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We aimed to evaluate the clinical efficacy and safety of lenvatinib in patients with advanced anaplastic thyroid cancer (ATC) in real-world practice. This multicenter, retrospective cohort study included 14 patients with advanced ATC who received lenvatinib. We evaluated the response rate according to RECIST. Ten patients had de novo ATC, and lenvatinib was used as a neoadjuvant treatment in eight patients. During a median follow-up of 6.7 months, patients received lenvatinib at a median dose of 13 mg daily. Overall, four patients (29%) showed partial response, nine (64%) had stable disease, and one (7%) had progressive disease. Tumor burden was reduced in 13 patients (93%), and the median best percent change from the baseline was −15.8%. The median progression-free survival and overall survival were 5.7 months (95% confidence interval [CI], 2.2–8.3) and 6.7 months (95% CI, 3.0–8.4), respectively. All patients experienced adverse events (AEs). Most AEs were manageable but two AEs—tracheal perforation, and pneumothorax and pneumomediastinum—were life-threatening. One patient underwent flap surgery for reconstruction of their tracheal perforation, and another died of pneumothorax and pneumomediastinum, which seemed to be related to lenvatinib. In this multicenter real-world study, lenvatinib demonstrated limited clinical activity in advanced ATC. It effectively reduced the tumor burden but showed doubtful survival benefit. Although most AEs were manageable, one fatal AE was related to rapid tumor shrinkage. Further studies are needed to clarify the efficacy and optimal dose of lenvatinib in patients with advanced ATC.

Background: Recently, the role of radioactive iodine (RAI) ablation in the treatment of low risk differentiated thyroid carcinoma (DTC), especially for papillary thyroid microcarcinoma (PTMC), is controversial. This study aims to compare quality of life (QoL) parameters in patients with PTMC underwent total thyroidectomy (TT) versus TT with RAI ablation. Methods: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: 12-item short-form health survey (SF-12), thyroid cancer specific quality of life (THYCA-QOL), and fear of progression (FoP). Results: The TT and TT with RAI groups comprised 107 and 183 patients, respectively. The TT with RAI group had significantly lower serum TSH level than TT group. However, after matching of TSH level between the groups (TT with RAI = 100, TT = 100), there was no significant difference in baseline characteristics. According to the SF-12, the score for general health showed significantly lower in TT with RAI group than TT group (p = 0.047). The THYCA-QOL also showed statistically significant difference in felt chilly score between the groups (p = 0.023). No significant differences in FoP scores were seen between the groups. Conclusion: Patients with PTMC underwent TT with RAI ablation experienced more health-related problems than those managed by TT alone. These findings support RAI ablation should be carefully determined in patients with low-risk DTCs.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy without effective therapeutic options to improve survival. Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator whose amplification and/or overexpression has been identified in many cancers. In this study, we explored the expression of SRC-3 in ATCs and the effects of a new class of SRC-3 inhibitor-2 (SI-2) in human ATC cells (THJ-11T and THJ-16T cells) and mouse xenograft models to assess therapeutic potential of SI-2 for the treatment of ATC. SRC-3 protein abundance was significantly higher in human ATC tissue samples and ATC cells than in differentiated thyroid carcinomas or normal controls. SI-2 treatment effectively reduced the SRC-3 expression in both ATC cells and ATC xenograft tumors induced by these cells. Cancer cell survival in ATC cells and tumor growth in xenograft tumors were significantly reduced by SI-2 treatment through induction of cancer cell apoptosis and cell cycle arrest. SI-2 also reduced cancer stem-like cells as shown by an inhibition of tumorsphere formation, ALDH activity, and expression of stem cell markers in ATC. These findings indicate that SRC-3 is a potential therapeutic target for treatment of ATC patients and that SI-2 is a potent and promising candidate for a new therapeutic agent.

Based on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort.This study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA.The mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%.This multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC.

Objective To investigate the association between sarcopenia, sarcopenic obesity (SO), metabolic syndrome (MetS), and occupational history. Methods Using data from the Korea National Health and Nutrition Examination Survey, men more than or equal to 65 years of age (n = 679) were grouped according to occupation. Results Mean skeletal muscle mass index was higher and mean body fat mass was lower in agribusiness and low-level (AL) workers than white-collar (WC), blue-collar (BC), and pink-collar (PC) workers. The risk of sarcopenia was highest in BC, followed by WC, PC, and AL. The risk of SO was higher in WC than AL and MetS was higher in WC and BC than AL. Conclusions The development of sarcopenia, SO, and MetS is related to lifetime occupation, with BC workers being most affected by sarcopenia and WC workers being most affected by SO and MetS.

Objective Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Design Retrospective cohort study. Methods This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension. Results The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12–4.16, P = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n = 121) and matched cPTC. However, CCV group (n = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11–70.33, P = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (P = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66–11.00, P = 0.001). Conclusions When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

Recent studies have reported improved survival in patients with thyroid cancer. This study evaluated the changes in disease-specific survival (DSS) of patients with differentiated thyroid cancer (DTC) in association with clinicopathologic characteristics from 1996 to 2005 in Korea.This was a retrospective, multicenter cohort study. A total of 4398 DTC patients were included, and they were classified according to the year of initial surgery: 1996-2000 (period 1), 2001-2003 (period 2), and 2004-2005 (period 3).During the study period, patient age and the proportion of papillary thyroid cancer increased gradually. Primary tumors became smaller (2.3 ± 1.4 cm at period 1 to 1.5 ± 1.2 cm at period 3; p 0.001). The proportion of high-volume lymph node metastases decreased significantly (20% at period 1 to 13% at period 3; p for trend0.001). DSS differed significantly according to period during the median 10 years follow-up (p = 0.002). The 10-year DSS rates were 98.0%, 98.7%, and 99.2% in periods 1, 2, and 3, respectively. After adjusting for various characteristics, the disease-specific mortality risk was significantly lower during period 2 (hazard ratio = 0.49 [confidence interval CI 0.25-0.90], p = 0.021) and period 3 (hazard ratio = 0.40 [confidence interval 0.21-0.77], p = 0.006) compared to that of period 1. This trend was also significant in a subgroup analysis of low (I-II) and high (III-IV) TNM stages.The disease-specific mortality of patients with DTC in Korea decreased over time. Earlier detection of small DTCs with less extensive disease and standardization of treatment may be associated with this phenomenon.

Background Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. Methods We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. Results The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. Conclusion The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

Objective: The aims of this study were to stratify the risk of malignancy in thyroid incidentalomas detected on 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG...

OBJECTIVE We aimed to evaluate differences in serum thyroid-stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI). STUDY DESIGN Sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean population. PATIENTS Research subjects were selected by two-stage stratified cluster sampling of the population and housing census data. A total of 5639 subjects aged >18 years, who were not pregnant, and had undergone thyroid function testing during the survey period, were included. MEASUREMENT The level of serum TSH according to smoking status, iodine intake and presence of TPOAb were evaluated. RESULTS In the reference population, mean serum TSH level in current smokers (1.87 mIU/L, 95% CI, 0.52-5.37 mIU/L) was significantly lower than that in nonsmokers (2.33 mIU/L, 95% CI, 0.79-6.69 mIU/L, P

OBJECTIVE Distinguishing malignancy from benign thyroid nodule has always been challenging, especially in follicular lesions. Thyroid nodules with small size and indeterminate cytology do not lead to immediate surgery. We tried to evaluate whether tumour size and tumour growth rate can distinguish follicular thyroid carcinoma (FTC) from follicular adenoma (FA). DESIGN AND PATIENTS This retrospective study included patients with pathologically proven FTCs (n = 50) and FAs (n = 110) who underwent preoperative serial neck ultrasonography (US) at least 3 times: it comprises 30% of all follicular tumours (32% FAs and 25% FTCs). The growth rates of follicular tumours on serial US were measured using at least 3 consecutive examinations during a median follow-up of 4.1 years (range, 0.7-13.3 years) by experienced radiologists. RESULTS The FA and FTC groups showed no significant difference in clinicopathological characteristics, including age, proportion of large nodules (>4 cm) and preoperative cytology. The maximum diameter of thyroid nodule was gradually increased in both groups with statistical significance (P

Background Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor previously known as noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The absence of BRAFV600E mutations has been considered characteristic of NIFTPs. However, a recent study from Korea found that 28.6% of NIFTPs harbored a BRAF mutation. This study evaluated BRAF and RAS mutations in NIFTPs and invasive subtype of EFVPTCs. Methods This study enrolled 32 patients with NIFTP and 48 with invasive EFVPTC. BRAF, NRAS, HRAS, and KRAS mutations were evaluated by direct sequencing using DNA from fresh-frozen tissues and formalin-fixed, paraffin-embedded tissue samples. Results The primary tumor size of NIFTP was smaller than that of invasive EFVPTC (median 2.8 cm vs. 3.2 cm; p = 0.03). Cervical lymph node metastases were found in only four (8%) patients with invasive EFVPTC. There was no BRAF mutation in NIFTPs, whereas invasive EFVPTCs had three (6%) BRAFV600E mutations and one (2%) BRAFK601E mutation. RAS mutations were detected in 15 (47%) NIFTPs and 22 (46%) invasive EFVPTCs. NRAS mutations in codon 61 were the most common mutations in NIFTPs (34%) and invasive EFVPTCs (27%). There was no significant difference in the frequency of RAS mutations between the two groups. Conclusions There was no BRAF mutation in any of the NIFTPs. RAS mutations, particularly mutations in codon 61 of NRAS, were the most common mutations in both NIFTPs and invasive EFVPTCs. The presence of a RAS mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs.

Regional lymph node metastases (LNM) have prognostic significance in differentiated thyroid cancer (DTC). However, there was no distinction between N1a and N1b in the final staging classification in the eighth edition of the tumor-node-metastasis (TNM) staging system. This study aimed to evaluate the prognostic implication of N1b classification for predicting disease-specific survival (DSS) in DTC patients with stage I/II disease.A total of 3089 patients with stage I/II DTC who underwent thyroid surgery between 1996 and 2005 were included. DSS was evaluated according to N classification and number of LNM. A modification of the TNM was assessed that classified N1b cases in patients aged ≥55 years as stage IIB and the remaining cases as stage IIA.The mean patient age was 45.6 years, and the median follow-up period was 10.0 years. In patients aged ≥55 years, patients with N1b had significantly poorer DSS compared to those with N0 (hazard ratio [HR] = 11.0; p 0.001) and N1a (HR = 4.2; p = 0.013). The large-volume LNM group had significantly poorer DSS compared to the N0 (HR = 10.1; p 0.001) and small-volume LNM (HR = 3.9; p = 0.019) groups. When patients were reclassified using the modified TNM staging system, DSS was significantly poorer in stage IIB patients than in stage IIA patients (HR = 2.9; p = 0.030).N1b classification has a significant prognostic implication in patients with stage I/II DTC, especially in older patients. Modified TNM staging employing N1b classification could be more useful for the prediction of DSS.

The risk of recurrence in patients with differentiated thyroid cancer (DTC) can be estimated based on their response to initial therapy. The aim of this study was to evaluate an adequate follow-up strategy for DTC patients with an excellent response by assessing the characteristics of structural recurrence.This historical cohort study included 1359 DTC patients who had excellent response to total thyroidectomy with radioactive iodine remnant ablation.Among 1359 patients, 703 (54%) patients were classified as stage I according to the seventh tumor node metastasis staging system, and 987 (73%) patients were classified as intermediate risk according to the American Thyroid Association's risk stratification after initial therapy. During a median of 8.7 years of follow-up, only 13 (1%) patients were confirmed to have structural recurrence. All of the recurrences were locoregional disease, and there were no distant metastases. Recurrences were detected late at a median of 5.5 years after the initial surgery (range 3.6-10.7 years). All structural recurrences were detected on neck ultrasonography. Non-stimulated serum thyroglobulin (Tg) was detectable (≥0.2 ng/mL) in four (31%) patients, and serum anti-Tg antibodies were positive in one (8%) patient. However, non-stimulated serum Tg levels were stably low (0.2 ng/mL) in eight (62%) patients when recurrences were detected. In addition to these 13 patients, 14 patients also presented with biochemical persistent disease at the end of follow-up.Recurrences of DTC in patients with an excellent response to initial therapy were detected relatively late. The intensity and frequency of follow-up of neck ultrasonography as well as serum Tg and anti-Tg antibody measurements should be reduced, especially within five years of the initial therapy, in DTC patients who have an excellent response.

Research Objectives To evaluate the relationship between several measures of sarcopenia and incidence of falls in elderly. Design A 2-year prospective cohort study. Setting Community. Participants A total of 2252 subjects (1065 males; 1187 females; 70-84 years) were recruited. Interventions Demographic information, comorbidities and history of falls within 1 year were assessed. Cognitive performance was assessed using the Korean version of Mini Mental State Examination (K-MMSE) and muscle mass was measured via dual-energy X-ray absorptiometry. Grip strength and gait speed also measured at baseline and 2-year follow-up. Main Outcome Measures History of falls within 1 year at 2-year follow-up. Results History of previous falls and poor cognitive performance at baseline were significantly associated with incidence of falls during follow-up period. Subjects who had fallen during follow-up period showed poor hand grip strength and poor gait speed compared with those who had not. In females, the muscle mass index of body mass index (BMI) adjustment were significantly associated with incidence of falls. Multiple logistic regression analysis revealed that poor gait speed was a significant risk factor of falling in females. Conclusions The predictive value of individual measures of sarcopenia vary by genders. Poor physical performance was significantly associated with incidence of falls in females, but there was no significant associations between muscle mass indices, strength, and physical performance and falling in males. Author(s) Disclosures No conflict of interest.

This study validated the dynamic risk stratification (DRS) system with regard to its association with structural recurrence and risk factors associated with non-excellent responses in patients45 years with stage I classical papillary thyroid cancer (PTC).This historical cohort study included 598 patients with stage I classical PTC45 years of age treated with total thyroidectomy followed by radioactive iodine remnant ablation (n = 440), total thyroidectomy without radioactive iodine remnant ablation (n = 23), and thyroid lobectomy alone (n = 135).The median follow-up period was 123 months. Structural recurrence occurred in 4.2% (n = 18/432) of the patients with an excellent response, 17.1% (18/105) of patients with an indeterminate response, 44.7% (17/38) of patients with a biochemically incomplete response, and 82.6% (19/23) of patients with a structurally incomplete response (p 0.001) during the follow-up. The disease-free survival curves of each response showed significant differences (p 0.001). Extensive extrathyroidal extension and extranodal extension were the independent risk factors associated with non-excellent response (p 0.05).DRS may reduce unnecessary additional treatments by reclassifying initial risk estimates of structural recurrence. Furthermore, applying the risk factors associated with non-excellent response to initial therapy may be a more useful and viable surrogate of the risk for structural recurrence in stage I PTC patients45 years of age.

SummaryObjective Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimoto's thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status. Design Retrospective cohort study. Patients 1369 patients with PTC who underwent total thyroidectomy with central compartment neck dissection. Measurements Metastatic LN ratio, defined as number of metastatic LNs divided by number of removed LNs, was used to evaluate the extent of LN dissection as well as the status of LN metastasis. Disease-free survival and dynamic risk stratification were compared for clinical outcomes. Results Presence of HT did not lower the risk of cervical LN metastasis (61.6% in patients with HT vs 65.1% in patients without HT, P = .292). Patients with HT had significantly larger numbers of removed LNs than patients without HT (11 vs 8, respectively, P

Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC.This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels.Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57).TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.

BACKGROUND The incidence of thyroid cancer has increased very rapidly in Korea; however, most previous studies suggested that the mortality rate for thyroid cancer remained stable. The objective of the current study was to evaluate recent changes in standardized thyroid cancer mortality using data from Statistics Korea. METHODS Population and mortality data from 1985 through 2015 were obtained from Statistics Korea. Age-standardized mortality rates (ASMRs) from thyroid cancer per 100,000 population were calculated based on the World Health Organization standard population. RESULTS In Korea, the ASMRs from thyroid cancer increased from 0.17 (95% confidence interval [CI], 0.17-0.18) per 100,000 in 1985 to 0.85 (95% CI, 0.83-0.86) per 100,000 in 2004, which was the highest among all countries. Subsequently, the ASMRs continuously decreased to 0.42 (95% CI, 0.41-0.43) per 100,000 between 2004 and 2015. The estimated annual percent change (APC) from 1985 to 2004 was 7.94 (95% CI, 6.43-9.46), and the corresponding value from 2004 to 2015 was −4.10 (95% CI, −5.76 to −2.40). Changes in the ASMRs reflected similar patterns in men (1985-2003: APC, 8.51; 2003-2015: APC, −4.32) and women (1985-2004: APC, 7.62; 2004-2015: APC, −4.38) and were also observed in older patients (aged ≥ 55 years). CONCLUSIONS Thyroid cancer mortality in Korea increased until 2004 and then continuously decreased until 2015. Increases in the early diagnosis of thyroid cancer, changes in exposure to risk factors, and standardization in diagnosis and treatment may be associated with the decrease in thyroid cancer mortality in Korea. Cancer 2017. © 2017 American Cancer Society.

Serum thyroid-stimulating hormone level was influenced by several factors, including age, gender, thyroid auto-antibodies, race, and intake of dietary iodine. We evaluated age-specific reference interval of serum thyroid-stimulating hormone levels in Korea, an iodine excess area. This nationwide population-based cross-sectional study included representative civilian, non-institutional population (n = 6564) who underwent thyroid function tests from Korea National Health and Nutrition Examination Survey VI (2013–2015). The reference interval of serum thyroid-stimulating hormone levels was defined between the 2.5th and 97.5th percentiles in the reference population. The geometric mean of serum thyroid-stimulating hormone levels in the reference population was 2.17 mIU/L with a reference interval of 0.62–6.84 mIU/L. In the reference population, the geometric mean of serum TSH levels in each age group of 10–18, 19–29, 30–39, 40–49, 50–59, 60–69, and equal or older than 70 years was 2.47, 2.20, 2.07, 2.04, 2.23, 2.12, and 2.27 mIU/L, with a reference interval of 0.74–7.35, 0.67–6.42, 0.63–6.04, 0.62–6.20, 0.56–7.37, 0.57–6.90, and 0.42–6.58 mIU/L, respectively. In the reference population, the urinary iodine concentrations were consistently high in all age groups (median 298.5 μg/L). Subjects aged 10–18 years had the highest urinary iodine concentrations. There was no shift toward higher levels with age in the distribution of serum thyroid-stimulating hormone levels. The reference interval of serum thyroid-stimulating hormone levels was consistently high in all age group, especially from adolescence 10–18 years in a Korean population who had excessive intake of dietary iodine.

Objective Active surveillance is an option for patients with papillary thyroid microcarcinoma (PTMC). However, the long-term clinical outcomes after delayed surgery remain unclear. We compared the long-term clinical outcomes of PTMC patients according to the time interval between initial diagnosis and surgery. Design and methods In this individual risk factor-matched cohort study, PTMC patients were classified into three groups according to the delay period: ≤6 months, 6–12 months and >12 months. Patients were matched by age, sex, extent of surgery, initial tumor size as measured by ultrasonography (US), and by the presence of extrathyroidal extension, multifocal tumors and central cervical lymph node metastasis. We compared the dynamic risk stratification (DRS) and the development of structural persistent/recurrent disease of patients. Results A total of 2863 patients were assigned to three groups. Their mean age was 50 years, 81% were female and 66% underwent lobectomy. The mean tumor size at the initial US was 0.63 cm. There were no significant differences in clinicopathological characteristics between groups after individual risk factor matching. Comparison of the DRS revealed no significant difference according to the delay period (P = 0.07). During the median 4.8 years of follow-up, there were no significant differences in the development of structural recurrent/persistent disease (P = 0.34) and disease-free survival (P = 0.25) between groups. Conclusions In PTMC patients, delayed surgery was not associated with higher risk of structural recurrent/persistent disease compared to immediate surgery. These findings support the notion that surgical treatment can be safely delayed in patients with PTMC under close monitoring.

[Purpose] The purpose of this case study was to determine the effectiveness of bandaging the arm of a patient with secondary lymphedema on the patient's quality of life, arm volume and arm function using an additional pad and taping along with some other standard therapy modalities for lymphedema. [Subjects and Methods] I used a bandage with an additional pad and taping, along with MLD, exercise, and skin care to treat a patient with unilateral breast-cancer-related arm lymphedema who had fibrotic tissue on her lower arm and hand. I made a pad called a "muff" and applied it under tape while using Vodder's technique. Treatment was performed during 5 therapy sessions a week for 2 weeks. [Results] After the physiotherapy sessions, the excess edema volume decreased to 608 ml, and the percentage of excess volume (PEV) was 9.6%. The therapeutic efficacy, measured as percentage reduction of excess volume (PREV), was -79.5%, meaning that the edema volume was reduced 79.5%. The use of an additional pad and taping on a large edematous site with fibrotic changes can produce more efficacious lymphedema care. [Conclusion] The use of an additional pad and taping on a large edematous site with fibrotic changes has demonstrated a positive result in lymphedema management for a post mastectomy patient and, therefore, further studies on this method are suggested with a larger sample size.

The clinical course of patients with lung metastases of differentiated thyroid carcinoma (DTC) vary, and cancer-specific survival (CSS) can be associated with tumor burden. This study evaluated the growth kinetics of lung metastases from DTC using serial chest computed tomography for Response Evaluation Criteria in Solid Tumors assessment and its prognostic implications.Forty-four patients with macronodular lung metastases (≥1 cm) of DTC were included. The time intervals to disease progression of lung metastases were measured and compared to CSS rates.On the basis of the time to progression, 15 (34%), 17 (39%), and 12 (27%) patients were classified into the slow (≥3 years), moderate (1-3 years), and rapid groups (1 year), respectively. The growth kinetics of lung metastases exhibited a linear pattern in the three groups. The doubling time of tumor burden was 1.8 years (RThis is the first study to demonstrate objectively that tumor growth kinetics within the first year are an independent predictor of CSS in patients with macronodular lung metastases. Performing chest computed tomography at least twice a year in the early phase of the disease in patients with macronodular lung metastases may be helpful for identifying high-risk patients who are eligible for treatment with tyrosine kinase inhibitors.

Most of the increase in thyroid cancer in recent decades has been due to papillary thyroid microcarcinoma (PTMC). We evaluated the efficacy of radioiodine remnant ablation (RRA) in patients with PTMC. This historical cohort study included 1932 PTMC patients without lateral cervical lymph node (LN) or distant metastasis who underwent total thyroidectomy (TT) during the median 8.3 years of follow-up. The clinical outcomes of patients with or without RRA were compared using weighted logistic regression models with the inverse probability of treatment weighting (IPTW) method and considering risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality, and central cervical LN metastasis. The median primary tumor size of the RRA group was significantly larger than that of the no-RRA group (0.7 vs. 0.5 cm, P

SummaryObjectives Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN metastasis. Design and Patients This retrospective cohort study with a nested, matched case–control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched. Results Compared with the N0 NED group, the N1b group was younger (

Context Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. Objective To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance. Design and setting A retrospective cohort study. Participants In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume. Results The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination. Conclusion Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.

Background/Aims There have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans. Methods This study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection. Results H. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04). Conclusions In our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis.

For patients with lung metastases of differentiated thyroid carcinoma (DTC), there is no consensus on the maximal size of metastatic lesions to use when determining the intensity of follow-up and additional therapeutic options. This study evaluated the clinical outcomes and survival of patients with metastatic DTC confined to the lung, using the maximal diameter of lung lesions in the initial computed tomography.This retrospective cohort study included 112 DTC patients with metastases confined to the lung. The clinical responses were evaluated according to changes in the serum levels of stimulated thyroglobulin or antithyroglobulin antibody, disease status was evaluated according to radiological findings, progression-free survival (PFS), and cancer-specific survival (CSS).Macronodular lung metastases (≥1 cm) were observed in 27 (24%) patients, and these patients had significantly poor biochemical responses and disease status (p 0.001, and p 0.001, respectively), irrespective of radioactive iodine (RAI) avidity. After adjusting for age, sex, primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, time of lung metastasis, and RAI avidity, the macronodular group also had shorter PFS and CSS (p = 0.009 and p = 0.03, respectively) than the micronodular group. From the multivariate analyses, RAI avidity was not an independent prognostic factor predicting PFS and CSS. In the subgroup analyses, RAI avidity was a significant prognostic factor associated with better PFS and CSS (p = 0.013 and p = 0.021, respectively) in the micronodular group only.The initial largest diameter of metastatic lesions is the most important prognostic factor for predicting poor clinical outcomes and survival in patients with metastatic DTC confined to the lung.

BACKGROUND No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea. METHODS Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). RESULTS The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively. CONCLUSION The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea.

Objective: Thyrotoxic periodic paralysis (TPP) is characterized by acute onset paralysis and hypokalemia predominantly in male patients with thyrotoxicosis. Recent studies have emphasized the importance of potassium channels, which might explain the underlying mechanism of TPP. The KCNJ2 gene encodes the inward-rectifying potassium channel. In this study, we evaluated the role of KCNJ2 in the development of TPP. Design: Case-control analysis of KCNJ2 genetic association with TPP. Patients: 83 male patients with Graves’ disease (GD) were recruited for this study; 43 patients had TPP, whereas 40 patients had no history of TPP. Measurements: We analyzed the genotype and allelic frequency of a single-nucleotide polymorphism (SNP; rs312691) (C>T) adjacent to the KCNJ2 gene that is known to be related to TPP development. Results: The frequency of the CC genotype of the rs312691 SNP was 0.51 in TPP patients and 0.05 in controls (p-value=6.18×10−6). The C allele frequency of the SNP was 0.67 in the TPP group and 0.38 in the control group (odds ratio 3.24; 95% confidence interval 1.65–6.51; p-value, 3.1×10−4). The rs312691 SNP was significantly associated with TPP. Conclusions: We demonstrated that the rs312691 SNP was significantly associated with TPP. These findings suggest that KCNJ2 plays an important role in the pathophysiology of TPP in Korean GD patients with TPP.

The present study investigated the prevalence and risk factors of adhesive capsulitis of the shoulder in breast cancer patients between 13 and 18 months after surgery. This study included 271 women who underwent surgery for breast cancer with a postoperative period of 13–18 months. Current adhesive capsulitis was defined as restriction of external rotation and one or more additional directional restrictions with history of shoulder pain. Cumulative adhesive capsulitis was defined as current adhesive capsulitis or a previous history of adhesive capsulitis after breast cancer surgery. Multivariate logistic regression analysis was performed to examine associations between current or cumulative adhesive capsulitis and potential risk factors. Among the 271 study patients, 28 (10.3%) and 21 (7.7%) had cumulative or current adhesive capsulitis, respectively. The incidences of cumulative and current adhesive capsulitis were higher in those aged 50–59 years (odds ratio [OR], 9.912; 95% confidence interval [CI], 1.790–54.880; and OR, 12.395; 95% CI, 1.187–129.444, respectively) and those who underwent mastectomy (OR, 6.805; 95% CI, 1.800–25.733; and OR, 9.645; 95% CI, 2.075–44.829, respectively) or mastectomy with reconstruction (OR, 13.122; 95% CI, 2.488–69.218; and OR, 20.075; 95% CI, 2.873–140.261, respectively). Adhesive capsulitis of the shoulder is a common problem after breast cancer treatment. An age of 50–59 years and mastectomy are major risk factors for adhesive capsulitis, and breast reconstruction additionally increases the risk. Patients with these risk factors require greater attention for early diagnosis and proper treatment.

Background Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation. Methods In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire. Results The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the "felt chilly" score between groups (P=0.023). No significant differences in FoP scores were observed between the groups. Conclusion Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

Background: Treatment for patients with radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC) is challenging. Recently, two tyrosine kinase inhibitors (sorafenib and lenvatinib...

The aim of this study was to evaluate the long-term clinical outcomes of papillary thyroid carcinoma (PTC) patients exhibiting biochemical incomplete response (BIR) to initial therapy. We evaluated 102 patients with PTC showing a BIR during the first 12–24 months after total thyroidectomy and radioactive iodine therapy. Patients were divided into three groups according to changes in stimulated thyroglobulin (Tg) and anti-Tg antibody (TgAb) levels: the increasing TgAb group (n = 19, 18.6%), the decreasing Tg group (n = 58, 56.9%), and the increasing Tg group (n = 25, 24.5%). With a median follow-up of 12 years, 43 (42%) patients had structural persistent disease as follows: 36 (84%) at regional sites and 7 (16%) at distant sites. The rate of structural persistent disease was significantly different between groups, with 21%, 41%, and 60% in the increasing TgAb, decreasing Tg, and increasing Tg groups, respectively (P = 0.012). Among patients without structural persistent disease, only 19 (18.6%) showed no evidence of disease and 40 (39.2%) were of a biochemical persistent status at the time of final follow-up. Increasing Tg after initial therapy was a significant risk factor for structural persistent disease in patients with BIR (HR, 4.16; 95% confidence interval (CI): 1.38–12.54, P = 0.011). PTC patients with BIR showed a high rate of structural persistent disease and Tg change after initial therapy is the most important prognostic factor for determining clinical outcomes of these patients.

Background: Tumor volume doubling time (TVDT) is considered as a dynamic indicator of tumor growth and progression. We aimed to clarify whether TVDT should be considered in the cytological diagnosi...

The recent sharp increase in thyroid cancer incidence is mainly due to increased detection of small papillary thyroid microcarcinoma (PTMC). Due to the indolent nature of the disease, active surveillance (AS) of low-risk PTMCs is suggested as an alternative to immediate surgery to reduce morbidity from surgery. For appropriately selected PTMC patients, AS can be a good management option and surgical intervention can be safely delayed until progression occurs. Many considerations must be taken into account at the time of initiation of AS, including radiological tumor characteristics and clinical characteristics of the patient. A specialized medical team should be assembled to monitor patients during AS with an appropriate follow-up protocol. The fact that some patients require surgery for disease progression after long-term follow-up is a major drawback of the current AS protocol. Evaluation of tumor kinetics by three-dimensional tumor volume measurement during the initial 2–3 years of AS may be helpful for discrimination of PTMCs that need early surgical intervention. In this review, we will discuss the clinical outcomes of surgical intervention and AS, considerations during AS, and unresolved questions about AS.

Objective: To investigate the association of metabolic syndrome with the development of knee osteoarthritis. Design: Cross-sectional nationwide survey study. Subjects: Data obtained from the 2010–2012 Korea National Health and Nutrition Examination Survey. Methods: Subjects aged 50 years or older were included. Knee osteoarthritis (≥grade 2 Kellgren-Lawrence) and severe knee osteoarthritis (≥grade 3 Kellgren-Lawrence) were evaluated based on radiological findings. Medical information and demographic data were obtained from survey records. Multivariate regression analysis was performed to investigate the relationship between knee osteoarthritis and metabolic syndrome, and the number of metabolic syndrome components for dose-response relationship evaluation. Analyses were adjusted by age group (model 1) or by age group, education, smoking, alcohol consumption, and physical activity (model 2). Results: A total of 8,491 subjects (3,684 men and 4,807 women) were included in the study. In women, metabolic syndrome increased the risk of knee osteoarthritis (odds ratio (OR) = 1.644, p

OBJECTIVE It remains unclear whether the time interval between total thyroidectomy and radioactive iodine therapy (RAIT) affects clinical outcomes in papillary thyroid carcinoma (PTC). Therefore, we evaluated the impact of timing of the first post-thyroidectomy RAIT in intermediate-to-high-risk PTC. DESIGN AND PATIENTS This retrospective propensity score-matched cohort study included 720 PTC patients who received RAIT for

Background We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAFV600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. Methods To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAFV600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. Results First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. Conclusion Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

The use of antithyroid drug (ATD) therapy in patients with Graves' disease (GD) hyperthyroidism has been increasing, but ATD therapy is associated with a higher relapse rate. We aimed to evaluate clinical factors for predicting relapse of GD after ATD therapy.Patients (n = 149) with newly diagnosed GD who achieved remission of hyperthyroidism after ATD therapy (≥6 months) were followed up for18 months after ATD withdrawal. We evaluated the predictive factors of relapse during a median of 6.9 years of follow-up.Disease relapse occurred in 52 patients (34.9%). By multivariate analyses, a duration of the minimum maintenance dose therapy (MMDT) of 6 months was a significant factor in disease relapse (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.47-4.52; p 0.001), and a T3/free T4 (fT4) ratio 120 at ATD withdrawal was significantly more frequent in patients with relapse (HR 2.43; 95% CI, 1.36-4.34; p = 0.002). In the prediction-of-relapse model, the likelihood of relapse was greater in the high-risk group, which had a short MMDT duration and a T3/fT4 ratio ≥120 (HR, 5.81; 95% CI, 2.52-13.39; p 0.001) and the intermediate-risk group, which had a short MMDT duration or a T3/fT4 ratio 120 (HR, 2.77; 95% CI, 1.26-6.13; p 0.001), than in the low-risk group, which had a long MMDT duration and a T3/fT4 ratio 120.An MMDT longer than 6 months and a high T3/fT4 ratio at ATD withdrawal were independent predictors of relapse in patients who achieved initial remission after ATD for GD. These factors could be used to determine the optimal time to withdraw ATD during the treatment of GD hyperthyroidism.

Background: Tumor volume (TV) of papillary thyroid carcinoma (PTC) increases exponentially during active surveillance, and the growth rate differs for each patient. TV doubling time (TVDT) is consi...

The characteristics of critically ill surgical patients differ from those of medical patients. Few studies have evaluated rehabilitation in surgical intensive care units (SICUs), particularly in non-Western countries and in elderly patients.The objective of this study was to investigate the rehabilitation characteristics, safety, and functional recovery in non-Western SICU patients.Data from patients who received active rehabilitation in 2016 were retrospectively reviewed. Clinical characteristics, functional recovery, and safety were investigated and compared in patients aged65 or ≥65 years. Potential safety events were also compared between the two age groups and according to the reason for SICU admission.Data from 157 patients were included in the analysis. The number of patients who were able to stand or walk increased from the beginning of rehabilitation to the time of ICU discharge (from 52 to 102 patients, P 0.01). The Activity Measure for Post-Acute Care (AM-PAC) score also increased during rehabilitation (from 11.6 to 13.9, P 0.01). Functional recovery did not differ between the two age groups. During 780 rehabilitation sessions, 23 potential safety events (3.0%) were noted; no significant differences were seen between the two age groups. A significant difference was noted when patients were grouped according to the reason for SICU admission (1.7% in postoperative care patients vs 4.5% in patients admitted for other reasons, P = 0.02).Active rehabilitation in critically ill surgical patients is feasible and safe and resulted in improved mobility, regardless of age. However, the reason for SICU admission should be considered.

Given the emerging evidence supporting the lack of prognostic significance of gross extrathyroidal extension invading only strap muscles (strap-gETE), this study investigated whether lobectomy is feasible for patients with strap-gETE. A retrospective cohort study was conducted with 636 patients who had 1- to 4-cm-sized papillary thyroid carcinoma (PTC) treated with thyroid lobectomy. Patients with gross invasion of perithyroidal organs other than strap muscles or synchronous distant metastasis were excluded from the study. Disease-free survival (DFS) was compared according to the presence of strap-gETE. Strap-gETE was present in 50 patients (7.9%), with the remaining 586 patients (92.1%) showing no evidence of gETE. During the median follow-up period of 7.4 years, 6% of the patients with strap-gETE and 5.1% of the patients without gETE experienced structural persistent/recurrent disease (p = 0.99). No differences in DFS were observed between the two groups (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.38–4.08; p = 0.720). After adjustment for five major risk factors (age, gender, tumor size, multifocality, and cervical lymph node metastasis status) in the multivariate analysis, the presence of strap-gETE did not exhibit an independent role in the development of structural persistent/recurrent disease (HR 1.05; 95% CI 0.24–4.53, p = 0.950). Strap-gETE did not increase the risk of structural persistent/recurrent disease for the patients who underwent lobectomy for 1- to 4-cm-sized PTC. The study data support the limited role of strap-gETE in clinical outcomes and may broaden the indications for lobectomy for patients with PTCs.

BACKGROUND CONTEXT Lumbosacral disc herniation (LDH) is one of the most frequent musculoskeletal diseases causative of sick leave in the workplace and morbidity in daily activities. Nonsurgical managements are considered as first line treatment before surgical treatment. PURPOSE This clinical practice guideline (CPG) is intended to provide physicians who treat patients diagnosed with LDH with a guideline supported by scientific evidence to assist in decision-making for appropriate and reasonable treatments. STUDY DESIGN/SETTING A systematic review. PATIENT SAMPLE Studies of human subjects written in Korean or English that met the following criteria were selected: patients aged ≥18 years, clinical presentation of low back and radicular leg pain, diagnosis of LDH on radiological evaluation including computed tomography or magnetic resonance imaging. OUTCOMES MEASURES Pain and functional evaluation scales such as visual analogue scale, numeric rating scale, and Oswestry disability index METHODS The MEDLINE (PubMed), EMBASE, Cochrane Review, and KoreaMed databases were searched for articles regarding non-surgical treatments for LDH published up to July 2017. Of the studies fulfilling these criteria, those investigating clinical results after non-surgical treatment including physical and behavioral therapy, medication, and interventional treatment in terms of pain control and functional improvements were chosen for this study. RESULTS Nonsurgical treatments were determined to be clinically effective with regards to pain reduction and functional improvement in patients with LDH. Nevertheless, the evidence level was generally not evaluated as high degree, which might be attributed to the paucity of well-designed randomized controlled trials. Exercise and traction were strongly recommended despite moderate level of evidence. Epidural injection was strongly recommended with high degree of evidence and transforaminal approach was more strongly recommended than caudal approach. CONCLUSIONS This CPG provides new and updated evidence-based recommendations for treatment of the patients with LDH, which suggested that, despite an absence of high degrees of evidence level, non-surgical treatments were clinically effective.

Background. The trends in pediatric patients having thyroid nodules have not been well evaluated. Here, we analyzed the clinicopathological features of the children who have presented with thyroid nodules at our center over several decades in order to determine a change of trend. Materials and Methods. We analyzed 215 pediatric patients who had undergone a thyroidectomy between 1990 and 2014 at our single tertiary center. The clinicopathological features were analyzed according to age, sex, and the year of diagnosis. Results. The most common reason for hospital admission was a palpable anterior neck mass (76.7%). The males in the patient cohort were younger than the females (13 vs. 15 years old, p<0.05). The female patients increased from 50.0% to 83.0% with age (p<0.05). The rate of malignancy did not increase with age (p<0.05). However, the malignancy rate was higher in the more recently seen patients (23.8% during the early study period and 86.8% in the late study period; p<0.05). Conclusion. Following a thyroidectomy in children with thyroid nodules, there was no change in the rate of detection of thyroid cancer over time with age, although the detected frequency of malignancy has increased in more recent patients. Therefore, early thyroid nodule detection for malignant screening is likely to be required for pediatric patients in the near future.

The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody (TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease-free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30-0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28-0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31-0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38-1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16-0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.

Background: In pheochromocytoma and paraganglioma (PPGL), germline and somatic mutations in one of the known susceptibility genes are present in about 60% of tumors. However, the genetic events that drive the malignant progression of the disease are yet poorly understood. We aimed to evaluate the mutational profiles of metastatic PPGLs by targeted next-generation sequencing (NGS) to characterize the genetic events in metastatic PPGLs. Methods: Among the previously reported metastatic PPGL series from Asan Medical Center (AMC), Seoul, Korea, fifteen patients with available formalin-fixed, paraffin embedded (FFPE) archival samples for targeted exome sequencing were enrolled in this study. We also analyzed accessible data of aggressive PPGLs from The Cancer Genome Atlas (TCGA) and compared with findings of AMC samples. Results: A total of 115 germline and 34 somatic variants were identified in AMC cohort. Tumors of AMC cohort had median 0.58 per megabase tumor mutation burden. Most frequently mutated mutations were SDHB germline mutation (27%), and SETD2, NF1, HRAS somatic mutations (13%). Genes are subtyped into pseudohypoxia group (n=5), kinase group (n=5) and unknown (n=5) group. In unknown subgroup, two samples showed ATRX mutations and one accompanied SETD2 mutation. In copy number variation analysis, the most frequently observed pattern was deletion of 1p arm where SDHB is present. In survival analysis, SDHB mutation and pseudohypoxia subtype was significantly associated with poor prognosis. Conclusion: The analysis of NGS from patients with metastatic PPGLs demonstrated rare genetic events as well as well-known mutations. The pseudohypoxia subtype presented poor prognosis than kinase or unknown subtypes. Subjects who had no deletion in 1p arm showed favorable treatment response. Further studies to discover driver events and markers of metastasis are warranted.

Background: The pediatric lung transplant is a very important treatment for patients with end-stage lung diseae, and pulmonary rehabilitation (PR) is also an important factor in determining the prognosis. However, there is no much literature available on pulmonary rehabilitation in pediatric patients’ post lung transplant. Through this case report, we would like to present our intensive PR program for pediatric patients’ post-lung transplant. Patient concerns: The 10-year-old boy's breathing before receiving a lung transplant continued to deteriorate and he eventually became dependent on a wheelchair. Diagnosis: He was diagnosed with infantile acute lymphoblastic leukemia at 6 months of age. At the age of one year, he underwent allogeneic bone marrow transplantation, but was diagnosed with post-transplantation bronchiolitis obliterans (PTBO) two months later. He had a lung transplant at the age of 10. Interventions: He was hospitalized and received an initial assessment. This assessment included functional, cognitive, and psychological evaluations. He additionally completed PR exercises twice daily for two weeks. After discharge, he continued to participate in an outpatient-based PR program for three months. During the outpatient phase, PR exercises were performed once weekly, in addition to home-based cognitive training. Outcomes: Our intensive post-lung PR program improved our patient's exercise capacity, lung function, and quality of life. As a comprehensive rehabilitation service, our program also included a cognitive training component. Conclusion: We describe an intensive PR program tailored to pediatric patients’ post-lung transplant. The program was feasible and resulted in improvements in functional exercise capacity, lung function, and quality of life. Future research into our method is necessary for continued improvement of this novel program.

SummaryObjective Age >45 years is included as a variable in the tumor, node, metastases (TNM) staging of differentiated thyroid cancer (DTC), but a higher cut-off value has been suggested to be more clinically relevant and prevent over-staging. We evaluated the optimal age cut-off to predict disease-specific survival (DSS) in patients with DTC. Design and Patients This cohort study included 6333 patients with DTC who underwent thyroid surgery at two tertiary referral centres between 1996 and 2005. The optimal age cut-off value between 45 and 65 years for prediction of DSS was assessed. The proportion of variation explained (PVE) and Harrell's c-index was calculated to compare the predictability of each model. Results The median age of patients was 46·0 years (IQR 37·8–54·6), and 5498 (87%) were female. Median follow-up period was 10·0 years, and 10-year DSS rate was 98%. Using TNM staging with 45 years as the cut-off (TNM45), 10-year DSS rates of stage I–IV were 99·4%, 96·1%, 97·7% and 85·9%, respectively (PVE = 3·0%, Harrell's c-index = 0·693); and using 55 years as the cut-off (TNM55), 99·4%, 92·2%, 95·3% and 79·7%, respectively (PVE = 4·3%, Harrell's c-index = 0·776). On receiver operating characteristic curve analysis, the optimal age cut-off for prediction of DSS was 55·4 years (area under the curve = 0·837, P < 0·001). About 20% of patients were down-staged to stage I using TNM55 compared to that using TNM45. Conclusions The cut-off age of 55 years was more appropriate for TNM staging to achieve better predictability for DSS in patients with DTC. This change would prevent over-staging in low-risk patients and prevent over-aggressive treatment.