Ethanol ablation for the treatment of thyroglossal duct cysts: follow-up results for longer than 2 years.

OBJECTIVES: To evaluate the long-term efficacy and safety of ethanol ablation (EA) for the treatment of thyroglossal duct cysts (TGDCs). METHODS: This retrospective study included 81 consecutive patients diagnosed with and treated for symptomatic TGDCs at two institutions between Jan 2008 and Oct 2018. Preprocedural evaluation included US assessment with calculation of the TGDC volume. EA was performed under US guidance using 99% ethanol. Post-treatment follow-up was scheduled within 3 months, 6 months, and then annually. Immediate success was defined as a volume reduction ratio (VRR; ratio of the volume difference after EA to the initial TGDC volume) > 50% within 3 months. Long-term success was defined as VRR > 50% or resolution or improvement of cosmetic problems and symptoms without recurrence at last follow-up. RESULTS: Seventy-seven patients underwent EA, and outcomes were assessed in 68 patients with available follow-up data. The immediate success rate of the first EA was 81% (55/68), with a mean VRR within 3 months of 73% ± 31%. One patient (1.5%, 1/68) developed wound inflammation after the first EA. Forty-two patients were followed up for longer than 2 years. For the median follow-up of 69 months (range, 24-131 months), the long-term success rate was 83% (35/42), with a mean VRR at last follow-up of 81% ± 35%. No patients developed malignancy from the ablated TGDCs. CONCLUSIONS: EA for treatment of TGDCs achieved acceptable rates of immediate and long-term efficacy with a low complication rate, and can be considered as a first-line treatment for the management of TGDCs. KEY POINTS: • The immediate success rate of EA for the treatment of TGDCs was 81% (55/68), with a mean VRR within 3 months of 73% ± 31%. • For the median follow-up of 69 months (range, 24-131 months), the long-term success rate was 83% (35/42), with a mean VRR at last follow-up of 81% ± 35%. • No patients developed malignancy from the ablated TGDCs but one patient (1.5%, 1/68) developed wound inflammation after the first EA.

Treatment Efficacy and Safety of Ethanol Ablation for Thyroglossal Duct Cysts: A Comparison with Surgery.

OBJECTIVE: To compare the efficacy and safety of ethanol ablation (EA) for thyroglossal duct cyst (TGDC) against surgery. METHODS: This study included 345 patients (289, surgery; 56, EA) treated for TGDC at four institutions between May 2005 and June 2014. Surgery (whole surgery and Sistrunk operation which is the current standard surgical method) and EA were compared with respect to the treatment failure and complication rates. The cost of EA and surgery was also compared. The Cox regression hazard model and linear regression were used for the adjustment of covariates. RESULTS: EA demonstrated higher treatment failures (19.6% vs. 2.4%, p < 0.001[whole surgery] and 1.2%, p = 0.004 [Sistrunk operation]), but fewer complications (1.8% vs. 10.0%, p = 0.04 [whole surgery] and 10.2%, p = 0.06 [Sistrunk operation]), and lower cost (₩423,801 vs. ₩1,435,707 [whole surgery]) than surgery. EA achieved 85.7% of treatment success up to second session. The mean volume reduction rate after EA was 82.3% at last follow-up. Young age and EA were correlated with treatment failure (p = 0.01 and 0.001, respectively). CONCLUSION: Both surgery and EA had acceptable treatment efficacy in the management of TGDC. Although there is a higher likelihood of treatment failure with EA, it has a better safety profile than surgery. KEY POINTS: • Both surgery and ethanol ablation show acceptable treatment efficacy for TGDC. • Considering treatment failure, surgery manages TGDC more effectively than EA. • EA is safer than surgery and presents no major complications. • EA could be an alternative treatment for TGDC in selected patients.

Depletion of p18/LAMTOR1 promotes cell survival via activation of p27(kip1) -dependent autophagy under starvation.

The MAPK and mTOR signal pathways in endosomes or lysosomes play a crucial role in cell survival and death. They are also closely associated with autophagy, a catabolic process highly regulated under various cellular stress or nutrient deprivation. Recently we have isolated a protein, named p18/LAMTOR1, that specifically regulates the ERK or mTOR pathway in lysosomes. p18/LAMTOR1 also interacts with p27(kip1) . Here we examined how p18/LAMTOR1 plays a role in autophagy under nutrient deprivation. The p18(+/+) MEF cells were more susceptible to cell death under starvation or in the presence of AICAR in comparison with p18(-/-) MEF cells. Cleavage of caspase-3 was increased in p18(+/+) MEF cells under starvation, and phosphorylation at the threonine 198 of p27(kip1) was highly elevated in starved p18(-/-) MEF cells. Furthermore, LC3-II formation and other autophagy-associated proteins were largely increased in p18-deficient cells, and suppression of p27(kip1) expression in p18(-/-) MEF cells mitigated starvation-induced cell death. These data suggest that ablation of p18/LAMTOR1 suppresses starvation-induced cell death by stimulating autophagy through modulation of p27(kip1) activity.

Clinical characteristics of papillary thyroid microcarcinoma less than or equal to 5 mm on ultrasonography.

Management of papillary thyroid microcarcinoma sized ≤5 mm identified on ultrasonography is controversial. In this study, we evaluated the clinical characteristics of papillary thyroid microcarcinoma sized ≤5 mm on ultrasonography in comparison to those >5 mm and sought to present rationales for optimal management in papillary thyroid microcarcinoma ≤5 mm. The medical records of 396 patients who underwent surgery for papillary thyroid carcinoma between 2009 and 2011 were retrospectively analyzed. The patients were grouped into A (≤5 mm, n = 132) or B (>5 mm, n = 264) and the clinicopathologic characteristics of the patients were reviewed and compared between the two groups. Tumor capsular invasion (45.5 vs. 59.8 %, p = 0.007) and cervical lymph node metastasis (18.2 vs. 29.2 %, p = 0.018) were more frequent in group B. Nonetheless, group A presented lymph node metastasis in 42.3 % of multifocal cases showing no difference to that of group B (41.5 %, p = 0.946) and also included five cases (3.8 %) of lateral neck metastasis. Multifocality was the only predictive factor for lymph node metastasis in group A (p < 0.001). Over half (55.3 %) of the patients of group A were diagnosed with papillary carcinoma in private clinics; however, only 5.5 % of these patients underwent assessment of lateral neck lymph nodes initially. In conclusion, higher risk of cervical lymph node metastasis should be considered in evaluation and surgical decision of papillary thyroid microcarcinoma ≤5 mm identified on ultrasonography with multifocality. Evaluation of the cervical lymph nodes including the lateral neck should not be overlooked when suspicious thyroid nodule suggesting malignancy sized ≤5 mm shows multifocal lesions.

Partial cutting of sternothyroid muscle during total thyroidectomy: impact on postoperative vocal outcomes.

BACKGROUND: Cutting the sternothyroid (ST) muscle is a useful technique to expose the superior pole of thyroid gland during thyroidectomy. In this study, we evaluated the impact of partial cutting of the ST muscle on postoperative vocal outcomes after total thyroidectomy. METHODS: A retrospective review of 57 patients who underwent total thyroidectomy with central neck dissection for micropapillary thyroid carcinoma was conducted. Group A (n = 26) included those without cutting the ST muscle, while group B (n = 31) included patients whose muscle was partially cut at the superior pole. All patients underwent voice analysis before the operation and 2 weeks and 1 month after the surgery, and the outcomes were compared between the two groups. RESULTS: There were no differences between the two groups regarding the outcomes at each time of voice analysis. Group A showed a decrease of maximum frequency 2 weeks after surgery but showed no difference after 1 month. Group B showed a mild decrease in maximum frequency 2 weeks after surgery, but the difference was not significant. CONCLUSION: Partial cutting of ST muscle during thyroidectomy is useful to expose the superior pole without significant negative impact on postoperative outcomes of vocal analysis.

Complications encountered in the treatment of benign thyroid nodules with US-guided radiofrequency ablation: a multicenter study.

PURPOSE: To evaluate clinical aspects and imaging features of complications encountered in the treatment of benign thyroid nodules with radiofrequency (RF) ablation. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. From June 2002 to September 2009, 1459 patients underwent RF ablation of 1543 thyroid nodules with an RF system with internally cooled electrodes at 13 thyroid centers, which were members of Korean Society of Thyroid Radiology. Numbers and types of major and minor complications were assessed. RESULTS: The authors observed 48 complications (3.3%), 20 major and 28 minor. The major complications were voice changes (n = 15), brachial plexus injury (n = 1), tumor rupture (n = 3), and permanent hypothyroidism (n = 1). The minor complications were hematoma (n = 15), skin burn (n = 4), and vomiting (n = 9). All patients recovered spontaneously except for one with permanent hypothyroidism and one who underwent surgery. CONCLUSION: Although the complication rate of RF ablation is low, various complications may occur; comprehension of complications and suggested technical tips may prevent complications or properly manage those that occur.

US-Guided Radiofrequency Ablation for Low-Risk Papillary Thyroid Microcarcinoma: Efficacy and Safety in a Large Population.

OBJECTIVE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in a large population. MATERIALS AND METHODS: Cases of 152 biopsy-proven PTMCs from 133 patients who had undergone RFA for PTMC between May 2008 and January 2017 were included in this study. All patients were either of high surgical risk or refused to undergo surgery. They were followed up for at least 6 months after initial RFA. Ultrasonography (US) and computed tomography were performed to evaluate the PTMC and the presence of neck metastasis before treatment. RFA was conducted using an internally cooled thyroid-dedicated electrode system. Follow-up US was performed at 1 week, and 2, 6, and 12 months, after the initial RFA, and then at every 6-12 months. We evaluated serial changes of ablated tumors, newly developed cancers, lymph node (LN) or distant metastasis and complications. RESULTS: Complete disappearance was found in 91.4% (139/152) of ablated tumors. Among the 13 tumors in patients who did not show complete disappearance, no tumor displayed any regrowth of the residual ablated lesion during the follow-up period. The mean follow-up period was 39 months. During the follow-up period, there were no local recurrence, no LN or distant metastasis, and no newly developed thyroid cancers. No patients were referred to surgery. The overall complication rate was 3% (4/133) of patients, including one voice change. There were no life-threatening complications or procedure-related deaths. CONCLUSION: Our results suggest that RFA is an effective and safe option for treating low-risk PTMC patients who are of high surgical risk or refuse surgery.

Ethanol Ablation of the Thyroid Nodules: 2018 Consensus Statement by the Korean Society of Thyroid Radiology.

Minimally invasive treatment of symptomatic thyroid nodules is now commonplace. Ethanol ablation (EA) of thyroid cystic nodules has been performed since the 1990s, but there is no global consensus or guideline. Although various limitations of EA have been described, recommendations for practical application are necessary. Therefore, the Task Force Committee of the Korean Society of Thyroid Radiology initiated the present consensus statement and here we provide recommendations for the role of EA in the management of symptomatic thyroid nodules. These recommendations are based on evidence to date from the literature and expert opinion.

Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A Prospective Multicenter Study.

Objective: To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. Materials and Methods: From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15-79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1-80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. Results: The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. Conclusion: Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules.

2017 Thyroid Radiofrequency Ablation Guideline: Korean Society of Thyroid Radiology.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed recommendations for the optimal use of radiofrequency ablation for thyroid tumors in 2012. As new meaningful evidences have accumulated, KSThR decided to revise the guidelines. The revised guideline is based on a comprehensive analysis of the current literature and expert consensus.

Core Needle Biopsy of the Thyroid: 2016 Consensus Statement and Recommendations from Korean Society of Thyroid Radiology.

Core needle biopsy (CNB) has been suggested as a complementary diagnostic method to fine-needle aspiration in patients with thyroid nodules. Many recent CNB studies have suggested a more advanced role for CNB, but there are still no guidelines on its use. Therefore, the Task Force Committee of the Korean Society of Thyroid Radiology has developed the present consensus statement and recommendations for the role of CNB in the diagnosis of thyroid nodules. These recommendations are based on evidence from the current literature and expert consensus.

Image reporting and characterization system for ultrasound features of thyroid nodules: multicentric Korean retrospective study.

OBJECTIVE: The objective of this retrospective study was to develop and validate a simple diagnostic prediction model by using ultrasound (US) features of thyroid nodules obtained from multicenter retrospective data. MATERIALS AND METHODS: Patient data were collected from 20 different institutions and the data included 2000 thyroid nodules from 1796 patients. For developing a diagnostic prediction model to estimate the malignant risk of thyroid nodules using suspicious malignant US features, we developed a training model in a subset of 1402 nodules from 1260 patients. Several suspicious malignant US features were evaluated to create the prediction model using a scoring tool. The scores for such US features were estimated by calculating odds ratios, and the risk score of malignancy for each thyroid nodule was defined as the sum of these individual scores. Later, we verified the usefulness of developed scoring system by applying into the remaining 598 nodules from 536 patients. RESULTS: Among 2000 tumors, 1268 were benign and 732 were malignant. In our multiple regression analysis models, the following US features were statistically significant for malignant nodules when using the training data set: hypoechogenicity, marked hypoechogenicity, non-parallel orientation, microlobulated or spiculated margin, ill-defined margins, and microcalcifications. The malignancy rate was 7.3% in thyroid nodules that did not have suspicious-malignant features on US. Area under the receiver operating characteristic (ROC) curve was 0.867, which shows that the US risk score help predict thyroid malignancy well. In the test data set, the malignancy rates were 6.2% in thyroid nodules without malignant features on US. Area under the ROC curve of the test set was 0.872 when using the prediction model. CONCLUSION: The predictor model using suspicious malignant US features may be helpful in risk stratification of thyroid nodules.

Radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: consensus statement and recommendations.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus.

Autophagy protects the rotenone-induced cell death in alpha-synuclein overexpressing SH-SY5Y cells.

Loss of dopaminergic cells induced by alpha-synuclein accumulation in substantia nigra causes the development of Parkinson's disease (PD). To date, although autophagy has been implicated in the pathology of PD, the molecular mechanism is still unclear. To study the role of autophagy in PD pathogenesis, we established stable SH-SY5Y cell lines overexpressing wild-type or mutant alpha-synuclein proteins (A30P or A53T). Overexpression of mutant alpha-synuclein induced some protein aggregates and cell death in the absence of drug. LC3-II protein, a critical marker for autophagy, was produced in an autophagy-dependent manner. The rotenone-induced cell death was interrupted by autophagy stimulation. Autophagy activation also restored the mitochondrial membrane potential (MMP) impaired by rotenone in mutant alpha-synuclein expressing cells. Additionally, autophagy activation significantly relieved rotenone-induced ROS accumulation and HIF-1alpha expression in neuronal cells expressing mutant alpha-synuclein proteins. These findings indicate that autophagy plays an important scavenger role against harmful influence of toxic protein aggregates produced in rotenone-treated cells.

Proteomic analysis in NSAIDs-treated primary cardiomyocytes.

NSAIDs (non-steroidal anti-inflammatory drugs) are widely used for the treatment of a variety of inflammatory diseases, but many of them were withdrawn from the market due to their cardiovascular toxicity. In this study, we tried to identify proteins responding to the cellular toxicity in NSAIDs-treated primarily cultured cardiomyocytes using 2-D proteomic analysis. We used seven different NSAIDs (celecoxib, rofecoxib, valdecoxib, diclofenac, naproxen, ibuprofen, and meloxicam) possessing each different degree of cardiovascular risk. Overall protein spots were similar in all NSAIDs-treated cells although numbers of decreased proteins were about 2-fold higher in celecoxib or rofecoxib-treated cells than in cells incubated with other NSAIDs. Many stress-related proteins, cardiac muscle movement proteins and proteins involved in membrane organization have been isolated. Among them, Septin-8, a filament scaffolding protein, showed its specific expression pattern depending on the extent of drug toxicity. Its expression level was low in cells treated by relatively high toxic drugs such as celecoxib, diclofenac, valdecoxib, and rofecoxib. On the contrary, Septin-8 was similarly expressed in control cells in the presence of less toxic drugs such ibuprofen, naproxen, and meloxicam. This data suggests that Septin-8 differentially responds to each NSAID.

Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats.

Autophagy has been implicated in cardiac cell death during ischemia/reperfusion (I/R). In this study we investigated how propofol, an antioxidant widely used for anesthesia, affects the autophagic cell death induced by the myocardial I/R injury. The infarction size in the myocardium was dramatically reduced in rats treated with propofol during I/R compared with untreated rats. A large number of autophagic vacuoles were observed in the cardiomyocytes of I/R-injured rats but rarely in I/R-injured rats treated with propofol. While LC3-II formation, an autophagy marker, was up-regulated in the I/R-injured myocardium, it was significantly down-regulated in the myocardial tissues of I/R-injured and propofol-treated rats. Moreover, propofol inhibited the I/R-induced expression of Beclin-1, and it accelerated phosphorylation of mTOR during I/R and Beclin-1/Bcl-2 interaction in cells, which indicates that it facilitates the inhibitory pathway of autophagy. These data suggest that propofol protects the autophagic cell death induced by the myocardial I/R injury.

Comparative analysis of fat and muscle proteins in fenofibrate-fed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein.

Fenofibrate, an agonist of PPARalpha, plays an important role in activating many proteins catalyzing lipid metabolism, and it also has a considerable effect on improvement of insulin sensitivity in the diabetic condition. To investigate fenofibrate-dependent expression of peripheral tissue proteins in diabetes, we analyzed whole muscle or fat proteins of fenofibrate-fed OLETF rats, an animal model of type II diabetes, using 2-dimensional gel electrophoresis. We found that many proteins were specifically expressed in a fenofibrate-dependent manner in these diabetic rats. In particular, a functionally unknown C11orf59 protein was differentially expressed in the muscle tissues (about 5-fold increase) in fenofibrate-fed OLETF rats as compared to control rats. Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose tissues. We suggest here that these proteins might be involved in controlling lipid or carbohydrate metabolism in diabetes via PPARalpha activation.