Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

A Time Trend Analysis of 5,000 Robotic Thyroidectomies via Bilateral Axillo-Breast Approach.

BACKGROUND: This study aimed to investigate the time trends of surgical outcomes in patients who underwent bilateral axillo-breast approach robotic thyroidectomy (BABA RT) over the last 14 years. METHODS: From February 2008 to September 2021, we conducted a retrospective medical chart review of 5,011 consecutive patients who underwent BABA RT at three Seoul National University-affiliated hospitals. The patients were divided into three groups based on the main model of the da Vinci robotic surgical system to evaluate trends in surgical treatment strategies and outcomes after BABA RT. RESULTS: Of the 5,011 patients (4,706 malignant and 305 benign), the most common histological subtype was papillary thyroid carcinoma (n = 4,584; 97.4%). The mean tumor size significantly increased from 0.8 cm to 1.2 cm (p < 0.05). The mean numbers of metastatic and harvested lymph nodes from the central neck dissection and the lateral neck dissection showed a significant difference and tendency to increase (from 0.9 to 1.6, 4.7 to 6.2, p < 0.05, and from 0.6 to 3.9, 5.3 to 17.9, p < 0.05), respectively, throughout the study period. Permanent hypoparathyroidism decreased from 3.4 to 2.9%. The rate of transient and permanent vocal cord palsy decreased from 15.2 to 2.7% and from 0.7 to 0.2%, respectively. CONCLUSION: With advancements in robotic surgical systems and improvements in the BABA RT technique, surgical indications have expanded to include more advanced thyroid diseases, and surgical outcomes have improved over the last 14 years.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Clinicopathological indicators for TERT promoter mutation in papillary thyroid carcinoma.

OBJECTIVE: Mutations in the telomerase reverse transcriptase (TERT) promoter have been reported as a convincing prognostic factor in papillary thyroid carcinomas (PTCs). We aimed to investigate the frequency of TERT promoter mutations in patients with thyroid cancer and identify the clinicopathological factors associated with them in PTCs. DESIGN: A total of 1086 consecutive cases of thyroid cancer composed of mostly PTCs were included in this study. TERT promoter and BRAF mutations were detected by pyrosequencing and their associations with clinicopathological features of tumour were analyzed. RESULTS: TERT promoter mutations were observed in 1.9% of PTCs, 6.7% of follicular thyroid carcinomas, 8.3% of Hurthle cell carcinomas and 25.0% of poorly differentiated thyroid carcinomas and in a single case of anaplastic thyroid carcinoma. In PTCs, aggressive clinicopathological features, higher stage and BRAF V600E mutation were all found to be associated with TERT promoter mutations. Distant metastasis and disease recurrence were more frequent in TERT promoter-mutated PTCs. In multivariate analysis, age ≥55 years, tall cell variant, mitoses ≥3/10 high-power fields, tumour necrosis, and gross extrathyroidal extension (ETE) were identified as independent factors associated with TERT promoter mutations in PTCs. CONCLUSIONS: This study revealed a relatively low frequency of TERT promoter mutations in Korean patients with PTC. Certain clinicopathological features including old age, tall cell variant, increased mitoses, tumour necrosis and gross ETE were found to be indicative of TERT promoter mutations in PTCs, suggesting that mutational analysis in a particular group of PTCs can be effective in regions with low mutation rates.

Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA. DESIGN: A retrospective case-control study. PATIENTS: Consecutive patients who underwent unilateral adrenalectomy for PA (n = 180). Patients with adrenal Cushing's syndrome (CS) (n = 29) and nonfunctioning adenoma (n = 6) as comparator groups. MEASUREMENTS: A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE). RESULTS: Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS (p < .001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success. CONCLUSIONS: Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.

Comparison of Perioperative Outcomes Using the da Vinci S, Si, X, and Xi Robotic Platforms for BABA Robotic Thyroidectomy.

Background and Objectives: Robotic thyroidectomy via the bilateral axillo-breast approach (BABA), first introduced in Korea in 2008, has become a standard method of thyroid removal worldwide. The introduction of robotic surgical systems has enabled more patients to benefit from BABA robotic thyroidectomy, with good postoperative and excellent cosmetic results. To date, no studies have compared the benefits of the four currently available da Vinci robotic systems (S, Si, X, and Xi) for BABA robotic thyroidectomy. To determine the da Vinci model most suitable for BABA robotic thyroidectomy, the present study compared the perioperative outcomes in patients who underwent BABA robotic thyroidectomy using the four da Vinci models. Materials and Methods: This retrospective study evaluated outcomes in patients (n = 750) who underwent BABA robotic thyroidectomy using the four da Vinci systems from 2013 to 2019. The clinicopathologic data, including operation time, were compared. Substudy A compared the da Vinci models S and Si from 2013 to 2017, and substudy B compared models Si, X, and Xi from 2018 to 2019. Results: Substudy A, comparing the da Vinci S and Si systems, found no statistically significant differences between the two groups, whereas substudy B found that operation time was shorter in patients who underwent BABA robotic thyroidectomy with the da Vinci Xi system than with the Si and X systems. Conclusions: The da Vinci model Xi system can benefit patients undergoing BABA robotic thyroidectomy by shortening the operation time.

Comparison of Recurrent Laryngeal Nerve Identification Time in the Lower Central Triangle during Thyroid Surgery Using Neurophysiological Mapping and Monitoring.

Background and Objectives: Preserving the recurrent laryngeal nerve (RLN) is important in thyroid surgery. However, no standardized surgical method for locating the RLN has been established. We defined a new anatomical definition termed "lower central triangle" (LCT) for consistent identification of RLN and used intraoperative nerve monitoring (IONM) to aid in identification and dissection of RLN. Materials and Methods: Patients undergone thyroidectomy were reviewed retrospectively in Seoul National University Bundang Hospital from January to September 2017. Patients with papillary thyroid carcinoma, follicular neoplasm, and Graves' Disease were included while right side non-RLN in arteriosus lusoria, cancer invasion, pre-existing vocal cord palsy, or under the age of 18 were excluded. RLNs were tested with IONM within LCT consisting of the lower pole as the apex and the common carotid artery as the opposite side. The samples were divided into two groups, IONM and non-IONM. Results: Forty lobes in total were included, 22 in IONM group and 18 in non-IONM group. Groups were not significantly different in age, cancer proportion, and accompanying thyroiditis while sex and nodule size differed. RLN detection time was 10.43 s shorter (p < 0.001), and confirmation time was 10.67 s shorter (p = 0.09) in IONM group than in non-IONM group. Both right and left RLNs were located predominately in the middle of LCT. No transient or permanent vocal cord palsy occurred. Conclusions: While IONM is an appropriate aid for thyroidectomy, our approach using LCT to locate the RLN is a novel definition of anatomy that provides prompt identification of the RLN in thyroid surgery.

Papillary Thyroid Cancers of the Thyroid Isthmus: The Pattern of Nodal Metastasis and the Significance of Extrathyroidal Extension.

BACKGROUND: Cancers of the thyroid isthmus are less frequent compared with the lobar cancers yet have their own unique clinicopathological characteristics. Herein, we sought to examine the isthmic papillary thyroid carcinomas (PTCs) for the pattern of and risk factors for nodal metastasis and the significance of extrathyroidal extension (ETE). METHODS: The medical records of 3138 patients diagnosed with solitary PTC who had undergone surgery were retrospectively reviewed. Of these, 122 isthmic PTCs were matched to common lobar PTCs at a ratio of 1:3 for age, sex, and nodule size. Patient demographics, surgical findings, and pathology reports were analyzed. RESULTS: Isthmic PTCs comprised 4.6% of all PTCs and had more lymphatic invasion (22.1% vs. 13.4%, p = 0.021), ETE (73.0% vs. 57.1%, p = 0.002), and perithyroidal and prelaryngeal node metastasis (18.0% vs. 9.0%, p = 0.006) compared with lobar PTCs. However, there were no significant differences in the rate of central and lateral node metastasis between the two groups. ETE was identified not to be a risk factor for isthmic PTCs for central and lateral node metastasis, in contrast to lobar PTCs in which ETE was a significant risk factor (odds ratio 3.18, 95% confidence interval [CI] 1.89-5.34; and 4.72, 95% CI 1.04-21.41). CONCLUSION: The rates of central and lateral node metastasis of isthmic PTCs are comparable with that of lobar PTCs despite a higher rate of ETE in the isthmic counterpart. Although the extent of surgery for isthmic PTCs remains to be investigated, careful dissection of perithyroidal and prelaryngeal nodes may be necessary for isthmic PTCs.

Postoperative Chylothorax after Modified Radical Neck Dissection for Thyroid Carcinoma: A Missable Rare Complication of Thyroid Surgery.

Background and objectives: Currently, few studies have been conducted on postoperative chylothorax, specifically in total thyroidectomy with modified radical neck dissection (MRND) in papillary thyroid carcinoma patients. This study provides the actual incidence, etiology, and clinical features of postoperative chylothorax and reports the clinical outcomes after treatment, which were dependent upon the severity of the complications. Materials and Methods: The medical charts of 111 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy with modified radical neck dissection from January 2016 to December 2018 were reviewed retrospectively. The results were compared in three groups: the no chylothorax group, the subclinical (asymptomatic) group, and the clinical (symptomatic) group. Results: Chylothorax occurred in 23 patients (20.7%, 23/111). Nineteen (82.6%, 19/23) were subclinical chylothorax cases, which implies a small amount of chyle leakage with no respiratory symptoms. Four (17.4%, 4/23) were clinical, meaning they had either respiratory symptoms, such as dyspnea, desaturation, or a large amount of chylothorax in the images. The incidence was significantly higher in patients who underwent left modified radical neck dissection, and this corresponds to the side in which chylothorax occurred. There were also statistical differences in the drainage color, peak amount, or drain removal time. Conclusions: Postoperative chylothorax is a rare complication following neck dissection. However, it can be fatal if the condition progresses. Therefore, patients who undergo total thyroidectomy with modified radical neck dissection, especially on the left side, should be monitored for respiratory symptoms, and serial chest x-ray images obtained.

Does Thyroidectomy Impact Quality of Life: Retrospective Case-Control Study of Post-Thyroidectomy Patients and Matched Individuals from the General Population.

Background and objectives: The study assesses quality of life (QoL) in patients who underwent thyroidectomy compared to the general population. Materials and Methods: QoL data from post-thyroidectomy patients and individuals with no subjective health concerns, who had attended a routine health screening visit, were evaluated. QoL was assessed using the modified version of Korean Short Form 12 questionnaire (SF-12). Patients and controls were matched using the propensity score approach and a ratio of 1:4. Results: Data from a total of 105 patients and 420 controls were analyzed. For five SF-12 items, lower QoL was found in patients (p < 0.05). Multivariate analysis revealed that a follow-up duration of <1-year, female sex, and an age of >50 years were independent risk factors. No significant difference was found between controls and patients who were >1-year post-surgery. Conclusions: For specific SF-12 items, QoL was lower in post-thyroidectomy patients than in controls. No intergroup difference in QoL was found >1-year post-surgery.

Lateral Transperitoneal Adrenalectomy Versus Posterior Retroperitoneoscopic Adrenalectomy for Benign Adrenal Gland Disease: Randomized Controlled Trial at a Single Tertiary Medical Center.

OBJECTIVE: The aim of this study was to compare the surgical outcomes of lateral transperitoneal adrenalectomy (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA) for benign adrenal tumor. BACKGROUND: Although LTA is the standard treatment for benign adrenal gland tumor, PRA has recently gained popularity. Studies comparing the surgical outcomes of the 2 approaches have reported conflicting findings and thus it remains unclear which approach is superior. METHODS: This trial was conducted between September 2012 and February 2016. Patients were randomized to either LTA or PRA groups in a 1:1 ratio using web-based randomization. The primary outcome was operative time, and the secondary outcomes were blood loss, intraoperative hemodynamic stability, postoperative pain, recovery of bowel movement, and complication rates. This trial was registered with ClincalTrials.gov, number NCT01676025. RESULTS: A total of 83 patients were randomly assigned to the LTA group (n = 42) or the PRA group (n = 41). Median follow-up was 31.3 months. The mean operative times of LTA and PRA were comparable (59.7 ±â€Š18.6 vs 67.6 ±â€Š28.7 minutes, P = 0.139). Logistic regression analysis showed that male sex [odds ratio (OR) = 4.20] and pheochromocytoma (OR = 5.06) were associated with an operative time ≥60 minutes. There were no differences in the secondary outcomes between the groups. One patient in the PRA group required open conversion. CONCLUSION: Both LTA and PRA were performed safely with similar operative outcomes, and thus are comparable options for the treatment of benign adrenal gland tumor.

The application of subcapsular saline injection during bilateral axillo-breast approach robotic thyroidectomy: a preliminary report.

PURPOSE: Saving the parathyroid gland during robotic thyroidectomy is challenging. This study evaluated the application of a novel method, subcapsular saline injection (SCASI), to save the parathyroid gland during bilateral axillo-breast approach (BABA) robotic total thyroidectomy. METHODS: Of the 81 included patients operated on from 2014 to 2016, 31 and 50 underwent BABA robotic total thyroidectomy with and without SCASI, respectively. Serum concentrations of parathyroid hormone (PTH), calcium, and ionized calcium were measured at 1 day and 9 months postoperatively. Transient hypoparathyroidism was defined as PTH < 10.0 pg/mL after 1 day and permanent hypoparathyroidism as PTH < 15.0 pg/mL at 9 months. RESULTS: There were no significant clinicopathologic differences between the two groups. The rate of transient hypoparathyroidism was significantly lower in the SCASI group than in the non-SCASI group [16.1% (5/31) vs. 44% (22/50), p < 0.01]. However, the rates of permanent hypoparathyroidism [0% (0/31) vs. 4% (2/50), p = 0.699] did not differ significantly. CONCLUSIONS: SCASI is a feasible and safe method of saving the parathyroid gland during BABA robotic total thyroidectomy.

Comparison of Immunohistochemistry and Direct Sequencing Methods for Identification of the BRAFV600E Mutation in Papillary Thyroid Carcinoma.

BACKGROUND: BRAFV600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAFV600E-specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods. METHODS: Our institution began using the BRAFV600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance. RESULTS: BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA. CONCLUSIONS: IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAFV600E mutation in classic PTC.

Robotic-assisted modified radical neck dissection using a bilateral axillo-breast approach (robotic BABA MRND) for papillary thyroid carcinoma with lateral lymph node metastasis.

BACKGROUND: Although safe in patients with papillary thyroid carcinoma (PTC), robotic thyroidectomy using a bilateral axillo-breast approach (BABA) has not been frequently performed in patients with advanced PTC. This study describes surgical outcomes in patients with PTC and lymph node metastasis (LNM) in lateral neck compartment who underwent robotic-assisted modified radical neck dissection with BABA (robotic BABA MRND). METHODS: The medical records of patients with PTC and lateral LNM who underwent robotic BABA MRND from March 2010 to July 2016 were retrospectively reviewed. RESULTS: Fifteen patients, 14 women and 1 man, of mean age 37.1 ± 9.3 years, were enrolled. Mean operation time was 272.7 ± 33.8 min. A mean 20.7 ± 7.2 lymph nodes were retrieved from the lateral neck compartment, with a mean 5.3 ± 4.4 lymph nodes being metastatic. The rates of transient and permanent hypocalcemia were 46.7 and 0%, respectively, and the rates of transient and permanent vocal cord palsy were 6.7 and 0%, respectively. Fourteen patients (93.3%) had stimulated thyroglobulin concentrations below 2 ng/mL after the first treatment with radioactive iodine. CONCLUSIONS: Robotic BABA MRND could be safely performed and may be a good surgical option in selected patients with PTC and lateral LNM.

Development of a surgical training model for bilateral axillo-breast approach robotic thyroidectomy.

BACKGROUND: Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) is an excellent surgical method, being oncologically safe and with anatomic views similar to those of open surgery. BABA RT, however, requires training and a learning curve for proficiency. We evaluated the educational effectiveness of a surgical training model for BABA RT, comparing objective BABA scores with scores on the da Vinci Skills Simulator (dVSS). METHODS: Medical students, surgical residents, and surgical fellows performed structured tasks with the BABA training model and dVSS under the same conditions. All tasks were videotaped. BABA scores were compared with dVSS scores and with objective evaluation scores (GEARS and OSATS). RESULTS: Eight medical students, ten surgical residents, and eight surgical fellows participated in this study. The educational effect of BABA training improved from one to two (p < 0.001), two to three (p = 0.003), and one to three (p < 0.001) procedures. Statistically significant differences were found when students were compared with residents (p = 0.025) and fellows (p < 0.001) in the BABA training model, and between students and fellows (p = 0.004) in dVSS. BABA scores showed similar distribution patterns in the three groups to GEARS and OSATS scores (p < 0.001 each). CONCLUSIONS: The BABA training model is an excellent educational tool for surgical residents and surgical fellows to learn and practice BABA RT. Assessment by BABA score yielded objective results comparable to those of traditional scoring methodologies.

Case-Control Study of Papillary Thyroid Carcinoma on Urinary and Dietary Iodine Status in South Korea.

BACKGROUND: The association between iodine levels and the risk of papillary thyroid cancer (PTC) has been suggested, but not definitively established. This study is to compare the iodine status of a group of patients with PTC (with and without BRAF V600E) with that of a healthy population cohort. METHODS: A cohort of patients scheduled for thyroidectomy was enrolled, along with a community-based health-screening cohort with no known history of thyroid disease. Median urinary iodine (UI) levels, creatinine-adjusted median UI levels, and food frequency questionnaire (FFQ) scores (mean ± SD) were compared. In a subgroup analysis, these values were compared between BRAF V600E-positive and BRAF V600E-negative patients in the PTC group. RESULTS: The PTC group consisted of 210 patients, and the control group consisted of 90 healthy individuals. Among the 191 PTC patients whose BRAF V600E mutational status was reported, 169 (88.5%) were revealed positive for the mutation. The median UI levels were significantly higher in the PTC group (786.0 µg/l) than the control group (112.0 µg/l; p < 0.001), as was the case with creatinine-adjusted median UI levels (884.6 µg/g creatinine versus 182.0 µg/g creatinine; p < 0.001) and FFQ scores (66.2 ± 17.5, range 13-114 versus 54.6 ± 21.5, range 16-134; p < 0.001). No significant differences were seen in the subgroup analysis between BRAF V600E-positive and BRAF V600E-negative patients. CONCLUSIONS: Our results indicate that iodine status differs significantly between patients with PTC and healthy controls, suggesting that iodine may be involved in the occurrence of PTC, although the association between iodine levels and BRAF mutational status did not reach statistical significance.

Upregulation of the ESR1 Gene and ESR Ratio (ESR1/ESR2) is Associated with a Worse Prognosis in Papillary Thyroid Carcinoma: The Impact of the Estrogen Receptor α/ß Expression on Clinical Outcomes in Papillary Thyroid Carcinoma Patients.

BACKGROUND: A gender disparity exists with respect to the incidence of papillary thyroid cancer (PTC), suggesting that sex hormones such as estrogen play a role in PTC development and progression. In this study, we compared estrogen receptor gene expression patterns in PTCs to determine the clinical significance of estrogen gene expression in PTC. METHODS: We analyzed ESR1 and ESR2 messenger RNA expression counts using data from The Cancer Genome Atlas (TCGA). To validate the results of TCGA analysis, we analyzed microarray data (GSE 54958) from the Gene Expression Omnibus. RESULTS: ESR1 gene expression and ESR ratio (ESR1/ESR2) were significantly higher in PTC tissues than in paired normal thyroid tissues (mean 659.427 vs. 264.045 for ESR1, 92.017 vs. 19.064 for ESR ratio). Among female patients, ESR1 expression and ESR ratio were negatively correlated with increased age. ESR1 expression and ESR ratio were higher in patients with classic PTC, lymphovascular invasion, BRAF V600E mutation, and radioiodine therapy. Classification analysis demonstrated that higher ESR1 expression and a higher ESR ratio faced a worse overall survival (hazard ratio 6.348 for ESR1, 4.031 for ESR ratio). Validation microarray analysis demonstrated that ESR1 expression and ESR ratio were higher in tumor tissues, classic PTC, and BRAF V600E. CONCLUSION: Higher ESR1 expression and a higher ESR ratio were associated with aggressive prognostic factors and worse overall survival in female PTC patients. Our results suggest that ESR1 and ESR ratio can be used as prognostic markers to predict female patient survival and have potential as a therapeutic target.

Surgical safety and oncological completeness of robotic thyroidectomy for thyroid carcinoma larger than 2 cm.

BACKGROUND: The safety of robotic thyroidectomy (RT) for small-sized thyroid carcinomas has been well established. The surgical outcomes of bilateral axillo-breast approach RT for thyroid carcinomas larger than 2 cm were evaluated and compared with those of open thyroidectomy (OT). METHODS: The medical records of patients who underwent total thyroidectomy or hemithyroidectomy followed by completion thyroidectomy for differentiated thyroid carcinomas measuring 2-4 cm were retrospectively reviewed. RESULTS: The study included 86 patients who underwent RT (n = 21) or OT (n = 65) with mean ages of 30.8 and 51.6 years, respectively. The mean tumor size was 2.8 cm in both groups. There were no significant differences between the RT and OT groups in vocal cord palsy rate (transient, 19.0 vs. 9.2 %; permanent, 0 vs. 1.5 %), postoperative hypoparathyroidism rate (transient, 19.0 vs. 33.8 %; permanent, 4.8 vs. 1.5 %), and the number of retrieved central lymph nodes in papillary thyroid carcinoma patients (6.4 ± 3.5 vs. 6.1 ± 3.9, respectively). The proportion of the patients with serum stimulated thyroglobulin level of <1.0 ng/ml at the initial radioactive iodine treatment was 64.7 % (11/17) for RT group and 66.0 % (35/53) for OT group (p = 0.920). There were three patients (1 RT and 2 OT) who had a biochemical incomplete response, and there was no case of anatomical recurrence or mortality during the median follow-up period of 40.2 months. CONCLUSION: RT is a safe and oncologically sound treatment option for differentiated thyroid carcinomas measuring 2-4 cm in a selected group of patients. The role of RT should be evaluated in correlation with technological advances and increased experience.

Intraoperative localization of the parathyroid glands with indocyanine green and Firefly(R) technology during BABA robotic thyroidectomy.

BACKGROUND: It is unclear whether near-infrared (NIR) light-induced indocyanine green (ICG) fluorescence can effectively identify, and thus permit the preservation of, parathyroid glands in bilateral axillo-breast approach (BABA) robotic thyroidectomy. This case-control study with a prospectively recruited consecutive series and a retrospectively selected control group assessed the usefulness of ICG with Firefly(R) technology to identify the parathyroid glands intraoperatively during BABA robotic thyroidectomy. METHODS: All consecutive patients (N = 22) who were scheduled to undergo BABA robotic thyroidectomy for papillary thyroid carcinoma in December 2013-August 2015 and met the study eligibility criteria were recruited prospectively. ICG fluorescence was used with the Firefly system (NIR illuminator: 805 nm; filter: 825 nm) integrated in the da Vinci Si robot system to identify the lower parathyroid glands. Parathyroid hormone levels were recorded on postoperative days 0, 1, 2, and 14. Propensity score matching was used to identify an age-, gender-, tumor size-, and operation type-matched group of control patients who underwent BABA robotic thyroidectomy without the Firefly system. The two groups were compared in terms of parathyroid-related outcomes. RESULTS: ICG fluorescence-mediated identification of the parathyroid and thyroid glands required on average (range) 203 ± 89 (125-331) and 207 ± 112 (130-356) s, respectively. The mean (range) fluorescence duration in these glands was 20.8 ± 6.0 (16.6-35.8) and 20.1 ± 7.3 (15.5-33.8) min, respectively. The ICG group had a significantly lower rate of incidental parathyroidectomy than the control group (0 vs. 15.9%, P = 0.048). CONCLUSIONS: ICG with NIR light may feasibly and safely identify the parathyroid glands in BABA robotic thyroidectomy.