Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population.

BACKGROUND: Recently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country's medical system. METHODS: A Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model's variables. RESULTS: From the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000. CONCLUSION: In the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.

Prospective voice assessment after uncomplicated thyroidectomy: A comprehensive analysis of a single centre experience.

OBJECTIVES: Voice change after uncomplicated thyroidectomy has been an important issue in the field of thyroid surgery. The aim of this study was to promote understanding of voice change after uncomplicated thyroidectomy by analysing the results for a large number of patients from a single institute. DESIGN: We retrospectively reviewed the medical records of 2879 consecutive patients who underwent thyroidectomy and voice evaluation between January 2014 and December 2019 in a single institute. All the patients had their vocal status assessed using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) scores preoperatively and at 1, 3, and 6 months postoperatively. We analysed the pattern of voice changes over time and differences in voice parameters based on clinical factors. To confirm the usefulness of the TVSQ, the correlation between TVSQ scores and objective parameters was analysed. Lastly, predictive factors for persistent voice symptoms were analysed. SETTING: Tertiary referral hospital. RESULTS: The frequency ranges and TVSQ scores exhibited significant deterioration until 6 months following surgery. Among clinical factors, the extents of thyroidectomy and neck dissection were associated with worse voice parameters. The TVSQ score was significantly correlated with objective voice parameters. The extents of thyroidectomy and neck dissection were predictive of persistent voice symptoms at 6 months after thyroidectomy. CONCLUSION: After uncomplicated thyroidectomy, most voice parameters tended to recover, but some parameters remained aggravated even at 6 months after surgery. With more extensive surgery, worse voice quality and the higher risk of persistent voice symptoms may be anticipated.

Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review.

Papillary thyroid microcarcinoma (PTMC) has indolent features and low mortality. Recently, active surveillance (AS) instead of early surgery (ES) has been introduced as one treatment option but economical preference has not been established. The study objective was to systemically review the literature relating to cost-effectiveness of AS compared to ES for PTMC. Keywords were selected through PICO (Population, Intervention, Comparison, and Outcomes) tools. The search was conducted using PubMed, Cochrane, EMBASE, and Elsevier databases. Papers that had irrelevant titles were written in foreign languages, or had no original results were excluded. Out of the 62 papers extracted, five relevant to the subject matter of this study were identified. Three papers made their own decision models and proceeded with cost-effectiveness analysis (CEA), but the remaining two simply compared costs rather than cost-effectiveness. In terms of cost-effectiveness, three papers preferred AS, one preferred ES, and one preferred neither. The major differences in the CEA might arise from variations in each country's medical insurance system, the utility score systems, and decision models used. In subgroup analysis, two papers preferred AS to ES for patients at a younger age at diagnosis in terms of cost-effectiveness as well as tumor biological characteristics. Although AS has been generally more cost-effective than ES in previous publications, younger age at diagnosis could be one factor contributing to preference for ES. The CEA of prospective cohorts based on the decision model and utility score for thyroid cancer should be undertaken to confirm the cost-effectiveness of AS.

High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid.

Follicular-patterned tumors of the thyroid in the adult population frequently harbor RAS mutations or PAX8-PPARG rearrangement, but little is known about molecular profiles in the pediatric patients with thyroid tumors, which is rare. To identify the molecular profile of pediatric follicular-patterned tumors, we enrolled 41 pediatric patients with follicular-patterned tumors from two institutions. We did next-generation sequencing using a mutation panel targeting 49 thyroid-tumor-related genes and a fusion panel targeting 88 types of thyroid-related gene fusions. We identified nonsynonymous mutations in at least one target gene in most of the tumors (28/41, 68%). Somatic DICER1 mutations (22%, n = 9) were the most common genetic alteration, followed by mutations of NRAS (15%), FGFR3 (15%), PTEN (12%), and STK11 (10%). Infrequent genetic alterations (≤ 5% of all cases) included mutations of HRAS, APC, TSHR, CTNNB1, TP53, EIF1AX, FGFR4, GNAS, RET, and SOS1, and gene fusion of THADA-IGF2BP3. DICER1 and RAS mutations were mutually exclusive. No patients had tumors related to the DICER1 syndrome or the Cowden syndrome. There was no significant difference in total mutation burden or distribution between follicular adenoma and follicular carcinoma. In the literature, the DICER1 mutation has been reported in 20 to 53% of pediatric patients with follicular-patterned tumors. In conclusion, our study reinforces the role of the DICER1 mutation in the development of pediatric thyroid tumors. Gene fusions rarely occur in pediatric follicular-patterned tumors. Mutation or gene fusion alone could not distinguish benign from malignant follicular-patterned tumors in pediatric patients.

Analysis of voice changes after thyroidectomy using the thyroidectomy-related voice and symptom questionnaire.

OBJECTIVE: After thyroidectomy, many patients suffer from voice problems and vague neck discomfort. The Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) is a self-administered questionnaire used to evaluate pre- and post-operative vocal status as well as throat and neck discomfort. We investigated voice conditions in thyroidectomy patients using the TVSQ as well as correlations between TVSQ responses and objective voice parameters. Also, we examined whether any clinicopathologic or surgical factors affect phonetic change after thyroidectomy. METHODS: We retrospectively reviewed the records of 242 patients who underwent total thyroidectomy to treat papillary carcinoma between January to December of 2019. Of these, we enrolled 232 who exhibited normal vocal cord mobility after surgery. TVSQ responses and acoustic voice analysis results were examined preoperatively and at 1, 3, and 6 months postoperatively. We subclassified patients into favorable and unfavorable TVSQ groups based on the increase in TVSQ score (△TVSQ ≥20) at 1 month postoperatively. We then investigated the difference of acoustic characteristics between two groups and analyzed the correlations between acoustic parameters and various clinical and surgical factors including pathologic results and lymph node status by subgroup. RESULT: All acoustic voice parameters except for the noise-to-harmonics ratio were significantly worse at 1 month postoperatively and recovered over time, but the TVSQ score did not recover from the 1-month value until 6 months postoperatively. In the subgroups, among the many clinicopathologic factors examined, advanced N stage (p = 0.002) and high positive total and central-and-lateral-neck lymph node ratios were significantly associated with an increased risk of an unfavorable TVSQ (p = 0.049, 0.027, <0.01, respectively). Among the acoustic parameters, only the changes in TVSQ total score and voice score were correlated with deterioration in jitter and shimmer at 1 month postoperatively. However, the correlations was not statistically significant and had disappeared at 6 months postoperatively. CONCLUSION: We figured out that TVSQ was able to capture the negative effects of lymph node status and lymph node dissection on vocal outcomes after thyroidectomy. Although there was a weak correlation between worsened perturbation value and TVSQ changes, no other acoustic analysis parameters were statistically significant correlated with the TVSQ score.

Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis.

BACKGROUND: Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis. METHODS: We analyzed the serum Cyfra 21.1 level in 51 consecutive patients with thyroid cancer manifesting distant metastasis treated with prior total thyroidectomy. Serum Cyfra 21.1 levels of 26 thyroid cancer patients without metastasis and 50 healthy individuals were used for comparison. RESULTS: Higher serum Cyfra 21.1 levels were detected in thyroid cancer patients with distant metastasis compared with healthy subjects and thyroid cancer patients without metastasis (p = 0.012). Serum Cyfra 21.1 levels were significantly increased in patients with positive BRAF V600E mutation (p = 0.019), undergoing Tyrosine Kinase Inhibitor (TKI) therapy (p = 0.008), with radioiodine-refractory status (p = 0.047), and in disease progression compared with those manifesting stable disease (p = 0.007). In progressive disease with undetectable or unmonitored thyroglobulin because of thyroglobulin antibody, serum Cyfra 21.1 was useful as a biomarker for follow-up of disease course. CONCLUSION: Serum Cyfra 21.1 in thyroid cancer patients might represent an alternative biomarker predicting tumor progression, especially in cases not associated with serum Tg levels.

Comparison of long-term surgical outcome between transaxillary endoscopic and conventional open thyroidectomy in patients with differentiated thyroid carcinoma: a propensity score matching study.

BACKGROUND: There is an increased use of endoscopic thyroidectomy (ET), including robotic-assisted thyroidectomy (RT), to avoid postoperative scars on the anterior neck. The objective of this study was to compare the surgical and oncologic outcomes between ET and conventional open thyroidectomy (COT) for differentiated thyroid carcinoma (DTC). METHODS: We reviewed 4129 patients with DTC who underwent thyroid lobectomy at Seoul St. Mary's Hospital (Seoul, Korea) from January 2009 to December 2014. Patients were categorized according to the type of surgery and statistically compared using propensity score matching analysis. RESULTS: The mean operation time was significantly longer in the ET group than in the OT group (101.2 ± 26.2 min vs. 86.4 ± 27.0 min, p < 0.001). The number of harvested lymph nodes was significantly lower in the ET group than in the OT group (5.5 ± 4.2 vs. 8.3 ± 6.2, p < 0.001). There was no significant difference in the recurrence rate between the two groups (p = 0.879). Kaplan-Meier analysis revealed no significant difference in the disease-free survival after propensity score matching (p = 0.811). The mean follow-up duration was 90.4 ± 21.0 months. CONCLUSIONS: Transaxillary ET including RT for DTC is a safe and feasible alternative to COT with a cosmetically desirable outcome. Further studies are required to confirm our results.

A survey investigating the current situation of the international visiting scholar program at the department of surgery in Korea.

PURPOSE: The number of international visiting scholars has been on the increase in Korea and we aim to investigate the program's current situation. METHODS: This cross-sectional study is based on an online survey questionnaire responded by international visiting scholars in surgical departments of 8 Korean hospitals between 2014 and 2018 about their experiences and satisfaction with the visiting scholar program. RESULTS: A total of 1,496 international scholars from 80 countries visited various surgical departments in 8 Korean hospitals between 2014 and 2018. The numbers have been on the increase over the years. Out of 355 visiting scholars in 2018, 71 replied to the online survey, of whom 52 were male and 19 female, and mostly in their 30s and 40s. Information about the program was accessed mostly through friends or colleagues (42.3%) and international conferences (36.6%). The commonest funding source was private (35.2%) and more than half stayed for less than 3 months. The visiting scholar's main roles were mostly observation or participation in surgery and clinical research. All but 1 were satisfied with the program (98.6%) and would recommend it to friends and colleagues, although the language barrier was identified as an inconvenience. Those aged 20-39 years with governmental or institutional funding were associated with stays of more than 1 year. CONCLUSION: The number of international visiting scholars at surgical departments in Korean hospitals has been on the increase with high satisfaction levels. Improvements need to be made on funding sources and lengthening visiting period to maximize the benefits of the program.

Voice change after thyroidectomy without vocal cord paralysis: Analysis of 2,297 thyroidectomy patients.

BACKGROUND: Some patients experience long-term voice change after thyroidectomy. One of the most common symptoms of voice change is pitch lowering, which is closely related to unfavorable voice quality. Here we observed voice outcomes for 6 months of follow-up after thyroidectomy to identify factors closely related to low-pitched voice. METHODS: We retrospectively reviewed the records of 2,297 patients who underwent thyroidectomy between January 2014 and December 2017. All the patients had their vocal status examined using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy-Related Voice Questionnaire scores. We stratified patients into 2 groups (low-pitched voice versus favorable voice) according to pitch lowering (reduction in speaking fundamental frequency ≥12 Hz 1 month after thyroidectomy compared to the preoperative value). We compared preoperative data with postoperative data collected 1, 3, and 6 months after thyroidectomy to identify factors contributing to low-pitched voice. RESULTS: Univariate logistic regression analyses showed that factors related to low-pitched voice were female sex, older age, low body weight, short stature, and a high positive lymph node ratio. Multivariate analyses showed that female sex and older age were significantly associated with a negative prognosis for low-pitched voice 1 month after thyroidectomy (odds ratios 0.41 and 1.04, respectively; P < .001). Receiver operating characteristic curves for predicting sustained low-pitched voice during 6 months showed that speaking fundamental frequency ≥12.48 Hz 1 month after thyroidectomy was the optimal cutoff value, with 87.9% sensitivity and 95.8% specificity (P < .001). CONCLUSION: Female sex and older age are strongly associated with increased risk for low-pitched voice after thyroidectomy. Speaking fundamental frequency ≥12.48 Hz 1 month after thyroidectomy can be used to predict sustained low-pitched voice after thyroidectomy.

How Can We Predict the Recovery from Pitch Lowering After Thyroidectomy?

BACKGROUND: Some of patients are suffered from pitch lowering of voice after thyroidectomy. We sought to identify factors predictive of a recovery from lowered pitch voice after thyroid surgery. METHODS: We retrospectively reviewed the records of 133 patients who underwent total thyroidectomy to treat papillary carcinoma between January 2012 and February 2013. Of these, we enrolled 78 who exhibited a lower-pitched voice (SFF fall > 12 Hz) at 2 weeks post-operatively than pre-operatively and investigated pitch recovery after 3 months. We subclassified patients into recovery and non-recovery groups and compared videostroboscopic findings, acoustic voice data, and thyroidectomy-related voice questionnaire scores pre-operatively and 2, 8, and 12 weeks post-operatively. RESULTS: Vocal cord asymmetry on videostroboscopic examination at 2 weeks post-operatively (odds ratio 19.056, p = 0.001*) was more frequent in the non-recovery group. In acoustic analysis, mean pre-operative SFF was higher in the non-recovery group than the recovery group (190.9 ± 27.5 and 180.9 ±  24.6 Hz, respectively; p = 0.030*). Also, a reduction in the SFF of > 19.6 Hz, at 2 weeks post-operatively versus pre-operatively, predicted non-recovery of pitch-lowering in patients with reduced SFF within post-operative 3 months, with 72.0% sensitivity and 71.2% specificity. After 6 months of follow-up, no patient who exhibited an SFF fall > 19.6 Hz recovered to within 10 Hz of the pre-operative value. CONCLUSION: A reduction in the speaking fundamental frequency (SFF) > 19.6 Hz at 2 weeks post-operatively predicted persisting lowering of voice pitch after thyroidectomy among those with lower-pitched voices after surgery. Pre-operative high SFF and post-operative stroboscopic findings including vocal cord asymmetry at 2 weeks post-operatively also predicted persisting lowering of voice pitch for 3 months.

Risk Stratification Using a Novel Genetic Classifier Including PLEKHS1 Promoter Mutations for Differentiated Thyroid Cancer with Distant Metastasis.

Background: Although most differentiated thyroid carcinomas (DTCs) have indolent behavior, DTCs with distant metastasis have a poor prognosis. However, there are no validated markers that predict the risk of distant metastasis and the prognosis of DTC. We aimed to develop a genetic classifier for predicting the outcomes of DTC patients with distant metastases. Methods: Targeted deep sequencing of 157 cancer-related genes was performed for 61 DTCs with distant metastases. A candidate mutation was validated with independent thyroid cancer samples using digital polymerase chain reaction. Results: The most frequently mutated gene in the 61 DTCs was BRAF (n = 31, 51%), followed by TERT promoter (n = 28, 46%), NRAS (n = 13, 11%), PLEKHS1 promoter (n = 6, 10%), and STK11 (n = 6, 10%) mutations. PLEKHS1 promoter mutations were more common in the radioactive iodine (RAI)-refractory cases (p = 0.003). Losses of 9q and 11q were associated with RAI-refractory disease (p = 0.002) and cancer-specific mortality (p = 0.028), respectively. In multivariate analysis, bone metastasis (adjusted odds ratio [aOR] = 15.17, 95% confidence interval [CI 3.38-68.06], p < 0.001) and at least one mutation in the TERT promoter, the PLEKHS1 promoter, or TP53 (aOR = 7.64 [CI 1.78-32.76], p = 0.006) remained significant factors associated with RAI-refractoriness. In independently collected papillary thyroid carcinomas without initial distant metastasis (n = 75), a PLEKHS1 promoter mutation was only found in one case that developed distant metastasis during the follow-up period. We developed a genetic classifier consisting of BRAF, RAS, the TERT promoter, the PLEKHS1 promoter, and TP53 for categorizing the prognosis of patients with DTC with distant metastasis. In the poor-prognosis group, 61% of the patients were RAI-refractory and death occurred in 21% during the follow-up. In the intermediate-prognosis group, 29% were RAI-refractory, but no death occurred. In the good-prognosis group, all patients were RAI-responsive and no death occurred. Conclusions: Mutations in the PLEKHS1 promoter are a novel genetic marker of aggressive DTC. Our genetic classifier can be useful for predicting RAI-refractory disease and poor prognosis in DTC patients with distant metastases.

CYFRA 21-1 in Lymph Node Fine Needle Aspiration Washout Improves Diagnostic Accuracy for Metastatic Lymph Nodes of Differentiated Thyroid Cancer.

Fine needle aspiration cytology (FNAC) and washout thyroglobulin (Tg) measurements are the standard for evaluating a metastatic lymph node (LN) in thyroid cancer. However, patients rarely benefit from these procedures due to false results. This study aims to identify a reliable biomarker that significantly improves the diagnosis of metastatic LNs, in addition to FNAC and washout Tg. This study analyzed 130 LNs that were suspected to have metastases on thyroid ultrasonography, from June 2016 to December 2017. All subjects underwent FNAC, washout Tg measurements and a new biomarker, washout Cytokeratin fragment 21-1 (CYFRA 21-1) measurement. The final LN outcomes were confirmed by surgical histology, repeat FNAC, or follow-up image. The diagnostic values of the presence of washout CYFRA 21-1 for diagnosing metastatic LNs were evaluated according to final LN outcomes. Among the 130 LNs, 42 were metastatic lesions and 88 were benign. The washout CYFRA 21-1 levels were significantly higher in metastatic LNs than in benign LNs. In contrast to the findings of washout Tg, washout CYFRA 21-1 showed little overlap between benign and malignant LNs, and its diagnostic cutoff values were not affected by surgery. The combinations of FNAC and washout CYFRA 21-1 showed higher sensitivity (91.9%), specificity (96.5%), negative predictive value (98.8%), and diagnostic accuracy (94.2%) than FNAC with washout Tg. The combination of FNAC, washout Tg, and washout CYFRA 21-1 showed the best sensitivity (98.8%). When washout CYFRA 21-1 was applied to the discordant results that were observed between FNAC and washout Tg, 20 of 22 LNs were correctly diagnosed. Washout CYFRA 21-1 measurements in thyroid LNs provide a diagnostic modality.

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma.

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients.

Lowered cutoff of lymph node fine-needle aspiration thyroglobulin in thyroid cancer patients with serum anti-thyroglobulin antibody.

OBJECTIVE: Fine needle aspiration cytology (FNAC) and measurement of thyroglobulin (Tg) in needle washout (FNA-Tg) are recommended for the diagnosis of metastatic or recurrent lymph nodes (LNs) in differentiated thyroid cancer (DTC). However, the effect of serum Tg antibody (TgAb) on FNA-Tg levels still remains unclear in the preoperative setting. We analyze the interference of serum TgAb on FNA-Tg levels as proof of concept in the diagnostic advantage of serum TgAb combined with FNA-Tg. SUBJECTS AND METHODS: A total of 370 suspicious cervical LNs from 273 patients with DTC were included. The primary tumor was confirmed as DTC on preoperative pathology in all patients. We performed FNA-Tg measurement and FNAC on suspicious LNs and evaluated the diagnostic performance of FNAC and FNA-Tg according to TgAb status. Final diagnoses were confirmed by histological examination of excised specimens or by follow-up ultrasonography for at least 6 months. RESULTS: Data from 273 subjects with suspicious 370 LNs were evaluated. Fifty-five LNs (14.9%) were from TgAb+ positive serum TgAb (TgAb+) patients. Serum Tg and FNA-Tg levels were significantly lower in patients with TgAb+ than in those with TgAb-negative (TgAb-). Final pathology confirmed 109 LNs (29.5%) as malignant. Diagnostic performance of FNA-Tg at the same cutoff level was lower in the TgAb+ than TgAb- group. FNA-Tg cutoff levels determined by ROC curve were lower in the TgAb+ group. CONCLUSION: The results suggested that the cutoff value of FNA-Tg should be lowered in suspicious LN before thyroidectomy in thyroid cancer patients with TgAb.

Thyroid nodule parameters influencing performance of ultrasound elastography using intrinsic compression.

The influence of nodule parameters on the diagnostic accuracy of ultrasound (US) elastography in differentiating thyroid nodules was evaluated. One hundred seventy-six nodules (83 benign, 93 malignant) from 156 patients were included. Conventional B-mode and elastography examinations were performed. External compression with a transducer was not applied, as the pulsation from the carotid artery was used. Three nodule parameters (size, depth and distance to the carotid artery) were measured. The elasticity contrast index, in which increases with the stiffness of the nodules, was correlated with distance to the carotid artery (correlation coefficient = 0.283 in all nodules and 0.415 in malignant nodules, p < 0.01 in both groups). The diagnostic accuracy of elastography was significantly associated with a nodule's distance to the carotid artery (p < 0.05). No significant correlation was found between the diagnostic accuracy of elastography and the other parameters. Elastography results for nodules close to the carotid artery should be interpreted with caution.

Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy.

Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.

Correlation between obesity and clinicopathological factors in patients with papillary thyroid cancer.

PURPOSE: Epidemiological studies have shown that obesity is associated with an increased risk of thyroid cancer. However, the exact nature of the relationship, especially with respect to the behavior of the cancer, remains uncertain. The objective of this study was to evaluate the correlation between the body mass index (BMI) and clinicopathological features of thyroid cancer patients. METHODS: From January 2009 to April 2010, 716 consecutive patients (602 females and 114 males; mean age 47.02 ± 11.73 years) with papillary thyroid cancer (PTC) were analyzed retrospectively. Patients were divided into two subgroups according to age (<45 years, ≥45 years). The BMI groupings were based on standardized categories set by the World Health Organization. The relationships between the BMI and these parameters were assessed. RESULTS: A non-overweight BMI was associated with a younger age and female gender. Tumor multiplicity was related to a higher BMI. In an age-related subgroup analysis, a higher BMI was correlated with more lymph node involvement (p = 0.004), lymphatic invasion (p = 0.003) and tumor multiplicity (p = 0.008) in patients ≥45 years of age. The absence of an association between the BMI and T stage, nodal status, vascular invasion, lymphatic invasion, and extrathyroidal extension was noted in a statistical analysis. In the subgroup of patients <45 years of age, no positive associations were observed between the BMI and any parameters other than age and sex. CONCLUSIONS: In PTC patients ≥45 years of age, a higher BMI was associated with more aggressive tumor features, such as lymph node metastasis, lymphatic invasion, and tumor multiplicity.

Impact of NRAS Mutations on the Diagnosis of Follicular Neoplasm of the Thyroid.

Background. Most patients with a preoperative diagnosis of thyroid follicular neoplasm (FN) undergo diagnostic surgery to determine whether the nodule is benign or malignant. Point mutations at NRAS codon 61 are the most common mutations observed in FN. However, the clinical significance of NRAS mutation remains unclear. Methods. From 2012 to 2013, 123 consecutive patients undergoing thyroidectomy for FN were evaluated prospectively. Molecular analyses for NRAS codon 61 were performed with pyrosequencing. Results. The overall malignancy rate in FN was 48.8% (60/123). Of 123 FNs, 33 (26.8%) were positive for the NRAS mutation. The sensitivity, specificity, positive predictive value, and negative predictive value of a NRAS mutation-positive FN specimen to predict malignancy were 37%, 83%, 67%, and 58%, respectively. Patients with a NRAS-positive FN had a higher malignancy rate in additional thyroid nodules beyond the FN than patients with a NRAS-negative FN. The overall malignancy rate of patients with a NRAS-positive FN was significantly higher than that of patients with a NRAS-negative FN (79% versus 52%; P = 0.008). Conclusions. Determining NRAS mutation status in FN helps to improve the accuracy of thyroid cancer diagnosis and to predict cancer risk in accompanying thyroid nodules.

Expression of receptor activator of nuclear factor kappa-B as a poor prognostic marker in breast cancer.

PURPOSE: Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL) and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity in bone. However, little is known about the role of RANK-related molecules in breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and the associated clinical impact in breast cancer. METHODS: Tissue microarray (TMA) from 185 patients with primary breast cancer was established. Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic features and survival outcomes associated with expression of RANK, RANKL, and OPG were analyzed. RESULTS: RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and 45.9% of patients, respectively. RANKL expression was associated with lower Ki-67 level. OPG expression was related to small tumor size, node negativity, and low Ki-67. There was no significant difference in clinicopathologic features between tumors with RANK and those without RANK. RANK expression was significantly associated with poor disease-free survival in univariate analysis (P = 0.04) and multivariate analysis (P = 0.02). RANKL expression was associated with improved skeletal disease-free survival in multivariate analysis (P = 0.03). CONCLUSIONS: The RANK/RANKL pathway regulated by OPG may have a role in predicting progression and prognosis of breast cancer.

Clinical implication of the BRAFV600E mutation in papillary thyroid carcinoma.

BACKGROUND: The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). In recent studies, the BRAFV600E mutation has been associated with poor clinicopathological characteristics, such as lymph node metastasis, extrathyroidal extension, and advanced stage. However, other studies have failed to establish an association between the BRAFV600E mutation and clinicopathological features. Therefore, we investigated the relationship between the BRAFV600E mutation and its clinicopathological factors at a single institution. METHODS: A total of 327 consecutive patients with PTC were enrolled in this study and underwent thyroid surgery at Yeouido St. Mary's Hospital between February 2010 and December 2011.BRAFV600E mutation analysis was performed using polymerase chain reaction (PCR)-based amplification of DNA extracted from paraffin-embedded tumour specimens. RESULTS: The BRAFV600E mutation was detected in the tumours of 241 (73.7%) patients. Lymph node metastasis, TNM stage, and multifocality were not significantly associated with the BRAFV600E mutation. However, larger tumour size, extrathyroidal extension, histologic type (classic type), and concurrent Hashimoto's thyroiditis were associated with the BRAFV600E mutation in the univariate analysis, although no clinicopathological features were associated with the BRAFV600E mutation in the multivariate analysis. CONCLUSION: There was no idependent prognostic factor associated with BRAFV600E mutation status in this study. The BRAFV600E mutation is unlikely to serve as a prognostic factor for PTC.