Background: Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants. Methods: We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared. Results: No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAFV600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence. Conclusion Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.

Background: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. Methods: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). Results: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025);nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. Conclusion We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic.Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Purpose: To evaluate and compare the diagnostic outcomes of ultrasonography (US)-guided fine needle aspiration (FNA) and core needle biopsy (CNB) performed on the same thyroid nodule using a surgical specimen for direct comparison. Materials and Methods: We included 89 thyroid nodules from 88 patients from February 2015 to January 2016. The inclusion criterion was thyroid nodules measuring ≥ 20 mm (mean size: 40.0 ± 15.3 mm). Immediately after surgical resection, FNA and subsequent CNB were performed on the surgical specimen under US guidance. FNA and CNB cytopathologic results on the specimen were compared with the surgical diagnosis. Results: Among the 89 nodules, 30 were malignant and 59 were benign. Significantly higher inconclusive rates were seen in FNA for malignant than benign nodules (80.0% vs. 39.0%, p < 0.001). For CNB, conclusive and inconclusive rates did not differ between benign and malignant nodules (p = 0.796). Higher inconclusive rates were seen for FNA among cancers regardless of US features, and in the subgroup of size ≥ 40 mm (62.5% vs. 22.9%, p = 0.028). Eleven cancers were diagnosed with CNB (36.7%, 11/30), while none was diagnosed using FNA. Conclusion In this experimental study using surgical specimens, CNB showed a potential to provide improved diagnostic sensitivity for thyroid cancer, especially when a conclusive diagnosis is limited with FNA.

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results. Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages. Conclusion LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Background and Objectives: Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. Materials and Methods: Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. Results: THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. Conclusion Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

Purpose: Paragangliomas (PGL) are rare neuroendocrine tumors derived from chromaffin cells of the autonomic nervous system. We aim to describe our experience and the long-term outcome of abdominal PGL over the last decade. Methods: A retrospective review of patients diagnosed with PGL in our hospital between November 2005 and June 2017 was conducted. All nonabdominal PGL were excluded and the clinicopathological features and long-term outcomes of the patients were analyzed. Results: A total of 46 patients were diagnosed with abdominal PGL. The average age of diagnosis was 55.4 years and there was no sex predilection. The average tumor size was 5.85 cm and they were predominantly located in the infrarenal position (50%). The mean follow-up period was 42 months (range, 1.8–252 months). All patients with metastases had Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of ≥4. One patient presented with synchronous metastases while 2 developed local recurrence and distant metastases. One presented with only local recurrence. One patient died 5 years after diagnosis. Conclusion Abdominal PGL is a rare tumor with excellent long-term prognosis. Recurrence although uncommon, can occur decades after initial diagnosis. Long-term follow-up is therefore recommended for all patients with PGL, especially in patients with PASS of ≥4.

Background: Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. Methods: Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. Results: In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets. Conclusion The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

PURPOSE: Recently, posterior retroperitoneoscopic adrenalectomy (PRA) has been reported to have some advantages over laparoscopic transperitoneal adrenalectomy (LTA). The objectives of this study were to report our experience over 12 years with laparoscopic adrenalectomy for primary hyperaldosteronism (PHA) and to examine surgical outcomes of PRA compared with LTA in patients with PHA. METHODS: The medical records of 527 patients who underwent minimally invasive adrenalectomy, including LTA or PRA, from January 2006 until May 2017 were reviewed at Severance Hospital (Seoul, Korea). Clinicopathologic characteristics and surgical outcomes of 146 patients with PHA who underwent LTA (19 patients) or PRA (127 patients) were analyzed retrospectively by complete chart review. RESULTS: The overall rates of biochemical and clinical cure were 91.1% and 93.1%, respectively. The mean operation time of the PRA group was significantly shorter than that of the LTA group (72.3 ± 24.1 minutes vs. 115.7 ± 69.7 minutes, P = 0.015). The length of hospital stay in the PRA group was significantly shorter than in the LTA group (3.5 ± 1.3 days vs. 4.2 ± 1.6 days, P = 0.029), and the first meal after surgery came earlier in the PRA group (0.3 ± 0.5 days vs. 0.6 ± 0.5 days, P = 0.049). The number of pain-killers used was also significantly smaller in the PRA group (2.3 ± 2.1 vs. 4.3 ± 2.3, P < 0.001). CONCLUSION: PRA offers an alternative or likely superior method for treatment of small adrenal diseases such as PHA, with improved surgical outcomes.
Adrenalectomy ; Humans ; Hyperaldosteronism ; Laparoscopy ; Length of Stay ; Meals ; Medical Records ; Methods ; Retrospective Studies

PURPOSE: Recently, the American Thyroid Association (ATA) dynamic risk stratification (DRS) has been verified to be more valuable than the static anatomical staging system for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The purpose of this retrospective study was to compare the clinical usefulness of DRS, which is based on the response to initial treatment, with that of ATA initial risk stratification in pediatric patients. METHODS: A total of 144 pediatric patients underwent thyroid operation from August 1982 to December 2013 at Yonsei University Hospital (Seoul, Korea). Among them, 128 patients with complete clinical data were enrolled in this study. Clinicopathologic features and surgical outcomes were retrospectively analyzed by medical chart review. The mean follow-up duration was 11.5 years. RESULTS: The mean tumor size was 2.1 cm; 80.4% of patients were diagnosed with conventional papillary thyroid carcinoma, and 7.0% of patients were diagnosed with follicular thyroid carcinoma. Low-risk patients had the highest probability of an excellent response to initial treatment (66.6%). High-risk patients had the highest probability of a structural incomplete response (100%) and the lowest probability of an excellent response (11.1%). The ATA risk stratification and the DRS system were independent risk factors for disease-free survival (DFS) (P = 0.041 and P < 0.001, respectively). CONCLUSION: The DRS system, which is based on the response to initial treatment, can offer more useful prognostic information compared with ATA risk stratification in pediatric patients with DTC.
Adenocarcinoma, Follicular ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Pediatrics ; Prognosis ; Retrospective Studies ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms*

PURPOSE: With the increasing incidence of papillary thyroid microcarcinoma (PTMC), familial papillary thyroid microcarcinoma (FPTMC) is now recognized more frequently. However, the biological behavior of FPTMC is poorly understood. The aim of this study was to investigate the prevalence of FPTMC and its biological aggressiveness. METHODS: Between March 2006 and July 2010, 2,414 patients underwent primary surgical therapy for PTMC and 149 (6.2%) were further classified as FPTMC. To determine the biological aggressiveness of FPTMC, we compared the clinicopathological features and prognosis between FPTMC and sporadic PTMC (SPTMC). RESULTS: The male-to-female ratio was higher in FPTMC than in sporadic papillary thyroid microcarcinoma (SPTMC: 1:4.5 vs. 1:7.2, P = 0.041). The central lymph node (LN) metastasis rate was significantly higher in FPTMC than in SPTMC (36.2% vs. 24.2%, P = 0.002). The local recurrence rate was also higher in FPTMC than in SPTMC (4.5% vs. 0.6%, P < 0.001). We identified familial occurrence in 6.2% of cases of PTMC. FPTMC is associated with a high rate of central LN metastasis and local recurrence. CONCLUSION: These findings suggest that close follow-up can be beneficial in FPTMC patients to detect local recurrence.
Aggression ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Neoplasm Metastasis ; Prevalence ; Prognosis ; Recurrence ; Thyroid Gland*