• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.120-127
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• 2003

Purpose: To evaluate diagnostic sensitivity of nuclear imaging in the detection of residual thyroid tissue and metastatic lesion, we have compared neck scintigrams with Tc-99m pertechnetate (Tc-99m scan) and high dose I-131 iodide (I-131 scan) in patients with differentiated thyroid cancer. Subjects and Methods: One hundred thirty-five thyroidectomized patients for differentiated thyroid cancer were enrolled in this study. Twenty-three had a previous history of radioiodine therapy. Planar and pin-hole images of anterior neck with Tc-99m were acquired at 20 minutes after injection, followed by I-131 scan three days after high-dose radioiodine therapy within 7 days interval. Patients were asked to discontinue thyroid hormone replacement more than 4 weeks. Results: All subjects were in hypothyroid state. Seventy out of 135 patients (51.9%) showed concordant findings between Tc-99m and I-131 scans. I-131 scan showed higher number of uptake foci in all of 65 patients showing discordant finding. Tc-99m scan showed no thyroid bed uptake in 34 patients, whereas 23 of them (67.6%) showed bed uptake in I-131 scan. Tc-99m scan did not show any uptake in thyroid bed in 11 of 112 patients without previous history of radioiodine therapy, but 9 of them showed bed uptake in I-131 scan. Tc-99m scan showed no bed uptake in all of the 23 patients with previous history of radioiodine therapy, in contrast 14 of them (60.9%) showed bed uptake in I-131 scan. Conclusion: These results suggest that Tc-99m scan has poor detectability for residual thyroid tissue or metastatic lesion in thyroidectomized differentiated thyroid cancer patients, compared to high dose I-131 therapy scan. Tc-99m scan could not detect any remnant tissue or metastatic lesion in patients with previous history of radioiodine treatment, especially.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.152-160
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• 2004

Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice xenografted with human melanoma, glioma, breast cancer or prostate cancer, rats with subcutaneous thyroid tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition, the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a therapeutic agent when combined with radioiodide injection. Better NIS-mediated imaging and tumor treatment by radioiodide requires a more efficient and specific system of gene delivery with better retention of radioiodide in tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a therapeutic strategy for a variety of human diseases.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.138-142
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• 2015

L-thyroxine (LT4) withdrawal prior to radioactive iodine (RAI) ablation therapy is a commonly used method for successful treatment of patients with papillary thyroid cancer (PTC). However, a prolonged period of hypothyroidism induced by LT4 withdrawal is sometimes associated with impaired quality of life and cardiopulmonary dysfunction in PTC patients. Furthermore, LT4 withdrawal may have a trophic effect on residual cancer by means of increased thyrotropin. We report on 2 cases of metastatic PTC patients with malignant pleural effusion (MPE) whose disease showed rapid worsening after LT4 withdrawal and RAI therapy. The first case is a 65-year-old woman who had PTC with multiple distant metastases and MPE. During LT4 withdrawal for RAI therapy, MPE showed rapid worsening, and the patient required repetitive therapeutic thoracentesis. The second case is a 49-year-old woman with PTC who underwent 3 additional operations for cancer recurrence in the neck lymph nodes and 6 times of RAI treatments. While preparing for the $7^{th}$ RAI treatment by withdrawing LT4, she developed MPE which became progressively aggravated after RAI therapy. Both patients experienced increased pleural effusion during the LT4 withdrawal period and a rise in the thyroglobulin level was observed after RAI therapy. MPE was not controlled with therapeutic thoracentesis and pleurodesis. Eventually, both patients died of rapid disease progression after RAI therapy. In summary, LT4 withdrawal may have an adverse effect on metastatic PTC patients, particularly those with MPE.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4211-4214
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• 2015

Background: Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. Materials and Methods: A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. Results: 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value <0.001), extrathyroidal extension (p-value <0.001), level VI positive ((p-value <0.001) and level VII positive ((p-value <0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Conclusions: Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

• Korean Journal of Head & Neck Oncology
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• v.34 no.2
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• pp.61-64
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• 2018

Malignant lesion of the trachea predominantly results from direct spread of adjacent tumors, whereas primary tracheal malignancies are rarely observed. Tracheal tumors are usually diagnosed late on account of delayed specific symptoms: dyspnea, stridor, coughing and hemoptysis. Primary tracheal tumors, although very rare, may extend into the thyroid gland and present as a thyroid mass. Surgery, followed by adjuvant radiotherapy, is the treatment of choice. A case of primary tracheal cancer with thyroid invasion is reported, and a review of the literature is presented.

• Korean Journal of Head & Neck Oncology
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• v.20 no.1
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• pp.7-12
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• 2004

Background and Objectives: Brain metastasis from well-differentiated thyroid carcinoma is uncommon, and the treatment remains controversial. In this study, we analyzed cases of brain metastasis from well differentiated thyroid carcinoma to determine optimal treatment. Material and Methods: From March 1986 to May 2003, we experienced 13 cases of brain metastases from well-differentiated thyroid carcinomas. There were 6 men and 7 women with a mean age of 62.3 years. The time interval detecting the brain metastasis, treatment methods, outcomes, and the prognostic factors were analyzed. Results: In 11 patients, brain metastasis was found at a mean of 96 months after thyroid surgery (range, 1-204months). In 1 patient, brain metastasis was found simultaneously with the thyroid cancer. In the remaining one, brain metastasis was presented as the first sign. Treatment included gamma knife therapy in 2, external radiation therapy (ExRT) in 2, resection and ExRT in 2, gamma knife therapy and ExRT in 2 and intracranial holmium injection in 1. Three patients received no treatment. The mean survival was 20.5months (1-119 months). Only 2 patients with early detection remained alive after treatment (23months and 119months). The age, sex, primary tumor size, combined organs of distant metastasis and treatment methods did not affect the prognosis. There were noticeable symptomatic improvements in patients who received any kind of treatment for brain metastasis. Conclusion: Early detection and treatment of brain metastasis appears to bring symptomatic relief and improve survival. Therefore, early screening for brain metastasis is recommended for patients with symptoms. However, further study is needed to determine the optimal method of treatment.

• The Korean Journal of Cytopathology
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• v.17 no.2
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• pp.116-119
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• 2006

The diagnosis of papillary thyroid cancer is generally based on the findings of intranuclear cytoplasmic inclusions and nuclear grooves. Although anisokaryosis and poikilokaryosis, in papillary thyroid cancer, are not distinct when compared to other cancers, cytological examination can provide useful preoperative information. Our study evaluated the diagnostic role of computer-assisted image analysis for the pre-surgical assessment of papillary thyroid carcinoma. Thyroid aspirates from twenty female patients who were histologically confirmed to have both papillary carcinoma and benign nodules were studied. Different populations of 50 benign cells and 50 malignant cells were analyzed. Five morphometric parameters were selected for analysis: nuclear area, perimeter, maximum length, maximum width and intensity standard variation. The values obtained for papillary carcinomas were higher than the surrounding benign nodules as follows: nuclear area 63.5 vs. 36.1 (p=0.000), nuclear perimeter were 29.4 vs. 22.0 (p=0.000), maximum length 9.6 vs. 7.1 (p=0.000), maximum width 8.2 vs. 6.3 (p=0.000), the ratio between maximal length and maximal width 1.16 vs. 1.13 (p=0.000), the standard variation of intensity 14.9 vs. 15.9 (p=0.101) respectively. Therefore, morphometric information can be helpful for the differential cytological diagnosis of papillary thyroid carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2175-2178
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• 2012

Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsular or vascular invasion. To date, no reliable and practical method has been introduced to discriminate this malignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrix metalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, have been shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of this study was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine their usefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemically for MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statistical significance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Our results show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirm diagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed to show any differential diagnostic value for caspase-3 in thyroid follicular neoplasms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.707-711
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• 2013

Purpose: To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with a background of benign disease. Method: A total of 709 patients with papillary thyroid carcinoma undergoing surgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroid disease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examination of surgical specimens but were not detected by preoperative imaging studies. In the other group, according to the pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified as concomitant PTC and 309 cases were clarified as dominant PTC. Results: Incidental PTC was more common in women, about 85.7%, the mean age was $47.6{\pm}11.3$ years old. Average tumor diameter was $4.4{\pm}2.2$ mm, multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147). After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), there was no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10 and 14 year respectively. Conclusion: Incidental PTC with a background of benign lesions is common, and the generally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperative finding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, but with a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomy or immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unless lymphadenectasis is present.