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Purpose: The goal of this study was to evaluate the diagnostic accuracy of preoperative fine needle aspiration biopsy cytology (FNAB-C) in predicting lateral lymph node metastasis in papillary thyroid cancer patients. Methods: A total of 592 patients who underwent thyroid cancer surgery and intraoperative lateral cervical LN frozen section or RND, from January 2002 to December 2011, were evaluated retrospectively. Among them, 228 cases had suspicious findings in FNAB-C of lateral nodes. We reviewed their radiological and pathological reports. Results: Intra-operative frozen section examination was performed in 540 cases and RND was performed in 314 cases. This study included 534 women (83.4%) and 106 men (16.6%). Patients’ ranged in age from 9 to 83 years (mean, 45.65 years). FNAB-C was performed in 228 cases. The sensitivity and specificity of FNAB-C was 71.5% and 78.6%, respectively; 35.9% of cases had a false negative result. The combination of FNAB-C and intra-operative frozen section test sensitivity and specificity was 87.2% and 93.6%, respectively. Conclusion: The results for sensitivity in FNAB-C actually appear low, and false negative results were very high. In papillary thyroid cancer in patients with FNAB-C, even if the result is negative, if lymph node metastasis is suspected based on radiologic evidence, frozen section examination should be performed for determination of metastasis.

Papillary thyroid microcarcinoma (PTMC) has been increasing, without a consensus for the management of this condition. In the present study, we analyzed the clinicopathological features of patients with PTMC to examine the impact of initial therapy and establish appropriate treatment. A total of 2,018 patients with PTMC were enrolled at a single university hospital. Of them, 1,245 patients (61.8%) underwent total thyroidectomy, and 1,838 patients (91.3%) underwent central lymph node (LN) dissection. Five-and 10-yr recurrence rates were 3.2% and 4.6%, respectively. In univariate analysis, the prognostic factors for recurrence were N stage, the number of LN metastases, and extrathyroidal extension. However, multivariate analysis revealed LN metastases and N stage as the only significant prognostic factors after adjusting for confounding factors (P < 0.001). Additionally, multivariate analysis of a subgroup consisting of PTMC patients without N1b revealed the number of central LN metastases as the only significant factor. Therefore, intraoperative examination for central LN metastasis may discriminate high or low risk group.

Theodor Kocher, at the turn of the past century, made outstanding contributions to the understanding of thyroid disease. By 1901, he had performed 2,000 .thyroid operations, and the overall operative mortality had decreased from 50.0% to 4.5%.5 Since that time, there have been considerable advances in the understanding of thyroid disorders and in the effective management of patients with thyroid nodules. Numerous controversies remain, however, regarding the preoperative evaluation and extent of treatment for patients with thyroid carcinoma. Use of fine-needle aspiration (FNA) biopsy for the preoperative assessment of patients with thyroid nodules has resulted in a two-fold increase in the yield of thyroid carcinoma at operation, and FNA has become the single most important diagnostic test.87 Fine-needle aspiration, however, continues to have some limitations when used as the sole preoperative diagnostic test and should never overrule good

Purpose: Regional lymph node (LN) metastases are detected in 57?85% of patients with papillary thyroid carcinoma (PTC) and are associated with increased tumor recurrence. However, the management of lymphatic disease in patients with PTC has been ongoing source of debate. We have prospectively assessed the usefulness and accuracy of sentinel LN (SLN) biopsy for the detection of LN metastases in patients with PTC on preoperative imaging using single photon emission computed tomography/computed tomography (SPECT/CT) and 99mTc phytate. Methods: We prospectively assessed 39 patients with PTC who had risk factors for recurrence or with the necessity of intraoperative LN sampling for suspicious LN metastases on preoperative imaging from August 2010 to March 2011. The patients underwent preoperative lymphoscintigraphy and SPETC/CT and intraoperative SLN biopsy (SLNB). Results: 99mTc lymphoscintigraphy and SPECT/CT localized SLN in 38 patients (97.4%), with the gamma probe identifying 2.15 mean SLNs in the lateral neck of the 39 patients. Skip metastasis was found in one patient, and lateral compartment LN metastasis in 17 (43.5%). The sensitivity, specificity, and accuracy of SLNB for lateral compartment LN metastasis were 88.2%, 100%, and 94.8%, respectively. SLNB was more accurate and useful for lateral than for central compartment LN metastasis. Conclusion: SPECT/CT improved SLN detection and anatomical localization compared with lymphoscintigraphy. SLNB in patients with risk factors for recurrence or the necessity of intraoperative LN sampling for suspected LN metastases on preoperative imaging was accurate in detecting LN metastases and may help in deciding whether to perform lateral compartment dissection in patients with PTC.

Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been complicated by its susceptibility to proteolysis and its low level of expression in thyrocytes and many transfected cells. Controversy exists over its size and structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100 kDa) have been recently identified in immunoblots of crude plasma membranes prepared from COS-7 cells transfected with rat or human cDNA, but the relationship of these receptor species to the TSHR in human thyroid tissue has been heretofore unknown. We have developed a technique for immunoprecipitation of the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR residues 352-366. We have used immunoprecipitation to isolate the previously characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa precursor forms of the TSHR from plasma membrane prepared from transfected COS-7 cells and human thyroid tissue. The presence of all three forms was not altered by the addition of reducing agent to the sample buffer, demonstrating the single polypeptide structure of the TSHR. This is, to our knowledge, the first report of the purification from transfected COS-7 cells of these TSHR species identified previously only in immunoblots of crude plasma membrane, and the first report of the identification by any means of these TSHR forms in human thyroid tissue. The isolation of TSHR from human thyroid tissue requires confirmation by direct means, but promises to make the receptor available in a soluble form for studies of its structure and function.

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [(131)I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [(124)I]-PET/CT and [(18)F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [(131)I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [(18)F]-FDG-PET/CT and [(124)I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [(18)F]-FDG (5/19, 26.3%) or [(124)I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [(18)F]-FDG-PET/CT and [(124)I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.

One hundred patients who underwent bilateral subtotal thyroidectomy for Graves' disease between January 1980 and September 1984 have been evaluated. The observation period ranged from 5 to 9 years, the average being 6.2 years. Postoperative thyroid function was evaluated with T3, T4 and TSH and compared with their clinical manifestations. Eighty-two patients became euthyroid, 14 patients had recurrence and 4 patients developed hypothyroidism. The thyroid hormone level of euthyroid patients were in an unstable state up to 5 years after the operation. Sixteen variables which might influence the postoperative recurrence and hypothyroidism were analyzed but no statistically significant factors were determined, although recurrences were found frequently in patients over 30 years, the patients with lower infiltration of lymphocytes and absent of fibrosis of thyroid tissue. The results obtained in the present study suggest that mean 6.0 gm of remnant thyroid is suitable for maintaining euthyroidism postoperatively in a majority of patients. In addition, patients should be followed closely for many years and should undergo hormonal determination periodically because recurrence and hypothyroidism can occur at 5 years or more after the operation.

Among 545 surgically treated Graves' disease patients, 17 were found to have coexisting thyroid neoplasms. Of these 17 patients, 11 turned out to have thyroid carcinomas. These patients could be divided into 2 groups; Group I with a diffusely enlarged gland with a clinically palpable nodule (n = 6) and Group II without a palpable nodule (n = 5). In Group I, 4 patients were diagnosed by preoperative fine needle aspiration cytology, and the remaining 2 by intraoperative frozen-section examination. In Group II, none of the patients were suspected of any concurrent thyroid carcinoma preoperatively, and only 2 were identified by intraoperative frozen-section examination. Thus, 8 of the 11 patients were diagnosed preoperatively or intraoperatively. These observations suggest that in all patients with Graves' disease and concurrent thyroid nodules, the suspicion of associated malignancy may be raised. And also, fine needle aspiration cytology in every case of Graves' disease with a palpable nodule and intraoperative frozen-section examination of the suspicious lobe in the cases of non-palpable nodules appear worthwhile in detecting a concurrent thyroid carcinoma.

Purpose: Surgical approaches for papillary thyroid carcinoma remain controversial. Moreover, previous reports regarding surgical strategy for papillary carcinoma of thyroid isthmus are very few. The aims of this study are to analyze the clinicopathologic features of papillary thyroid carcinoma of the isthmus and to develop more appropriate surgical strategies. Methods: Prospectively, papillary carcinoma arising thyroid isthmus (n=35) was included in this study from June 2006 to December 2008. All of the patients had total thyroidectomy with bilateral central compartment node dissection performed. Lateral nodes were sampled for frozen biopsy when metastasis was suspected by preoperative study. Thirty-five patients, who had unilateral papillary thyroid carcinoma, had total thyroidectomy with bilateral central compartment node dissection as control group and compared with papillary thyroid carcinoma of isthmus. Results: Lymph node metastasis was higher than control group in patients of isthmus cancer (51% vs 20%, P＜0.05). Capsular invasion and multifocality observed in 63% and 23% respectively, but there was no significant difference compared to control group, statistically. Capsular invasion showed a positive correlation with lymph node metastasis by univariate and multivariate analysis. Analysis of ipsilateral nodal metastatic distribution revealed no definite metastatic pattern. Tracheal adhesion was observed in 4 cases of isthmus cancer group. Conclusion: In conclusion, it is recommended that bilateral CCND is needed as an appropriate primary surgical procedure for localized papillary carcinoma of thyroid isthmus.

Background Without angiogenesis, tumours cannot grow larger than a few millimetres in size, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and is a major regulator of physiological and pathological angiogenesis. Higher levels of VEGF messenger RNA expression and VEGF production and secretion have been found in FTC-133 cells than normal thyroid cells. Methods To investigate the relationship between VEGF and thyroid tumour angiogenesis and growth, human dermal matrix inoculated with FTC-133 cells was xenografted into nude mice or directly injected subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally 100 μg per 0·2 ml twice weekly. As control, an antibody of the same isotype (immunoglobulin G1), directed against the gP120 protein (Ab 5B6), or phosphate-buffered saline (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, rhVEGF was inoculated into the dermal matrix pocket and xenografted into mice. Results In vivo study using the dermal matrix showed that the number of blood vessel ingrowths paralleled the concentration of rhVEGF and was highest at the concentration of 100 ng ml−1. Mice treated with the mAb A.4.6.1 developed fewer blood vessels (mean 7 per high-power field (HPF)) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS) (P < 0·01). The size of tumours between mAb A.4.6.1- and Ab 5B6- or PBS-treated groups showed a significant difference from the second week after the inoculation of FTC-133 cells. The tumours from mice treated with mAb A.4.6.1 were smaller (mean(s.d.) 0·09(0·02) g at 5 weeks) than tumours from mice treated with Ab 5B6 (5·38(1·15) g) or PBS (4·00(0·72) g) (P < 0·001, two-tailed unpaired t test). Conclusion VEGF is produced by thyroid cancer cell line FTC-133 and stimulates angiogenesis and growth of thyroid cancer. More importantly, this stimulation can be blocked by mAb A.4.6.1.

Objective Thyroidectomy is associated with a high incidence of postoperative nausea and vomiting (PONV), ranging from 60% to 84%. We conducted this study to compare the antiemetic effects and safety of granisetron 20 μg/kg and ramosetron 4 μg/kg in patients undergoing elective thyroidectomy under standard anaesthetic technique. Methods One hundred and thirteen patients were randomized to receive placebo ( n = 41), granisetron 20 μg/kg ( n = 36) or ramosetron 4 μg/kg ( n = 36) intravenously over 2-5 minutes immediately before the induction of anaesthesia. The incidence of PONV, nausea severity score (NSS), adverse events and the need for rescue antiemetics were assessed during the first 1 hour (0-1 h) and following 23 hours (1-24 h) after anaesthesia. Results During the first hour after anaesthesia, the incidence of PONV was 36.6% for placebo, 11.1% for granisetron ( p = 0.012 vs placebo) and 25.0% for ramosetron. During 1 hour to 23 hours after anaesthesia, the incidence of PONV was 51.2% for placebo, 30.6% for granisetron and 41.7% for ramosetron. There were no significant differences between the three groups. Overall (0-24 h), the corresponding incidence of PONV were 61.0%, 30.6% and 50.0%, respectively, showing a significantly lower value in the granisetron group than in the placebo group ( p = 0.008). The incidence of vomiting and rescue antiemetic requirement during the first 24 hours after anaesthesia was significantly lower with the granisetron group than with placebo ( p = 0.021 and 0.030, respectively). The most common adverse events in the three groups were headache and dizziness. Conclusion Only granisetron 20 μg/kg was superior to placebo for the prevention of PONV after thyroidectomy.