Giancarlo Bizzarri

Ultrasound-guided laser thermal ablation for treatment of benign thyroid nodules.

OBJECTIVE To evaluate the efficacy of ultrasound (US)-guided laser thermal ablation (LTA) in reducing the volume of hypofunctioning benign thyroid lesions. METHODS The criteria for entry into the study were as follows: (1) presence of a hypofunctioning thyroid nodule with a volume exceeding 8 mL, (2) benign cytologic findings, (3) local compression symptoms or patient concern, and (4) refusal of or ineligibility for surgical treatment. Twenty patients (15 women and 5 men; mean age, 63.3 +/- 14.1 years) fulfilling the entry criteria were enrolled in the study. Under US monitoring, a 75-mm, 21-gauge spinal needle was inserted into the thyroid gland, and a flat-tipped 300-microm quartz fiberoptic guide was placed through the needle into the tissues. LTA was performed with use of a 1.064-microm continuous-wave neodymium yttrium-aluminum-garnet laser that had an output power of 3 W for 10 minutes. US scans were used to assess the decrease in nodule volume at 1 month and 6 months after LTA. RESULTS After LTA, mean nodule volume decreased from a baseline value of 24.1 +/- 15.0 mL to 13.3 +/- 7.7 mL at 1 month and to 9.6 +/- 6.6 mL at 6 months. Mean nodule volume reduction in comparison with baseline was 43.8 +/- 8.1% at 1 month and 63.8 +/- 8.9% at 6 months. LTA induced burning cervical pain, which rapidly decreased after the laser energy was turned off. Three patients (15%) required treatment with betamethasone for 48 hours. No patient had local bruising, cutaneous burning, or dysphonia. CONCLUSION LTA may be an effective procedure for the treatment of benign cold thyroid nodules that cause pressure symptoms in patients who are not candidates for surgical treatment or who refuse to undergo a surgical procedure.

Percutaneous Laser Ablation in the Treatment of Hepatocellular Carcinoma with Small Tumors: Analysis of Factors Affecting the Achievement of Tumor Necrosis

PURPOSE To identify the factors that affect the achievement of tumor necrosis with percutaneous laser ablation (PLA) in patients with hepatocellular carcinoma (HCC) and tumor size no larger than 4.0 cm. MATERIALS AND METHODS Ultrasound-guided biopsy results were retrospectively studied in 99 lesions (range, 0.5-4.0 cm; mean, 2.7 cm) from 82 patients (44 men, 38 women; age range, 50-80 years; median, 68 y) who had undergone PLA. RESULTS Complete tumor ablation was obtained in 90 lesions (90.9%). Of the nine cases in which complete tumor necrosis was not achieved, six had tumors located in sites that did not allow the optimal placement of fibers, and five of these had a tumor diameter greater than 3 cm. Early discontinuation of PLA as a result of decompensation of liver cirrhosis was the reason for not achieving a complete tumor ablation in three other cases. There was a clear relationship between the energy delivered and the volume of necrosis achieved (r = 0.56; P < .001) regardless of the initial size of HCC tumors. The number of illuminations required, and consequently the amount of energy delivered, was also affected by tumor location. In fact, lesions adjacent to large vessels (> or = 3 mm) required a greater number of illuminations than the other lesions to achieve complete ablation (2.9 +/- 1.4 vs 2.3 +/- 0.9; P = .043). The eight cases with undifferentiated histology required more illuminations than the cases with other histologic types (3.4 +/- 0.9 vs 2.2 +/- 0.9; P < .001). However, these cases were located in sites that did not allow the optimal placement of fibers, therefore requiring multiple treatments. CONCLUSION PLA is a highly effective treatment in HCC with a tumor size of 4.0 cm or smaller. In this setting, two variables, tumor size and tumor location, affect the achievement of complete tumor ablation and the number of treatments required to obtain tumor necrosis.

Outcomes and Risk Factors for Complications of Laser Ablation for Thyroid Nodules: A Multicenter Study on 1531 Patients.

BACKGROUND Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity. PATIENTS Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function. METHODS LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure. RESULTS Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed. CONCLUSIONS Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Percutaneous ultrasound-guided laser ablation is effective for treating selected nodal metastases in papillary thyroid cancer.

CONTEXT Mini-invasive procedures may be useful for control of local neck nodal metastases of papillary thyroid cancer (PTC) in high-risk patients. OBJECTIVE Our objective was to assess the effectiveness and safety of ultrasound (US)-guided laser ablation (LA) for nonsurgical treatment of small-size neck metastases of PTC. DESIGN AND SETTING We conducted a pilot study on a surgically controlled metastasis, followed by a prospective trial with a 12-month follow-up. PARTICIPANTS Participants included five patients with previous total thyroidectomy and neck dissection for PTC, with eight new lymph node metastases in an area already treated with surgical dissection and lymph node volume less than 2 ml and absent radioiodine uptake. OUTCOME MEASURES We evaluated thyroglobulin (Tg) and US changes of the lymph nodes 6 and 12 months after LA as well as tolerability and side effects of the procedure. RESULTS A single LA treatment induced progressive volume reduction of the eight metastatic lymph nodes. Mean baseline volume decreased from 0.64 ± 0.58 to 0.07 ± 0.06 ml at 12-month control. Mean volume reduction was 64.4 ± 0.19% at 6 months (P < 0.02 vs. baseline) and 87.7 ± 0.11% at 12 months (P < 0.01 vs. baseline). No regrowth was registered. Mean serum Tg on LT4 decreased from 8.0 ± 3.2 ng/ml to 2.0 ± 2.5 ng/ml at 12-month control (P < 0.02 vs baseline). In three patients (60%) Tg levels were undetectable at 12-month control. Pain was tolerable in two cases and mild in three cases. Transient dysphonia in one patient was the only complication. After 1 yr, no cancer seeding was present. CONCLUSION LA is a well-tolerated outpatient procedure that results in a rapid cytoreduction of cervical nodal metastases of PTC. Mini-invasive procedures may be used in lieu of surgery as an adjunctive therapy for small-burden local/regional disease recurrence. They are occasionally associated with an anatomical or biochemical cure, but long-term follow-up or controlled trials are needed.

Ultrasound-Guided Laser Ablation of Incidental Papillary Thyroid Microcarcinoma: A Potential Therapeutic Approach in Patients at Surgical Risk

BACKGROUND Incidental papillary thyroid microcarcinoma (PTMC), a frequent clinical problem, is usually associated with a favorable outcome. During long-term follow-up, only a minority of cases show aggressive behavior with either lymph node or distant metastases. Recently, we had an opportunity to evaluate the efficacy of nonsurgical, ultrasound (US)-guided percutaneous laser ablation (PLA) for local treatment of PTMC in an otherwise inoperable patient. PATIENT AND METHODS Neck US examination revealed an incidental, solitary, 8 × 7 × 7 mm hypoechoic nodule with microcalcifications of the right thyroid lobe. The patient suffered from decompensated liver cirrhosis, renal failure, and recent surgery followed by external beam radiation therapy for breast cancer. Cytologic diagnosis showed papillary thyroid carcinoma, but the patient declined surgery because of high risk of thyroid surgery. After local anesthesia with 2% xylocaine, PLA was performed according to the previously reported procedure with an Nd:YAG laser. SUMMARY The procedure was well tolerated, without side effects, and the patient required no analgesics. US-guided fine-needle aspiration biopsy and core-needle biopsy were performed at 1 and 12 months after PLA, which demonstrated necrotic material and inflammatory cells with no viable neoplastic cell. At the 24 months US follow-up examination, the area of necrosis further decreased, demonstrating a 4 × 4 mm hypoechoic zone and a small hyperechoic area due to fibrotic changes. A fine-needle aspiration biopsy confirmed the absence of malignant cells. CONCLUSIONS Laser-induced thermal ablation was a safe and effective ablative treatment for a patient with PTMC confined to the thyroid gland who was at high surgical risk. This approach should be considered only in elderly patients and/or in those with comorbidities that might expose the patients to an undue high surgical risk and only after the evaluation by neck US, computed tomography, magnetic resonance imaging, or positron emission tomography/computed tomography rules out lymph-node involvement or metastatic disease.

A randomized trial of ultrasound-guided anterior subcostal liver biopsy versus the conventional Menghini technique.

An ultrasound-guided double pass biopsy technique using a large bore cutting needle via an anterior subcostal route (USAB) is described. The diagnostic adequacy of this biopsy procedure was evaluated in comparison with the traditional Menghini technique in 200 cases of suspected chronic liver disease randomly assigned to the two different procedures. Retrieval rate was better in the USAB group. The sample length was less than 15 mm in four cases in the USAB group and in 19 cases in the Menghini group. In three cases in the USAB group the second pass modified the diagnosis of the first specimen from chronic active hepatitis to active cirrhosis. In order to evaluate the safety and discomfort of the two procedures 340 patients assigned to the different techniques had liver ultrasound scans 6 and 24 h following percutaneous biopsy. USAB was associated with a reduced frequency of complications (one out of 170 patients vs. seven out of 170 patients who had the intercostal Menghini procedure). In our study, USAB seems to offer better sampling and size of individual samples, together with reduced frequency of major and minor complications.

Long-term Efficacy of Ultrasound-Guided Laser Ablation for Benign Solid Thyroid Nodules. Results of a Three-Year Multicenter Prospective Randomized Trial

BACKGROUND The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure. PATIENTS Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6-17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment. METHODS Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment. RESULTS One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was -49 ± 22%, -59 ± 22%, -60 ± 24%, and -57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers. CONCLUSIONS A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.

Morphological changes in a hyperfunctioning thyroid adenoma after percutaneous ethanol injection: Histological, enzymatic and sub-microscopical alterations

Ultrasound-guided ethanol injection (PEI) is an effective treatment of autonomously functioning thyroid nodules (AFTN) but little is known about the tissue lesions induced by alcohol. We report morphological changes of an AFTN which was removed after successful PEI treatment. At histological evaluation, the adenoma showed multiple areas of coagulative necrosis with eosinophilic ghost follicles, hemorrhages, small vessel thrombosis and a wedge-shaped hemorrhagic infarction. The peripheral adenomatous tissue and the surrounding thyroid parenchyma were free of regressive changes and/or lympho-monocytic inflammatory reactions. Enzyme histochemistry confirmed the hyperfunctioning character of the lesion and showed reduction of succinic dehydrogenase and cytochrome-c-oxydase activity in the viable tissue surrounding the central necrotic areas. By electron microscopy, the hyperfunctioning follicular epithelium showed submicroscopical alterations of the adenomatous cells surrounding the areas of coagulative necrosis. These results suggest that control of hyperthyroidism, after PEI, is due to: a) directly induced, irreversible damage (coagulative necrosis and vascular thrombosis with hemorrhagic infarction) in the central areas of the lesion; b) potentially reversible damage (reduction of intracellular enzyme activity and ultrastructural changes) in the peripheral areas.

Percutaneous laser ablation of benign and malignant thyroid nodules.

Purpose of reviewPercutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. Recent findingsIn several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels.Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. SummaryLaser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation.Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy.Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

The advent of ultrasound-guided ablation techniques in nodular thyroid disease: towards a patient-tailored approach.

Surgery is the long-established therapeutic option for benign thyroid nodules, which steadily grow and become symptomatic. The cost of thyroid surgery, the risk of temporary or permanent complications, and the effect on quality of life, however, remain relevant concerns. Therefore, various minimally invasive treatments, directed towards office-based management of symptomatic nodules, without requiring general anaesthesia, and with negligible damage to the skin and cervical tissues, have been proposed during the past two decades. Today, ultrasound-guided percutaneous ethanol injection and thermal ablation with laser or radiofrequency have been thoroughly evaluated, and are accessible procedures in specialized centres. In clinical practice, relapsing thyroid cysts are effectively managed with percutaneous ethanol injection treatment, which should be considered therapy of choice. In solid non-functioning thyroid nodules that grow or become symptomatic, trained operators may safely induce, with a single session of laser ablation treatment or radiofrequency ablation, a 50% volume decrease and, in parallel, improve local symptoms. In contrast, hyperfunctioning nodules remain best treated with radioactive iodine, which results in a better control of hyperthyroidism, also in the long-term, and fewer side-effects. Currently, minimally invasive treatment is also investigated for achieving local control of small size neck recurrences of papillary thyroid carcinoma in patients who are poor candidates for repeat cervical lymph node dissection. This particular use should still be considered experimental.