• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Korean Journal of Head & Neck Oncology
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• v.34 no.1
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• pp.9-13
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• 2018

Background/Objectives: Brain metastasis (BM) is a rare form of distant metastasis with papillary thyroid cancer (PTC). Patients with BM of PTC carry a poor prognosis. The aim of this study was to contribute to the understanding of this disease by analyzing patients with BM of PTC. Materials & Methods: Between March 2003 and December 2013, the patient database was conducted to identify thyroid cancer patients treated. Among the 22,758 thyroid cancer patients, 14 (0.06 %) were identified to have metastasis to the brain during follow-up. The medical records of 14 patients with BM were retrospectively reviewed, focusing on the following: patient characteristics, synchronous or previous distant metastasis, treatments including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) and surgery, and characteristics on radiologic findings, time interval between first diagnosis of primary thyroid cancer and BM and survival after BM. Results: The mean age at initial diagnosis and BM were $50.9{\pm}15.8years$ and $61.3{\pm}12.7years$. The mean duration between initial diagnosis and BM was $10.4{\pm}7.9years$. Patients were treated with varied combinations of surgery, SRS and WBRT except 4 patients who had refused treatment. The median overall survival (OS) time after BM diagnosis was 10 months (range 1 - 19). Patients receiving treatment (WBRT and/or surgery, SRS) had a significant longer median OS of 16.5 months in comparison to 3.5 months for those treated without treatment. (p = 0.005) Conclusion: Patients who received aggressive treatment had a longer OS than those with only supportive care. Treatment such as surgery, SRS and WBRT should be considered in patients with BM.

• Korean Journal of Head & Neck Oncology
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• v.35 no.2
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• pp.11-17
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• 2019

Background/Objectives: Papillary thyroid carcinoma (PTC) has generally an indolent character with a good prognosis. However, recurrence remains a major concern for the patients during their lifetime. Despite the slowly progressing character of PTC, recurrence can occur within a short period after initial surgery. This study aimed to determine the clinical findings and cause of recurrence in patients who underwent re-operative surgery due to neck node recurrence by reviewing the CT (computed tomographic) scan imaging of the recurrence of PTC retrospectively. Materials & Methods: We reviewed the medical records of patients referred to Ajou University Hospital from January 2002 to January 2018. All patients had re-operative surgery due to neck node recurrence and CT scan results of preoperative evaluation and postoperative follow up. Over this period, 110 patients who underwent re-operation due to neck node recurrence with a CT scan were included in our cohort, resulting in a total of 220 re-operations. Results: The time from initial operation to first re-operation was examined in 110 patients. The median time to re-operation was 28 months, with a range of 4 months to 186 months. Most re-operations (82.7%) occurred within the first five years, 43.6% were in the first two years from the initial surgery. The result of the retrospective CT review showed newly developed cases (21,19.1%), missed diagnosis cases (42,38.2%), real recur cases after surgery (33,30.0%), and remnant lymph nodes (LNs) cases (14,12.7%). We further sub-analyzed 14 cases with remnant LNs. Reasons for remnant LNs included insufficient operation (N=5) and beyond general surgical extent. (N=9). Conclusion: Re-operation due to cervical lymph node recurrence is mostly a persistent disease. They included a missed diagnosis and incomplete operation. These finding may reduce the reoperation of cervical lymph node recurrence by accurate preoperative evaluation and complete surgical resection at the initial surgery.

• Korean Journal of Head & Neck Oncology
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• v.35 no.2
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• pp.19-25
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• 2019

Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

• The Korean Journal of Nuclear Medicine
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• v.16 no.1
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• pp.41-48
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• 1982

113 patients with nodular goiter were studied cytologically by needle aspiration for differential diagnosis at the department of internal medicine, Chung Nam National University Hospital since October 1980 till July 1981, and the final diagnosis taken from biopsies were compared with the cytologic method on the 44 cases who received operation. The results were obtained as follows: 1. Among the 113 cases of total patients, male were 15 cases (13.3%) and female were 98 cases (86.7%) and the sex ratio (M:F) was 1 : 6.5. The peak age incidence was in the third decade followed by forth and second decades. 2. The findings of cytological diagnosis in 113 cases showed benign adenoma in 69 cases (61.1 %), Subacute and chronic thyroiditis in 22 cases(19.5%), papillary carcinoma in 15 cases (13.3%) and follicular carcinoma in 7 cases (6.2%), respectively, and 48 cases (69.6%) of the.adenomas and 2 cases(9.1%) of papillary carcinomas showed combined cystic degeneration of the nodules. 3. The diameter of the nodules by palpation revealed within $2\sim5cm$ in 88 cases (77.9%) out of 113 cases, below 2 cm in 17 cases and over 5cm in 8 cases and there were no significant relationship between the size of the nodule and disease entity. 4. The findings of thyroid scintigram using $^{131}I$ in 113 cases of nodular goiter showed "cold nodule" in 111 cases (98.2%) and normal scan (radioactivity) in 2 cases (1.8%) which showed adenoma in cytology and there was no cases with "hot nodule". 5. The thyroid functions of the 113 cases revealed as euthyroidism in 108 cases (95. 6%), hypothyroidism in 2 cases (1.8%) who showed chronic thyroiditis and hyperthyroidism in 3 cases (2.7%) in adenomas but there was no evidence that the nodules of the above 3 cases were the reason of hyperthyroidism. 6. In 44 operated cases, the histological diagnosis revealed 23 cases of adenoma out of 27 cases(85.2%) who were diagnosed as adenoma by cytology and 15 cases of malignancy out of 17 cases (88.2 %), and the overall diagnostic accuracy of aspiration cytology was 86.4 %.

• The Korean Journal of Nuclear Medicine
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• v.11 no.1
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• pp.49-58
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• 1977

For the assessment of antithyroid effect of lithium carbonate, it was administered to the 17 hyperthyroid and 5 euthyroid patients, who visited the Seoul National University Hospital from Jan. to Aug., 1977. Thyroid function tests were performed just before the administration of Lithium carbonate, 2 weeks and 2 months after lithium treatment. The results were as follows; 1) In the 5 euthyroid patients, no significant changes in thyroid function tests were obtained before and after lithium treatment. 2) In the 17 hyperthyroid patients, the values of the $T_3RIA$ were $370{\pm}121ng/dl$ 2 weeks after lithium treatment as compared with $506{\pm}121ng/dl$ before the administration, of which the mean percentage fall was 26.9%. $T_3RU$ was varied from $56.8{\pm}8.0%\;to\;47.3{\pm}8.1%$ (16.7% in mean percentage fall), $T_4$ was changed from $24.2{\pm}2.4ug/dl\;to\;22.0{\pm}4.2ug/dl$ (9.1% in mean fall), and $T_7$, from $13.82{\pm}2.25\;to\;10.55{\pm}3.12$ (23.7% in mean fall). 3) In the 5 hyperthyroid patients, serial thyroid function tests were performed 2 weeks and 2 months later. The mean percentage falls of $T_3RIA$ were 36.6 and 61.3%, 2 weeks and 2 months after lithium treatment respectively. Those of $T_3RU$ were 17.5 and 35.1%, those of $T_4$ were 20.4 and 44.0%, $T_7$, 35.0 and 60.7%. 4) Approximately $45{\sim}60%$ of mean fall in thyroid function tests were obtained within the second week. Normal thyroid function tests were observed in 2 among 17 patients within the second week, and 2 among 5 patients within the second month. 18 patients, however, became clinically euthyroid within the 4th week. 5) Single case of hypothyroidism was experienced, and 5 patients (29.4%) complained mild side effects. Lithium salts could be safely administered to hyperthyroid patients who are allergic to thioamides or iodine. Its use is indicated in cases of acute thyrotoxicosis in which it's necessary to reduce hormone levels very rapidly, and lithium-thioamides drug combination is a highly effective and safe means of initial routine control of hyperthyroidism.

• The Korean Journal of Nuclear Medicine
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• v.21 no.2
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• pp.133-141
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• 1987

To evaluate the values of the thyroid autoantibody measured by radioimmunoassay (RIA) and compare it with hemagglutination method (HA) in the normal and the thyroid disease, data were obtained from total 618 persons; 236 healthy persons, 217 patients with Graves' disease (including 113 patients with undertreated Graves' disease), 100 Hashimoto's disease, 31 thyroid nodule, and 34 simple goiter. RSR kit made in England was used and could be detected to at least 3 U/ml. The positive rates of normal group were antimicrosomal antibody (AMA) 31.8%, antithyroglobulin antibody (ATA) 44.5% by RIA and there was no considerable change in sex and age distribution. In Graves' disease, the positive rates of AMA and ATA were 90.4, 76.9% by RIA, 85, 39% by HA. In Hashimoto's disease, 94,91 % by RIA, and 87,48% by HA, respectively. The autoantibody titer by RIA in thyroid autoimmune disease as well as in normal group was more senisitive than that by HA, especially in ATA. There were linear relationships between the titer of RIA and that of HA in AMA of Graves' disease and AMA and ATA of Hashimoto's disease. There was no relationship among thyroid autoantibody, free $T_4$ index, TBII, and TSH. The titers of AMA and ATA were found to decrease in patients with Graves' disease during the course of antithyroid drug therapy. Of the 236 normal subjects, thirty-seven (15.7%) had concentrations of above 7.5 U/ml in AMA, forty. four (18.6%) above 9 U/ml in ATA. These values were considered as the upper limit for the normal range. In Graves' disease, 82.7, 53.8% were above 7.5, 9 U/ml, respectively; In Hashimoto's disease, 82, 79% were positive. We conclude that RIA was more sensitve than HA in measuring the thyoird autoantibody, but we will study further more for determining the normal range and its interpretation.

• Korean Journal of Head & Neck Oncology
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• v.13 no.1
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• pp.16-23
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• 1997

Although normal thyroid epithelial cells do not constitutively express HLA-DR antigen, their expression in wide spread within thyroid glands obtained from the human with autoimmune thyroid disease and with many neoplastic thyroids. We have, therefore, studied immunohistochemically with regard to the expression of HLA-DR antigen of thyroidectomy specimens from 50 patients of various thyroid diseases with use of paraffin-embedded tissue. One or two sections from each case were stained with commercially available mouse monoclonal antibody for class II HLA-DR antigen(HLA-DR/Alpha, DAKO) and examined by semiquantitative counting system for thyrocytes, neoplastic thyrocytes and other cells expressing HLA-DR antigen. All patients with lymphocytic thyroiditis(2/2) and diffuse hyperplasia(Graves' disease)(5/5), most patients with Hashimoto's disease(9/ll) expressed HLA-DR antigens in thyrocyte with abundant HLA-DR expressing lymphocytic infiltrates with lymph follicle formation in its vicinity or adjacent to the lesion. Most patients with papillary carcinoma(9/1l) had HLA-DR antigen detected in malignant thyrocytes ; while follicular carcinoma(0/3) and follicular adenoma(0/5) did not have detactable HLA-DR immunoreactivity. Adenomatous goiter(3/7) had HLA-DR antigen detected focally in lesser than half cases. Conversely, in four papillary carcinomas and three adenomatous goiters, HLA-DR expression of thyrocytes was found in the absence of HLA-DR expressing lymphoid infiltrates. In such cases therefore other factors more than thyroid autoimmunity must be causative for HLA-DR immunoreactivity. The results of this study indicate as follows. 1) The expression of HLA-DR on thyrocytes involved in autoimmune reactions appeared to be secondary to cytokine release from associated lymphocytic infiltrates. 2) Thyrocytes in thyroid lesions with equal degrees of lymphocytic infiltration without HLA­DR expression exhibited no HLA-DR immunoreactivity. 3) In neoplastic thyrocytes, most papillary carcinoma(9/11) exhibited detactable HLA-DR expression, while follicular carcinoma/adenoma(0/3/0/5) exhibited no detactable HLA-DR immunoreactivity which suggest the existence of divergent mechanisms inducing and modulating HLA-DR expression of different types of neoplastic thyrocytes.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.41-64
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• 2014

Objectives: This study was to evaluate the effect of Jaeumkanghwa-tang (JEKHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods: Six groups, each of 8 rats per group were used in the present study - intact vehicle control, PTU control, Levothyroxine ($LT_4$), JEKHT 500, 250 and 125 mg/kg treated groups. JEKHT were administered once a day for 42 days as an oral dose of 500, 250 and 125 mg/kg, and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body and organ weight, serum hormone and lipid profiles, liver and testis antioxidant defense factors were observed with histopathology of organs. Results were compared with $LT_4$ 0.5 mg/kg intraperitoneally treated rats in this experiment. Results: PTU treatment, marked decrease of body weight, increases of thyroid weight, decreases of liver, testis, epididymis and prostate weights, decreases of serum Tri-iodothyronine ($T_3$), and Thyroxine ($T_4$) level with increase of serum Thyroid-stimulating hormone (TSH) level, decreases of serum testosterone and dihydrotestosterone (DHT) level with increases of serum Follicular stimulating hormone (FSH) level, increases of serum High density lipoprotein (HDL), decrease of triglyceride content, increase of serum Aspartate aminotransferase (AST) level, decreases of liver and testis antioxidant defense factors were observed. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and diameters was additionally demonstrated with the decrease of hepatocyte numbers per unit area due to hypertrophy of hepatocytes related to lipid droplet depositions, increase of a/oligospermatic epididymal tubules with epididymal atrophic changes, seminiferous tubular atrophy with decrease of stage I~II seminiferous tubules in testis, prostate tubular atrophic changes at histopathological inspections. However, these PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of JEKHT 500, 250 and 125 mg/kg, and JEKHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Conclusions: JEKHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.697-701
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• 2018

Background and Objectives The aim of this study was to evaluate surgical completeness in endoscopic total thyroidectomy with central neck dissection via unilateral axillo-breast approach (UABA) compared with bilateral axillo-breast (BABA) and open approach (OA) by means of the radioactive iodine uptake (RAIU) ratio and thyroglobulin (Tg) of remnant thyroid. Subjects and Method From July 2010 to March 2013, 82 patients who had underwent total thyroidectomy with central neck dissection and postoperative radioactive iodine (RAI) ablation for papillary thyroid carcinoma were enrolled. Of these patients, 27 patients underwent UABA, 24 patients BABA, and 31 patients OA. Clinicopathologic data, surgical outcome, stimulated Tg and RAIU ratio on the first postoperative RAI ablation scan were compared among 3 groups. Results Patients in the endoscopic surgery groups (UABA, BABA) were younger than those in the OA groups. Invasiveness such as operation time, postoperative pain, and drain amount in UABA was less than that in BABA and severer than that in OA. Other variables regarding clinicopathologic and surgical data were not significantly different. Stimulated Tg and RAIU ratio did not show significant differences among 3 groups (p=0.659 and p=0.664). Conclusion The completeness of UABA was comparable with that of BABA and OA. The UABA may be a safe option for patients who need endoscopic thyroidectomy for papillary thyroid carcinoma.