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Published online before print May 20, 2004, 10.1148/radiol.2321021368
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(Radiology 2004;232:272-280.)
© RSNA, 2004

Vascular and Interventional Radiology

Thyroid Tissue: US-guided Percutaneous Laser Thermal Ablation1

Claudio Maurizio Pacella, MD, Giancarlo Bizzarri, MD, Stefano Spiezia, MD, Antonio Bianchini, MD, Rinaldo Guglielmi, MD, Anna Crescenzi, MD, Sara Pacella, MD, Vincenzo Toscano, MD and Enrico Papini, MD

1 From the Departments of Radiology and Diagnostic Imaging (C.M.P., G.B., A.B., A.C., S.P.) and Endocrine, Metabolic, and Digestive Diseases (R.G., E.P.), Ospedale Regina Apostolorum, Via San Francesco 50, 00041 Albano Laziale, Rome, Italy; Department of Physiopathology, La Sapienza University 2nd Campus, Rome, Italy (V.T.); and Surgery Unit of Neck Pathologies, Ospedale Santa Maria del Popolo degli Incurabili, Naples, Italy (S.S.). Received October 21, 2002; revision requested January 7, 2003; final revision received October 23; accepted November 17. Address correspondence to C.M.P. (e-mail: cmpacel@katamail.com).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate in vivo the safety and effectiveness of percutaneous laser thermal ablation (LTA) in the debulking of thyroid lesions.

MATERIALS AND METHODS: Twenty-five adult patients at poor surgical risk with cold nodules (n = 8), autonomously hyperfunctioning thyroid nodules (n = 16), or anaplastic carcinoma (n = 1) underwent LTA. One to four 21-gauge spinal needles were inserted with ultrasonographic (US) guidance into the thyroid lesions. A 300-µm-diameter quartz optical fiber was advanced through the sheath of the needle. Nd:YAG laser was used with output power of 3–5 W. Side effects, complications, and clinical and hormonal changes were evaluated at the end of LTA and during follow-up. Linear regression analysis was used to investigate the correlation between energy delivered and reduction in nodule volume. Volume of induced necrosis and reduction in nodule volume were assessed with US or computed tomography.

RESULTS: LTA was performed without difficulties in 76 LTA sessions. After treatment with 5 W, two patients experienced mild dysphonia, which resolved after 48 hours and 2 months. Improvement of local compression symptoms was experienced by 12 of 14 (86%) patients. Thyroid-stimulating hormone (TSH) was detectable in five of 16 (31%) patients with hyperfunctioning nodules at 6 months after LTA. Volume of induced necrosis ranged from 0.8 to 3.9 mL per session. Anaplastic carcinoma treated with four fibers yielded 32.0 mL of necrosis. Echo structure and baseline volume did not influence response. Energy load and reduction in nodule volume were significantly correlated (r2 = .75, P < .001). Mean nodule volume reduction at 6 months in hyperfunctioning nodules was 3.3 mL ± 2.8 (62% ± 21.4 [SD]) and in cold nodules was 7.7 mL ± 7.5 (63% ± 13.8).

CONCLUSION: LTA may be a therapeutic tool for highly selected problems in the treatment of thyroid lesions.

© RSNA, 2004

Index terms: Interventional procedures, technology, 273.1269 • Lasers, interstitial therapy, 273.1269 • Thyroid, neoplasms, 273.36, 273.37 • Thyroid, US, 273.12986


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Surgery and radioiodine therapy are the established methods for the definitive therapy of malignant lesions of the thyroid gland, but a few patients are not eligible for these treatments. In patients at poor surgical risk, the treatment of local or distant recurrence of thyroid carcinoma with scanty uptake of iodine 131 is problematic, and the therapeutic strategy for the debulking of hypofunctioning nodules that cause compressive symptoms is still unsatisfactory (1).

Ultrasonography (US)-guided ablation of thyroid tissue with percutaneous ethanol injection has been performed for autonomously hyperfunctioning thyroid nodules and hypofunctioning (cold) thyroid nodules (2–8). The procedure is effective but has some disadvantages and limitations, which include side effects due to alcohol seepage outside the lesions, need for repeated treatments, and difficult ablation of tissue to produce a regular, homogeneous, and reproducible pattern. These characteristics make percutaneous ethanol injection unsuitable for the ablation of neoplastic tissue in the thyroid gland of patients who are at poor surgical risk (6,7).

Light may be delivered interstitially by implanting a laser fiber directly into body tissues (9,10). Laser thermal ablation (LTA) has been applied experimentally (11–16) and clinically for palliative therapy in a variety of primary and secondary malignant neoplasms (17–26) and also in the ablation of benign lesions (27).

The purpose of our study was to evaluate in vivo the safety and effectiveness of percutaneous LTA in the debulking of thyroid lesions.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Entry criteria were patient ineligibility or refusal for surgery, patient refusal for 131I therapy in hyperfunctioning nodules, or local compression symptoms in hypofunctioning nodules. Exclusion criteria were small nodules (<5 mL) unless they were embedded in large goiters, lesions with suspect or malignant cytologic findings at fine-needle aspiration biopsy, and US criteria indicative of malignancy (microcalcifications or irregular margins).

Between October 1999 and June 2001, 25 volunteer patients (three men and 22 women; age range, 23–81 years; mean age, 54.2 years ± 14.8 [SD]) affected by thyroid lesions were enrolled in the study. Twenty-four of 29 patients with benign lesions who met the inclusion criteria were selected for LTA therapy. One patient with an advanced stage of anaplastic carcinoma that was unresectable and unresponsive to conventional therapies accepted LTA as palliative therapy. The patient was treated for humanitarian reasons and was not evaluated for statistical purposes.

Having been appropriately informed about our study, all patients gave their written informed consent for treatment with LTA with low-power energy output. The study was conducted in accordance with the Helsinki Declaration and was approved by the local bioethics committee.

Imaging, Interpretation, Cytology
The US and color Doppler US examinations were performed with a commercially available real-time US system (Au Idea, Ansaldo Esaote, Genoa, Italy; Sequoia, Acuson, Mountain View, Calif) equipped with a linear transducer operating at 7.5–13 MHz for morphologic study and at 4.7 MHz for color Doppler US evaluation. During US examination, the US pattern and volume of nodules (the three largest perpendicular diameters of the lesion multiplied by 0.525 [ellipsoid volume]) and thyroid paren-chyma were assessed (28). In the first author’s department, the intra- and interobserver variations in the measurements of thyroid nodule volume were 4.7% and 5.5%, respectively.

The echogenicity (hyperechoic, isoechoic, isoechoic with hypoechoic halo, hypoechoic, or mixed), echo structure (solid, mixed, or cystic), margins (well defined, irregular, or blurred), and presence of hyperechoic spots (microcalcifications) were evaluated (29,30). Color Doppler US examinations were performed with biplanar scanning (31,32). In each case, the amplifier gain was individually chosen to be at a level immediately under the point of appearance of random color noise. Pulse repetition frequency was 500–750 Hz, which is useful for slow-flow evaluation. US output power and write-echo priority were maintained at a constant value. The vascularity pattern was evaluated with sagittal and transverse US scans obtained along the maximum diameter of the nodule. Three types of vascularity were identified: type 0, absence of flow signals; type 1, vascularity in peripheral margins; and type 2, intranodular flow with multiple vascular images (32,33).

The US and color Doppler US examinations were performed separately, and findings were recorded by one of two radiologists (G.B., A.B.), each with 15 years of experience in US. After the US features were assessed, all patients underwent cytologic evaluation. US-guided fine-needle aspiration biopsy was performed by one of two endocrinologists (E.P., R.G.) together with one of the two radiologists. All the physicians had at least 10 years of experience in the performance of US-guided fine-needle aspiration biopsies with 27- and 23-gauge needles, according to the technique described in the literature (34–36). Cytologic material was smeared on slides immediately after aspiration and stained with May-Grünwald-Giemsa and Papanicolau stains. Cytologic specimens were evaluated by a cytopathologist (A.C.) with more than 10 years of experience to rule out any possibility of malignancy. Serum levels of thyroid-stimulating hormone (TSH) were determined with commercially available immunoradiometric assay (Sorin Biomedica, Saluggia, Italy). Levels of free triiodothyronine (T3) and free levorotatory thyroxine (T4) were determined with commercially available radioimmunologic assay kits (Radim, Pomezia, Italy).

Ablation Technique
A commercially available US scanner (Au Idea; Ansaldo Esaote) with a 7.5-MHz linear transducer was used for all procedures. In each treatment, as many as four 75-mm-long 21-gauge spinal needles (Becton-Dickinson, Rutherford, NJ) were inserted into thyroid lesions with US guidance. The needle tips were introduced into the nodule to be treated along its longest axis. Care was taken to place the needle tip in the deepest part of the nodule, with a distance of at least 15 mm from the inferior margin of the lesion, and to maintain the same distance between the needle tip and surrounding cervical structures. Tip position was confirmed with biplanar US images. A 300-µm-diameter plane-cut quartz optical fiber (Medical Energy, Pensacola, Fla) was inserted through the sheath of the needle, which was then withdrawn 5 mm to leave the fiber tip in direct contact with the tissue. The laser source, a continuous-wave Nd:YAG laser operating at 1.064 µm (Deka-Mela, Florence, Italy) was used with an optical beam-splitting device (Smart 1064 HCC; DEKA-MELA) with as many as four separate fibers that could be illuminated separately or concurrently (16,19,22–27,37,38). All laser treatments were monitored continuously with real-time US.

Both the number of needles and their arrangement were chosen on the basis of the size, shape, and location of the nodules. Needles were placed 1.0 cm apart in a straight line (in the patient with anaplastic carcinoma, four needles were placed in a square configuration) and simultaneously activated to obtain an adequate area of necrosis (37,38). To facilitate correct placement of the needles, we used a specifically designed and constructed plastic device (Esoate, Genoa, Italy). If warranted by the size of the lesion, we performed two laser illuminations (two treatments) in the same session. In this case, after an initial treatment with needle and fiber tips placed in the deepest part of the nodule, we performed a second treatment after withdrawing the needle(s) and fiber tips at least 15 mm from the previously treated area and repositioning them in the contiguous cranial area. The exact position of the fiber tips was determined on the basis of centimeter indicators on the needles. At the end of the LTA session, the laser was turned off and the optical fiber was slowly withdrawn. To prevent needle track seeding at the end of the procedure in the patient with anaplastic carcinoma, the optical fiber was withdrawn while the laser was still on. Once the needles were extracted, US scans were obtained in all patients to reveal intra- or extraglandular complications. The patients were monitored for 30 minutes without administration of any medication. During follow-up treatments, the needle and fiber tips were positioned in an untreated contiguous area at least 20 mm from the lesion previously treated with LTA.

On the basis of our experience and data from other authors (15,16,23,24), we delivered laser energy interstitially into the lesions with output power of 3–5 W to attain energy delivered of 1,600–1,800 J per fiber per treatment. Each laser treatment that lasted 5–10 minutes was considered one treatment, and no more than two treatments were scheduled per session. Our intention was to achieve substantial reduction in the volume of the lesions to be treated; thus, we scheduled the cycles of irradiation to involve one or more treatments or sessions with one or two needles. We considered the procedure to be ended when the volume of induced necrosis was at least 50% of the initial volume. We scheduled additional sessions when the induced necrosis was less than 50% as depicted at US or computed tomography (CT). LTA sessions were performed by one of two radiologists (C.M.P., G.B.) and one of two endocrinologists (E.P., R.G.); all the physicians had at least 10 years of experience in interventional procedures.

Assessment of Treatment Effectiveness
At 6–8 hours and again at 24 hours after treatment, a US scan was acquired to assess the changes over time in the appearance of laser-induced lesions (14,27). The volume of tissue necrosis (volume of coagulation achieved or thermal lesion size), obtained by multiplying the three largest perpendicular diameters of the area of necrosis by 0.525 (ellipsoid volume), as well as the decrease in nodule volume, were measured by means of static MR images obtained in the transverse, longitudinal, and anteroposterior planes. Two radiologists (C.M.P., G.B.), who worked independently with US and color Doppler US scans, measured images for each patient twice at the end of the procedure, at 24 hours after the last scheduled treatment or session, at 1 month, and every 3 months thereafter. In two patients, the volume of coagulation achieved (volume of tissue necrosis) was also measured by acquiring a CT scan before and after LTA.

At the end of the study, we determined the number of LTA treatments and sessions that each patient underwent, the total energy delivered per nodule, and the energy delivered per session. The decrease in volume of the treated lesions, as well as changes in serum levels of TSH, free T3, free T4, and thyroglobulin, were evaluated and recorded at the end of the procedure and every 3 months thereafter. Pressure symptoms were recorded before treatments, at the end of the procedure, and every 3 months thereafter.

Assessment of Side Effects and Complications
One radiologist (S.P.) and one endocrinologist (R.G.) evaluated with consensus the condition of each patient with respect to the presence of pain during the procedure, the need for analgesics after the procedure, the presence of local complications (hemorrhage, burning, damage to the surrounding cervical structures), and dysphonia. All patients were evaluated at the end of each LTA session and at 30 minutes, 24 hours, and 1 month after the procedure.

Statistical Analysis
Linear regression analysis was performed to assess the correlations between energy delivered and volume of laser-induced necrosis and between energy delivered and reduction in nodule size. The mean diameters of the lesions at US after laser irradiation were compared with the laser parameters by means of the Student t test for paired data. Volume reduction differences between nodules smaller and those larger than 10 mL were evaluated by means of the Student t test. Differences were considered significant when the P value was less than .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Baseline characteristics of the enrolled patients are presented in Table 1. Eight hypofunctioning cold thyroid nodules had baseline volumes of 4.1–65.0 mL (mean, 22.7 mL ± 21.2) (Table 2). Sixteen autonomously hyperfunctioning thyroid nodules had baseline volumes of 1.3–18.8 mL (mean, 8.0 mL ± 6.2), with suppressed TSH levels and free T3 and free T4 levels in the upper normal limits (Tables 3, 4). Volume of the unresectable anaplastic thyroid carcinoma increased from 21.0 to 42.0 mL after unsuccessful chemotherapy and radiation therapy.


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  		TABLE 1. Baseline Characteristics of Patients

 

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  		TABLE 2. Volume Changes in Cold Thyroid Nodules at End of LTA and at 6 Months after LTA, with Corresponding Energy Delivery

 

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  		TABLE 3. Volume Changes in Autonomously Hyperfunctioning Thyroid Nodules at 6 Months after LTA, with Corresponding Energy Delivery

 

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  		TABLE 4. Thyroid Hormonal Levels before and/or after LTA of Cold Nodules and Autonomously Hyperfunctioning Thyroid Nodules

 
Changes in Volume of Thyroid Lesions and Energy Deposition
Mean baseline volumes of the nodules before LTA, immediately after LTA, and at 6 months after LTA are shown in Tables 2 and 3. The echo structure of the treated nodules seemed not to influence the response to treatment (Table 5). Significant correlations were found between energy delivered and volume of coagulation achieved (laser-induced necrosis, thermal lesion size, or volume of tissue necrosis) (r2 = 0.74, P < .001) and between energy delivered and reduction in nodule size (r2 = 0.75, P = .001) (Fig 1). The reduction in nodule volume was similar in nodules larger and those smaller than 10 mL (49.8% ± 9.1 vs 47.5% ± 17.8, difference not significant).


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  		TABLE 5. Volume Changes in Solid and Mixed Nodules

 


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  		Figure 1. Scatterplot shows relationship between energy delivered and volume reduction (r2 = 0.75, P < .001).

 
Cold Nodules
In patients with cold nodules, cytologic findings at fine-needle aspiration biopsy were benign in all cases.

For the eight cold nodules, 51 LTA treatments (range, 2–16; median, 2.5; mean, 6.4 ± 6.1) were performed during 33 sessions (range, 2–9; median, 2.5; mean, 4.1 ± 2.9). Total energy used during each session ranged from 1,500 to 5,400 J (median, 3,000 J). Energy used per nodule ranged from 3,300 to 36,000 J (median, 10,150 J), with total energy deposition of 788 J/mL (range, 500–1,600 J/mL; median, 700 J/mL).

The volume of tissue necrosis induced with one fiber ranged from 0.9 to 1.5 mL (mean, 1.2 mL ± 0.4) and that induced with two fibers ranged from 2.3 to 2.8 mL (mean, 2.6 mL ± 0.3). We consistently used 5 W in all nodules.

Volume decreased from the baseline mean value of 22.7 mL ± 21 to 10.9 mL ± 9.1 at the end of LTA treatment (mean percentage volume reduction, 47.1% ± 11.6) and to 7.7 mL ± 7.5 (mean percentage volume reduction, 63.4% ± 13.8) 6 months later.

Autonomously Hyperfunctioning Thyroid Nodules
In the 16 autonomously hyperfunctioning thyroid nodules, 57 LTA treatments (range, 1–9; median, 2.0; mean, 3.6 ± 3.0) were performed during 43 sessions (range, 1–6; median, 1.5; mean 2.7 ± 2.0). The total energy used at each session ranged from 1,000 to 3,800 J (median, 2,400 J). The total energy used per nodule was 1,800–14,900 J (median, 4,200 J) with total energy delivered of 816 J/mL (range, 400–1,400 J/mL; median, 800 J/mL).

The volume of tissue necrosis induced with one fiber ranged from 0.6 to 1.4 mL (mean, 1.1 mL ± 0.4) and that induced with two fibers ranged from 2.8 to 3.9 mL (mean, 3.4 mL ± 0.8). We used 3 W in eight (50%) of 16 nodules and 5 W in the remaining eight nodules. We used one needle in 10 (62%) of 16 nodules and two needles in the remaining six nodules.

Mean nodule volume reduction, expressed in percentage of baseline volume, was 49% ± 15.3 at the end of LTA treatments (from 8.0 mL ± 6.2 to 4.1 mL ± 3.3). Six months later, the volume had decreased further (3.3 mL ± 2.8), with a mean percentage volume reduction versus baseline of 62.0% ± 21.8.

Before LTA, TSH was suppressed in all patients (Table 4), but it was detectable in five (31%) of 16 patients at 6 months after LTA treatments.

Anaplastic Carcinoma
In the patient with anaplastic carcinoma, we achieved 32 mL of coagulation (Fig 2) in one session. The session comprised one LTA treatment, which lasted 6 minutes and was performed with output power of 5 W and four fibers activated simultaneously, with total energy delivered of 7,200 J.



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  		Figure 2a. Transverse CT scans in neck of 75-year-old woman with anaplastic carcinoma. (a) Nonenhanced CT scan obtained before LTA treatment shows large hypoattenuating area (arrows) in left thyroid lobe, with coarse calcifications (arrowhead) in lower aspect of tumor mass. (b) Contrast material-enhanced CT scan obtained after LTA treatment shows large homogeneous hypoattenuating area as a result of coagulation necrosis in center of infiltrating tumor mass. Tumor displaces surrounding structures of upper neck and invades outer contiguous margin of trachea. Small rim (arrows) of lesion around central coagulation zone remained untreated (partial response; energy delivered, 7,200 J).

 


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  		Figure 2b. Transverse CT scans in neck of 75-year-old woman with anaplastic carcinoma. (a) Nonenhanced CT scan obtained before LTA treatment shows large hypoattenuating area (arrows) in left thyroid lobe, with coarse calcifications (arrowhead) in lower aspect of tumor mass. (b) Contrast material-enhanced CT scan obtained after LTA treatment shows large homogeneous hypoattenuating area as a result of coagulation necrosis in center of infiltrating tumor mass. Tumor displaces surrounding structures of upper neck and invades outer contiguous margin of trachea. Small rim (arrows) of lesion around central coagulation zone remained untreated (partial response; energy delivered, 7,200 J).

 
US Imaging
US images obtained during LTA treatment after a delay of about 30–60 seconds showed an echogenic area with ill-defined borders around the fiber tip. This region expanded slowly, and acoustic shadowing made the deep surface of the lesion difficult to identify precisely in all patients. This finding was more marked in cases of nodules with fluid collections because of the gas microbubbles produced by heating. The vapor was clearly visible in US images as small highly echogenic foci close to the laser-induced lesion. After 200–300 seconds, a plateau effect was seen with only slight further expansion of the echogenic zone (Fig 3).



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  		Figure 3a. US images in neck of 60-year-old woman. (a) Before LTA, longitudinal US image shows solid nodule (arrows) in left thyroid lobe. (b) At 60 seconds after laser irradiation, transverse US image shows two roughly spherical hyperhechoic areas (arrowheads) with associated acoustic shadowing. Areas were 1.0 cm apart in center of nodule. (c) At 360 seconds after LTA procedure, transverse US image shows two large hyperhechoic areas (arrowheads) with ill-defined borders around fiber tips with acoustic shadowing in center of nodule. (d) At 6 months after LTA, longitudinal US image shows marked volume reduction of nodule (arrows). In center of nodule is ill-defined hyperechoic zone with hypoechoic halo due to scar tissue. Scale is in centimeters.

 


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  		Figure 3b. US images in neck of 60-year-old woman. (a) Before LTA, longitudinal US image shows solid nodule (arrows) in left thyroid lobe. (b) At 60 seconds after laser irradiation, transverse US image shows two roughly spherical hyperhechoic areas (arrowheads) with associated acoustic shadowing. Areas were 1.0 cm apart in center of nodule. (c) At 360 seconds after LTA procedure, transverse US image shows two large hyperhechoic areas (arrowheads) with ill-defined borders around fiber tips with acoustic shadowing in center of nodule. (d) At 6 months after LTA, longitudinal US image shows marked volume reduction of nodule (arrows). In center of nodule is ill-defined hyperechoic zone with hypoechoic halo due to scar tissue. Scale is in centimeters.

 


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  		Figure 3c. US images in neck of 60-year-old woman. (a) Before LTA, longitudinal US image shows solid nodule (arrows) in left thyroid lobe. (b) At 60 seconds after laser irradiation, transverse US image shows two roughly spherical hyperhechoic areas (arrowheads) with associated acoustic shadowing. Areas were 1.0 cm apart in center of nodule. (c) At 360 seconds after LTA procedure, transverse US image shows two large hyperhechoic areas (arrowheads) with ill-defined borders around fiber tips with acoustic shadowing in center of nodule. (d) At 6 months after LTA, longitudinal US image shows marked volume reduction of nodule (arrows). In center of nodule is ill-defined hyperechoic zone with hypoechoic halo due to scar tissue. Scale is in centimeters.

 


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  		Figure 3d. US images in neck of 60-year-old woman. (a) Before LTA, longitudinal US image shows solid nodule (arrows) in left thyroid lobe. (b) At 60 seconds after laser irradiation, transverse US image shows two roughly spherical hyperhechoic areas (arrowheads) with associated acoustic shadowing. Areas were 1.0 cm apart in center of nodule. (c) At 360 seconds after LTA procedure, transverse US image shows two large hyperhechoic areas (arrowheads) with ill-defined borders around fiber tips with acoustic shadowing in center of nodule. (d) At 6 months after LTA, longitudinal US image shows marked volume reduction of nodule (arrows). In center of nodule is ill-defined hyperechoic zone with hypoechoic halo due to scar tissue. Scale is in centimeters.

 
Echogenic streaks radiating from the treated area and directed to the gland surface were visible as a result of fluid vaporization and formation of microbubbles of gas along tissue planes. At the end of the treatment, the entire treated zone appeared as an irregular and ill-defined hyperechoic area that progressively decreased over time. In US images obtained at 6 hours after LTA, the treated area appeared as a nonhomogeneous zone with mixed hypo- and hyperechoic US patterns but without the echogenic foci that result from fluid vaporization. Sonograms obtained 24 hours after LTA showed a small central hypoechoic area (zone of vaporization) surrounded by a hyperechoic rim (zone of carbonization) and by an outer hypoechoic zone (zone of coagulative necrosis) with regular margins (14,22–24,27) (Fig 4). This US image was nearly identical to those obtained at 1- and 3-month follow-up, except for a decrease in volume of both the central cavity and the entire heated area. At 6-month follow-up, these characteristic US findings were no longer visible, and US scans showed an ill-defined hyperechoic area with associated acoustic shadowing. Color Doppler US evaluation could not be performed in any patient during laser treatment. In all lesions, color Doppler US performed immediately after LTA and during follow-up showed no sign of vascularization of the treated area (Fig 4).



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  		Figure 4a. Longitudinal US scans in neck of 50-year-old woman at 24 hours after LTA. (a) US scan shows, from center of thermal lesion outward, small central hypoechoic cavity caused by vaporization surrounded by hyperechoic rim (arrowheads) caused by carbonization. Rim represents debris in margin of central cavity. Broad hypoechoic zone (arrows) is caused by coagulation necrosis. (b) Longitudinal color Doppler US scan shows no sign of vascularization in treated area (arrows). Proximal and upper areas of nodule remained untreated. Scale is in centimeters.

 


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  		Figure 4b. Longitudinal US scans in neck of 50-year-old woman at 24 hours after LTA. (a) US scan shows, from center of thermal lesion outward, small central hypoechoic cavity caused by vaporization surrounded by hyperechoic rim (arrowheads) caused by carbonization. Rim represents debris in margin of central cavity. Broad hypoechoic zone (arrows) is caused by coagulation necrosis. (b) Longitudinal color Doppler US scan shows no sign of vascularization in treated area (arrows). Proximal and upper areas of nodule remained untreated. Scale is in centimeters.

 
On precontrast CT scans obtained in two patients, the zone of tissue necrosis appeared as an irregular hyperattenuating area surrounded by a thin hypoattenuating rim. On contrast-enhanced CT scans, the entire area of necrosis appeared as a homogeneous hypoattenuating area surrounded by a thin enhancing peripheral halo as a result of hyperemia or untreated tissue (Fig 2).

Hormonal and Clinical Changes
The condition of all patients with cold nodules was euthyroid at baseline. Patients with autonomously hyperfunctioning thyroid nodules had a slight reduction in free T3 and free T4, and TSH was detectable in five (31%) of 16 patients at 6 months after LTA (Table 4). All eight patients with cold nodules and six (38%) of 16 patients with autonomously hyperfunctioning thyroid nodules experienced compression symptoms before LTA. Improvement of local compression symptoms was reported by 12 (86%) of these 14 patients at 1-month follow-up. The improvement remained unchanged during the follow-up period.

Side Effects and Complications
Needle insertion and fiber positioning were performed without problems or local complications. During laser irradiation, all patients experienced burning cervical pain, which was more intense when we used 5 W per fiber but was tolerated without analgesics during the procedure and rapidly decreased as soon as the energy was turned off. Two patients experienced intense cervical or right shoulder pain, and 500 mg of acetominophen (Tachipirina 500; Angelini, Rome, Italy) was given immediately after LTA and twice a day thereafter to relieve the pain. In these patients, treatment had been performed with an output power of 5 W and four fibers. In two of the three patients who experienced persistent local pain with dysphonia at the end of the treatment, direct laryngoscopy demonstrated vocal cord palsy. These patients were given 1.5 mg of betamethasone (Bentelan; Glaxo, Verona, Italy) twice daily for the next 7 days, and they recovered completely (confirmed by an ear, nose, and throat physician) after 48 hours and at 2-month follow-up. The remaining patients experienced mild to moderate cervical pain in the days following treatment, but the pain was tolerated without analgesics. Because we had intentionally left the laser on at the end of the procedure in the patient with anaplastic carcinoma, we observed hyperemia on the skin surface around the needle insertion points as a result of local inflammation. In all other patients, no damage was induced along the needle track or on the skin surface. No antibiotics were given before or after the procedure.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Since 1990 (2), US-guided ablation of thyroid tissue has been performed with percutaneous ethanol injection (2). Several authors (39–42) report satisfactory results of treatment with percutaneous ethanol injection in large benign nodules. The procedure is often painful despite local anesthesia, however, and complications such as periglandular adherence, which impedes subsequent surgery in case of treatment failure, or mild fever must be anticipated in some cases (43). In addition, the need for multiple ethanol injections is a limitation. In our experience, the number of percutaneous ethanol treatments needed to obtain a 50% volume reduction in benign thyroid nodules increases with increased volume of the nodules (8). Moreover, the difficulty of ablating tissue with homogeneous and reproducible US patterns makes percutaneous ethanol injection unsuitable for the treatment of neoplastic lesions. On the basis of these considerations and of our previous experience (26), we tested LTA as a tool for the ablation of benign and malignant thyroid lesions.

Feasibility of LTA
US-guided needle insertion into thyroid lesions was smoothly performed in all patients. The thinness of the optical fiber made it possible to use fine needles that could easily be positioned correctly in the target area. At US monitoring, the needle and fiber tips were always clearly visualized as hyperechoic spots. During laser irradiation, US of the area being treated showed an echogenic area that enlarged over time. At the end of the procedure, the dimensions of the echogenic zone provided a rough guide to the actual extent of thermal necrosis. Color Doppler US, however, provided precise definition of the margins of laser-induced damage produced immediately after the end of the illumination. US scans obtained 24 hours after LTA made it possible to assess the different constituents of the thermal lesion and to measure the actual extent of coagulation induced during the procedure (14,27). On the basis of US scans obtained in all patients and CT scans obtained in two patients, LTA, in contrast to percutaneous ethanol injection, induced a regular pattern of tissue damage that could be clearly visualized.

The presence of mixed echogenicity or fluid collections within the treated lesions is associated with a large number of microbubbles of gas that can further hamper US visualization of the area during treatment.

Safety of LTA
In all patients, LTA induced burning cervical pain, which rapidly decreased as soon as the energy was turned off. Pain was tolerable with a power output of 3 W per fiber but was too severe and required analgesics when 5 W per fiber was used. Two of the patients developed dysphonia at the end of the treatment, and direct laryngoscopy demonstrated ipsilateral vocal cord palsy. During follow-up, the damage was shown to be completely reversible with time and treatment with steroids.

Undifferentiated or poorly differentiated cancers should be treated with care because, as was demonstrated in our experience with the patient with anaplastic carcinoma, LTA can induce an area of tissue damage that is larger than expected. This is probably a result of the friability and poor vascular supply of undifferentiated neoplastic tissue.

In no patient (except the patient with anaplastic carcinoma, in whom the optical fiber was withdrawn with the laser on) did we observe cutaneous burning, hematomas, local infection, or damage to the vital structures of the neck.

Effectiveness of LTA
In agreement with earlier data derived from liver ablation procedures (23,24), data obtained in the current study showed that for a 1-mL reduction in tissue volume, 843–2,130 J of laser light was needed in cold nodules and 643–5,333 J was needed in hyperfunctioning nodules. The wide disparity observed in the effectiveness of thermal ablation is probably a result of various interfering conditions: the cooling effect of the blood supply; the presence of collections of colloid, which hamper energy transmission to the tissue; and the presence of connective tissue.

Thermal necrosis was not significantly correlated with the initial baseline volumes of the lesions. A significant correlation was observed, however, between total energy delivered and the extent of tissue ablated on the basis of the absolute volume decrease of the treated lesions. Thus, our results differ from the findings of Døssing et al (44) because they compared different outcomes with LTA.

The volume of ablated tissue was limited because the proximity of vital surrounding structures in the neck made it hazardous to attempt complete necrosis of lesions in the thyroid gland.

Potential Uses of LTA
On the basis of our experience (22–24,26) and in agreement with earlier authors (17–21,25), we believe that LTA could be employed for amelioration of local compression symptoms in patients with large hypofunctioning nodules who are at poor surgical risk and for reduction of the volume of neoplastic tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid carcinoma that are not amenable to surgical or radioiodine treatments (25). In our experience, LTA does not seem to be effective in the control of autonomously hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy.

In conclusion, findings in our study demonstrate that laser firing induced a mild burning sensation, which patients reported as painful but tolerable, at low power outputs, and that no serious damage was induced along the needle track or on the skin surface. Major complications can be induced with a higher power output (5 W per fiber), but the procedure was highly effective in the ablation of thyroid tissue. LTA may be a safe therapeutic tool in the treatment of benign and malignant thyroid lesions for selected thyroid problems. Further prospective randomized studies are needed to define the role of this procedure in the treatment of lesions in the thyroid gland.


   ACKNOWLEDGMENTS
 
We thank Roberto Valcavi, MD (Endocrinology Unit, Santa Maria Nuova Hospital, Reggio Emilia, Italy), for his useful advice in the preparation of our manuscript. We also thank Karen Christenfeld, BA, for her invaluable assistance in the revision of our manuscript for language usage.


   FOOTNOTES
 
Abbreviations: LTA = laser thermal ablation, TSH = thyroid-stimulating hormone, T3 = triiodothyronine, T4 = levorotatory thyroxine

Author contributions: Guarantor of integrity of entire study, C.M.P.; study concepts, C.M.P., G.B., E.P.; study design, C.M.P., G.B., R.G.; literature research, S.P., A.B.; clinical studies, E.P., R.G., S.S.; data acquisition, A.B., S.P.; data analysis/interpretation, C.M.P., R.G., A.C., A.B., S.S., S.P., V.T.; statistical analysis, E.P., R.G., V.T.; manuscript preparation, C.M.P., S.P.; manuscript definition of intellectual content, all authors; manuscript editing, A.B., S.P.; manuscript revision/review, C.M.P., R.G., E.P.; manuscript final version approval, all authors


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ross D. Diagnosis and treatment of thyroid nodules. Available at: UptoDate.com. Accessed January 2002.
  2. Livraghi T, Paracchi A, Ferrari C, et al. Treatment of autonomous thyroid nodules with percutaneous ethanol injection: preliminary results—work in progress. Radiology 1990; 175:827-829.[Abstract/Free Full Text]
  3. Paracchi A, Ferrari C, Livraghi T, et al. Percutaneous intranodular ethanol injection: a new treatment for autonomous thyroid adenoma. J Endocrinol Invest 1992; 15:353-362.[Medline]
  4. Martino E, Murtas ML, Loviselli A, et al. Percutaneous intranodular ethanol injection for treatment of autonomously functioning thyroid nodules. Surgery 1992; 112:1161-1164.[Medline]
  5. Monzani F, Goletti O, Caraccio N, et al. Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation. Clin Endocrinol (Oxf) 1992; 36:491-497.[Medline]
  6. Papini E, Panunzi C, Pacella CM, et al. Percutaneous ultrasound-guided ethanol injection: a new treatment of toxic autonomously functioning thyroid nodules? J Clin Endocrinol Metab 1993; 76:411-416.[Abstract]
  7. Papini E, Pacella CM, Verde G. Percutaneous ethanol injection (PEI): what is its role in the treatment of benign thyroid nodules? Thyroid 1995; 5:147-150.[Medline]
  8. Papini E, Pacella CM. Percutaneous ethanol injection of benign thyroid nodules and cysts using ultrasound. In: Baskin HJ, eds. Thyroid ultrasound and ultrasound-guided FNA biopsy. Boston, Mass: Kluwer Academic, 2000; 169-213.
  9. Bown SG. Phototherapy of tumors. World J Surg 1983; 7:700-709.[CrossRef][Medline]
  10. Matthewson K, Coleridge-Smith P, O’Sullivan P, et al. Biological effects of intrahepatic neodymium:yttrium-aluminium-garnet laser photocoagulation in rats. Gastroenterology 1987; 93:550-557.[Medline]
  11. Dachman AH, McGehee JA, Beam TE, et al. US-guided percutaneous laser ablation of liver tissue in a chronic pig model. Radiology 1990; 176:129-133.[Abstract/Free Full Text]
  12. Malone DE, Wyman DR, Moote DJ, et al. Sonographic changes during hepatic interstitial laser photocoagulation. Invest Radiol 1992; 27:804-813.[CrossRef][Medline]
  13. Higuchi N, Bleier AR, Jolesz FA, et al. Magnetic resonance imaging of the acute effects of interstitial neodymium:YAG laser irradiation on tissues. Invest Radiol 1992; 27:814-821.[CrossRef][Medline]
  14. Dachman AH, Smith MJ, Burris JA, et al. Interstitial laser ablation in experimental models and in clinical use. Semin Interv Radiol 1993; 10:101-112.
  15. Pacella CM, Rossi Z, Bizzarri G, et al. Ultrasound-guided percutaneous laser ablation of liver tissue in a rabbit model. Eur Radiol 1993; 3:26-32.
  16. Heisterkamp J, van Hillegersberg R, Ijzermans JNM. Interstitial laser coagulation for hepatic tumours. Br J Surg 1999; 86:293-304.[CrossRef][Medline]
  17. Huang GT, Wang TH, Sheu JC, et al. Low-power laserthermia for the treatment of small hepatocellular carcinoma. Eur J Cancer 1991; 27:1622-1627.
  18. Amin Z, Donald JJ, Masters A, et al. Hepatic metastases: interstitial laser photocoagulation with real-time US monitoring and dynamic CT evaluation of treatment. Radiology 1993; 187:339-347.[Abstract/Free Full Text]
  19. Nolsøe CP, Torp-Pedersen S, Burchart F, et al. Interstitial hyperthermia of colorectal liver metastases with a US-guided Nd:YAG laser with a diffuser tip: a pilot clinical study. Radiology 1993; 187:333-337.[Abstract/Free Full Text]
  20. Vogl TJ, Muller PK, Hammerstingl R, et al. Malignant liver tumor treated with MR imaging-guided laser-induced thermotherapy technique and prospective results. Radiology 1995; 196:257-265.[Abstract/Free Full Text]
  21. Pacella CM, Bizzarri G, Ferrari FS, et al. Interstitial photocoagulation with laser in the treatment of liver metastases. Radiol Med (Torino) 1996; 92:438-447.
  22. Pacella CM, Bizzarri G, Cecconi P, et al. Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization. Radiology 2001; 219:669-678.[Abstract/Free Full Text]
  23. Pacella CM, Bizzarri G, Magnolfi F, et al. Laser thermal ablation in the treatment of small hepatocellular carcinoma: results in 74 patients. Radiology 2001; 221:712-720.[Abstract/Free Full Text]
  24. Shankar A, Lees WR, Gillams AR, et al. Treatment of recurrent colorectal liver metastases by interstitial laser photocoagulation. Br J Surg 2000; 87:298-300.[CrossRef][Medline]
  25. Guglielmi R, Pacella CM, Dottorini ME, et al. Severe thyrotoxicosis due to hyperfunctioning liver metastasis from follicular carcinoma: treatment with 131I and interstitial laser ablation. Thyroid 1999; 9:173-177.[Medline]
  26. Pacella CM, Bizzarri G, Guglielmi R, et al. Thyroid tissue: US-guided percutaneous interstitial laser ablation—a feasibility study. Radiology 2000; 217:673-677.[Abstract/Free Full Text]
  27. Chapman R. New therapeutic technique for treatment of uterine leiomyomas using laser-induced intestinal thermotherapy (LITT) by a minimally invasive method. Lasers Surg Med 1998; 22:171-178.[CrossRef][Medline]
  28. Scheible W, Leopold GR, Woo VL, Gosink BB. High-resolution real-time ultrasonography of thyroid nodules. Radiology 1979; 133:413-417.[Abstract]
  29. Kerr L. High resolution thyroid ultrasound: the value of colour Doppler. Ultrasound Q 1994; 12:21-23.
  30. Solbiati L, Livraghi T, Ballarati E, et al. Thyroid gland. In: Solbiati L, Rizzatto G, Charboneau JW, eds. Ultrasound of superficial structures. Edinburgh, Scotland: Churchill-Livingstone, 1996; 48-85.
  31. Pacella CM, Papini E, Bizzarri G, et al. Assessment of the effect of percutaneous ethanol injection in autonomously functioning thyroid nodules by colour-coded duplex sonography. Eur Radiol 1995; 5:395-400.
  32. Solbiati L, Osti V, Cova L, et al. Ultrasound of thyroid, parathyroid glands and neck lymph nodes. Eur Radiol 2001; 11:2411-2424.[CrossRef][Medline]
  33. Rago T, Vitti P, Chiovato I, et al. Role of conventional ultrasonography and color flow-Doppler sonography in predicting malignancy in "cold" thyroid nodules. Eur J Endocrinol 1998; 138:41-46.[Abstract]
  34. Lagalla R, Caruso G, Midiri M, et al. Echo-Doppler-couleur et pathologie thyroidienne. J Echogr Med Ultrason 1992; 13:44-47.
  35. Linsk JA, Franzen S. Fine needle aspiration for the clinician Philadelphia, Pa: Lippincott, 1986; 16-25.
  36. Gharib H. Diagnosis of thyroid nodules by fine needle aspiration biopsy. Curr Opin Endocrinol Diabetes 1996; 3:433-438.
  37. Steger AC, Bown SG, Clark CG, et al. Multiple fibre interstitial laser hyperthermia studies in normal liver (abstr). Lasers Med Sci 1988; 3:339.
  38. Heisterkamp J, Hillegersberg R, Sinofsky EL, et al. Simultaneous multiple fibre application to increase the volume of interstitial laser coagulation using an optical beamsplitter. Lasers Med Sci 1999; 14:216-220.[CrossRef]
  39. Livraghi T, Paracchi A, Ferrari C, et al. Treatment of autonomous thyroid with percutaneous ethanol injection: 4-year experience. Radiology 1994; 190:529-533.[Abstract/Free Full Text]
  40. Monzani F, Caraccio N, Goletti O, et al. Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients. Clin Endocrinol (Oxf) 1997; 46:9-15.[CrossRef][Medline]
  41. Zingrillo M, Torlontano M, Ghiggi MR, et al. Radioiodine and percutaneous ethanol injection in the treatment of large toxic thyroid nodule: a long-term study. Thyroid 2000; 10:985-989.[Medline]
  42. Del Prete S, Russo D, Caraglia M, et al. Percutaneous ethanol injection of autonomous thyroid nodule with a volume larger than 40 mL: 3 years of follow-up. Clin Radiol 2001; 56:895-901.[CrossRef][Medline]
  43. Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003; 24:102-132.[Abstract/Free Full Text]
  44. Dossing H, Bennedbaek FN, Karstrup S, et al. Benign solitary solid cold thyroid nodules: US-guided interstitial laser photocoagulation—initial experience. Radiology 2002; 225:53-57.[Abstract/Free Full Text]



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