternating electric current oscillating between 200 and

1,200 kHz [2, 9]. Application of RF power to tissue agi-

tates tissue ions as they attempt to follow the changes indirection of the alternating current. Such agitation creates

frictional heat around the electrode [2, 9]. Although this

heat creates immediate damage to tumor tissue, the damageis significant only in regions very close to (thus, within a

few mm of) the electrode. Simultaneously, tumor tissue

more remote from the electrode is heated slowly, viathermal conduction from the hot region adjacent to the

electrode [10–12].

I. C. De Bernardi (&) ! C. Floridi ! A. Muollo !G. L. Dionigi ! G. CarrafielloUniversity of Insubria, Varese, Italye-mail: [email protected]

R. GiaccheroUniversity of Milan, Milan, Italy

A. Reginelli ! G. GattaSecond University of Naples, Naples, Italy

V. CantisaniUniversity of Rome ‘‘La Sapienza’’, Rome, Italy

R. GrassiDepartment of Radiology, Second University of Naples,Caserta, Italy

L. BruneseUniversity of Molise, Campobasso, Italy

123

Radiol med (2014) 119:512–520

DOI 10.1007/s11547-014-0411-2

❖ No New Data

❖ Just recommendations

❖ procedures

❖ patient selection

❖ No Society Recommendation

2014

IF 2,49

❖ The new guidance discusses the use of ethanol and radiofrequency for ablation of overactive nodules, options that have been used primarily outside the United States. The guidance notes that these approaches “can be considered in select patients where RAI, surgery or long-term ATD are inappropriate, contraindicated, or refused, and expertise in these procedures is available

❖ Hyperthyroidism

❖ Autonomous nodule

2015

The use of radiofrequency ablation (RFA) with local anesthesia in the treatment of recurrent thyroid cancer has been associated with a mean volume reduction that ranges between approximately 55-95% (881;882), and complete disappearance of the metastatic foci in 40-60% of the cases (845;882;883). As with alcohol ablation, multiple treatment sessions are often required. Complications include discomfort, pain, skin burn and changes in the voice (884). Similar to alcohol ablation techniques, it appears that RFA may be most useful in high risk surgical patients or in patient refusing additional surgery rather than as a standard alternative to surgical resection of metastatic disease (883-885). More recently, preliminary findings using ultrasound guided laser ablation for treatment of cervical lymph node metastases have been reported (886).

❖ Nodule Guideline - Cancer❖ [C21] Radiofrequency or Laser Ablation

2015

Efficacy and Safety of Radiofrequency Ablation VersusObservation for Nonfunctioning Benign Thyroid Nodules:A Randomized Controlled International Collaborative Trial

Maurilio Deandrea,1 Jin Yong Sung,2 Paolo Limone,1 Alberto Mormile,1 Francesca Garino,1

Federico Ragazzoni,1 Kyu Sun Kim,2 Ducky Lee,3 and Jung Hwan Baek4

Background: Percutaneous radiofrequency thermal ablation (RFA) has been reported as an effective tool for themanagement of benign thyroid nodules (BTN). However, large, randomized controlled trials (RCTs) arelacking.Objective: The aims of this study were to assess the volume reduction of BTN after a single RFA performedusing the moving-shot technique and to compare the volume reduction obtained in patients treated in twocenters with different experience of the moving-shot technique.Method: This study was an international prospective RCT. It was carried out at the Mauriziano Hospital (Turin,Italy) and the Asan Medical Center (Seoul, Korea). Eighty patients harboring solid, compressive, nonfunc-tioning BTN (volume 10–20 mL) were enrolled. Twenty patients in each country were treated by RFA using a18-Gauge internally cooled electrode (group A); 20 nontreated patients in each country were followed ascontrols (group B).Results: At six months, BTN volume significantly decreased in group A (15.1 – 3.1 mL vs. 4.2 – 2.7 mL;p < 0.0001), whereas it remained unchanged in group B (14.4 – 3.3 mL vs. 15.2 – 3.5 mL). The baseline volumewas larger in the Italian series (16.4 – 2.5 mL vs. 13.9 – 3.3 mL, p = 0.009). However, at six months, there wasno significant difference between the Korean group and the Italian group (3.7 – 2.9 mL vs. 5.5 – 2.2 mL). Bothcosmetic and compressive symptoms significantly improved (3.6 – 0.5 vs. 1.7 – 0.4 and 3.6 – 1.9 vs. 0.4 – 0.7,respectively; p < 0.001). No side effects occurred.Conclusions: RFA was effective in reducing the volume of BTN. The outcome was similar in centers withdifferent experience in the moving-shot technique.

Introduction

Thyroid nodules are very common in the generalpopulation, with a prevalence of about 50% in subjects

older than 60 years of age undergoing neck ultrasound (US)examination (1). In the majority of cases, thyroid nodules arebenign, but they can be responsible for compression of localstructures, which can result in discomfort and a decreasedquality of life. Large compressive benign thyroid nodules(BTN) may also result in life-threatening conditions, due to thepossible onset of acute respiratory crisis. Surgery and radio-iodine therapy are the main therapeutic approaches for com-pressive or toxic nodules (1–3). However, surgery is charged bythe possibility of immediate complications such as wound in-fection and compressive hematomas (requiring re-intervention)

in 0.2–2.7% of cases, and by laryngeal recurrent nerve palsy andhypoparathyroidism, which can either be transient (in 2–28% ofcases) or permanent (in 0.2–3% of cases) (4–7). Moreover, inthe case of surgery for recurrent goiter, the frequency of suchcomplications increases further (up to 37% for transient and7.8%, for permanent damage) (4–7). In addition, a number ofpatients with BTN with an indication for surgery refuse thisapproach. In some of these cases, radioiodine therapy may beineffective, especially in large nonfunctioning nodules (8,9).

Minimally invasive therapeutic options have been pro-posed to treat BTN when surgery or radioiodine is refused,contraindicated, or ineffective (10). Percutaneous radio-frequency ablation (RFA) is a minimally invasive procedurethat has been used to treat both malignant and benign tumornodules in many organs (11–15). RFA also represents a

1Endocrinology, Diabetes, and Metabolism Unit, A.O. Ordine Mauriziano di Torino, ‘‘Umberto I’’ Hospital, Turin, Italy.Departments of 2Radiology and 3Internal Medicine, Thyroid Center, Daerim St. Mary’s Hospital, Seoul, Korea.4Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul,

Korea.

THYROIDVolume 25, Number 8, 2015ª Mary Ann Liebert, Inc.DOI: 10.1089/thy.2015.0133

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Inclusion Critirea Exclusion Critirea

older than 18 years of age nodules w/ US features suggestive of malignancy

resence of a solid thyroid nodule (solid portion >70% (volume between 10 and 20 mL)

treatments for the thyroid nodule in the six months prior to enrollment in this study

presence of pressure symptoms or cosmetic problems

confirmation of benign findings in at least two separate US- guided core needle or fine-needle aspiration (FNA)

normal serum levels of thyroid hormones, thyrotropin (TSH), and calcitonin





Introduction






Korea.


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n=80

n=40observation

n=40RFA

n=20 n=20 n=20 n=20





Introduction






Korea.


890

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between the needle or the electrode tip to the expected lo-cation of the recurrent laryngeal nerve, thus minimizing therisks of injury to the nerve and/or to the esophagus. At the endof the procedure, an ice pack was applied to the patient’s neckwith mild compression, and the patient underwent observa-tion for about two hours.

Follow-up

The outcomes were assessed by investigators ( J.Y.S. andK.S.K. in Korea; F.R. and F.G. in Italy) who were blinded tothe group allocation. US examination was performed in orderto measure the nodule volume (and also the cystic area vol-ume), and compressive and cosmetic scores were recorded inboth treated and untreated subjects at one month and sixmonths after enrollment. Moreover, serum concentrations ofTSH, fT4, thyroglobulin, and calcitonin, as well as the titersof TgAb and TPOAb, were measured in both treated patientsand in controls at a six-month follow-up.

Study end points

The primary end points of the current study were (a) thequantitative volume reduction ratio of BTN between control(40 patients) and RFA (40 patients) at six months after theprocedure, and (b) the comparison of the volume reductionratio of the patients (20 vs. 20) of two centers after RFA. TheKorean center (the ‘‘more experienced group’’ in this field)had an experience of about 3000 cases of thyroid RFA; theItalian center (the ‘‘less experienced group’’ in this field) had asignificant experience in interventional US-guided therapies(both PEI and RFA by other devices), and had previouslytreated 50 cases of BTN with the moving-shot technique, afteran initial instruction given by a Korean radiologist ( J.H.B.).

The secondary end points for the clinical outcomes in-cluded the therapeutic success rate, in terms of improvementin symptoms and cosmetic problems, and the number ofmajor complications.

Major and minor complications were defined according tothe recommendations of the Society of Interventional Radi-ology (27).

Statistical analysis

Continuous variables describing patients and nodules wereexpressed as median with interquartile range; direct com-parisons were performed with a nonparametric test for un-paired samples (Mann–Whitney U-test). Two-sided p-valuesof <0.05 were considered statistically significant. Analysiswas performed using Analyse-itTM Software v3.76.5 (Leeds,United Kingdom).

Sample size calculation for the study was performed asfollows. Considering a volume reduction of 35% significancein the treated nodules in comparison with an expected max-imum volume reduction of 5% in the control group, enrol-ment of 40 patients for each group could guarantee statisticalpower of more than 80%.

Thirteen percent was chosen as the clinically relevantdifference between the experienced and less experiencedgroup, according to previous data of US measurement–remeasurement variability (the results of previous studieswere 5.1–6.6%, and relevant difference in the primary end-point was set as 13%, which is double 6.6%) (28,29).

Results

Baseline characteristics of patients in group A and group B areshown in Table 1. BTN volume, function, and US characteristics

Table 1. Demographic Data of Study Population

Korea Italy

RF Control RF Control p-Value*

Sex (M:F) 2:18 1:19 4:16 1:19 0.71Mean age 39.5 – 9.6 (26–60) 52.2 – 10.3 (35–71) 54.3 – 13.3 (34–83) 62.5 – 12.7 (37–82) 0.05Nodule largest

diameter (cm)4.0 – 0.5 (3.1–4.9) 2.8 – 0.3 (2.2–3.2) 4.0 – 0.4 (3.4–4.6) 3.9 – 0.5 (3.0–5.2) 0.95

Nodule volume (mL) 13.9 – 3.1 (10–19.7) 13.7 – 3.2 (10–19.8) 16.4 – 3.4 (12.6–25.1) 15.0 – 3.2 (9.4–20.2) 0.009Symptom score 3.4 – 0.9 (2–5) 3.1 – 0.8 (2–5) 4.0 – 2.7 (0–8) 3.9 – 2.1 (0–7) 0.001Cosmetic score 4.0 – 0 4.0 – 0 3.2 – 0.7 (2–4) 2.8 – 0.7 (1–4) 0.001

Values are reported as mean – standard deviation (SD). Range is reported in parentheses.*Comparison between Korean and Italian RFA groups.

Table 2. Treatment Parameters of RFA

Korea (n = 20) Italy (n = 20) p-Value

Mean ablation time (s) 435.8 – 142.4 819.5 – 225.9 0.0001Mean RF power (Watt) 75.3 – 10.4 49.7 – 4.7 0.0001Total energy ( Joule) 33,068.0 – 13,800.5 40,364.7 – 10,801.1 0.72Energy/mL ( J/mL) 2436.3 – 916.2 2521.7 – 803.6 0.84

Values are reported as mean – SD. Significant values are shown in bold.RFA, radiofrequency ablation.

892 DEANDREA ET AL.

faster w/ higher power

longer w/ less power

Same Energy





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Korea.


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did not significantly differ between the groups at baseline (Table1). The F/M ratio was similar in the two countries, while thegroup of patients from Korea was younger than the group ofpatients treated in Italy (Table 1).

Hormonal evaluation

All the patients were euthyroid at baseline, and showednormal calcitonin levels. After treatment, thyroid function, aswell as calcitonin levels, did not change. Thyroglobulin waselevated at baseline, and decreased significantly after treat-ment but did not normalize (Table 1). A minority of patientsin both countries (8/40) had elevated titers of thyroid auto-antibodies (more than twice the minimum value adopted forevery laboratory), and the pattern did not change over time ineither the treated or the control group.

Treatment modality

The treatment protocol described above allowed us tosupply the same energy per milliliter of nodule volume inboth countries ( p = n.s.). However, the treatment method wasdifferent: while in Korea the operators distributed morepower in a shorter time, in Italy the treatment was longer andless powerful (Table 2).

In all patients, RFA was safe and well tolerated. No sig-nificant side effects were observed, and no patient neededhospitalization after treatment. Local anesthesia preventedpain on needle insertion and electrode positioning. During theprocedure, all patients were asymptomatic, with the exceptionof a mild sensation of heat in the neck, which did not require

interrupting the treatment. After the procedure, no local ede-ma, pain, or other adverse effects were detected (Table 2).

Nodule volume

After treatment, the BTN volume significantly decreasedin the treated patients as a whole (group A; 15.1 – 3.1 atbaseline, 8.3 – 2.9 mL at 1 month, 4.2 – 2.7 mL at 6 months;p < 0.0001), whereas it remained unchanged in group B (14.4 –3.3 mL at baseline, 14.8 – 3.5 mL at 1 month, 15.2 – 3.5 mL at6 months; p = n.s.; Table 3).

When the results obtained in the Korean and the Italiancenters were compared, although the baseline nodule volumewas larger in the Italian series ( p = 0.009 vs. Korean), in bothcountries shrinkage was important, and no significant dif-ference in volume reduction was seen at either the one-monthor six-month evaluation (RFA group Korea 13.9 – 3.3 atbaseline, 7.0 – 2.6 mL at 1 month, 3.7 – 2.9 mL at 6 months;RFA group Italy 16.4 – 2.5 at baseline, 9.9 – 2.7 mL at 1month, 5.5 – 2.2 mL at 6 months; p = n.s.). Thirty-eight out of40 treated nodules showed shrinkage of >50%. Data and re-sults in the different groups are shown in Table 4.

Symptom score and clinical evaluation

The symptom score progressively improved in the treatedpatients both for compressive and for cosmetic symptoms. Ingroup A, the compressive score decreased from 3.6 – 1.9 atbaseline to 0.4 – 0.7 at the six-month evaluation ( p < 0.0001),and the cosmetic score decreased from 3.6 – 0.5 at baseline to1.7 – 0.84 at the six-month evaluation ( p < 0.0001). The re-sults were similar in the treated groups in both Korea andItaly. However, group B showed no change in the follow-upperiod (Table 4).

Discussion

US-guided minimally invasive procedures represent analternative to surgery for the treatment of benign thyroidnodules, which grow and become symptomatic due to com-pressive symptoms. These treatments achieve the relief ofneck complaints in most cases, are less expensive than sur-gery, preserve thyroid function, and can be performed on anoutpatient basis. The percutaneous ethanol injection is thetreatment of choice for thyroid cysts or predominantly cysticnodules due to its efficacy and the scarcity of adverse effects(30). Laser thermal ablation is a consolidated technique

Table 3. Comparison of Clinical CharacteristicsBetween RFA and Control Groups at Six Months

OutcomeRFA

(n = 40)Controls(n = 40) p-Value

% Volume reduction [IQR] 71 [21] - 3 [23] 0.0001Symptom score 0.4 – 0.7 3.3 – 1.7 0.0001Cosmetic score 1.7 – 0.8 3.5 – 0.7 0.0001TSH (lIU/mL) 0.9 – 0.8 1.0 – 0.9 0.190fT4 (pg/mL) 10.8 – 2.9 11.9 – 2.0 0.05Thyroglobulin (ng/mL) 31.5 – 38 13.6 – 22 0.02

Values are mean – SD; volume reduction values are reported asmedian.

IQR, interquartile range; TSH, thyrotropin; fT4, free thyroxine.

Table 4. Comparison of Treatment Outcomes Six Months Following RFA Between Korea and Italy

Outcomes Korea (n = 20) Italy (n = 20) p-Value Difference* [CI]

Primary end point% Volume reduction [IQR] 77 [25] 66 [24] 0.07 6.23 [ - 3.67 to 16.13]

Secondary end pointsSymptom score 0.4 – 0.6 0.6 – 1.18 0.529Cosmetic score 2.05 – 0.75 1.4 – 0.9 0.429Therapeutic success (%) 90 100Major complications None None > 0.99

Values of secondary end points are expressed as mean – SD. Therapeutic success is considered as an improvement in symptoms andcosmetic problems.

*Comparison of RF ablation groups between Korea and Italy.

RADIOFREQUENCY ABLATION FOR NONFUNCTIONING BENIGN THYROID NODULES 893

Technique

Advanced Ultrasound Skills

Oblique approachVertical approach

Radiofrequency Ablation

200-1200 KHz

friction heat

Radiofrequency Ablation

Fixed electrode technique

- ablate completely all the cancers

- effective in larger organs, liver, lungs

Moving-Shot Technique

Tree Dimension Treatment

Trans-Isthmic Access

Clearly visible anatomical

Prevent back leakage of hot liquid

Stability on swallowing,gag, or cough

Trans-isthmic approach: 5 AsAppearance

Trans-isthmic approach: 5 As

Alignment

Appearance

Target location


Alignment

Advance

Appearance

Target location


Alignment

Advance

All the length

Appearance

Target location

Seeing All the Length


Alignment

Advance

All the length

Appearance

Target locationAblation

Steps for Successful RFA

❖ Surgical Anatomy Familiarity

❖ Ultrasound Principles

❖ Ultrasound FNA experience

❖ Radiofrequency Training

Case 1 77 y/o women, isoechoic nodule, with hipoechoic halo, peripheral vascularization.

2.39 cm x 2,0cm x 1,39cm ( 3,47ml)bethesda II

Very Symptomatic

Case 1 77 y/o women, isoechoic nodule, with hipoechoic halo, peripheral vascularization.

2.39 cm x 2,0cm x 1,39cm ( 3,47ml)bethesda II

Very Symptomatic

1 month

Case 1 2,39 cm x 2,0cm x 1,39cm ( 3,47ml): 1,36cm x 1,36cm x 1,22cm (1,22ml)

% Volume Reduction = -64,8 %Became Asymptomatic

3 month

acknowledgement

Dr. Jung Suk Sim Dr. Cho

Thank You !

aula de radiofrequencia em nódulos tireoidianos

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