Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

The Prognostic Value of Central Lymph Node Yield and Ratio in Papillary Thyroid Carcinoma Patients Who Underwent Thyroidectomy with Prophylactic Central Compartment Neck Dissection

BACKGROUND AND OBJECTIVES: The impacts of prophylactic central compartment neck dissection (pCCND) on the prognosis of papillary thyroid cancer (PTC) are controversial. The aim of this study is to evaluate the relationship between nodal factors of pCCND and the prognosis of PTC patients. MATERIALS AND METHODS: A total of 1754 patients who underwent thyroidectomy with pCCND were retrospectively reviewed. Nodal factor was defined as the number of metastatic lymph node (MLN), lymph node yield (LNY) and lymph node ratio (LNR). In regarding the cutoff of nodal factors, patients were categorized as low/high MLN, LNR and LNY group. The correlation of clinicopathologic characteristics including nodal factors and recurrence free survival (RFS) were anlalyzed. RESULTS: Of these, 1195 patients underwent thyroidectomy with unilateral pCCND and 559 patients underwent total thyroidectomy with bilateral pCCND. During follow-up, 45 (2.57%) patients showed recurrent disease. Of these, 19 patients underwent bilateral pCCND and 26 cases were unilateral pCCND. Gross extrathyroidal extension (ETE), high MLN and LNR showed statistically significant on RFS in univariate analysis in unilateral pCCND. In multivariate analysis, gross ETE and high LNR were independent risk factor of recurrence in unilateral pCCND. In bilateral pCCND, larger tumor size, minimal ETE, high MLN and LNR were significant correlation with RFS in univariate analysis. However, in multivariate analysis, multiple larger tumor and high LNR showed significant correlation with RFS. LNY was not statistically significant in both unilateral and bilateral pCCND. CONCLUSION: In regarding nodal factors, high LNR was only independent risk factor to worse RFS in both unilateral and bilateral pCCND in cN0 PTC patients.

Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia.

Medullary thyroid carcinoma: a 30-year experience at one institution in Korea

PURPOSE: The objective of this study was to review the clinical outcome and prognosis of patients with sporadic and hereditary medullary thyroid cancer (MTC) who were treated at a single tertiary hospital in Korea. METHODS: We retrospectively reviewed the case files of 85 patients treated from August 1982 to February 2012. RESULTS: In all, 65 patients (76.5%) had sporadic MTC and 20 patients (23.5%) had hereditary MTC. Patients in the sporadic group were older than in the hereditary group (P < 0.001). However, the hereditary group had more tumor multiplicity (P < 0.001) and bilaterality (P < 0.001). Neither survival rate was significantly different between the sporadic and hereditary groups (P = 0.775 and P = 0.866). By multivariate analysis, distant metastasis was a significant prognostic factor for overall and progression-free survival. CONCLUSION: In general, patients with MTC have favorable outcomes. Distant metastasis appears to be the strongest predictor of overall and progression-free survival.

Multiple endocrine neoplasia type 1 with anterior mediastinal parathyroid adenoma: successful localization using Tc-99m sestamibi SPECT/CT

The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT.

Transaxillary Endoscopic Thyroidectomy versus Conventional Open Thyroidectomy for Papillary Thyroid Cancer: 5-year Surgical Outcomes / 대한내분비외과학회지

PURPOSE: The early surgical outcomes of endoscopic thyroidectomy in papillary thyroid cancer (PTC) are comparable to those of conventional open thyroidectomy; however, there is little evidence about long-term outcomes. The aim of this study was to compare the 5-year surgical outcomes of endoscopic versus open thyroidectomy. METHODS: We reviewed 804 patients with PTC who underwent thyroidectomy between October 2008 and October 2010. Of these, 703 patients received conventional open thyroidectomy (OT group) and 101patients underwent endoscopic thyroidectomy (ET group). The clinicopathologic characteristics and surgical outcomes were compared between those treatments. RESULTS: ET was applied significantly more often in young patients and females. The lobectomy and unilateral CCND were performed more frequently in ET, and the mean tumor size was smaller. The prevalence of extrathyroidal extension, multiplicity, and lymphatic invasion was more frequent in OT. The T and TNM stage were more advanced in OT, whereas the N status was similar between treatments. The mean surgical time was significantly longer for ET, while the number of retrieved lymph nodes was greater in OT. However, the stimulated thyroglobulin levels at first RAI ablation, total amount of RAI administration and 5-year recurrence rate did not significantly differ between groups. The incidence of transient hypocalcemia was significantly higher in OT, but the incidence of permanent hypocalcemia and transient/permanent recurrent laryngeal nerve injury were similar in both groups. CONCLUSION: Endoscopic thyroidectomy might be a safe and effective procedure in well-selected PTC patients

Robotic Thyroidectomy: Pros and Cons of Various Surgical Approaches / 대한내분비외과학회지

Robotic thyroidectomy has been a good option in the treatment of benign and early stage differentiated thyroid cancers, with several functional benefits. In the last few years, many surgeons have established their own robotic thyroidectomy techniques, and published many reports on the feasibility, safety and benefits of their robotic procedures. Although there are many different surgical techniques, robotic thyroidectomy can be classified according to the different means of remote access to the thyroid gland. Each method has advantages and disadvantages, and surgeons have modified each procedure in an effort to eliminate its shortcomings. With the remarkable innovation of robotic instruments and patient selection based on the appropriate indications, robotic thyroidectomy may usher a paradigm shift for thyroid surgery in the near future.

Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy

The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and beta-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including beta-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

Erratum: Correction of Nomenclature of BRAF Mutation

We made a mistake in our recently published article.

Overall Incidence of Posttransplant Malignancies and Clinicopathologic Features of Thyroid Cancer in Renal Allograft Recipients; 40-years Single Center's Experience / 대한내분비외과학회지

PURPOSE: Prolonged immunosuppression after kidney transplantation (KT) is known to increase the risk of various cancers; however, few studies on posttransplant thyroid carcinoma (TC) have been reported in the literature. We investigated the incidence of posttransplant malignancies (PTMs) and the clinicopathological features of postransplant TC. METHODS: We conducted a retrospective study of 1,622 patients who underwent KT from Mar. 1969 to Dec. 2008. Overall incidence and the standardized incidence ratio (SIR) of posttransplant TC according to the 2007 annual report of the Korea Cancer Center Registry were calculated. RESULTS: During the mean follow-up period of 109 months, 137 (8.4%) recipients were identified as having PTM, including five males and seven females with papillary TC. (0.74%) SIR of the TC was 12.4 in males and 0.5 in females. During the mean follow-up period of 69.1 months, three (25.0%) patients with TC developed loco-regional recurrence. CONCLUSION: Overall incidence of TC was higher compared to the general Korean population (0.74% vs 0.04%) without differences in gender distribution (P=0.086) and higher tendency of locoregional recurrence in clinical carcinoma (P=0.0512). Therefore, to ensure early detection and favorable outcome of posttransplant TC, frequent surveillance using ultrasonography and prophylactic central neck dissection should be considered.

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF). METHODS: We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having or =50% tall cells, respectively. RESULTS: TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (< or =1.0 cm in size). CONCLUSIONS: Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: A 17-year Experience at a Single Institution

PURPOSE: The diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is a rare histological subtype characterized by unique morphological features and aggressive behavior. The aim of this study was to evaluate the clinocopathologic features and outcome of DSPTC over 17 years. METHODS: Twenty-six cases of DSPTC (0.5%) were identified among 5,527 patients with papillary thyroid carcinoma treated between July 1990 and June 2007 at the Department of Surgery, Yonsei University College of Medicine. The clinicopathological features and outcome of these patients with DSPTC were evaluated. The median follow-up period was 46 months (range, 1~202 months). RESULTS: Twenty patients were females and 6 were males, the age ranged from 5 to 70 years (median 30.5 years). Histologically, most of the patients demonstrated diffuse involvement of one or both lobes of the thyroid, variable degree of lymphocytic infiltration, squamous metaplasia, psammoma bodies, extensive sclerosis and extracapsular extension, along with a high incidence of lateral neck node metastases (17/26, 65.4%). Treatment was by complete surgical resection by means of a total thyroidectomy (24/26, 92.3%), modified radical neck dissection (17/26, 65.4%) and postoperative radioactive iodine therapy (22/26, 84.6%). Recurrences were noted in 6 cases (5 locoregional recurrence and 1 distant metastasis in bone). One patient died of an unrelated disease. The 10-year overall survival and disease specific survival rates were 83.8% and 100%, retrospectively, but disease free survival was 48.0%. CONCLUSION: DSPTC showed an unfavorable clinical course with a low overall disease free survival. An aggressive therapeutic approach and close follow-up are recommended.

Urinary Tract Infection Following Voiding Cystourethrography

PURPOSE: Voiding cystourethrography(VCUG) is required to detect vesicoureteral reflux(VUR), which may manifest as urinary tract infection(UTI) in children. It is well known that VCUG can cause UTI(post-VCUG UTI). In this study, risk factors for post-VCUG UTI and the preventive effect of antibiotics against this complication of VCUG were explored. METHODS: Medical records of 284 patients who underwent VCUG at our hospital in 2007 were reviewed retrospectively. The incidence of post-VCUG UTI and risk factors for post-VCUG UTI, and the impact of antibiotic use on prevention of post-VCUG UTI were evaluated. According to antibiotics usage, we divided the enrolled patients into 4 groups of noantibiotics group, prophylactic antibiotics group(prophylactic antibiotics having been used before), antibiotics-for-VCUG group(antibiotics added for VCUG) and antibiotics-for-treatment group(treatment dose of antibiotics). RESULTS: Seven of 284 children(2.5%) developed UTI after they underwent VCUG. High-grade(grade> or =III) VUR was the only statistically significant risk factor(odds ratio[OR] 6.266, P=0.026) for post-VCUG UTI, while sex, age, and other anomalies of urinary system were not significant. Five post-VCUG UTI cases belonged to prophylactic antibiotics group. Antibiotics use (three groups using antibiotics vs. no-antibiotics group) or addition of antibiotics for VCUG (antibiotics-for-VCUG vs. other groups) did not have any effect on prevention of post-VCUG UTI. CONCLUSION: The risk factor for post-VCUG UTI was high-grade VUR. Antibiotics use did not prevent post-VCUG UTI in this study.

Two Cases of Acute Renal Failure Complicating Paroxysmal Nocturnal Hemoglobinuria in Children

Paroxysmal nocturnal hemoglobinuria(PNH) is an acquired hematologic disorder characterized by intravascular hemolysis, nocturnal hemoglobinuria, thrombotic events and bone marrow failure. It rarely occurs in children and can be complicated by acute renal failure(ARF). Here, we present two cases of ARF complicating PNH which has not been reported yet in Korean children. We suggest that PNH should be considered in differential diagnosis of ARF in children associated with intravascular hemolysis.