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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.

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

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.

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.

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

Summary Objective The aim of this study was to compare the clinical presentation and prognosis of poorly differentiated thyroid carcinoma (PDTC) with those of classical papillary thyroid carcinoma (PTC) to identify the appropriate surgical modalities for use in conjunction with radioactive iodide (131I) therapy and external radiotherapy for treating PDTC. Design Sixty-seven PDTC patients (mean age 50·3 ± 18·1 years, range 14–82 years) underwent surgery at the Chang Gung Medical Centre (CGMC), Linkou. To compare clinical presentations and treatment outcomes, 134 age- and gender-matched patients with classical PTC were selected randomly from the patient database at CGMC. Results Of the 67 PDTC patients, 53 underwent near-total thyroidectomy. Following surgery, 45 were administered 131I for remnant ablation and treatment of distant metastatic disease. Forty-one of the 67 (61·2%) patients with PDTC and 26/134 (19·4%) with classical PTC failed to achieve disease-free status. Twenty-four of the 67 (34·3%) PDTC patients eventually died of thyroid cancer after a mean follow-up of 5·9 ± 0·6 years. Age and TNM staging at surgery were significant indicators of PDTC patient survival and mortality. Conclusions As the prognosis for PDTC patients is poorer than that for classical PTC patients, 131I treatment following surgery is useful. To improve the survival rate, early diagnosis is crucial for PDTC.

Department of Electrical Engineering, National Tsing Hwa University, Hsingchu, TaiwanSummaryIn this paper, we present a blind and robust algorithm to jointly estimate the directions of arrival (DOAs) andpropagation delays in DS/CDMA systems. The rationale of the proposed approach is a hybrid of one-dimensional(1-D) multiple signal classification (MUSIC) algorithms and constrained spatial/temporal filtering processes.As previously addressed TST MUSIC, two temporal (T)-MUSIC and one spatial (S)-MUSIC are employedalternatively in the proposed algorithm to estimate the group delays and the DOAs respectively. However, byutilizing the structure of the data model, no training sequences are required. Furthermore, a constrained temporalfiltering process and a constrained spatial beamforming process, which minimize the filtered noise power under aset of judiciously chosen linear constraints, are now employed after the T-MUSIC and S-MUSIC respectively.These filtering processes aim to effectively partition the incoming rays and to be robust against the propagationerrors in the tree-structured estimation scheme so that the overall performance can be enhanced. Also, theincoming rays are grouped, isolated and estimated, and the pairing of the estimated delays and DOAs is auto-matically achieved without extra computational overhead. Furnished simulations show that the new approachcan exhibit satisfactory performance with low complexity compared with previous works. Copyright # 2005John Wiley & Sons, Ltd.KEY WORDS: DOA; TOA & AOA separation; MUSIC; CDMA1. IntroductionInwirelesscommunicationsystems,amultipathchan-nel is characterized by the directions of arrival(DOAs) as well as the time delay of the propagationpaths. Joint estimation of the angle and delay of eachpath can not only help us locate the mobile units, butalso attain improved channel estimates, which cansignificantly improve the system performance [1,2].Also, the number of paths can be larger than that ofantennas. As such, it is of importance to develop highresolution, yet low complexity algorithms to jointlyestimate these two channel parameters.The traditional DOA estimation algorithms [3] orthetimedelayestimationalgorithms[4],whichdonotmake full use of the space-time characteristics of the

Background: Hypothyroidism is commonly thought to cause decreased gastric emptying but is mostly associated with autoimmune disease. In the present study the gastric emptying function of thyroid cancer patients with severe hypothyroidism of short duration was evaluated with a radionuclide solid meal gastric emptying study. Methods: Twenty-two patients who had undergone surgical operation and 131I ablation for thyroid cancer participated in solid meal gastric emptying studies before the withdrawal of thyroxine and then again 4 weeks after the withdrawal of thyroxine. Eleven patients had an additional gastric emptying study at 6 weeks after withdrawal of thyroxine. Gastric emptying curves and emptying parameters were calculated. Student's paired t-test was used for statistical analysis of data for all cases between the baseline and at 4 weeks after withdrawal. An additional repeated measure anova with multiple comparisons was performed on data between baseline, 4 weeks and 6 weeks after withdrawal for the other 11 patients. All P values presented are two-tailed and the significance level is 0.05. Results: Hypothyroidism status was confirmed by the marked change of the serum thyroxine and thyroid-stimulating hormone 4 weeks and 6 weeks after withdrawal of the thyroxine replacement (P

Background To evaluate the results of treatment and the prognostic variables of papillary thyroid carcinoma patients after long-term follow-up. Patients and Methods Retrospective review of 1373 thyroid cancer patients. Of the 1016 papillary thyroid cancer patients, 394 patients received follow-up for more than 5 years, including 305 women (mean age, 38.4 ± 13.7 years) and 89 men (mean age, 44.0 ± 13.4 years). Of these papillary thyroid carcinoma patients, 227, 76, 68, and 23 patients were categorized in clinical stages I, II, III, and IV, respectively, at the time of diagnosis. Results After treatment, 36 (9.1%) patients died. Only 23 (5.8%) of them died of papillary thyroid carcinoma. The 1-, 5-, 10-, and 20-year survival rates were 0.980, 0.951, 0.901, and 0.731. Mortality factors of the papillary thyroid carcinoma patients related to age, gender, tumor size, and postoperative serum thyroglobulin (Tg) levels. Twenty-four patients progressed from clinical stages I, II, and III to stage IV during the follow-up period. Of these 24 patients, 12 died during the follow-up period. In this study, age, gender, 131I accumulated dose, postoperative serum Tg levels, and the survival rate were demonstrated to be statistically significant between the patients in early stage and advanced stage groups after treatment. Conclusion Twenty-four of the 47 papillary thyroid cancer patients with distant metastases were diagnosed during the follow-up period. This study suggests that distant metastasis may occur at a serum Tg level of 2.3 ng/mL with thyroxine replacement. Postoperative long-term close follow-up of these patients is recommended. © 2001 John Wiley & Sons, Inc. Head Neck 23: 140–146, 2001.

Background To investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients. Materials and methods In this study a retrospective analysis was performed with 204 thyroid cancer patients aged 60 years or older (132 women, with a mean age of 68.3 ± 6.6 years; 72 men, with a mean age of 67.0 ± 5.3 years). Results Of the 204 patients, 142 had well-differentiated thyroid carcinomas (96 papillary thyroid carcinomas, 43 follicular carcinomas, three Hurthle cell carcinomas) and three medullary carcinomas. Sixty-nine (33.8%) of the 204 patients died after treatment. Of these, three patients died of causes not related to thyroid cancer. For well-differentiated thyroid carcinomas, male gender, follicular carcinoma, and a larger tumour size indicated a poor prognosis. Of the 59 non-well-differentiated thyroid carcinomas, 39 were anaplastic thyroid carcinomas, nine metastatic cancers of the thyroid, seven lymphomas, and four squamous cell carcinomas. After treatment, 40 (67.8%) of the 59 patients died. In multivariant analysis of the differences in clinical parameters between aging and younger thyroid cancer patients, the current status, tumour size, follow-up period, sex, and stage at diagnosis were independent factors. From this data the delayed diagnosis of aging patients with thyroid cancer was of note when compared with younger patients. Conclusion Thyroid cancer in older patients is not a benign clinical disorder. Early diagnosis and urgent aggressive treatment are recommended courses of action for this type of cancer, especially for non-well-differentiated thyroid cancers.

Anaplastic thyroid carcinoma is one of the most lethal neoplasms, with poor prognosis being reported by most authors. The benefits of surgery for most cases of advanced disease remain controversial. In this study we asked the following question: Does surgical intervention alter outcomes for patients with advanced anaplastic thyroid carcinoma? Forty-six patients with advanced anaplastic thyroid carcinoma were analyzed. There were 20 patients with advanced localized disease (group 1), 15 of whom received surgery. Of the other 26 patients with evidence of distant metastases (group 2), 13 received surgery. For group 1 patients, the mean survival was 12.8 months versus 8.6 months in the surgical and nonsurgical subgroups (p = 0.46). For group 2 patients, the mean survival was 3.5 months versus 2.8 months in the surgical and nonsurgical subgroups (p = 0.72). These data suggest that surgery does not improve survival for patients with advanced anaplastic thyroid carcinoma. In conclusion, the mean survival showed no significant differences between surgical and nonsurgical patients (p = 0.43). This study suggests that surgical resection does not improve the survival of patients with advanced anaplastic thyroid carcinoma.

Background and Objectives Aggressive malignant thyroid tumors (AMTT) may mimic the clinical symptoms and signs of acute suppurative thyroiditis (AST) in the early course of the disease process. Our objective was to analyze the clinical features of these two conditions, to assess the best way of early diagnosis, and to propose proper treatment. Methods We retrospectively reviewed and analyzed the clinical features of 30 patients, who had similar clinical pictures of AST and were managed at Chang Gung Memorial Medical Center in Linkou, Taiwan, during the period from 1983 to 1996. These patients were consequently diagnosed as either AST or AMTT. The data were analyzed by the Mann-Whitney U, chi-square and Fisher's exact tests. Results Among the 30 patients, 25 patients (Male/Female (M/F) ratio = 9/16) were diagnosed as having AST and 5 (M/F ratio = 1/4) as AMTT. After statistical analysis we concluded that the presence of the following factors, namely, older age at diagnosis (P = 0.0155), history of dysphonia (P = 0.0325), right thyroid lobe involvement (P = 0.0151), large size of lesions (P = 0.0013), presence of anemia (P = 0.0075), and sterile pus cultures from thyroid aspirates (P = 0.0013) were cause to suspect a malignancy if the condition did not improve after antibiotics. Delay in diagnosis and management of AMTT may result in a poor prognosis (P = 0.0082). Conclusion Due to the high mortality rate of AMTT, we should closely observe the patients with poor prognostic variables of acute thyroiditis. Earlier detection and aggressive surgical intervention for AMTT might improve the outcome. J. Surg. Oncol. 1998;67:28–32.©1998 Wiley-Liss, Inc.

This series retrospectively reviewed 3657 patients who received thyroid ultrasonography with fine-needle aspiration cytological (FNAC) examinations at Chang Gung Memorial Hospital during the period from January 1, 1993 to December 31, 1993. Thyroid ultrasonography studies were performed using a real-time ultrasonographic machine with a 10 MHz transducer. The aspirates were air dried and stained by the Romanowsky-based Liu method. Three hundred seventy-eight cases (10.3%) received surgical treatment after the ultrasonographic and FNAC examinations. Benign lesions were diagnosed in 269 patients. Thyroid malignancy was confirmed histopathologically in 109 cases including 76 papillary thyroid carcinomas, 17 follicular carcinomas, 5 medullary thyroid carcinomas, 3 anaplastic carcinomas, 3 Hurthle cell carcinomas, and 3 lymphomas. Another 2 cases were metastatic cancer to thyroid. The results demonstrated that 28.8% of the surgically treated patients had histopathologically proven malignancies. The incidence of thyroid malignancy was 2.98% in this study. The sensitivity of the cytological diagnosis was 79.80% and the specificity was 98.66%. The positive predictive value was 96.34%. Negative predictive value was 91.70%. The false negative index was 20.20%. The diagnostic accuracy was 92.89%. Thyroid ultrasonography with the FNAC can provide high specificity and sensitivity in differentiating malignant lesions from benign.

Background Our aim was to establish Chinese human thyroid cancer cell lines and to provide the material for thyroid cancer research. Methods We collected thyroid cancer tissues from 93 patients with thyroid cancer for developing the primary culture. Thyroid cancer tissues were verified by frozen sections during the operations, then subjected to primary cell culture. During the first several passages, fibroblasts were removed by selective attachment. Results From the 93 cancer tissues used, two follicular cancer tissues from the metastatic area (CGTH W-1, CGTH W-2) and one papillary thyroid cancer tissue (CGTH W-3) could be passed over 50 times. Cellular transformation with loss of contact inhibition occurred during passages 5–8. Electron microscopic studies of the CGTH W-1 cell line showed the presence of an abundance of mitochondria and Golgi complex. Presence of microvilli with interdigitations between neighboring cells were found in CGTH W-2 and CGTH W-3 cell lines. Severe combined immunodeficient (SCID) mice were used to determine whether these cells were tumorigenic. Two months after transplantation of 1 × 107 CGTH W-1, 2, and 3 cells into SCID mice, subcutaneous tumors ∼ 2–2.5 cm in size were clearly visible. After affinity cross-linking, an IGF-I with insulin-like growth factor binding proteins complex corresponding to a molecular size of 41 kDa was observed in culture media collected from CGTH W-1, SW 579, and RO82 W-1 cells. Conclusions Three thyroid cancer cell lines were established, which may provide material for future thyroid cancer research. © 1996 Wiley-Liss, Inc.

SUMMARY To investigate the natural killer (NK) cell mediated immunity in Graves' disease (GD) and the effect of antithyroid drugs upon NK cell activity, 51Cr release assay for NK cytotoxicity against K562 cells was examined in patients with GD before and during antithyroid medication and after drug withdrawal. Fifty-eight patients were divided into three groups: the untreated thyrotoxic patients (n= 33), the euthyroid patients under antithyroid treatment (n= 19) and the euthyroid patients after drug withdrawal (n= 6). The results of the three groups were compared to 23,15 and 5 sex- and age-matched controls, respectively. The data revealed a significant NK dysfunction in the untreated hyperthyroid patients, although the number of the NK cells was not decreased. NK function was normal when patients were no longer taking antithyroid medication and in euthyroid state. However, euthyroid patients under antithyroid medication had markedly depressed NK activity, suggesting an immunosuppressive effect of the antithyroid drugs. This study demonstrated that both the hyperthyroid state and the antithyroid drugs exerted immunosuppressive effects upon the NK cells. Since such an immunosuppressive effect on NK cells might be associated with a decreased immune surveillance against tumour growth, this study implies that a long-term follow up of GD patients treated with antithyrdid drugs may be indicated to guard against a possible increased incidence of malignancy.