Young Kee Shong

Seoul National University Hospital, Sŏul, Seoul, South Korea

Are you Young Kee Shong?

Claim your profile

Publications (151)420.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Detecting persistent/recurrent disease of medullary thyroid carcinoma (MTC) is important. The tumor-node-metastasis (TNM) staging system is useful for predicting disease-specific mortality, but is a static system and does not include postoperative serum calcitonin levels. We have focused on the clinical usefulness of dynamic risk stratification (DRS) using the best response to the initial therapy in MTC patients. A total of 120 MTC patients were classified into three DRS groups based on their responses to initial therapy. Clinical outcomes were assessed according to TNM staging and DRS. In the DRS, 70, 23 and 7 % of the MTC patients were classified into excellent, biochemical incomplete, or structural incomplete response groups, respectively. On TNM staging, 37, 16, 13 and 35 % of patients were stages I-IV, respectively. There were significant differences in survivals according to TNM staging (p = 0.03) and DRS (p = 0.005). During the median follow-up of 6.2 years, 75 patients (63 %) demonstrated no evidence of disease (NED). About 60 and 17 % of patients in stages III and IV were NED, respectively. DRS predicted NED better than TNM staging according to the proportion of variance explained (PVE) (49.1 vs. 28.7 %, respectively). At the final follow-up, 88, 4 and 0 % of patients in excellent, biochemical incomplete, and structural incomplete response groups attained NED, respectively. DRS based on the best response to the initial therapy can provide useful prognostic information in addition to initial TNM staging for predicting of mortality, as well as the likelihood of NED in MTC patients.
    No preview · Article · Jan 2016 · Endocrine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC). Methods: Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing. Results: The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence. Conclusion: The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort.
    No preview · Article · Dec 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Thyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and gamma-aminobutyric acid receptor α3 subunit (GABRA3) genes. Methods: This study enrolled 48 men with Graves' disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups. Results: The frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (p=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (OR=2.46, 95% CI 0.81-8.09, p=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR=1.83, 95% CI 0.54-6.74, p=0.41). Conclusions: The polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.
    No preview · Article · Dec 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The early detection of papillary thyroid cancer has contributed to the increase in the incidence and improved clinical outcomes. However, recent changes of medullary thyroid carcinoma (MTC) over time remain unclear. We evaluated changes of the clinicopathological characteristics and clinical outcomes in patients with MTC in recent years. Methods: A total of 109 MTC patients were classified based on the year of initial surgery: 1996-2000 (n = 14), 2001-2006 (n = 39), and 2007-2011 (n = 56). Results: The primary tumor size significantly decreased and the proportion of microMTCs (size ≤1 cm) increased over time (P = 0.002 and P < 0.001, respectively). The proportion of patients with cervical lymph node (LN) metastasis significantly decreased (P = 0.037), and the ratio of metastatic LNs significantly decreased (P = 0.011). Disease-free survival (DFS) rate of patients was significantly improved over time (P = 0.007). There was no significant difference in DFS between microMTC and macroMTC patients. However, more advanced LN stage patients demonstrated more recurrences (P < 0.001). Especially, there were significantly more recurrences in patients with N1b diseases in comparison with patients without cervical LN metastases (P < 0.001). Conclusions: The prognosis of MTC patients has significantly improved in recent years. These changes could be associated with the early diagnosis before development of lateral and extensive cervical LN metastases. J. Surg. Oncol. 2016;113:152-158. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Journal of Surgical Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To compare single-session radiofrequency ablation (RFA) and ethanol ablation (EA) for treating predominantly cystic thyroid nodules (PCTNs). Materials and methods: This single-blind, randomized trial was approved by the Institutional Review Board of two centers and informed consent was obtained from all patients before enrollment. Fifty patients with a single PCTN (cystic portion less than 90% and greater than 50%) were randomly assigned to be treated by either RFA (25 patients) or EA (25 patients) at two hospitals. The primary outcome was the tumor volume reduction ratio (%) at the six-month follow-up and the superiority margin was set at 13% (RFA minus EA). Analysis was performed primarily in an intention-to-treat manner. The secondary outcomes were the therapeutic success rate, improvement of symptomatic and cosmetic problems, and the number of major complications. Results: The mean volume reduction was 87.5 ± 11.5% for RFA (n = 22) and 82.4 ± 28.6% for EA (n = 24) (p = 0.710; mean difference [95% confidence interval], 5.1% [-8.0 to 18.2]), indicating no significant difference. Regarding the secondary outcomes, therapeutic success (p = 0.490), mean symptom (p = 0.205) and cosmetic scores (p = 0.710) showed no difference. There were no major complications in either group (p > 0.99). Conclusion: The therapeutic efficacy of RFA is not superior to that of EA; therefore, EA might be preferable as the first-line treatment for PCTNs.
    Full-text · Article · Nov 2015 · Korean Journal of Radiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: A repeat fine needle aspiration (FNA) is recommended for thyroid nodules diagnosed as atypia of undetermined significance (AUS) in a previous cytology. We evaluated the utility of NRAS codon 61 (NRAS61) mutation analysis and core needle biopsy (CNB) for the diagnosis of thyroid nodules previously diagnosed as AUS. This study enrolled 236 patients who underwent both NRAS61 mutation analysis and CNB of thyroid nodules previously diagnosed as AUS at cytology. The NRAS61 mutation was detected in 36 nodules and was more frequently detected in the AUS and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN) categories, as determined by histological analysis of CNB, than in the benign group (p = 0.005). Sixty-one patients underwent surgery, and 29 nodules were finally diagnosed as malignant after surgery. Among 61 patients who underwent surgery, nodules with the NRAS61 mutation (42-65 %) had a significantly higher malignancy rate than nodules with wild-type NRAS61 (7-37 %, p = 0.038). The association between malignancy and the NRAS61 mutation was significant after adjusting for age, sex, nodule size, and histological diagnosis of CNB (p = 0.01). NRAS61 mutation analysis together with CNB could be helpful for arriving at a clinical decision in patients with thyroid nodules showing AUS in a previous cytology.
    No preview · Article · Nov 2015 · Endocrine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. Objective: To establish the differential clinicopathological risk of major PTC variants-conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). Methods: Retrospective study of clinicopathological outcomes of 6,282 PTC patients (4,799 females and 1,483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range [IQR], 33-56) and median follow-up time of 37 months (IQR 15-82). Results: The cohort consisted of 4,702 (74.8%) CPTC, 1,126 (17.9%) FVPTC, and 239 (3.8%) TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality and the use (need) of radioiodine treatment (all P < 0.001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC>CPTC≫FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3% and 6.7%, 16.1% and 2.5%, and 9.1% and 0.6%, corresponding to events per 1000 person-years (95% confidence interval-CI) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66) and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI 1.07-11.11) and 14.96 (95% CI 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients ≥ 45 years old. Conclusion: This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC.
    Full-text · Article · Nov 2015 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: The naturally occurring short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant which is clinically used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. In this study, we evaluate the effects of ALA on thyroid cancer cell proliferation, migration and invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62 and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2 and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways in thyroid cancer cells. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for treatment of advanced thyroid cancer, possibly as an adjuvant therapy with other systemic therapeutic agents.
    No preview · Article · Oct 2015 · Molecular and Cellular Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Malignant pheochromocytoma (PCC)/paraganglioma (PG) are rare neuroendocrine malignancies, and their clinical courses and prognoses are not well understood. This study aimed to evaluate prognostic factors associated with the survival of malignant PCC/PG. Methods: This retrospective study reviewed 299 patients with PCC and 46 with PG treated between 1997 and 2013 at our single tertiary hospital. Malignant PCC/PG was defined as the presence of distant metastasis or recurrence at sites where neuroendocrine tissue is normally not present. Results: Twenty-seven patients (9%) were confirmed with malignant PCC and six patients (13%) with malignant PG. Twenty-seven patients (82%) had distant metastases, nine patients (27%) presented with a metastasis at the initial diagnosis, whilst 24 patients (73%) were diagnosed with malignant PCC/PG during follow-up (median, 4.3 year). The median survival was 7.2 years, and the 5 year survival rate was 75.4%. Older age (>45 years), larger tumor size (>6 cm), synchronous metastasis, and absence of surgical excision were associated with poor survival by univariate analysis. By multivariate analysis, older age (HR = 4.3, P = 0.02) and synchronous metastasis (HR = 4.3, P = 0.01) were significantly associated with a poor prognosis. Conclusions: Patients with malignant PCC/PG have diverse clinical courses. Poor survival was independently associated with older age and synchronous metastasis. J. Surg. Oncol. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Oct 2015 · Journal of Surgical Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients. Methods: We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm³. Results: The mean age of the patients (11 males, 43 females) was 38.2 ± 14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n = 39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n = 15) users. The median duration of agranulocytosis was 5.5 days (range 1-20 days). No differences were observed between the long (≥ 6 days) and short recovery time (≤ 5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization. Conclusions: The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.
    Preview · Article · Sep 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time.
    Preview · Article · Sep 2015 · Endocrine Related Cancer
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal accumulation of defective mitochondria is the hallmark of oncocytes, which are frequently observed in thyroid Hürthle cell lesions. Autophagy is an essential cellular catabolic mechanism for the degradation of dysfunctional organelles and has been implicated in several human diseases. It is yet unknown how autophagic turnover of defective mitochondria in Hürthle cell tumors is regulated. We characterized the expression patterns of molecular markers including Beclin1, LC3, PINK1 and Parkin, which are required for autophagy or mitophagy, in human oncocytic lesions of the thyroid. To undertake mechanistic studies, we investigated autophagy and mitophagy using XTC.UC1 cells, the only in vitro model of Hürthle cell tumors. Beclin1 and LC3 were highly expressed in oncocytes of Hürthle cell tumors. XTC.UC1 showed autophagic responses to starvation and rapamycin treatment, whereas they displayed ineffective activation of mitophagy, which is triggered by the coordinated action of PINK1 and Parkin in response to CCCP. This resulted in a decreased turnover of abnormal mitochondria. The mechanisms underlying defective mitophagy and mitochondrial turnover were investigated by genetic analysis of the PARK2 gene in XTC.UC1 and Hürthle cell tumor tissues. XTC.UC1 and several tumors harbored the V380L mutation, resulting in dysfunctional autoubiquitination and decreased E3 ligase activity. Consistently, oncocytes in Hürthle cell tumors displayed comparable expression of PINK1 but decreased Parkin expression in comparison to normal thyrocytes. The introduction of wild-type Parkin sensitized XTC.UC1 to death induced by CCCP. This study provides a possible etiological basis for oncocytic formation in heterogeneous Hürthle cell tumors through insufficient mitophagy leading to ineffective turnover of aberrant mitochondria caused by dysfunctional Parkin-mediated pathways of mitochondria quality control.
    No preview · Article · Sep 2015 · Carcinogenesis
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objective: Type 2 diabetes is known to increase the risk and progression of certain types of cancer. Metformin treatment of diabetic patients is reported to have beneficial effects on some cancers. We evaluated the clinical outcome of diabetic patients with differentiated thyroid cancer (DTC) according to metformin treatment. Methods: We reviewed 943 patients diagnosed with DTC after total thyroidectomy between 1995 and 2005 in a tertiary hospital. The study involved 60 diabetic patients and 210 control patients matched for age, sex, body mass index (BMI), and tumor size. Results: There were no differences in the clinicopathological features and disease-free survival (DFS) between diabetic patients and the control group over 8.9 years of follow-up. Of the diabetic patients with DTC, 35 patients (58%) were treated with metformin. There were no differences in age, sex, BMI, tumor size, antidiabetic medication, glycated hemoglobin, or C-peptide levels in metformin and nonmetformin groups. However, cervical lymph node (LN) metastasis was more prevalent in the metformin group than in the nonmetformin group (OR 3.52, p = 0.035). Among diabetic patients with cervical LN metastasis of DTC, the metformin subgroup (17.1 years) was associated with longer DFS than the nonmetformin subgroup (8.6 years) (HR 0.16, p = 0.021); metformin treatment was also associated with longer DFS in this subgroup in multivariate analysis after adjusting age, BMI, duration of diabetes, presence of tumor at resection margin, and serum thyroglobulin level at ablation (HR 0.03, p = 0.035). Conclusions: Metformin treatment is associated with low recurrence in diabetic patients with cervical LN metastasis of DTC.
    No preview · Article · Aug 2015 · European Thyroid Journal

  • No preview · Article · Aug 2015 · Cancer Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Major problems of fine-needle aspiration (FNA) of thyroid nodules arise due to the non-diagnostic results caused by inadequately obtained FNA specimens. The purpose of this study is to evaluate the value of visual assessment of liquid-based cytology specimens during FNA of thyroid nodules for predicting the sampling adequacy. For three months, visual assessment of FNA specimens was used for 534, consecutive nodules in 534 patients. The FNA specimens were visually graded immediately following aspiration for each nodule, and the visual grades were classified into two categories, i.e. inadequate (less than six cell groups) and adequate (more than six cell groups). The cytology results were classified as diagnostic and non-diagnostic result based on the Bethesda System. We compared the US features and FNA characteristics between the diagnostic and non-diagnostic results. Multiple logistic regression analysis was used to determine factors independently predictive of non-diagnostic results. We also evaluated the inter-observer agreement regarding the visual assessment. Visual assessment was feasible in all patients, and the non-diagnostic rate was 11.6% (62/534). Non-diagnostic results were more frequent in the inadequate visual assessment group (38.1%) than in the adequate group (10.5%) (P = 0.001). Independent predictive factors for non-diagnostic results were inadequate visual assessment (odds ratio = 5.18), >50% vascularity (odds ratio = 3.98), and macrocalcification (odds ratio = 3.60). Interobserver agreement for the prediction of visual assessment was good (kappa value = 0.767, p < 0.001). Immediate visual assessment of a specimen during FNA of a thyroid nodule is a feasible method for predicting the sampling adequacy.
    No preview · Article · Jul 2015 · Endocrine Practice
  • [Show abstract] [Hide abstract]
    ABSTRACT: The accurate diagnosis of thyroid nodules is important for making management decisions. The purpose of this study is to evaluate the feasibility of core-needle biopsy with BRAF(V600E) mutation analysis (CNB+BRAF(V600E) ) and to compare the clinical usefulness of CNB+BRAF(V600E) and fine-needle aspiration with BRAF(V600E) mutation analysis (FNA+BRAF(V600E) ) in the diagnosis of thyroid malignancy. The results of BRAF(V600E) mutation analyses of 820 nodules from 820 patients (153 men, 667 women; mean age, 51.1 years), who underwent CNB+BRAF(V600E) (n=256) or FNA+BRAF(V600E) (n=564) between January 2011 and March 2012 were retrospectively evaluated. The feasibility of CNB+BRAF(V600E) was assessed by comparing its rate of detection of BRAF(V600E) mutations and positive predictive value with those of FNA+BRAF(V600E) . The clinical usefulness of CNB+BRAF(V600E) was determined by comparing rates of inconclusive results, the additional value of BRAF(V600E) mutation analysis, diagnostic surgery, and diagnostic performance with those of FNA+BRAF(V600E) . CNB+BRAF(V600E) and FNA+BRAF(V600E) had similar rates of BRAF(V600E) mutation detection (66.3% versus 64.4%, P = 0.883) and positive predictive value (100.0% versus 96.6%, P = 0.135). CNB+BRAF(V600E) had a significantly higher diagnostic accuracy rate (95.7% versus 85.9%, P < 0.001), and significantly lower rates of inconclusive results (8.2% versus 51.8%, P < 0.001), and diagnostic surgery (8.9% versus 22.3%, P = 0.006), than FNA+BRAF(V600E) . The greater diagnostic performance of CNB+BRAF(V600E) and its lower rate of inconclusive results than FNA+BRAF(V600E) suggest that CNB+BRAF(V600E) can reduce rates of preventable diagnostic surgery. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2015 · Clinical Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Lateral cervical lymph node (LCLN) metastasis, or pathologic N1b disease, is an important risk factor in papillary thyroid carcinoma (PTC). However, many patients have favorable prognosis even with pathologic N1b patients in clinical practice. The study aims to identify high- and intermediate-risk groups based on initial pathologic characteristics in these patients. Patients: This study included 518 classical PTC patients confirmed as pathologic N1b at initial surgery between 2001 and 2010. All patients underwent a single fixed activity (5.6 GBq) of radioactive I-131 remnant ablation. Results: Patients with a primary tumor larger than 4 cm, gross extrathyroidal extension, metastatic LN larger than 3 cm, or greater than 10 metastatic LCLN were classified as high-risk group. These comprehensive pathologic criteria were retrieved from cox proportional hazard models. Twenty two percent of patients (n = 113) were classified as high-risk and 78% (n = 405) as intermediate-risk group. Successful ablation was identified in only 32% of the patients in the high-risk group and 61% in the intermediate-risk group (p < 0.001). The difference between the two risk groups was independent to gender. There was a significant difference in disease-free survival between the high- and intermediate- risk N1b groups during 5.1 years of median follow-up (84% vs. 59%, p < 0.001). Distant metastasis was more prevalent in the high-risk group (20%) than in the intermediate-risk group (4%, p < 0.001). Conclusions: The prognosis of PTC patients with LCLN metastasis varies depending on initial pathologic characteristics. We proposed the comprehensive pathologic criteria for sub-classification of N1b into high- and intermediate-risk groups and this sub-classification may permit personalized management of N1b PTC patients.
    Full-text · Article · Jul 2015 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prognosis of papillary thyroid cancer (PTC) with cervical lymph node (LN) metastasis has changed with increased detection of subclinical metastatic LNs. The number and size of metastatic LNs were proposed as new prognostic factors in PTC with cervical LN metastasis (N1). To evaluate changes in N1 PTC characteristics and clinical outcome over time and to confirm the prognostic value of the number and size of metastatic LNs. This study included 1,815 N1 PTC patients diagnosed between 1997 and 2011. Patients were classified into three risk groups according to the number and size of metastatic LNs: very low risk, ≤ 5 and < 0.2 cm; low risk, ≤ 5 and ≥ 0.2 cm; and high risk, > 5. Response to initial therapy and disease -free survival (DFS) Results: Metastatic LNs became smaller and the ratio of metastatic LNs, which represents the extent of LN involvement and the completeness of surgery, decreased significantly over time. The proportion of patients with excellent response significantly increased from 33% to 67% over time (P < .001). These improvements were more evident in the low- and high-risk groups than in the very low-risk group. The DFS 5 years after initial surgery was also significantly increased from 73% to 91% over time (P < .001). The new LN classification was strongly associated with outcome. Patients in the very low-risk group had longer DFS than those in the low- and high-risk groups during the study period. The clinical outcome of N1 PTC has significantly changed over time with the earlier detection of thyroid cancers with less extensive LN involvement. More complete surgical neck dissection also might be responsible for these changes. The number and size of metastatic LNs are important prognostic factors of recurrence in N1 PTC.
    No preview · Article · Jun 2015 · The Journal of Clinical Endocrinology and Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The definitive diagnosis of minimal extrathyroid extension (ETE) is subjective because a well-defined true capsule is absent in the thyroid gland. We subclassified the extent of minimal ETE and investigated the clinicopathological significance of the presence of minimal ETE in patients with solitary papillary thyroid carcinomas (PTCs) and solitary papillary thyroid microcarcinomas (PTMCs). A series of 546 patients with solitary PTCs, including 144 patients with solitary PTMCs, were retrospectively analyzed. Whether the presence of minimal ETE had an effect on recurrence-free survival (RFS) along with other clinicopathological parameters was investigated. The only independent prognostic factor found to be associated with recurrence was the presence of LN metastasis in solitary PTC (p = 0.002) but not in solitary PTMC groups (p = 0.073). The presence of minimal ETE had no effect on RFS in both solitary PTC (p = 0.053) and solitary PTMC (p = 0.816). The presence of minimal ETE has no significant influence on RFS in solitary PTC and PTMC. There is a risk of overrepresenting the T3 category in solitary PTC and PTMC patients with minimal ETE.
    Preview · Article · Jun 2015 · Annals of Surgical Oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A diffuse hepatic uptake (DHU) on radioiodine whole-body scans (WBS) after (131)I therapy is caused by (131)I-labeled iodoproteins, particularly (131)I-labeled thyroglobulin (Tg). We hypothesized that the DHU intensity after (131)I therapy might correlate with subsequent serum Tg reduction, suggesting that DHU reflects destruction of functioning thyroid tissue as measured by serum Tg. We retrospectively reviewed the medical records and (131)I WBSs of 47 patients treated with (131)I therapy for distant metastasis from differentiated thyroid cancer (M:F = 15:32, median age 45 years, range 11-74 years). All patients received post-ablative (131)I scans (PAWBS) at first (131)I ablation after total thyroidectomy and post-therapy (131)I scan (PTWBS) at second (131)I therapy. The DHU intensities of the PAWBS and PTWBS were classified into 3 grades: 1, faint; 2, modest; and 3, intense. Serum thyroid-stimulating hormone-stimulated Tg (sTg) levels were measured at the time of each therapy and 1 year after the second (131)I therapy. One year after the second (131)I therapy, 10 patients (21.3 %) were in remission and 37 (78.7 %) had persistent disease. The DHU intensity on PAWBS correlated with the percentage sTg reduction at the next follow-up point (σ = 0.466, p = 0.0016). The patients with intense DHU on PTWBS tended to have a higher percentage sTg reduction than the other patients, although statistical significances were marginal (Spearman's rank correlation: σ = 0.304, p = 0.054; Kruskal-Wallis test: p = 0.067). In univariate analysis, the DHU grades on PAWBS and the initial sTg levels were significantly different between patients in remission and those with persistent disease (PAWBS: p = 0.022; initial sTg: p = 0.0059). In multivariate logistic regression analysis, after adjusting for initial sTg levels, a DHU grade of 3 on PAWBS was an independent predictor of remission (PAWBS: p = 0.028; initial sTg <100 ng/ml: p = 0.043). In patients with iodine-avid distant metastases, intensity of DHU on (131)I post-therapy scan correlated with subsequent percentage serum sTg reduction. Also, intense DHU could be one of the predictors of remission in these patients.
    Full-text · Article · May 2015 · Annals of Nuclear Medicine

Publication Stats

3k Citations
420.87 Total Impact Points

Institutions

  • 2015
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 1993-2015
    • University of Ulsan
      • • Department of Internal Medicine
      • • College of Medicine
      Ulsan, Ulsan, South Korea
  • 1990-2015
    • Asan Medical Center
      • Department of Endocrinology/Metabolism
      Sŏul, Seoul, South Korea
  • 2000-2014
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2012
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • Sungkyunkwan University
      • School of Medicine
      Sŏul, Seoul, South Korea
  • 1989-1990
    • Seoul National University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea