Role of laser ablation in multimodal treatment of radioiodine- refractory bone metastases of thyroid cancer: a retrospective study.

PURPOSE: To assess the efficacy, safety, and pain benefits of imaging-guided laser ablation (IGLA) in patients with radioiodine-refractory (RR) bone metastases from differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: The institutional medical records of patients with bone metastases from DTC treated with laser ablation (LA) were reviewed retrospectively. Local response, complications, and effects on pain relief were investigated. RESULTS: Six osteolytic lesions in five patients (one male, four females; mean age 65.4 ± 5.1 years, range 58-72) were treated with IGLA. All lesions were osteolytic and all have had previous treatments with high-dose radioiodine therapy followed by external radiotherapy (EBRT). All patients assumed opioid analgesics for severe pain. Overall, the lesions (mean size 5.8 ± 3.2 cm; median 5.0 cm, range 3.0-12.0 cm) underwent nine IGLA sessions (mean 1.8 ± 0.4 sessions; median 2.0 sessions, range 1-2). In four (80%) out five lesions, cross-sectional imaging showed a nearly complete response (CR) while the largest lesion was ablated by 80%. Pain changes were assessed with the Brief Pain Inventory-Short Form, that was administered before IGLA and during a 6-month follow-up. Patients experienced significant reduction in worst pain, average pain, and pain interference. Following IGLA, the average daily opioid requirement rapidly and progressively decreased. Treatments were well-tolerated and no major complications occurred. CONCLUSIONS: IGLA is an effective and safe debulking procedure and provides significant pain relief in patients suffering from DTC bone metastases that are not responsive to standard treatments. So, IGLA could be considered as part of a multimodality management of advanced thyroid cancer with RR metastatic skeletal involvement.

Predictive Value of Malignancy of Thyroid Nodule Ultrasound Classification Systems: A Prospective Study.

Context: British Thyroid Association (BTA), American Thyroid Association (ATA), and American Association of Clinical Endocrinologists (AACE/ACE/AME) recommend for thyroid nodules an ultrasound (US)-based stratification of risk of malignancy. Aim of our study was to assess the diagnostic accuracy of US classification systems and their reliability for indication to fine-needle aspiration (FNA). Design: Prospective study on 987 thyroid nodules consecutively referred for FNA. US images were independently reviewed by four experts for assignment of malignancy risk. Cytologically benign nodules had confirmation with a second FNA, whereas Bethesda class IV, V, and VI nodules were operated upon. Class III nodules had surgery or follow-up on the basis of clinical, immunocytochemical, and US features. Results: BTA: Malignancy rate was 2.8% in benign, 10.0% in indeterminate, 51.3% in suspicion, and 80.9% in malignant US class. Sensitivity was 0.74, specificity was 0.92, and accuracy was 0.89. ATA: Malignancy rate was 0.0% in benign, 2.2% in very low suspicion, 3.0% in low suspicion, 5.8% in intermediate, and 55.0% in high suspicion US class. Sensitivity was 0.81, specificity was 0.87, and accuracy was 0.86. AACE/ACE/AME: Malignancy rate was 1.1% in low-risk, 4.4% in intermediate-risk, and 54.9% in high-risk US class. Sensitivity was 0.82, specificity was 0.87, and accuracy was 0.86. K correlation coefficient was 78.9%, 76.9%, and 82.0% for BTA, ATA, and AACE/ACE/AME classifications. Conclusions: Classification systems had elevated predictive value of malignancy in high-risk classes. ATA and AACE/ACE/AME systems were effective for ruling out indication to FNA in low-US-risk nodules. A similar diagnostic accuracy and a substantial interobserver agreement was provided by the three- and the five-category classifications.

Shift from Levothyroxine Tablets to Liquid Formulation at Breakfast Improves Quality of Life of Hypothyroid Patients.

BACKGROUND: Until recently, treatment of hypothyroidism has been accomplished using monotherapy of synthetic L-thyroxine (L-T4) sodium tablets that should be taken 30-60 minutes before breakfast. Nowadays, a liquid preparation of levothyroxine is available and can effectively replace tablets without the need of waiting before having breakfast. Evidence of Quality of life (QoL) improvement when shifting from the former to the latter preparation, however, is still lacking. OBJECTIVE: The study aimed to assess changes in QoL of hypothyroid patients dissatisfied with their therapy with L-T4 sodium tablets who were switched from tablets taken 30-60 minutes before breakfast to liquid L-T4 at breakfast. METHODS: A total of 418 consecutive hypothyroid subjects treated by means of L-T4 tablets were asked about their satisfaction/dissatisfaction in order to take the medication 30-60 minutes before having breakfast. Overall, 110 patients (26.3%) complained of the timing of their L-T4 therapy (30-60 minutes before breakfast). A dedicated QoL questionnaire (ThyTSQ), taking just a few minutes to be filled in was then administered to these dissatisfied patients. They were therefore switched to L-T4 to be taken at breakfast. Aiming to avoid TSH elevation due to L-T4 tablets malabsorption caused by meal interference and gastric pH changes, patients were invited to take L-T4 liquid form, as this is claimed to be scarcely affected by the non-fasting state. The questionnaire (ThyTSQ) was administered again at the control visit 3 months later. TSH, FT4, FT3 serum concentrations and metabolic parameters were also recorded. RESULTS: An improved QoL, mainly due to an easier adherence to treatment, was reported by 66.6% of 102 patients who completed the study after shifting from taking medication 30-60 minutes before breakfast to at breakfast ingestion (P<0.01). An overall 10.7% of patients found the liquid formulation distasteful. Mean values of TSH, FT4, FT3, and of metabolic parameters did not significantly change but in eight patients (7.7%) who showed a TSH increase > 2mIU/L. CONCLUSION: In hypothyroid subjects dissatisfied with L-T4 tablets ingested 30-60 minutes before breakfast, the shift to the same dose of L-T4 in liquid form taken at breakfast improved QoL in the majority of patients, without affecting thyroid function.

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

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.

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 sensitivity for thyroid malignancy is increased by real-time elastography: a prospective multicenter study.

CONTEXT: Thyroid nodules are selected for biopsy on the basis of clinical and ultrasound (US) findings. Ultrasonography detects nodules at risk of malignancy, but its diagnostic accuracy does not rule out with certainty the possibility of cancer in lesions without suspicious findings. OBJECTIVE: The objective of the study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in thyroid nodules and to assess the improvement provided by combination of RTE, B-mode US, and color flow Doppler (CFD). DESIGN: This was a prospective multicenter study. PATIENTS: A consecutive series of 498 thyroid nodules was blindly evaluated by US, CFD, and RTE before biopsy or surgery. Nodules were classified at RTE by four-class color scale. Patients with benign cytology underwent follow-up over 12 months, whereas patients with indeterminate, suspicious, or malignant cytology were surgically treated. RESULTS: At follow-up, 126 nodules were malignant and 372 benign. RTE classes III-IV showed 81% sensitivity and 62% specificity. The presence of at least one US risk factor (hypoechogenicity, microcalcifications, irregular margins, intranodular vascularization, and taller than wide shape) had 85% sensitivity and 91% negative predictive value. When RTE was combined with US, the presence of at least one of the six parameters had 97% sensitivity and 97% negative predictive value, with an odds ratio of 15.8 (95% confidence interval 5.7-43.8). CONCLUSIONS: RTE is a valuable tool for detecting malignant thyroid lesions with a sensitivity similar to traditional US and CFD features. By adding RTE evaluation, the sensitivity for malignancy of US findings is markedly increased and the selection of nodules that do not need cytology is made more reliable.

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.

"Hypoechoic triangle": a new sonographic sign or marker of advanced autoimmune thyroiditis.

BACKGROUND: Ultrasonography (US) changes have been noted in patients with autoimmune thyroiditis (AT). Here, we report that some patients with late stage AT have a distinctive, previously unreported finding on US that we call the "hypoechoic triangle sign" (HET). METHODS: On US, the HET sign was characterized as a well-defined area of low echogenicity, about 10 mm in diameter, between the lateral margin of one or both thyroid lobes, the medial wall of the carotid artery, and, posteriorly, the prevertebral muscles. Twenty-six patients with AT who had the HET sign (Group 1) were compared with 71 patients with AT who had normal serum thyrotropin (TSH) and free thyroid hormones levels (Group 2) and with 154 normal controls (Group 3). TSH was tested at least twice, first as part of their regular clinical care and then in follow-up. The groups were similar in terms of age, sex, and body mass index. Thyroid volume by US, TSH, free triiodothyronine, free thyroxine, antithyroid antibodies, and l-thyroxine treatment were evaluated. Sonographic gray-scale analysis and three-dimensional reconstruction of HET region were performed in five of the Group 1 patients. RESULTS: Thyroid volume was significantly smaller (p < 0.01) in Group 1 than in Groups 2 and 3 (6.9 ± 2.18 vs. 10.4 ± 2.1 and 9.8 ± 2.5 mL, respectively). In Group 1, 61.5% of subjects were taking l-thyroxine for hypothyroidism; none of the Group 2 or 3 patients was taking thyroid hormone. Serum TSH was significantly higher (p < 0.01) in Group 1 versus Groups 2 and 3 (3.6 ± 1.3 vs. 2.18 ± 1.4 and 1.9 ± 1.1 mIU/L, respectively). None of the Group 2 or 3 patients had the HET sign. Gray-scale US demonstrated an overlap between HET zone and the surrounding muscle tissue. CONCLUSIONS: The HET sign seems to be specific for overt thyroid failure in patients with AT as it was not noted in patients with AT not having overt thyroid failure. The incidental finding of the HET sign during cervical US examination should prompt obtaining thyroid function tests to rule out hypothyroidism. Our study provides data regarding specificity but not sensitivity of the HET sign for AT and thyroid failure because a consecutive group of AT patients with thyroid failure was not studied. In addition, the specificity of the HET sign for AT needs to be evaluated further by studying a diverse group of thyroid diseases.