The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

US Predictors of Papillary Thyroid Microcarcinoma Progression at Active Surveillance.

Background Active surveillance (AS) is an accepted strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). While previous studies have evaluated the prognostic value of US features, results have been inconsistent. Purpose To determine if US features can help predict tumor progression in patients with low-risk PTMC undergoing AS. Materials and Methods This prospective study enrolled 1177 participants with PTMC from three hospitals between June 2016 and January 2021. Participants were self-assigned to either immediate surgery or AS, and those with two or more US examinations in the absence of surgery were included in the analysis. A χ2 test was used to compare estimated tumor progression rate at 4 years between participants stratified according to US features. Multivariable Cox regression analysis was used to assess the association of clinical and US features with overall tumor progression and specific progression criteria. Results Among 699 participants included in the analysis, 68 (mean age, 49 years ± 12 [SD]; 40 female participants) showed tumor progression (median follow-up, 41.4 months ± 16 [SD]). Tumor progression was associated with the US features of diffuse thyroid disease (DTD) (hazard ratio [HR], 2.3 [95% CI: 1.4, 3.7]; P = .001) and intratumoral vascularity (HR, 1.7 [95% CI: 1.0, 3.0]; P = .04) and the participant characteristics of male sex (HR, 2.8 [95% CI: 1.7, 4.6]; P < .001), age less than 30 years (HR, 2.9 [95% CI: 1.2, 6.8]; P = .01), and thyroid-stimulating hormone level of 7 µU/mL or higher (HR, 6.9 [95% CI: 2.7, 17.4]; P < .001). The risk of tumor progression was higher for participants with DTD (14%, P = .001) or intratumoral vascularity (14%, P = .02) than for participants without these features (6%). DTD and intratumoral vascularity were associated with tumor enlargement (HR, 2.7 [95% CI: 1.4, 5.1]; P = .002) and new lymph node metastasis (HR, 5.0 [95% CI: 1.3, 19.4]; P = .02), respectively. Conclusion DTD and intratumoral vascularity were associated with an increased risk of tumor progression in participants with PTMC undergoing AS. Clinical trial registration no. NCT02938702 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Reuter and the review "International Expert Consensus on US Lexicon for Thyroid Nodules" by Durante et al in this issue.

Predictions for Three-Month Postoperative Vocal Recovery after Thyroid Surgery from Spectrograms with Deep Neural Network.

Despite the lack of findings in laryngeal endoscopy, it is common for patients to undergo vocal problems after thyroid surgery. This study aimed to predict the recovery of the patient's voice after 3 months from preoperative and postoperative voice spectrograms. We retrospectively collected voice and the GRBAS score from 114 patients undergoing surgery with thyroid cancer. The data for each patient were taken from three points in time: preoperative, and 2 weeks and 3 months postoperative. Using the pretrained model to predict GRBAS as the backbone, the preoperative and 2-weeks-postoperative voice spectrogram were trained for the EfficientNet architecture deep-learning model with long short-term memory (LSTM) to predict the voice at 3 months postoperation. The correlation analysis of the predicted results for the grade, breathiness, and asthenia scores were 0.741, 0.766, and 0.433, respectively. Based on the scaled prediction results, the area under the receiver operating characteristic curve for the binarized grade, breathiness, and asthenia were 0.894, 0.918, and 0.735, respectively. In the follow-up test results for 12 patients after 6 months, the average of the AUC values for the five scores was 0.822. This study showed the feasibility of predicting vocal recovery after 3 months using the spectrogram. We expect this model could be used to relieve patients' psychological anxiety and encourage them to actively participate in speech rehabilitation.

Singing voice range profile: New objective evaluation methods for voice change after thyroidectomy.

BACKGROUND: After surgery in the thyroid region, patients may present with phonation or singing difficulty, even within their vocal range. We designed a novel voice evaluation method that reflects subjective and objective voice complications of the surgery. METHODS: This tool recorded patients' voice ranges while singing, which was named the singing voice range profile (singing VRP). Patients were asked to sing "Happy Birthday," which has a one-octave scale, at a comfortable tone and intensity. The singing VRP, standard VRP and voice handicap index-10 (VHI-10) results were recorded before thyroidectomy and 1 and 3 months after thyroidectomy for 128 patients. For subgroup analysis, a group where the maximum F0 of standard VRP in 1 month postoperatively was lower than the highest singing F0 of the preoperative singing VRP was defined as "Collapsed group" and the other group was "Preserved group." RESULTS: The changes in the highest, lowest and range of singing fundamental frequency (F0 ) had decreased at 1 month postoperatively. Subsequently, they had improved significantly at 3 months postoperatively but were lower than those preoperatively (all P < .05, except for the change in the lowest singing F0 between 1 and 3 months postoperatively, P = .274). In the subgroup analysis, the singing range of the collapsed group (n = 65) showed significantly lower VHI-10 scores, range of vocal F0 and singing F0 than those of the preserved group (n = 63) at 1 and 3 months postoperatively (all P < .001). At 3 months postoperatively, the singing F0 range in the preserved group had recovered to the range before surgery (13.0 ± 1.3 vs. 13.1 ± 1.4, P = .746 for the preserved group, and 13.0 ± 1.3 vs 11.5 ± 2.4, P < .001 for the collapsed group). CONCLUSIONS: Parameters measured by singing VRP showed a trend similar to the change in VHI-10 and the maximum F0 of standard VRP. In addition, singing VRP allowed a qualitative classification of the postoperative voice function when combined with standard VRP. Therefore, it can be used as a supplementary voice evaluation tool to reflect the physiologic and functional aspects of voice.

Analysis of postoperative ultrasonography surveillance after total thyroidectomy in patients with papillary thyroid carcinoma: a multicenter study.

Background In papillary thyroid carcinoma (PTC) patients, postoperative ultrasonography (US) surveillance is recommended at intervals of six or 12 months even though evidence is weak. Purpose To determine the optimal interval of postoperative US surveillance in patients after total thyroidectomy for the treatment of PTC using multicenter data. Material and Methods A total of 1400 patients from seven tertiary hospitals who underwent total thyroidectomy for treatment of PTC were included. Based on a retrospective review of clinical and pathologic results, multiple factors were analyzed according to recurrence/persistence or no recurrence/persistence. In recurrence/persistence group, the interval and number of follow-up US sessions in the initial detection of recurrence/persistence were investigated. Results Of the 1400 patients, 115 (8.2%) showed tumor recurrence/persistence on follow-up US. Of 115 recurrence/persistence cases, 89 (77.4%) were initially detected on US: nodal recurrence/persistence (n = 92), non-nodal recurrence/persistence (n = 22), and both (n = 1). Among the clinical and pathologic factors, only tumor size and N stage were significant predictors for recurrence/persistence. In the recurrence/persistence group, the mean interval and number of follow-up US sessions in the initial detection of recurrence/persistence was 22.3 ± 16.8 months and 2.2 ± 1.9, respectively. Approximately two-thirds of recurrence/persistence cases (76/115, 66.1%) were detected in follow-up US within two years after total thyroidectomy. Conclusion In PTC patients after total thyroidectomy, the optimal interval of the first US follow-up may be one to two years after thyroid surgery, and the appropriate number of postoperative US surveillance sessions within the first five years may be only one or two.

ANALYSIS OF POSTOPERATIVE ULTRASONOGRAPHY SURVEILLANCE AFTER HEMITHYROIDECTOMY IN PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA: A MULTICENTER STUDY.

OBJECTIVE: The optimal follow-up interval for postoperative ultrasonography (US) surveillance after hemithyroidectomy in patients with papillary thyroid microcarcinoma (PTMC) is unclear. The purpose of this study was to evaluate the prevalence of tumor recurrence/persistence and to investigate the appropriateness of postoperative US surveillance in PTMC patients who underwent hemithyroidectomy. METHODS: Our institutional review board approved this retrospective study. From 2000 to 2011, 800 patients underwent hemithyroidectomy as treatment for PTMC, as well as at least one session of postoperative follow-up US, at four different institutions. The images and data of postoperative US surveillance were retrospectively investigated by experienced radiologists at each institution. Based on the follow-up US and histopathologic results, locoregional tumor recurrence/persistence was determined. RESULTS: Of the 800 patients, 82.2% had T1a, 17.8% had T3, and none had T1b, T2, T4a, or T4b disease; 6.9% had unknown N stage, 80.1% had N0, 13% had N1a, and none had N1b, based on histopathology. There were also no cases of distant metastasis after hemithyroidectomy. Among the patients, 784 (98%) showed no tumor recurrence/persistence, and 16 (2%) showed locoregional tumor recurrence/persistence during the follow-up period. The patients differed in the number of sessions and the intervals of postoperative follow-up US. In the 16 patients with tumor recurrence/persistence, the mean interval of postoperative follow-up US since the first US detection of tumor recurrence/persistence was 42.9 ± 25.9 months. All recurrence/persistence cases were subcentimeter. CONCLUSION: Postoperative US surveillance at 1-or 2-year intervals may be unnecessary because of the very low recurrence rate in PTMC. ABBREVIATIONS: EMR = electronic medical record; PTMC = papillary thyroid microcarcinoma; TNM = tumor, node, metastasis; US = ultrasonography; US-FNA = ultrasonography-guided fine-needle aspiration.

Postoperative ultrasonography surveillance in patients with follicular thyroid carcinoma: a multicenter study.

OBJECTIVE: This study aimed to evaluate the locoregional recurrence rate of follicular thyroid carcinoma (FTC) and to assess the appropriate frequency of postoperative ultrasonography (US) surveillance for detecting tumor recurrence. METHODS: The review boards of the seven participating institutions approved this study. From 2000 to 2011, 186 patients underwent at postoperative US at least once; US was performed by experienced radiologists at each institution. Based on the US and histopathological results, locoregional tumor recurrence was assessed. RESULTS: The T stages of the 186 patients were T1a (8.1%), T1b (21.5%), T2 (39.8%), T3 (30.6%), T4a (0%), and T4b (0%). The N stages were unknown (24.2%), N0 (71.5%), N1a (3.2%), and N1b (1.1%), and the M stages unknown (29.6%), M0 (66.1%), and M1 (4.3%). Tumors recurred in only 6 (3.2%) patients during the follow-up period over 5 years. Among them, no patients showed the initial suspicion of recurrences on routine follow-up US. The session number and interval of postoperative US differed significantly between patients with recurrence and those without recurrence. The mean interval of postoperative follow-up US at the first detection time of tumor recurrence was 37.5 ± 18.5 months (range 9-62 months). Significantly more FTCs were at an advanced N and M stage in the recurrence group than in the non-recurrence group (p < 0.05). CONCLUSIONS: Routine postoperative US surveillance may be unnecessary for detecting tumor recurrence after thyroid surgery in FTC patients.

Predictive factors for extrathyroidal extension of papillary thyroid carcinoma based on preoperative sonography.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance and predictive factors of extrathyroidal extension of papillary thyroid carcinoma based on preoperative sonography. METHODS: Preoperative sonography was performed for 568 patients who underwent surgery for papillary thyroid cancer between May 2009 and December 2010. Patients' T stages based on preoperative sonography were compared with their T stages based on pathologic examination, and we statistically analyzed the discriminatory performance of sonography. Among the 568 patients enrolled in this study, we selected 320 patients in whom extrathyroidal extension was suspected on sonography. We analyzed several predictive factors for extrathyroidal extension. RESULTS: Two hundred seventy-five of the 568 patients were proven to have pathologic extrathyroidal extension of papillary thyroid cancer after surgery (75.9% diagnostic accuracy, 83.3% sensitivity, 68.9% specificity, 71.6% positive predictive value, and 81.5% negative predictive value). Of 320 patients with sonographically suspected extrathyroidal extension, a larger lesion size (P < .001) and a higher lymph node stage on sonography (P = .004) were the best predictors of extrathyroidal extension among the features that we measured. There were no significant differences in terms of the lesion site or thyroid parenchymal background echogenicity. Thyroid capsular protrusion had a higher predictive value than the abutting ratio (P = .001). However, increasing the abutting ratio enabled the prediction of extrathyroidal extension on sonography (P = .009). CONCLUSIONS: Preoperative sonography is a helpful tool for predicting pathologic extrathyroidal extension of papillary thyroid cancer. In particular, clinicians should focus on the lesion size, nodal stage, and abutment or capsular protrusion of the lesion while performing sonography because these are the most useful predictive factors for extrathyroidal extension.

Surgical targeting of recurrent thyroid cancer using a novel mixture of 99m-technetium macroaggregated albumin and indocyanine green.

BACKGROUND: Precise targeting has played a pivotal role in the success of surgery for recurrent differentiated thyroid cancers (DTCs). To improve on current targeting methods, we developed a novel technique using (99m)Tc-macroaggregated human serum albumin and indocyanine green (TIGMA), with which surgeons effectively target lesions in real time by radiofluorescence dual guidance. METHODS: Seven patients with 10 recurrent DTC lesions were retrospectively enrolled in the study. Prior to the operation, we injected TIGMA into the target lesion under the guidance of ultrasonography. Resection was concurrently monitored using a gamma probe and a specially designed near infrared fluorescence camera. Outcomes were evaluated using imaging, surgical, and pathological records. RESULTS: In all enrolled cases, both injection of TIGMA and radiofluorescence dual guidance were well tolerated and easy to implement. The technical success rates were 100%, confirmed by final pathological examination, postoperative ultrasonography, and I-131 scan clearance. Complications such as temporary postoperative neck pain (n = 2) were minimal. CONCLUSIONS: TIGMA using radiofluorescence dual guidance facilitated the precise targeting of recurrent lesions. The entire procedure was feasible, safe, and successful. This method would help enhance surgical outcomes for recurrent DTCs.

Malignancy risk stratification of thyroid nodules according to echotexture and degree of hypoechogenicity: a retrospective multicenter validation study.

Various risk stratification systems show discrepancies in the ultrasound lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity. From June to September 2015, we retrospectively evaluated 5601 thyroid nodules with final diagnoses from 26 institutions. Nodules were stratified according to the echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We calculated the malignancy risk according to composition and suspicious features. Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017), except in partially cystic nodules. Malignancy risks were not significantly different between homogeneous versus heterogeneous nodules in both hypoechoic (P ≥ 0.086) and iso- hyperechoic nodules (P ≥ 0.05). Heterogeneous iso-hyperechoic nodules without suspicious features showed a low malignancy risk. The malignancy risks of markedly and moderately hypoechoic nodules were not significantly different in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) nodules. The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. The degree of hypoechogenicity could be stratified as mild versus moderate to marked hypoechogenicity.

Gene Expression Analyses of Mutant Flammulina velutipes (Enokitake Mushroom) with Clogging Phenomenon.

Regulation of proper gene expression is important for cellular and organismal survival, maintenance, and growth. Abnormal gene expression, even for a single critical gene, can thwart cellular integrity and normal physiology to cause diseases, aging, and death. Therefore, gene expression profiling serves as a powerful tool to understand the pathology of diseases and to cure them. In this study, the difference in gene expression in Flammulina velutipes was compared between the wild type (WT) mushroom and the mutant one with clogging phenomenon. Differentially expressed transcripts were screened to identify the candidate genes responsible for the mutant phenotype using the DNA microarray analysis. A total of 88 genes including 60 upregulated and 28 downregulated genes were validated using the real-time quantitative PCR analysis. In addition, proteomic differences between the WT and mutant mushroom were analyzed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Interestingly, the genes identified by these genomic and proteomic analyses were involved in stress response, translation, and energy/sugar metabolism, including HSP70, elongation factor 2, and pyruvate kinase. Together, our data suggest that the aberrant expression of these genes attributes to the mutant clogging phenotype. We propose that these genes can be targeted to foster normal growth in F. velutipes.

A Cross-Sectional Survey of Patient Treatment Choice in a Multicenter Prospective Cohort Study on Active Surveillance of Papillary Thyroid Microcarcinoma (MAeSTro).

Background: Active surveillance (AS) is offered as a choice to patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to identify patient and physician factors associated with the choice of AS. Methods: We conducted a cross-sectional survey of patients with low-risk PTMC who were enrolled in a prospective study comparing outcomes following AS and surgery. Patients completed a questionnaire to assess their prior knowledge of the disease, considerations in the decision-making process, and reasons for choosing the treatment. We also surveyed 19 physician investigators about their disease management preferences. Variables affecting the patients' choice of AS, including patients' characteristics and their decision-making process, were analyzed in a multivariable analysis. Results: The response rate of the patient survey was 72.8% (857/1177). Among the patients who responded to the survey, 554 patients (128 male; mean age 49.4 ± 11.6 years; response rate 73.4%) with low-risk PTMC chose AS (AS group), whereas 303 patients (55 male; 46.6 ± 10.7 years; 71.8%) chose immediate surgery (iOP group). In the AS group, 424 patients (76.5%) used a decision aid, and 144 (47.5%) used it in the iOP group. The choice of AS was associated with the following variables: patient age >50 years (odds ratio 1.713 [confidence interval, CI 1.090-2.690], p = 0.020), primary tumor size ≤5 mm (odds ratio 1.960 [CI 1.137-3.379], p = 0.015), and consulting an endocrinologist (odds ratio 114.960 [CI 48.756-271.057], p < 0.001), and use of a decision aid (odds ratio 2.469 [CI 1.320-4.616], p = 0.005). The proportion of patients who were aware of AS before their initial consultation for treatment decision was higher in the AS group than in the iOP group (64.6% vs. 56.8%). Family members were reported to have influenced the treatment decisions more in the iOP group (p = 0.025), whereas the AS group was more influenced by information from the media (p = 0.017). Physicians' attitudes regarding AS of low-risk PTMC tended to be more favorable among endocrinologists than surgeons and all became more favorable as the study progressed. Conclusions: Emerging evidence suggests that physicians' attitudes and communication tools influence the treatment decision of low-risk PTMC patients. Support is needed for patient-centered decision making. (Clinical trial No: NCT02938702).

Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.

Comparison of the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System for thyroid malignancy with three international guidelines.

PURPOSE: This study compared the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS) for thyroid malignancy with three international guidelines. METHODS: From June to September 2015, 5,708 thyroid nodules (≥1.0 cm) in 5,081 consecutive patients who underwent thyroid ultrasound (US) at 26 institutions were evaluated. The US features of the thyroid nodules were retrospectively reviewed and classified according to all four guidelines. In the modified K-TIRADS, the biopsy size threshold was changed to 2.0 cm for K-TIRADS 3 and 1.0 or 1.5 cm for K-TIRADS 4 (K-TIRADS1.0cm and K-TIRADS1.5cm, respectively). We compared the diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rates for thyroid malignancy between the modified K-TIRADS and three international guidelines. RESULTS: Of the 5,708 thyroid nodules, 4,597 (80.5%) were benign and 1,111 (19.5%) were malignant. The overall sensitivity was highest for the modified K-TIRADS1.0cm (91.0%), followed by the European (EU)-TIRADS (84.6%), American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.5%), American College of Radiology (ACR)-TIRADS (76.1%), and modified K-TIRADS1.5cm (76.1%). For large nodules (>2.0 cm), the sensitivity increased to 98.0% in both the modified K-TIRADS1.0cm and K-TIRADS1.5cm. For small nodules (≤2.0 cm), the unnecessary FNAB rate was lowest with the modified K-TIRADS1.5cm (17.6%), followed by the ACR-TIRADS (18.6%), AACE/ACE/AME (19.3%), EU-TIRADS (28.1%), and modified K-TIRADS1.0cm (31.2%). CONCLUSION: The modified K-TIRADS1.5cm can reduce the unnecessary FNAB rate for small nodules (1.0-2.0 cm), while maintaining high sensitivity for detecting malignancies >2.0 cm.

Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer.

OBJECTIVE: Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs). STUDY DESIGN: Retrospective cohort study. SETTING: A comprehensive cancer center. METHODS: Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection. RESULTS: Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all P < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients (P < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients. CONCLUSION: Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence. LEVEL OF EVIDENCE: 4.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma.

BACKGROUND: A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. METHODS: Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. CONCLUSION: KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

2021 Korean Thyroid Imaging Reporting and Data System and Imaging-Based Management of Thyroid Nodules: Korean Society of Thyroid Radiology Consensus Statement and Recommendations.

Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1-2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.

Effect of Initial Treatment Choice on 2-year Quality of Life in Patients with Low-risk Papillary Thyroid Microcarcinoma.

CONTEXT: The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear. OBJECTIVE: The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months. MAJOR OUTCOME MEASURE: We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation. RESULTS: Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression. CONCLUSIONS: This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment.

The Korean Version of the Voice Symptom Scale for Patients with Thyroid Operation, and Its Use in a Validation and Reliability Study.

OBJECTIVES: The Voice Symptom Scale (VoiSS) questionnaire is a self-reported measure of voice function. Compared with previous voice-rating tools, the VoiSS focuses more on communication difficulties, pharyngeal symptoms, and psychosocial distress. This study aimed to translate the VoiSS into the Korean language, validate it, and assess its reliability. STUDY DESIGN: This is a prospective patient study utilizing questionnaires and acoustic analysis. METHODS: A recognized methodology was used to translate the questionnaires. The final Korean version was used in 31 patients scheduled for thyroidectomy between November 2013 and February 2015 for preoperative voice assessment, and at 2 weeks, 3 months, and 6 months postoperatively. The participants included had no specific vocal disorders before surgery and no vocal cord paralysis after surgery, and completed the Korean versions of the VoiSS and Voice Handicap Index (VHI), and acoustic analysis. RESULTS: The Korean version of the VoiSS demonstrated high internal consistency (α = 0.97) and test-retest reliability of its subscales. There was a significant correlation between the VoiSS and VHI scores in the total thyroidectomy group at each time-point. With regard to subjective symptoms, the VoiSS appeared to be more accurate than the VHI in terms of physical and functional subscales. CONCLUSIONS: The Korean version of the VoiSS is ready for use for the assessment of voice dysfunction in Korean patients. It is an applicable and useful supplementary tool for evaluating patients' perceptions of voice dysfunction after thyroidectomy, for identifying multiple factors affecting patients' voices, and for measuring treatment efficacy before and after therapeutic intervention.