Long-term therapeutic outcomes of papillary thyroid carcinoma with concomitant hyperparathyroidism: A single center case-control study.

BACKGROUND: Papillary thyroid carcinoma occasionally presents with concomitant hyperparathyroidism; however, the clinical significance has not been well established. This study aimed to evaluate the long-term cancer prognosis following a multimodality therapy. METHODS: We conducted a case-control study using prospectively maintained data from a medical center thyroid cancer database between 1980 and 2013. The study cohort comprised patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patients with papillary thyroid carcinoma only were matched using the propensity score method. Therapeutic outcomes, including the non-remission rate of papillary thyroid carcinoma and patient mortality, were compared. RESULTS: We identified 27 study participants from 2537 patients with papillary thyroid carcinoma, with 10 patients having primary hyperparathyroidism and 17 having renal hyperparathyroidism. Eighty-five percent of the cohort was found to have tumor-node-metastasis stage I disease. During a mean follow-up of 7.7 years, we identified 3 disease non-remission and 4 mortality events. The non-remission risk did not increase (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.43-6.40; p = 0.47); however, the overall mortality risk significantly increased (HR, 4.43; 95% CI, 1.11-17.75; p = 0.04). All mortality events were not thyroid cancer related, including two identified cardiovascular diseases. CONCLUSIONS: Patients with papillary thyroid carcinoma who present with concomitant hyperparathyroidism are usually diagnosed at an early cancer stage with compatible therapeutic outcomes. However, hyperparathyroidism-related comorbidity may decrease long-term survival.

Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan Acromegaly Registry.

BACKGROUND/PURPOSE: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). RESULTS: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (ß = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (ß = -4.720, p = 0.046 and ß = -5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (ß = -5.839, p = 0.034 and ß = -7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (ß = -26.632, p = 0.013; ß = -28.353, p = 0.024; ß = -25.648, p = 0.026; and ß = -34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. CONCLUSION: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions.

Targeting PLKs as a therapeutic approach to well-differentiated thyroid cancer.

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.

Diagnostic pitfalls and therapeutic outcomes of the macrofollicular variant of papillary thyroid carcinoma.

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.

A registry of acromegaly patients and one year following up in Taiwan.

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.

Frailty and health care use among community-dwelling older adults with diabetes: a population-based study.

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. A total 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.

Circulating Epithelial Cell Characterization and Correlation with Remission and Survival in Patients with Thyroid Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: The EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively. CONCLUSIONS: CEC 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.

The efficacy of radioactive iodine for the treatment of well-differentiated thyroid cancer with distant metastasis.

OBJECTIVE: Radioactive iodine (I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of I (>600 mCi) for the treatment of well-differentiated thyroid cancer. PATIENTS AND METHODS: In this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016. RESULTS: For our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075). CONCLUSION: I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated I doses were administered.

The effect of suppressive thyroxine therapy in nodular goiter in postmenopausal women and 2 year's bone mineral density change.

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.

Activity of roniciclib in medullary thyroid cancer.

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.

Outcomes and prognostic factors in thyroid cancer patients with cranial metastases: A retrospective cohort study of 4,683 patients.

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.

Potent effects of roniciclib alone and with sorafenib against well-differentiated thyroid cancer.

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 treatment in vivo retarded 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.

Subclinical hypothyroidism and metabolic risk factors association: A health examination-based study in northern Taiwan.

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 < 0.05). CONCLUSION: Because SCH is more prevalent in women and the risk increases with age, greater attention to the risk of MetS development is warranted. As for men, regardless of thyroid function, the risk of MetS development with age still warrants attention. Thus, our data suggest that national guidelines for screening for thyroid disease using serum TSH levels in the elderly are mandatory.

Integrated analysis of fine-needle-aspiration cystic fluid proteome, cancer cell secretome, and public transcriptome datasets for papillary thyroid cancer biomarker discovery.

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.

Differentiation of the Follicular Variant of Papillary Thyroid Carcinoma From Classic Papillary Thyroid Carcinoma: An Ultrasound Analysis and Complement to Fine-Needle Aspiration Cytology.

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.

Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody.

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 48cells/ml and 10cells/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.

The long-term outcomes of thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism.

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 < 0.001). 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.

Circulating epithelial cell counts for monitoring the therapeutic outcome of patients with papillary thyroid carcinoma.

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<0.0001). Patients with structural incomplete response had higher counts for all three CECs subtypes when compared to other patients. EpCAM+-CECs was better in distinguishing patients with excellent response from structural incomplete response among the three subtypes of CECs. The sensitivity and specificity of the assay was 84.4% and 95.6%, respectively, when the cut off value was 39 EpCAM+-CECs/mL. CECs testing can supplement the current standard methods for monitoring the therapeutic outcome of PTC.

Effects of roniciclib in preclinical models of anaplastic thyroid cancer.

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.

Acromegaly determination using discriminant analysis of the three-dimensional facial classification in Taiwanese.

OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.