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Background Recently, adhesive skin electrodes have been reported to be useful for recording electromyographic signals from intrinsic laryngeal muscles for intraoperative neuromonitoring in thyroid surgery and have shown good results compared to existing recording methods. In this study, we investigated the optimal attachment location of adhesive skin electrodes for intraoperative neuromonitoring in both porcine models and human cases. Methods Attachment locations were divided vertically into upper, middle, and lower locations and horizontally into medial and lateral locations to determine the optimal location of placing adhesive skin electrodes preclinically in four porcine models. This study included a total of 78 patients who underwent thyroidectomy under intraoperative neuromonitoring with adhesive skin electrodes. Sixteen patients were monitored using both adhesive skin electrodes and an electromyographic endotracheal tube. Two pairs of skin electrodes were attached to the level of the thyroid cartilage lamina. Evoked electromyographic data, including data on mean amplitude and latency, obtained by stimulating the recurrent laryngeal nerve and vagus nerve, were collected. Results Lateral attachment of adhesive skin electrodes showed significantly higher evoked amplitudes than medial attachment in both animal models and human patients. In cases where skin electrodes and an electromyographic endotracheal tube were used together, the electromyographic endotracheal tube showed a significantly higher amplitude than skin electrodes, and laterally attached skin electrodes showed a significantly higher amplitude than medially attached skin electrodes. Conclusion Intraoperative neuromonitoring using adhesive skin electrodes was feasible in both animal models and human patients. We suggest that it would be better to attach adhesive skin electrodes to the lateral side of the thyroid cartilage lamina. Lateral attachment closer to the cricoarytenoid joint may be better for measuring muscle movement around the cricoarytenoid joint.

Background: The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.Methods: Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).Results: Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).Conclusion: The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Metastasis to the thyroid gland is rare, and the incidence of thyroid metastasis is from 1.4% to 3% for all thyroid malignancies. The most common metastatic malignancy to the thyroid gland is renal cell carcinoma. Ultrasonography is useful to assess the malignancy risk of thyroid nodules, and the ultrasonographic features of metastatic renal cell carcinoma in the thyroid gland are hypoechoic solid nodules with increased vascularity. Here, we report a case of metastatic clear cell renal carcinoma with benign ultrasonographic features and fine-needle aspiration cytology in the thyroid gland. A 76-year-old woman visited our hospital for surgical management of a growing left thyroid mass. Her history comprised previous left nephrectomy for an unknown reason. Thyroid ultrasonography revealed a well-defined, isoechoic, solid mass. Left thyroidectomy was performed, and the final diagnosis was metastatic clear cell renal carcinoma of the thyroid gland.

Background: Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC.Methods: Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues.Results: The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs.Conclusion: This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

Background and Objectives The American Joint Committee on Cancer (AJCC) staging system 8th Edition has stated that gross extrathyroid extension (ETE) is more important than microscopic ETE, and that it plays an important factor in the classification of T stages. Therefore, the prediction of gross ETE before surgery is important in establishing the clinical stage and determining the surgical extent. However, there are few studies predicting gross ETE using preoperative ultrasonography (US). The purpose of this study is to predict the gross ETE of papillary thyroid carcinoma (PTC) using preoperative US. Subjects and Method The preoperative US findings of 688 patients with PTC were compared with gross ETE confirmed during the surgery. The efficacy of preoperative US was statistically analyzed. Results A total of 70 (10%) patients were confirmed of their gross ETE. Thyroid tumors were classified into three groups (isolation, capsular contact, and capsular protrusion) according to their relationship with capsules, and evaluated using the preoperative US. There was a significant difference in gross ETE between groups (ppp=0.187). There was no difference in the degree of protrusion (p=0.868), but the difference in tumor size was significant (p

Highlights Dopant-tunable transparent conductive oxide (≤ 50 nm) fabricated via electric-field-driven metal implantation (m-TCOs; m= Ni, Ag, and Cu) is demonstrated.The m-TCOs exhibit ultrahigh transparency, low sheet resistance, and broad work function tunability, leading to outstanding performance in various optoelectronic devices.The work function change is attributed to the interstitial metal atoms that provide the empty d-orbital, resulting in the shift of the Fermi level. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00735-y., Ultrathin film-based transparent conductive oxides (TCOs) with a broad work function (WF) tunability are highly demanded for efficient energy conversion devices. However, reducing the film thickness below 50 nm is limited due to rapidly increasing resistance; furthermore, introducing dopants into TCOs such as indium tin oxide (ITO) to reduce the resistance decreases the transparency due to a trade-off between the two quantities. Herein, we demonstrate dopant-tunable ultrathin (≤ 50 nm) TCOs fabricated via electric field-driven metal implantation (m-TCOs; m = Ni, Ag, and Cu) without compromising their innate electrical and optical properties. The m-TCOs exhibit a broad WF variation (0.97 eV), high transmittance in the UV to visible range (89–93% at 365 nm), and low sheet resistance (30–60 Ω cm−2). Experimental and theoretical analyses show that interstitial metal atoms mainly affect the change in the WF without substantial losses in optical transparency. The m-ITOs are employed as anode or cathode electrodes for organic light-emitting diodes (LEDs), inorganic UV LEDs, and organic photovoltaics for their universal use, leading to outstanding performances, even without hole injection layer for OLED through the WF-tailored Ni-ITO. These results verify the proposed m-TCOs enable effective carrier transport and light extraction beyond the limits of traditional TCOs. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00735-y.

Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents. (J Liver Cancer 2021;21:124-138)

Economic evaluation is a type of comparative analysis between interventions in terms of both their resource use and health outcomes. Due to the good prognosis of thyroid cancer (TC), the socioeconomic burden of TC patients post-diagnosis is increasing. Therefore, economic evaluation studies focusing on TC are recommended. This study aimed to describe the concept and methods of economic evaluation and reviewed previous TC studies. Several previous studies compared the costs of interventions or evaluated recurrence, complications, or quality of life as measures of their effectiveness. Regarding costs, most studies focused on direct costs and applied hypothetical models. Cost-minimization analysis should be distinguished from simple cost analysis. Furthermore, due to the universality of the term “cost-effectiveness analysis” (CEA), several studies have not distinguished CEA from cost-utility analysis; this point needs to be considered in future research. Cost-benefit analyses have not been conducted in previous TC research. Since TC has a high survival rate and good prognosis, the need for economic evaluations has recently been pointed out. Therefore, correct concepts and methods are needed to obtain clear economic evaluation results. On this basis, it will be possible to provide appropriate guidelines for TC treatment and management in the future.

Branchial cleft cysts are the most common lateral neck mass, and usually have well-delineated cystic structures under ultrasonography. Ultrasonography and fine needle aspiration cytology is very helpful during preoperative diagnosis. However, these cysts may occur in unusual locations and have a sonographic morphology similar to malignant thyroid neoplasm. A 61-year-old woman presented with thyroid nodules, and ultrasonography revealed a 0.8-cm, hypoechoic, solid nodule with microcalcifications in the right lobe of thyroid in the lower portion. Postoperative histopathological examination revealed the 0.8-cm hypoechoic nodule to be a branchial cleft cyst. In addition, concurrent medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) were found. Herein, we present a rare case of branchial cleft cyst mimicking malignant thyroid neoplasm concurrent with medullary and PTC.

Current literature suggests 12–18 months of antithyroid drug (ATD) treatment for patients with Graves’ disease, but the risk of relapse is high. Although some studies reported better outcomes of long-term ATD treatment, recent data that suggest the optimal treatment duration are limited. We performed a multicenter retrospective cohort study of 908 patients newly diagnosed with Graves’ disease between 2006 and 2013. The relapse rate according to ATD treatment duration was analyzed. After initial ATD treatment, 338 patients (37.2%) had relapsed. The relapse rate according to ATD treatment duration was 42.4% at 1 year, 38.5% at 2 years, 33.8% at 3 years, 31.7% at 4 years, 30.2% at 5 years, 27.8% at 6 years, and 19.1% at more than 6 years, respectively, demonstrating a significant decreasing trend (p = 0.003). In a multivariable Cox regression analysis, ATD treatment duration was an independent risk factor for relapse (p = 0.043). The longer that ATD therapy is used, the lower the relapse rate is in patients with Graves’ disease. Long-term ATD treatment may be considered in Graves’ patients who do not show complications or an economic burden from hyperthyroidism.

Background: A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.Methods: Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.Conclusion: KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

A hybrid manufacturing method consisting of micro-electrical discharge machining and focused ion beam milling to fabricate single-crystal Cu micropillars with a diameter of several tens of microns or more was proposed. The method first utilized micro-electrical discharge machining, which adopted a micro-tool made of WC-Co material, to fabricate the coarse micropillars, one by one. It took approximately 70 s to fabricate each coarse micropillar. Seventy-six coarse micropillars were fabricated in the process of exploring optimum input parameters of supply voltage and capacitance value. Energy dispersive spectroscopy and electron backscatter diffraction analyses revealed that pristine Cu material could be obtained by removing only 1.2 μm of surface layer. The micropillar was finished using a focused ion beam to form a 15 μm diameter smooth micropillar with an aspect ratio of 3. The desired micropillar was produced by removing a surface layer of 6 μm or more from the side surface to avoid the micro-electrical discharge machining effect. It took approximately 2.5 h to complete the fabrication of a micropillar by stepwise annular milling. In the case of the hybrid method, it was possible to fabricate a high-quality micropillar 17 times faster than the focused ion beam only method.

Objective Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. Design A nationwide cohort study Methods Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). Results During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. Conclusions Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

This paper was developed as part of an effort by the National Institute for Occupational Safety and Health (NIOSH) to identify risk factors associated with bumps in the prevention of fatalities and accidents in highly stressed, bump-prone ground conditions. Changes of failure mechanism with increasing confinement, from extensional-to shear-dominated failure, are widely observed in the rupture of intact specimens at the laboratory scale and in rock masses. In the previous analysis conducted in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of some specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength (AUCS) to unconfined compressive strength (UCS), the damage characteristics, and the post-yield dilatancy. These mechanical characteristics were found to be strongly anisotropic as a function of the orientation of the cleats relative to the loading direction. However, the transition from extensional to shear failure at the given confinements was not clearly identified. In this study, a total of 20 specimens were additionally prepared from the same coal sample used in the previous study and then tested under both unconfined and triaxial compressive conditions. The different confining stresses are used as analogs for different width-to-height (W/H) ratios of pillar strength. Although the W/H ratios of the specimens were not directly considered during testing, the equivalent W/H ratios of a pillar as a function of the confining stresses were estimated using an existing empirical solution. According to this relationship, the W/H at which in-situ pillar behavior would be expected to transition from brittle to ductile is identified.

Background The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC). Methods This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell's C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS). Results In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (Pl0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (Pl0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (Pl0.001) were independent risk factors for DSS. Conclusion WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Background/Aims: Considering the high prevalence and mortality of hepatocellular carcinoma (HCC) in Korea, accurate statistics for HCC are important. We evaluated the characteristics of Korean patients with newly diagnosed HCC. Methods: We retrospectively evaluated data from the Korean Primary Liver Cancer Registry (KPLCR). The baseline characteristics, treatment modalities, and overall survival (OS) of 4,572 patients with HCC registered in the KPLCR between 2012 and 2014 were investigated. Results: At the time of HCC diagnosis, the median age was 60.0 years, with male predominance (79.6%). Hepatitis B virus infection was the most common etiology (59.1%). The rates of Barcelona Clinic Liver Cancer (BCLC) stages 0, A, B, C, and D at diagnosis were 3.9%, 36.9%, 12.5%, 39.4%, and 7.3%, respectively. The proportion of very early or early stage HCC at diagnosis (BCLC stage 0 or A) in the 2012-2014 cohort was significantly lower than that in the 2008-2011 cohort (40.8% vs. 48.3%, P

Spontaneous tumor rupture is a serious but rare complication of hepatocellular carcinoma (HCC) and has a low survival rate. Here, we report a case of massive HCC that ruptured and was treated successfully with transarterial chemoembolization (TACE). A 55-year-old man with abdominal pain was diagnosed with a 12-cm-wide ruptured HCC at segment 8. The overall liver function was scored as Child-Pugh A, but the single nodule tumor had ruptured; therefore, TACE treatment was initiated. After the first TACE treatment, residual tumors were found; thus, secondary TACE was performed 5 months later. No new lesions or extrahepatic metastases were found 16 months after the first TACE treatment, so hepatic resection was performed for curative treatment. The postoperative pathology results did not reveal any cancer cells; hence, TACE alone resulted in a cure. We report this case because the cure has been maintained for more than 3 years after resection. (J Liver Cancer 2020;20:154-159)

Background Vandetanib is the most widely used tyrosine kinase inhibitor for the treatment of patients with advanced medullary thyroid cancer (MTC). However, only limited data regarding its use outside clinical trials are available. We aimed to evaluate the efficacy and safety of vandetanib in patients with advanced MTC in routine clinical practice. Methods In this multicenter retrospective study, 12 patients with locally advanced or metastatic MTC treated with vandetanib at four tertiary hospitals were included. The primary outcome was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors. The progression-free survival (PFS), overall survival (OS), and toxicities were also evaluated. Results Eleven patients (92%) had distant metastasis and 10 (83%) had disease progression at enrollment. Partial response was observed in five patients (ORR, 42%) and stable disease lasting ≥24 weeks was reported in an additional five patients (83%). During the median 31.7 months of follow-up, disease progression was seen in five patients (42%); of these, two died due to disease progression. The median PFS was 25.9 months, while the median OS was not reached. All patients experienced adverse events (AEs) which were generally consistent with the known safety profile of vandetanib. Vandetanib was discontinued in two patients due to skin toxicity. Conclusion Consistent with the phase III trial, this study confirmed the efficacy of vandetanib for advanced MTC in terms of both ORR and PFS in the real-world setting. Vandetanib was well tolerated in the majority of patients, and there were no fatal AEs.

Objective To investigate the role of motor cerebellar connectivity in future development of freezing of gait, because it is a complex network disorder in Parkinson's disease (PD). Methods We recruited 26 de novo patients with PD who experienced freezing of gait within 5 years from magnetic resonance imaging acquisition (vulnerable PD group), 61 patients with PD who had not experienced freezing of gait within 5 years (resistant PD group), and 27 healthy control subjects. We compared the resting state functional connectivity between the motor cerebellum and the whole brain between the groups. In addition, we evaluated the relationship between motor cerebellar connectivity and freezing of gait latency. Results The vulnerable PD group had increased functional connectivity between the motor cerebellum and parieto-occipito-temporal association cortices compared with the control group or the resistant PD group. Connectivity between lobule VI and the right superior parietal lobule, right fusiform gyrus, and left inferior temporal gyrus; between lobule VIIb and the right superior parietal lobule, right hippocampus, and right middle temporal gyrus; and between lobule VIIIb and the bilateral fusiform gyri, right middle occipital gyrus, and bilateral parietal lobes was inversely proportional to freezing of gait latency. The freezing of gait latency-related cortical functional connectivity from the motor cerebellum was also significantly higher in the vulnerable PD group compared with the control group, as well as the resistant PD group. Conclusions The data suggest that the motor cerebellar functional connectivity with the posterior cortical areas play an important role in future development of freezing of gait in PD. © 2020 International Parkinson and Movement Disorder Society.

We aimed to investigate inflammation indices based on preablation hematological parameter of the lymphocyte-to-monocyte ratio (LMR) to predict the clinical outcome in papillary thyroid cancer (PTC) patients with low- and intermediate-risk stratification. This retrospective study analyzed 772 patients with low- and intermediate-risk PTC who underwent total thyroidectomy followed by radioiodine therapy between July 2005 and July 2009 with a median of 10 years. Kaplan–Meier statistics were used to test differences in recurrence-free survival (RFS) between groups based on the optimal cutoff point of biomarkers identified using receiver operating characteristic curves. With an optimal cutoff point of 7.05, 215 patients (29.8%) were classified as having low LMR and 557 patients (71.2%) were classified as having high LMR. High LMR was significantly associated with a prolonged RFS (hazard ratio [HR]: 2.048, 95% confidence interval [CI]: 1.062–4.359, p = 0.001). Multivariate analysis showed that low LMR (HR = 2.035, 95% CI: 1.011–4.095, p = 0.012), tumor size over 2 cm (HR = 2.762, 95% CI: 1.303–5.852, p = 0.008), and high preablative simulated thyroglobulin level over 10 ng/ml (HR = 7.826, 95% CI: 2.353–26.033, p

Background: Lenvatinib, an oral multikinase inhibitor, is the latest addition to the treatment options for radioactive iodine (RAI)-refractory progressive differentiated thyroid carcinoma (DTC). Th...

Backgrounds/Aims: Backgrounds/Aims: In Korea, hepatocellular carcinoma (HCC) is the sixth most common cancer and results in the second-highest cancer death rate among all cancers. We aimed to describe the characteristics of patients who were newly diagnosed with HCC in Korea between 2008 and 2011. Methods: The Korean Primary Liver Cancer Registry (KPLCR) is a random sample consisting of approximately 15% of patients with newly diagnosed primary liver cancer registered in the Korean Central Cancer Registry. We investigated the baseline characteristics, treatment modalities, and overall survival (OS) of patients with HCC registered in the KPLCR between 2008 and 2011. Results: A total of 6,083 patients were histologically or radiologically diagnosed with HCC. The hepatitis B virus was the predominant HCC etiology (72.0%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stages 0, A, B, C, and D accounted for 8.6%, 39.7%, 11.5%, 33.8%, and 6.9%, respectively. Transarterial therapy (41.7%) was the most commonly performed initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapies (10.6%). The overall rate of adherence to the BCLC treatment guideline was only 37.7%. The 1-, 3-, and 5-year OS rates were 65.6%, 46.2%, and 36.8%, respectively. Conclusions: Between 2008 and 2011, approximately half of patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A), but one-third of patients (33.8%) had advanced HCC (BCLC stage C). Transarterial therapy was the most commonly conducted initial treatment and the 5-year OS rate was 36.8% in this period. (J Liver Cancer 2020;20:41-52)

Background Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients. Methods This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified-TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB. Results The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P

Background: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in pa tients with type 2 diabetes mellitus. Methods: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeo static model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed. Results: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P

Background Accumulating evidence suggests that BMI1 confers protective effects against Alzheimer’s disease (AD). However, the mechanism remains elusive. Based on recent pathophysiological evidence, we sought for the first time to identify genetic variants in BMI1 as associated with AD biomarkers, including amyloid-β. Methods We used genetic, longitudinal cognition, and cerebrospinal fluid (CSF) biomarker data from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (N = 1565). First, we performed a gene-based association analysis of common single nucleotide polymorphisms (SNPs) (minor allele frequency (MAF) > 5%) located within ± 20 kb of the gene boundary of BMI1, an optimal width for including potential regulatory SNPs in the 5′ and 3′ untranslated regions (UTR) of BMI1, with CSF Aβ1-42 levels. Second, we performed cross-sectional and longitudinal association analyses of SNPs in BMI1 with cognitive performance using linear and mixed-effects models. We replicated association of SNPs in BMI1 with cognitive performance in an independent cohort (N=1084), Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). Results Gene-based genetic association analysis showed that BMI1 was significantly associated with CSF Aβ1-42 levels after adjusting for multiple testing using permutation (permutation-corrected p value=0.005). rs17415557 in BMI1 showed the most significant association with CSF Aβ1-42 levels. Participants with minor alleles of rs17415557 have increased CSF Aβ1-42 levels compared to those with no minor alleles. Further analysis identified and replicated the minor allele of rs17415557 as being significantly associated with slower cognitive decline rates in AD. Conclusions Our findings provide fundamental evidence that BMI1 rs17415557 may serve as a protective mechanism related to AD pathogenesis, which supports the results of previous studies linking BMI1 to protection against AD.

Changes of failure mechanism with increasing confinement, from extensional to shear-dominated failure, are widely observed in the rupture of intact specimens at the laboratory scale and in rock masses. In an analysis published in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of 84 specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength to unconfined compressive strength (UCS), the damage characteristics, and the post-yield dilatancy. These mechanical characteristics were found to be strongly anisotropic as a function of the orientation of the cleats relative to the loading direction, defined as the included angle. A total of four different included angles were used in the work performed in 2018. The authors found that the degree of anisotropic strength differed according to the included angle. However, the transition from extensional to shear failure at the given confinements was not clearly identified. In this study, a total of 20 specimens were additionally prepared from the same coal sample used in the previous study and then tested under both unconfined and triaxial compressive conditions. Because the authors already knew the most contrasting cases of the included angles from the previous work using the four included angles, they chose only two of the included angles (0° and 30°) for this study. For the triaxial compressive tests, a greater confining stress than the mean UCS was applied to the specimens in an attempt to identify the brittle-ductile transition of the coal. The new results have been compiled with the previous results in order to re-evaluate the confinement-dependency of the coal behavior. Additionally, the different confining stresses are used as analogs for different width-to-height (W/H) conditions of pillar strength. Although theW/Hratios of the specimens were not directly considered during testing, the equivalentW/Hratios of a pillar as a function of the confining stresses were estimated using an existing empirical solution. According to this relationship, theW/Hat which in situ pillar behavior would be expected to transition from brittle to ductile is identified.

Background The purpose of this study was to assess the accuracy and safety of procedures using ultrasound equipment for acupuncture treatment. Methods A pilot, prospective randomized, single blinded, crossover clinical study on the accuracy and safety of ultrasound-guided Gyeontonghyeol; (BP-LE6) acupuncture treatment was conducted. Patients (n; = 13) with shoulder pain were randomly divided into 2 groups. During Visit 1, ultrasound-guided BP-LE6 acupuncture was administered to the experimental group. In the control group, patients received BP-LE6 acupuncture (without checking ultrasound images) by manipulating the ultrasound probe as if administering ultrasound-guided acupuncture. Visit 2 was arranged within 7-14 days and the remaining procedures, other than those administered in Visit 1, were performed. In both the experimental group and control group, the number of needle insertions, and time required for the treatment to result in the patients feeling de-qi; was recorded. The numeric rating scale (NRS) score for shoulder pain was recorded before and after the acupuncture treatment. Results The number of needle insertions was 5.31 ± 3.50 times in the experimental group, and 6.62 ± 3.38 times in the control group, however, there was no statistically significant difference between the groups (p; > 0.05). The mean time required to perform the procedure was 151.54 ± 48.59 seconds in the experimental group and 86.69 ± 37.17 seconds in the control group, which was statistically significantly different (p; < 0.05). The changes observed in numerical rating scale scores between groups were not statistically significantly different. Conclusions Although there was no statistically significant difference, administering acupuncture using ultrasound guidance may lead to accurate needling with a reduced number of needle insertion attempts. A large-scale clinical study of better design should be conducted in the future.

Purpose – As the well-known Structure-Conduct-Performance paradigm implies, risk structure of a corporation may affect its risk management activity and the activity may in turn determine its performance. Depending on its goal, Foreign Direct Investment (FDI) can shape its risk structure, risk management and its performance. Under this assumption, we investigate the relationship between the goals of FDI and risk management for the first time in academics. Design/methodology – This empirical research uses a survey of 279 current Korean enterprises’ FDIs in China with the recently developed business risk quadrant model. Companies are classified into either a market- or an efficiency-seeking group, to identify how each group perceives and manages risks, and values the performance of risk management. Also, we apply integrated risk management method that multinational corporations have introduced in China, then verify the mediating effect between risk factors and performance. Findings – Our research shows the FDIs can expose themselves to differing risk structure although risk management activities simply represent the level of empowerment given to local management by headquarter due to limit of sample size despite diversity of risk and risk management tools. To sum, market seekers are found to have more strategic risk (revenue related risk) than efficiency seekers with financial risk (cost related risk). The market seekers can manage their risk by empowering their local organisation while the efficiency does the opposite ways. The risk management appears to be successful in general. Originality/value – Previous studies on small and medium enterprises’ FDIs to China have concentrated on the analysis of entry determinants, withdrawal factors and individual risk management. Meanwhile, this research establishes enterprise-wide risk factors faced by the companies that advance into China, according to the method of the classification by ERM and verifies if they could synthetically improve performance through risk corresponding measures.

The brain is known to play a central role in controlling the desire to eat. We aimed to evaluate the brain regions that might have a long-term effect on eating behavior and weight changes. We utilized the data of cognitively normal subjects who are examined by several neurologic tests, and followed-up for 36 months from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, and investigated to search the brain regions that are associated with future weight change. The weight of each subject was measured on each visit at baseline (W0), 36 (W36) months after brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). Percentage (%) change of weight was calculated as follows: [(W36–W0)/W0]*100. We classified each subject’s change into one of three categories: weight loss, stable, and weight gain. Dynamic 3-dimensional scans of six 5-min frames were acquired 30 mins after injection of 185 MBq of FDG. Image analysis was done using Statistical Parametric Mapping 12. Ninety-six subjects were included in this study (male 54, female 42). Subjects with future weight gain showed hypometabolism in left cerebellum compared with those with future weight loss & stable. Percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. In conclusion, subjects with future weight gain showed hypometabolism in left cerebellum, and percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. This study raises the possibility that the brain glucose metabolism precedes the future weight change.

BACKGROUND To the authors' knowledge, the indications for radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC) are unclear; treatment decisions are based on physician judgment. The objective of the current study was to identify the degree of concordance between postsurgical RAI therapy recommended by Watson for Oncology (WFO), a clinical decision support system for oncological therapy, and that recommended by physicians for patients with DTC. METHODS The current retrospective cohort study included 207 patients with DTC who underwent thyroidectomy between 2017 and 2018. Treatment recommendations were considered concordant if WFO rendered recommendations consistent with those of the physicians. RESULTS Treatment recommendations were concordant for 160 patients (77%). The concordance rate significantly differed according to the American Thyroid Association (ATA) risk category (P

Specialised knowledge on analytics algorithms is necessary to conduct a data analysis; thus, there are limits to how a manufacturing manager who is not a data analysis expert conducts analysis task...

BACKGROUND Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete. METHODS This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health. RESULTS At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P

Objectives This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort. Materials and methods We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS). Results During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group. Conclusion Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Background: No studies evaluating the clinical outcomes of radiotherapy (RT) for hepatocellular carcinoma (HCC) in the caudate lobe have been available to date. The purpose of this study was to evaluate the effectiveness and safety of RT for HCC in the caudate lobe.Material and Methods: Seventy patients with HCC in the caudate lobe treated with RT from a multi-institutional database were included in this study. The median equivalent dose in 2 Gy (EQD2) was 80.0 Gy10 (range, 31.3–99.3), and freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were evaluated.Results: The median time of follow-up was 47.9 months (range, 3.4–127), and the 5-year FFLP, PFS, and OS rates were 80.6% [95% confidence interval (CI), 70.8–91.8], 13.8% (95% CI, 7.5–25.4), and 51.3% (95% CI, 39.9–66.1), respectively. In the multivariate analysis, the radiation dose was significantly associated with the FFLP rate [hazard ratio (HR), 0.57 per 10 Gy10 increase, p = 0.001], and the status of FFLP was significantly associated with OS (HR, 2.694, p = 0.014). The overall rate of ≥grade 3 adverse events was 5.7% (4 of 70), and RT-related mortality was not observed.Conclusion: RT for HCC in the caudate lobe showed promising FFLP and OS rates with safe toxicity profiles. These findings suggest that RT may be a promising treatment option for HCC in the caudate lobe.

Background We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Approximately 50% and 30% of hepatocellular carcinoma (HCC) cases worldwide are attributed to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, respectively. Antiviral therapy using nucleos(t)ide analogs (NA) reduces HCC occurrence and recurrence in HBV-related HCC. NA therapy also improves overall survival by preventing liver function deterioration and decompensation. Indefinite antiviral therapy is recommended for most patients with HBV-related HCC. For HCV-related HCC, antiviral therapy using an interferon-based or interferon-free regimen reduces the risk of HCC. Despite an earlier debate, there is no convincing long-term data regarding direct-acting antiviral (DAA) therapy increasing HCC recurrence, whereas interferon-based antiviral therapy decreased HCC recurrence after curative treatment. However, DAA therapy improves the overall and liver-related mortality, especially in patients with complete response after curative treatment. Patients with HCV-related HCC who are eligible for curative treatment should receive DAA therapy after the completion of HCC treatment.

This study aimed to elaborate upon prior findings suggestive of the altered lateralization of structural connectivity in the developing preterm brain by using diffusion tensor imaging tractography to explore how network topological asymmetries in fronto-limbic neural circuitry are altered at 36–41 weeks, postmenstrual age in 64 preterm infants without severe brain injury and 33 term-born infants. We compared the pattern of structural connectivity and network lateralization of the betweenness centrality in the medial fronto-orbital gyrus, superior temporal gyrus, amygdala, and hippocampus—the structures comprising the fronto-limbic brain circuit—between preterm and term infants. Global efficiency, local efficiency, and small-world characteristics did not differ significantly between the two hemispheres in term-born infants, suggesting that integration and segregation are balanced between the left and right hemispheres. However, the preterm brain showed significantly greater leftward lateralization of small-worldness (P = 0.033); the lateralization index of the betweenness centrality revealed that the medial fronto-orbital gyrus (P = 0.008), superior temporal gyrus (P = 0.031), and hippocampus (P = 0.028) showed significantly increased leftward asymmetry in preterm infants relative to term-infants independent of sex, age at imaging, and bronchopulmonary dysplasia. The altered lateralization of fronto-limbic brain circuitry might be involved in the early development of social–emotional disorders in preterm infants.

Background Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

A substantial proportion of patients with hepatocellular carcinoma (HCC) present with portal vein invasion (PVI). The extent of portal vein tumor thrombosis (PVTT) can be classified into 4 categories: Vp1, existence of PVTT distal to the second-order branches of portal vein; Vp2, existence of PVTT in the second-order branches of portal vein; VP3, PVTT in the first-order branches of portal vein; and VP4, existence of PVTT in main portal trunk or portal branches contralateral to primary involved lobe. The degree of PVTT has shown the close association with prognosis of HCC across all treatment options. Clinical practice guidelines recommend systemic therapy for advanced HCC with PVI based on the highest level of evidence. Sorafenib has firstly shown to improve overall survival of patients with advanced HCC in 2007 [1]. Among 299 sorafenib-treated patients, 108 (36%) had macrovascular invasion. Subgroup analysis consistently demonstrated significantly longer overall survival (8.1 vs. 4.9 months; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.49-0.93) and time to progression (4.1 vs. 2.7 months; HR, 0.57; 95% CI 0.39-0.84) in sorafenib-treated patients with macrovascular invasion [2]. Lenvatinib, another 1st-line systemic agent, has proven non-inferiority to sorafenib in advanced HCC [3]. The REFLECT study included patients with macroscopic portal vein invasion (199/954, 21%); however, it excluded patients with main portal vein invasion. Recently approved systemic agents, atezolizumab plus bevacizumab was superior to sorafenib in overall survival and progression-free survival [4]. Of 336 atezolizumab-bevacizumab treated patients, 38% had macrovascular invasion. Atezolizumab with bevacizumab also showed significant efficacy in patients with microvascular invasion (HR 0.58 [95% CI, 0.38-0.89] for overall survival; HR 0.53 [95% CI, 0.37-0.76] for progression-free survival). Transarterial therapy and/or radiotherapy can also be an option for HCC with PVI. A single-center randomized controlled study has demonstrated that transarterial chemoembolization with external beam radiotherapy significantly improved progression-free survival and overall survival compared with sorafenib in patients with macroscopic vascular invasion [5]. Earlier studies reported that transarterial chemoembolization improved overall survival of HCC patients with PVTT compared to supportive care [6,7] Recent meta-analysis indicated that radioembolization was safer and more effective than sorafenib in HCC with PVI [8].

Background:After high tibial valgus osteotomy (HTO), rotational changes in the tibia may occur, which can affect the biomechanics of the patellofemoral joint and may lead to anterior knee pain.Purpose:To compare the rotational changes in the tibia between closing wedge HTO (CWHTO) and opening wedge HTO (OWHTO).Study Design:Cohort study; Level of evidence, 3.Methods:Among the patients who underwent HTO between May 2012 and August 2015, 53 (28 CWHTO and 25 OWHTO) who had computed tomography scans before and at 1 year after the HTO were included. The following parameters were compared between CWHTO and OWHTO: (1) tibial torsion angle, (2) knee rotation angle, and (3) tibial tuberosity–trochlear groove (TT-TG) distance. During the last follow-up, patients were asked to rate their anterior knee pain when climbing the stairs, using the visual analog scale.Results:The tibial torsion angle significantly decreased (internal rotation of the distal fragment) after CWHTO (mean ± SD, –2.1°± 4.1°; P = .019) and OWHTO (–1.8°± 3.3°; P = .029). The knee rotation angle significantly decreased (external rotation of the proximal fragment) after OWHTO (–1.8°± 3.4°; P = .039) but was not changed after CWHTO (0.1°± 3.1°; P = .859). The mean TT-TG distance significantly decreased after CWHTO (–3.1 ± 3.0 mm; P < .001) but increased after OWHTO (2.0 ± 4.3 mm; P = .012). At the final follow-up (minimum, 4 years), the visual analog scale pain score during stair climbing was significantly higher after OWHTO than after CWHTO (3.1 ± 1.4 vs 2.2 ± 1.3, P = .024).Conclusion:Internal rotation of the distal fragment occurred after both CWHTO and OWHTO. However, external rotation of the proximal fragment and increased TT-TG distance occurred after OWHTO. Because such rotational changes could affect anterior knee pain, further studies are warranted to investigate the definite relationship between tibial rotational changes and anterior knee pain after HTO.

BackgroundAlthough infrequent, distant metastasis from differentiated thyroid cancer is the main cause of mortality in patients and mostly involves the lung, bone, and brain. Distant metastases to other sites in differentiated thyroid cancer patients are rare, thus, the clinical course of unusual metastases has not been adequately researched. In the present study, the clinico-pathological findings and treatment outcomes of unusual metastases in differentiated thyroid cancer patients in Korea were evaluated.Patients and methodsWe retrospectively reviewed the medical records of differentiated thyroid cancer patients with unusual metastases in four Korean tertiary hospitals (Chonnam National University Hwasun Hospital, Asan Medical Center, Busan National University Hospital, Severance Hospital). Unusual metastases were diagnosed using (1) cytology or histology and/or (2) imaging studies including fluorodeoxyglucose F 18 positron emission tomography/computed tomography and/or iodine 131 whole body scans with simultaneously elevated serum levels of thyroglobulin. The pathological findings of primary thyroid cancer, diagnostic method for unusual metastases, and treatment responses of unusual metastases were examined.ResultsIn all, 25 unusual metastatic foci of 19 patients were analyzed; 13 patients (68.4%) had papillary thyroid carcinoma including 4 follicular variant papillary thyroid carcinomas. The median time interval between the first diagnosis of primary thyroid cancer and unusual metastases diagnosis was 110 months (11.0-138.0 months). Only 4 patients (21.1%) had synchronous unusual metastases and 6 patients (31.6%) were symptomatic. Unusual metastases included 19 metastases to solid organs (6 to kidney, 5 to liver, 4 to pancreas, 3 to adrenal gland, and 1 to ovary) and 6 to the skin and muscles. Unusual metastases were pathologically proven in 10 patients (52.6%) and 11 of 16 patients (68.8%) who received iodine 131 whole body scans had radioiodine-refractory differentiated thyroid cancer. Among 5 patients treated with tyrosine kinase inhibitors, 4 treated with lenvatinib showed stable disease or a partial response at the first treatment response. Six patients (31.6%) died due to disease progression during the median 20.0-month follow-up period (11.0-55.0 months).ConclusionUnusual metastases from differentiated thyroid cancer are thought to be underestimated due to disease rarity and their metachronous nature with other distant metastases. The most of unusual metastases in differentiated thyroid cancer patients are existed with usual distant metastasis and clinical outcomes of those could not be significantly different from the prognosis of usual distant metastasis.

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: Proton beam has an excellent depth dose distribution due to its unique physical properties, and thus proton beam therapy (PBT) has been tried and showed promising outcomes in hepatocellular carcinoma (HCC). The purpose of this phase II study is to evaluate the efficacy of hypofractionated PBT in HCC. Methods: The eligibility criteria for this study were as follows: patients with HCC lesion(s) who were failed after, were difficult to treat with, or refused to other local treatments; tumor size and number of ≤7 and ≤2 cm, respectively, and HCC lesion(s) of ≥2 cm from gastrointestinal organs; Child–Pugh score of ≤7; Eastern Cooperative Oncology Group performance status ≤1; and age ≥18 years. The prescribed dose of PBT was 70 Gy equivalent in 10 fractions. The primary endpoint was 3-year local progression-free survival (LPFS) rate. Results: Forty-five patients were prospectively enrolled, and there were 35 men and 10 women with a median age of 63 years (range, 46–78 years). Thirty-seven patients had recurrent and/or residual disease, and eight patients had treatment-naive disease. All patients received the planned treatments without treatment interruption, and grade ≥3 acute toxicity did not occur. The median follow-up duration was 35.1 months (range, 11.2–56.3 months) and local progression occurred in two patients (8.7%). The 3-year rates of LPFS and overall survival (OS) were 95.2% (95% confidence interval [CI], 89.1%−100%) and 86.4% (95% CI, 72.9–99.9%), respectively. Conclusion: Hypofractionated PBT showed promising LPFS and OS, and further studies are warranted to compare PBT with other local modalities.

Thyroid dysfunction is frequently associated with functional disturbances of the brain. We performed a meta-analysis of previous positron emission tomography and single-photon emission computed tomography studies using a coordinate-based technique of activation-likelihood estimation (ALE) to investigate the potential background of neuropsychiatric complications in patients with hypo- and hyperthyroidism. We performed a systematic search of MEDLINE and EMBASE for English-language publications using the keywords of "positron emission tomography", "single-photon emission computed tomography", and "thyroid". The software GingerALE ver 2.3.6 was used to transform all reported coordinates into stereotactic Montreal Neurological Institute space. A threshold of uncorrected p 0.001 (minimum volume of 200 mm