Ka Hee Yi

Changes in the Clinicopathological Characteristics and Outcomes of Thyroid Cancer in Korea over the Past Four Decades

BACKGROUND Thyroid cancer has increased globally, with a prominent increase in small, papillary thyroid cancers (PTC). The Korean population has a high iodine intake, high prevalence of BRAF V600E mutations, and family histories of thyroid cancer. We examined the clinicopathological characteristics and outcomes of thyroid cancers in Korean patients over four decades. METHODS The medical records of 4500 thyroid cancer patients, between 1962 and 2009 at a single center, including 3147 PTC patients, were reviewed. RESULTS The mean age of the patients was 46.8±13.2 years; women accounted for 82.9% of the patients, and the median follow-up duration was 4.8 years (mean 7.0±5.8 years, range 1-43 years). The number of patients visiting the clinic increased from 411 during 1962-1990 to 2900 during 2000-2009. Age at diagnosis increased from 39.6±12.9 to 48.6±12.4 years. The male to female ratio increased from 1:6 to 1:4.5. The proportion of small (<1 cm) tumors increased from 6.1% to 43.1%, and the proportion of cancers with lymph node (LN) involvement or extrathyroidal extension (ETE) decreased from 76.4% to 44.4% and from 65.5% to 54.8% respectively. Although there were decreases in the proportion of LN involvement and ETE, these decreasing rates were not proportional to the expected rates based on the decreased proportion of large tumors. The overall recurrence and mortality rates were 13.3% and 1.4%. The five-year recurrence rate significantly decreased (from 11% to 5.9%), and the five-year mortality also improved (from 1.5% to 0.2%). CONCLUSIONS The incidence of thyroid cancer has rapidly increased, with a decrease in tumors of large size, LN involvement, and ETE, although the decreasing rates of LN involvement and ETE were not as prominent as decreasing rates of large size tumors. The mortality and recurrence rates have also decreased. Future long-term follow-up of patients diagnosed in the most recent decade is needed to confirm the prognostic characteristics of Korean PTC patients.

Prognostic factors for Korean patients with anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC), although rare, is one of the most aggressive human cancers, and patients with ATC have extremely poor prognoses despite various therapeutic measures. We wished to determine the prognostic factors of survival and effect of treatment on survival rate in patients with ATC.

The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance

Atypia or follicular lesions of undetermined significance (AUS/FLUS) is a broad cytological category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound (US) analysis of thyroid nodules with AUS/FLUS.

Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients.

Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes.

Thyroglobulin in Washout Fluid From Lymph Node Fine-needle Aspiration Biopsy in Papillary Thyroid Cancer: Large-scale Validation of the Cutoff Value to Determine Malignancy and Evaluation of Discrepant Results

CONTEXT There are still some controversies regarding the cutoff value and the influential factors of thyroglobulin (Tg) concentration in washout fluid from fine-needle aspiration (FNA) biopsy (FNA-Tg) on cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC). OBJECTIVE Our aims were to validate the cutoff value of FNA-Tg in diagnosing malignant LNs on a large scale and to investigate the influential factors that could result in the discrepancy between the final diagnosis and FNA-Tg. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study based on hospital records with 528 cases of FNA-Tg measurement from 419 PTC patients. MAIN OUTCOME MEASURE The cutoff value of FNA-Tg was obtained from receiver operating characteristic analysis with final diagnosis. Binary logistic regression analysis was performed to investigate the influential factors. RESULTS In the final diagnosis, 190 LNs were malignant, and 338 LNs were benign. The median FNA-Tg was 521.2 (3676.8) ng/mL in malignant LNs, and 0.1 (0.2) ng/mL in benign LNs. The optimal cutoff value of FNA-Tg in distinguishing malignant LNs from benign LNs was 1.0 ng/mL (sensitivity, 93.2%; specificity, 95.9%) in all cases. Combining FNA-Tg and FNA cytology showed superior diagnostic power (sensitivity, 98.4%; specificity, 94.4%) when compared with diagnostic strategy using either FNA cytology or FNA-Tg alone. FNA-Tg, serum TSH, and serum Tg were higher in nonthyroidectomized patients than in thyroidectomized patients (P < .001, respectively). FNA-Tg was correlated with serum TSH and Tg levels (P < .001, respectively), and binary logistic regression analysis showed that serum TSH suppression and serum Tg presence independently affected the diagnosis made by FNA-Tg. CONCLUSIONS Our results validated 1.0 ng/mL of FNA-Tg as a cutoff value for diagnosing LN metastasis of PTC and suggested that serum TSH suppression and serum Tg presence should be considered in diagnosing LN malignancy with FNA-Tg in PTC patients.

The diagnosis and management of hyperthyroidism in Korea: consensus report of the korean thyroid association.

Hyperthyroidism is one of the causes of thyrotoxicosis and the most common cause of hyperthyroidism in Korea is Graves disease. The diagnosis and treatment of Graves disease are different according to geographical area. Recently, the American Thyroid Association and the American Association of Clinical Endocrinologists suggested new management guidelines for hyperthyroidism. However, these guidelines are different from clinical practice in Korea and are difficult to apply. Therefore, the Korean Thyroid Association (KTA) conducted a survey of KTA members regarding the diagnosis and treatment of hyperthyroidism, and reported the consensus on the management of hyperthyroidism. In this review, we summarized the KTA report on the contemporary practice patterns in the diagnosis and management of hyperthyroidism, and compared this report with guidelines from other countries.

The Revised 2016 Korean Thyroid Association Guidelines for Thyroid Nodules and Cancers: Differences from the 2015 American Thyroid Association Guidelines

Increased detection of thyroid nodules using high-resolution ultrasonography has resulted in a world-wide increase in the incidence of differentiated thyroid cancer (DTC). Despite the steep increase in its incidence, the age-standardized mortality rate of thyroid cancer has remained stable, which leads toward a trend of more conservative treatment. The latest American Thyroid Association (ATA) guidelines for thyroid nodules and thyroid cancer revised in 2015 suggested that fine needle aspiration biopsy should be performed for thyroid nodules larger than 1 cm and lobectomy might be sufficient for 1 to 4 cm intrathyroidal DTC. In addition, active surveillance instead of immediate surgical treatment was also recommended as a treatment option for papillary thyroid microcarcinoma based on the results of a few observational studies from Japan. The Korean Thyroid Association (KTA) has organized a task force team to develop revised guidelines for thyroid nodules and DTC after an extensive review of articles and intense discussion on whether we should accept the changes in the 2015 ATA guidelines. This paper introduces and discusses the updated major issues and differences in the ATA and the KTA guidelines.

Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status.

CONTEXT The widespread use of thyroid tests in asymptomatic individuals identifies many patients with transient subclinical hypothyroidism. OBJECTIVE Our objective was to determine the effect of seasonal change on serum TSH levels and the transition between subclinical hypothyroid and euthyroid status. DESIGN, SETTING, AND SUBJECTS This was a retrospective longitudinal study of 1751 subclinical hypothyroid and 28 096 euthyroid subjects aged over 18 years who underwent serial thyroid function tests at a health screening center between October 2003 and May 2011. MAIN OUTCOME MEASURES Age-adjusted geometric mean values of the TSH level by month were calculated using linear mixed models. Adjusted odds ratios of test season and multiple baseline clinical factors were determined using generalized estimating equations. RESULTS During a median 36 months of follow-up, 57.9% of subclinical hypothyroid subjects reverted to euthyroidism, and 4.3% of euthyroid subjects developed subclinical hypothyroidism. The monthly distribution of follow-up TSH levels indicated a biphasic pattern, ie, an increase during the winter-spring season and a decrease during the summer-fall season, with a maximal TSH difference of 0.69 mIU/L in subclinical hypothyroid and 0.30 mIU/L in euthyroid subjects. Normalization of subclinical hypothyroidism was increased 1.4-fold in follow-up tests during the summer-fall follow-up, whereas subclinical hypothyroidism increased 1.4-fold in euthyroid subjects during the winter-spring follow-up. CONCLUSIONS The season in which thyroid testing was performed was independently related to the transition between subclinical hypothyroid and euthyroid status. Seasonal variations in TSH concentration should be considered before deciding on treatment of subclinical hypothyroidism, particularly in the areas with a wide annual temperature range.

Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo.

Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling.

Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling.

Wnt/β-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf-1 (Dkk-1) is an inhibitor of Wnt/β-catenin signaling. We investigated the therapeutic potential of Dkk-1 in human PTC cell lines, SNU-790, B-CPAP, and BHP10-3. Dkk-1 reversed the aberrant expression of β-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF-dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in a dose-dependent manner and adenoviral transduction of constitutively active β-catenin blocked these effects, thus suggesting that the Dkk-1 anti-tumoral effect is mediated by Wnt/β-catenin signaling. Bromodeoxyuridine assay showed minimal effects of Dkk-1 on cell proliferation. Flow cytometric analysis with Annexin V staining showed marked induction of cell apoptosis by Dkk-1 treatment. Dkk-1 also restored the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion. In conclusion, Dkk-1 inhibited the survival and migration of human PTC cells by regulating Wnt/β-catenin signaling and E-cadherin expression.