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Chyle leakage (CL) due to lymphatic injuries is one of the rare complications that can develop after thyroidectomy. There are few studies on lymphatic embolization performed in case of CL after thyroid surgery. We report two cases of CL after thyroid surgery that were effectively treated by thoracic duct embolization. The patients had previously undergone total thyroidectomy with central compartment neck dissection with or without modified radical neck dissection. The amount of drainage from the operative site was ＞1000 mL per day in one patient and ＞500 mL per day in the other. In both cases, CL stopped after the thoracic duct embolization. Thoracic duct embolization seems to be an effective and important treatment option for CL after thyroid surgery.

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Background/objective The diagnostic accuracy of fine needle aspiration biopsy (FNAB) seems limited in large thyroid nodules with Bethesda Cat. 2 result. We aimed to determine the incidence of carcinoma with benign cytology and the reason for the high false-positive rate in thyroid nodules ≥4 cm. Methods The records of 103 patients with thyroid nodules ≥4 cm with preoperative cytological diagnosis of Bethesda Cat. 2 who underwent thyroidectomy were consecutively reviewed. Characteristics between patients with malignant vs. benign pathology were compared. Results Forty patients (38.8%) had malignancy. Malignancy was subclassified into follicular variant of papillary thyroid carcinoma (43%), minimally invasive follicular thyroid carcinoma (20.0%), and minimally invasive Hurthle cell thyroid carcinoma (10.9%). Patients with malignant cytology had significantly more suspicious ultrasound findings than those with benign cytology (p = 0.001). Conclusions Preoperative FNAB showed high false-negative rates in patients with thyroid nodules ≥4 cm with benign cytology. These nodules have a high malignancy rate with suspicious ultrasound findings.

The incidence rates of structural persistent disease (PD) and recurrent disease (RD) after thyroidectomy, and their clinicoradiological (CT) characteristics, remain poorly understood. Therefore, we characterized differentiated thyroid cancer (DTC) patients who underwent re-operations, with a focus on preoperative CT scans. We examined neck CT scans obtained prior to initial surgery and reoperation, and classified the disease into four categories according to the persistence/recurrence and neck dissection/non-dissection status. In total, 121 of 9,173 DTC patients underwent reoperations to treat PD or RD; the mean time to reoperation was 25.5 and 54.1 months, respectively. Of all reoperations, 19% (23/121) were performed to treat RD; 81% (98/121) were performed to treat PD. Compared to RD, PD was commonly detected in the non-dissected neck. Tumor multiplicity and the number of pathologically positive lymph nodes were greater in the non-dissected than dissected neck. A review of the CT data revealed more false-negative findings on the 60-s- versus 30–40-s-delay scans of PD patients with non-dissected necks. In conclusion, most of the reoperations performed on DTC patients were for management of PD. Improved preoperative CT assessments and initial surgery, based on the information of clinico-radiological characteristics, are required in the care of DTC patients.

This study investigated the correlation between basal thyroglobulin (Tg) and recombinant human thyroid-stimulating hormone (rhTSH)-stimulated Tg in differentiated patients with thyroid cancer, and sought to determine whether the basal Tg level predicts the rhTSH-stimulated Tg level. We retrospectively enrolled 177 patients with papillary thyroid cancer (mean age = 44 years; 50 males, 127 females) who received rhTSH before radioiodine therapy (RIT). Serum Tg levels were measured 7 days before the 1st rhTSH injection (basal Tg) and on the days of RIT (rhTSH-stimulated Tg). Patients were divided into 3 groups according to rhTSH-stimulated Tg cut-off levels of 2, 5, and 10 ng/mL. The correlation between basal Tg and rhTSH-stimulated Tg levels was assessed, and whether basal Tg was useful in predicting the rhTSH-stimulated Tg level was determined. A significant positive correlation was observed between basal and rhTSH-stimulated Tg levels (|rho| = 0.48, P 0.3 or 0.5 ng/mL, then the rhTSH-stimulated Tg level can be expected to be sufficiently high to necessitate clinical examination.

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.

Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC., The senescence-associated secretory phenotype of stromal cells can promote tumorigenesis. Here, the authors show that senescent cancer cells are localized at the invasive front in human papillary thyroid carcinoma, and that senescent cancer cells drive collective invasion via CXCL12 in mouse models.

We investigated the clinical significance of diffuse uptake in remaining thyroid after unilateral lobectomy for thyroid cancer.A total of 144 thyroid cancer patients who underwent (18)F-FDG PET/CT after lobectomy were enrolled in the present study. The PET/CT images were evaluated for the presence of diffuse (18)F-FDG uptake with maximum SUV (SUVmax)2.0 in the residual thyroid and placed into one of two groups: with diffuse uptake and without diffuse uptake group. Clinical, laboratory, and PET/CT parameters in both groups were compared. Correlations between SUVmax of thyroid and available parameters were analyzed.Forty-two of 144 patients (29.2%) had diffuse thyroid uptake (mean SUVmax: 3.2 ± 1.1). All patients with diffuse uptake and 96 (94.1%) without diffuse uptake were receiving thyroxine therapy (P = 0.09). Thyroid function tests showed that most patients were euthyroid status (78.6 vs. 85.3%, P = 0.36). TgAb levels were significantly higher in patients with diffuse uptake (338.0 ± 664.6 vs. 57.3 ± 46.4, P 0.0001). Mean attenuation values in the diffuse uptake group were significantly lower (72.2 ± 15. vs. 97.0 ± 16.0, P 0.0001). An inverse correlation was found between SUVmax and mean attenuation values of residual thyroid in all patients (r = -0.57, P 0.0001) and subgroup with diffuse uptake (r = -0.31, P 0.05).In this study, diffuse (18)F-FDG uptake in the residual thyroid after unilateral lobectomy was a relatively frequent finding and may be associated with chronic thyroiditis. This uptake is not influenced by thyroid status or thyroxine therapy. The (18)F-FDG uptake is inversely correlated with mean attenuation value of thyroid.

The clinical behaviors and treatment outcomes of thyroid carcinomas in patients with Graves' disease is a matter of controversy. This study aimed to identify the clinicopathologic features, treatment outcome, and the indicators for predicting recurrence, and to suggest the optimal extent of surgery in these patients. We retrospectively analyzed data of 58 patients who underwent surgical treatment for differentiated thyroid cancer and concurrent Graves' disease. The follow-up period ranged from 23 to 260 months (mean+/-standard deviation, 116.8+/-54.0). In our series, the mean age was 40.8+/-12.7 yr (range, 15-70), with a male-to-female ratio of 1: 6.25. The mean tumor size was 13+/-9 mm (range, 3-62). The surgical methods included 19 cases of total thyroidectomy, 38 cases of subtotal thyroidectomy, and 1 case of completion total thyroidectomy. Locoregional recurrence occurred in four patients (6.9%). The 10-yr overall survival and disease-free survival of patients were 95.8% and 91.1%, respectively. Age over 45 yr (p=0.031), tumor size over 10 mm (p=0.049), multiplicity (p=0.007), extracapsular invasion (p=0.021), and clinical cancer (p=0.035) were significantly more prevalent in patients with locoregional recurrence than in those without recurrence. We recommend that Graves' disease patients should undergo regular ultrasonography screening for early detection of thyroid carcinoma. We also suggest that the choice of extent of surgery should depend on the diagnostic timing (clinical or incidental) and factors for predicting recurrence.

Purpose: Breast cancers in the early phase frequently undergo distant metastasis and survival of patients is greatly dependent on distant metastasis. The occurrence of micrometastasis has been suggested to relate with prognostic features of breast cancer, such as lymph node metastasis and the presence of vascular invasion. The aim of this study was to examine the presence of keratin-19 mRNA of epithelial tumors in bone marrow aspirates obtained from breast cancer patients and its possible correlation with tumor staging and disease-free survival. Methods: Bone marrow samples were obtained from 59 breast cancer patients at the time of surgery. We separated the mononuclear fraction from the samples and carried out nested reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of keratin-19 mRNA with two different pairs of primers. After operation, the patients were followed up at 3month intervals. We studied the possible correlation of the detection of keratin-19 mRNA with tumor size, nodal involvement, stage and recurrence rate. Results: Bone marrow micrometastasis was detected by nested RT-PCR for keratin-19 mRNA in one of four patients with ductal carcinoma in situ (DCIS), 13 of 30 patients with T1, 11 of 20 patients with T2 and all four patients with T3 lesion. Recurrence was observed in seven cases and all of them were positive for micrometastasis in bone marrow. Conclusion: The method of nested RT-PCR to detect the presence of keratin-19 mRNA in bone marrow from patients with breast cancer is sensitive and reliable. Moreover, early recurrence was observed in the patients with the tumor mRNA detected in bone marrow. Additional studies with larger numbers of patients and longer follow-up are desirable.

Objectives: We evaluated the utility of the VE1 antibody that can detect a mutant protein resulting from the BRAF V600E mutation as a diagnostic tool for thyroid fine-needle aspiration cytology (FNAC). Methods: We performed VE1 immunocytochemistry on 202 FNAC specimens from surgically confirmed thyroid nodules. The results were compared with the molecular analyses of the BRAF mutation in these specimens matched with their corresponding histology. Results: Diagnoses of FNAC specimens included benign (9.4%), atypia of undetermined significance/follicular lesion of undetermined significance (11.4%), follicular neoplasm/suspicious for follicular neoplasm (2.0%), suspicious for malignancy (9.4%), and malignancy (65.8%). VE1 immunostaining was positive in 71.3% of FNAC specimens. The overall sensitivity of the VE1 antibody was 88.8%, specificity was 71.2%, positive predictive value was 88.2%, negative predictive value was 72.4%, and diagnostic accuracy was 83.7%. Conclusions: VE1 immunocytochemistry in thyroid FNAC as a screening test for BRAF mutations is highly specific for malignant category cases but can be suboptimal due to its high false-positive rate for the nonmalignant cases.

We investigated whether (131)I whole-body scintigraphy could predict functional changes in salivary glands after radioiodine therapy.We evaluated 90 patients who received initial high-dose (≥3.7 GBq) radioiodine therapy after total thyroidectomy. All patients underwent diagnostic (DWS) and post-ablation (TWS) (131)I whole-body scintigraphy. Visual assessment of salivary radioiodine retention on DWS and TWS was used to divide the patients into two types of groups: a DWS+ or DWS- group and a TWS+ or TWS- group. Salivary gland scintigraphy was also performed before DWS and at the first follow-up visit. Peak uptake and %washout were calculated in ROIs of each gland. Functional changes (Δuptake or Δwashout) of salivary glands after radioiodine therapy were compared between the two groups.Both peak uptake and the %washout of the parotid glands were significantly lower after radioiodine therapy (all p values0.001), whereas only the %washout were significantly reduced in the submandibular glands (all p values0.05). For the parotid glands, the TWS+ group showed larger Δuptake and Δwashout after radioiodine therapy than did the TWS- group (all p values0.01). In contrast, the Δuptake and Δwashout of the submandibular glands did not significantly differ between the TWS+ and TWS- groups (all p values0.05). Likewise, no differences in Δuptake or Δwashout were apparent between the DWS+ and DWS- groups in either the parotid or submandibular glands (all p values0.05).Salivary gland radioiodine retention on post-ablation (131)I scintigraphy is a good predictor of functional impairment of the parotid glands after high-dose radioiodine therapy.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hurthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hurthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hurthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Purpose: Papillary thyroid cancer (PTC) is the most frequent subtype among thyroid cancers. B-type Raf kinase (BRAF) mutation can be found in...

Primary aldosteronism (PA) is a frequent cause of secondary hypertension and is amenable to surgical intervention when it is caused by aldosterone-producing adenoma (APA). Many patients, however, continue to require antihypertensive medications to control their blood pressure after adrenalectomy. The aim of this study was to determine the preoperative factors that predict clinical outcomes after adrenalectomy in patients with APA. We studied 27 patients (mean age 45+/-4 yr) who had APA and underwent unilateral adrenalectomy between December 1995 and September 2008 at our institution. Clinical and biochemical data were evaluated at baseline and after a mean follow-up of 51.8+/-47.0 months (range, 6-159). At the end of the follow-up, 16 patients (59.3%) were considered to experience "complete resolution" without postoperative medications, whereas 7 patients (25.9%) "improved" with medications and 4 patients (14.8%) were "uncontrolled." Three factors (< or =2 antihypertensive medications [P=0.007], duration of hypertension

B-RafV600E mutant is found in 40–70% of papillary thyroid carcinoma (PTC) and has an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein that mediates active iodide transport into the thyroid follicular cells, and B-RafV600E has been known to be associated with the loss of NIS expression. In this study, we found that B-RafV600E inhibited NIS expression by the upregulation of its promoter methylation, and that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC were highly methylated compared with surrounding normal tissue. Although DNA methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1 expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes. Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-κB activation. These results led us to conclude that NIS promoter methylation, which was induced by B-RafV600E, is one of the possible mechanisms involved in NIS downregulation in PTC.

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.

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.

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.