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Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer (WDTC)), were evaluated in this study. Volasertib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Volasertib treatment reduced cells in the S phase and increased cells in the G2/M phase. Volasertib activated caspase-3 activity and induced apoptosis. Drug combinations of volasertib and sorafenib showed mostly synergism in four well-differentiated thyroid carcinoma cell lines in vitro. Volasertib treatment in vivo retarded the growth of a papillary thyroid tumor model. Furthermore, the combination of volasertib with sorafenib was more effective than a single treatment of either in a follicular thyroid cancer xenograft model. Promising safety profiles appeared in animals treated with either volasertib alone or volasertib and sorafenib combination therapy. These findings support volasertib as a potential drug for the treatment of patients with WDTC.

Objective The aim of this study was to evaluate outcomes of the recurrent and non-recurrent groups including disease-specific mortality of patients with well-differentiated thyroid carcinoma after multimodality treatment. In addition, prognostic factors for disease-specific mortality were analyzed. Summary of Background Data Among 2,844, there were 166 patients with recurrent disease. Recurrent disease was defined as the presence of papillary or follicular thyroid cancer 6 months after the initial thyroidectomy, including locoregional or distant metastasis, diagnosed using diagnostic or therapeutic 131I scans or other imaging techniques. Methods The study was a retrospective analysis of prospectively collected data for a long-term follow-up result of well-differentiated thyroid carcinoma patients. Results The mean age of 166 patients was 45.8 ± 1.2 years, 116 (69.9%) were women, 111 (66.9%) had locoregional neck recurrence, and 55 (33.1%) had metastatic recurrence in distant organs. We found that when recurrences were observed, more than half were detected within the first 5 years following the initial therapy. The longest period of time before relapse was 29.8 years. After a mean follow-up period of 12.7 ± 0.5 years, 37 (22.3%) patients experienced disease-specific mortality. Multivariable analysis revealed that older age, male sex, and development of a second primary malignancy were associated with disease-specific mortality. Higher post-operative levels of thyroglobulin predicted a shorter time to relapse. Conclusions These data indicate that among the recurrent cases over 50% of recurrent well-differentiated thyroid carcinomas were diagnosed within 5 years after initial thyroidectomy. Additionally, more than 20% of the patients died of thyroid cancer.

Background: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. Methods: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. Result: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. Conclusions: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC. Keywords: Total thyroidectomy, Thyroglobulin, Radioactive iodide, Cancer-specific mortality

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p

Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer.Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses.The EpCAMCEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.

Chia-Lin Li,1,2 Fiona F Stanaway,3 Jen-Der Lin,2 Hsing-Yi Chang4 1Department of Health Care Management, College of Management, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Tao-Yuan 333, Taiwan; 3Sydney School of Public Health, University of Sydney, Sydney 2006, NSW, Australia; 4Division of Preventive Medicine and Health Service Research, Institute of Population Health Sciences, National Health Research Institutes, Maoli 350, Taiwan Purpose: The aims of this study were to investigate the prevalence of frailty and its relationship with health care use among community-dwelling older adults with diabetes.Methods: We analyzed data from a nationally representative sample of people aged 65 years and above (n=3,203) participating in the 2013 National Health Interview Survey in Taiwan. Atotal of 719 participants had a history of self-reported physician-diagnosed diabetes. The presence of frailty was determined based on the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) scale proposed by the International Association of Nutrition and Aging. FRAIL scores range from 0 to 5 and are categorized as frail (3–5), pre-frail (1–2), and robust (0). Participants were asked whether they had been hospitalized or had visited an emergency department in the past year.Results: Among community-dwelling older adults with diabetes, 9.4% of participants were frail and 35.3 % were pre-frail. After adjustment for other factors, being frail was significantly associated with hospitalization during the past year (OR =5.31, 95% CI =1.87–15.10), whereas being pre-frail was not associated with hospitalization. Both being pre-frail and frail were significantly associated with emergency department visits during the past year (OR =2.64, 95% CI =1.35–5.17 and OR =4.05, 95% CI =1.31–12.49, respectively) after adjustment for other factors.Conclusion: Our results highlight the high prevalence of frailty in community-dwelling older adults with diabetes. Furthermore, being frail is associated with a greater burden of hospitalizations and emergency department visits. Keywords: diabetes mellitus, elderly, frailty, health care use, Taiwan&nbsp

Altered cyclin-dependent kinase activity is observed in many human malignancies. Cyclin-dependent kinases that promote cell cycle progression may be promising targets in the treatment of cancer. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for medullary thyroid cancer were investigated in the present study. Roniciclib inhibited medullary thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib induced caspase-3 activity and contributed to apoptosis. Cell cycle progression was arrested in the G2 phase. In vivo, roniciclib treatment retarded the growth of tumors of medullary thyroid cancer xenografts. In addition, roniciclib in combination with sorafenib was more effective than either single treatment in a xenograft model. No morbidity was observed in animals treated with single roniciclib therapy and combination treatment of roniciclib and sorafenib. These data provide a rationale for clinical assessment of using roniciclib in the treatment of patients with medullary thyroid cancer.

Background Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg. Methods A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM+-CECs and TSHR+-CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n = 7) and remission group (n = 18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM+-CECs and TSHR+-CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity + specificity − 1). Results The median numbers of EpCAM+-CECs (72.5 vs. 10.75) and TSHR+-CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM+-CECs (0.937) and TSHR+-CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM+-CECs and TSHR+-CECs were set at 48 cells/ml and 10 cells/ml, respectively and showed a sensitivity (EpCAM+-CECs: 85.7%; TSHR+-CECs: 85.7%) and a specificity (EpCAM+-CECs: 100%; TSHR+-CECs: 77.8%) in predicting the recurrence. Conclusions Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg.

// Chia-Chun Wu 1, * , Jen-Der Lin 4, * , Jeng-Ting Chen 7 , Chih-Min Chang 1 , Hsiao-Fen Weng 4 , Chuen Hsueh 5 , Hui-Ping Chien 5 and Jau-Song Yu 1, 2, 3, 6 1 Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan 2 Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan 3 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 5 Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 6 Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan 7 Department of Surgery, Department of Medical Research and Development Linkou Branch, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan * These authors contributed equally to this work Correspondence to: Jau-Song Yu, email: yusong@mail.cgu.edu.tw Keywords: papillary thyroid carcinoma; fine needle aspiration cystic fluid; proteome profiles; secretome; biomarker Received: April 20, 2017 Accepted: November 15, 2017 Published: January 04, 2018 ABSTRACT Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively. Comparative analysis revealed that 191 proteins were detected in the PTC but not the benign cystic fluid samples, and thus may represent potential PTC biomarkers. Among these proteins, 101 were detected in the PTC cell line secretomes, and seven of them (NPC2, CTSC, AGRN, GPNMB, DPP4, ERAP2, and SH3BGRL3) were reported in public PTC transcriptome datasets as having 4681 elevated mRNA expression in PTC. Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies from near 100 pairs of PTC tissue and their adjacent non-tumor counterparts further showed that AGRN ( n = 98), CTSC ( n = 99), ERAP2 ( n = 98) and GPNMB ( n = 100) were significantly ( p < 0.05) overexpressed in PTC and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis of PTC patients. Collectively, our results indicate that an integrated analysis of FNA cystic fluid proteome, cancer cell secretome and tissue transcriptome datasets represents a useful strategy for efficiently discovering novel PTC biomarker candidates.

The efficacy of thyroxine suppressive therapy in reducing nodular growth and its effect to bone mineral density (BMD) in postmenopausal women is still debated. This study aimed to evaluate the therapeutic effect of thyroxine and its influence on BMD. Postmenopausal women with nodular or multinodular goiter during 2013-2015 at Chang Gung Memorial Hospital were enrolled and retrospectively traced back to the first date of visit or treatment. Ninety-four eligible patients were enrolled, of whom 45 were thyroxine-treated (LT-4 group) and 49 were treatment-naïve (control group). Data, including volume of nodules, were analyzed retrospectively. BMD was measured in each LT-4 group patient since the year of enrollment. Nodular volumes were reduced in both LT-4 (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, p = 0.033) and control group (3.48 ± 4.36 to 3.09 ± 2.88 mL, p = 0.239) at initial 2-year follow-up. Nodular volume in LT-4 group increased insignificantly (from 4.89 ± 4.46 to 4.91 ± 5.40 mL, p = 0.711) at the end of 7-year follow-up. The best cut-off predictive nodular volume that may have responded to thyroxine is 2.6 mL (AUC, 0.740; sensitivity, 0.750; specificity, 0.733) during first 2 year. Lumbar spine, total hip and femoral neck BMD were not significantly changed during 2 year's thyroxine suppression therapy. In conclusion, thyroxine suppressive therapy in postmenopausal women had significant reduction in nodule volume at initial 2 years of treatment, especially in volume larger than 2.6 mL. Prolonged thyroxine treatment did not benefit nodular size reduction and may affect BMD minimally in postmenopausal women.

Background Surgical management of Graves' disease (GD) is changing from subtotal to total thyroidectomy because the latter eliminates the risk of recurrence. However, to preserve thyroid function in a euthyroid state, subtotal thyroidectomy is still performed for GD in non-Western countries. Therefore, we designed a study to investigate the long-term outcomes in GD patients after subtotal thyroidectomy and the correlation between remnant weight and postoperative thyroid function. Materials and methods This was a retrospective cohort observation study. Between January 2005 and December 2011, 415 consecutive GD patients treated by subtotal thyroidectomy were enrolled. All data were collected from 385 patients who underwent bilateral subtotal thyroidectomy and 57 patients who underwent the Hartley-Dunhill operation. The median postoperative follow-up time was 72 months (range 12-144 months). Results The mean weight of the preserved thyroid remnant was 5.1 g. Persistent or recurrent hyperthyroidism was observed in 119 (28.7%) patients. The median time of recurrence was 36 months (range 12-120 months). Hypothyroidism developed in over 50% of patients. A euthyroid state was achieved in only 19.3% of patients, and the rate did not increase significantly as remnant weight increased. Based on a Cox regression analysis, the remnant weight is an independent risk factor for persistent or recurrent hyperthyroidism (hazard ratio: 1.323, 95% confidence interval: 1.198-1.461, P Conclusions Subtotal thyroidectomy with the intent to maintain a euthyroid state is not an optimal surgical strategy for the definitive treatment of GD because the persistence or recurrence rate is high and the euthyroid rate is lower than expected.

// Shu-Fu Lin 1 , Jen-Der Lin 1 , Chuen Hsueh 2 , Ting-Chao Chou 3, 4 and Richard J. Wong 5 1 Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 2 Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 3 Laboratory of Preclinical Pharmacology Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Current address: PD Science, Inc., Paramus, NJ, USA 5 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Shu-Fu Lin, email: mmg@cgmh.org.tw Keywords: roniciclib, cyclin-dependent kinase, anaplastic thyroid cancer Received: March 02, 2017 Accepted: May 23, 2017 Published: July 08, 2017 ABSTRACT Many human cancers have altered cyclin-dependent kinase activity. Inhibition of cyclin-dependent kinases may arrest cell cycle progression and represents an important strategy in the treatment of malignancies. We evaluated the therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor, as a treatment for anaplastic thyroid cancer. Roniciclib inhibited anaplastic thyroid cancer cell proliferation in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in G2/M phase. In vivo , the growth of anaplastic thyroid cancer xenograft tumors was retarded by roniciclib treatment without evidence of toxicity. These data provide a rationale for further clinical evaluation using roniciclib in the treatment of patients with anaplastic thyroid cancer.

Objectives It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. Methods The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. Results The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I–III) had a median US risk score of 6 (range, 0–11), which was higher than that of nodules with high categorization (IV–VI; median, 3; range, 0–11). Conclusions The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

Aims The aims of the present study were to investigate the co-occurrence of depressive symptoms and cognitive impairment in community dwelling older adults with diabetes and its relationship with specific diabetes self-care behaviors. Methods We analyzed data from two national samples of older adults (65 years or older) with self-reported physician-diagnosed diabetes (N = 1034), who participated in the 2005 or 2009 National Health Interview Survey in Taiwan. The Mini-Mental State Examination was used to assess cognitive function. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms. The study assessed self-care behaviors including medication adherence, exercise, healthy diet, and self-monitoring of blood glucose. Results In this study, 8.8% of participants with diabetes had both depressive symptoms and cognitive impairment. After adjusting for other factors, participants with both cognitive impairment and depressive symptoms were less likely to exercise (Prevalence Ratios (PR) = 0.66; 95% Confidence Intervals (CI) = [0.47–0.91]; P-value = 0.011), and have a healthy diet (PR = 0.82; 95%CI = [0.70–0.96]; P-value = 0.012). Conclusions Our results illustrate the high prevalence of combined depressive symptoms and cognitive impairment and that this combination is associated with worse self-care behaviors in older adults with diabetes. These findings highlight the difficulty that some older adults with diabetes may have in maintaining self-care behaviors in the presence of depressed mood and cognitive impairment, particularly in the areas of diet and exercise. The results emphasize the importance of providing more support for these aspects of self-care to such older adults.

// Shu-Fu Lin 1 , Jen-Der Lin 1 , Chuen Hsueh 2 , Ting-Chao Chou 3, 7 , Chun-Nan Yeh 4 , Ming-Huang Chen 5 and Richard J. Wong 6 1 Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 2 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3 Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 4 Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan 5 Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 6 Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 7 Current address: PD Science, Inc., Paramus, NJ, USA Correspondence to: Shu-Fu Lin, email: mmg@cgmh.org.tw Keywords: HSP90 inhibitor, ganetespib, thyroid cancer Received: October 29, 2016 Accepted: March 30, 2017 Published: April 18, 2017 ABSTRACT Heat shock protein 90 is a molecular chaperon that maintains the correct folding and function of multiple client proteins. The inhibition of heat shock protein 90, which leads to the simultaneous degradation of multiple proteins involved in oncogenic signaling pathways, has revealed an innovative strategy to treat a variety of cancer types. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90 inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferation in a dose-dependent manner in eight cell lines originating from four major histologic types of thyroid cancer (papillary, follicular, anaplastic and medullary). Ganetespib decreased cyclin-dependent kinase 1 and arrested cell cycle progression in G2/M phase. The expression of proteins involved in RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways was also inhibited. The RET level was decreased in a medullary thyroid cancer cell line. Ganetespib increased Bim expression, activated caspase-3 and induced apoptosis. In vivo , ganetespib retarded the tumor growth of anaplastic and medullary thyroid cancer xenografts with acceptable safety profiles. These findings indicate that ganetespib has potential in the treatment of patients with thyroid cancer.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Objective The aim of this study was to investigate the prevalence, characteristics, and acute care utilization of community dwelling disabled older adults with an absence of help for activities of daily living (ADL). Methods We analyzed cross-sectional data from a nationally representative sample of people aged 65 years and over (n = 2904) participating in the 2009 National Health Interview Survey in Taiwan. Disability was defined as self-reporting a lot of difficulty or complete inability to carry out one or more ADL tasks. Participants with disability were asked whether they received help in the form of personal assistance or assistive devices to complete ADL tasks, with a yes response indicating the presence of help and a no response indicating the absence of help. Hospitalization and emergency department visits was assessed as a dichotomous variable (any or none), respectively. Results An absence of available help for ADL disability was reported in 16.6% of disabled older adults. Disabled older adults reporting an absence of help were more likely to be female. After adjustment for other factors, compared to older adults without disability, older adults with disability not receiving help for ADL tasks were highly related to hospitalization (OR = 4.57; 95%CI = [1.51–13.82]) and emergency department visits (OR = 3.52; 95%CI = [1.15–10.76]) during the past year, respectively. Conclusions We found that there is high prevalence of absence of help to perform ADL tasks in older adults with disability, and that this absence of help for ADL disability is associated with a greater burden of acute care utilization than those without disability.

Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is common and clinical presentation can vary from minimal to extensive locoregional involvement. Although PTC is generally considered the most benign among all thyroid carcinomas, it may present with local invasion with poor prognosis. Our retrospective study involved 3267 PTC patients undergoing regular follow-up at Chang Gung Medical Center in Linkou, Taiwan. Among them, 269 were PTC cases with ETE, having tumors greater than 1 cm in size and treated with total or complete thyroidectomy with or without lymph node dissection for which the follow-up period was over 10 years. The mean age of 269 cases was 46.8 ± 15.1 (range 11–83 years) years. The number of females was 204 (75.8 %). Patients were categorized into minimal ETE (175 cases) and extensive ETE (94 cases) groups according to surgical findings and pathological reports. Mean follow-up period was 13.3 ± 5.5 (range 0.2–29.3) years, during which 28 (10.4 %) patients died of thyroid cancer; and 63 (23.4 %) of all-cause mortality. Multivariate analysis showed that age, gender, extensive ETE, and lymph node metastasis had a statistically significant effect on thyroid cancer mortality. Survival rates were significantly different between minimal ETE and extensive ETE groups (p

Background This study examines whether the measurement of circulating epithelial cells (CECs) facilitates the identification and follow-up of a patient with thyroid cancer. Methods A 29-y-old woman with no cancer history was enrolled as a healthy control in a CEC study. CECs were enriched from the peripheral blood by the negative selection system PowerMag. Various medical examinations were performed on the patient to establish the diagnosis and to follow-up her disease status during treatment. Results This patient had unexpectedly high CEC counts that were sustained for more than two weeks. Thyroid gland ultra-sonography revealed lesions in the left lobe that could not be confirmed as cancer by magnetic resonance imaging, 18 F–fludeoxyglucose-positron emission tomography–computed tomography or cytopathological analysis, but were histologically confirmed after thyroidectomy as papillary thyroid microcarcinoma. Both the CEC count and serum thyroglobulin (Tg) concentration were significantly decreased after thyroidectomy, and they and the patient's disease status were correlated during remnant ablation therapy. The CEC count returned to normal when the patient was disease-free 10 months after thyroidectomy. Conclusions CEC testing facilitates the identification of individuals at risk for cancer. Longitudinal follow-up of the CEC count may complement serum Tg testing for monitoring the status of patients with thyroid cancer.

Recent studies conducted in patients with chronic diseases have reported an inverse association between body mass index (BMI) and mortality. However, the question as to whether BMI may predict prognosis in patients with metastatic cancer remains open. We therefore designed the current retrospective study to investigate the potential association between BMI and overall survival (OS) in patients with distant metastases (DM) and a favorable performance status. Between 2000 and 2012, a total of 4010 cancer patients with DM who required radiotherapy (RT) and had their BMI measured at the initiation of RT were identified. The relation between BMI and OS was examined by univariate and multivariable analysis. The median OS time was 3.23 months (range: 0.1–122.17) for underweight patients, 6.08 months (range: 0.03–149.46) for normal‐weight patients, 7.99 months (range: 0.07–158.01) for overweight patients, and 12.49 months (range, 0.2–164.1) for obese patients (log‐rank: P

Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in the G2/M phase. Roniciclib treatmentin vivoretarded the growth of two well-differentiated thyroid tumors in xenograft models in a dose-dependent fashion. Furthermore, the combination of roniciclib with sorafenib was more effective than either single treatment in a follicular thyroid cancer xenograft model. Acceptable safety profiles appeared in animals treated with either roniciclib alone or roniciclib and sorafenib combination therapy. These findings support roniciclib as a potential drug for the treatment of patients with well-differentiated thyroid cancer.

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[

Background Cranial metastasis of thyroid cancer is rare. The aim of this study was to analyse the clinical characteristics, treatments and outcomes of thyroid cancer patients with cranial metastasis and to identify the associated prognostic factors. Materials and methods Between January 1977 and August 2017, a total of 4683 patients were histologically confirmed to have thyroid cancer. Among them, 25 patients (0.53%) were identified as having cranial metastases, and their medical records were reviewed. The Kaplan-Meier method with a log-rank test was performed with cancer-specific survival as the main outcome. Cox regression analysis was used to examine the potential prognostic factors influencing patient survival. Results Of the 25 patients, 21 were female, and 4 were male. The median age at the time of diagnosis of cranial metastasis was 63 years. Sixteen patients had metastases to the brain, and nine patients had metastases involving the skull only. Papillary carcinoma and follicular carcinoma accounted for 84.0% of cases. Twenty-four cases (96.0%) had extracranial metastases at the time of diagnosis of cranial metastases. Twenty patients received surgery, and 4 patients received palliative radiotherapy. One patient received supportive care only. The median cancer-specific survival after the diagnosis of cranial metastases was 27 months. According to the Kaplan-Meier test, 3 factors had a significant impact on survival, the metastatic site, histological types and surgical resection. According to the Cox regression analysis, skull metastases (HR: 0.274, 95% CI: 0.083–0.904, p = 0.033) and surgical resection (HR: 0.134, 95% CI: 0.019–0.929, p = 0.042) were identified as independent prognostic factors for a better outcome. Conclusions Surgical resection is the mainstay therapy for thyroid cancer patients with cranial metastasis. Cranial metastases involving the skull only are associated with a better outcome.

Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC.

The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1α,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1α,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1α,25(OH)2D3. The anti-metastatic effect of 1α,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1α,25(OH)2D3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC.

Background and Objectives : The purpose of this study was to retrospectively analyze the features of patients with papillary thyroid carcinoma (PTC) presenting with neck lymph node (LN) metastasis. Methods : The study enrolled 909 patients with PTC who had undergone total thyroidectomy. After a median follow‐up of 14.6 years, 73 (8.0%) patients died of thyroid cancer. A total of 536 patients had the tumor confined to the thyroid (intra‐thyroid), 111 had lymph node (LN) metastasis, 225 showed soft tissue invasion, and 37 had distant metastasis. Results : Compared with the intra‐thyroid group, the group with LN metastases showed larger tumor size, higher postoperative thyroglobulin levels, advanced TNM stage, higher recurrence rates (5.2% vs. 31.5%), and higher disease‐specific mortality (1.3% vs. 12.6%). Of the 111 patients with PTC and LN metastases, 35 (31.5%) were diagnosed with recurrence during a mean follow‐up period of 16.9 ± 0.6 years. Among the 35 patients with recurrent PTC, 14 (40.0%) died of thyroid cancer. The mortality group was characterized by older, mostly male patients who presented with larger initial tumor size compared with survivors. Conclusions : In patients with PTC, the rates of recurrence and cancer mortality were higher in the group with LN metastasis than that in the intra‐thyroid tumor group. J. Surg. Oncol. 2015 111:149–154. © 2015 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

The incidence and histopathological characteristics of metastatic cancers to the thyroid (MCT) are different in various geographic areas. The aim of this study was to elucidate the clinical features of MCT, including histocytological diagnosis and therapeutic outcomes. A retrospective analysis of patients with thyroid cancer treated and followed up at the Chang Gung Medical Center in Linkou was performed. Among 3957 patients with thyroid cancer, a total of 56 patients with MCT were evaluated. Of them, 47 patients (83.9 %) were diagnosed with malignancy or suspected malignancy via fine needle aspiration cytology of the thyroid. Synchronous primary cancers were diagnosed in 44 of the patients with MCT. Of the MCT, metastasis of lung cancer to the thyroid was the leading category. Other primary sites of MCT were the head and neck, gastrointestinal tract, kidneys, breast, cervix, and unknown primary site. The mean 5-, 10-, 20-, and 60-month survival rates were 46.4, 32.1, 21.4, and 7.9 % for the patients. Patients with metachronous thyroid carcinoma had significantly better survival than patients with synchronous cancer. In conclusions, the incidence of MCT in patients with thyroid cancer is low; however, the prognosis of patients with MCT is poor, especially in patients diagnosed with synchronous primary tumors. In this study, MCT commonly originated in organs located near the thyroid, such as the lungs, head, and neck. Close monitoring of these malignancies may improve the prognosis of patients with MCT in the future.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan. Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment. A total of 43 patients (18 men and 25 women; mean age 51 ± 13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ± 0.304 (0.088–1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004–1.134]) and distant metastases based on 131I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938–44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment. Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

The aim of this study was to assess the size, angles and positional characteristics of facial anthropometry between "acromegalic" patients and control subjects. We also identify possible facial soft tissue measurements for generating discriminant functions toward acromegaly determination in males and females for acromegaly early self-awareness.This is a cross-sectional study. Subjects participating in this study included 70 patients diagnosed with acromegaly (35 females and 35 males) and 140 gender-matched control individuals. Three-dimensional facial images were collected via a camera system. Thirteen landmarks were selected. Eleven measurements from the three categories were selected and applied, including five frontal widths, three lateral depths and three lateral angular measurements. Descriptive analyses were conducted using means and standard deviations for each measurement. Univariate and multivariate discriminant function analyses were applied in order to calculate the accuracy of acromegaly detection.Patients with acromegaly exhibit soft-tissue facial enlargement and hypertrophy. Frontal widths as well as lateral depth and angle of facial changes were evident. The average accuracies of all functions for female patient detection ranged from 80.0-91.40%. The average accuracies of all functions for male patient detection were from 81.0-94.30%. The greatest anomaly observed was evidenced in the lateral angles, with greater enlargement of "nasofrontal" angles for females and greater "mentolabial" angles for males. Additionally, shapes of the lateral angles showed changes. The majority of the facial measurements proved dynamic for acromegaly patients; however, it is problematic to detect the disease with progressive body anthropometric changes.The discriminant functions of detection developed in this study could help patients, their families, medical practitioners and others to identify and track progressive facial change patterns before the possible patients go to the hospital, especially the lateral "angles" which can be calculated by relative point-to-point changes derived from 2D lateral imagery without the 3D anthropometric measurements. This study tries to provide a novel and easy method to detect acromegaly when the patients start to have awareness of abnormal appearance because of facial measurement changes, and it also suggests that undiagnosed patients be urged to go to the hospital as soon as possible for acromegaly early diagnosis.

// Ching-Ping Tseng 1, 2, 3, 4 , Kong-Kit Leong 1 , Miaw-Jene Liou 5 , Hsueh-Ling Hsu 1 , Hung-Chih Lin 2 , Yi-An Chen 1 and Jen-Der Lin 5 1 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC 2 Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC 3 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC 4 Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC Correspondence to: Jen-Der Lin, email: einjd@adm.cgmh.org.tw Ching-Ping Tseng, email: ctseng@mail.cgu.edu.tw Keywords: circulating epithelial cells, epithelial cell adhesion molecule, papillary thyroid carcinoma, podoplanin, therapeutic response Received: May 01, 2017 Accepted: August 08, 2017 Published: August 24, 2017 ABSTRACT Loco-regional recurrence or distant metastasis usually leads to the death of patients with papillary thyroid carcinoma (PTC). Whether or not circulating epithelial cells (CECs) count is a valuable marker in monitoring the therapeutic outcome of PTC was investigated. Patients with PTC (n=129) were treated in our medical center and were categorized into 4 groups with excellent (n=45), biochemical incomplete (n=15), indeterminate (n=37), and structural incomplete (n=32) responses. CECs were enriched from the peripheral blood by the PowerMag negative selection system. Three subtypes of CECs expressing epithelial cell adhesion molecule (EpCAM), thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells), and podoplanin (PDPN, a marker related to poor prognosis in patients with PTC) were defined by immunofluorescence staining, respectively. The median number of CECs (cells/mL of blood) expressing EpCAM, TSHR, and PDPN was 23 (interquartile range 10-61), 19 (interquartile range 8-50), and 8 (interquartile range 3-22), respectively, for patients enrolled in this study. The number of EpCAM + -CECs, TSHR + -CECs, and PDPN + -CECs was statistically different among patients in different treatment response groups without interference from anti-thyroglobulin antibody (P

ObjectivePatients with diabetes mellitus have an increased risk of coronary heart disease; however, many patients with diabetes remain untreated or undertreated for coronary heart disease risk factors. The incidence of type 2 diabetes is rapidly increasing in Taiwan. The aim of this study was to assess the lipid-lowering effects of atorvastatin in Taiwanese diabetic patients with hyperlipidemia.Materials and MethodsThis 12-week open-label study, conducted at six hospitals in Taiwan, included 157 outpatients (aged 18–80 years old) with type 2 diabetes and concomitant hyperlipidemia. Individuals were randomized (1:1:1) to three dosage groups, as follows: 52 patients received 10 mg of atorvastatin per day; 52 patients received 20 mg of atorvastatin per day; and the remaining 53 patients received 40 mg of atorvastatin per day. Treatment targets were established according to the recommendations of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III. The response was evaluated by Cochran-Mantel-Haenszel tests. The change from the baseline level of all lipid parameters and high-sensitivity C-reactive protein (hs-CRP) was determined through analysis of covariance and was assessed at each time point.ResultsThe primary endpoint—a low-density lipoprotein-cholesterol (LDL-C) response of >100 mg/dL at Week 12—was achieved in a dose-dependent manner. The percentage of patients improving to this level was higher in the 20 mg/day group (82%) and 40 mg/day group (82%) than in the 10 mg/day group (56%; p = 0.002). The percentage of patients achieving the more aggressive LDL-C goal of >70 mg/dL was 9.6%, 31.4%, and 47.1% in the 10 mg/day, 20 mg/day, and 40 mg/day groups, respectively (p

Background: Subclinical hypothyroidism (SCH) is defined as elevation in serum thyroid-stimulating hormone (TSH) levels despite normal serum levels of free thyroxine. It remains controversial whether people with SCH have higher total cholesterol and low-density lipoprotein cholesterol levels compared to normal-thyroid subjects. The aim of this study was to assess the metabolic risk factors for SCH. Methods: Subjects were recruited from the health examination center of Chang Gung Memorial Hospital, Linkou, from January 1, 2010 to December 31, 2011. This was a cross-sectional review of medical records. The subjects were ethnic Taiwanese residents without known thyroid disease at baseline. Results: A total of 22,324 subjects received annual health examination at Chang Gung Memorial Hospital from 2010 to 2011. Among them, 15,943 subjects were included as the normal thyroid group (NG), and 203 subjects (101 men and 102 women) met the criteria for SCH. The prevalence of metabolic syndrome (MetS) in the NG was 26.2% in men and 18.7% in women, whereas that in the SCH group was 39.6% in men and 29.4% in women. Women in the SCH group showed significantly higher cholesterol, triglyceride, non-high density lipoprotein (HDL) and cholesterol/HDL levels than those in the NG (p

The aims of this study were to investigate papillary and follicular thyroid carcinomas with bone metastasis in various clinical presentations and to determine the prognostic factors after multimodality treatment. A retrospective analysis was performed of 3,120 patients with papillary and follicular thyroid carcinoma. Of these patients, 131 (including 97 women, 71.8%) were diagnosed with bone metastasis and underwent follow-up at the Chang Gung Medical Center. Patients with bone metastasis were categorized into two groups. Group A was comprised of patients who were diagnosed with bone metastasis either before thyroidectomy or within 6 months of the initial thyroidectomy (90 patients, 68.7%). Group B was comprised of patients with bone metastasis who received a diagnosis 6 months post-thyroidectomy in the follow-up period (41 patients, 31.3%). After a mean follow-up period of 8.4 ± 7.0 years, there were 88 deaths (67.2%) attributed to thyroid cancer and 13 patients (9.9%) achieved disease-free status. A multivariate analysis showed that older age, early diagnosis, and brain metastasis were each associated with a poor prognosis. The difference in disease-specific mortality rates between groups A and B was significant (p < 0.0001). In conclusion, papillary and follicular thyroid cancers with bone metastasis have a high rate of mortality. Despite this high mortality, 9.9% patients still had an excellent response to treatment.

To investigate the correlation between gender and the clinical presentation of papillary thyroid cancer and the long-term followup results, 435 patients who underwent total or near-total thyroidectomy were enrolled in this study. Among these papillary thyroid cancer patients, 12.2% showed lymph node metastases and a higher incidence of male patients in the N1b group. There were 65 from 316 female (20.6%) and 49 from 120 male (40.8%) patients who had a postoperative disease progression. A total of 55 (12.6%) patients died of thyroid cancer. Male patients showed a higher thyroid cancer mortality than the females. Multiple regression analysis showed that male gender was an independent risk factor for cancer recurrence and mortality. Male patients with TNM stages II to IV of papillary thyroid cancer need to adopt aggressive surgical and postoperative131I therapy.

Objective: The objective of this study was to determine the therapeutic outcome of papillary thyroid cancer (PTC) patients in different risk groups in one institute. Methods: A total of 1,759 PTC patients were categorized into low- (n = 1,123), intermediate- (n = 75), and high-risk (n = 561) groups according to tumor-node-metastasis (TNM) stage. Results: Of the patients, 15.1% presented with lymph node metastases, and 4.6% presented with distant metastases at the time of thyroid operation. After 8.0 ± 0.1 years of follow-up, 73 (4.2%) patients died of thyroid cancer. Tumor size, local invasion, and lymph node metastases adversely influenced recurrence and survival. Of the patients in the 3 groups, 9 (0.8%), 8 (10.7%), and 56 (10.0%) died of thyroid cancer, respectively. In addition, 88 (7.8%), 14 (18.7%), and 144 (25.8%) patients showed recurrence during the follow-up period. Patients with highly aggressive histological patterns showed increased recurrence and cancer mortality compared with the low-risk group; otherwise, values were not higher than those of the high-risk group. Conclusions: The cancer-related mortality was nearly 10% in the intermediate- and high-risk groups, and the patients in these groups required aggressive surgical and postoperative adjuvant therapies.

Aims Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). This study is to investigate the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tek/Tie-2 receptor, and vascular endothelial growth factors (VEGF) in normal, benign thyroid tissues and different stage of PTC. We expect angiogenetic factors are important in the presentation of local-regional neck or distant metastases in PTC. Materials and Results A total of 101 tissues from the subjects underwent thyroidectomy were enrolled in the study. There were 22 control and 79 thyroid cancer patients in different TNM stagings were collected. Ang-1 illustrated highest mean immunostaining score in metastatic group. Comparing with normal and benign thyroid tissues, thyroid cancer tissues illustrated significantly high expression of three angiogenetic factors and Tie-2 receptor. Of the PTC, significantly high expression of three angiogenetic factors and Tie-2 receptor were illustrated in recurrent cases. VEGF showed statistical difference in disease-free cancer mortality, and recurrent groups. Conclusions Immunochemical staining illustrated VEGF, Ang-1, Ang-2 expression in PTC tissues related to clinical staging; however, we need more information concerning these factors with long-term follow-up results. J. Surg. Oncol. 2011; 103:395–399. © 2010 Wiley-Liss, Inc.

Patients with thyroid cancer usually have good prognosis. However, 15-20% of patients ultimately develop recurrence and disease-related death. In this study, we investigate whether the number of circulating tumor cells (CTCs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN, a marker related to poor prognosis in patients with thyroid cancer), or thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells) is a prognostic marker for non-remission and disease-specific mortality (DSM) of patients with thyroid cancer. Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. After enrichment of CTCs by a negative selection PowerMag system, enumeration and subtyping of the CD45-depleted cells were performed by immunofluorescence staining using the antibodies aginst EpCAM, TSHR, and PDPN, respectively. Our data revealed that the number of EpCAM+-CTCs (p < 0.001) and PDPN+-CTCs (p < 0.001), and TSHR+-CTCs (p < 0.001) for patients in the non-remission group (n = 43) was significantly higher when compared to the remission group (n = 85). At the cutoff of 40, 14, and 47 cells/mL for EpCAM+-CTCs, TSHR+-CTCs, and PDPN+-CTCs, the accuracy of the assay was equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CTCs (p < 0.001), PDPN+-CTCs (p = 0.013), and TSHR+-CTCs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). At the cutoff of 27, 25, and 9 cells/mL for EpCAM+-CTCs, TSHR+-CTCs, and PDPN+-CTCs, the accuracy of the assay was equivalent to 69.5%, 67.2%, and 68.5%, respectively. These data together indicate that CTC testing is worthy to be considered as a routine clinical test to benefit clinical care of patients with thyroid cancer. Citation Format: Ching-Ping Tseng, Jen-Der Lin, Miaw-Jene Liou, Wei-Shan Hung, Hsueh-Ling Hsu, Kong-Kit Leong, Yu-Ting Chen, Ju-Chien Cheng. Circulating tumor cells as the prognostic marker for non-remission and disease-specific mortality of patients with thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5586.

The aim of the present study was to examine the anatomical differences in volumetric and intraparenchymal vascular parameters between the two thyroid lobes of patients with goiter, using three-dimensional power Doppler ultrasound. A total of 89 outpatients with goiter, including 55 with autoimmune thyroid disease (ATD) and 34 with simple goiter (SG), were evaluated by three-dimensional power Doppler ultrasound. Volumetric and intraparenchymal vascular indices including vascularization index, flow index and vascular flow index of each lobe were measured using the Virtual Organ Computer-Aided Analysis system. In all patients with goiter, the volume and vascular indices (vascularization index, flow index and vascular flow index) of the right thyroid lobe were significantly greater than those of the left lobe (p < 0.05). Differences in vascular indices were present in SG but not in ATD. ATD was associated with a larger thyroid volume and higher vascular indices compared with those of SG (p < 0.001), but there were no significant differences in volumetry and vascular indices between euthyroid ATD and SG. In conclusion, the right thyroid lobe was found to be significantly larger and more vascular than the left lobe in subjects with goiter, as measured by three-dimensional power Doppler ultrasound. In addition, ATD was associated with a higher thyroid volume and vascular indices compared with those of SG.

In this paper, we present a fast algorithm for joint estimation of the two-dimensional (2-D) directions of arrival (DOAs) and frequencies of the incoming signals in wireless communications using a hierarchical space-time decomposition (HSTD) technique. Based on the HSTD, the proposed algorithm makes use of a sequence of one-dimensional (1-D) Unitary estimation of signal parameters via rotational invariance technique (ESPRIT) algorithms to estimate these parameters alternatively in a hierarchical tree structure. Also, in between every other 1-D Unitary ESPRIT algorithm, a temporal filtering process or a spatial beamforming process is invoked to partition the incoming signals into finer groups stage by stage to enhance the estimation accuracy as well as to alleviate the contaminated noise. Furthermore, with such a tree-structured estimation scheme, the pairing of these parameters is automatically determined without extra computational overhead. Simulation results show that the new algorithm provides satisfactory performance but with drastically reduced computations compared with previous works.

Ultrasound and fine needle aspiration cytology are advocated as first-line examinations for the assessment of thyroid nodules. This review investigates the incidence of thyroid cancer in thyroid nodules after ultrasonographic examination. Furthermore, patient characteristics, histological patterns, and therapeutic results among patients who received thyroid ultrasound and fine needle aspiration cytology are discussed. The incidence of thyroid cancer in thyroid nodules, as detected by thyroid ultrasound, was found to range from 7.9% to 32.7% depending on the selected population. The incidence of thyroid cancer in thyroid nodules reported depends on the studied cohort, ethnic group, age, sex and iodine intake. Radiation exposure is also an important factor. Of the 6,330 patients with thyroid nodules who underwent surgical treatment, benign lesions were observed in 75.5% (4,782 cases) of the cases. Papillary thyroid carcinoma was observed in 79.8% (1,236 cases) of the 1,548 malignant cases. The percentage of malignancy was found to increase after the age of 50 in both men and women. A decrease in tumor size correlated with decreased cancer mortality; however, the beneficial effects of a small tumor size were not seen in older patients. Radiation-exposed populations and thyroid nodules or thyroid cancer were major problems from the atomic bomb in World War II and the Chernobyl nuclear accident. However, most occupational radiation exposure studies have not illustrated this harmful effect of radiation. In summary, over the time course in the diagnosis of thyroid cancer in nodules, there is a trend of decrease in tumor size and increase in the patient's age. The diagnosis and treatment of non-well-differentiated thyroid cancer in ageing patients is a major obstacle that needs to be overcome in the future.

Background: Metabolic syndrome (MetS) and hyperuricemia are important risk factors for cardiovascular disease. However, findings regarding the relationship between serum uric acid (UA) level and components of MetS have been inconsistent. This study was performed to explore the potential value of UA level as a marker of MetS among male and female Chinese of different ages.Methods: A total of 5896 subjects (2960 females and 2936 males) were recruited from the Department of Health Management at the Chang Gung Medical Center. Hyperuricemia was defined as a serum UA value >7.0 mg/dL for males or >6.0 mg/dL for females. MetS was defined according to the criteria of the Adult Treatment Panel III, as modified for Chinese subjects. Serum UA was used to differentiate MetS and to calculate epidemiological indices by means of discriminate analysis and logistic regression.Results: The sensitivity and specificity of serum UA concentration as a marker of MetS ranged from 55.2% to 61.4% and 61.9% to 68.4%, respectively. Subjects with high UA had a higher risk of MetS, with odds ratios ranging from 1.23 to 1.82 (P < 0.01). A positive correlation between serum UA and MetS was observed in both sexes. Serum UA and the occurrence of MetS rose with increasing age in females; in males, however, UA values did not vary with age.Conclusions: Serum UA is more closely associated with MetS in females than in males. High UA among middle-aged women may predict the development of MetS.

The aim of this study was to evaluate the efficacy, safety, and tolerability of weekly alendronate administration on male osteoporosis in Taiwan. This 6-month, randomized, open-label controlled trial enrolled 46 men with osteoporosis who were randomized to either 70 mg alendronate once weekly (n = 23) or control (n = 23). Bone mineral density (BMD) of lumbar spine and hip and biochemical bone turnover markers were measured; adverse events and tolerability were assessed. Subjects treated with alendronate showed a significant increase in BMD of 5.5% (vs. 2% in control group) at the lumbar spine and 2.7% (vs. 0.7%) at the femoral neck (P < 0.05) at 6 months, respectively. There were also significant decreases in serum level of bone formation marker (bone-specific alkaline phosphatase) and urinary excretion of bone resorption marker (deoxypyridinoline) at 3 and 6 months. Thus, alendronate showed anti-osteoporotic effects by increasing BMD and decreasing the concentrations of bone markers. The adverse events were mild and showed no significant difference between the two groups on safety assessments.

We performed a retrospective analysis of follicular neoplasm data obtained from frozen section examinations of thyroid nodules. A total of 5,660 patients underwent preoperative neck ultrasonography and fine-needle aspiration cytology (FNAC), surgical treatment, and follow-up at a medical institute. Patients with papillary thyroid microcarcinoma were excluded from this study. In 971 cases, frozen section examination was performed during the surgical treatment of follicular neoplasm that was diagnosed via FNAC. Thyroid malignancies were histologically confirmed in 25.1% of cases (244/971). Among the patients with papillary thyroid carcinoma, 45 were diagnosed with the follicular variant of papillary thyroid carcinomas (27.4%). The diagnostic sensitivity of frozen section for the nonfollicular variant of papillary thyroid carcinoma was better than that for the follicular variant of papillary thyroid carcinoma (89.1% versus 78.9%; P = 0.1023). For 12 cases the diagnosis was atypical follicular adenomas. The diagnostic accuracy of frozen section in cases of follicular neoplasm was 76.9% with a sensitivity of 84.8% and a specificity of 98.9%. In conclusion, our analysis revealed high rates of accuracy when using frozen tissue sections for early diagnosis and treatment of follicular neoplasm; thus, an early decision to extent of surgery prevents a risky follow-up surgery.

Purpose. To correlate sonographic (US) characteristics and results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with surgical pathological findings. Method. Forty AT patients with 40 nodular lesions were analyzed retrospectively. Five sonographic characteristics were recorded for each nodule: diameter, echogenicity, microcalcification, halo sign, and margin. Preoperative sonograms and FNAB results were compared with postoperative histopathological findings. Result. Twenty-four of the 40 nodules were malignant, including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic thyroiditis, and 1 each follicular adenoma and Hurthle cell adenoma. The only US parameter that was significant in malignant vs. benign nodules was the presence of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly identified. The positive predictive value was 78.6%, and the negative predictive value was 93.7%. Conclusion. No single US parameter can predict thyroid malignancy in patients with AT. A combination of US and FNAB provides the most sensitive and specific approach available preoperatively. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009

The occurrence of recurrent papillary and follicular thyroid carcinomas is not unusual. Numerous studies have reported the association between risk factors of initial surgery and recurrence of papillary and follicular thyroid carcinomas. However, we do not have sufficient data to analyze the time of postoperative recurrence associated with therapeutic results and cancer mortality. We hypothesized that an early recurrence of papillary and follicular thyroid cancers implies a rapid growth of cancer resulting in high mortality rate.We conducted a retrospective study in a medical center in northern Taiwan. The investigation included 2148 cases of papillary and follicular thyroid carcinoma, including 325 recurrent cases during the period between 1977 and 2006. The studied cases were categorized into early or late recurrence groups. Cases with an early recurrence were defined as those in which recurrence occurred in the first year following thyroid surgery.Tumor size, radioactive iodide treatment, multifocality, and tumor-node metastasis stage were independent predictors of recurrence. After a mean follow-up of 8.7 +/- 0.1 years, death due to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the 325 recurrent cases, early recurrence was detected in 185 cases, and late recurrence was detected in 140 cases. Early recurrence was mostly observed in older male patients; a high mortality rate was associated with these cases. Distant metastases were observed in about 80% of the cases in the early recurrence group, whereas localized metastases in the neck region were observed in more than half the cases in the late recurrence group. The percentage of patients with a non-disease-free status and distant metastases in the early recurrence group was higher than that in the late recurrence group. The 10-year disease-specific survival rates were 52.5% and 85.1% for the early and late recurrence groups, respectively.Early recurrent papillary and follicular thyroid carcinomas are associated with high mortalities. Tumor size and multifocality deserve consideration as indicators of recurrence. Therefore, patients whose primary follicular or papillary thyroid carcinoma has features associated with early recurrence should probably receive more aggressive initial treatment.