Adjustable-tip needles versus fixed-tip needles in radiofrequency ablation of symptomatic benign thyroid nodules: a single-center Italian experience.

PURPOSE: In this retrospective, observational study we aim to compare the outcomes of the RFA treatment of benign thyroid nodules, carried out respectively with the standard fixed-needle approach (FTN) and the adjustable-tip needle technique (ATN), considered a more tailored, quicker and easier technical approach. METHODS: We enrolled 36 patients who underwent RFA treatment of symptomatic, benign, thyroid nodule, 18 with the ATN and 18 with the FTN approach, respectively. Data about absolute volume reduction, volume reduction rate (VRR) and success rate (defined as VRR ≥ 50%), after 1, 3 and 6 months of follow-up were compared. RESULTS: Our study suggested no substantial difference between the approaches, up to 6 months of follow-up, both in terms of absolute reduction (p = 0.27) and VRR (p = 0.14). These results were confirmed when the success rates, both in terms of 50%-reduction (p = 0.12) and absolute reduction (p = 0.42), was considered. Only at the 6-month evaluation, the FTN procedure showed a better success rate, yet without statistical significance (88.9% vs. 61.1%, p = 0.12). No difference emerged both in terms of patients' satisfaction and safety. CONCLUSION: Our small experience suggested no substantial difference between ATN and FTN, in terms of outcomes. On the other hand, ATN was considered to be more straightforward and could consequently allow for a shorter operator learning curve.

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Benign thyroid nodules classified as ACR TI-RADS 4 or 5: Imaging and histological features.

BACKGROUND: American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) being most widely applied in clinical practice, there is an overlap in US imaging manifestations between benign and malignant thyroid nodules. OBJECTIVES: To analyze the imaging and histological characteristics of pathological benign thyroid nodules categorized as American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 4 or 5, and to explore the correlation between the suspicious sonographic signs resulting in the misdiagnoses and the histopathological features. MATERIALS AND METHODS: Overall, 227 benign thyroid nodules (215 patients) in ACR TI-RADS 4 or 5 sampled through surgical excision were analyzed between December 2020 and August 2022. We retrospectively reread the ultrasound (US) images of the pathological discordant cases, after which we performed a systematic analysis focusing on the histopathological characteristics of thyroid lesions and recorded the findings. Qualitative US features and pathological significance of the thyroid nodules were analyzed using the chi-square and Fisher's exact tests. RESULTS: The pathological type of 227 thyroid nodules (n = 103 in ACR TI-RADS 4 and n = 124 in ACR TI-RADS 5) was nodular goiter together with other histopathological features, namely, fibrosis (n = 103, 45.4 %), calcification (n = 70, 30.8 %), adenomatous hyperplasia (n = 31, 13.7 %), follicular epithelial hyperplasia (n = 23, 10.1 %), Hashimoto's thyroiditis (n = 18, 7.9 %), and cystic degeneration (n = 16, 7.1 %). Fibrosis was the most common histopathological feature in both ACR TI-RADS 4 (n = 42, 40.8 %) and 5 (n = 61, 49.2 %) categories of benign thyroid nodules. Thyroid nodules with fibrosis demonstrated sonographic features of "taller than wide" (p < 0.05), while lesions with follicular epithelial hyperplasia were likely to be detected with irregular and/or lobulated margins and very hypoechoic on US (p < 0.05 for both). CONCLUSION: Benign thyroid nodules with histopathological findings such as fibrosis are associated with suspicious US features, which may give inappropriately higher TIRADS stratification.

A clinical practice review of percutaneous ethanol injection for thyroid nodules: state of the art for benign, cystic lesions.

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

Radiofrequency ablation for thyroid nodules in Ecuador: a cross-sectional study.

OBJECTIVES: To describe the demographic characteristics and clinical outcomes following the first cohort of patients with Bening Thyroid Nodule (BTN) and (Papillary Thyroid Microcarcinoma) (PTMC) treated with Radiofrequency Ablation (RFA)in Ecuador. METHODS: Single-center, cross-sectional study. We included adults undergoing RFA for BTN and PTMC between July 2019 and May 2022. Descriptive statistics and the Wilcoxon signed-rank test were used to compare some pre- and post-intervention outcomes. RESULTS: We included 44 patients with 36 BTNs and eight PTMCs. The median age was 45.80 years (IQR 16-79 years), and most patients had normal thyroid function (72.72%). The median follow-up time was 7.80 months (IQR1.0-34.0). Nodules were primarily solid (43.21%) or predominantly solid (56.81%). The pre-RFA median volume in the benign lesions group was 10.30 ml (IQR 1.86-18.97). After ablation, the 1-month, 3-month, 6-month, and 12-month median volumes were 6.90 (IQR 0.48-10.15; p < 0.01) mL, 5.72 (IQR 0.77-7.25; p = 0.045); 0.98 (IQR 0.25-3.64; p < 0.01), and 0.11 (IQR 0.07-11.26; p = 0.026), respectively. The volume rate reduction was 47.20%, 72.20%, 74.00%, and 96.20% at 1, 3, 6, and 12-month follow-ups, respectively. The pre-RFA median volume in the PTMC group was 0.25 ml (IQR 0.19-0.48). After ablation, the 1-month, 3-month, and 6-month mean volumes were 0.19 (range 0.12-0.31; p = 0.120) mL, 0.10 (IQR 0.05-0.15; p = 0.13), and 0.01 (IQR 0.005-0.04; p = 0.364), respectively. CONCLUSIONS: In this first report from Ecuador, we found that RFA may be a feasible alternative for treating benign and malignant thyroid nodules in the short term. Long-term data are needed to evaluate oncologic outcomes in PTMC patients.

RUNX1 methylation as a cancer biomarker in differentiating papillary thyroid cancer from benign thyroid nodules.

Aim: It remains a challenge to accurately identify malignancy of thyroid nodules when biopsy is indeterminate. The authors aimed to investigate the abnormal DNA methylation signatures in papillary thyroid cancer (PTC) compared with benign thyroid nodules (BTNs). Methods: The authors performed genome profiling by 850K array and RNA sequencing in early-stage PTC and BTN tissue samples. The identified gene was validated in two independent case-control studies using mass spectrometry. Results: Hypomethylation of RUNX1 in PTC was identified and verified (all odds ratios: ≥1.50). RUNX1 methylation achieved good accuracy in differentiating early-stage PTC from BTNs, especially for younger women. Conclusion: The authors disclosed a significant association between RUNX1 hypomethylation and PTC, suggesting RUNX1 methylation as a potential biomarker for companion diagnosis of malignant thyroid nodules.

General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement.

Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules. Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided. Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.

High-intensity focused ultrasound for benign thyroid nodules: Systemic review and meta-analysis.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a less invasive option offered for the treatment of large, compressive, benign thyroid nodules. METHODS: Observational studies of more than five participants using HIFU in the management of benign thyroid nodules from 2000 to 2021 were identified using predefined inclusion criteria. The primary outcome was an estimate of the effectiveness of HIFU. RESULTS: Out of 158 studies reviewed, 8 articles were included with 297 patients and 300 nodules. HIFU significantly reduced nodule volume from 1 to 24 months following therapy (weighted mean difference [WMD], 47.68, 95 % confidence interval [CI], 34.13-59.66, p < 0.0001) and achieved favorable success rates (risk ratio [RR], 1.49, 95 % CI, 1.15-1.84, p < 0.001) for 50 % volume reduction. CONCLUSIONS: HIFU appears to be a feasible, safe, and effective treatment modality for patients with benign thyroid nodules. Future research, including randomized controlled trials, is needed to determine therapy optimization, and patient selection to identify the potential role of this new therapy.

Influence factors and nomogram for volume reduction rate in benign thyroid nodule after thermal ablation.

BACKGROUND: Thermal ablation is a minimally invasive and safe treatment for benign thyroid nodules, and the volume reduction rate (VRR) of nodule is a primary clinical efficacy indicator. PURPOSE: To screen factors influencing VRR in benign thyroid nodules after thermal ablation and establish a predictable nomogram. MATERIALS AND METHODS: This retrospective study enrolled 238 patients with benign thyroid nodules who underwent thermal ablation between January 2016 and September 2021. Clinical information and imaging characteristics in routine ultrasound (US) and contrast-enhanced ultrasound (CEUS) were evaluated. Factors influencing the VRR ≥75% were screened using multivariate logistic regression, and a predictable nomogram was established. RESULTS: At the 12-month follow-up, the VRR of nodule was 77.0 ± 20.6% (18.4-100%). Seven factors influencing the VRR ≥75.0% were identified: echogenicity, component, calcification, enhancement degree, enhancement defect, ring enhancement, and energy of ablation. A nomogram was established based on the above factors, and the predictive ability of the model was confirmed by internal validation with 1000 bootstrap repetitions. The area under the receiver-operating characteristic curve (AUC) of the model was 0.926, and the calibration curve and decision curve analysis (DCA) revealed that this model demonstrated predictive ability. CONCLUSION: Seven factors influencing VRR in benign thyroid nodules after thermal ablation were screened out in the present study and used to establish a nomogram to predict the probability of VRR ≥75% at the 12-month follow-up. It would be beneficial to make personalized medical decisions to trigger thermal ablation in patients with benign thyroid nodules.

Organochlorine pesticides induce thyroid tumors through oxidative stress; an in vivo and in silico study.

Thyroid disease is one of the most common endocrine problems around the world. Among the numerous factors, exposure to environmental elements such as pesticides is associated with an increase in the incidence of thyroid disorders. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) in induction of oxidative stress (OS) and development of thyroid tumors. This case-control study was conducted on 61 patients with papillary thyroid carcinoma (PTC), 70 patients with benign thyroid nodules (BTN), and 73 healthy individuals as control. Seven derived OCPs residues measured by gas chromatography (GC), and enzyme activities of acetylcholinesterase (AChE), superoxide dismutase3 (SOD3), catalase (CAT), glutathione peroxidase3 (GPx3) and paraoxonase1 (PON1) and also, non-enzymatic antioxidant including; malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), and nitric oxide (NO) biomarkers in all participants were investigated. Furthermore, all of the above enzymes were docked against measured OCPs. The results revealed that ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4-DDT, and 4,4-DDT levels along with MDA, NO, and PC levels were elevated, while AChE, SOD3, GPx3, CAT, and PON1 activities and TAC levels were decreased in the PTC and BTN groups compared with the control group. Therefore, OCPs might play a role in the development of thyroid tumors through several mechanisms including generation of OS. Importantly, in silico analysis confirmed the in vivo findings.

Comparison of Transoral Endoscopic Thyroidectomy Vestibular Approach and Conventional Open Thyroidectomy in Benign Thyroid Tumors.

Conventional open thyroidectomy remains the standard treatment of surgery for benign thyroid tumors but leaves a permanent scar in the neck. We conducted this study to compare the surgical outcomes of transoral endoscopic thyroidectomy vestibular approach (TOETVA) versus conventional open thyroidectomy (COT), and thence analyze the safety and viability of this approach. Seventy-eight patients who had undergone either COT or TOETVA from 2020 to 2021 in our institution to treat benign thyroid tumors were prospectively studied. Outcomes between the two groups were analyzed, including time of operation, blood loss, hospital stay, postoperative complications, and level of satisfaction. A total of 78 patients, in which TOETVA was applied to 47 patients and COT thyroid surgery was applied to 31 patients, participated in this study. COT has a shorter operative time (59.8 ± 10.8 min versus 102.3 ± 34.9 min, p < .001). TOETVA is less painful postoperatively (visual analog scale score on day 4 of 1.1 ± 1.2 versus 1.8 ± 0.7, p < .001). There were no significant differences between TOETVA and COT groups regarding incidences of transient recurrent laryngeal nerve (RLN) injury (10.6% and 6.5%, respectively, p = .697) and both transient and permanent hypoparathyroidism (8.5% versus 3.5%, p = .644 with transient and 0% versus 6.7%, p = .166 with permanent). Other complications were comparable between two arms such as bleeding, seroma, and infection. At 3 months after surgery, the TOETVA group had the significantly higher proportion of the very satisfied level than the COT group (80.9% versus 35.4%, p < .001). TOETVA in patients with favorable features is a safe, viable alternative to open thyroidectomy regarding postoperative outcomes and provide higher satisfaction after surgery in the long term.

Efficacy and safety of radiofrequency ablation for calcified benign thyroid nodules: results of over 5 years' follow-up.

PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for treating calcified benign thyroid nodules (CBTNs). METHODS: Fifty-two patients with 52 CBTNs who underwent RFA in our hospital were included in this retrospective study. According to the size of calcifications, CBTNs were divided into two groups: the punctate echogenic foci (PEF) group and macrocalcification group. Moreover, the macrocalcification group was further subdivided into two groups, the strong group and the weak group, based on their morphologic characteristics. After the RFA procedure, routine ultrasound (US) and clinical evaluation were performed at 1, 3, 6 and 12 months postoperatively and every 12 months thereafter. RESULTS: The mean follow-up time was 68.98 ± 7.68 months (60-87 months), and the 5-year mean volume reduction rate (VRR) after RFA was 92.95%, with a complication rate of 0.6% (3/52). The mean initial volume of the macrocalcification group was significantly larger than that of the PEF group (9.94 ± 24.60 ml vs. 0.23 ± 0.22 ml, respectively; P = 0.011). Thus, their VRRs were not comparable between the two groups. However, baseline characteristics did not show statistically significant differences between the strong and weak macrocalcification subgroups. The VRRs of the strong subgroup were significantly lower than those of the weak subgroup at the 3-year, 4-year, and 5-year follow-ups. CONCLUSION: RFA was effective and safe for treating CBTNs. Strong macrocalcification was related to the VRR of CBTNs after the RFA procedure.

Preoperative platelet distribution width-to-platelet ratio combined with serum thyroglobulin may be objective and popularizable indicators in predicting papillary thyroid carcinoma.

OBJECTIVES: The incidence of papillary thyroid carcinoma (PTC) has increased more rapidly than that of any other cancer type in China. Early indicators with high sensitivity and specificity during diagnosis are required. To date, there has been a paucity of studies investigating the relationship between preoperative platelet distribution width-to-platelet count ratio (PPR) and PTC. This study thus aimed to assess the diagnostic value of PPR combined with serum thyroglobulin (Tg) in patients with PTC. METHODS: A total of 1001 participants were included in our study. 876 patients who underwent surgery for nodular goiter were divided into the PTC group or benign thyroid nodule (BTN) group according to pathology reports, and 125 healthy controls (HCs) were included. Preoperative hemogram parameters and serum Tg levels were compared among three groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of PPR combined with serum Tg for diagnosing PTC. RESULTS: Platelet distribution width (PDW) and PPR levels were higher in the PTC group than in the BTN and HC groups (both p < 0.05) but did not significantly differ between the BTN and HC groups. PDW and PPR levels significantly differed in the presence/absence of lymph node metastasis, the presence/absence of capsule invasion (p = 0.005), and TNM stages (p < 0.001). Multivariable analyses indicated that high serum Tg levels [adjusted odds ratio (OR), 1.007; 95% confidence interval (CI), 1.004-1.009; p < 0.001], high neutrophil-to-lymphocyte ratio (NLR,adjusted OR, 1.928; 95% CI, 1.619-2.295; p < 0.001), and high PPR (adjusted OR, 1.378; 95% CI, 1.268-1.497; p < 0.001) were independent risk factors for PTC. In ROC analysis, the areas under the curves (AUCs) of serum Tg, PDW, PPR, and NLR for predicting PTC were 0.603, 0.610, 0.706, and 0.685, respectively. PPR combined with serum Tg (PPR + Tg) had a higher diagnostic value (AUC, 0.738; sensitivity, 60%; specificity, 74.7%) compared with PDW + Tg (AUC, 0.656; sensitivity, 64.4%; specificity, 59.9%) and NLR + Tg (AUC, 0.714; sensitivity, 61.6%; specificity, 71.1%). CONCLUSIONS: Preoperative PPR combined with serum Tg may be objective and popularizable indicators for effective predicting PTC.

Tracheal necrosis following thyroid radiofrequency ablation.

INTRODUCTION: Radiofrequency ablation for benign thyroid nodules has a low rate of complications in experienced hands for selected indications, but tracheal necrosis is a major complication. CASE REPORT: A 60 year-old female patient underwent percutaneous radiofrequency ablation of an unesthetic benign isthmic thyroid nodule. The procedure was performed with a cooled electrode, using the "moving shot" technique on a trans-isthmic approach, under general anesthesia. Postoperative course was complicated by dysphonia and cervical pain implicating a third-degree skin burn of the medial cervical region progressing to severe soft-tissue and cervical tracheal necrosis. DISCUSSION: Risk factors in the present case included the general anesthesia, isthmic location and thyroid nodule volume. To avoid this kind of complication, the procedure should be performed under local anesthesia, using cooled dextrose solution hydrodissection between trachea, thyroid and skin. Ahead of radiofrequency ablation, patients should be informed of possible major complications, especially if the indication is cosmetic.

The Year in Surgical Thyroidology: Recent Technological Developments and Future Challenges.

Background: The field of surgical and interventional thyroidology is rapidly evolving. In the past few years, we have seen the introduction and establishment of many novel surgical adjuncts, techniques, and disruptive ablative technologies that have impacted the field. Methods: We identified the most influential articles on technological developments in surgical and interventional thyroidology that were published from September 1, 2020, to August 1, 2021. We searched three electronic databases and consulted experts. Results: Major findings are summarized. Continuous intraoperative nerve monitoring (cIONM) lowered the risk of early postoperative vocal cord palsy 1.8-fold and permanent palsy 29 · 4-fold compared with intermittent intraoperative nerve monitoring. Parathyroid autofluorescence yielded a diagnostic odds ratio (OR) of 228.9 for detection of parathyroid glands over visualization, with 96% sensitivity and 92% specificity. There was no significant difference in the incidence of major complications between the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transcervical thyroidectomy (1.5% vs. 2.1%, p = 0.75), and a higher body mass index did not lead to a significant increase in the odds of cumulative complication with TOETVA for the overweight (OR = 0.52 [95% confidence interval {CI} 0.17-1.58]) and obese groups (OR = 1.69 [CI 0.74-3.88]). Radiofrequency ablation (RFA) for benign thyroid nodules typically resulted in a 50-85% volume reduction with faster recovery times, less pain levels, and higher social and psychological well-being compared with conventional thyroidectomy at 15 months post-treatment, although physical well-being levels were higher in the conventional thyroidectomy group at this time. RFA for papillary thyroid microcarcinoma showed no significant difference in local tumor progression (1.8% vs. 3.3%, p = 0.209), lymph node metastasis (0.6% vs. 0.6%, p = 1.000), recurrence (1.2% vs. 2.4%, p = 0.244), and 4-year recurrence-free survival rates (98.2% vs. 97.0%, p = 0.223) when compared with transcervical lobectomy. Conclusions: cIONM, parathyroid autofluorescence, transoral vestibular approach thyroid surgery, and RFA for benign and malignant thyroid nodules are some of the latest additions to the surgeon's and interventionalist's armamentarium to manage thyroid disease. These technological advancements demonstrate promise to improve outcomes, decrease complications, and enhance a patient's quality of life, but further rigorous studies are needed to define their utility and value.

Factors related to the absorption rate of benign thyroid nodules after image-guided microwave ablation: a 3-year follow-up.

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.

Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma.

Thyroid carcinoma (TC) is the most common endocrine malignancy, and papillary TC (PTC) is the most frequent subtype of TC, accounting for 85-90% of all the cases. Aberrant histone acetylation contributes to carcinogenesis by inducing the dysregulation of certain cancer-related genes. However, the histone acetylation landscape in PTC remains elusive. Here, we interrogated the epigenomes of PTC and benign thyroid nodule (BTN) tissues by applying H3K27ac chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) along with RNA-sequencing. By comparing the epigenomic features between PTC and BTN, we detected changes in H3K27ac levels at active regulatory regions, identified PTC-specific super-enhancer-associated genes involving immune-response and cancer-related pathways, and uncovered several genes that associated with disease-free survival of PTC. In summary, our data provided a genome-wide landscape of histone modification in PTC and demonstrated the role of enhancers in transcriptional regulations associated with prognosis of PTC.

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

Background: Nearly 20 years after the first feasibility study, minimally invasive ultrasound (US)-guided therapeutic techniques are now considered as a safe and effective alternative to surgery for symptomatic benign thyroid nodules. Radiofrequency ablation (RFA) is one of the most widely used treatment in specialized thyroid centers but, due to the relatively recent introduction into clinical practice, there are limited long-term follow-up studies. Aim of our work was to review the outcomes of RFA on solid nonfunctioning and on autonomous thyroid nodules (AFTN) on a long-time period for assessing the results in term of efficacy, complications, and costs and to compare them to the current indications of RFA. Methods: A systematic review was performed using EMBASE and Medline library data between 2008 and 2021. Seventeen studies evaluated RFA for the treatment of benign solid (nonfunctioning or autonomous) thyroid nodules, with an at least 18 months of follow-up. Data extraction and quality assessment were performed by two endocrinologist according to PRISMA guidelines. Anthropometric data, safety and efficacy parameters were collected. Results: The majority of the studies was retrospective study and reported 933 nodules, mostly solid. Baseline volume ranged between 6.1 ± 9.6 and 36.3 ± 59.8 ml. Local analgesia was used and the time duration of the treatment was between 5 ± 2 and 22.1 ± 10.9 min. The volume reduction rate at 12 months ranged from 67% to 75% for the nodule treated with a single procedure and reached to 93.6 ± 9.7% for nodules treated with repeat ablations. The regrowth rate at 12 months ranged from 0% to 34%. Conclusion: All the studies under examination consistently validated the long-term clinical efficacy and the substantial safety of RFA for the treatment of benign thyroid nodules. Thermal ablation, however, is an operator-dependent technique and should be performed in centers with specific expertise. The selection of the patients should be rigorous because the nodule size and the structural and functional characteristics influence the appropriateness and the outcomes of the treatment. Future perspectives as the treatment of micro-papillary thyroid cancer or cervical recurrence need further investigations.

Horner's Syndrome During High-Intensity Focused Ultrasound Ablation for a Benign Thyroid Nodule.

OBJECTIVE: Horner's syndrome (HS) is a rare complication of high-intensity focused ultrasound (HIFU) and radiofrequency ablation for thyroid nodules. We present such a case and discuss how to avoid this complication in the future. METHODS: This case occurred during HIFU treatment of a benign thyroid nodule (BTN). Ultrasound and fine-needle aspiration cytology (FNAC) were performed before the procedure. Volume reduction was evaluated at 6 weeks, 3, 6, and 12 months. Technical success was ≥50% reduction at 6 months. RESULTS: A 30-year-old woman presented with a solitary symptomatic thyroid nodule. Her thyroid stimulating hormone was 1.16 (ref 0.4-3.6) µUI/mL), ultrasound found a 13 mL right-thyroid EU-TIRADS 4 nodule. Two FNACs were read as Bethesda II. The subsequent HIFU procedure was conducted with local 2% lidocaine anesthesia. The procedure was painful (visual analogic scale 10/10) and ipsilateral partial ptosis occurred during the procedure. Volume reduction at 12 months was 34.6% of the initial volume with persisting functional and cosmetic complaints, discomfort, and partial ptosis. As the volume reduction was ≤50%, the procedure was a technical failure. A new FNAC was read as Bethesda IV. A right lobectomy was performed without postoperative outcomes and without requiring hormonal replacement therapy. Pathological evaluation found no malignant cells. CONCLUSION: HS is a rare complication of HIFU for management of BTNs. It may be symptomatic and have sequalae that persist for months. Severe neck pain may by associated, but further investigation is needed.

Efficacy and safety of radiofrequency ablation for benign thyroid nodules in patients with previous thyroid lobectomy.

BACKGROUND: Radiofrequency ablation (RFA) is recommended for the treatment of benign thyroid nodules. However, data on the clinical role of RFA for benign thyroid nodules in patients with history of thyroid lobectomy are insufficient. The purpose of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) for benign thyroid nodules in patients who had previously undergoing thyroid lobectomy. METHODS: From May 2015 to October 2018, a total of 20 patients (19 females, 1 male, mean age 49.50 ± 14.26 years, range 22-74 years) with 20 benign thyroid nodules (mean volume 15.04 ± 21.17 ml, range 0.40-69.67 ml) who had undergone previous thyroid lobectomy were included in this retrospective study. Patients were followed up at 3, 6, 12 months after RFA and every 12 months thereafter by ultrasound, clinical evaluation and thyroid function. Volume, volume reduction rate (VRR), symptom score and cosmetic score were evaluated. RESULTS: During the mean follow-up time of 21.24 ± 16.41 months, the mean nodule volume decreased significantly from 15.04 ± 21.17 ml to 1.29 ± 1.17 ml (P = 0.018) with a mean VRR of 85.41 ± 12.17%. Therapeutic success was achieved in a single session for all thyroid nodules. The symptom score (P = 0.001) and cosmetic score (P = 0.001) were both significantly reduced at the last follow-up. The levels of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone were not significantly different at the last follow-up from those prior to treatment (all P > 0.05). No life-threatening complications or sequelae occurred after RFA. CONCLUSIONS: As a minimally invasive modality, RFA was a safe, effective, and thyroid function-preserving option for patients with symptomatic benign thyroid nodules after a previous lobectomy.