Role of Locoregional Therapies in the Treatment of Thyroid Pathology: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The role of locoregional therapy in the management of thyroid pathology is rapidly evolving. The Society of Interventional Radiology Foundation commissioned an international research consensus panel consisting of physicians from multiple disciplines with expertise in the management of benign and malignant thyroid disease. The panel focused on identifying gaps in the current body of literature to establish research priorities that have the potential to shape the landscape of minimally invasive thyroid interventions. The topics discussed were centered on the emerging role of ablation for malignant thyroid tumors and the treatment of large functioning nodules with embolization and ablation. Specifically, the panel prioritized identifying nodule characteristics, including size and location, that are associated with ideal outcomes following thermal ablation for papillary thyroid microcarcinoma through the development of an international registry or a prospective, multi-institutional trial. The panel also prioritized evaluating the role of locoregional therapy in Stage T1b papillary thyroid cancer through a sequence of two studies: a Phase I study of ablation followed by immediate resection of Stage T1b papillary thyroid cancer, which may lead to a Phase II prospective, multi-institutional study of ablation followed by biopsy for Stage T1b papillary thyroid cancer. Lastly, the panel prioritized investigating the treatment of large, functioning thyroid nodules greater than 20 ml in volume through a randomized clinical trial or prospective registry comparing embolization alone with embolization followed by ablation.

Ten-Year Outcomes of Radiofrequency Ablation for Locally Recurrent Papillary Thyroid Cancer.

OBJECTIVE: This study investigates the long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC). MATERIALS AND METHODS: We retrospectively analyzed 39 consecutive patients with 61 locally recurrent PTCs (14 males, 25 females; mean ± standard deviation age, 52.8 ± 16.7 years; range 21-92 years) who underwent US-guided RFA with curative intent between September 2008 and April 2012. A subgroup of 24 patients with 37 recurrent PTCs who had a follow-up of at least 10 years were analyzed separately. All patients were followed for changes in lesion size on US and thyroglobulin (Tg) levels at 1, 3, 6, and 12 months after RFA, with follow-up every 6-12 months thereafter. Any complications were documented during the follow-up period. Recurrence-free survival (RFS) rates were assessed using Kaplan-Meier estimates. Long-term outcomes were evaluated in patients with follow-up of at least 10 years. RESULTS: The follow-up period ranged from 7 to 180 months (median 133 months). The RFS rates for the 39 patients at 3, 5, and 10 years were 86.8%, 75.5%, and 60.6%, respectively. Among the 24 patients with 37 recurrent PTCs followed for more than 10 years, the volume reduction rate was 99.9% (range 96%-100%), and the complete tumor disappearance rate was 91.9%. The mean serum Tg level also decreased significantly, from 2.66 ± 86.5 mIU/L before ablation to 0.43 ± 0.73 mIU/L (P < 0.001) at the final follow-up. In 14 (58.3%) of the 24 patients, Tg levels were undetectable (below 0.08 mIU/L) at the last follow-up. No life-threatening or delayed complications were observed during the 10-year follow-up period. CONCLUSION: The high RFS throughout the follow-up period, with efficacy and safety lasting beyond 10 years, supports US-guided RFA as a valuable option for local control of recurrent PTCs.

Radiofrequency Ablation for the Treatment of Benign Thyroid Nodules: 10-Year Experience.

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4) or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4) or newly detected thyroid tumors (n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

Enhancement on CT for preoperative diagnosis of metastatic lymph nodes in thyroid cancer: a comparison across experience levels.

OBJECTIVES: To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience. MATERIALS AND METHODS: This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LNA) and venous phase (LNV), LNA normalized to the common carotid artery (NAVCCA), internal jugular vein (NAVIJV), and sternocleidomastoid muscle (NAVSCM), attenuation difference [AD; (LNA - MAVSCM)], and relative washout ratio [((LNA - LNV)/LNA) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated. RESULTS: Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LNV showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAVCCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAVIJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist. CONCLUSION: Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement. CLINICAL RELEVANCE STATEMENT: When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary. KEY POINTS: Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs.

Comparative efficacy and safety of radiofrequency ablation and microwave ablation in benign thyroid nodule treatment: a systematic review and meta-analysis.

OBJECTIVE: Ultrasound-guided thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), has become one of the main options for treating benign thyroid nodules (BTNs). To assess the efficacy of thermal ablation of BTNs, we performed a systematic review and meta-analysis of relevant studies. MATERIALS AND METHODS: A comprehensive search of MEDLINE, EMBASE, and COCHRANE databases was performed up to September 25, 2023, to identify studies directly comparing RFA and MWA for pathologically proven BTNs and reporting clinical outcomes and complications. Data extraction and quality assessment were independently performed by two radiologists according to PRISMA guidelines. The analysis yielded the serial volume reduction ratios (VRRs) of ablated nodules for up to 12 months, symptom and cosmetic scores, and complications. RESULTS: This analysis included nine studies with 1305 BTNs treated by RFA and 1276 by MWA. VRRs at 1 month, 3 months, and 6 months were similar between RFA and MWA, but RFA showed a significantly higher VRR (83.3%) than MWA (76.9%) at 12 months (p = 0.02). Complication rates showed no significant difference between the two methods. Symptom and cosmetic scores significantly decreased after ablation, without a significant difference between the methods. Subgroup analysis indicated a significantly higher VRR at 12 months for RFA than for MWA for less experienced investigators (≤ 10 years), but no significant difference for more experienced investigators (> 10 years). CONCLUSION: RFA and MWA are both effective and safe methods for treating BTNs. RFA showed a higher VRR at 12 months and seems more suitable for less experienced investigators. CLINICAL RELEVANCE STATEMENT: RFA and MWA are both effective and safe treatments for BTNs, with RFA showing a higher VRR at 12 months. Both methods offer minimally invasive and reliable treatment for thyroid nodules. KEY POINTS: The most effective thermal ablation technique for BTNs remains undetermined. RFA showed a higher VRR at 12 months than MWA. Both techniques are effective for treating thyroid nodules; RFA offers greater benefits, particularly for less experienced investigators.

Effectiveness of microvascular flow imaging for radiofrequency ablation in recurrent thyroid cancer: comparison with power Doppler imaging.

OBJECTIVES: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.

Tumor Growth Kinetics Based on Initial Tumor Volume Doubling Time in Active Surveillance of Low-Risk Papillary Thyroid Carcinoma.

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

Paradigm Shift in Rhinoplasty with Virtual 3D Surgery Software and 3D Printing Technology.

Most Asians have a nose with a short columella and a low dorsum; augmentation rhinoplasty using implants is commonly performed in Asian countries to achieve a taller and more well-defined nasal dorsum. However, the current knowledge is insufficient to fully understand the various subjective desires of patients, reflect on them during surgery, or to objectively analyze the results after surgery. Advances in digital imaging technologies, such as 3D printing and 3D scanning, have transformed the medical system from hospital-centric to patient-centric throughout the medical field. In this study, we applied these techniques to rhinoplasty. First, we used virtual 3D plastic surgery software to enable surgical planning through objectified numerical calculations based on the visualized data of the patient's medical images rather than simple virtual plastic surgery. Second, the customized nasal implant was manufactured by reflecting the patient's anatomical shape and virtual 3D plastic surgery data. Taken together, we describe the surgical results of applying these rhinoplasty solutions in four patients. Our experience indicates that high fidelity and patient satisfaction can be achieved by applying these techniques.

Ethanol Ablation of Ranulas and Risk Factor Analysis for Recurrence.

Importance: Ethanol ablation (EA) was shown to be safe and effective for treating ranula, but few studies have assessed long-term outcomes and recurrence of ranula after EA. Objective: To evaluate the long-term outcomes and the risk factors for recurrence and receipt of subsequent surgery in patients who underwent treatment with EA for ranula. Design, Setting, and Participants: This case-series study was conducted at a single tertiary hospital and assessed patients who were treated with EA between July 2009 and March 2021. Among 70 consecutive patients, those with follow-up loss or who were followed up for less than 24 months were excluded. Exposures: EA for ranula. Main Outcomes and Measures: The primary outcome was recurrence at last follow-up after single or multiple EA sessions. Secondary outcomes included receipt of subsequent surgery and the recurrence-free survival (RFS) rate after initial EA. Factors possibly associated with outcomes included patient age and sex; ranula site, type, diameter, volume, and echogenicity; the presentation-to-EA interval; parapharyngeal space extension; and sublingual gland herniation. Risk factors were identified on logistic regression analyses. Two-year RFS rates were analyzed for the initial cohort using the Kaplan-Meier method and compared by log-rank tests. Results: A total of 57 patients (mean [SD] age, 26.4 [12.1] years; 24 female individuals [42%]) who were followed up for a median of 57 months (range, 24-167 months) were included. The recurrence rate was 33% (n = 19), and 11 (19%) underwent subsequent surgery. Among patients with recurrence, 86% (31 of 36) experienced first recurrence within 12 months after initial EA. A presentation-to-EA interval of 12 months or longer was associated with an increased risk of recurrence (adjusted odds ratio [OR], 3.74; 95% CI, 1.01-13.82). No risk factors were significantly associated with subsequent surgery (highest OR in parapharyngeal space extension: adjusted OR, 4.96; 95% CI, 0.94-26.35). Among the initial cohort of 70 patients, 2-year RFS was lower in a maximum diameter of ranula of 5 cm or greater than less than 5 cm (24% [95% CI, 7%-41%] vs 50% [95% CI, 34%-66%]; difference, 26% [95% CI, -4% to 56%]; log-rank test, P = .02). Conclusions and Relevance: This case-series study found that the recurrence rate of ranula after EA was 33%. A presentation-to-EA interval of 12 months or longer may be a risk factor for recurrence, suggesting that early intervention with EA might minimize recurrence. Most first recurrences occurred within 12 months after EA, with a maximum diameter of ranula of 5 cm or greater being a possible risk factor.

Knot-and-ear sign: a pathognomonic ultrasonographic feature of suture granuloma after thyroid surgery.

PURPOSE: This study investigated the clinical and ultrasonographic (US) findings of suture granulomas and recurrent tumors, and aimed to identify specific characteristics of suture granulomas through an experimental study. METHODS: This retrospective study included 20 pathologically confirmed suture granulomas and 40 recurrent tumors between January 2010 and December 2020. The clinical findings included suture material, surgery, and initial TNM stage. The US findings included shape, size, margin, echogenicity, heterogeneity, vascularity, and internal echogenic foci. The distribution, paired appearance, and "knot-and-ear" appearance of internal echogenic foci were assessed. An experiment using pork meat investigated the US configuration of suture knots. RESULTS: Eighteen patients with 20 suture granulomas (15 women; mean age, 52±13 years) and 37 patients with 40 recurrent tumors (24 women; 54±18 years) were included. Patients with suture granulomas exhibited earlier initial T and N stages than those with recurrent tumors. The knot-and-ear appearance, defined as an echogenic dot accompanied by two adjacent echogenic dots or lines based on experimental findings, was observed in 50% of suture granulomas, but not in recurrent tumors (P<0.001). Central internal echogenic foci (68.8%, P=0.023) and paired appearance (75.0%, P<0.001) were more frequent in suture granulomas. During follow-up, 94.1% of suture granulomas shrunk. CONCLUSION: The knot-and-ear appearance is a potential pathognomonic finding of suture granuloma, and central internal echogenic foci with paired appearance were typical US features. Clinically, suture granulomas showed early T and N stages and size reduction during follow-up. Understanding these features can prevent unnecessary biopsy or diagnostic surgery.

Malignancy risk of indeterminate lymph node at the central compartment in patients with thyroid cancer and concomitant sonographic thyroiditis.

BACKGROUND: To evaluate the malignancy risk of sonographic (US) indeterminate lymph node (LN)s at the central compartment in thyroid cancer patients with US-thyroiditis (ST). METHODS: Among the central compartments of suspicious, indeterminate, and probably benign LN US categories, the malignancy rates were compared between ST and non-US-thyroiditis (non-ST) groups. Those of indeterminate category were compared with suspicious and probably benign categories. RESULTS: At 531 central compartments from 349 patients, the malignancy rate was lower in ST group (34.4% [44/128]) than non-ST group (43.4% [175/403]), although statistically not significant (p = 0.08). The malignancy rate of indeterminate category in ST group (35.7% [5/14]) was lower than non-ST group (71.9% [23/32]) (p = 0.047). Within ST group, the malignancy rate of indeterminate category (35.7% [5/14]) did not differ from probably benign category (29.1% [30/103]) (p = 0.756), but was lower than suspicious category (81.8% [9/11]) (p = 0.042). CONCLUSIONS: The malignancy risk of US indeterminate LNs at the central compartment in thyroid cancer patients with US thyroiditis was lower than that in patients without US thyroiditis.

The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy.

BACKGRUOUND: We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB). METHODS: This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy. RESULTS: Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system. CONCLUSION: Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

Impact of Region-of-Interest Size on the Diagnostic Performance of Shear Wave Elastography in Differentiating Thyroid Nodules.

This study investigated the impact of different region-of-interest (ROI) sizes (Max, 1 mm, and 2 mm) on shear wave elastography (SWE) in differentiating between malignant and benign thyroid nodules. The study cohort comprised 129 thyroid nodules (50 malignant, 79 benign) and 78 normal subjects. Diagnostic efficacy was assessed through pairwise comparisons of area under the curve (AUC) values in receiver operating characteristic analysis by using DeLong's test. Our results indicated significant differences in all SWE elasticity metrics between the groups, with malignant nodules exhibiting higher values than benign nodules (p < 0.05). Smaller ROIs (1 and 2 mm) were found to outperform the max ROI in terms of diagnostic accuracy, particularly for the Emax and Emin elasticity metrics. Emax(1mm) had the highest diagnostic accuracy, with an AUC of 0.883, sensitivity of 74.0%, and specificity of 86.1%. This study underscores the significant influence of ROI size selection on the diagnostic performance of SWE, offering valuable insights for future research and clinical applications in thyroid nodule assessment.

Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration.

PURPOSE: Active surveillance (AS) is an alternative treatment approach for small, low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to assess the clinical outcomes of small, highly suspicious nodules lacking initial cytological confirmation. METHODS: This study included 112 patients with highly suspicious nodules measuring ≤ 10 mm who underwent serial ultrasound at Asan Medical Center, Korea, between 2010 and 2023. RESULTS: The median participant age was 51.9 years, and 74.1% were female. The median maximal tumor diameter and tumor volume (TV) were 4.5 (interquartile range [IQR] 3.7-5.2, range 2.2-9.3) mm and 25.2 (IQR 13.1-49.2) mm3, respectively. During a median follow-up period of 4.8 years, four (3.6%) patients showed a ≥ 3 mm increase in maximal diameter, and two (1.8%) developed new lymph node (LN) metastasis. Disease progression was associated with a TV doubling time (TVDT) of < 5 years and a ≥ 75% increase in TV (p = 0.017 and p < 0.005, respectively). Furthermore, 34.8% of patients underwent fine needle aspiration (FNA), primarily at their own request, yielding 46.2%, 5.1%, 41.0%, and 12.8 % malignant, benign, indeterminate, and non-diagnostic results, respectively. Of 18 patients with PTMC, 8 (44.4%) underwent surgery and 10 continued AS, with no LN metastasis during AS and no postoperative recurrence. CONCLUSION: Small, highly suspicious nodules had a low disease progression rate during AS without FNA. Disease progression was associated with a TVDT of < 5 years and a ≥ 75% increase in TV. FNA can be performed more conservatively than it currently is in patients with highly suspicious nodules measuring ≤ 10 mm.

Impact of Additional Preoperative Computed Tomography Imaging on Staging, Surgery, and Postsurgical Survival in Patients With Papillary Thyroid Carcinoma.

OBJECTIVE: We investigated the impacts of computed tomography (CT) added to ultrasound (US) for preoperative evaluation of patients with papillary thyroid carcinoma (PTC) on staging, surgical extent, and postsurgical survival. MATERIALS AND METHODS: Consecutive patients who underwent surgery for PTC between January 2015 and December 2015 were retrospectively identified. Of them, 584 had undergone preoperative additional thyroid CT imaging (CT + US group), and 859 had not (US group). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for 14 variables and balance the two groups. Changes in nodal staging and surgical extent caused by CT were recorded. The recurrence-free survival and distant metastasis-free survival after surgery were compared between the two groups. RESULTS: In the CT + US group, discordant nodal staging results between CT and US were observed in 94 of 584 patients (16.1%). Of them, CT accurately diagnosed nodal staging in 54 patients (57.4%), while the US provided incorrect nodal staging. Ten patients (1.7%) had a change in the extent of surgery based on CT findings. Postsurgical recurrence developed in 3.6% (31 of 859) of the CT + US group and 2.9% (17 of 584) of the US group during the median follow-up of 59 months. After adjustment using IPTW (580 vs. 861 patients), the CT + US group showed significantly higher recurrence-free survival rates than the US group (hazard ratio [HR], 0.52 [95% confidence interval {CI}, 0.29-0.96]; P = 0.037). PSM analysis (535 patients in each group) showed similar HR without statistical significance (HR, 0.60 [95% CI, 0.31-1.17]; P = 0.134). For distant metastasis-free survival, HRs after IPTW and PSM were 0.75 (95% CI, 0.17-3.36; P = 0.71) and 0.87 (95% CI, 0.20-3.80; P = 0.851), respectively. CONCLUSION: The addition of CT imaging for preoperative evaluation changed nodal staging and surgical extent and might improve recurrence-free survival in patients with PTC.

Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPß) stability and accelerates adipogenesis and lipid accumulation.

Dysregulation of the ubiquitin-proteasome system has been implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes, and non-alcoholic fatty liver disease; however, the mechanisms controlling pathogenic metabolic disorders remain unclear. Transcription factor CCAAT/enhancer binding protein beta (C/EBPß) regulates adipogenic genes. The study showed that the expression level of C/EBPß is post-translationally regulated by the deubiquitinase ubiquitin-specific protease 1 (USP1) and that USP1 expression is remarkably upregulated during adipocyte differentiation and in the adipose tissue of mice fed a high-fat diet (HFD). We found that USP1 directly interacts with C/EBPß. Knock-down of USP1 decreased C/EBPß protein stability and increased its ubiquitination. Overexpression of USP1 regulates its protein stability and ubiquitination, whereas catalytic mutant of USP1 had no effect on them. It suggests that USP1 directly deubiquitinases C/EBPß and increases the protein expression, leading to adipogenesis and lipid accumulation. Notably, the USP1-specific inhibitor ML323-originally developed to sensitize cancer cells to DNA-damaging agents-decreased adipocyte differentiation and lipid accumulation in 3T3-L1 cells without cytotoxicity. Oral gavage of ML323 was administered to HFD-fed mice, which showed weight loss and improvement in insulin and glucose sensitivity. Both fat mass and adipocyte size in white adipose tissues were significantly reduced by ML323 treatment, which also reduced the expression of genes involved in adipogenesis and inflammatory responses. ML323 also reduced lipid accumulation, hepatic triglycerides, free fatty acids, and macrophage infiltration in the livers of HFD-fed mice. Taken together, we suggest that USP1 plays an important role in adipogenesis by regulating C/EBPß ubiquitination, and USP1-specific inhibitor ML323 is a potential treatment option and further study by ML323 is needed for clinical application for metabolic disorders.

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Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. In Korea, RFA for thyroid nodules was first performed in 2002, and a large population study was published in 2008. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed its first recommendations for RFA in 2009, which were revised in 2012 and 2018. The KSThR guideline was the first guideline for RFA of thyroid nodules worldwide and has become a guideline for physicians to perform thyroid RFA in Korea and other countries around the world. These guidelines have contributed significantly to the establishment and widespread use of RFA worldwide. In addition, since 2015, the KSThR has conducted intensive hands-on courses depending on the level of the participants. In this article, the authors introduce the history of eduction for RFA conducted by the KSThR and describe the learning curve of RFA and current training programs in Korea, along with future directions for training programs.