A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol

Background@#Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. @*Methods@#This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. @*Conclusion@#The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol

Background@#Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. @*Methods@#This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. @*Conclusion@#The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Borderline Thyroid Tumors: a Surgeon's Perspectives

Borderline thyroid tumors are composed of hyalinizing trabecular tumor (HTT), well differentiated tumor of uncertain malignant potential (WDT-UMP), follicular tumor of uncertain malignant potential (FT-UMP) and non-invasive follicular tumor with papillary like nuclear feature (NIFTP) by World Health Organization (WHO) definition. They have different pathological feature from each other. However, it is difficult to diagnose with diagnostic imaging, fine needle aspiration (FNA) or core biopsy preoperatively. Thus, the diagnosis is usually made after diagnostic lobectomy. Main surgical concerns about borderline tumor are not performing total thyroidectomy because of relatively indolent nature of these tumors. Unfortunately, some of these tumors can be diagnosed as malignant tumor preoperatively. The other surgical concern is performing completion thyroidectomy or not after diagnostic lobectomy. Decision making is difficult even though it is generally considered that lobectomy alone is enough. In this article, we will discuss clinical features of borderline malignant tumors and surgical strategy for these tumors.

Surgical Treatment Guidelines for Patients with Differentiated Thyroid Cancer: The Korean Association of Thyroid and Endocrine Surgeons (KATES) Guidelines Taskforce / 대한내분비외과학회지

No abstract available.

2016 Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer

No abstract available.

2016 Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer

No abstract available.

Risk Factors for Distant Metastasis in Patients with Follicular Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: The major issue of follicular thyroid carcinoma (FTC) diagnosed after hemithyroidectomy is whether to undergo further treatments. The aim of this study is to examine the clinico-pathological characteristics of FTC and to evaluate the risk factors for distant metastasis. METHODS: From 1993 to 2010, 274 patients underwent initial thyroid surgery and were subsequently diagnosed as FTC. After review of the histological sections by an experienced pathologist, 211 patients were confirmed as FTC and were enrolled in this study. Clinicopathological features were compared based on the presence or absence of distant metastases, and the risk factors for distant metastases and distant metastases-free survival (DMFS) rates were analyzed. RESULTS: The patients included 39 males (18.5%) and 172 females (81.5%), with a mean age of 44.0±14.5 years. The median follow-up period was 99.5 months (range, 13.0~222.0). Distant metastases were detected in 23 patients (10.9%), including 15 synchronous distant metastases and 8 metachronous distant metastases. In multivariate analysis, age ≥45 years, widely invasive FTC, tumor size ≥4.3 cm, and vascular invasion were independent risk factors for distant metastasis. DMFS rates in patients with these risk factors were significantly poorer than those in patients without these risk factors. CONCLUSION: Older age, aggressive histological classification, larger tumor size, and vascular invasion were independent risk factors for distant metastasis. FTC patients with these risk factors may be candidates for further treatments after diagnostic thyroid hemithyroidectomy.

Clinical Meaning of Neutrophil-to-Lymphocyte Ratio (NLR)in Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammatory response, which is inexpensive, easily calculated, and known to show correlation with prognosis of cancer. The aim of this study was to evaluate the relationship between NLR and prognosis of papillary thyroid carcinoma. METHODS: A total of 1,142 patients who underwent total thyroidectomy for papillary thyroid carcinoma between 1995~2005 at Asan Medical Center were enrolled in this study. Patients were categorized according to two groups based on NLR and clinico-pathological variables and disease survival were compared between the two groups. RESULTS: Median age of patients was 45.4 years, and the median follow-up period was 48 months. The cut-off value of NLR for prediction of disease-free survival (DFS) was 2. Comparison of DFS between two groups stratified by NLR (NLR ≤2, NLR>2) showed little statistical difference (P=0.48). After adjusting for risk (N stage), there was no significant difference according to N stage (N0: P=0.86, N1a: P=0.4, N1b: P=0.12). CONCLUSION: NLR did not show correlation with disease free survival of papillary thyroid carcinoma.

The Korean guideline for thyroid cancer screening

Thyroid cancer is the most common malignancy in Korea; in 2012, about 44,000 new cases (19.6% of all malignancies) were registered and the estimated age-standardized incidence rate of thyroid cancer was 73.6 per 100,000 (17.3 and 88.6 per 100,000 in men and women, respectively). Despite the steep increase in its incidence, the age-standardized mortality rate of thyroid cancer has remained stable and 10-year relative survival rate is 99.2%. Increased detection using high-resolution ultrasonography may have contributed to the increased incidence of thyroid cancer if not all. However, the effectiveness of thyroid cancer screening using ultrasonography has not been fully evaluated as to whether screening and early diagnosis could decrease the morbidity or mortality of thyroid cancer. A multidisciplinary expert committee for developing a guideline for thyroid cancer screening was organized and established a recommendation for thyroid cancer screening using ultrasonography in Korea based on scientific evidence for the first time. In conclusion, the current evidence is insufficient to assess the balance of benefits and harms of the thyroid cancer screening by ultrasonography and the recommendation is that thyroid ultrasonography is not routinely recommended for healthy subjects.

Definition and Prognostic Factor of Minimally Invasive Follicular Thyroid Carcinoma / 대한내분비외과학회지

Minimally invasive follicular thyroid carcinoma (MIFTC) is a subtype of follicular thyroid carcinoma. The definition of MIFTC is somewhat confusing; as a result, diagnosis of MIFTC is difficult. MIFTC is known to have an excellent prognosis. Thus, no further treatment is usually required after diagnostic lobectomy. However, some patients with MIFTC experience distant metastasis after initial lobectomy. In this review, we will discuss the definition of MIFTC and risk factors of distant metastasis after initial lobectomy.

Right Paraesophageal Lymph Node Metastasis in Papillary Thyroid Cancer and Prophylactic Dissection: A Retrospective Study / 대한내분비외과학회지

PURPOSE: The purpose of this study is to determine the status of nodal disease, including the right paraesophageal node, in papillary thyroid carcinoma (PTC). METHODS: A total of 116 patients with PTC underwent total thyroidectomy and prophylactic central node dissection, including right paraesophageal lymph nodes (RPE LNs). Metastases to RPELNs were analyzed by site and clinicopathologic variables. Recurrence rate and post-operative complications were also evaluated by comparing the right paraesophageal lymph node dissection (RPE LND) with the non-RPE LND group. RESULTS: Central node metastases were detected in 57 (49.1%) patients; paratracheal and pre-tracheal lymph node metastases, total RPE LN metastases, and metastases only in RPE LN occurred in 50 (43.1%), 18 (15.5%), and 5 (4.3%) patients, respectively. Age, tumor size, tumor longitudinal location, extrathyroidal extension, and multicentricity were insignificant in RPE LN metastasis (P>.05). Although there was no significant statistical difference, tumors with lymphatic invasion and larger tumors (>1 cm) had more frequent RPE LN metastases. RPE LN metastases were frequent in deeply located tumors instead of superficially located tumors (P=0.015). Compared with the non-RPE LND group, the incidence of post-operative complications (transient hypocalcemia and vocal cord palsy) was not significantly different and there was no recurrence in both groups during the follow up period. CONCLUSION: The metastatic rate of the right paraesophageal lymph nodes was 15.5%; 83.3% of these were macrometastatic. Prophylactic RPE dissection compared with the non-RPE LND group, however, did not show a survival difference for 5 years.

Preoperative Serum Thyroglobulin as a Useful Predictive Marker to Differentiate Follicular Thyroid Cancer from Benign Nodules in Indeterminate Nodules

Indeterminate cytology results increase the number of repetitive procedure and unnecessary surgery. This study was designed to find useful and simple predictive tools to differentiate malignant thyroid nodules from indeterminate nodules. We retrospectively enrolled 164 patients who had undergone thyroid surgery as a result of indeterminate cytology in the National Cancer Center. We reviewed patients' age at diagnosis, sex, preoperative biochemical markers such as thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical and pathological findings, which were subjected to statistical analysis. We found several clinical and sonographical predictive factors that showed significant differences. Young age, male, preoperative high Tg level, and hypoechoic nodule on sonography all increased cancer probability significantly in multivariate analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity were 54.8% and 90.1%, respectively (AUC 0.748, P 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg > 70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038). Preoperative Tg levels had very high specificity in predicting thyroid cancer in case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful marker for differentiating thyroid cancer from benign thyroid nodules in the cytological diagnosis of indeterminate nodules.

Gene expression profiling of papillary thyroid carcinomas in Korean patients by oligonucleotide microarrays / 대한외과학회지

PURPOSE: The incidence of papillary thyroid carcinomas (PTCs) is rapidly increasing in Korea. Analyzing the gene expression profiling (GEP) of PTCs will facilitate the advent of new methods in diagnosis, prognostication, and treatment. We performed this study to find the GEP of Korean PTCs. METHODS: We performed oligonucleotide microarray analysis with 19 PTCs and 7 normal thyroid glands. Differentially expressed genes were selected using a t-test (|fold| >3) and adjusted Benjamini-Hochberg false discovery rate P-value < 0.01. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was used to validate microarray data. A classification model was developed by support vector machine (SVM) algorithm to diagnose PTCs based on molecular signatures. RESULTS: We identified 79 differentially expressed genes (70 up-regulated and 9 down-regulated) according to the criteria. QRT-PCR for five genes (CDH3, NGEF, PROS1, TGFA, MET) was confirmatory of the microarray data. Hierarchical cluster analysis and a classification model by the SVM algorithm accurately differentiated PTCs from normal thyroid gland based on GEP. CONCLUSION: A disease classification model showed excellent accuracy in diagnosing PTCs, thus showing the possibility of molecular diagnosis in the future. This GEP could serve as baseline data for further investigation in the management of PTCs based on molecular signatures.

Preoperative Staging of Well-Differentiated Thyroid Carcinoma: Importance of Radiological Imaging / 대한갑상선학회지

Staging is the process of determining how much cancer there is in the body and where it is located. Correct staging helps the oncologist to plan a treatment and determine a prognosis. For the surgeon's perspective, planning of surgical treatment is the main concern in preoperative staging. Preoperative staging would be synonym of "preoperative planning" or "preoperative localization" in this context. Extent of primary tumor and lymph node status is the main factor to decide initial surgical treatment of well-differentiated thyroid carcinomas (WDTC). Precise description of lymph node status is also important in the planning of surgery for WDTC. Surgeon performed preoperative ultrasound is highly recommended in the planning of surgery, especially in recurrent cases. There have been debates for what the best imaging modality is in the preoperative staging of WDTC. Surgeon should understand pros and cons of each modality and should communicate with radiologist to decide surgical plan. In this article, we will discuss importance of radiological imaging in preoperative staging of WDTC.

Comparison of the Results for Sentinel Lymph Node Mapping in the Breast Cancer Patients using 99mTc-Antimony Trisulfide Colloid, 99mTc-Tin Colloid, and 99mTc-Human Serum Albumin / 핵의학분자영상

PURPOSE: In the breast cancer patient, lymphatic mapping and sentinel lymph node biopsy are the most important procedure for axillary lymph node staging. We aimed to compare the three radiocolloids [99mTc-antimony trisulfide colloid (ASC), 99mTc-tin colloid (TC), and 99mTc-human serum albumin (HSA)] for sentinel lymph node mapping. SUBJECTS AND METHODS: Totally, 397 patients with clinically N0 stage were enrolled. 99mTc-ASC was injected in 202 out of 397 patients, 99mTc-TC was injected in 120 patients, and 99mTc-HSA was injected in the remaining 75 patients. The sentinel lymph nodes were localized by lymphoscintigraphy and selected using intraoperative gamma probe. All sentinel lymph nodes were investigated by intraoperative pathologic consultation. The axillary lymph nodes which were harvested by the lymph node dissection were also investigated. RESULTS: The patients of each group showed similar clinical characteristics. There were no significant differences (p>0.05) in the identification rate of sentinel lymph nodes (IR), false negative rate (FNR), and negative predictive value (NPV). The axillary lymphadenectomy revealed axillary lymph node metastases in those three groups (ASC-33.2%, TC-31.7%, HSA-22.7%). The IR, FNR, and NPV were not significantly different among those groups. CONCLUSION: Those three 99mTc-labeled radiocolloids showed equivalent results in sentinel lymph node mapping of breast cancer.

Primary Malignant Teratoma with a Primitive Neuroectodermal Tumor Component in Thyroid Gland: A Case Report

Teratomas comprise the most common extragonadal germ cell tumors in childhood. Most teratomas involving the thyroid are benign and occur in children. However, the adult cases reported are mostly malignant and commonly arise in the thyroid. We report a case of a 31-yr-old female with a huge neck mass. Pathologic examination revealed it to be malignant teratoma composed of primitive neuroepithelial tissue with primitive neural tubes and loose myxoid to fibrous immature mesenchymal stroma. The patient underwent extensive evaluation of the thyroid gland with computed tomography (CT) scan and positron emission tomography (PET) scan, which revealed no evidence of metastatic disease. She underwent total thyroidectomy with bilateral modified radical neck dissection, intensive chemotherapy and radiotherapy. At 22-months of follow-up, the patient has remained euthyroid and showed no evidence of recurrence. This is the first case, to our knowledge, of malignant thyroid teratoma with a exuberant primitive neuroectodermal tumor component in Korea.

Regulation of Sodium-iodine Symporter Expression by Retinoic Acid in Thyroid Cancer Cell Lines / 대한내분비외과학회지

PURPOSE: Response to radioiodine therapy for thyroid cancer is related to the loss of sodium-iodine symporter protein caused by dedifferentiation of thyroid cancer cells. So we aimed to study mRNA expression of CD97, dedifferentiation marker, and sodium-iodine symporter after retinoic acid treatment according to retinoids receptor status. METHODS: Thyroid cancer cell lines; ARO, FRO, NPA, TPO, and FTC133 were prepared. 5µM of all trans retinoic acid were administered to each cell lines and then expression of m RNA for retinoids receptors (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ), CD97, and Sodium-Iodine symporter by RT-PCR. RESULTS: RARs and RXRs were differently expressed in each cell line. After retinoic acid treatment, relative density of retinoic acid receptor mRNA were increased by time dependently in each cell line except TPO cell line. Expression of CD97 also was decreased in every cell lines (P<0.001). Retinoic acid increased expression of sodium-iodine symporter only in FTC133 cell line (P<0.001), and TSH or forskolin did not enhance NIS expression by retinoic acid. RARβ and RXRγ were expressed only in FTC 133cell line before treatment. Induction of sodium-iodine symporter by retinoids disappeared after RARβ specific antagonist LE135 or pan RXR antagonist PA452 administration. CONCLUSION: Retinoic acid reduced expression of CD97 in five thyroid cancer cell lines. However, retinoic acid could restore sodium-iodine symporter expression in only FTC 133 cell line specifically containing RARβ and RXRγ. Restoration of sodium-iodine symporter expression by retinoic acid is related to RARβ and RXRγ expression.

Development of International Medical Teleconference System Using Advanced Research Network and Digital Video Transport System(DVTS) / 대한의료정보학회지

OBJECTIVE: The purpose of this study is to develop telesurgical conference system by establishing a gigabit broad-banded network between hospitals in Korea and Japan using Digital Video Transport System(DVTS) on internet protocol, and to audit performance of this system through questionnaire study. METHODS: The Korea Advanced Research Network(Korean side), the Fukuoka Gigabit Highway(Japanese side), and the Korea-Japan Cable Network(international line)were used for assuring a high speed network connectivity. DVTS streaming was propagated with 30 M bps bandwidth for two channels on IPv4 network. Network security was built with virtual private network solution to guarantee protecting patient's privacy. Technological performance and satisfaction of users were evaluated following the events. RESULTS: The teleconference sessions and live surgery transmission with DVTS on internet protocol using advanced research network were performed successfully. Bandwidth of 60 Mbps for two-line transmission was maintained throughout the conference. The quality of the transmitted pictures had no frame loss with the rate of 30 frames per second. The sound was also clear and the time delay was less than 0.3 sec. Effectiveness of telesurgical conference using advanced network was felt beneficial for 94% of the attendants in questionnaire study. CONCLUSION: Establishing an international telesurgical conference system with high quality digital video transmission over internet protocol using international gigabit network was performed successfully. With the improvement of network engineering, this system is expected to contribute penetration of medical skills and knowledge through network infrastructure.

The Effects of Tibolone in Breast Cancer Cell Lines: The Role of Tibolone in Phospholipase D Signal Transduction Pathway / 한국유방암학회지

PURPOSE: Tibolone is a tissue specific steroid hormone newly recognized as an estrogenic agent for hormone replacement therapy (HRT). The aim of the study is to characterize the basic mechanism of tibolone in the PLD signal transduction pathway of breast cancer cell lines. METHODS: The levels of phospholipase D (PLD), caspase 3 mRNA and protein, and the cell counts were measured in estrogen receptor positive MCF-7 and negative MDA-MB-231 cell lines treated with estradiol, tamoxifen and tibolone and three metabolite forms of tibolone (3 beta-OH-tibolone, delta4 isomer, 3 alpha-OH-tibolone). Multimodality methods such as RT-PCR, immunoblot analysis and in vivo enzyme activity assay were used. RESULTS: The addition of estradiol to MCF-7 cell line resulted in cell proliferation in a time-dependent manner while that of tamoxifen and tibolone showed antiproliferative effects. The addition of tamoxifen or tibolone to MCF-7 and MDA- MB-231 cell lines resulted in the elevation of caspase 3 mRNA levels, indicating the induction of apoptosis. PLD mRNA level was elevated in both cell lines treated with tamoxifen, but decreased in those treated with the various tibolones, except for 3 beta- OH-tibolone. In immunoblot analysis, while MCF-7 cell line treated with tamoxifen showed an increased level of PLD expression, in MDA-MB-231 cell line the expression was decreased. Similar results were observed in the addition of tibolones, which resulted in an increase of PLD expression level in MCF-7 cell line and a decrease in MDA-MB-231 cell line. In vitro PLD activity assay showed decreased activity after estradiol treatment and increased activity after tamoxifen and tibolone treatment in MDA-MB231 cell line. In MCF-7 cell line, among the tibolones only delta4 isomer increased PLD activity. Tiboloneshowed antiproliferative and apoptosis-inducing effects on MCF-7 and MDA-MB-231 cell lines. But its influence on the signal transduction pathway varied slightly between the two cell lines. CONCLUSION: we were able to find the antiestrogenic properties of the estrogenic agent tibolone.

The Investigation of an Age as a Prognostic Factor of Breast Cancer

PURPOSE: It has been known that the prognosis of a young woman's breast cancer is poorer than the other woman. However, the effect of age on the prognosis is not well- defined. We performed this study to investigate age as a prognostic factor of breast cancer. METHODS: A retrospective study was conducted of 1782 breast cancer patients who underwent operations in Department of Surgery, Seoul National University Hospital between January 1981 and December 2000. The patients were divided into two groups: young age (35) groups. Tumor stage, histopathological characteristics (such as histology, nuclear grade, histologic grade, hormonal receptor, etc), overall survival and disease free survival rates were compared between the two groups. RESULTS: The ages ranged from 17 to 88 years. 306 patients (17.3%) were included in the young age group (median age=32 years) and 1, 476 (82.7%) in the old age group (median age=47 years). The median follow-up period was 42 and 51 months in young and old age groups, respectively. Histologically, a medullary carcinoma was more common in the young age group (P=0.000), and a papillary carcinoma in the old age group (P<0.05). Statically, the young age group had more advanced TMN stages (P= 0.033). From log-rank tests, the young age group had poorer overall survival and disease free survival rates (P<0.05, P=0.0002). However, in multivariate analysis, only N stage was a significant independent prognostic factor (P=0.009). CONCLUSION: Our study showed that the young aged patients had a poorer survival rate, but age was not an independent prognostic factor.