Search

Annals of surgical treatment and research 100(3), 127-136 (2021). doi:10.4174/astr.2021.100.3.127, Published by Korean Surgical Society, Seoul

Purpose The aim of this study was to compare the large multi-institutional data of surgical outcomes of bilateral axillo-breast approach (BABA) robotic (RT) and endoscopic thyroidectomy (ET) and to evaluate the merits of robotic thyroidectomy. Methods From 2004 to 2015, 1,029 patients underwent BABA ET, and from 2008 to 2015, 2003 patients underwent BABA RT in 3 large volume centers in Korea. Two groups were retrospectively compared in terms of clinicopathologic characteristics, complications, surgical completeness, and long-term outcomes using propensity score matching analysis. Results Both groups had similar demographic characteristics including age, sex, tumor size, pathologic stage, and hospital stay after matching. Each group had similar rate of transient hypoparathyroidism, however, ET showed significantly higher rate of permanent hypoparathyroidism (ET 5.2% vs. RT 2.3%, P = 0.05), and transient vocal cord palsy (ET 14.4% vs. RT 9.1%, P = 0.006). Total operation time was longer in the ET group irrespective of surgical extents, including lobectomy (P = 0.016), total thyroidectomy (P = 0.031), and total thyroidectomy with central lymph node dissection (P = 0.019). The rate of patients with off-Tg under 1.0 ng/mL after 1st ablation was significantly higher in RT than ET group (ET 64.6% vs. RT 92.7%, P < 0.001). In long-term follow-up of cancer patients, 1.4% experienced recurrence after ET (10 cases), while 0.3% cases experienced recurrence after RT (5 cases) (P < 0.001). Conclusion Both ET and RT can be safe and effective methods to treat thyroid diseases. However, the application of robotic system may help to overcome the limitations of the instruments and surgeon's skills.

The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC).We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors.This was a retrospective analysis from 1982 to 2012.Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012).These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin.Mean tumour size (from 2·5 cm to 1·7 cm, P0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po-BCR) increased with time (from 39·6% to 76·1%, P0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po-BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14-472·11; P0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size2 cm (HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality.Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival.

Introduction During examination of the vocal cords (VC) using transcutaneous laryngeal ultrasonography (TLUSG), 3 sonographic landmarks (namely, false VC [FC], true VC [TC], and arytenoids [AR]) are often seen. However, it remains unclear which landmark provides a more reliable assessment and whether seeing more landmarks improves the diagnostic accuracy and reliability. Methods We evaluated prospectively 245 patients from 2 centers. One assessor from each center performed all TLUSG examinations and their findings were validated by direct laryngoscopy. All 3 sonographic landmarks were routinely visualized whenever possible. The rate of visualization and diagnostic accuracy between the 3 landmarks were compared. Results Eighteen patients suffered postoperative VC palsy (VCP). Both centers had comparable visualization or assessability rate of ≥1 sonographic landmark (94.9 and 95.3%; P = 1.000) and 100% sensitivity on postoperative TLUSG. The rates of FC, TC, and AR visualization were 92.7%, 36.7%, and 89.8%, respectively. The sensitivity, specificity, and diagnostic accuracy and the proportion of true positives, false positives, and true negatives between using 1, 2, landmarks and 3 landmarks were comparable (P > .05). Conclusion Each sonographic landmark had similar reliability and diagnostic accuracy. Identifying all 3 sonographic landmarks was not mandatory and visualizing normal movement in one of the sonographic landmarks would be sufficient to exclude VCP.

Thyroid cancer has increased globally, with a prominent increase in small, papillary thyroid cancers (PTC). The Korean population has a high iodine intake, high prevalence of BRAF V600E mutations, and family histories of thyroid cancer. We examined the clinicopathological characteristics and outcomes of thyroid cancers in Korean patients over four decades.The medical records of 4500 thyroid cancer patients, between 1962 and 2009 at a single center, including 3147 PTC patients, were reviewed.The mean age of the patients was 46.8±13.2 years; women accounted for 82.9% of the patients, and the median follow-up duration was 4.8 years (mean 7.0±5.8 years, range 1-43 years). The number of patients visiting the clinic increased from 411 during 1962-1990 to 2900 during 2000-2009. Age at diagnosis increased from 39.6±12.9 to 48.6±12.4 years. The male to female ratio increased from 1:6 to 1:4.5. The proportion of small (1 cm) tumors increased from 6.1% to 43.1%, and the proportion of cancers with lymph node (LN) involvement or extrathyroidal extension (ETE) decreased from 76.4% to 44.4% and from 65.5% to 54.8% respectively. Although there were decreases in the proportion of LN involvement and ETE, these decreasing rates were not proportional to the expected rates based on the decreased proportion of large tumors. The overall recurrence and mortality rates were 13.3% and 1.4%. The five-year recurrence rate significantly decreased (from 11% to 5.9%), and the five-year mortality also improved (from 1.5% to 0.2%).The incidence of thyroid cancer has rapidly increased, with a decrease in tumors of large size, LN involvement, and ETE, although the decreasing rates of LN involvement and ETE were not as prominent as decreasing rates of large size tumors. The mortality and recurrence rates have also decreased. Future long-term follow-up of patients diagnosed in the most recent decade is needed to confirm the prognostic characteristics of Korean PTC patients.

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms.

Free radicals induced by cigarette smoking have been strongly linked to increased oxidative stress in vivo, contributing to the pathobiology of various diseases. This study was performed to investigate the effects of Haematococcus astaxanthin (ASX), which has been known to be a potent antioxidant, on oxidative stress in smokers. Thirty-nine heavy smokers (≥20 cigarettes/day) and 39 non-smokers were enrolled in this study. Smokers were randomly divided into three dosage groups to receive ASX at doses of 5, 20, or 40 mg (n=13, each) once daily for 3 weeks. Oxidative stress biomarkers such as malondialdehyde, isoprostane, superoxide dismutase, and total antioxidant capacity, and ASX levels in plasma were measured at baseline and after 1, 2, and 3 weeks of treatment. Compared with baseline, the plasma malondialdehyde and isoprostane levels decreased, whereas superoxide dismutase level and total antioxidant capacity increased in all ASX intervention groups over the 3-week period. In particular, isoprostane levels showed a significant dose-dependent decrease after ASX intake. The results suggest that ASX supplementation might prevent oxidative damage in smokers by suppressing lipid peroxidation and stimulating the activity of the antioxidant system in smokers.

BACKGROUND: The effects of the BRAFV600E mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta-analysis to assess the strength of associations between these conditions and the BRAFV600E mutation. METHODS: The authors identified the clinical studies that examined the association of the BRAFV600E mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty-one relevant studies were hand-searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model. RESULTS: The average prevalence rate of the BRAFV600E mutation was 49.4%. In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAFV600E mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14-fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The associations were generally consistent across the different study populations. CONCLUSIONS: This meta-analysis demonstrates that the BRAFV600E mutation is closely related to the high-risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAFV600E mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients. Cancer 2012;. © 2011 American Cancer Society.

목적：일차성, 이차성, 삼차성 부갑상선 기능 항진증은 각각 원인과 치료방법 그리고 임상 경과가 서로 다르지만 부갑상선 절제술이 표준치료로 알려져 있다. 본 연구에서는 각각의 부갑상선 항진증의 수술 전후의 임상적 변화를 알아보고 부갑상선 절제술의 의미를 재고 해보고자 하였다. 방법：1996년부터 2009년까지 총 126명이 서울대학교 병원에서 부갑상선 절제술을 시행 받았으며 각각 일차성 96명, 이차성 24명, 삼차성 6명이었다. 환자들의 나이, 성별, 생화학적 검사, 수술방법, 병리학적 검사 결과를 전자 의무기록을 통해 후향적으로 분석하였다. 결과：모든 세 군의 환자에서 혈청 칼슘, 부갑상선 호르몬, 이온화 칼슘이 수술 전보다 호전을 보였다. 이차성 환자군은 다른 두 군에 비해 수술 전, 후의 부갑상선 호르몬이 높았으며(p 결론：부갑상선 절제술은 생화학 검사상의 호전을 위한 치료 방법으로 추천될 수 있으며, 이차성에서는 제한적 절제를 하는 경우 지속적 부갑상선 항진증의 빈도가 더 높으므로 부갑상선 아전 및 전 절제술을 시행해야 한다.

The majority of patients having a diagnosis of Hürthle cell neoplasm (HCN) on fine-needle aspiration (FNA) of a thyroid nodule have a diagnostic thyroid lobectomy to make the final diagnosis. If the nodule is malignant, they require a completion thyroidectomy. The objective of this study was to devise a simple clinical scheme capable of predicting malignancy in patients with cytologic diagnosis of HCN and, therefore, guide the extent of initial thyroid surgery.A total of 57 patients who underwent thyroid surgery after an FNA diagnosis of HCN were retrospectively studied. The patients were examined for clinical features, preoperative imaging studies, and pathology reports. The risk of malignancy was calculated using a multiple logistic regression model.The overall rate of malignancy in patients with HCN was 46% (26/57). The predictors of malignancy based on multiple logistic regression analysis were tumor size1.5 cm (odds ratio [95% confidence interval] = 8.0 [1.9-33.4]) and patient age45 years (odds ratio [95% confidence interval] = 2.3 [0.6-8.6]). In patients with nodules larger than 1.5 cm, the predicted probability of malignancy was greater in patients over 45 years than in younger patients (65% for45 years vs. 44% for ≤45 years). In patients with a nodule 1.5 cm or less, the probability of malignancy was relatively low and not significantly different between the two age categories (18% for45 years vs. 10% for ≤45 years).This study suggests that tumor size and age can be integrated into decision making for patients with an FNA diagnosis of HCN to facilitate patient selection for surgical referral and, particularly, to determine in which patients a thyroidectomy rather than a lobectomy should be the initial surgery.

The detection of papillary microcarcinomas of the thyroid is increasing due to frequent use of ultrasound and fine-needle aspiration biopsy. Although most of the papillary microcarcinomas remain quiescent and follow an indolent clinical course, some behave aggressively and metastasize early, giving rise to clinically significant disease. There have been few studies concerning factors predictive of lymph node metastasis in papillary microcarcinomas. We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (>or=5 vs

Background. Fine-needle aspiration cytology (FNAC) is diagnostic standard for thyroid nodules. However, the influence of size on FNAC accuracy remains unclear especially in too small or too large thyroid nodules. The objective of this retrospective cohort study was to investigate the effect of nodule size on FNAC accuracy. Methods. All consecutive patients who underwent thyroidectomy for nodules in 2010 were enrolled. FNAC results (according to the Bethesda system) were compared to pathological diagnosis. The nodules were categorized into groups A–E on the basis of maximal diameter on ultrasound (≤0.5, >0.5–1, >1-2, >2–4, and >4 cm, resp.). Results. There were 502 cases with 690 nodules. Overall FNAC sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.4%, 98.2%, 99.4%, 86.4%, and 96.0%, respectively. False-negative rates (FNRs) of groups A–E were 3.2%, 5.1%, 1.3%, 13.3%, and 50%, respectively. Accuracy rates of groups A–E were 96.8%, 94.8%, 99%, 94.7%, and 87.5%, respectively. Conclusion. Although accuracy rates of FNAC in thyroid nodules smaller than 0.5 cm are comparable to the other group, thyroid nodules larger than 4 cm with benign cytology carry a higher risk of malignancy, which suggest that those should be considered for intensive follow-up or repeated biopsy.

Context: Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. Objective: This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. Design: This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. Patients: A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. Main Outcome Measure: Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. Results: RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22–1.06) when a 2-year latency period was accounted for. High-dose RAI (≥120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05–0.62) in the cohort with a 2-year latency period. Conclusions: The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer.

BACKGROUND Using the new 2003 American Joint Committee on Cancer (AJCC) staging system, the authors evaluated the usefulness of the staging bone scan in patients with primary breast carcinoma. METHODS The authors examined 1939 patients with primary breast carcinoma for staging bone scan who were treated at a single institution. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging systems. RESULTS Bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of 154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with Stage IIIB disease according to the 1988 AJCC staging system. The authors found a significant difference in the bone metastasis rate between patients with Stages IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the patients by the 2003 system resulted in significant upstaging, especially for patients with Stage II/III disease. According to the 2003 staging system, bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4 of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2 of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients with Stage IIIC disease. It was noteworthy that there was a significant difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010). CONCLUSIONS Stage reclassification using the new AJCC staging system resulted in upstaging of high-risk patients, as well as a significant decrease in the bone metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost-effectiveness of staging bone scan, the data suggested that it was of little value for patients with Stage I and II breast carcinoma, but was highly recommended for patients with worse than Stage III disease by the new 2003 staging system. Cancer 2005. © 2005 American Cancer Society.

ObjectiveWith the recent increasing rates of screening for thyroid cancer, the cancers now tend to be smaller and less aggressive than those that are diagnosed when presented with symptoms, suggesting changes in the clinical validity of conventional prognostic factors for outcomes. We performed the retrospective study to identify the secular trends in the prognostic factors of thyroid cancer.MethodsWe used medical records of 3147 patients diagnosed with papillary thyroid cancer (PTC) at the Seoul National University Hospital Thyroid Cancer Clinic between 1962 and 2009.ResultsDuring the median 5.1-year follow-up, the overall recurrence rate was 13.3%, and male sex, tumor size, lymph node (LN) involvement, and extrathyroidal extension (ETE) were the significant prognostic factors for recurrence. Thyroid cancer-specific mortality was 1.4%, and the associated prognostic factors were older age, male sex, and LN involvement. For tumor recurrence, the hazard ratio (HR) for male sex decreased from 2.809 (95% CI, 1.497–5.269) in the pre-1989 period to 1.142 (95% CI, 0.736–1.772) in the post-1999 period. The pathologic characteristics, such as tumor size, LN involvement, and ETE, showed similar or increasing HRs over the time periods. For cancer-specific mortality, the HR for male sex decreased from 6.460 (95% CI, 1.714–24.348) in the pre-1990 period to 0.781 (95% CI, 0.083–7.379) in the post-1999 period.ConclusionThe risk for poor outcomes in PTC associated with male sex decreased over time; in contrast, the risk associated with pathologic characteristics remained the same or increased over time. These trends might be associated with recent changes in the characteristics of patients with thyroid cancer.

Utilizing BRAFV600E mutation as a marker may reduce unnecessary prophylactic central neck dissection (pCND) in clinically nodal negative (cN0) neck for small (≤2 cm) classical papillary thyroid carcinoma (PTC). We aimed to assess whether BRAF is a significant independent predictor of occult central nodal metastasis (CNM) and its contribution to the overall prediction after adjusting for other significant preoperative clinical factors in small PTC. Primary tumor tissue (paraffin-embedded) from 845 patients with small classical cN0 PTC who underwent pCND was tested for BRAF mutation. Clinicopathologic factors were compared between those with and without BRAF. BRAF was evaluated to see if it was an independent factor for CNM. Prediction scores were generated using logistic regression models and their predictability was measured by the area under the ROC curve (AUC). The prevalence of BRAF was 628/845 (74.3%) while the rate of CNM was 285/845 (33.7%). Male sex (odds ratio (OR): 2.68, 95% CI: 1.71–4.20), large tumor size (OR: 2.68, 95% CI: 1.80–4.00), multifocality (OR: 1.49, 95% CI: 1.07–2.09), lymphovascular permeation (OR: 10.40, 95% CI: 5.18–20.88), and BRAF (OR: 1.65, 95% CI: 1.10–2.46) were significant independent predictors of CNM, while coexisting Hashimoto's thyroiditis (OR: 0.56, 95% CI: 0.40–0.80) was an independent protective factor. The AUC for prediction score based on tumor size and male sex was similar to that of prediction score based on tumor size, male sex, and BRAF status (0.68 vs 0.69, P=0.60). Although BRAF was an independent predictor of CNM, knowing its status did not substantially improve the overall prediction. A simpler prediction score based on male sex and tumor size might be sufficient.

Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the standard method for resecting benign adrenal gland tumors. Recently, however, laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular as an alternative method. This systematic review evaluates current evidence on adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic adrenalectomy with robotic adrenalectomy.Methods. PubMed, Embase, and ISI Web of Knowledge databases were searched systematically for studies comparing surgical outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic adrenalectomy. The studies were evaluated according to the PRISMA statement.Results. Eight studies comparing laparoscopic PRA and LTA showed that laparoscopic PRA was superior or at least comparable to laparoscopic LTA in operation time, blood loss, pain score, hospital stay, and return to normal activity. Conversion rates and complication rates were similar. Six studies comparing robotic and laparoscopic adrenalectomy found that outcomes and complications were similar.Conclusion. Laparoscopic PRA was more effective than LTA, especially in reducing operation time and hospital stay, but there was no evidence showing that robotic adrenalectomy was superior to laparoscopic adrenalectomy. Cost reductions and further technical advances are needed for wider application of robotic adrenalectomy.

Purpose: To evaluate the antiadhesive effects and safety of an oxidized regenerated cellulose (Interceed) after thyroidectomy. Methods: Seventy-six thyroidectomized patients were prospectively randomized into two groups with regard to the use of Interceed. We evaluated each group for their adhesive symptoms using four subjective and four objective items at the 2nd week, 3rd and 6th month after thyroidectomy. All patients were examined for vocal cord motility by indirect laryngoscope at each period. Results: Total adhesion scores at each postoperative follow-up period decreased with time, but were not significantly different in each group. The median score for swallowing discomfort for liquid was significantly lower in the Interceed group than in the control group 2 weeks after surgery. In addition, the severity of skin adhesion to the trachea was reduced in the Interceed group compared with the control group 6 months after surgery. During the study, there were no adverse effects or significant differences in postoperative complications between the groups. Conclusion: Interceed appeared to be safe and effective in improving neck discomfort at early postoperative periods and preventing skin adhesion to the trachea 6 months after thyroidectomy.

Various energy devices had been used in thyroid surgery. Aim of study is to develop canine model for recurrent laryngeal nerve injury by harmonic scalpel and to evaluate feasibility of using this model for evaluating the safety use of harmonic scalpel during thyroid surgery. Nine dogs were divided into 3 groups according to distance between harmonic scalpel application and recurrent laryngeal nerve; group 1 (1 mm), 2 (2 mm), and 3 (3 mm). Vocal cord function was assessed pre- and postoperatively using video laryngoscopy. Harmonic scalpel was applied adjacent to left recurrent laryngeal nerve and, two weeks later, right recurrent laryngeal nerve at assigned distances. Recurrent laryngeal nerves were evaluated for subacute and acute morphologic changes. Laryngoscopy demonstrated 3 abnormal vocal cords in group 1, 1 in group 2, and no in group 3 (P=0.020). Subacute histologic changes were observed in nerves with abnormal function. Acute histologic changes were observed 5/8 (62.5%) in group 1, 1/7 (14.3%) in group 2, and not in group 3. We developed canine model for recurrent laryngeal injury. The functional outcomes matched with the histologic changes. These warrant further study to determine the safety margin for energy device in vicinity of recurrent laryngeal nerve.

Purpose: Thyroid cancer is the most common malignancy in Korean females and can be treated with good prognosis. However, drugs to treat aggressive types of thyroid cancer such as poorly differentiated or anaplastic thyroid cancer have not yet been established. To that end, we analyzed the effects of berberine on human thyroid cancer cell lines to determine whether this compound is useful in the treatment of aggressive thyroid cancer. Materials and Methods: The two thyroid cancer cell lines 8505C and TPC1, under adherent culture conditions, were treated with berberine and analyzed for changes in cell growth, cell cycle duration, and degree of apoptosis. Results: Following berberine treatment, both cell lines showed a dose-dependent reduction in growth rate. 8505C cells showed signifi cantly increased levels of apoptosis following berberine treatment, whereas TPC1 cells showed cell cycle arrest at the G0/G1 phase. Immunobloting of p-27 expression following berberine treatment showed that berberine induced a little up-regulation of p-27 in 8505c cells but relatively high up-regulation of p-27 in TPC1 cells. Conclusion: These results suggest that berberine treatment of thyroid cancer can inhibit proliferation through apoptosis and/or cell cycle arrest. Thus, berberine may be a novel anticancer drug for the treatment of poorly differentiated or anaplastic thyroid cancer.

We investigated the combined effect of glutamine (GLN) and growth hormone (GH) on bacterial translocation (BT) in sepsis. After single intraperitoneal injection of lipopolysaccharide (10 mg/kg), 48 rats were divided randomly into four groups of 12 animals each: the control group received chow orally; the GLN group received chow plus 10% GLN; GH group received chow plus GH; and the GLN/GH group received chow, 10% GLN, and GH. Twenty-four and 96 hr later, rats were sacrificed. Portal blood culture, bacterial colony counts of cultured mesenteric lymph nodes, mucosal thickness, malondialdehyde (MDA), and glutathione (GSH) levels in the gut mucosa were measured. There was no significant change of the rate of portal blood culture between all treatment groups at 24 and 96 hr. At 24 hr, the rats receiving combined treatment of GLN and GH showed lower bacterial colony counts and mucosal MDA levels than the control rats, and higher mucosal GSH levels than the control and GLN-treated rats. At 96 hr, rats treated with both GLN and GH exhibited lower bacterial colony counts and mucosal MDA levels, and higher mucosal thickness and GSH levels than control, GLN, or GH-treated rats. This study suggests that the combination of GLN and GH may synergistically reduce BT over time in sepsis.

Introduction Thyroid cancer incidence in Korea is the highest in the world and has recently increased steeply. However, factors contributing to this sudden increase have not been fully elucidated, and few studies have explored the postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was initiated with three aims: (1) to identify factors predicting quality of life, recurrence, and incidence of other diseases after thyroid cancer treatments; (2) to investigate environmental exposure to radiation, toxicants and molecular factors in relation to tumour aggressiveness; and (3) to evaluate gene–environment interactions that increase thyroid cancer in comparison with healthy participants from a pool of nationwide population-based healthy examinees. Methods and analysis T-CALOS enrols patients with incident thyroid cancer from three general hospitals, Seoul National University Hospital, Seoul National University Bundang Hospital and National Medical Center, Korea. The study is an ongoing project expecting to investigate 5000 patients with thyroid cancer up until 2017. Healthy examinees with a normal thyroid confirmed by sonography have been enrolled at the Healthy Examination Center at Seoul National University Hospital. We are also performing individual matching using two nationwide databases that are open to the public. Follow-up information is obtained at patients’ clinical visits and by linkage to the national database. For statistical analysis, we will use conditional logistic regression models and a Cox proportional hazard regression model. A number of stratifications and sensitivity analyses will be performed to confirm the results. Ethics and dissemination Based on a large sample size, a prospective study design, comprehensive data collection and biobank, T-CALOS has been independently peer-reviewed and approved by the three hospitals and two funding sources (National Research Foundation of Korea and Korean Foundation for Cancer Research). The results of T-CALOS will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

Purpose: The aim of this study was to evaluate the feasibility of monitoring external branch of the superior laryngeal nerve (EBSLN) during robotic thyroid surgery. Methods: A total of 10 patients undergoing bilateral axillo-breast approach (BABA) robotic thyroid surgery were enrolled. The nerve integrity monitor (NIM Response 2.0 System) was used for EBSLN monitoring. We performed voice assessments preoperatively and at 1 and 3 months postoperatively using Voice Handicap Index-10 (VHI-10), maximal phonation time (MPT), phonation efficient index (PEI), and laryngeal electromyography (EMG). Results: A total of 19 EBSLNs were at risk and 14 EBSLNs (73.7%) were identified using neuromonitoring. VHI-10 showed a change of voice over time (0.1 vs. 3.6 vs. 1.3); however, this was not statistically significant. VHI-10 scores normalized at 3 months postoperatively compared to the preoperative scores. MPT (a) (16.0 vs. 15.6 vs. 15.4), and MPT (e) (20.1 vs. 15.4 vs. 18.5) showed no significant differences preoperatively compared to the values obtained 1 and 3 months postoperatively. There was a significant change of PEI over time (4.8 vs. 1.1 vs. 4.6) (P = 0.036); however, the values normalized at 3 months postoperatively. Laryngeal EMG results showed 4 cases (21.2%) of neuropathy of EBSLNs at 1 month postoperatively, and electrodiagnostic studies revealed nearly complete recovery of the function of EBSLNs in 4 patients at 3 months postoperatively. Conclusion: It is suggested that neuromonitoring of EBSLNs during BABA robotic thyroid surgery is feasible and might be helpful to preserve voice quality.

Purpose: Surgical excision is the definitive treatment for localized recurrence of papillary thyroid carcinoma. Reoperation for recurrence, however, is challenging and associated with increased operative times and complication rates. For safe and effective reoperation, ultrasound-guided charcoal tattooing localization can be used. The aim of this study was to investigate the feasibility and safety of the ultrasound-guided charcoal tattooing localization. Methods: Between November 2012 and August 2013, ten patients underwent preoperative charcoal tattooing localization for twelve recurrent lesions. Patient demographics, pathologic features, and operation results were reviewed. Results: The technical success rate of charcoal tattooing was 100%. Eight patients had one recurrent lesion, and two patients had double lesions. Among these 12 recurrent lesions, three (25%) were found in level II, four (33%) in level IV, four (33%) in level VI, and one (8%) was found in the thyroidectomy bed site. The mean size of lesions was 0.87 ± 0.35 cm. Of these 10 patients, eight patients underwent selective lymph node dissection, one patient underwent modified radical neck dissection, and one patient underwent recurrent mass excision. Transient hypocalcemia developed in one patient, and no recurrent laryngeal nerve palsy occurred. There were no major complications related to the injection of the charcoal. The mean follow-up period after reoperation was 8.6 ± 2.7 months; in the follow-up ultrasound, there were no remnant lesions in all patients. Conclusion: Preoperative ultrasound-guided charcoal tattooing localization for recurrent thyroid cancer appears to be a feasible and safe procedure for reoperation. Further evaluation is warranted in larger patients" cohorts.

Multiple endocrine neoplasia type 2 (MEN2) syndromes are inherited in an autosomal dominant fashion with high penetrance. There are three subtypes, namely, MEN2A (multiple endocrine neoplasia type 2A), MEN2B (multiple endocrine neoplasia type 2B), and familial medullary thyroid carcinoma. The variations in the RET gene play an important role in the MEN2 syndromes. In this work, we have developed a RET oligonucleotide microarray of 67 oligonucleotides to quickly detect RET mutations in MEN2 syndromes. The predominant RET mutations are missense mutations and are restricted to nine codons (codons 609, 611, 618, 620, 630, 634, 768, 804, and 918) in MEN2 syndromes. Missense mutations at codons 609, 611, 618, 620, and 634 have been identified in 98% of MEN2A families and in 85% of familial medullary thyroid carcinoma families. More than 95% of MEN2B patients also had a predominant mutation type at codon 918 (Met--Thr). RET oligonucleotide microarray can detect RET missense mutations at these nine codons. Theoretically, a total of 55 missense mutation types can occur at eight codons (codons 609, 611, 618, 620, 630, 634, 768, and 804). RET oligonucleotide microarray is designed to detect all of these 55 missense mutation types at these eight codons and one predominant type at codon 918. Fifty-six oligonucleotides were designed for the 56 mutation types at nine codons, and 11 oligonucleotides were designed for the wild types and positive controls. We found RET mutations in all eight of the Korean MEN2A families (a total of 75 members; 27 affected members, 19 gene carriers, and 29 unaffected members) using the developed RET oligonucleotide microarray and an automatic sequencing. Because we found only five mutation types from eight MEN2A families, the international collaborations are required to see whether the RET oligonucleotide microarray may be used as a genetic diagnostic tool. Taken together, the RET oligonucleotide microarray can function as a fast and reliable genetic diagnostic device, which simplifies the process of detecting RET mutations.

BACKGROUND: Incidence of thyroid cancer has been rapidly increased, in not only small sizes with improved detection devices but also large size of tumors whose underlying mechanisms remain unclear. Body size and weight change in adulthood were examined as the potential risk factors for thyroid cancer development. METHODS: A large scale case-control study was conducted with constructed questionnaire for their height, weight (current, 2 years ago, at the age of 20 and 35 years old) and confounders. Medical charts were reviewed for cancer histology, tumor aggressiveness and BRAF mutation status. A total of 2,003 cases (1,611 females and 392 males) and individually matched 17,700 controls (13,983 females and 3,717 males) by age, sex, 12-year education and birth year were included. Logistic regression model were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Having a tall height and heavy weight was associated with increased risk in both females [OR and 95%CI for height and weight: 1.46 (1.25-1.71) and 2.66 (2.24-3.15), respectably] and males [OR and 95%CI for height and weight: 1.71 (1.25-2.34) and 2.80 (2.00-3.92), respectably] compared to those in the lowest quartile for the body sizes. This study observed approximated tripled the risk of thyroid cancer [OR and 95%CI: 3.03 (2.10-4.37)] when female subjects gained 10kg or more within recent 2 years. Males who gained 10 kg or more after 35 years old were more likely to have a greater tumor size [ CONCLUSION: The results support plausible hormonal and metabolic factors related height, weight, and rapid weight gain in adulthood increase thyroid carcinogenesis. Citation Format: Yunji Hwang, Kyu-Eun Lee, Young Joo Park, Do Joon Park, Yeo-Kyu Youn, Yohwan Yeo, Seung-Hyun Ma, Daehee Kang, Keun-Young Yoo, Sue K. Park. Height, weight and weight changes during adulthood and thyroid cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2163. doi:10.1158/1538-7445.AM2014-2163

Received January 15, 2014 / Revised May 10, 2014 / Accepted May 20, 2014 Correspondence: Kyu Eun Lee, MD, PhD, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2018, Fax: 82-2-766-3975, E-mail: kyulee@medimail.co.kr This study was supported by the Seoul National University Hospital Research Fund (Grant Number 04-2013-0070).

Purpose To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). Materials and Methods We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. Results The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. Conclusion Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

Purpose: A number of researchers have suggested the use of sodium hyaluronate carboxymethyl cellulose (HA-CMC) membrane for preventing postoperative adhesion. This study evaluated the antiadhesive effect and safety of HA-CMC membrane in thyroidectomy for papillary thyroid cancer. Methods: One hundred sixty-two patients who underwent thyroidectomy were prospectively randomized. In the study group of 80 patients, the 7.5 cm × 13 cm HA-CMC membrane was applied to the operative field after thyroidectomy. The subjects were asked about complications including adhesive symptoms using an 8-item questionnaire at 2 weeks, 3 months, and 6 months after surgery. In addition, items on the appearance of neck wrinkles and scars were evaluated by a physician who had no information about the patient’s allocation. Results: There were no significant differences in complications such as swallowing difficulty, and wrinkles between study and control groups. Both groups presented significantly decreased scores over time in swallowing difficulty, and wrinkles. There were no complications regarding the HA-CMC membrane. Conclusion: The antiadhesive effect of HA-CMC membrane in thyroid surgery is still uncertain, although it is biologically safe. Further investigation is needed to confirm the antiadhesive effect of HA-CMC membrane in thyroid surgery.

A regionalization strategy is a model for improving the performance of the emergency medical service (EMS) system. The regionalization strategy has goals to provide appropriate, timely, effective, and efficient EMS in a region. However, the current EMS regionalization model in Korea is insufficient to achieve these goals due to a shortage of resources in rural regions, crowded emergency departments in metropolitan regions, and non-customized and mismatched levels of emergency departments. Recently, the concept of the regionalization model has been changed from a general regionalized model to a specialty care regionalization one. For example, the trauma care system, cardiac arrest care system, stroke care system, and ST elevation myocardial infarction care system are modern regionalization strategies to improve the performance of EMS. This is a new method of customizing and matching between region-based needs and the supply of EMS. If we can implement this strategy, we can expect improved performance of regional EMS systems.

We are presenting perspectives of how thyroid surgery has evolved from the past to the future. Technological process in thyroid surgery is the history of modern surgery and the evolution of knowledge of thyroid gland led us to the fields of organ preservation, hemostasis, cancer surgery, and minimally invasive surgery. Thyroid surgery in the present time is characterized by low mortality rate, low complication rate, and considerations about the quality of life of patients. Robotic surgery has been adopted to thyroid surgery for these reasons and now has advanced significantly to perform safe and effective operations. The future of thyroid surgery will be evolved beyond our imagination; however the advances of the skills should be focused on the safety and convenience of patients.

Purpose: Anaplastic thyroid cancer (ATC) is rare and has a poor prognosis. The aim of this study was to analyze the clinicopathologic characteristics of patients diagnosed with ATC expected to undergo curative thyroidectomy, with the goal of finding differences between patients surviving ≥6 months and ＜6 months. Methods: From 1981 to 2010, 24 patients underwent thyroidectomy due to ATC. Among those patients, 12 suspected of distant metastasis preoperatively were excluded. The remaining 12 patients were analyzed by retrospective review of electronic medical records. Results: Median age was 55 years, and the male to female ratio was 1:5. All patients presented with neck mass at initial diagnosis. Five patients lived ＜6 months and seven patients lived ≥6 months after operation. In patients surviving ≥6 months, all lesions were ＜5 cm and all patients underwent total thyroidectomy. In patients surviving ＜6 months, two of the four lesions were ＞5 cm, and two of the five patients underwent less than total thyroidectomy (P = 0.287 and 0.152, respectively). All patients with lesion size ＜5 cm underwent total thyroidectomy and showed a shorter median operation time (P = 0.182 and 0.033, respectively). Conclusion: ATC showed female predominance. Patients initially presented with neck mass, and median age was 55 years. In patients with ATC who are expected to undergo curative thyroidectomy, surgery should actively be considered as primary therapy for patient survival when the size is ＜5 cm.

Thank you for your pointing out some potential discrepancy that some well known thyroid cancer cell lines are not derived from thyroid cell origin in our recent study (1). Schweppe et al. (2) evaluated 40 reported thyroid cancer-derived cell lines using short tandem repeat (STR) and single nucleotide polymorphism (SNP) array analysis. They found some misidentified cell lines in August 2008; the ARO matched the HT-29 colon cancer cell line, and the NPA matched the the M14/MD-MB-435S melanoma cell line (2). In this report, they already admitted that STR or SNP profiling did not provide any information regarding tissue origin and the result of their study was due to cross-contamination of cell lines. Actually we started our study from 2004, four years earlier that the submission date of paper from Schweppe et al. and thyroid cancer cell lines (NPA, FRO, ARO) were kindly donated by Dr. Shong, who reported several good articles using these undifferentiated, anaplastic thyroid cancer cell lines which are his major concern of interest (3). We did not deal with cancer cell lines other than F9, thyroid cancer cell lines at that time. Therefore, we thought that our cells were not cross-contaminated with cancer cell lines derived from other cell origin. In the article of Scheweppe et al. (2), they reported that NPA was identical to M14 cell line and MBA-MB-435S cell line. Before mentioning about the relation between NPA cells and M14/MBA-MB-435S cells, the M14 cell line was not identical to the MBA-MB-435S cell which Hollestelle A and Schutte M (4) revealed in 2009. The M14 cell was originated from human male melanoma and MBA-MB-435S was originated from human female breast cancer. M14/MBA-MB-435S cells have been reported to express only heterozygous BRAF V600E mutations, but NPA cells showed homo/heterozygous BRAF V600E mutations by Scheweppe et al. (2), and they suggested that the difference was due to LOH occurred during culturing. Likewise, ARO cells have been reported to express homo/hemizygous or heterozygous BRAF mutations, but HT-29 cells showed only heterozygous mutation by Scheweppe et al. (2). Therefore, the report that the NPA cell is identical to M14/MBA-MB-435S cell and ARO cell is identical to HT-29 cell was based on their suggestions not on true scientific data. In conclusion, we insist that the NPA or ARO cells used for our study are of true thyroid undifferentiated, anaplstic thyroid cancer cell origin, and the claims by Scheweppe et al. (2) are due to cross-contaminations during cell passages in the laboratory as they described.

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.

Purpose: Breast ultrasonography (US) is not recommended for recurrence monitoring after breast cancer surgery due to the lack of evidence for its advantage. The purpose of this study was to evaluate the usefulness of US for detecting local recurrence (LR), regional recurrence (RR) and contralateral breast cancer (CBC) in breast cancer patients during follow-up. Methods: The medical records of 5,833 breast cancer patients who underwent breast cancer surgery between January 2003 and December 2009 were reviewed retrospectively. Physical examination (PE), mammography (MMG), and US were done routinely to detect recurrences. Detection rate for locoregional and contralateral recurrence was compared between the three modalities. Results: During the follow-up period, 125 LR, 46 RR, 83 CBC, and 29 synchronous local and regional recurrences developed in 245 patients among the study population of 5,833 breast cancer patients. Median time to recurrence was 34.7 months. The recurrence detection rate was 51.9%, 43.5%, and 90.1% for PE, MMG, and US, respectively. Mean size of the recurrent lesions detected by US (1.57 cm) was smaller than that of PE (2.69 cm) and MMG (2.03 cm) (p =0.002). Conclusion: Breast US had higher recurrence detection rate for LR, RR, and CBC than PE or MMG after breast cancer surgery.

Purpose: Papillary thyroid carcinomas (PTCs) measuring 1.0 cm or less were separately defined as papillary thyroid microcarcinomas (PTMs) by the World Health Organization, emphasizing on their benign behavior. However, some reported that PTMs may have aggressive behavior, can cause regional, or even distant metastases. But till now, the characteristics of PTMs were only reviewed and described by the clinicopathological parameters, and no analysis of PTM by the gene level is available. We report on the gene expression profiles of PTMs by the oligonucleotide microarrays and the results of comparative analysis with those of PTCs. Materials and Methods: The gene expression profiles of 25 pairs of PTMs and their normal thyroid tissue counterparts, and 11 pairs of PTCs and their normal counterparts, were analyzed by Affymetrix Human Genome U133A. Data were analyzed by the SAM and the DAVID 2008 program to detect differentially expressed genes in supervised sample classification. Results: Two-hundred thirteen statistically significant up-regulated genes and -183 significant down-regulated genes of PTMs compared with their normal counterpart thyroid tissues, which were mainly cell adhesion-related genes and immune response genes, were detected. Two-hundred sixty-one up-regulated and -157 down-regulated genes of PTCs were also detected. In the comparative analyses of gene expression profiles of PTMs and PTCs, no significant difference was found. Conclusion: PTM should not be considered as the simple occult indolent thyroid cancer, but as the earlier stage of disease which eventually evolves into PTC, because the gene expression profiles of PTMs were not different from those of PTCs.